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Sample records for antineoplastic agents

  1. Thyroid Dysfunction from Antineoplastic Agents

    Science.gov (United States)

    Larsen, P. Reed; Marqusee, Ellen

    2011-01-01

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

  2. Anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma

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    Kwak TW

    2015-04-01

    Full Text Available Tae Won Kwak,1,* Hee Jae Shin,2,* Young-Il Jeong,1 Myoung-Eun Han,3 Sae-Ock Oh,3 Hyun-Jung Kim,4 Do Hyung Kim,5 Dae Hwan Kang1 1Biomedical Research Institute, Pusan National University Hospital, Busan, 2Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Ansan, 3Department of Anatomy, School of Medicine, Pusan National University, Gyeongnam, 4Genewel Co Ltd. Gyeonggi-do, 5School of Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea *These authors contributed equally to this work Background: The aim of this study is to investigate the anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma. Methods: The anticancer activity of streptochlorin was evaluated in vitro in various cholangiocarcinoma cell lines for apoptosis, proliferation, invasiveness, and expression of various protein levels. A liver metastasis model was prepared by splenic injection of HuCC-T1 cholangiocarcinoma cells using a BALB/c nude mouse model to study the systemic antimetastatic efficacy of streptochlorin 5 mg/kg at 8 weeks. The antitumor efficacy of subcutaneously injected streptochlorin was also assessed using a solid tumor xenograft model of SNU478 cells for 22 days in the BALB/c nude mouse. Results: Streptochlorin inhibited growth and secretion of vascular endothelial growth factor by cholangiocarcinoma cells in a dose-dependent manner and induced apoptosis in vitro. In addition, streptochlorin effectively inhibited invasion and migration of cholangiocarcinoma cells. Secretion of vascular endothelial growth factor and activity of matrix metalloproteinase-9 in cholangiocarcinoma cells were also suppressed by treatment with streptochlorin. Streptochlorin effectively regulated metastasis of HuCC-T1 cells in a mouse model of liver metastasis. In a tumor xenograft study using SNU478 cells, streptochlorin significantly inhibited tumor growth without changes in body weight

  3. Infiltrative Lung Diseases: Complications of Novel Antineoplastic Agents in Patients with Hematological Malignancies

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    Bobbak Vahid

    2008-01-01

    Full Text Available Infiltrative lung disease is a well-known complication of antineoplastic agents in patients with hematological malignancies. Novel agents are constantly being added to available treatments. The present review discusses different pulmonary syndromes, pathogenesis and management of these novel agents.

  4. A probabilistic assessment of the impact of interventions on oncology nurses' exposure to antineoplastic agents

    NARCIS (Netherlands)

    Meijster, T.; Fransman, W.; Hemmen, J. van; Kromhout, H.; Heederik, D.; Tielemans, E.

    2006-01-01

    Objective: The main goal was to investigate the potential of a probabilistic approach for exposure assessment and use this information to evaluate the impact of a complex of policy actions/interventions on dermal exposure to antineoplastic agents among oncology nurses. The central theme of this

  5. Discovery and development of antineoplastic agents from natural sources.

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    Cragg, G M; Newman, D J

    1999-01-01

    Nature has provided many effective anticancer agents in current use, such as the microbially derived drugs; dactinomycin; bleomycin and doxorubicin; and the plant-derived drugs, vinblastine, irinotecan, topotecan, etoposide, and paclitaxel. The search for novel antitumor agents from natural sources continues through collaboration among scientists worldwide in the investigation of coral reefs, rainforests, and deep subsurface thermal vents for novel bioactive compounds. The potential for drug discovery is being further enhanced by recent advances in procedures for microbial cultivation and the extraction of nucleic acids from environmental samples, resulting in the identification of novel microbes that provide a vast untapped reservoir of genetic and metabolic diversity. Manipulation of the biosynthetic pathways of microbial polyketides through genetic engineering permits the biosynthesis of bioactive polyketides not generated naturally.

  6. Antineoplastic Drugs

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    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  7. Occupational exposure to antineoplastic agents induces a high level of chromosome damage. Lack of an effect of GST polymorphisms

    International Nuclear Information System (INIS)

    Testa, Antonella; Giachelia, Manuela; Palma, Selena; Appolloni, Massimo; Padua, Luca; Tranfo, Giovanna; Spagnoli, Mariangela; Tirindelli, Donatella; Cozzi, Renata

    2007-01-01

    The aim of our study was to investigate whether occupational exposure to antineoplastic drugs (AND) resulted in genetic damage, possibly indicative of adverse health effects in the long term. We performed a chromosomal aberrations (CA) analysis in peripheral blood lymphocytes (PBL) of a group of 76 trained nurses occupationally exposed to AND. Furthermore, we analysed whether genetic polymorphisms in four metabolic genes of the glutathione S-transferase (GST) family involved in antineoplastic drugs detoxification (GSTM1, GSTT1, GSTP1, GSTA1) had any effect on the yield of chromosomal aberrations in nurses exposed to antineoplastic agents. The exposed group showed a very significant increase of genetic damage (p < 0.0001) potentially indicative of an increased risk of cancer. Unexpectedly, besides the elevated level of chromatid-type aberrations usually related to exposure to chemical agents, we found also severe chromosome damages such as chromosome deletions and dicentric chromosomes, usually related to radiation exposure. No significant association was detected between all GSTs genotypes and chromosome damage. In conclusion, our data show how the occupational exposure to AND is associated to a potential cancer risk, suggesting that current prevention methods do not completely eliminate opportunities for exposure and supporting the need to improve the actual safety practices

  8. Oral antineoplastic agent interactions with medicinal plants and food: an issue to take into account.

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    Collado-Borrell, Roberto; Escudero-Vilaplana, Vicente; Romero-Jiménez, Rosa; Iglesias-Peinado, Irene; Herranz-Alonso, Ana; Sanjurjo-Sáez, María

    2016-11-01

    To review interactions between oral antineoplastic agents (OAAs) for the treatment of solid and hematological tumors and common food and medicinal plants. All potential interactions between OAAs, medicinal plants and food were reviewed. OAAs were considered to be drugs for oral administration that have direct antitumor activity and were approved by the European Medicines Agency in April 2015. We performed the literature search in Pubmed(®) considering only medicinal plants and food. In addition, available data were analyzed from each OAA in secondary data sources taken from Thomson Micromedex(®) and Lexi-comp(®), as well as in the summary of product characteristics. Fifty-eight OAAs were analyzed. We found interactions in 60.3 % of OAAs. Those with most interactions described were: imatinib and procarbazine (4 interactions) and erlotinib, vemurafenib, pomalidomide, medroxyprogesterone and methotrexate (3 interactions). We found 39 interactions (74.4 % important). St. John's wort was the medicinal plant with most interactions (92.6 % were considered important). The rest were: important (ginseng-imatinib, methotrexate-cola and tobacco-erlotinib and tobacco-pomalidomide) and moderate (caffeine-vemurafenib/medroxyprogesterone, medroxyprogesterone-ruxolitinib/St. John's wort, garlic-anagrelide and ginseng-procarbazine). Twenty-six interactions (61.5 % important). Grapefruit had most interactions (82.4 % were considered important). The rest were: important (alcohol-procarbazine) and moderate (dairy-estramustine, methotrexate-ethanol, procarbazine-tyramine, vitamin A-tretinoin/bexarotene and grapefruit-bexarotene/etoposide/sunitinib). A review of interactions of medicinal plants and food should be taken into account in the management of OAAs, since more than half have interactions with MPs and food, of which 70.3 % are considered important. The most relevant are HSJ, grapefruit, ginseng and tobacco. This review is intended to serve as a support to all healthcare

  9. Efficacy of Two Cleaning Solutions for the Decontamination of 10 Antineoplastic Agents in the Biosafety Cabinets of a Hospital Pharmacy.

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    Anastasi, Marco; Rudaz, Serge; Queruau Lamerie, Thomas; Odou, Pascal; Bonnabry, Pascal; Fleury-Souverain, Sandrine

    2015-08-01

    This study aimed to evaluate two cleaning solutions for the chemical decontamination of antineoplastic agents on the surfaces of two biosafety cabinets routinely used for chemotherapy preparation in a hospital pharmacy. For almost 1 year (49 weeks), two different solutions were used for the weekly cleaning of two biosafety cabinets in a hospital pharmacy's centralized cytotoxic preparation unit. The solutions evaluated were a commercial solution of isopropyl alcohol (IPA) and water (70:30, vol:vol), and a detergent solution constituted by 10(-2)M of sodium dodecyl sulfate (SDS) with 20% IPA. Seven areas in each biosafety cabinet were wiped 14 times throughout the year, before and after the weekly cleaning process, according to a validated procedure. Samples were analyzed using a validated method of high-performance liquid chromatography coupled to mass spectrometry. The decontamination efficacy of these two solutions was tested for 10 antineoplastic agents: cytarabine, gemcitabine, methotrexate, etoposide phosphate, irinotecan, cyclophosphamide, ifosfamide, doxorubicin, epirubicin, and vincristine. Overall decontamination efficacies observed were 82±6% and 49±11% for SDS solution and IPA, respectively. Higher contamination levels were distributed on areas frequently touched by the pharmacy technicians-such as sleeves and airlock handles-than on scale plates, gravimetric control hardware, and work benches. Detected contaminations of cyclophosphamide, ifosfamide, gemcitabine, and cytarabine were higher than those of the others agents. SDS solution was almost 20% more efficient than IPA on eight of the antineoplastic agents. Both cleaning solutions were able to reduce contamination levels in the biosafety cabinets. The efficacy of the solution containing an anionic detergent agent (SDS) was shown to be generally higher than that of IPA and, after the SDS cleaning procedure, biosafety cabinets demonstrated acceptable contamination levels. © The Author 2015

  10. Characterizing interspecies uncertainty using data from studies of anti-neoplastic agents in animals and humans

    International Nuclear Information System (INIS)

    Price, Paul S.; Keenan, Russell E.; Swartout, Jeffrey C.

    2008-01-01

    For most chemicals, the Reference Dose (RfD) is based on data from animal testing. The uncertainty introduced by the use of animal models has been termed interspecies uncertainty. The magnitude of the differences between the toxicity of a chemical in humans and test animals and its uncertainty can be investigated by evaluating the inter-chemical variation in the ratios of the doses associated with similar toxicological endpoints in test animals and humans. This study performs such an evaluation on a data set of 64 anti-neoplastic drugs. The data set provides matched responses in humans and four species of test animals: mice, rats, monkeys, and dogs. While the data have a number of limitations, the data show that when the drugs are evaluated on a body weight basis: 1) toxicity generally increases with a species' body weight; however, humans are not always more sensitive than test animals; 2) the animal to human dose ratios were less than 10 for most, but not all, drugs; 3) the current practice of using data from multiple species when setting RfDs lowers the probability of having a large value for the ratio. These findings provide insight into inter-chemical variation in animal to human extrapolations and suggest the need for additional collection and analysis of matched toxicity data in humans and test animals

  11. Concanavalin A: A potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wen-wen; Yu, Jia-ying; Xu, Huai-long [School of Life Sciences and State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610064 (China); Bao, Jin-ku, E-mail: jinkubao@yahoo.com [School of Life Sciences and State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610064 (China)

    2011-10-22

    Highlights: {yields} ConA induces cancer cell death targeting apoptosis and autophagy. {yields} ConA inhibits cancer cell angiogenesis. {yields} ConA is utilized in pre-clinical and clinical trials. -- Abstract: Concanavalin A (ConA), a Ca{sup 2+}/Mn{sup 2+}-dependent and mannose/glucose-binding legume lectin, has drawn a rising attention for its remarkable anti-proliferative and anti-tumor activities to a variety of cancer cells. ConA induces programmed cell death via mitochondria-mediated, P73-Foxo1a-Bim apoptosis and BNIP3-mediated mitochondrial autophagy. Through IKK-NF-{kappa}B-COX-2, SHP-2-MEK-1-ERK, and SHP-2-Ras-ERK anti-angiogenic pathways, ConA would inhibit cancer cell survival. In addition, ConA stimulates cell immunity and generates an immune memory, resisting to the same genotypic tumor. These biological findings shed light on new perspectives of ConA as a potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis in pre-clinical or clinical trials for cancer therapeutics.

  12. Accelerator mass spectrometry analysis of 14C-oxaliplatin concentrations in biological samples and 14C contents in biological samples and antineoplastic agents

    Science.gov (United States)

    Toyoguchi, Teiko; Kobayashi, Takeshi; Konno, Noboru; Shiraishi, Tadashi; Kato, Kazuhiro; Tokanai, Fuyuki

    2015-10-01

    Accelerator mass spectrometry (AMS) is expected to play an important role in microdose trials. In this study, we measured the 14C concentration in 14C-oxaliplatin-spiked serum, urine and supernatant of fecal homogenate samples in our Yamagata University (YU) - AMS system. The calibration curves of 14C concentration in serum, urine and supernatant of fecal homogenate were linear (the correlation coefficients were ⩾0.9893), and the precision and accuracy was within the acceptance criteria. To examine a 14C content of water in three vacuum blood collection tubes and a syringe were measured. 14C was not detected from water in these devices. The mean 14C content in urine samples of 6 healthy Japanese volunteers was 0.144 dpm/mL, and the intra-day fluctuation of 14C content in urine from a volunteer was little. The antineoplastic agents are administered to the patients in combination. Then, 14C contents of the antineoplastic agents were quantitated. 14C contents were different among 10 antineoplastic agents; 14C contents of paclitaxel injection and docetaxel hydrate injection were higher than those of the other injections. These results indicate that our quantitation method using YU-AMS system is suited for microdosing studies and that measurement of baseline and co-administered drugs might be necessary for the studies in low concentrations.

  13. Accelerator mass spectrometry analysis of {sup 14}C-oxaliplatin concentrations in biological samples and {sup 14}C contents in biological samples and antineoplastic agents

    Energy Technology Data Exchange (ETDEWEB)

    Toyoguchi, Teiko, E-mail: tteiko@med.id.yamagata-u.ac.jp [Department of Pharmacy, Yamagata University Hospital, 2-2-2 Iida-Nishi, Yamagata-shi, Yamagata 990-9585 (Japan); Kobayashi, Takeshi; Konno, Noboru; Shiraishi, Tadashi [Department of Pharmacy, Yamagata University Hospital, 2-2-2 Iida-Nishi, Yamagata-shi, Yamagata 990-9585 (Japan); Kato, Kazuhiro; Tokanai, Fuyuki [Department of Physics, Faculty of Science, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata-shi, Yamagata 990-8560 (Japan)

    2015-10-15

    Accelerator mass spectrometry (AMS) is expected to play an important role in microdose trials. In this study, we measured the {sup 14}C concentration in {sup 14}C-oxaliplatin-spiked serum, urine and supernatant of fecal homogenate samples in our Yamagata University (YU) – AMS system. The calibration curves of {sup 14}C concentration in serum, urine and supernatant of fecal homogenate were linear (the correlation coefficients were ⩾0.9893), and the precision and accuracy was within the acceptance criteria. To examine a {sup 14}C content of water in three vacuum blood collection tubes and a syringe were measured. {sup 14}C was not detected from water in these devices. The mean {sup 14}C content in urine samples of 6 healthy Japanese volunteers was 0.144 dpm/mL, and the intra-day fluctuation of {sup 14}C content in urine from a volunteer was little. The antineoplastic agents are administered to the patients in combination. Then, {sup 14}C contents of the antineoplastic agents were quantitated. {sup 14}C contents were different among 10 antineoplastic agents; {sup 14}C contents of paclitaxel injection and docetaxel hydrate injection were higher than those of the other injections. These results indicate that our quantitation method using YU-AMS system is suited for microdosing studies and that measurement of baseline and co-administered drugs might be necessary for the studies in low concentrations.

  14. Administration of anti-neoplastic agents to treat malignancies in solid organ transplant recipients

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    Omar Al Ustwani

    2015-12-01

    Full Text Available The management of advanced malignancies in solid organ transplant (SOT recipients is not well-structured as the patients need immunosuppressive agents to avoid graft rejection. Simultaneous administration of chemotherapy and immunosuppressive agents may increase treatment toxicities. The data of SOT recipients treated at Roswell Park Cancer Institute (RPCI was reviewed for different malignancies to assess their treatment patterns, tolerance and outcomes. Chart review of 40 SOT patients seen at RPCI (2000–2012 for cancer management was conducted. The median age was 61.5 years and 50% were males. The median lag time between SOT and cancer diagnosis was 8.4 years. It was found that 46% of solid tumors were metastatic at diagnosis, 78% received chemotherapy and 22% had hormonal therapy alone. In the chemotherapy group, the patients received an average of 1.8 lines of therapy, where 13% were given definitive chemotherapy and radiotherapy while 26% received chemotherapy in the neoadjuvant/adjuvant setting. Treatment delays were necessary in 32%, and dose omission or reduction in 42%. The most common hematologic adverse events (AEs were anemia (78% and thrombocytopenia (59%. Febrile neutropenia occurred in 12.5%. The most common non-hematologic AEs were fatigue (55% and hepatic dysfunction (45%. The most common grade 3/4 hematologic AEs were neutropenia (33% and leukopenia (27% while non-hematologic grade 3/4 AEs was fatigue (12.5%. At the time of analysis, 26% patients were still alive. The median overall survival period of the patients was 28.5 months. In conclusion, SOT patients can tolerate chemotherapy; however AEs, dose reductions and delays occur. Thus, the treating physicians should be cautious on dosing chemotherapy in these cases.

  15. Cordycepin, a Natural Antineoplastic Agent, Induces Apoptosis of Breast Cancer Cells via Caspase-dependent Pathways.

    Science.gov (United States)

    Wang, Di; Zhang, Yongfeng; Lu, Jiahui; Wang, Yang; Wang, Junyue; Meng, Qingfan; Lee, Robert J; Wang, Di; Teng, Lesheng

    2016-01-01

    Cordycepin, a major compound separated from Cordyceps sinensis, is known as a potential novel candidate for cancer therapy. Breast cancer, the most typical cancer diagnosed among women, remains a global health problem. In this study, the anti-breast cancer property of cordycepin and its underlying mechanisms was investigated. The direct effects of cordycepin on breast cancer cells both in in vitro and in vivo experiments were evaluated. Cordycepin exerted cytotoxicity in MCF-7 and MDA-MB-231 cells confirmed by reduced cell viability, inhibition of cell proliferation, enhanced lactate dehydrogenase release and reactive oxygen species accumulation, induced mitochondrial dysfunction and nuclear apoptosis in human breast cancer cells. Cordycepin increased the activation of pro-apoptotic proteins, including caspase-8, caspase-9, caspase-3 and Bax, and suppressed the expression of the anti-apoptotic protein, B-cell lymphoma 2 (Bcl-2). The inhibition on MCF-7-xenografted tumor growth in nude mice further confirmed cordycepin's anti-breast cancer effect. These aforementioned results reveal that cordycepin induces apoptosis in human breast cancer cells via caspase-dependent pathways. The data shed light on the possibility of cordycepin being a safe agent for breast cancer treatment.

  16. Inhibition of RecBCD enzyme by antineoplastic DNA alkylating agents.

    Science.gov (United States)

    Dziegielewska, Barbara; Beerman, Terry A; Bianco, Piero R

    2006-09-01

    To understand how bulky adducts might perturb DNA helicase function, three distinct DNA-binding agents were used to determine the effects of DNA alkylation on a DNA helicase. Adozelesin, ecteinascidin 743 (Et743) and hedamycin each possess unique structures and sequence selectivity. They bind to double-stranded DNA and alkylate one strand of the duplex in cis, adding adducts that alter the structure of DNA significantly. The results show that Et743 was the most potent inhibitor of DNA unwinding, followed by adozelesin and hedamycin. Et743 significantly inhibited unwinding, enhanced degradation of DNA, and completely eliminated the ability of the translocating RecBCD enzyme to recognize and respond to the recombination hotspot chi. Unwinding of adozelesin-modified DNA was accompanied by the appearance of unwinding intermediates, consistent with enzyme entrapment or stalling. Further, adozelesin also induced "apparent" chi fragment formation. The combination of enzyme sequestering and pseudo-chi modification of RecBCD, results in biphasic time-courses of DNA unwinding. Hedamycin also reduced RecBCD activity, albeit at increased concentrations of drug relative to either adozelesin or Et743. Remarkably, the hedamycin modification resulted in constitutive activation of the bottom-strand nuclease activity of the enzyme, while leaving the ability of the translocating enzyme to recognize and respond to chi largely intact. Finally, the results show that DNA alkylation does not significantly perturb the allosteric interaction that activates the enzyme for ATP hydrolysis, as the efficiency of ATP utilization for DNA unwinding is affected only marginally. These results taken together present a unique response of RecBCD enzyme to bulky DNA adducts. We correlate these effects with the recently determined crystal structure of the RecBCD holoenzyme bound to DNA.

  17. Novel meroterpenoids from Cystoseira mediterranea: use of the crown-gall bioassay as a primary screen for lipophilic antineoplastic agents.

    Science.gov (United States)

    Fadli, M; Aracil, J M; Jeanty, G; Banaigs, B; Francisco, C

    1991-01-01

    Using a slight modification of the crown-gall potato disc bioassay, we were able to apply this test for two previously described antineoplastic lipophilic metabolites, didemnin B and mediterraneol A [1], and to use it as a guide for chromatographic separations of meroterpenoids from Cystoseira mediterranea. An active compound, mediterraneone [3], was isolated, and its structure was found to be a novel norsesquiterpenoid by chemical and spectral methods.

  18. Evaluation of real-time data obtained from gravimetric preparation of antineoplastic agents shows medication errors with possible critical therapeutic impact: Results of a large-scale, multicentre, multinational, retrospective study.

    Science.gov (United States)

    Terkola, R; Czejka, M; Bérubé, J

    2017-08-01

    Medication errors are a significant cause of morbidity and mortality especially with antineoplastic drugs, owing to their narrow therapeutic index. Gravimetric workflow software systems have the potential to reduce volumetric errors during intravenous antineoplastic drug preparation which may occur when verification is reliant on visual inspection. Our aim was to detect medication errors with possible critical therapeutic impact as determined by the rate of prevented medication errors in chemotherapy compounding after implementation of gravimetric measurement. A large-scale, retrospective analysis of data was carried out, related to medication errors identified during preparation of antineoplastic drugs in 10 pharmacy services ("centres") in five European countries following the introduction of an intravenous workflow software gravimetric system. Errors were defined as errors in dose volumes outside tolerance levels, identified during weighing stages of preparation of chemotherapy solutions which would not otherwise have been detected by conventional visual inspection. The gravimetric system detected that 7.89% of the 759 060 doses of antineoplastic drugs prepared at participating centres between July 2011 and October 2015 had error levels outside the accepted tolerance range set by individual centres, and prevented these doses from reaching patients. The proportion of antineoplastic preparations with deviations >10% ranged from 0.49% to 5.04% across sites, with a mean of 2.25%. The proportion of preparations with deviations >20% ranged from 0.21% to 1.27% across sites, with a mean of 0.71%. There was considerable variation in error levels for different antineoplastic agents. Introduction of a gravimetric preparation system for antineoplastic agents detected and prevented dosing errors which would not have been recognized with traditional methods and could have resulted in toxicity or suboptimal therapeutic outcomes for patients undergoing anticancer treatment.

  19. Effect of alpha-interferon alone and combined with other antineoplastic agents on renal cell carcinoma determined by the tetrazolium microculture assay.

    Science.gov (United States)

    Homma, Y; Aso, Y

    1994-01-01

    The antiproliferative effect of various alpha-interferons (alpha-IFNs), alone or combined with other agents, on a renal cell carcinoma cell line was evaluated by the tetrazolium microculture assay to examine the rationale for combination therapies. Cells incubated in 96-week microculture plates at 5 x 10(3)/well were exposed to various agents for 3 days. There were no obvious differences in the growth inhibition caused by the 5 kinds of alpha-IFN examined as single agents. The combination of alpha-IFN with the following agents was also assessed: 5-fluorouracil (5FU), methotrexate (MTX), mitomycin C, bleomycin, cis-diaminedichloroplatinum (CDDP), vinblastine, etoposide (ETOP), alpha-IFN, tumor necrosis factor-alpha (TNF), and alpha-difluoromethylornithine. Synergism was observed for the combination of alpha-IFN+TNF, while the other combinations had additive or subadditive effects. No interference or antagonism was found. Trimodal combinations of alpha-IFN+MTX with either 5FU, ETOP, or CDDP all showed subadditive effects. These results indicated that an increased antiproliferative effect, although not necessarily synergistic, was obtained by the combination of alpha-IFN with a variety of antineoplastic agents, providing a rationale to seek for combination therapies including alpha-IFN for treating renal cell carcinoma.

  20. Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) in vivo

    Czech Academy of Sciences Publication Activity Database

    Weber, T.; Lu, M.; Anděra, Ladislav; Lahm, H.; Gellert, N.; Fariss, M. W.; Kořínek, Vladimír; Sattler, W.; Ucker, D. S.; Terman, A.; Schroder, A.; Erl, W.; Brunk, U. T.; Coffey, R. J.; Weber, C.; Neuzil, J.

    2002-01-01

    Roč. 8, - (2002), s. 863-869 ISSN 1078-0432 R&D Projects: GA ČR GA312/99/0348 Institutional research plan: CEZ:AV0Z5052915 Keywords : Vitamin E, Antineoplastic Agent, Tumor Necrosis Factor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.991, year: 2002

  1. Prevention of disease progression in a patient with a gastric cancer-re-recurrence. Outcome after intravenous treatment with the novel antineoplastic agent taurolidine. Report of a case

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    Menenakos Charalambos

    2006-06-01

    Full Text Available Abstract Background Taurolidine (TRD is a novel agent with multimodal antineoplastic effects. We present the case of a tumor remission after intravenous administration of taurolidine in a patient with gastric cancer re-recurrence. Case presentation A 58 years old male patient suffering from a gastric adenocarcinoma was submitted to partial gastrectomy and partial liver resection (pT2, pN1, pM1L (liver segment 2, N0, V0. 24 months later a local recurrence was diagnosed and the patient was reoperated. Postoperatively the patient underwent a palliative chemotherapy with eloxatin, FU, and leucovorin. A subsequent CT-revealed a liver metastasis and a recurrence adjacent to the hepatic artery. After successful radiofrequency ablation of the liver metastasis the patient was intravenously treated with 2% taurolidine. The patient endured the therapy well and no toxicity was observed. CT-scans revealed a stable disease without a tumor progression or metastatic spread. After 39 cycles the patient was submitted to left nephrectomy due to primary urothelial carcinoma and died 2 days later due to myocardial infarction. Postmortem histology of the esophageal-jejunal anastomosis and liver revealed complete remission of the known metastasized gastric adenocarcinoma. Conclusion The intravenous treatment with 2% taurolidine led to a histological remission of the tumor growth without any toxicity for the patient.

  2. Bringing Radiotracing to Titanium-Based Antineoplastics: Solid Phase Radiosynthesis, PET and ex Vivo Evaluation of Antitumor Agent [45Ti](salan)Ti(dipic)

    DEFF Research Database (Denmark)

    Severin, Gregory; Nielsen, Carsten H.; Jensen, Andreas Tue Ingemann

    2015-01-01

    We present a novel solid-phase based 45Ti radiolabeling methodology and the implementation of 45Ti-PET in titanium-based antineoplastics using the showcase compound [45Ti](salan)Ti(dipic). This development is intended to allow elucidation of the biodistribution and pharmacokinetics of promising n...

  3. Antineoplastic treatment of patients with renal insufficiency

    International Nuclear Information System (INIS)

    Rajec, J.; Mego, M.; Rajec, J.

    2011-01-01

    Kidneys are the main route of elimination for many antineoplastic drugs and their metabolites. The kidney dysfunction may lead to the drug cumulation in organism with the resulting increased systemic toxicity. A lot of used cytostatics requires a dose modification at different levels of renal insufficiency. Due to the lack of data from clinical trials, the limiting of systemic toxicity is difficult especially in patients with severe renal impairment or patients undergoing chronic hemodialysis. The following article is focused on the preventive strategies dealing with recommended dosing modification of various antineoplastic agents in patients with renal insufficiency. (author)

  4. Análisis de las dosificaciones en los esquemas de citostáticos en el cáncer de mama Analysis of the dosages in the antineoplastic agents schemes in breast cancer

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    Maritza Ramos Fernández

    2005-08-01

    Full Text Available Se realizó un estudio retrospectivo entre enero y junio de 2003, en el que se revisaron las órdenes médicas y las historias clínicas respectivas de 183 pacientes con cáncer de mama, atendidas en el Instituto de Oncología y Radiobiología, las cuales incluyeron en sus tratamientos esquemas de mezclas intravenosas de citostáticos. Para el análisis realizado se tuvieron en cuenta variables como edad, peso, talla, antecedentes patológicos, esquemas de tratamientos citostáticos prescritos y posología, lo cual permitió establecer la selección adecuada de los tratamientos y definir la dosificación correcta que debía recibir cada paciente. En la muestra objeto de estudio predominaron las pacientes comprendidas en edades entre 40-59 años; 67 pacientes presentaron antecedentes patológicos, y se observó la mayor frecuencia en edades superiores a los 50 años. Las mezclas de citostáticos más utilizadas correspondieron a los fármacos ciclofosfamida-metotrexate-5-fluourouracilo (CMF y ciclofosfamida-adriamicina-5-fluoracilo (CAF. Se detectaron 61 errores de medicación, que representó el 33,3 % del total de la muestra analizada; de ellos 40 pacientes (22 % por subdosificación, 20 pacientes (11 % por sobredosificación y 1 paciente que por sus antecedentes patológicos, tenía contraindicado el uso de adriamicina. Se demostró que es necesario la incorporación del profesional farmacéutico en el equipo multidisciplinario de quimioterapia oncológica, para brindar un servicio asistencial de mayor calidad y evitar riesgos potenciales o reales por el uso inadecuado de los agentes citostáticos.A retrospective study was conducted between January and June, 2003 to review the medical indications and the medical histories of 183 patients with breast cancer that received attention at the Institute of Oncology and Radiobiology, and that were administered intravenous mixtures of antineoplastic agents as part of their treatment. Variables such as

  5. Role of Oxidative Stress in the Induction of Metallothionein-2A and Heme Oxygenase-1 Gene Expression by the Antineoplastic Agent Gallium Nitrate in Human Lymphoma Cells

    Science.gov (United States)

    Yang, Meiying; Chitambar, Christopher R.

    2008-01-01

    The mechanisms of action of gallium nitrate, an antineoplastic drug, are only partly understood. Using a DNA microarray to examine genes induced by gallium nitrate in CCRF-CEM cells, we found that gallium increased metallothionein-2A (MT2A) and heme oxygenase-1 (HO-1) gene expression and altered the levels of other stress-related genes. MT2A and HO-1 were increased after 6 and 16 h of incubation with gallium nitrate. An increase in oxidative stress, evidenced by a decrease in cellular GSH and GSH/GSSG ratio, and an increase in dichlorodihydrofluoroscein (DCF) fluorescence, was seen after 1 – 4 h incubation of cells with gallium nitrate. DCF fluorescence was blocked by the mitochondria-targeted antioxidant mitoquinone. N-acetyl-L-cysteine blocked gallium-induced MT2A and HO-1 expression and increased gallium’s cytotoxicity. Studies with a zinc-specific fluoroprobe suggested that gallium produced an expansion of an intracellular labile zinc pool, suggesting an action of gallium on zinc homeostasis. Gallium nitrate increased the phosphorylation of p38 mitogen-activated protein kinase and activated Nrf-2, a regulator of HO-1 gene transcription. Gallium-induced Nrf-2 activation and HO-1 expression were diminished by a p38 MAP kinase inhibitor. We conclude that gallium nitrate induces cellular oxidative stress as an early event which then triggers the expression of HO-1 and MT2A through different pathways. PMID:18586083

  6. Serine deprivation enhances antineoplastic activity of biguanides.

    Science.gov (United States)

    Gravel, Simon-Pierre; Hulea, Laura; Toban, Nader; Birman, Elena; Blouin, Marie-José; Zakikhani, Mahvash; Zhao, Yunhua; Topisirovic, Ivan; St-Pierre, Julie; Pollak, Michael

    2014-12-15

    Metformin, a biguanide widely used in the treatment of type II diabetes, clearly exhibits antineoplastic activity in experimental models and has been reported to reduce cancer incidence in diabetics. There are ongoing clinical trials to evaluate its antitumor properties, which may relate to its fundamental activity as an inhibitor of oxidative phosphorylation. Here, we show that serine withdrawal increases the antineoplastic effects of phenformin (a potent biguanide structurally related to metformin). Serine synthesis was not inhibited by biguanides. Instead, metabolic studies indicated a requirement for serine to allow cells to compensate for biguanide-induced decrease in oxidative phosphorylation by upregulating glycolysis. Furthermore, serine deprivation modified the impact of metformin on the relative abundance of metabolites within the citric acid cycle. In mice, a serine-deficient diet reduced serine levels in tumors and significantly enhanced the tumor growth-inhibitory actions of biguanide treatment. Our results define a dietary manipulation that can enhance the efficacy of biguanides as antineoplastic agents that target cancer cell energy metabolism. ©2014 American Association for Cancer Research.

  7. Isolation and characterization of antineoplastic alkaloids from ...

    African Journals Online (AJOL)

    The antineoplastic alkaloids; vinblastine and vincristine, were isolated by the use of vacuum liquid chromatographic column on silica gel : aluminium oxide (1:1) mixed bed vacuum liquid chromatography (VLC), Charcoal column, and finally purified by centrifugally accelerated radial chromatography (Chromatotrone).

  8. Non-Invasive Markers of Tumor Growth, Metastases, and Sensitivity to Anti-Neoplastic Therapy

    Science.gov (United States)

    2009-01-01

    breast cancer (21), the detection of an antineoplastic agent Iproplatin in murine RIF-1 tumors (27), and for detecting early response to cyclophospha...conducted in com- pliance with protocols approved by the animal care pro- tocols in Memorial Sloan-Kettering Cancer Center. Phantom Preparation A two... manipulating the slice gradient profile, this binomial pulse acts as a spectral- spatial pulse, although higher-order binomial pulses are desirable for

  9. Adherence to safe handling guidelines by health care workers who administer antineoplastic drugs.

    Science.gov (United States)

    Boiano, James M; Steege, Andrea L; Sweeney, Marie H

    2014-01-01

    The toxicity of antineoplastic drugs is well documented. Many are known or suspected human carcinogens where no safe exposure level exists. Authoritative guidelines developed by professional practice organizations and federal agencies for the safe handling of these hazardous drugs have been available for nearly three decades. As a means of evaluating the extent of use of primary prevention practices such as engineering, administrative and work practice controls, personal protective equipment (PPE), and barriers to using PPE, the National Institute for Safety and Health (NIOSH) conducted a web survey of health care workers in 2011. The study population primarily included members of professional practice organizations representing health care occupations which routinely use or come in contact with selected chemical agents. All respondents who indicated that they administered antineoplastic drugs in the past week were eligible to complete a hazard module addressing self-reported health and safety practices on this topic. Most (98%) of the 2069 respondents of this module were nurses. Working primarily in hospitals, outpatient care centers, and physician offices, respondents reported that they had collectively administered over 90 specific antineoplastic drugs in the past week, with carboplatin, cyclophosphamide, and paclitaxel the most common. Examples of activities which increase exposure risk, expressed as percent of respondents, included: failure to wear nonabsorbent gown with closed front and tight cuffs (42%); intravenous (I.V.) tubing primed with antineoplastic drug by respondent (6%) or by pharmacy (12%); potentially contaminated clothing taken home (12%); spill or leak of antineoplastic drug during administration (12%); failure to wear chemotherapy gloves (12%); and lack of hazard awareness training (4%). The most common reason for not wearing gloves or gowns was "skin exposure was minimal"; 4% of respondents, however, reported skin contact during handling and

  10. Glycaemic adverse drug reactions from anti-neoplastics used in ...

    African Journals Online (AJOL)

    235625 records ... Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer. ... Based on the emphasized nine antineoplastic drugs with high hyperglycemic ADR incidence, we found: fluorouracil, sorafenib and pemetrexed with high ADR record of metabolism and nutrition disorders; ...

  11. Nurses with dermal exposure to antineoplastic drugs: Reproductive outcomes

    NARCIS (Netherlands)

    Fransman, W.; Roeleveld, N.; Peelen, S.; Kort, W.de; Kromhout, H.; Heederik, D.

    2007-01-01

    BACKGROUND: Nurses and other hospital workers are exposed to antineoplastic drugs during daily activities. Previous studies suggest that antineoplastic drugs at occupational exposure levels may be toxic to reproduction, but these studies are not consistent or conclusive. METHODS: Self-administered

  12. Applying dose banding to the production of antineoplastic drugs: a narrative review of the literature

    Directory of Open Access Journals (Sweden)

    Pablo Pérez Huertas

    2015-07-01

    Full Text Available The dosage of antineoplastic drugs has historically been based on individualized prescription and preparation according to body surface area or patient´s weight. Lack of resources and increased assistance workload in the areas where chemotherapy is made, are leading to the development of new systems to optimize the processing without reducing safety. One of the strategies that has been proposed is the elaboration by dose banding. This new approach standardizes the antineoplastic agents doses by making ranges or bands accepting a percentage of maximum variation. It aims to reduce processing time with the consequent reduction in waiting time for patients; to reduce errors in the manufacturing process and to promote the rational drug use. In conclusion, dose banding is a suitable method for optimizing the development of anticancer drugs, obtaining reductions in oncologic patients waiting time but without actually causing a favorable impact on direct or indirect costs.

  13. [Applying dose banding to the production of antineoplastic drugs: a narrative review of the literature].

    Science.gov (United States)

    Pérez Huertas, Pablo; Cueto Sola, Margarita; Escobar Cava, Paloma; Borrell García, Carmela; Albert Marí, Asunción; López Briz, Eduardo; Poveda Andrés, José Luis

    2015-07-01

    The dosage of antineoplastic drugs has historically been based on individualized prescription and preparation according to body surface area or patient´s weight. Lack of resources and increased assistance workload in the areas where chemotherapy is made, are leading to the development of new systems to optimize the processing without reducing safety. One of the strategies that has been proposed is the elaboration by dose banding. This new approach standardizes the antineoplastic agents doses by making ranges or bands accepting a percentage of maximum variation. It aims to reduce processing time with the consequent reduction in waiting time for patients; to reduce errors in the manufacturing process and to promote the rational drug use. In conclusion, dose banding is a suitable method for optimizing the development of anticancer drugs, obtaining reductions in oncologic patients waiting time but without actually causing a favorable impact on direct or indirect costs. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  14. Does applying technology throughout the medication use process improve patient safety with antineoplastics?

    Science.gov (United States)

    Bubalo, Joseph; Warden, Bruce A; Wiegel, Joshua J; Nishida, Tess; Handel, Evelyn; Svoboda, Leanne M; Nguyen, Lam; Edillo, P Neil

    2014-12-01

    Medical errors, in particular medication errors, continue to be a troublesome factor in the delivery of safe and effective patient care. Antineoplastic agents represent a group of medications highly susceptible to medication errors due to their complex regimens and narrow therapeutic indices. As the majority of these medication errors are frequently associated with breakdowns in poorly defined systems, developing technologies and evolving workflows seem to be a logical approach to provide added safeguards against medication errors. This article will review both the pros and cons of today's technologies and their ability to simplify the medication use process, reduce medication errors, improve documentation, improve healthcare costs and increase provider efficiency as relates to the use of antineoplastic therapy throughout the medication use process. Several technologies, mainly computerized provider order entry (CPOE), barcode medication administration (BCMA), smart pumps, electronic medication administration record (eMAR), and telepharmacy, have been well described and proven to reduce medication errors, improve adherence to quality metrics, and/or improve healthcare costs in a broad scope of patients. The utilization of these technologies during antineoplastic therapy is weak at best and lacking for most. Specific to the antineoplastic medication use system, the only technology with data to adequately support a claim of reduced medication errors is CPOE. In addition to the benefits these technologies can provide, it is also important to recognize their potential to induce new types of errors and inefficiencies which can negatively impact patient care. The utilization of technology reduces but does not eliminate the potential for error. The evidence base to support technology in preventing medication errors is limited in general but even more deficient in the realm of antineoplastic therapy. Though CPOE has the best evidence to support its use in the

  15. Nanoparticles applied to antineoplastic agents: a patent landscape.

    Science.gov (United States)

    Fierro, Iolanda M; de Menezes Alencar, Maria Simone; Lins Mendes, Flavia Maria; de Souza Mendes, Cristina d'Urso; Nunes, Bernardo Furtado; de Souza Antunes, Adelaide Maria

    2014-01-01

    Recently, research in the field of cancer nanotechnology has made notable progress, and, with the fast development of nanomaterials, new treatment strategies using nanoparticles are being explored that have the potential to overcome existing problems. The present review focuses on patenting as a key indicator of trends in nanoparticles with applications in the treatment of cancer. The impact of cancer on health and the use of nanoparticles are briefly described. Next, a survey of patents filed in the last 14 years is presented, the patents granted in the last four years are identified, and the focus areas of the main applicants are analyzed. The mix of targets identified for patented nanoparticles systems suggests that polymers and proteins are the main focus of the innovative efforts in this field.

  16. Dental anomalies in children submitted to antineoplastic therapy

    Directory of Open Access Journals (Sweden)

    Camila Merida Carrillo

    2014-06-01

    Full Text Available Cancer is the third most frequent cause of death in children in Brazil. Early diagnosis and medical advances have significantly improved treatment outcomes, which has resulted in higher survival rates and the management of late side effects has become increasingly important in caring for these patients. Dental abnormalities are commonly observed as late effects of antineoplastic therapy in the oral cavity. The incidence and severity of the dental abnormalities depend on the child's age at diagnosis and the type of chemotherapeutic agent used, as well as the irradiation dose and area. The treatment duration and aggressivity should also be considered. Disturbances in dental development are characterized by changes in shape, number and root development. Enamel anomalies, such as discoloration, opacities and hypoplasia are also observed in these patients. When severe, these abnormalities can cause functional and esthetic sequelae that have an impact on the children's and adolescents' quality of life. General dentists and pediatric dentists should understand these dental abnormalities and how to identify them aiming for early diagnosis and appropriate treatment.

  17. Antineoplastic mechanisms of Iodine in cancers that take up Iodine

    Directory of Open Access Journals (Sweden)

    Carmen Aceves

    2015-12-01

    Full Text Available Purpose: In addition to being a component of thyroid hormone (TH, iodine can be an antioxidant as well as an antiproliferative and differentiation agent that helps to maintain the integrity of several organs with the ability to take up iodine.Methods and Results: Studies from our laboratory shown that in preclinical (cell culture, induced animal cancer and xenographs and clinical studies (mammary cancer protocol, molecular iodine (I2 supplementation exerts suppressive effects on implantation, development, and progression of cancer neoplasias. These effects can be mediated by a variety of mechanisms and pathways, including direct actions, in which the oxidized iodine modulates the immune/tumor response and through iodolipid formation and the activation of peroxisome proliferator-activated receptors type gamma (PPARγ triggering apoptotic and/or differentiation pathways.Conclusion: The absence of side effects and the easy availability and handling of I2 have allowed the establishment of clinical protocols to utilize I2 supplementation as an adjuvant in therapies against cancers that take up iodine.-----------------------------------------Cite this article as:  Aceves C, Anguiano B. Antineoplastic mechanisms of Iodine in cancers that take up Iodine. Int J Cancer Ther Oncol 2015; 3(4:3401.[This abstract was presented at the BIT’s 8th Annual World Cancer Congress, which was held from May 15-17, 2015 in Beijing, China.

  18. A Novel Insight into the Cardiotoxicity of Antineoplastic Drug Doxorubicin

    Directory of Open Access Journals (Sweden)

    Zbynek Heger

    2013-10-01

    Full Text Available Doxorubicin is a commonly used antineoplastic agent in the treatment of many types of cancer. Little is known about the interactions of doxorubicin with cardiac biomolecules. Serious cardiotoxicity including dilated cardiomyopathy often resulting in a fatal congestive heart failure may occur as a consequence of chemotherapy with doxorubicin. The purpose of this study was to determine the effect of exposure to doxorubicin on the changes in major amino acids in tissue of cardiac muscle (proline, taurine, glutamic acid, arginine, aspartic acid, leucine, glycine, valine, alanine, isoleucine, threonine, lysine and serine. An in vitro interaction study was performed as a comparison of amino acid profiles in heart tissue before and after application of doxorubicin. We found that doxorubicin directly influences myocardial amino acid representation even at low concentrations. In addition, we performed an interaction study that resulted in the determination of breaking points for each of analyzed amino acids. Lysine, arginine, β-alanine, valine and serine were determined as the most sensitive amino acids. Additionally we compared amino acid profiles of myocardium before and after exposure to doxorubicin. The amount of amino acids after interaction with doxorubicin was significantly reduced (p = 0.05. This fact points at an ability of doxorubicin to induce changes in quantitative composition of amino acids in myocardium. Moreover, this confirms that the interactions between doxorubicin and amino acids may act as another factor most likely responsible for adverse effects of doxorubicin on myocardium.

  19. Surface wipe sampling for antineoplastic (chemotherapy) and other hazardous drug residue in healthcare settings: Methodology and recommendations.

    Science.gov (United States)

    Connor, Thomas H; Zock, Matthew D; Snow, Amy H

    2016-09-01

    Surface wipe sampling for various hazardous agents has been employed in many occupational settings over the years for various reasons such as evaluation of potential dermal exposure and health risk, source determination, quality or cleanliness, compliance, and others. Wipe sampling for surface residue of antineoplastic and other hazardous drugs in healthcare settings is currently the method of choice to determine surface contamination of the workplace with these drugs. The purpose of this article is to review published studies of wipe sampling for antineoplastic and other hazardous drugs, to summarize the methods in use by various organizations and researchers, and to provide some basic guidance for conducting surface wipe sampling for these drugs in healthcare settings.  Recommendations on wipe sampling methodology from several government agencies and organizations were reviewed. Published reports on wipe sampling for hazardous drugs in numerous studies were also examined. The critical elements of a wipe sampling program and related limitations were reviewed and summarized.  Recommendations and guidance are presented concerning the purposes of wipe sampling for antineoplastic and other hazardous drugs in the healthcare setting, technical factors and variables, sampling strategy, materials required, and limitations. The reporting and interpretation of wipe sample results is also discussed.  It is recommended that all healthcare settings where antineoplastic and other hazardous drugs are handled consider wipe sampling as part of a comprehensive hazardous drug "safe handling" program. Although no standards exist for acceptable or allowable surface concentrations for these drugs in the healthcare setting, wipe sampling may be used as a method to characterize potential occupational dermal exposure risk and to evaluate the effectiveness of implemented controls and the overall safety program. A comprehensive safe-handling program for antineoplastic drugs may

  20. Antineoplastic effects of an Aurora B kinase inhibitor in breast cancer

    Directory of Open Access Journals (Sweden)

    Velazquez-Torres Guermarie

    2010-02-01

    Full Text Available Abstract Background Aurora B kinase is an important mitotic kinase involved in chromosome segregation and cytokinesis. It is overexpressed in many cancers and thus may be an important molecular target for chemotherapy. AZD1152 is the prodrug for AZD1152-HQPA, which is a selective inhibitor of Aurora B kinase activity. Preclinical antineoplastic activity of AZD1152 against acute myelogenous leukemia, multiple myeloma and colorectal cancer has been reported. However, this compound has not been evaluated in breast cancer, the second leading cause of cancer deaths among women. Results The antineoplastic activity of AZD1152-HQPA in six human breast cancer cell lines, three of which overexpress HER2, is demonstrated. AZD1152-HQPA specifically inhibited Aurora B kinase activity in breast cancer cells, thereby causing mitotic catastrophe, polyploidy and apoptosis, which in turn led to apoptotic death. AZD1152 administration efficiently suppressed the tumor growth in a breast cancer cell xenograft model. In addition, AZD1152 also inhibited pulmonary metastatic nodule formation in a metastatic breast cancer model. Notably, it was also found that the protein level of Aurora B kinase declined after inhibition of Aurora B kinase activity by AZD1152-HQPA in a time- and dose-dependent manner. Investigation of the underlying mechanism suggested that AZD1152-HQPA accelerated protein turnover of Aurora B via enhancing its ubiquitination. Conclusions It was shown that AZD1152 is an effective antineoplastic agent for breast cancer, and our results define a novel mechanism for posttranscriptional regulation of Aurora B after AZD1152 treatment and provide insight into dosing regimen design for this kinase inhibitor in metastatic breast cancer treatment.

  1. Glycaemic Adverse Drug Reactions from Anti-Neoplastics Used in ...

    African Journals Online (AJOL)

    2017-06-01

    Jun 1, 2017 ... in cancer treatment. The aim was to analyze the blood glucose‑related ADR of antineoplastics in treating pancreatic cancer. Materials and Methods: .... Figure 2: Record numbers on general adverse drug reactions (metabolism and nutrition disorder ratio = metabolism and nutrition disorder/total number.

  2. Glycaemic Adverse Drug Reactions from Anti-Neoplastics Used in ...

    African Journals Online (AJOL)

    2018-01-24

    Jan 24, 2018 ... Hyperglycemia is one of the severe adverse drug reactions (ADRs) in cancer treatment. The aim was to analyze the blood glucose‑related ADR of ... can be suggested. Keywords: Adverse drug reaction, antineoplastic, hyperglycemia, pancreatic cancer, VigiBase. Glycaemic Adverse Drug Reactions from ...

  3. Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study.

    Science.gov (United States)

    Hon, Chun-Yip; Chua, Prescillia Ps; Danyluk, Quinn; Astrakianakis, George

    2014-06-01

    Occupational exposure to antineoplastic drugs has been documented to result in various adverse health effects. Despite the implementation of control measures to minimize exposure, detectable levels of drug residual are still found on hospital work surfaces. Cleaning these surfaces is considered as one means to minimize the exposure potential. However, there are no consistent guiding principles related to cleaning of contaminated surfaces resulting in hospitals to adopt varying practices. As such, this pilot study sought to evaluate current cleaning protocols and identify those factors that were most effective in reducing contamination on drug preparation surfaces. Three cleaning variables were examined: (1) type of cleaning agent (CaviCide®, Phenokil II™, bleach and chlorhexidine), (2) application method of cleaning agent (directly onto surface or indirectly onto a wipe) and (3) use of isopropyl alcohol after cleaning agent application. Known concentrations of antineoplastic drugs (either methotrexate or cyclophosphamide) were placed on a stainless steel swatch and then, systematically, each of the three cleaning variables was tested. Surface wipes were collected and quantified using high-performance liquid chromatography-tandem mass spectrometry to determine the percent residual of drug remaining (with 100% being complete elimination of the drug). No one single cleaning agent proved to be effective in completely eliminating all drug contamination. The method of application had minimal effect on the amount of drug residual. In general, application of isopropyl alcohol after the use of cleaning agent further reduced the level of drug contamination although measureable levels of drug were still found in some cases.

  4. Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines

    Directory of Open Access Journals (Sweden)

    Candelaria Myrna

    2006-01-01

    Full Text Available Abstract Background Among the epigenetic alterations occurring in cancer, DNA hypermethylation and histone hypoacetylation are the focus of intense research because their pharmacological inhibition has shown to produce antineoplastic activity in a variety of experimental models. The objective of this study was to evaluate the combined antineoplastic effect of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in a panel of cancer cell lines. Results Hydralazine showed no growth inhibitory effect on cervical, colon, breast, sarcoma, glioma, and head & neck cancer cell lines when used alone. On the contrary, valproic acid showed a strong growth inhibitory effect that is potentiated by hydralazine in some cell lines. Individually, hydralazine and valproic acid displayed distinctive effects upon global gene over-expression but the number of genes over-expressed increased when cells were treated with the combination. Treatment of HeLa cells with hydralazine and valproic acid lead to an increase in the cytotoxicity of gemcitabine, cisplatin and adriamycin. A higher antitumor effect of adriamycin was observed in mice xenografted with human fibrosarcoma cells when the animals were co-treated with hydralazine and valproic acid. Conclusion Hydralazine and valproic acid, two widely used drugs for cardiovascular and neurological conditions respectively have promising antineoplastic effects when used concurrently and may increase the antitumor efficacy of current cytotoxic agents.

  5. Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines

    Science.gov (United States)

    Chavez-Blanco, Alma; Perez-Plasencia, Carlos; Perez-Cardenas, Enrique; Carrasco-Legleu, Claudia; Rangel-Lopez, Edgar; Segura-Pacheco, Blanca; Taja-Chayeb, Lucia; Trejo-Becerril, Catalina; Gonzalez-Fierro, Aurora; Candelaria, Myrna; Cabrera, Gustavo; Duenas-Gonzalez, Alfonso

    2006-01-01

    Background Among the epigenetic alterations occurring in cancer, DNA hypermethylation and histone hypoacetylation are the focus of intense research because their pharmacological inhibition has shown to produce antineoplastic activity in a variety of experimental models. The objective of this study was to evaluate the combined antineoplastic effect of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in a panel of cancer cell lines. Results Hydralazine showed no growth inhibitory effect on cervical, colon, breast, sarcoma, glioma, and head & neck cancer cell lines when used alone. On the contrary, valproic acid showed a strong growth inhibitory effect that is potentiated by hydralazine in some cell lines. Individually, hydralazine and valproic acid displayed distinctive effects upon global gene over-expression but the number of genes over-expressed increased when cells were treated with the combination. Treatment of HeLa cells with hydralazine and valproic acid lead to an increase in the cytotoxicity of gemcitabine, cisplatin and adriamycin. A higher antitumor effect of adriamycin was observed in mice xenografted with human fibrosarcoma cells when the animals were co-treated with hydralazine and valproic acid. Conclusion Hydralazine and valproic acid, two widely used drugs for cardiovascular and neurological conditions respectively have promising antineoplastic effects when used concurrently and may increase the antitumor efficacy of current cytotoxic agents. PMID:16448574

  6. New solid state forms of antineoplastic 5-fluorouracil with anthelmintic piperazine

    Science.gov (United States)

    Moisescu-Goia, C.; Muresan-Pop, M.; Simon, V.

    2017-12-01

    The aim of the present study was to asses the formation of solid forms between the 5-fluorouracil chemotherapy drug and the anthelmintic piperazine. Two new solid forms of antineoplastic agent 5-fluorouracil with anthelmintic piperazine were obtained by liquid assisted ball milling and slurry crystallization methods. The Nsbnd H hydrogen bonding donors and C = O hydrogen bonding acceptors of 5-fluorouracil allow to form co-crystals with other drugs delivering improved properties for medical applications, as proved for other compounds of pharmaceutical interest. Both new solid forms were investigated using X-ray powder diffraction (XRD), differential thermal analysis (DTA) and Fourier transform infrared (FTIR) spectroscopy. The XRD results show that by both methods were successfully synthesized new solid forms of 5-fluorouracil with piperazine. According to FTIR results the form prepared by lichid assisted grinding process was obtained as co-crystal and the other one, prepared by slurry method, resulted as a salt.

  7. Recent Advances on Pathophysiology, Diagnostic and Therapeutic Insights in Cardiac Dysfunction Induced by Antineoplastic Drugs

    Directory of Open Access Journals (Sweden)

    Marilisa Molinaro

    2015-01-01

    Full Text Available Along with the improvement of survival after cancer, cardiotoxicity due to antineoplastic treatments has emerged as a clinically relevant problem. Potential cardiovascular toxicities due to anticancer agents include QT prolongation and arrhythmias, myocardial ischemia and infarction, hypertension and/or thromboembolism, left ventricular (LV dysfunction, and heart failure (HF. The latter is variable in severity, may be reversible or irreversible, and can occur soon after or as a delayed consequence of anticancer treatments. In the last decade recent advances have emerged in clinical and pathophysiological aspects of LV dysfunction induced by the most widely used anticancer drugs. In particular, early, sensitive markers of cardiac dysfunction that can predict this form of cardiomyopathy before ejection fraction (EF is reduced are becoming increasingly important, along with novel therapeutic and cardioprotective strategies, in the attempt of protecting cardiooncologic patients from the development of congestive heart failure.

  8. The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

    Directory of Open Access Journals (Sweden)

    Reza Heidari

    2016-03-01

    Full Text Available Taurine (2-aminoethane sulfonic acid is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 μM, 100 μM and 1000 μM of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5 Fluorouracil, Doxorubicin and Dacarbazine via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+. Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug treated livers. It was found that taurine (5 and 10 mM and glycine (5 and 10 mM administration significantly mitigated the biomarkers of liver injury and attenuated drug induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.

  9. Aloin enhances cisplatin antineoplastic activity in B16-F10 melanoma cells by transglutaminase-induced differentiation.

    Science.gov (United States)

    Tabolacci, Claudio; Rossi, Stefania; Lentini, Alessandro; Provenzano, Bruno; Turcano, Lorenzo; Facchiano, Francesco; Beninati, Simone

    2013-01-01

    Aloin, a natural anthracycline from aloe plant, is a hydroxyanthraquinone derivative shown to have antitumor properties. This study demonstrated that aloin exerted inhibition of cell proliferation, adhesion and invasion abilities of B16-F10 melanoma cells under non-cytotoxic concentrations. Furthermore, aloin induced melanoma cell differentiation through the enhancement of melanogenesis and transglutaminase activity. To improve the growth-inhibiting effect of anticancer agents, we found that the combined treatment of cells with aloin and low doses of cisplatin increases the antiproliferative activity of aloin. The results suggest that aloin possesses antineoplastic and antimetastatic properties, exerted likely through the induction of melanoma cell differentiation.

  10. Review of the impact of antineoplastic therapies on the risk for cholelithiasis and acute cholecystitis.

    Science.gov (United States)

    Jayakrishnan, Thejus T; Groeschl, Ryan T; George, Ben; Thomas, James P; Clark Gamblin, T; Turaga, Kiran K

    2014-01-01

    Development of cholecystitis in patients with malignancies can potentially disrupt their treatment and alter prognosis. This review aims to identify antineoplastic interventions associated with increased risk of cholecystitis in cancer patients. A comprehensive search strategy was developed to identify articles pertaining to risk factors and complications of cholecystitis in cancer patients. FDA-issued labels of novel antineoplastic drugs released after 2010 were hand-searched to identify more therapies associated with cholecystitis in nonpublished studies. Of an initial 2,932 articles, 124 were reviewed in the study. Postgastrectomy patients have a high (5-30 %) incidence of gallstone disease, and 1-7 % develop symptomatic disease. One randomized trial addressing the role of cholecystectomy concurrent with gastrectomy is currently underway. Among other risk groups, patients with neuroendocrine tumors treated with somatostatin analogs have a 15 % risk of cholelithiasis, and most are symptomatic. Hepatic artery based therapies carry a risk of cholecystitis (0.02-24 %), although the risk is reduced with selective catheterization. Myelosuppression related to chemotherapeutic agents (0.4 %), bone marrow transplantation, and treatment with novel multikinase inhibitors are associated with high risk of cholecystitis. There are several risk factors for gallbladder-related surgical emergencies in patients with advanced malignancies. Incidental cholecystectomy at index operation should be considered in patients planned for gastrectomy, and candidates for regional therapies to the liver or somatostatin analogs. While prophylactic cholecystectomy is currently recommended for patients with cholelithiasis receiving myeloablative therapy, this strategy may have value in patients treated with multikinase inhibitors, immunotherapy, and oncolytic viral therapy based on evolving evidence.

  11. Inhalation and dermal exposure to eight antineoplastic drugs in an industrial laundry facility.

    Science.gov (United States)

    Fransman, Wouter; Huizer, Daan; Tuerk, Jochen; Kromhout, Hans

    2007-04-01

    The aims of the study were to quantify levels of dermal and inhalation exposure to antineoplastic drugs in an industrial laundry service in the Netherlands and to test the removal efficiency of the washing procedure for removal of antineoplastic drugs. During four workdays dermal and inhalation exposure to eight frequently used antineoplastic drugs (cyclophosphamide, ifosfamide, methotrexate, 5-fluorouracil, etoposide, cytarabine, gemcitabine and chlorambucil) were measured for all job titles involved in handling unwashed laundry. To test the removal efficiency of the washing procedure, 10 x 10 cm sections were excised before and after the washing procedure. These sections were taken from 15 bed sheets that were collected in hospitals of patients who were treated with one of the selected antineoplastic drugs. During none of the four measurement days, detectable levels of any of the eight antineoplastic drugs (cyclophosphamide, ifosfamide, methotrexate, 5-fluorouracil, etoposide, cytarabine, gemcitabine, or chlorambucil) were found on workers' skin of hands or in any of the air samples. Only four out of the 15 bed sheets from patients that were treated with antineoplastic drugs appeared to be contaminated with detectable levels of antineoplastic drugs before the washing procedure (range 13.0-3,060 ng/100 cm(2)). After the pre-washing and after the complete washing procedure, no detectable levels of any of the eight antineoplastic drugs were found anymore in the selected bed sheets. The implementation of guidelines for working with antineoplastic drugs seems to be successful in reducing exposure to antineoplastic drugs of workers in this laundry facility to an acceptable, non-detectable level and to remove antineoplastic drug contamination from bed linen.

  12. Antineoplastic effects of Chlorella pyrenoidosa in the breast cancer model.

    Science.gov (United States)

    Kubatka, Peter; Kapinová, Andrea; Kružliak, Peter; Kello, Martin; Výbohová, Desanka; Kajo, Karol; Novák, Miroslav; Chripková, Martina; Adamkov, Marián; Péč, Martin; Mojžiš, Ján; Bojková, Bianka; Kassayová, Monika; Stollárová, Nadežda; Dobrota, Dušan

    2015-04-01

    There has been considerable interest in both clinical and preclinical research about the role of phytochemicals in the reduction of risk for cancer in humans. The aim of this study was to determine the antineoplastic effects of Chlorella pyrenoidosa in experimental breast cancer in vivo and in vitro. In this experiment, the antineoplastic effects of C. pyrenoidosa in the chemoprevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats were evaluated. Chlorella powder was administered through diet at concentrations of 0.3% and 3%. The experiment was terminated 14 wk after carcinogen administration. At autopsy, mammary tumors were removed and prepared for histopathological and immunohistochemical analysis. In vitro cytotoxicity assay, parameters of apoptosis, and proliferation after chlorella treatment in human breast adenocarcinoma (MCF-7) cells were carried out. Basic parameters of experimental carcinogenesis, mechanism of action (biomarkers of apoptosis, proliferation, and angiogenesis), chosen metabolic variables, and side effects after long-term chlorella treatment in animals were assessed. Chlorella at higher concentration suppressed tumor frequency by 61% (P chlorella treatment. In a parallel in vitro study, chlorella significantly decreased survival of MCF-7 cells in a dose-dependent manner. In chlorella-treated MCF-7 cells, a significant increase in cells having sub-G0/G1 DNA content and significant increase of early apoptotic and late apoptotic/necrotic cells after annexin V/PI staining assay were found. Decreases in mitochondrial membrane potential and increasing reactive oxygen species generation were observed in the chlorella-treated MCF-7 cells. This study is the first report on the antineoplastic effects of C. pyrenoidosa in experimental breast cancer in vivo and in vitro. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and invention of boron tracedrugs as innovative future-architectural drugs.

    Science.gov (United States)

    Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji

    2010-09-01

    We describe herein for the first time our medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and boron tracedrugs as newly emerging drug classes. A new area of antineoplastic drugs and treatments has recently focused on neoplastic cells of the tumor environment/microenvironment involving accessory cells. This tumor hypoxic environment is now considered as a major factor that influences not only the response to antineoplastic therapies but also the potential for malignant progression and metastasis. We review our medicinal electronomics bricolage design of hypoxia-targeting drugs, antiangiogenic hypoxic cell radiosensitizers, sugar-hybrid hypoxic cell radiosensitizers, and hypoxia-targeting 10B delivery agents, in which we design drug candidates based on their electronic structures obtained by molecular orbital calculations, not based solely on pharmacophore development. These drugs include an antiangiogenic hypoxic cell radiosensitizer TX-2036, a sugar-hybrid hypoxic cell radiosensitizer TX-2244, new hypoxia-targeting indoleamine 2,3-dioxygenase (IDO) inhibitors, and a hypoxia-targeting BNCT agent, BSH (sodium borocaptate-10B)-hypoxic cytotoxin tirapazamine (TPZ) hybrid drug TX-2100. We then discuss the concept of boron tracedrugs as a new drug class having broad potential in many areas.

  14. 77 FR 38297 - Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare...

    Science.gov (United States)

    2012-06-27

    ... Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings in... and provided a list of drugs that were considered hazardous and required special handling. In 2010... Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012 AGENCY: National Institute for Occupational...

  15. Hyperthermia and chemotherapy agent

    International Nuclear Information System (INIS)

    Roizin-Towle, L.; Hall, E.J.

    1981-01-01

    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

  16. The ribosome inhibiting protein riproximin shows antineoplastic activity in experimental pancreatic cancer liver metastasis.

    Science.gov (United States)

    Murtaja, Ahmed; Eyol, Ergül; Xiaoqi, Jiang; Berger, Martin R; Adwan, Hassan

    2018-02-01

    Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognoses of all malignancy types. To improve the survival of patients with PDAC, the development of novel anticancer agents is warranted. Riproximin (Rpx) is a newly identified plant lectin, which was isolated from Ximenia americana . The ribosome inactivating protein of type II exhibits potent anticancer activity as recently demonstrated. The rat PDAC cell line ASML was used for in vitro and in vivo studies. The antiproliferative effect of Rpx was assessed using an MTT assay. The modulation of proteins involved in apoptosis was evaluated using western blotting. Tumor-bearing nude rats were treated with Rpx, gemcitabine (GEM) or dinaline (DIN) as single agents, or a combination of Rpx with GEM, or DIN. Rpx was administered intraperitoneally at doses of 1.7-5.4 µg/kg, three times/week, GEM was administered intravenously (50 mg/kg/week) and DIN perorally (10 mg/kg, 5 times/week). Rpx inhibited ASML cell proliferation at IC 50 -values of 0.8-172 pM, caused apoptosis and reduced tumor growth significantly by 90% (P<0.05). The survival rate of rats was significantly increased (21.8 days for Rpx treated vs. 17.6 days for control rats; P=0.05). Higher doses of Rpx caused no further reduction in tumor size when compared with the low dose of Rpx or a combination of Rpx with GEM, or DIN. The standard drug GEM alone was less effective compared with Rpx. In addition, DIN was ineffective, and in combination, reduced the activity of Rpx. These results suggest that Rpx has an evident potential for use in pancreatic cancer treatment. Further experiments are required in order to elucidate its affinity for certain cancer cells and to optimize the combination therapy with other antineoplastic agents.

  17. BEL β-trefoil: a novel lectin with antineoplastic properties in king bolete (Boletus edulis) mushrooms.

    Science.gov (United States)

    Bovi, Michele; Cenci, Lucia; Perduca, Massimiliano; Capaldi, Stefano; Carrizo, Maria E; Civiero, Laura; Chiarelli, Laurent R; Galliano, Monica; Monaco, Hugo L

    2013-05-01

    A novel lectin was purified from the fruiting bodies of king bolete mushrooms (Boletus edulis, also called porcino, cep or penny bun). The lectin was structurally characterized i.e its amino acid sequence and three-dimensional structure were determined. The new protein is a homodimer and each protomer folds as β-trefoil domain and therefore we propose the name Boletus edulis lectin (BEL) β-trefoil to distinguish it from the other lectin that has been described in these mushrooms. The lectin has potent anti-proliferative effects on human cancer cells, which confers to it an interesting therapeutic potential as an antineoplastic agent. Several crystal forms of the apoprotein and of complexes with different carbohydrates were studied by X-ray diffraction. The structure of the apoprotein was solved at 1.12 Å resolution. The interaction of the lectin with lactose, galactose, N-acetylgalactosamine and T-antigen disaccharide, Galβ1-3GalNAc, was examined in detail. All the three potential binding sites present in the β-trefoil fold are occupied in at least one crystal form and are described in detail in this paper. No important conformational changes are observed in the lectin when comparing its co-crystals with carbohydrates with those of the ligand-free protein.

  18. Sesquiterpene lactones: Mechanism of antineoplastic activity; relationship of cellular glutathione to cytotoxicity; and disposition

    International Nuclear Information System (INIS)

    Grippo, A.A.

    1987-01-01

    Helenalin, a sesquiterpene lactone, inhibited the growth of P388 lymphocytic and L1210 lymphoid leukemia, and Ehrlich ascites and KB carcinoma cells. The L1210 leukemia cells were most sensitive to the cytotoxic effects of helenalin. Helenalin's antineoplastic effects were due to inhibition of DNA synthesis by suppressing the activities of enzymes involved in this biosynthetic pathway; i.e., IMP dehydrogenase, ribonucleoside diphosphate reductase, thioredoxin complex, GSH disulfide oxidoreductase and DNA polymerase α activities. The relationship of reduced glutathione (GSH) to the cytotoxic effects of helanalin was evaluated. L1210 cells, which were more sensitive to helenalin's toxicity, contained lower basal concentrations of GSH. Helenalin decreased the concentration of reduced glutathione in both L1210 and P388 leukemia cells. Concurrent administration of helanalin with agents reported to raise GSH concentrations did not substantially effect GSH levels, nor were survival times of tumor-bearing mice enhanced. Following intraperitoneal administration of 3 H-plenolin, no radioactive drug and/or metabolite was sequestered in the organs of BDF 1 mice. Approximately 50% of 3 H-plenolin and/or its metabolites were eliminated via urine while lesser amounts of radioactive drug and/or metabolites were eliminated in the feces

  19. Effect of solcoseryl on antitumour action and acute toxicity of some antineoplastic drugs.

    Science.gov (United States)

    Danysz, A; Sołtysiak-Pawluczuk, D; Czyzewska-Szafran, H; Jedrych, A; Jastrzebski, Z

    1991-01-01

    The in vivo effect of Solcoseryl on the antitumour activity and acute toxicity of some antineoplastic drugs was examined. It was found that Solcoseryl does not inhibit the antineoplastic effectiveness of the drugs against transplantable P 388 leukaemia in mice. Studies of the effect of Solcoseryl on acute toxicity of selected antineoplastic drugs in mice revealed that the biostimulator could exert a modifying influence. The prior administration of Solcoseryl significantly decreases the acute toxicity of methotrexate but has no effect on acute toxicity of 5-fluorouracil, increases the acute toxicity of bleomycin and vinblastine and has no effect on acute toxicity of methotrexate and mitoxantron. On the other hand, Solcoseryl administered simultaneously with the antineoplastic drugs increases acute toxicity of 5-fluorouracil, bleomycin and mitoxantron. The protective effect of the biostimulator noted exclusively against acute toxicity of 5-fluorouracil was also observed after multiple administration of this anticancer drug.

  20. Health Care Workers' Knowledge, Perceptions, and Behaviors Regarding Antineoplastic Drugs: Survey From British Columbia, Canada.

    Science.gov (United States)

    Hon, Chun-Yip; Teschke, Kay; Shen, Hui

    2015-01-01

    Although nurses are knowledgeable regarding the risk of exposure to antineoplastic drugs, they often do not adhere with safe work practices. However, the knowledge, perceptions, and behavior of other health care job categories at risk of exposure has yet to be determined. This study aimed to survey a range of health care workers from British Columbia, Canada about their knowledge, perceptions, and behaviors regarding antineoplastic drugs. A self-administered questionnaire was sent to participants querying the degree of contact with antineoplastics, knowledge of risks associated with antineoplastics, perceptions of personal risk, previous training with respect to antineoplastics, and safe work practices. Subjects were recruited from health care facilities in and around Vancouver. Fisher's exact tests were performed to ascertain whether there were differences in responses between job categories. We received responses from 120 participants representing seven different job categories. Pharmacists, pharmacy technicians, and nurses were more knowledgeable regarding risks than other job categories examined (statistically significant difference). Although 80% of respondents were not afraid of working with or near antineoplastics, there were concerns about the suitability of current control measures and practices employed by co-workers. Only half of respondents felt confident that they could handle all situations where there was a potential for exposure. Only one of the perception questions, self-perceived risk of exposure to antineoplastic drugs, differed significantly between job categories. Not all respondents always wore gloves when directly handling antineoplastic drugs. Further, hand hygiene was not regularly practiced after glove usage or after being in an area where antineoplastic drugs are handled. The majority of responses to questions related to safe work practices differed significantly between job categories. Our results suggest that knowledge regarding risks

  1. Near-infrared fluorescence imaging and photodynamic therapy with indocyanine green lactosome has antineoplastic effects for hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Takumi Tsuda

    Full Text Available Anticancer agents and operating procedures have been developed for hepatocellular carcinoma (HCC patients, but their prognosis remains poor. It is necessary to develop novel diagnostic and therapeutic strategies for HCC to improve its prognosis. Lactosome is a core-shell-type polymeric micelle, and enclosing labeling or anticancer agents into this micelle enables drug delivery. In this study, we investigated the diagnostic and therapeutic efficacies of indocyanine green (ICG-loaded lactosome for near-infrared fluorescence (NIF imaging and photodynamic therapy (PDT for HCC.The human HCC cell line HuH-7 was treated with ICG or ICG-lactosome, followed by PDT, and the cell viabilities were measured (in vitro PDT efficiency. For NIF imaging, HuH-7 cells were subcutaneously transplanted into BALB/c nude mice, followed by intravenous administration of ICG or ICG-lactosome. The transplanted animals were treated with PDT, and the antineoplastic effects were analyzed (in vivo PDT efficiency.PDT had toxic effects on HuH-7 cells treated with ICG-lactosome, but not ICG alone. NIF imaging revealed that the fluorescence of tumor areas in ICG-lactosome-treated animals was higher than that of contralateral regions at 24 h after injection and thereafter. PDT exerted immediate and continuous phototoxic effects in the transplanted mice treated with ICG-lactosome.Our results demonstrate that ICG-lactosome accumulated in xenograft tumors, and that PDT had antineoplastic effects on these malignant implants. NIF imaging and PDT with ICG-lactosome could be useful diagnostic and/or therapeutic strategies for HCC.

  2. Antineoplastic Effect of Decoy Oligonucleotide Derived from MGMT Enhancer

    Science.gov (United States)

    Refael, Miri; Zrihan, Daniel; Siegal, Tali; Lavon, Iris

    2014-01-01

    Silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1) within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA) modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN). Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy. PMID:25460932

  3. Antineoplastic effect of decoy oligonucleotide derived from MGMT enhancer.

    Directory of Open Access Journals (Sweden)

    Tamar Canello

    Full Text Available Silencing of O(6-methylguanine-DNA-methyltransferase (MGMT in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1 within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN. Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy.

  4. Antineoplastic chemotherapy and congenital tooth abnormalities in children and adolescents

    Directory of Open Access Journals (Sweden)

    Ewa Krasuska-Sławińska

    2016-12-01

    Full Text Available Aim of the study : Chemotherapeutic treatment in children and adolescents carries a risk of congenital tooth disorders and dentinoma. Study objective is to assess the correlation between tooth abnormalities, early complications of multidrug chemotherapy, and chemotherapeutics used in different antineoplastic therapies in children and adolescents. Material and methods : Enamel defects (developmental defects of enamel index – DDE index and defects in tooth number, size, and structure were assessed clinically and radiologically in 60 patients who underwent chemotherapy on average 4.9 ±3.4 years earlier (PCH, and 60 generally healthy subjects (control group – CG, aged 6–18 years. Höltta’s defect index (DeI was calculated. Medical files provided information on neoplasm type, age at treatment start and chemotherapy duration, chemotherapeutic type and dose, vomiting, and mucositis (CTCAE v4.0. Statistical significance of differences between groups was assessed with the Mann-Whitney U test and the correlation between dental defects and chemotherapy with Spearman’s rank correlation coefficient (significance p ≤ 0.05. Results: Enamel defects, tooth agenesis, microdontia, root resorption, taurodontism, and dentinoma occurred statistically significantly more often in the PCH group. A correlation was established between vincristine use and dose and all types of dental defects; cyclophosphamide, doxorubicin, and isophosphamide and hypodontia; microdontia, root resorption, and enamel defects; etoposide and cisplatin and microdontia, root resorption, and enamel defects; methotrexate root resorption and enamel defects; carboplatin and dentinoma and enamel defects. Mucositis and vomiting promoted root resorption, microdontia, and enamel defects. Conclusions : Dental defects are related to both the use of respective chemotherapeutics, especially vincristine, cyclophosphamide, doxorubicin, and isophosphamide, and to early complications in multidrug

  5. [Blending powdered antineoplastic medicine in disposable ointment container].

    Science.gov (United States)

    Miyazaki, Yasunori; Uchino, Tomonobu; Kagawa, Yoshiyuki

    2014-01-01

    On dispensing powdered antineoplastic medicines, it is important to prevent cross-contamination and environmental exposure. Recently, we developed a method for blending powdered medicine in a disposable ointment container using a planetary centrifugal mixer. The disposable container prevents cross-contamination. In addition, environmental exposure associated with washing the apparatus does not arise because no blending blade is used. In this study, we aimed to confirm the uniformity of the mixture and weight loss of medicine in the blending procedure. We blended colored lactose powder with Leukerin(®) or Mablin(®) powders using the new method and the ordinary pestle and mortar method. Then, the blending state was monitored using image analysis. Blending variables, such as the blending ratio (1:9-9:1), container size (35-125 mL), and charging rate (20-50%) in the container were also investigated under the operational conditions of 500 rpm and 50 s. At a 20% charging rate in a 35 mL container, the blending precision of the mixtures was not influenced by the blending ratio, and was less than 6.08%, indicating homogeneity. With an increase in the charging rate, however, the blending precision decreased. The possible amount of both mixtures rose to about 17 g with a 20% charging rate in a 125 mL container. Furthermore, weight loss of medicines with this method was smaller than that with the pestle and mortar method, suggesting that this method is safer for pharmacists. In conclusion, we have established a precise and safe method for blending powdered medicines in pharmacies.

  6. Antineoplastic agents. 398. Isolation and structure elucidation of cephalostatins 18 and 19.

    Science.gov (United States)

    Pettit, G R; Tan, R; Xu, J; Ichihara, Y; Williams, M D; Boyd, M R

    1998-07-01

    Continued investigation of murine leukemia (P-388) active fractions from the African marine worm Cephalodiscus gilchristi has resulted in the discovery of cephalostatins 18 (1b) and 19 (1c). The structures were determined by interpretation of their highfield (500 MHz) 1H, 13C, and 2D NMR and HRMS. Both of these new methoxy steroidal alkaloids exhibited strong activity against the murine P-388 lymphocytic leukemia cell line (ED50 ca. 10(-3) microg/mL), a mini panel of human cancer cell lines (GI50 <10(-3) microg/mL), and the U.S. National Cancer Institute's 60 human cancer cell line panel (mean panel GI50 ca. 10(-9) M).

  7. [Application of the A.S.I.A. model to activities of manipulation of antineoplastic drugs].

    Science.gov (United States)

    Placentino, R A; Cesarini, L; Sacco, A; Magnavita, N

    2003-01-01

    Risk management of occupational exposure in hospital personnel involved in the preparation and administration of antineoplastic drugs was performed using the A.S.I.A. model. The first step was auditing of compliance. Training of workers specifically addressed the areas of deviation from guidelines. Medical surveillance, and risk assessment, were oriented toward observed deviations.

  8. 78 FR 33097 - NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2014: Proposed...

    Science.gov (United States)

    2013-06-03

    ... Alert: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care... Appendix A which was a list of drugs that were deemed to be hazardous and may require special handling... of these drugs had safe handling recommendations from the manufacturer and NIOSH is following the...

  9. 76 FR 46299 - NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012: Proposed...

    Science.gov (United States)

    2011-08-02

    ...: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings was... which was a list of drugs that were deemed to be hazardous and may require special handling. This list... evaluated for reclassification, two drugs are radio- pharmaceuticals which are covered by specific handling...

  10. Comet assay as a human biomonitoring tool: application in occupational exposure to antineoplastic drugs

    Directory of Open Access Journals (Sweden)

    Carina Ladeira

    2015-05-01

    Occupational exposure to antineoplastic drugs is associated with genotoxic effects, although comet assay analyzed parameters were higher in exposed comparing with controls, were not significant. Also the study of the susceptibility biomarkers did not show statistical significant differences, the small size of our sample hampered the finding of a possible association, let alone a causality relationship.

  11. 77 FR 41190 - Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare...

    Science.gov (United States)

    2012-07-12

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012, Correction AGENCY: National Institute for...

  12. Cost avoidance from dose rounding biologic and cytotoxic antineoplastics.

    Science.gov (United States)

    Vandyke, Thomas H; Athmann, Paul W; Ballmer, Corey M; Kintzel, Polly E

    2017-07-01

    Background To reduce product wastage, our institution allows automatic dose rounding of biologic and cytotoxic anticancer agents. The purpose of this project was to determine the actual annual cost avoidance due to pharmacist-managed automatic dose rounding of anticancer treatments. Methods Financial impact was assessed within the context of our departmental standard work which supports automatic dose rounding of biologic anticancer agents (±10%) and cytotoxic anticancer agents (±5%) to the nearest vial size for body surface area- or weight-based doses. Exclusions to automatic dose rounding include multiple dose vial products, pediatric orders, clinical trial drugs, and parenteral busulfan. The amount of cost avoidance for each rounded dose was determined using the product acquisition cost of the smallest available product amount. Data were collected from anticancer treatment orders for the fiscal year 1 July 2013 to 30 June 2014. Results A total of 6216 doses of anticancer drugs were checked for dose rounding during the period of data collection. Almost $200,000 in product acquisition cost was avoided with pharmacist-managed automatic dose rounding. Six different biologic products accounted for approximately 7% of the total doses analyzed and 78% of the cost avoidance. Fifteen drugs comprised the array of cytotoxic agents rounded. Approximately, 37% and 4% of the biologic and cytotoxic doses were rounded up to the vial size. Conclusion Routine dose rounding of biologic anticancer agents (±10%) and cytotoxic products (±5%) achieved cost avoidance through reduction of drug wastage at our institution.

  13. Antineoplastic Efficacy of Novel Polyamine Analogues in Human Breast Cancer

    Science.gov (United States)

    2006-06-01

    product analogs. J Am Chem Soc 1978; 100: 2551–2553. 39 Burri C, Brun R. Eflornithine for the treatment of human African trypanosomiasis . Parasitol Res...ototoxicity) at high therapeutic doses [29]. Currently, DFMO is the front-line agent in the treatment of African trypanosomiasis and is undergoing...Polyamine Analogues in Human Breast Cancer. PRINCIPAL INVESTIGATOR: Yi Huang, M.D., Ph.D. CONTRACTING ORGANIZATION: Johns

  14. Integrative review of factors related to the nursing diagnosis nausea during antineoplastic chemotherapy.

    Science.gov (United States)

    Moysés, Aline Maria Bonini; Durant, Lais Corsino; Almeida, Ana Maria de; Gozzo, Thais de Oliveira

    2016-10-10

    to identify factors related to the nursing diagnosis nausea among cancer patients undergoing chemotherapy. integrative review conducted in four electronic databases (PUBMED, EMBASE, CINAHL and LILACS) using the key words: neoplasia, antineoplastic agents and nausea. only 30 out of 1,258 papers identified met the inclusion criteria. The most frequent related factors were: being younger than 50 years old, motion sickness, being a woman, emetogenic potential of the chemotherapy, anxiety, conditioned stimulus, and expecting nausea after treatment. this review's findings, coupled with the incidence of nausea among cancer patients undergoing chemotherapy, reveal an important difference between evidence found and that used by NANDA International, Inc. Even though it provides an appropriate definition of related factors, it does not mention chemotherapy, despite the various studies addressing the topic using different designs and presenting various objectives and outcomes. identificar os fatores relacionados ao diagnóstico de enfermagem náusea entre pacientes oncológicos durante o tratamento quimioterápico. revisão integrativa de quatro bases eletrônicas de dados (PUBMED, EMBASE, CINAHL e LILACS) com as palavras-chaves neoplasia, agentes antineoplásicos e náusea. dos 1258 artigos identificados, somente 30 atenderam aos critérios de inclusão. Os fatores relacionados mais frequentes foram: idade abaixo de 50 anos, doença do movimento, sexo feminino, potencial emético do quimioterápico, ansiedade, estímulo condicionado e expectativa de náuseas depois do tratamento. diante dos resultados encontrados e da incidência de náusea entre os pacientes oncológicos em tratamento quimioterápico, observa-se diferença importante entre as evidências encontradas e as utilizadas pela NANDA International, Inc. Apesar da definição estar adequada entre os fatores relacionados, não há menção à quimioterapia mesmo com inúmeros estudos, com diferentes delineamentos

  15. A Potential Adjuvant Agent of Chemotherapy: Sepia Ink Polysaccharides

    Directory of Open Access Journals (Sweden)

    Fangping Li

    2018-03-01

    Full Text Available Sepia ink polysaccharide (SIP isolated from squid and cuttlefish ink is a kind of acid mucopolysaccharide that has been identified in three types of primary structures from squid (Illex argentinus and Ommastrephes bartrami, cuttlefish Sepiella maindroni, and cuttlefish Sepia esculenta ink. Although SIP has been proved to be multifaceted, most of the reported evidence has illuminated its chemopreventive and antineoplastic activities. As a natural product playing a role in cancer treatment, SIP may be used as chemotherapeutic ancillary agent or functional food. Based on the current findings on SIP, we have summarized four topics in this review, including: chemopreventive, antineoplastic, chemosensitive, and procoagulant and anticoagulant activities, which are correlative closely with the actions of anticancer agents on cancer patients, such as anticancer, toxicity and thrombogenesis, with the latter two actions being common causes of death in cancer cases exposed to chemotherapeutic agents.

  16. Dental root agenesis following radiation and antineoplastic therapy: A Case Report.

    Science.gov (United States)

    Hafiz, Abdul; Mufeed, Abdulla; Bharadwaj, Punit; Rao, Dinesh

    2016-01-01

    The survival rates of patients suffering from various childhood neoplasms have improved dramatically with the advent of chemo-radiation therapy. The harmful effects of chemo-radiation therapy in the oro-facial region such as root agenesis, short roots, impaired amelogenesis, dentinogenesis, radiation caries, and other soft tissue pathologies are well recognized. In spite of these documented risks, the antineoplastic treatment modalities continue to serve the patient for overall improvement in survival and quality of life. However, a thorough understanding of the growth and development process and its relation with the complex antineoplastic treatment is very important for all clinicians. Such awareness could significantly improve the status of patients in the posttreatment period with the implementation of proper preventive and interceptive measures. This article intends to document a case of root agenesis that developed secondary to chemo-radiation therapy in a 12-year-old girl.

  17. Dental root agenesis following radiation and antineoplastic therapy: A Case Report

    Directory of Open Access Journals (Sweden)

    Abdul Hafiz

    2016-01-01

    Full Text Available The survival rates of patients suffering from various childhood neoplasms have improved dramatically with the advent of chemo-radiation therapy. The harmful effects of chemo-radiation therapy in the oro-facial region such as root agenesis, short roots, impaired amelogenesis, dentinogenesis, radiation caries, and other soft tissue pathologies are well recognized. In spite of these documented risks, the antineoplastic treatment modalities continue to serve the patient for overall improvement in survival and quality of life. However, a thorough understanding of the growth and development process and its relation with the complex antineoplastic treatment is very important for all clinicians. Such awareness could significantly improve the status of patients in the posttreatment period with the implementation of proper preventive and interceptive measures. This article intends to document a case of root agenesis that developed secondary to chemo-radiation therapy in a 12-year-old girl.

  18. Andrographolide: A New Plant-Derived Antineoplastic Entity on Horizon

    Directory of Open Access Journals (Sweden)

    Astha Varma

    2011-01-01

    Full Text Available Plant-derived natural products occupy an important position in the area of cancer chemotherapy. Molecules such as vincristine, vinblastine, paclitaxel, camptothecin derivatives, epipodophyllotoxin, and so forth, are invaluable contributions of nature to modern medicine. However, the quest to find out novel therapeutic compounds for cancer treatment and management is a never-ending venture; and diverse plant species are persistently being studied for identification of prospective anticancer agents. In this regard, Andrographis paniculata Nees, a well-known plant of Indian and Chinese traditional system of medicines, has drawn attention of researchers in recent times. Andrographolide, the principal bioactive chemical constituent of the plant has shown credible anticancer potential in various investigations around the globe. In vitro studies demonstrate the capability of the compound of inducing cell-cycle arrest and apoptosis in a variety of cancer cells at different concentrations. Andrographolide also shows potent immunomodulatory and anti-angiogenic activities in tumorous tissues. Synthetic analogues of the compound have also been created and analyzed, which have also shown similar activities. Although it is too early to predict its future in cancer chemotherapy, the prologue strongly recommends further research on this molecule to assess its potential as a prospective anticancer agent.

  19. Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde

    Czech Academy of Sciences Publication Activity Database

    Mušák, L.; Šmerhovský, Z.; Halásová, E.; Osina, O.; Letková, L.; Vodičková, Ludmila; Poláková, Veronika; Buchancová, J.; Hemminki, K.; Vodička, Pavel

    2013-01-01

    Roč. 39, č. 6 (2013), s. 618-630 ISSN 0355-3140 Grant - others:MŠVV(SK) 26220220111; UK(SK) 1/0576/10 VEGA; MZd(SK) 2007/48-UK-13; GA MŠMT(CZ) Prvouk-P27/LF1/1 Institutional support: RVO:68378041 Keywords : anesthesiologist * antineoplastic drug * chromosomal aberration Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.095, year: 2013

  20. Anti-inflammatory drugs and uterine cervical cancer cells: Antineoplastic effect of meclofenamic acid

    OpenAIRE

    SORIANO-HERNANDEZ, ALEJANDRO D.; MADRIGAL-PÉREZ, DANIELA; GALVAN-SALAZAR, HECTOR R.; MARTINEZ-FIERRO, MARGARITA L.; VALDEZ-VELAZQUEZ, LAURA L.; ESPINOZA-GÓMEZ, FRANCISCO; VAZQUEZ-VUELVAS, OSCAR F.; OLMEDO-BUENROSTRO, BERTHA A.; GUZMAN-ESQUIVEL, JOSE; RODRIGUEZ-SANCHEZ, IRAM P.; LARA-ESQUEDA, AGUSTIN; MONTES-GALINDO, DANIEL A.; DELGADO-ENCISO, IVAN

    2015-01-01

    Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. Inflammation has been identified as an important component of this neoplasia; in this context, anti-inflammatory drugs represent possible prophylactic and/or therapeutic alternatives that require further investigation. Anti-inflammatory drugs are common and each one may exhibit a different antineoplastic effect. As a result, the present study investigated different anti-inflammatory models of UCC ...

  1. The caries experience and dentistry following evaluation of children submitted to antineoplastic therapy

    OpenAIRE

    Hanna, Leila Maués Oliveira; de Araújo, Rodolfo José Gomes; Vilarino, Ewerson Fernando Almeida; Mayhew, Andressa Soraia Barros

    2016-01-01

    Aim: To evaluate the caries experience and the dentistry following of children submitted to antineoplastic therapy of a reference Hospital to this type of treatment in Para state, Brazil.Material and Methods: The sample consisted of 46 children. It was included children in the ages of 2 to 12 years diagnosed with cancer that would be submitted to chemotherapy treatment. The evaluation was performed before the chemotherapy treatment and consisted of anamnesis and oral clinical examination. In ...

  2. Enhanced Topical and Transdermal Delivery of Antineoplastic and Antiviral Acyclic Nucleoside Phosphonate cPr-PMEDAP

    Czech Academy of Sciences Publication Activity Database

    Vávrová, K.; Kovaříková, P.; Školová, B.; Líbalová, M.; Roh, J.; Čáp, R.; Holý, Antonín; Hrabálek, A.

    2011-01-01

    Roč. 28, č. 12 (2011), s. 3105-3115 ISSN 0724-8741 R&D Projects: GA MŠk 1M0508 Grant - others:GA ČR(CZ) GAP207/11/0365 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * antiviral s * antineoplastics * permeation enhancer * topical skin application * transdermal delivery Subject RIV: CC - Organic Chemistry Impact factor: 4.093, year: 2011

  3. Toxicity classification and evaluation of four pharmaceuticals classes: antibiotics, antineoplastics, cardiovascular, and sex hormones

    International Nuclear Information System (INIS)

    Sanderson, Hans; Brain, Richard A.; Johnson, David J.; Wilson, Christian J.; Solomon, Keith R.

    2004-01-01

    Four different classes of environmental concern are quantitatively and qualitatively assessed for environmental hazards; antibiotics (n = 226), antineoplastics (n = 81), cardiovascular (n = 272), and sex hormones (n 92). These along with an ECOSAR scan of all pharmaceuticals (n = 2848) were then classified according to the OECD aquatic toxicity classification system. The predicted species susceptibility is: daphnid > fish > algae, and the predicted rank order of relative toxicity: sex hormones > cardiovascular antibiotics > antineoplastics (Table 1). Generally, a relatively large proportion (1/3) of all pharmaceuticals are potentially very toxic to aquatic organisms (Table 2). The qualitative risk assessment ranking relative to probability and potential severity for human and environmental health effects is: antibiotics > sex hormones > cardiovascular > antineoplastics. (Q)SARs and pharmacodynamic information should be used to prioritize and steer experimental risk assessments of pharmaceuticals, and potentially, also be used in new drug discovery optimizing efficacy and in minimising environmental hazards of new products. Nuclear receptors are relatively well conserved in evolution. Currently, antibacterial resistance represents the most significant human health hazard, and potentially the largest non-target organism hazard is sex hormones acting as endocrine modulators in wildlife. Data for the individual compounds are accessible via http://www.uoguelph.ca/~hsander/

  4. Evaluation of respiration of mitochondria in cancer cells exposed to mitochondria-targeted agents.

    Czech Academy of Sciences Publication Activity Database

    Klučková, Katarína; Dong, L. F.; Bajziková, Martina; Rohlena, Jakub; Neužil, Jiří

    2015-01-01

    Roč. 1265, 07 Oct 2015 (2015), s. 181-194 ISSN 1940-6029 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Animals * Antineoplastic Agents * drug effects * *pharmacology Subject RIV: EB - Genetics ; Molecular Biology

  5. Extraction and Isolation of Antineoplastic Pristimerin from Mortonia greggii (Celastraceae).

    Science.gov (United States)

    Mejia-Manzano, Luis Alberto; Barba-Dávila, Bertha A; Gutierrez-Uribe, Janet A; Escalante-Vázquez, Edgardo J; Serna-Saldivar, Sergio O

    2015-11-01

    The aim of this research was to identify, extract and isolate pristimerin in leaves, stems and roots of the Mexican plant Mortonia greggii (Celastraceae). The principal objective was to determine the best laboratory experimental conditions for the extraction and isolation of this powerful natural anticancer agent from the root tissue. Six experimental factors in solid-liquid pristimerin extraction were analyzed: solvent systems, number of extractions, ratio of plant weight (g)/solvent volume (mL) used, time of extraction, temperature and agitation. A mathematical model was generated for pristimerin purity and yield. Ethanol, first extraction, 0.5 ratio of plant weight/solvent volume (g/mL), 0.5 h, 200 rpm and 49.7°C were optimal conditions for the extraction of this phytochemical. The degree of purification of pristimerin root extract was studied by size-exclusion chromatography (SEC) using Sephadex LH-20 reaching fractions with purification indexes (PI) greater than 2 and recoveries of 28.3%. When fractions with purification indices higher than 1 and less than 2 were accumulated, the recovery of pristimerin increased by about 73.6%. By combining the optimum extracts and SEC purification protocols, an enriched fraction containing 245.6 mg pristimerin was obtained from 100 g of root bark, representing about 14.4%, w/w, pristimerin from the total solids presented in the fraction.

  6. Anti-neoplastic drugs increase caveolin-1-dependent migration, invasion and metastasis of cancer cells.

    Science.gov (United States)

    Díaz-Valdivia, Natalia I; Calderón, Claudia C; Díaz, Jorge E; Lobos-González, Lorena; Sepulveda, Hugo; Ortíz, Rina J; Martinez, Samuel; Silva, Veronica; Maldonado, Horacio J; Silva, Patricio; Wehinger, Sergio; Burzio, Verónica A; Torres, Vicente A; Montecino, Martín; Leyton, Lisette; Quest, Andrew F G

    2017-12-19

    Expression of the scaffolding protein Caveolin-1 (CAV1) enhances migration and invasion of metastatic cancer cells. Yet, CAV1 also functions as a tumor suppressor in early stages of cancer, where expression is suppressed by epigenetic mechanisms. Thus, we sought to identify stimuli/mechanisms that revert epigenetic CAV1 silencing in cancer cells and evaluate how this affects their metastatic potential. We reasoned that restricted tissue availability of anti-neoplastic drugs during chemotherapy might expose cancer cells to sub-therapeutic concentrations, which activate signaling pathways and the expression of CAV1 to favor the acquisition of more aggressive traits. Here, we used in vitro [2D, invasion] and in vivo (metastasis) assays, as well as genetic and biochemical approaches to address this question. Colon and breast cancer cells were identified where CAV1 levels were low due to epigenetic suppression and could be reverted by treatment with the methyltransferase inhibitor 5'-azacytidine. Exposure of these cells to anti-neoplastic drugs for short periods of time (24-48 h) increased CAV1 expression through ROS production and MEK/ERK activation. In colon cancer cells, increased CAV1 expression enhanced migration and invasion in vitro via pathways requiring Src-family kinases, as well as Rac-1 activity. Finally, elevated CAV1 expression in colon cancer cells following exposure in vitro to sub-cytotoxic drug concentrations increased their metastatic potential in vivo . Therefore exposure of cancer cells to anti-neoplastic drugs at non-lethal drug concentrations induces signaling events and changes in transcription that favor CAV1-dependent migration, invasion and metastasis. Importantly, this may occur in the absence of selection for drug-resistance.

  7. New approaches to wipe sampling methods for antineoplastic and other hazardous drugs in healthcare settings

    Science.gov (United States)

    Connor, Thomas H.; Smith, Jerome P.

    2017-01-01

    Purpose At the present time, the method of choice to determine surface contamination of the workplace with antineoplastic and other hazardous drugs is surface wipe sampling and subsequent sample analysis with a variety of analytical techniques. The purpose of this article is to review current methodology for determining the level of surface contamination with hazardous drugs in healthcare settings and to discuss recent advances in this area. In addition it will provide some guidance for conducting surface wipe sampling and sample analysis for these drugs in healthcare settings. Methods Published studies on the use of wipe sampling to measure hazardous drugs on surfaces in healthcare settings drugs were reviewed. These studies include the use of well-documented chromatographic techniques for sample analysis in addition to newly evolving technology that provides rapid analysis of specific antineoplastic Results Methodology for the analysis of surface wipe samples for hazardous drugs are reviewed, including the purposes, technical factors, sampling strategy, materials required, and limitations. The use of lateral flow immunoassay (LFIA) and fluorescence covalent microbead immunosorbent assay (FCMIA) for surface wipe sample evaluation is also discussed. Conclusions Current recommendations are that all healthcare settings where antineoplastic and other hazardous drugs are handled include surface wipe sampling as part of a comprehensive hazardous drug-safe handling program. Surface wipe sampling may be used as a method to characterize potential occupational dermal exposure risk and to evaluate the effectiveness of implemented controls and the overall safety program. New technology, although currently limited in scope, may make wipe sampling for hazardous drugs more routine, less costly, and provide a shorter response time than classical analytical techniques now in use. PMID:28459100

  8. Implementation of a robot for the preparation of antineoplastic drugs in the Pharmacy Service

    Directory of Open Access Journals (Sweden)

    María de la Paz Pacheco Ramos

    2015-01-01

    Full Text Available Objective: To describe the implementation of a robot for the preparation of antineoplastic drugs in the Pharmacy Service and to be able to analyze the added value to pharmacotherapy. Methods: The implementation was carried out in June 2012 at a tertiary level Hospital, taking place in two periods: 1- test period with the installation of the robot, with technical configuration of the equipment and validation of 29 active ingredients and the integration of electronic prescribing software with the robot application (9 months. 2- Usage period (22 months. On the other hand, training was given to pharmacists and nurses. The robot uses image recognition, barcode identification and gravimetric controls for proper operation. These checks provide information about the error ratio in the preparation, with a margin of ± 10%, which after a pilot study was restricted to a range of ±4%. The robot was programmed to recognize bags, infusion pumps, syringes and vials. The added value was assessed for 31 months by identifying preparation´s errors. Results: 11,865 preparations were made by the robot, which meant approximately 40% of all antineoplastic prepared from 29 different active ingredients. 1.12% (n=133 of the errors were identified by the robot and therefore didn´t reach the patient (negative desviation - 4%. These errors were corrected manually. Conclusion: The implementation of a robot in the preparation of antineoplastic drugs allows to identify errors therefore preventing them to arrive to the patient. This promotes safety and quality of the process, reducing the exposure to cytotoxic drugs from the manipulator

  9. Pharmaceutical validation as a process of improving the quality of antineoplastic treatment.

    Science.gov (United States)

    Serrano Fabiá, Amparo; Cavero Rodrigo, Elisa; Albert Marí, Asunción; Almenar Cubells, Daniel; Jiménez Torres, N Victor

    2005-06-01

    To quantify the improvement added by standardization of pharmaceutical validation (PV) of antineoplastic treatment to the processes of prescription and preparation of the pharmacotherapeutic sequence, in terms of prevention and reduction of medication errors (ME). Prospective cohort study during two years (from 2001-2002) for oncohaematologic patients (inpatients and outpatients) that compared the percentage of medication errors detected and resolved and the number of medication errors with potential clinical significance (severity value >or=4) intercepted during PV in both years. During the PV processes, 202 ME were identified and resolved, which is the equivalent of 16.88 ME/1,000 patient-days. In 2001 14.08 ME/1,000 patient-days were detected and 19.83 ME/1,000 patient-days in 2002. This means that the effectiveness of the identification method increased by 41%. The number of ME intercepted with clinical significance (severity value >or=4) increased in a statistically significant manner by 2.18 times in 2002. This study shows that the standardization of PV is an effective method of improving the quality of antineoplastic treatment use, by increasing the ability to intercept ME.

  10. Occupational Exposure to Antineoplastic Drugs: Identification of Job Categories Potentially Exposed throughout the Hospital Medication System.

    Science.gov (United States)

    Hon, Chun-Yip; Teschke, Kay; Chua, Prescillia; Venners, Scott; Nakashima, Lynne

    2011-09-01

    Studies examining healthcare workers' exposure to antineoplastic drugs have focused on the drug preparation or drug administration areas. However, such an approach has probably underestimated the overall exposure risk as the drugs need to be delivered to the facility, transported internally and then disposed. The objective of this study is to determine whether drug contamination occurs throughout a facility and, simultaneously, to identify those job categories that are potentially exposed. This was a multi-site study based in Vancouver, British Columbia. Interviews were conducted to determine the departments where the drugs travel. Subsequent site observations were performed to ascertain those surfaces which frequently came into contact with antineoplastic drugs and to determine the job categories which are likely to contact these surfaces. Wipe samples were collected to quantify surface contamination. Surface contamination was found in all six stages of the hospital medication system. Job categories consistently found to be at risk of exposure were nurses, pharmacists, pharmacy technicians, and pharmacy receivers. Up to 11 job categories per site may be at risk of exposure at some point during the hospital medication system. We found drug contamination on select surfaces at every stage of the medication system, which indicates the existence of an exposure potential throughout the facility. Our results suggest that a broader range of workers are potentially exposed than has been previously examined. These results will allow us to develop a more inclusive exposure assessment encompassing all healthcare workers that are at risk throughout the hospital medication system.

  11. ESMO International Consortium Study on the availability, out-of-pocket costs and accessibility of antineoplastic medicines in countries outside of Europe.

    Science.gov (United States)

    Cherny, N I; Sullivan, R; Torode, J; Saar, M; Eniu, A

    2017-11-01

    The availability and affordability of safe, effective, high-quality, affordable anticancer therapies are a core requirement for effective national cancer control plans. Online survey based on a previously validated approach. The aims of the study were to evaluate (i) the availability on national formulary of licensed antineoplastic medicines across the globe, (ii) patient out-of-pocket costs for the medications, (iii) the actual availability of the medication for a patient with a valid prescription, (iv) information relating to possible factors adversely impacting the availability of antineoplastic agents and (v) the impact of the country's level of economic development on these parameters. A total of 304 field reporters from 97 countries were invited to participate. The preliminary set of data was posted on the ESMO website for open peer review and amendments have been incorporated into the final report. Surveys were submitted by 135 reporters from 63 countries and additional peer-review data were submitted by 54 reporters from 19 countries. There are substantial differences in the formulary availability, out-of-pocket costs and actual availability for many anticancer medicines. The most substantial issues are in lower-middle- and low-income countries. Even among medications on the WHO Model List of Essential Medicines (EML) the discrepancies are profound and these relate to high out-of-pocket costs (in low-middle-income countries 32.0% of EML medicines are available only at full cost and 5.2% are not available at all, and for low-income countries, the corresponding figures are even worse at 57.7% and 8.3%, respectively). There is wide global variation in formulary availability, out-of-pocket expenditures and actual availability for most licensed anticancer medicines. Low- and low-middle-income countries have significant lack of availability and high out-of-pocket expenditures for cancer medicines on the WHO EML, with much less availability of new, more expensive

  12. Peroxisome Proliferator-Activated Receptors (PPARs as Potential Inducers of Antineoplastic Effects in CNS Tumors

    Directory of Open Access Journals (Sweden)

    Lars Tatenhorst

    2008-01-01

    Full Text Available The peroxisome proliferator-activated receptors (PPARs are ligand-inducible transcription factors which belong to the superfamily of nuclear hormone receptors. In recent years it turned out that natural as well as synthetic PPAR agonists exhibit profound antineoplastic as well as redifferentiation effects in tumors of the central nervous system (CNS. The molecular understanding of the underlying mechanisms is still emerging, with partially controverse findings reported by a number of studies dealing with the influence of PPARs on treatment of tumor cells in vitro. Remarkably, studies examining the effects of these drugs in vivo are just beginning to emerge. However, the agonists of PPARs, in particular the thiazolidinediones, seem to be promising candidates for new approaches in human CNS tumor therapy.

  13. Nursing diagnoses in adult/elderly patients undergoing outpatient antineoplastic chemotherapy: a review.

    Science.gov (United States)

    Jomar, Rafael Tavares; Gomes, Rebeca Anselmo Furtado; Leite, Dayana Carvalho; Gomes, Helena Ferraz; Peres, Ellen Marcia; Junior, Eugenio Fuentes Perez

    2017-01-01

    To search in the scientific literature for nursing diagnoses identified in adult/elderly patients undergoing antineoplastic chemotherapy in an outpatient setting. Review of studies published in Portuguese, English, or Spanish which were searched in five electronic databases in March 2016, using the descriptors nursing process, nursing diagnosis, neoplasms, drug therapy and hospital outpatient clinic. In the four studies selected for review, 40 nursing diagnoses were identified, namely unbalanced nutrition, less than body requirements, risk of deficient fluid volume, diarrhoea, fatigue, impaired home maintenance, deficient knowledge, disturbed body image, interrupted family processes, ineffective sexuality pattern, anxiety, powerlessness, fear, readiness for enhanced religiosity, risk of infection, impaired dentition, risk of impaired skin integrity, acute pain, and nausea. The nursing diagnoses identified can support the selection of interventions and the creation of nursing guidelines in outpatient oncology services.

  14. Robotic system for i.v. antineoplastic drug preparation: description and preliminary evaluation under simulated conditions.

    Science.gov (United States)

    Cote, D D; Torchia, M G

    1989-11-01

    A robotic system for preparing doses of i.v. antineoplastic drugs is described, and measurements made with the system are compared for accuracy and reproducibility with those made by pharmacists and technicians. System hardware consists of a robotic arm, a 16-bit microcomputer, a bar-code reader, a voice synthesizer, and an electronic balance. The software includes a menu-driven main program, executable files for each robotic activity, and an interface to allow control to pass between the program and the files. The program has routines for matching the software to the hardware; for entering information about the patient, the name of the drug ordered, and the dose; for checking the dose; for selecting the number and size of the vials to be used; for specifying the manipulations of the robotic arm; for printing labels; and for maintaining records. The robot fills an order by getting and placing a vial, inserting a needle into it and withdrawing the drug, weighing the vial, agitating the container to dissolve its contents, reading a bar code, placing a syringe in a syringe manipulator, and getting an i.v. container and injecting the drug into it. Detection of any errors by a series of self-checks arrests execution of an order. No significant differences in accuracy and precision were found between the robotic system and humans performing the same tasks under simulated conditions. The robotic system required less time than humans and eliminated the possibility of direct human contact with the i.v. admixture. Under simulated conditions, a robotic system developed to assist in the preparation of i.v. antineoplastic drugs was as accurate as a manual system and was more time efficient.

  15. [Antineoplastic treatment impact on nutritional status in patients with breast cancer].

    Science.gov (United States)

    Monroy Cisneros, Karina; Astiazarán García, Humberto; Esparza Romero, Julián; Guevara Torres, Alfonso Genaro; Valencia Juillerat, Mauro E; Méndez Estrada, Rosa Olivia; Tortoledo Ortiz, Orlando; Pacheco Moreno, Bertha Isabel

    2014-10-01

    Breast cancer is the most commonly diagnosed malignancy in women in Mexico and also has the highest mortality. Although treatment has improved significantly, it can affect the nutritional status of the recipients. The aim of this study was to assess the impact of the initial phase of antineoplastic therapy on the nutritional status in patients with breast cancer. Forty subjects with primary diagnosed of invasive breast cancer were studied in a before and after intervention (six month apart) using a quasi-experimental design. Basal and six month after intervention measurements included were anthropometry, body composition by dual X-ray absorptiometry (DEXA), diet by 24-hour recall and food frequency questionnaire, as well as serum -carotene and retinol. The therapy effect was analyzed using repeated measurements mixed linear regression. Lean tissue decreased after the studied period (p=0.032). Addicionally, there was an interaction between weight, BMI and body fat parameters with menopausal status, increasing in these variables due to therapy only premenopausal patients (p=0.005, 0.006 and 0.001, respectively). Decreased serum retinol (p=0.049) despite the improvement in -carotene status (p=0.03). In general there was an increase the consumption of vegetables food products whilst a decrease in animal foods. The breast cancer antineoplastic treatment had a negative effect on weight and body fat, especially in young women. Although there were some positive dietary changes, vegetables consumption remained insufficient, which was also reflected in serum biomarkers. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  16. Antineoplastic-related cardiotoxicity, morphofunctional aspects in a murine model: contribution of the new tool 2D-speckle tracking

    Directory of Open Access Journals (Sweden)

    Coppola C

    2016-11-01

    Full Text Available Carmela Coppola,1 Gennaro Riccio,1 Antonio Barbieri,2 Maria Gaia Monti,3 Giovanna Piscopo,1 Domenica Rea,2 Claudio Arra,2 Carlo Maurea,1 Claudia De Lorenzo,4,5 Nicola Maurea1 1Division of Cardiology, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”, IRCCS, Naples, Italy; 2Animal Facility Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”, IRCCS, Naples, Italy; 3Department of Translational Medical Sciences, University Federico II, Naples, Italy; 4Department of Molecular Medicine and Medical Biotechnology, University Federico II, Naples, Italy; 5CEINGE Biotecnologie Avanzate, Naples, Italy Objective: Considering that global left ventricular systolic radial strain is a sensitive technique for the early detection of left ventricular dysfunction due to antineoplastics and the analysis of segmental myocardial contractility, we evaluated this technique for early detection of trastuzumab-related cardiotoxicity by comparing it with cardiac structural damage.Methods: Groups of six mice were injected with trastuzumab or doxorubicin, used either as single agents or in combination. Cardiac function was evaluated by transthoracic echocardiography measurements before and after treatment for 2 or 7 days, by using a Vevo 2100 high-resolution imaging system. After echocardiography, mice were euthanized, and hearts were processed for histological evaluations, such as cardiac fibrosis, apoptosis, capillary density, and inflammatory response.Results: Trastuzumab-related cardiotoxicity was detected early by 2D strain imaging. Radial strain was reduced after 2 days in mice treated with trastuzumab alone (21.2%±8.0% vs 40.5%±4.8% sham; P<0.01. Similarly, trastuzumab was found to induce apoptosis, capillary density reduction, and inflammatory response in cardiac tissue after 2 days of treatment, in a fashion similar to doxorubicin. On the contrary, fractional

  17. [A 26-week oral repeated dose toxicity study of a new antineoplastic agent S-1 in rats].

    Science.gov (United States)

    Hakoi, K; Hayashi, T; Ohmae, S; Besshi, K

    1996-11-01

    S-1 was administered to male and female rats by gavage for 26 weeks at 0, 1, 5, and 10 mg/kg/day followed by 5-week recovery period for the control, 5, and 10 mg/kg/day groups. Treatment at 5 or 10 mg/kg/day in both sexes produced keratosis of the tail, palm or sole. Weight gain and average food consumption were lowered by the treatment. Urine showed increases in protein and epithelial or white blood cells and a decrease in specific gravity. The blood showed decreases in red blood cell count, hemoglobin, and hematocrit as well as increases in MCH, platelet count, fibrinogen, and MCV. A/G ratio, albumin, and chloride were decreased while total cholesterol, free cholesterol, triglycerides, and phospholipids were increased. Histopathologically, treatment-related changes at 5 and 10 mg/kg/day were observed mainly in the lymphoid tissues and kidneys. Those changes included atrophy in the lymphoid tissues and chronic nephropathy-like changes in the kidneys. Other changes in the 10 mg/ kg/day group, included acanthosis and/or inflammation in the epidermis of the tail, sole, or palm, degeneration and disarrangement of ameloblasts, and atrophy of the testes. In a recovery study, although some changes in the sole, palm, or tail, and the kidneys remained, they were less extensive than they had been at the end of the treatment period. Based upon these observations, the non-toxic dose level was estimated to be 1 mg/kg/day (2.3 mg/kg/day, as the summed doses of tegafur, CDHP, and Oxo) in both sexes.

  18. Validated Spectrophotometric Methods for the Determination of Mycophenolate: An Anti-Neoplastic Agent in Bulk and Pharmaceutical Dosage Forms

    Directory of Open Access Journals (Sweden)

    A. Narendra

    2013-01-01

    Full Text Available Three simple, precise and cost-effective spectrophotometric methods have been developed for the determination of Mycophenolate in bulk and its pharmaceutical formulations. Mycophenolate shows max at 250.0 nm in zero-derivative spectrum (method A, 258.0 nm in first-derivative spectrum (method B and method C is based on the calculation of area under curve (AUC for analysis of Mycophenolate in the wavelength range of 240.0–260.0 nm. The drug follows the Beer-Lambert's law in the concentration range of 1.0–150.0 μg/mL for all the methods. The methods were validated by following the analytical performance parameters suggested by the International Conference on Harmonization. All validation parameters were within the acceptable range. The developed methods were successfully applied to estimate the amount of Mycophenolate in bulk and pharmaceutical dosage forms.

  19. Formation and rejoining of deoxyribonucleic acid double-strand breaks induced in isolated cell nuclei by antineoplastic intercalating agents.

    Science.gov (United States)

    Pommier, Y; Schwartz, R E; Kohn, K W; Zwelling, L A

    1984-07-03

    The biochemical characteristics of the formation and disappearance of intercalator-induced DNA double-strand breaks (DSB) were studied in nuclei from mouse leukemia L1210 cells by using filter elution methodology [Bradley, M. O., & Kohn, K.W. (1979) Nucleic Acids Res. 7, 793-804]. The three intercalators used were 4'-(9-acridinylamino)-methanesulfon-m-anisidide (m-AMSA), 5-iminodaunorubicin (5-ID), and ellipticine. These compounds differ in that they produced predominantly DNA single-strand breaks (SSB) (m-AMSA) or predominantly DNA double-strand breaks (ellipticine) or a mixture of both SSB and DSB (5-ID) in whole cells. In isolated nuclei, each intercalator produced DSB at a frequency comparable to that which is produced in whole cells. Moreover, these DNA breaks reversed within 30 min after drug removal. It thus appeared that neither ATP nor other nucleotides were necessary for intercalator-dependent DNA nicking-closing reactions. The formation of the intercalator-induced DSB was reduced at ice temperature. Break formation was also reduced in the absence of magnesium, at a pH above 6.4 and at NaCl concentrations above 200 mM. In the presence of ATP and ATP analogues, the intercalator-induced cleavage was enhanced. These results suggest that the intercalator-induced DSB are enzymatically mediated and that the enzymes involved in these reactions can catalyze DNA double-strand cleavage and rejoining in the absence of ATP, although the occupancy of an ATP binding site might convert the enzyme to a form more reactive to intercalators. Three inhibitors of DNA topoisomerase II--novobiocin, nalidixic acid, and norfloxacin--reduced the formation of DNA strand breaks.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. The comet assay as a rapid test in biomonitoring occupational exposure to DNA-damaging agents and effect of confounding factors

    DEFF Research Database (Denmark)

    Møller, P; Knudsen, Lisbeth E.; Loft, S

    2000-01-01

    of occupational exposures encompassing styrene, vinyl chloride, 1,3-butadiene, pesticides, hair dyes, antineoplastic agents, organic solvents, sewage and waste materials, wood dust, and ionizing radiation. Eleven of the occupational studies were positive, whereas seven were negative. Notably, the negative studies...

  1. Histological vis-a-vis biochemical assessment on the toxic level and antineoplastic efficacy of a synthetic drug Pt-ATP on experimental animal models.

    Science.gov (United States)

    Pal, Shipra; Sadhu, Arpita Sengupta; Patra, Swarup; Mukherjea, Kalyan K

    2008-11-12

    Cisplatin, a platinum based anticancer drug has played a vital role in the treatment of cancers by chemical agents, but in view of the serious toxicity including nephrotoxicity of cisplatin, various other platinum based drugs have been synthesized and screened to overcome its toxicity. A Pt-ATP compound was prepared in our laboratory hoping to have reduced or no toxicity along with the potentiality of reducing neoplasm growth. A Pt-ATP compound was prepared. It was first screened for its antineoplastic efficacy. Confirming that, subsequent experiments were carried on to test its toxicity on animals, viz. Albino Swiss mice. The animals were randomly divided into four sets--Set I: Erhlich Ascites Carcinoma (EAC) challenged mice; Set II: Normal mice; Set III: Drug treated mice, Set IVA Cisplatin (CDDP) treated mice, Set IV B EAC challenged Cisplatin treated mice. Set I was used to test antineoplasticity of the drug, Set II and Set III for studying drug toxicity and Set IV was treated with CDDP. Set II was used as a control. Animals were sacrificed after 5 days, 10 days 15 days and 20 days of drug administration on the 6th, 11th, 16th and 21st days respectively for Set I, II and III. Set IVA was sacrificed only on the 16th day and Set IV B on 6th and 11th days. For Set I only tumor cell count and packed cell volume (PCV) of tumor cells were recorded. For Set II and III, aspartate aminotransferase (AST), alanine aminotransferase (ALT) assays were done using serum while blood creatinine and creatine were assayed from blood filtrate. For cytotoxicity assessment liver, spleen and kidney tissues were collected and subjected to scanning electron microscopy (SEM) after extensive treatment. Set IV A was only studied for the biochemical parameters viz. aspartate aminotransferase (AST), alanine aminotransferase (ALT) assays were done using serum while blood creatinine and creatine were assayed from blood filtrate. Set IV B was studied for tumor cell count after treatment with

  2. Use of oral antineoplastic in special situations in a third level hospital: real life results

    Directory of Open Access Journals (Sweden)

    José Miguel Ferrari-Piquero

    2018-01-01

    Full Text Available Objective: To analyse the effectiveness and safety of oral antineoplastic drugs (ANEOs that are authorized in special situations in a third-level hospital and to compare the results obtained with the clinical evidence used for this authorization. Method: Descriptive observational and retrospective study. We included all adult patients who started treatment with ANEO in special situations during the year 2016. We collected demographic, treatment-related and clinical variables (overall survival (OS, progression-free survival (PFS. Adverse reactions and detected interactions were collected. An unadjusted comparison was made between the results of the available evidence and those of the study patients. Results: 34 patients were treated, 50% were men, the median age was 58 years (38-80 and they presented ECOG 1 in 64.7%. Most of the treated patients were diagnosed with advanced colorectal cancer, treated with trifluridine-tipiracil, followed by palbociclib in breast cancer, obtaining results similar to those of the evidence. The median PFS was 2.8 months (95% CI 0.8- 4.8 and the 8-month SG (95% CI 3.4-12.5 for all patients. 26% of patients required dose reduction because of treatment toxicity. We found 13 interactions, which affected 15 patients, only two of category X. Conclusions: The effectiveness of ANEO in special situations in our center is similar to that of available evidence. The impact on survival is low and adverse effects are common.

  3. New Trends on Antineoplastic Therapy Research: Bullfrog (Rana catesbeiana Shaw Oil Nanostructured Systems

    Directory of Open Access Journals (Sweden)

    Lucas Amaral-Machado

    2016-04-01

    Full Text Available Bullfrog oil is a natural product extracted from the Rana catesbeiana Shaw adipose tissue and used in folk medicine for the treatment of several diseases. The aim of this study was to evaluate the extraction process of bullfrog oil, to develop a suitable topical nanoemulsion and to evaluate its efficacy against melanoma cells. The oil samples were obtained by hot and organic solvent extraction processes and were characterized by titration techniques and gas chromatography mass spectrometry (GC-MS. The required hydrophile-lipophile balance and the pseudo-ternary phase diagram (PTPD were assessed to determine the emulsification ability of the bullfrog oil. The anti-tumoral activity of the samples was assessed by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay for normal fibroblast (3T3 and melanoma (B16F10 cell lines. Both extraction methods produced yielded around 60% and the oil was mainly composed of unsaturated compounds (around 60%. The bullfrog oil nanoemulsion obtained from PTPD presented a droplet size of about 390 nm and polydispersity = 0.05 and a zeta potential of about −25 mV. Both the bullfrog oil itself and its topical nanoemulsion did not show cytotoxicity in 3T3 linage. However, these systems showed growth inhibition in B16F10 cells. Finally, the bullfrog oil presented itself as a candidate for the development of pharmaceutical products free from cytotoxicity and effective for antineoplastic therapy.

  4. New Trends on Antineoplastic Therapy Research: Bullfrog (Rana catesbeiana Shaw) Oil Nanostructured Systems.

    Science.gov (United States)

    Amaral-Machado, Lucas; Xavier-Júnior, Francisco H; Rutckeviski, Renata; Morais, Andreza R V; Alencar, Éverton N; Dantas, Teresa R F; Cruz, Ana K M; Genre, Julieta; da Silva-Junior, Arnóbio A; Pedrosa, Matheus F F; Rocha, Hugo A O; Egito, Eryvaldo S T

    2016-04-30

    Bullfrog oil is a natural product extracted from the Rana catesbeiana Shaw adipose tissue and used in folk medicine for the treatment of several diseases. The aim of this study was to evaluate the extraction process of bullfrog oil, to develop a suitable topical nanoemulsion and to evaluate its efficacy against melanoma cells. The oil samples were obtained by hot and organic solvent extraction processes and were characterized by titration techniques and gas chromatography mass spectrometry (GC-MS). The required hydrophile-lipophile balance and the pseudo-ternary phase diagram (PTPD) were assessed to determine the emulsification ability of the bullfrog oil. The anti-tumoral activity of the samples was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for normal fibroblast (3T3) and melanoma (B16F10) cell lines. Both extraction methods produced yielded around 60% and the oil was mainly composed of unsaturated compounds (around 60%). The bullfrog oil nanoemulsion obtained from PTPD presented a droplet size of about 390 nm and polydispersity = 0.05 and a zeta potential of about -25 mV. Both the bullfrog oil itself and its topical nanoemulsion did not show cytotoxicity in 3T3 linage. However, these systems showed growth inhibition in B16F10 cells. Finally, the bullfrog oil presented itself as a candidate for the development of pharmaceutical products free from cytotoxicity and effective for antineoplastic therapy.

  5. Study of antineoplastic action of novel isomeric derivatives of 4-thiazolidinone

    Directory of Open Access Journals (Sweden)

    М. R. Fil

    2014-12-01

    Full Text Available Pyrazole- and aryl-substituted derivatives of 4-thiazolidinone belong to a perspective group of compounds with potential antitumor action. Earlier, we have demonstrated high toxicity in vitro of several 4-thiazolidinones derivatives towards tumor cell lines. To further enhance the antitumor activity of novel 4-thiazolidinones, their chemical scaffold was optimized, and new pyrazole-thiazolidinones were synthesized. That allowed us to combine in one molecule the potential pharmacophore centres of previously tested compounds. As a result, “hybrid” 4-thiazolidinones exhibit higher toxicity in vitro toward tumor cells of various origin. The molecular mechanisms of antineoplastic activity of these compounds and intensity of induction of apoptosis strongly depended on the position of the substituent in the thiazolidinone cycle. In particular, Les-3661 compound, containing pyrazoline fragment in the 4th position of thiazolidinone core, exhibits 14 times higher cytotoxic activity towards tumor cells (LC50 = 3 µM in comparison to its 2-substituted isomer Les-3713 (LC50 = 42 µM. It is demonstrated that in terms of underlying molecular mechanisms for cytotoxic effect the Les-3661 compound induced caspase-8 and caspase-9 dependent mixed-type of apoptosis, while Les-3713 induced apoptosis mediated only by the caspase-8.

  6. [Evaluation of genotoxic effects in subjects occupationally exposed to antineoplastic drugs].

    Science.gov (United States)

    Moretti, Massimo; Villarini, Milena; Dominici, Luca; Fatigoni, Cristina; dell'Omo, Marco; Elisei, Emanuela; Muzi, Giacomo; Monarca, Silvano

    2013-01-01

    The present molecular epidemiology study was carried out to evaluate the genotoxic effects of occupational exposure to antineoplastic drugs (ANP). The study was conducted in 52 hospital workers involved in the preparation, handling or administration of ANP in a hospital in Perugia (central Italy) and in 52 non-exposed control subjects matched for age, gender and smoking habits to the exposed subjects. Both comet assay and the micronucleus test were used to evaluate genome damage in peripheral blood lymphocytes in study subjects. The extent of primary DNA damage, as evaluated by the comet assay, was significantly increased in exposed personnel with respect to matched controls. On the other hand, no significant differences in micronuclei frequency was observed between the two groups. Multivariate linear regression analysis showed an association between years of occupational exposure over 10 years and higher extent of primary DNA damage in the exposed group. The results of this study confirm that handling ANP without appropriate precautions carries a genotoxic risk for exposed healthcare workers. These results address the need for regular biological effect monitoring of staff occupationally-exposed to ANP.

  7. Relevance of the OCT1 transporter to the antineoplastic effect of biguanides

    Energy Technology Data Exchange (ETDEWEB)

    Segal, Eric D.; Yasmeen, Amber; Beauchamp, Marie-Claude; Rosenblatt, Joshua [Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Pollak, Michael [Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Department of Oncology, McGill University, Montreal, Quebec (Canada); Gotlieb, Walter H., E-mail: walter.gotlieb@mcgill.ca [Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Department of Oncology, McGill University, Montreal, Quebec (Canada)

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer siRNA knockdown of OCT1 reduced sensitivity of EOC cells to metformin, but not to another biguanide, phenformin. Black-Right-Pointing-Pointer Suppression of OCT1 also affects the activation of AMP kinase in response to metformin, but not to phenformin. Black-Right-Pointing-Pointer Direct actions of metformin may be limited by low OCT1 expression in EOC tumors. Black-Right-Pointing-Pointer Phenformin could be used as an alternative biguanide. -- Abstract: Epidemiologic and laboratory data suggesting that metformin has antineoplastic activity have led to ongoing clinical trials. However, pharmacokinetic issues that may influence metformin activity have not been studied in detail. The organic cation transporter 1 (OCT1) is known to play an important role in cellular uptake of metformin in the liver. We show that siRNA knockdown of OCT1 reduced sensitivity of epithelial ovarian cancer cells to metformin, but interestingly not to another biguanide, phenformin, with respect to both activation of AMP kinase and inhibition of proliferation. We observed that there is heterogeneity between primary human tumors with respect to OCT1 expression. These results suggest that there may be settings where drug uptake limits direct action of metformin on neoplastic cells, raising the possibility that metformin may not be the optimal biguanide for clinical investigation.

  8. Effects of organizational safety practices and perceived safety climate on PPE usage, engineering controls, and adverse events involving liquid antineoplastic drugs among nurses.

    Science.gov (United States)

    DeJoy, David M; Smith, Todd D; Woldu, Henok; Dyal, Mari-Amanda; Steege, Andrea L; Boiano, James M

    2017-07-01

    Antineoplastic drugs pose risks to the healthcare workers who handle them. This fact notwithstanding, adherence to safe handling guidelines remains inconsistent and often poor. This study examined the effects of pertinent organizational safety practices and perceived safety climate on the use of personal protective equipment, engineering controls, and adverse events (spill/leak or skin contact) involving liquid antineoplastic drugs. Data for this study came from the 2011 National Institute for Occupational Safety and Health (NIOSH) Health and Safety Practices Survey of Healthcare Workers which included a sample of approximately 1,800 nurses who had administered liquid antineoplastic drugs during the past seven days. Regression modeling was used to examine predictors of personal protective equipment use, engineering controls, and adverse events involving antineoplastic drugs. Approximately 14% of nurses reported experiencing an adverse event while administering antineoplastic drugs during the previous week. Usage of recommended engineering controls and personal protective equipment was quite variable. Usage of both was better in non-profit and government settings, when workers were more familiar with safe handling guidelines, and when perceived management commitment to safety was higher. Usage was poorer in the absence of specific safety handling procedures. The odds of adverse events increased with number of antineoplastic drugs treatments and when antineoplastic drugs were administered more days of the week. The odds of such events were significantly lower when the use of engineering controls and personal protective equipment was greater and when more precautionary measures were in place. Greater levels of management commitment to safety and perceived risk were also related to lower odds of adverse events. These results point to the value of implementing a comprehensive health and safety program that utilizes available hazard controls and effectively communicates

  9. Antineoplastic treatment effect on bone mineral density in Mexican breast cancer patients.

    Science.gov (United States)

    Monroy-Cisneros, Karina; Esparza-Romero, Julián; Valencia, Mauro E; Guevara-Torres, Alfonso G; Méndez-Estrada, Rosa O; Anduro-Corona, Iván; Astiazarán-García, Humberto

    2016-11-08

    Breast cancer is the most deadly malignancy in Mexican women. Although treatment has improved, it may significantly affect bone mineral status in those who receive it. The aim of this study was to assess the impact of cancer treatment on bone mineral density (BMD) and bone mineral content (BMC), in patients with breast cancer and explore the interaction of menopausal status and clinical stage with cancer treatment on such changes. A quasi-experimental design was applied with measurements before and after a chemotherapy treatment in 40 patients with primary diagnosis of invasive breast cancer. BMD and body composition measurements were taken by dual X-ray absorptiometry (DXA) and changes in these variables due to therapy were analyzed using mixed regression for repeated measurements. Significant loss was found in femoral neck and L2-L4 BMD (p osteoporosis received calcium + vitamin D supplementation (600 mg/200 IU day). It showed a protective effect in the decrease of femoral neck BMD and total BMC. BMD loss in both femoral neck and L2-L4 BMD was higher in premenopausal women: 0.023 g/cm 2 in femoral neck and 0.063 g/cm 2 in L2-L4 (p < 0.001), while in postmenopausal women BMD loss was 0.015 g/cm 2 in femoral neck and 0.035 g/cm 2 in L2-L4 (p = 0.021 and p = 0.001 respectively). Change in lumbar spine BMD was prominent in premenopausal women with advanced clinical stage (IIB, IIIA, IIIB): 0.066 g/cm 2 (p = 0.003). The antineoplastic breast cancer treatment with chemotherapy had a negative impact on BMD, in premenopausal women overall, although a differential effect was found according to clinical stage and calcium supplementation status.

  10. Psidium guajava L. anti-neoplastic effects: induction of apoptosis and cell differentiation.

    Science.gov (United States)

    Bontempo, P; Doto, A; Miceli, M; Mita, L; Benedetti, R; Nebbioso, A; Veglione, M; Rigano, D; Cioffi, M; Sica, V; Molinari, A M; Altucci, L

    2012-02-01

    Curative properties of medicinal plants such as Psidium guajava L. (Myrtaceae) have often been indicated by epidemiological studies on populations in which these fruits are consumed daily. However, complete characterization of the active principles responsible for this ability has never been performed. Here, we have characterized P. guajava's anti-cancer potential and identified the parts of the fruit involved in its anti-neoplastic action. We studied morphology of our cells, cell cycle characteristics and apoptosis and performed immunostaining, differentiation and western blot analyses. We report that the P. guajava extract exerted anti-cancer control on both haematological and solid neoplasias. P. guajava extract's anti-tumour properties were found to be tightly bound to induction of apoptosis and differentiation. Use of ex vivo myeloid leukaemia blasts corroborated that P. guajava was able to induce cell death but did not exhibit anti-cancer effects on all malignant cells investigated, indicating selective activity against certain types of tumour. Analyses of P. guajava pulp, peel and seeds identified the pulp as being the most relevant component for causing cell cycle arrest and apoptosis, whereas peel was responsible for causing cell differentiation. P. guajava itself and its pulp-derived extract were found to induce apoptosis accompanied by caspase activation and p16, p21, Fas ligand (FASL TNF super-family, member 6), Bcl-2-associated agonist of cell death (BAD) and tumour necrosis factor receptor super-family, member 10b (DR5), overexpression. Our findings showed that P. guajava L. extract was able to exert anti-cancer activity on cultures in vitro and ex vivo, supporting the hypothesis of its anti malignant pro-apoptotic modulation. © 2011 Blackwell Publishing Ltd.

  11. The husk fiber of Cocos nucifera L. (Palmae) is a source of anti-neoplastic activity.

    Science.gov (United States)

    Koschek, P R; Alviano, D S; Alviano, C S; Gattass, C R

    2007-10-01

    In the present study, we investigated the in vitro anti-tumoral activities of fractions from aqueous extracts of the husk fiber of the typical A and common varieties of Cocos nucifera (Palmae). Cytotoxicity against leukemia cells was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Cells (2 x 10(4)/well) were incubated with 0, 5, 50 or 500 microg/mL high- or low-molecular weight fractions for 48 h, treated with MTT and absorbance was measured with an ELISA reader. The results showed that both varieties have almost similar antitumoral activity against the leukemia cell line K562 (60.1 +/- 8.5 and 47.5 +/- 11.9% for the typical A and common varieties, respectively). Separation of the crude extracts with Amicon membranes yielded fractions with molecular weights ranging in size from 1-3 kDa (fraction A) to 3-10 kDa (fraction B) and to more than 10 kDa (fraction C). Cells were treated with 500 microg/mL of these fractions and cytotoxicity was evaluated by MTT. Fractions ranging in molecular weight from 1-10 kDa had higher cytotoxicity. Interestingly, C. nucifera extracts were also active against Lucena 1, a multidrug-resistant leukemia cell line. Their cytotoxicity against this cell line was about 50% (51.9 +/- 3.2 and 56.3 +/- 2.9 for varieties typical A and common, respectively). Since the common C. nucifera variety is extensively cultured in Brazil and the husk fiber is its industrial by-product, the results obtained in the present study suggest that it might be a very inexpensive source of new antineoplastic and anti-multidrug resistant drugs that warrants further investigation.

  12. Radiobiological studies on the importance of tumor oxygenation for anti-neoplastic therapy

    International Nuclear Information System (INIS)

    Grau, C.

    1994-01-01

    The aim of the twelve studies included in the present thesis was to determine the importance of hypoxia for various anti-neoplastic treatment modalities, and to evaluate possible ways of overcoming the hypoxia problem by combined modality therapy. The murine tumor systems were the C3H mammary carcinoma with 5-12% hypoxic cells, and the SCCVII squamous cell carcinoma with 2% hypoxic cells. The radiation response was significantly improved by the use of hypoxic cell radiosensitizers such as nimorazole or misonidazole, or by allowing the mice to breathe oxygen or carbogen during irradiation. In contrast, the radiation response was significantly impaired by carbon monoxide breathing at a level comparable to what has been observed in heavy smokers. The clamped TCD 50 assay was used to classify cancer chemotherapeutic drugs according to their preferential cytotoxicity towards the different tumor subpopulations. Methotrexate had no effect on hypoxic cells and was only borderline toxic towards aerobic cells. Three drugs had significant effect against oxic cells only (5-fluorouracil, bleomycin and cisplatin). Similarly, three drugs were toxic towards hypoxic cells only (etoposide, carmustine, and mitomycin c). Three drugs were effective towards both cell types (vincristine, adriamycin, cyclophosphamide). Hypoxic cells in areas with insufficient blood supply, poor nutrition and increased acidity is known to be highly sensitive to hyperthermia. In a study where cisplatin, heat and x-rays were given together, the local tumor control was not improved when compared to radiation + heat, apparently due to a lack of enhancement in the killing of hypoxic cells. These studies have demonstrated the influence of tumor oxygenation on tumor response to treatment with drugs, hyperthermia and irradiation. New strategies targeted also against perfusion-limited hypoxia is needed. One of the most important conclusions from the present thesis can be implemented without expensive trials or

  13. Antineoplastic treatment effect on bone mineral density in Mexican breast cancer patients

    International Nuclear Information System (INIS)

    Monroy-Cisneros, Karina; Esparza-Romero, Julián; Valencia, Mauro E.; Guevara-Torres, Alfonso G.; Méndez-Estrada, Rosa O.; Anduro-Corona, Iván; Astiazarán-García, Humberto

    2016-01-01

    Breast cancer is the most deadly malignancy in Mexican women. Although treatment has improved, it may significantly affect bone mineral status in those who receive it. The aim of this study was to assess the impact of cancer treatment on bone mineral density (BMD) and bone mineral content (BMC), in patients with breast cancer and explore the interaction of menopausal status and clinical stage with cancer treatment on such changes. A quasi-experimental design was applied with measurements before and after a chemotherapy treatment in 40 patients with primary diagnosis of invasive breast cancer. BMD and body composition measurements were taken by dual X-ray absorptiometry (DXA) and changes in these variables due to therapy were analyzed using mixed regression for repeated measurements. Significant loss was found in femoral neck and L2-L4 BMD (p < 0.001). Patients diagnosed with osteopenia or osteoporosis received calcium + vitamin D supplementation (600 mg/200 IU day). It showed a protective effect in the decrease of femoral neck BMD and total BMC. BMD loss in both femoral neck and L2-L4 BMD was higher in premenopausal women: 0.023 g/cm 2 in femoral neck and 0.063 g/cm 2 in L2-L4 (p < 0.001), while in postmenopausal women BMD loss was 0.015 g/cm 2 in femoral neck and 0.035 g/cm 2 in L2-L4 (p = 0.021 and p = 0.001 respectively). Change in lumbar spine BMD was prominent in premenopausal women with advanced clinical stage (IIB, IIIA, IIIB): 0.066 g/cm 2 (p = 0.003). The antineoplastic breast cancer treatment with chemotherapy had a negative impact on BMD, in premenopausal women overall, although a differential effect was found according to clinical stage and calcium supplementation status

  14. Gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency in populations of pulmonary adenocarcinoma (A549).

    Science.gov (United States)

    Coyne, Cody P; Narayanan, Lakshmi

    2017-03-01

    One molecular-based approach that increases potency and reduces dose-limited sequela is the implementation of selective 'targeted' delivery strategies for conventional small molecular weight chemotherapeutic agents. Descriptions of the molecular design and organic chemistry reactions that are applicable for synthesis of covalent gemcitabine-monophosphate immunochemotherapeutics have to date not been reported. The covalent immunopharmaceutical, gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R] was synthesized by reacting gemcitabine with a carbodiimide reagent to form a gemcitabine carbodiimide phosphate ester intermediate which was subsequently reacted with imidazole to create amine-reactive gemcitabine-(5'-phosphorylimidazolide) intermediate. Monoclonal anti-IGF-1R immunoglobulin was combined with gemcitabine-(5'-phosphorylimidazolide) resulting in the synthetic formation of gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R]. The gemcitabine molar incorporation index for gemcitabine-(5'-phosphoramidate)-[anti-IGF-R1] was 2.67:1. Cytotoxicity Analysis - dramatic increases in antineoplastic cytotoxicity were observed at and between the gemcitabine-equivalent concentrations of 10 -9  M and 10 -7  M where lethal cancer cell death increased from 0.0% to a 93.1% maximum (100.% to 6.93% residual survival), respectively. Advantages of the organic chemistry reactions in the multistage synthesis scheme for gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R] include their capacity to achieve high chemotherapeutic molar incorporation ratios; option of producing an amine-reactive chemotherapeutic intermediate that can be preserved for future synthesis applications; and non-dedicated organic chemistry reaction scheme that allows substitutions of either or both therapeutic moieties, and molecular delivery platforms. © 2016 The Authors Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.

  15. Intravenous bisphosphonate-related osteonecrosis of the jaws: Influence of coadjuvant antineoplastic treatment and study of buccodental condition

    Science.gov (United States)

    Bagán, José; Poveda-Roda, Rafael

    2013-01-01

    Objectives: To determine whether coadjuvant antineoplastic treatment can influence the number and size of bone exposures among patients with intravenous bisphosphonate-related osteonecrosis of the jaws (iBRONJ), and to analyze the buccodental condition of these patients. Material and methods: The study sample comprised 67 patients with iBRONJ, 53 patients without iBRONJ receiving treatment with intravenous bisphosphonates, and 36 healthy subjects. In all three groups, measurements were made of the CAO index and of resting whole saliva and stimulated whole saliva. In the patients with iBRONJ, the size (cm) and number of bone exposures were recorded. The data obtained were subjected to analysis of variance (ANOVA), the Mann-Whitney U-test, and multivariate logistic regression analysis. Results: A total of 57.6% of the patients presented single bone exposure, 25.4% presented two, and 17% more than two exposures. The mean exposure size was 2.3±1.9 cm. Neither the bivariate analysis nor the multivariate multiple regression analysis found coadjuvant antineoplastic treatment to exert a statistically significant effect upon the number and size of bone exposures. On the other hand, there were statistically significant differences among the three study groups in relation to the CAO index (p=0.02) and the number of missing teeth (p=0.00). The resting whole saliva and stimulated whole saliva levels were similar in the three groups, though the patients with osteonecrosis of the jaws showed comparatively lower SWS levels. Conclusions: Coadjuvant antineoplastic treatment alone appears to exert no influence upon the size and number of bone exposures in iBRONJ. The patients with this disease show a higher CAO index and a larger number of missing teeth. Key words:Osteonecrosis of the jaws, bisphosphonates, bone exposure, CAO index, resting whole saliva, stimulated whole saliva. PMID:23229272

  16. Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys

    NARCIS (Netherlands)

    Kromhout, H.; Hoek, F.; Uitterhoeve, R.; Huijbers, R.; Overmars, R.F.; Anzion, R.; Vermeulen, R.

    2000-01-01

    Dermal exposure to anti-neoplastic drugs has been suggested as a potentially important route of exposure of hospital workers. Three small-scale workplace surveys were carried out in several hospitals focusing on contamination by leakage from IV infusion systems; contamination by spilled urine of

  17. Oncogenic targets, magnitude of benefit, and market pricing of antineoplastic drugs.

    Science.gov (United States)

    Amir, Eitan; Seruga, Bostjan; Martinez-Lopez, Joaquin; Kwong, Ryan; Pandiella, Atanasio; Tannock, Ian F; Ocaña, Alberto

    2011-06-20

    The relationship between market pricing of new anticancer drugs and the magnitude of clinical benefit caused by them has not been reported. Randomized clinical trials (RCTs) that evaluated approved new agents for solid tumors by the U.S. Food and Drug administration since the year 2000 were assessed. Hazard ratios (HRs) and 95% CIs were extracted for time-to-event end points described for each RCT. HRs were pooled for three groups: agents directed against a specific molecular target, for which the target population is selected by a biomarker (group A); less specific biologic targeted agents (group B); and chemotherapeutic agents (group C). Monthly market prices of these different drugs were compared. For overall survival (OS), the pooled HR was 0.69 (95% CI, 0.59 to 0.81) for group A (six drugs, six trials); it was 0.78 (95% CI, 0.74 to 0.83) for group B (seven drugs, 14 trials); and it was 0.84 (95% CI, 0.79 to 0.90) for group C (eight drugs, 12 trials). For progression-free survival (PFS), the pooled HR was 0.42 (95% CI, 0.36 to 0.49) for group A (six drugs, seven trials); it was 0.57 (95% CI, 0.51 to 0.64) for group B (seven drugs, 14 trials); and it was 0.75 (95% CI, 0.66 to 0.85) for group C (six drugs, 10 trials). Tests for heterogeneity between subgroups were highly significant for PFS (P prices for standard doses of drugs were $5375 for group A, $5644 for group B, and $6584 for group C (P = .87). New agents with specific molecular targets are clinically the most beneficial, but their monthly market prices are not significantly different from those of other anticancer agents.

  18. Antineoplastic Activities of MT81 and Its Structural Analogue in Ehrlich Ascites Carcinoma-Bearing Swiss Albino Mice

    Directory of Open Access Journals (Sweden)

    Sujata Maiti Choudhury

    2010-01-01

    Full Text Available Many fungal toxins exhibit in vitro and in vivo antineoplastic effects on various cancer cell types. Luteoskyrin, a hydroxyanthraquinone has been proved to be a potent inhibitor against Ehrlich ascites tumor cells. The comparative antitumor activity and antioxidant status of MT81 and its structural analogue [Acetic acid-MT81 (Aa-MT81] having polyhydroxyanthraquinone structure were assessed against Ehrlich ascites carcinoma (EAC tumor in mice. The in vitro cytotoxicity was measured by the viability of EAC cells after direct treatment of the said compounds. In in vivo study, MT81 and its structural analogue were administered (i.p. at the two different doses (5, 7 mg MT81; 8.93, 11.48 mg Aa-MT81/kg body weight for 7 days after 24 hrs. of tumor inoculation. The activities were assessed using mean survival time (MST, increased life span (ILS, tumor volume, viable tumor cell count, peritoneal cell count, protein percentage and hematological parameters. Antioxidant status was determined by malondialdehyde (MDA and reduced glutathione (GSH content, and by the activity of superoxide dismutase (SOD and catalase (CA T. MT81 and its structural analogues increased the mean survival time, normal peritoneal cell count. They decreased the tumor volume, viable tumor cell count, hemoglobin percentage and packed cell volume. Differential counts of WBC, total counts of RBC & WBC that altered by EAC inoculation, were restored in a dose-dependent manner. Increased MDA and decreased GSH content and reduced activity of SOD, and catalase in EAC bearing mice were returned towards normal after the treatment of MT81 and its structural analogue. Being less toxic than parent toxin MT81, the structural analogue showed more prominent antineoplastic activities against EAC cells compared to MT81. At the same time, both compounds exhibit to some extent antioxidant potential for the EAC-bearing mice.

  19. Biological activities, mechanisms of action and biomedical prospect of the antitumor ether phospholipid ET-18-OCH3 (edelfosine), a proapoptotic agent in tumor cells

    OpenAIRE

    Gajate, Consuelo; Mollinedo, Faustino

    2002-01-01

    The antitumor ether lipid ET-18-OCH3 (edelfosine) is the type of a new class of antineoplastic agents, synthetic analogues of lysophosphatidylcholine, that shows a high metabolic stability, does not interact with DNA and shows a selective apoptotic response in tumor cells, sparing normal cells. Unlike currently used antitumor drugs, ET-18-OCH3 does not act directly on the formation and function of the replication machinery, and thereby its effects are independent of the proliferative state of...

  20. Bioactive substances with anti-neoplastic efficacy from marine invertebrates: Bryozoa, Mollusca, Echinodermata and Urochordata

    Science.gov (United States)

    Sima, Peter; Vetvicka, Vaclav

    2011-01-01

    The marine environment provides a rich source of natural products with potential therapeutic application. This has resulted in an increased rate of pharmaceutical agents being discovered in marine animals, particularly invertebrates. Our objective is to summarize the most promising compounds which have the best potential and may lead to use in clinical practice, show their biological activities and highlight the compounds currently being tested in clinical trials. In this paper, we focused on Bryozoa, Mollusca, Echinodermata and Urochordata. PMID:22087434

  1. A study protocol for the evaluation of occupational mutagenic/carcinogenic risks in subjects exposed to antineoplastic drugs: a multicentric project

    Directory of Open Access Journals (Sweden)

    Gelatti Umberto

    2011-03-01

    Full Text Available Abstract Background Some industrial hygiene studies have assessed occupational exposure to antineoplastic drugs; other epidemiological investigations have detected various toxicological effects in exposure groups labeled with the job title. In no research has the same population been studied both environmentally and epidemiologically. The protocol of the epidemiological study presented here uses an integrated environmental and biological monitoring approach. The aim is to assess in hospital nurses preparing and/or administering therapy to cancer patients the current level of occupational exposure to antineoplastic drugs, DNA and chromosome damage as cancer predictive effects, and the association between the two. Methods/Design About 80 healthy non-smoking female nurses, who job it is to prepare or handle antineoplastic drugs, and a reference group of about 80 healthy non-smoking female nurses not occupationally exposed to chemicals will be examined simultaneously in a cross-sectional study. All the workers will be recruited from five hospitals in northern and central Italy after their informed consent has been obtained. Evaluation of surface contamination and dermal exposure to antineoplastic drugs will be assessed by determining cyclophosphamide on selected surfaces (wipes and on the exposed nurses' clothes (pads. The concentration of unmetabolized cyclophosphamide as a biomarker of internal dose will be measured in end-shift urine samples from exposed nurses. Biomarkers of effect and susceptibility will be assessed in exposed and unexposed nurses: urinary concentration of 8-hydroxy-2-deoxyguanosine; DNA damage detected using the single-cell microgel electrophoresis (comet assay in peripheral white blood cells; micronuclei and chromosome aberrations in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e. glutathione S-transferases will also be analysed. Using standardized questionnaires

  2. Antibiotic Agents

    Science.gov (United States)

    ... Superbugs and Drugs" Home | Contact Us General Background: Antibiotic Agents What is an antibacterial and how are ... with the growth and reproduction of bacteria. While antibiotics and antibacterials both attack bacteria, these terms have ...

  3. Inciting and etiologic agents of colitis.

    Science.gov (United States)

    Silva, J; Fekety, R; Werk, C; Ebright, J; Cudmore, M; Batts, D; Syrjamaki, C; Lukens, J

    1984-01-01

    Since 1979, 3,115 stool samples were tested for detection of Clostridium difficile and its cytotoxin; these were obtained from patients who had drug-related diarrhea. Presumed or proven colitis due to C. difficile was diagnosed in 130 patients. Drugs implicated most commonly as causing or associated with the onset of enterocolitis due to C. difficile were ampicillin (38 episodes), cephalosporins (71), clindamycin (36), and the aminoglycosides (45). The hamster model of colitis was employed to explore the role of other inducing agents. Altering the usual diet of hamsters to one with a higher protein content decreased the time to death due to C. difficile cecitis following the administration of cefazolin (10 mg). Several cathartics also were studied for their effect on the lethality of antibiotic-induced cecitis. Daily administrations of castor oil (0.5 ml per day) and vegetable oil (1.0 ml per day) improved survival against lethal doses of clindamycin. Milk of magnesia or mineral oil provided no protection. Four patients with C. difficile colitis induced by therapy with cytotoxic drugs also were identified. Methotrexate induced cecitis when administered orally and daily to hamsters, and C. difficile and its cytotoxin were identified in the hamsters' stools. Death due to methotrexate-induced cecitis was prevented by daily administration of folinic acid or vancomycin. These data demonstrate that a variety of antibiotics, antineoplastic agents, cathartics, and diet changes can induce C. difficile colitis in humans and hamsters.

  4. studies on hair growth, hair density, hair diameter, hair shape, trichodynia and skin-specific quality of life on women with breast cancer under antineoplastic treatment

    OpenAIRE

    Lindner, Julia

    2013-01-01

    The purpose of this study was to investigate changes of hair growth rates, hair density, hair diameter, hair shape, trichodynia and skin-specific quality of life under antineoplastic treatment. Participants in this prospective study were 34 women, suffering from breast cancer, receiving either chemotherapy (n = 17) or tamoxifen (n = 17). The following methods were used: TrichoScan for the evaluation of hair density, anagen and telogen hair rates, optical coherence tomography for the determina...

  5. Interactions of radiation repair systems in escherichia colt with antineoplastic anthracyclines

    International Nuclear Information System (INIS)

    Kacinski, B.M.; Rupp, W.D.

    1984-01-01

    The authors have studied the interactions of several anthracylines with the UVR DN*a repair system of E. coli. The authors found that doxorubicin is quite toxic for uvr- but not for uvr+strains. They also found that exposure of cells carrying a multicopy plasmid to this agent yielded plasmid DNA molecules with lesions which were recognized and cleaved by purified E. coli UVRABC DNA repair endonuclease. A derivative of doxorubicin was not measurably toxic for either uvr+ or uvr- strains but nevertheless produced lesions which were substrates for the UVRABC endonuclease. The authors propose that anthracycline toxicity in uvr- E. coli may correlate with clinical toxicity while anthracylcine antineopolastic activity may correlate with their ability to produce UVRABC endonuclease-sensitive DNA damage

  6. Organotypic Culture of Breast Tumor Explants as a Multicellular System for the Screening of Natural Compounds with Antineoplastic Potential

    Directory of Open Access Journals (Sweden)

    Irma Edith Carranza-Torres

    2015-01-01

    Full Text Available Breast cancer is the leading cause of death in women worldwide. The search for novel compounds with antitumor activity, with less adverse effects and higher efficacy, and the development of methods to evaluate their toxicity is an area of ​​intense research. In this study we implemented the preparation and culture of breast tumor explants, which were obtained from precision-cut breast tumor slices. In order to validate the model we are proposing to screen antineoplastic effect of natural compounds, we selected caffeic acid, ursolic acid, and rosmarinic acid. Using the Krumdieck tissue slicer, precision-cut tissue slices were prepared from breast cancer samples; from these slices, 4 mm explants were obtained and incubated with the selected compounds. Viability was assessed by Alamar Blue assay, LDH release, and histopathological criteria. Results showed that the viability of the explants cultured in the presence of paclitaxel (positive control decreased significantly (P<0.05; however, tumor samples responded differently to each compound. When the explants were coincubated with paclitaxel and compounds, a synergic effect was observed. This study shows that ex vivo culture of breast cancer explants offers a suitable alternative model for evaluating natural or synthetic compounds with antitumor properties within the complex microenvironment of the tumor.

  7. Identification and characterization of riproximin, a new type II ribosome-inactivating protein with antineoplastic activity from Ximenia americana.

    Science.gov (United States)

    Voss, Cristina; Eyol, Ergül; Frank, Martin; von der Lieth, Claus-W; Berger, Martin R

    2006-06-01

    The aim of this study was to identify and characterize the active component(s) of Ximenia americana plant material used to treat cancer in African traditional medicine. By a combination of preextraction, extraction, ion exchange and affinity chromatography, a mixture of two cytotoxic proteins was isolated. Using degenerated primers designed on the de novo sequence of two tryptic peptides from one of these proteins, a DNA fragment was amplified and the sequence obtained was used to determine the complete cDNA sequence by the RACE method. Sequence analysis and molecular modeling showed that the new protein, riproximin, belongs to the family of type II ribosome inactivating proteins. These results are in good agreement with the ability of riproximin to inhibit protein synthesis in a cell-free system, as well as with the cytotoxicity of riproximin, as demonstrated by its IC50 value of 0.5 pM in MCF7, 1.1 pM in HELA and 0.6 pM in CC531-lacZ cells. To assess the antineoplastic efficacy of the purified riproximin in vivo, the CC531-lacZ colorectal cancer rat metastasis model was used. Significant anticancer activity was found after administration of total dosages of 100 (perorally) and 10 (intraperitoneally) pmol riproximin/kg. These results suggest that riproximin has distinct potential for cancer treatment.

  8. Antioxidants Impair Anti-Tumoral Effects of Vorinostat, but Not Anti-Neoplastic Effects of Vorinostat and Caspase-8 Downregulation

    Science.gov (United States)

    Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel

    2014-01-01

    We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat induces formation of reactive oxygen species and DNA damage. To investigate the role of oxidative stress as anti-neoplastic mechanism, we have evaluated the effects of different antioxidants (Bha, Nac and Tiron) on endometrial carcinoma cell line Ishikawa treated with Vorinostat. We show that Bha, Nac and Tiron markedly inhibited the cytotoxic effects of Vorinostat, increasing cell viability in vitro. We found that all three antioxidants did not inhibited accumulation of acetyl Histone H4, so that antioxidants did not inhibit Vorinostat activity. Finally, we have evaluated the effects of antioxidants on anti-tumoral activity of Vorinostat as monotherapy or in combination with caspase-8 downregulation in vivo. Interestingly, antioxidants blocked the reduction of tumour growth caused by Vorinostat, but they were unable to inhibit anti-tumoral activity of Vorinostat plus caspase-8 inhibition. PMID:24651472

  9. Evaluation of Oral Mucositis Occurrence in Oncologic Patients under Antineoplastic Therapy Submitted to the Low-Level Laser Coadjuvant Therapy.

    Science.gov (United States)

    Leite Cavalcanti, Alessandro; José de Macêdo, Dário; Suely Barros Dantas, Fernanda; Dos Santos Menezes, Karla; Filipe Bezerra Silva, Diego; Alves de Melo Junior, William; Fabia Cabral Cavalcanti, Alidianne

    2018-04-24

    Low-level laser therapy has been widely used in treating many conditions, including oral mucositis. The purpose of this study was to evaluate the occurrence of oral mucositis in patients undergoing antineoplastic therapy submitted to preventive and therapeutic treatment with low-level laser therapy. This cross-sectional study was carried out with 51 children and adolescents of both sexes with malignant neoplasias who developed oral mucositis and underwent low-level laser therapy. Data were collected on sex, age, type and degree of neoplasia, region affected, and remission time. 64.7% of the patients were male and were between 3 and 6 years of age (39.2%). Acute lymphoid leukemia was the most frequent neoplasm (37.3%). Regarding the maximum oral mucositis, grade 2 (41.2%) was predominant, with jugal mucosa (29.9%) and tongue (17.7%) being the most affected regions. The majority of cases presented lesion remission time between 4 and 7 days (44.0%). Most patients were young, male, and diagnosed with acute lymphoid leukemia. Predominance of grade 2 oral mucositis was observed, with jugal mucosa and tongue being the most affected regions, with the majority of cases presenting lesion remission time between 4 and 7 days. Low-level laser therapy has been shown to be an essential therapy in the prevention and treatment of these lesions, since it is a non-invasive and low-cost method.

  10. Evaluation of Oral Mucositis Occurrence in Oncologic Patients under Antineoplastic Therapy Submitted to the Low-Level Laser Coadjuvant Therapy

    Directory of Open Access Journals (Sweden)

    Alessandro Leite Cavalcanti

    2018-04-01

    Full Text Available Low-level laser therapy has been widely used in treating many conditions, including oral mucositis. The purpose of this study was to evaluate the occurrence of oral mucositis in patients undergoing antineoplastic therapy submitted to preventive and therapeutic treatment with low-level laser therapy. This cross-sectional study was carried out with 51 children and adolescents of both sexes with malignant neoplasias who developed oral mucositis and underwent low-level laser therapy. Data were collected on sex, age, type and degree of neoplasia, region affected, and remission time. 64.7% of the patients were male and were between 3 and 6 years of age (39.2%. Acute lymphoid leukemia was the most frequent neoplasm (37.3%. Regarding the maximum oral mucositis, grade 2 (41.2% was predominant, with jugal mucosa (29.9% and tongue (17.7% being the most affected regions. The majority of cases presented lesion remission time between 4 and 7 days (44.0%. Most patients were young, male, and diagnosed with acute lymphoid leukemia. Predominance of grade 2 oral mucositis was observed, with jugal mucosa and tongue being the most affected regions, with the majority of cases presenting lesion remission time between 4 and 7 days. Low-level laser therapy has been shown to be an essential therapy in the prevention and treatment of these lesions, since it is a non-invasive and low-cost method.

  11. The antineoplastic drug flavopiridol reverses memory impairment induced by Amyloid-ß1-42 oligomers in mice.

    Science.gov (United States)

    Leggio, Gian Marco; Catania, Maria Vincenza; Puzzo, Daniela; Spatuzza, Michela; Pellitteri, Rosalia; Gulisano, Walter; Torrisi, Sebastiano Alfio; Giurdanella, Giovanni; Piazza, Cateno; Impellizzeri, Agata Rita; Gozzo, Lucia; Navarria, Andrea; Bucolo, Claudio; Nicoletti, Ferdinando; Palmeri, Agostino; Salomone, Salvatore; Copani, Agata; Caraci, Filippo; Drago, Filippo

    2016-04-01

    The ectopic re-activation of cell cycle in neurons is an early event in the pathogenesis of Alzheimer's disease (AD), which could lead to synaptic failure and ensuing cognitive deficits before frank neuronal death. Cytostatic drugs that act as cyclin-dependent kinase (CDK) inhibitors have been poorly investigated in animal models of AD. In the present study, we examined the effects of flavopiridol, an inhibitor of CDKs currently used as antineoplastic drug, against cell cycle reactivation and memory loss induced by intracerebroventricular injection of Aß1-42 oligomers in CD1 mice. Cycling neurons, scored as NeuN-positive cells expressing cyclin A, were found both in the frontal cortex and in the hippocampus of Aβ-injected mice, paralleling memory deficits. Starting from three days after Aβ injection, flavopiridol (0.5, 1 and 3mg/kg) was intraperitoneally injected daily, for eleven days. Here we show that a treatment with flavopiridol (0.5 and 1mg/kg) was able to rescue the loss of memory induced by Aβ1-42, and to prevent the occurrence of ectopic cell-cycle events in the mouse frontal cortex and hippocampus. This is the first evidence that a cytostatic drug can prevent cognitive deficits in a non-transgenic animal model of AD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Oxidative Stress Induced in Nurses by Exposure to Preparation and Handling of Antineoplastic Drugs in Mexican Hospitals: A Multicentric Study

    Directory of Open Access Journals (Sweden)

    Leobardo Manuel Gómez-Oliván

    2014-01-01

    Full Text Available The impact of involuntary exposure to antineoplastic drugs (AD was studied in a group of nurses in diverse hospitals in Mexico. The results were compared with a group of unexposed nurses. Anthropometric characteristics and the biochemical analysis were analyzed in both groups. Also, lipid peroxidation level (LPX, protein carbonyl content (PCC, and activity of the antioxidant enzymes superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GPx were evaluated in blood of study participants as oxidative stress (OS biomarkers. The group of occupationally exposed (OE nurses consisted of 30 individuals ranging in age from 25 to 35 years. The control group included 30 nurses who were not occupationally exposed to the preparation and handling of AD and whose anthropometric and biochemical characteristics were similar to those of the OE group. All biomarkers evaluated were significantly increased (P<0.5 in OE nurses compared to the control group. Results show that the assessment of OS biomarkers is advisable in order to evaluate exposure to AD in nurses.

  13. Antioxidants impair anti-tumoral effects of Vorinostat, but not anti-neoplastic effects of Vorinostat and caspase-8 downregulation.

    Science.gov (United States)

    Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel; Matias-Guiu, Xavier; Dolcet, Xavier

    2014-01-01

    We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat induces formation of reactive oxygen species and DNA damage. To investigate the role of oxidative stress as anti-neoplastic mechanism, we have evaluated the effects of different antioxidants (Bha, Nac and Tiron) on endometrial carcinoma cell line Ishikawa treated with Vorinostat. We show that Bha, Nac and Tiron markedly inhibited the cytotoxic effects of Vorinostat, increasing cell viability in vitro. We found that all three antioxidants did not inhibited accumulation of acetyl Histone H4, so that antioxidants did not inhibit Vorinostat activity. Finally, we have evaluated the effects of antioxidants on anti-tumoral activity of Vorinostat as monotherapy or in combination with caspase-8 downregulation in vivo. Interestingly, antioxidants blocked the reduction of tumour growth caused by Vorinostat, but they were unable to inhibit anti-tumoral activity of Vorinostat plus caspase-8 inhibition.

  14. PEGylated DX-1000: Pharmacokinetics and Antineoplastic Activity of a Specific Plasmin Inhibitor

    Directory of Open Access Journals (Sweden)

    Laetitia Devy

    2007-11-01

    Full Text Available Novel inhibitors of the urokinase-mediated plasminogen (plg activation system are potentially of great clinical benefit as anticancer treatments. Using phage display, we identified DX-1000 a tissue factor pathway inhibitor-derived Kunitz domain protein which is a specific high-affinity inhibitor of plasmin (pin (Ki = 99 pM. When tested in vitro, DX-1000 blocks plasminmediated pro-matrix metal loproteinase-9 (proMMP-9 activation on cells and dose-dependently inhibits tube formation, while not significantly affecting hemostasis and coagulation. However, this low-molecular weight protein inhibitor (~ 7 kDa exhibits rapid plasma clearance in mice and rabbits, limiting its potential clinical use in chronic diseases. After site-specific PEGylation, DX-1000 retains its activity and exhibits a decreased plasma clearance. This PEGylated derivative is effective in vitro, as well as potent in inhibiting tumor growth of green fluorescent protein (GFP-labeled MDA-MB-231 cells. 4PEG-DX-1000 treatment causes a significant reduction of urokinase-type plasminogen activator (uPA and plasminogen expressions, a reduction of tumor proliferation, and vascularization. 4PEG-DX-1000 treatment significantly decreases the level of active mitogenactivated protein kinase (MAPK in the primary tumors and reduces metastasis incidence. Together, our results demonstrate the potential value of plasmin inhibitors as therapeutic agents for blocking breast cancer growth and metastasis.

  15. Brain tumor chemo-radiotherapy: a study of direct intratumoral perfusion with antineoplastic drugs

    International Nuclear Information System (INIS)

    Rousseau, J.

    2007-10-01

    High grade gliomas are aggressive tumors for which current treatments remain palliative. Radiotherapy efficacy is restricted by the surrounding brain tissue tolerance. One method based on the concomitant use of chemotherapeutic drugs and external photon irradiation has been proposed to improve the treatment outcome. The systemic administration of drugs is not effective in achieving the therapeutic level of drug needed for brain tumor treatment. This is due to the blood brain barrier (BBB) that prevents molecules passing through the vascular endothelium. Recent methods have been developed to circumvent the BBB. Among them, convection-enhanced delivery (CED) relies on the continuous infusion of a fluid containing a therapeutic agent, under a pressure gradient. It permits a homogeneous and controlled drug distribution. The aims of this study were to characterise the CED method, and then to utilize it for glioma treatment in preclinical studies. Several drugs were tested: cisplatin, carbo-platin, oxaliplatin, and iodo-deoxyuridine. Two radiation modalities were evaluated: synchrotron stereotactic radiotherapy (monochromatic beam < 100 keV) and high energy irradiation (6 MV) obtained with a conventional medical linear accelerator. The results obtained reveal that the effectiveness of the combined treatment (platinated drug plus photon irradiation) is highly related to that of the chemotherapy. The data, obtained with the platinated chemotherapy, also show that high-energy X-ray irradiation (6 MV) is as effective as synchrotron X-ray irradiation. The results broaden the applicability of this chemotherapeutic approach to clinical trials. (author)

  16. Mitochondria play a central role in apoptosis induced by alpha-tocopheryl succinate, an agent with antineoplastic activity: comparison with receptor-mediated pro-apoptotic signaling

    Czech Academy of Sciences Publication Activity Database

    Weber, T. D.; Dalen, H.; Anděra, Ladislav; Negre-Salvayre, A.; Auge, N.; Sticha, M.; Lloret, A.; Terman, A.; Witting, P. K.; Higuchi, M.; Plasilova, M.; Zivny, J.; Gellert, N.; Weber, C.; Neuzil, J.

    2003-01-01

    Roč. 42, č. 14 (2003), s. 4277-91 ISSN 0006-2960 R&D Projects: GA MŠk LN00A026 Institutional research plan: CEZ:AV0Z5052915 Keywords : apoptosis, TRAIL, TOS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.922, year: 2003

  17. Marketed nonsteroidal anti-inflammatory agents, antihypertensives, and human immunodeficiency virus protease inhibitors: as-yet-unused weapons of the oncologists’ arsenal

    Directory of Open Access Journals (Sweden)

    Papanagnou P

    2015-05-01

    Full Text Available Panagiota Papanagnou,1 Panagiotis Baltopoulos,2 Maria Tsironi1 1Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta, 2Department of Sports Medicine and Biology of Physical Activity, Faculty of Physical Education and Sport Science, National and Kapodistrian University of Athens, Athens, Greece Abstract: Experimental data indicate that several pharmacological agents that have long been used for the management of various diseases unrelated to cancer exhibit profound in vitro and in vivo anticancer activity. This is of major clinical importance, since it would possibly aid in reassessing the therapeutic use of currently used agents for which clinicians already have experience. Further, this would obviate the time-consuming process required for the development and the approval of novel antineoplastic drugs. Herein, both pre-clinical and clinical data concerning the antineoplastic function of distinct commercially available pharmacological agents that are not currently used in the field of oncology, ie, nonsteroidal anti-inflammatory drugs, antihypertensive agents, and anti-human immunodeficiency virus agents inhibiting viral protease, are reviewed. The aim is to provide integrated information regarding not only the molecular basis of the antitumor function of these agents but also the applicability of the reevaluation of their therapeutic range in the clinical setting. Keywords: repositioning, tumorigenesis, pleiotropy, exploitation

  18. HER Specific TKIs Exert Their Antineoplastic Effects on Breast Cancer Cell Lines through the Involvement of STAT5 and JNK.

    Directory of Open Access Journals (Sweden)

    Daphne Gschwantler-Kaulich

    Full Text Available HER-targeted tyrosine kinase inhibitors (TKIs have demonstrated pro-apoptotic and antiproliferative effects in vitro and in vivo. The exact pathways through which TKIs exert their antineoplastic effects are, however, still not completely understood.Using Milliplex assays, we have investigated the effects of the three panHER-TKIs lapatinib, canertinib and afatinib on signal transduction cascade activation in SKBR3, T47D and Jurkat neoplastic cell lines. The growth-inhibitory effect of blockade of HER and of JNK and STAT5 signaling was measured by proliferation- and apoptosis-assays using formazan dye labeling of viable cells, Western blotting for cleaved PARP-1 and immunolabeling for active caspase 3, respectively.All three HER-TKIs clearly inhibited proliferation and increased apoptosis in HER2 overexpressing SKBR3 cells, while their effect was less pronounced on HER2 moderately expressing T47D cells where they exerted only a weak antiproliferative and essentially no pro-apoptotic effect. Remarkably, phosphorylation/activation of JNK and STAT5A/B were inhibited by HER-TKIs only in the sensitive, but not in the resistant cells. In contrast, phosphorylation/activation of ERK/MAPK, STAT3, CREB, p70 S6 kinase, IkBa, and p38 were equally affected by HER-TKIs in both cell lines. Moreover, we demonstrated that direct pharmacological blockade of JNK and STAT5 abrogates cell growth in both HER-TKI-sensitive as well as -resistant breast cancer cells, respectively.We have shown that HER-TKIs exert a HER2 expression-dependent anti-cancer effect in breast cancer cell lines. This involves blockade of JNK and STAT5A/B signaling, which have been found to be required for in vitro growth of these cell lines.

  19. Influence of pain severity on the quality of life in patients with head and neck cancer before antineoplastic therapy

    Science.gov (United States)

    2014-01-01

    Background The aim of this study was to assess the severity of pain and its impact on the quality of life (QoL) in untreated patients with head and neck squamous cell carcinoma (HNSCC). Methods A study group of 127 patients with HNSCC were interviewed before antineoplastic treatment. The severity of pain was measured using the Brief Pain Inventory (BPI) questionnaire, and the QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) and the head and neck module (QLQ-H&N35). Results The mean age of the patients was 57.9 years, and there was a predominance of men (87.4%). The most frequent site of the primary tumor was the oral cavity (70.6%), and the majority of the patients had advanced cancers (stages III and IV). QoL in early stage of cancer obtained better scores. Conversely, the patients with advanced stage cancer scored significantly higher on the symptom scales regarding fatigue, pain, appetite loss and financial difficulties, indicating greater difficulties. Regard to the severity of pain, patients with moderate-severe pain revealed a significantly worse score than patients without pain. Conclusions The severity of pain is statistically related to the advanced stages of cancer and directly affects the QoL. An assessment of the quality of life and symptoms before therapy can direct attention to the most important symptoms, and appropriate interventions can then be directed toward improving QoL outcomes and the response to treatment. PMID:24460780

  20. Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

    International Nuclear Information System (INIS)

    Taylor, David J; Parsons, Christine E; Han, Haiyong; Jayaraman, Arul; Rege, Kaushal

    2011-01-01

    Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward malignant cells over normal pancreatic epithelial cells

  1. Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

    Directory of Open Access Journals (Sweden)

    Taylor David J

    2011-11-01

    Full Text Available Abstract Background Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. Methods FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Results Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward

  2. Multicenter evaluation of a new closed system drug-transfer device in reducing surface contamination by antineoplastic hazardous drugs.

    Science.gov (United States)

    Bartel, Sylvia B; Tyler, Timothy G; Power, Luci A

    2018-02-15

    Results of a study to evaluate the effectiveness of a recently introduced closed system drug-transfer device (CSTD) in reducing surface contamination during compounding and simulated administration of antineoplastic hazardous drugs (AHDs) are reported. Wipe samples were collected from 6 predetermined surfaces in compounding and infusion areas of 13 U.S. cancer centers to establish preexisting levels of surface contamination by 2 marker AHDs (cyclophosphamide and fluorouracil). Stainless steel templates were placed over the 6 previously sampled surfaces, and the marker drugs were compounded and infused per a specific protocol using all components of the CSTD. Wipe samples were collected from the templates after completion of tasks and analyzed for both marker AHDs. Aggregated results of wipe sampling to detect preexisting contamination at the 13 study sites showed that overall, 66.7% of samples (104 of 156) had detectable levels of at least 1 marker AHD; subsequent testing after CSTD use per protocol found a sample contamination rate of 5.8% (9 of 156 samples). In the administration areas alone, the rate of preexisting contamination was 78% (61 of 78 samples); with use of the CSTD protocol, the contamination rate was 2.6%. Twenty-six participants rated the CSTD for ease of use, with 100% indicating that they were satisfied or extremely satisfied. A study involving a rigorous protocol and 13 cancer centers across the United States demonstrated that the CSTD reduced surface contamination by cyclophosphamide and fluorouracil during compounding and simulated administration. Participants reported that the CSTD was easy to use. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  3. Cell-based laboratory evaluation of coagulation activation by antineoplastic drugs for the treatment of lymphoid tumors

    Directory of Open Access Journals (Sweden)

    Misae Tsunaka

    2016-07-01

    Full Text Available Objectives: Combining vorinostat, L-asparaginase, and doxorubicin (Dox led to improved response rates in the treatment of lymphoid tumors. However, deep-vein thrombosis has been noted as one of the most serious side effects with these drugs, and how these regimens cause deep-vein thrombosis is unclear. Methods: We investigated the procoagulant effects of vorinostat, L-asparaginase, and doxorubicin in lymphoid tumors, focusing on tissue factor, phosphatidylserine, and antithrombin. The human vascular endothelial cell line EAhy926 as well as the lymphoid neoplastic cell lines HUT78 (cutaneous T-cell lymphoma, Molt4 (acute T-lymphoblastic leukemia, and Ramos (Burkitt lymphoma were employed to investigate these procoagulant effects. Results: Vorinostat, L-asparaginase, and doxorubicin induced exposure of phosphatidylserine and procoagulant activity on the surface of lymphoid tumor cells. Vorinostat and doxorubicin also induced phosphatidylserine exposure and increased procoagulant activity on EAhy926 cells. Expression of tissue factor antigen was induced by doxorubicin on the surface of each type of cells, whereas expression of tissue factor mRNA was unchanged. Secretion of antithrombin from HepG2 cells was reduced only by L-asparaginase. Conclusion: These data suggest that vorinostat and doxorubicin may induce procoagulant activity in vessels through apoptosis of tumor cells and through phosphatidylserine exposure and/or tissue factor expression on vascular endothelial cells. L-asparaginase may induce a thrombophilic state by reducing the secretion of anticoagulant proteins such as antithrombin. The laboratory methods described here could be useful to evaluate the procoagulant effects of antineoplastic drugs.

  4. 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

  5. ET-09DECOY OLIGONUCLEOTIDE DERIVED FROM MGMT ENHANCER HAS AN ANTINEOPLASTIC ACTIVITY IN-VITRO AND IN-VIVO

    Science.gov (United States)

    Canello, Tamar; Ovadia, Haim; Refael, Miri; Zrihan, Daniel; Siegal, Tali; Lavon, Iris

    2014-01-01

    INTRODUCTION: Silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) in tumors, correlates with a better therapeutic response and with increased survival. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through binding of p65/NF-kappaB homodimers to the non-canonical NF-KappaB motif (MGMT-kappaB1) within MGMT enhancer. METHODS AND RESULTS: In an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA) modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN). Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to MGMT enhancer, the potential of the MGMT-kB1-LODN to enhance cell killing was studied in vitro in two glioma cell lines (T98G and U87) and a melanoma cell line (A375P). All three cell lines manifested a significant enhanced cell killing effect following exposure to temozolomide (TMZ) when first transfected with MGMT-kb1-LODN, and also induced a significant cell killing when administered as monotherapy. These results were confirmed also in-vivo on A375P Melanoma xenografts. Intratumoral (Intralesional - IL) injection of MGMT-kB1-LODN with or without IP injection of TMZ induced significant tumor growth inhibition either as a monotherapy or in combination with TMZ. The long-term effect of MGMT-kB1-LODN monotherapy was evaluated using a repetitive IL injection every 4 to 5 days for 55 days with either MGMT-κB1 LODN or control ODN or vehicle. A significant difference (p < 0.01) in tumor volume was obtained by MGMT-κB1-LODN compared to both control groups. Moreover, two out of the seven mice treated with MGMT-κB1-LODN demonstrated tumor regression by day 55 and no tumor recurrence was observed five months later. CONCLUSION: The results of these experiments show that the MGMT-kB1-LODN has a substantial antineoplastic effect when used either in combination with

  6. 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.

  7. Synthesis and Biological Evaluation of Novel 1-Alkyltryptophan Analogs as Potential Antitumor Agents

    Directory of Open Access Journals (Sweden)

    Shih-Chen Wang

    2009-12-01

    Full Text Available To seek novel antitumor agents, we designed and synthesized new 1-tryptophan analogs based on tryptophan catabolism. 1-Alkyltryptophan analogues including 1-ethyltryptophan (1-ET, 1-propyltryptophan (1-PT, 1-isopropyltryptophan (1-isoPT and 1-butyltryptophan (1-BT were synthesized from tryptophan. We examined whether those compounds had the antiproliferative effects on SGC7901 and HeLa cells line by using MTT assay in vitro, respectively. Compared to tryptophan, all targeted compounds efficiently inhibited proliferation of two cancer cell lines at 2 mmol/L for 48 hours. Among these tryptophan analogs, 1-BT showed the most powerful cytotoxicity against SGC7901 and HeLa cells at 1 mmol/L and 2 mmol/L concentration. These data suggest that some specific tryptophan analogs could be developed as potential anti-neoplastic agents.

  8. Anti-Neoplastic Cytotoxicity of Gemcitabine-(C4-amide)-[anti-HER2/neu] in Combination with Griseofulvin against Chemotherapeutic-Resistant Mammary Adenocarcinoma (SKBr-3)

    Science.gov (United States)

    Coyne, CP; Jones, Toni; Bear, Ryan

    2015-01-01

    Introduction Gemcitabine is a pyrimidine nucleoside analog that becomes triphosphorylated and in this form it competitively inhibits cytidine incorporation into DNA strands. Diphosphorylated gemcitabine irreversibly inhibits ribonucleotide reductase thereby preventing deoxyribonucleotide synthesis. Functioning as a potent chemotherapeutic, gemcitabine decreases neoplastic cell proliferation and induces apoptosis which accounts for its effectiveness in the clinical treatment of several leukemia and carcinoma cell types. A brief plasma half-life due to rapid deamination, chemotherapeuticresistance and sequelae restricts gemcitabine utility in clinical oncology. Selective “targeted” gemcitabine delivery represents a molecular strategy for prolonging its plasma half-life and minimizing innocent tissue/organ exposure. Methods A previously described organic chemistry scheme was applied to synthesize a UV-photoactivated gemcitabine intermediate for production of gemcitabine-(C4-amide)-[anti-HER2/neu]. Immunodetection analysis (Western-blot) was applied to detect the presence of any degradative fragmentation or polymerization. Detection of retained binding-avidity for gemcitabine-(C4-amide)-[anti-HER2/neu] was determined by cell-ELISA using populations of chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) that highly over-express the HER2/neu trophic membrane receptor. Anti-neoplastic cytotoxicity of gemcitabine-(C4-amide)-[anti-HER2/neu] and the tubulin/microtubule inhibitor, griseofulvin was established against chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3). Related investigations evaluated the potential for gemcitabine-(C4-amide)-[anti-HER2/neu] in dual combination with griseofulvin to evoke increased levels of anti-neoplastic cytotoxicity compared to gemcitabine-(C4-amide)-[anti-HER2/neu]. Results Covalent gemcitabine-(C4-amide)-[anti-HER2/neu] immunochemotherapeutic and griseofulvin exerted anti-neoplastic cytotoxicity against chemotherapeutic

  9. Agent Building Software

    Science.gov (United States)

    2000-01-01

    AgentBuilder is a software component developed under an SBIR contract between Reticular Systems, Inc., and Goddard Space Flight Center. AgentBuilder allows software developers without experience in intelligent agent technologies to easily build software applications using intelligent agents. Agents are components of software that will perform tasks automatically, with no intervention or command from a user. AgentBuilder reduces the time and cost of developing agent systems and provides a simple mechanism for implementing high-performance agent systems.

  10. Competing agents in agent-mediated institutions

    OpenAIRE

    Plaza, Enric; Arcos, Josep Ll.; Noriega, Pablo; Sierra, Carles

    1998-01-01

    Social processes and agent interaction always take place in a specific context. A school of thought in social studies analyses them in the framework of institutions. We present in this paper the notion of agentmediated institutions and show how it is relevant for multi-agent systems (MAS) in general and, more specifically, for MAS that include human agents and software agents involved in socioeconomic interactions. We show how the social interactions of human and software agents taking place ...

  11. The Antineoplastic Effect of Nitric Oxide-Donating Acetylsalicylic Acid (NO-ASA) in Chronic Lymphocytic Leukemia (CLL) Cells is Highly Dependent on its Positional Isomerism

    Science.gov (United States)

    Gehrke, Iris; Razavi, Regina; Poll-Wolbeck, Simon Jonas; Berkessel, Albrecht; Hallek, Michael; Kreuzer, Karl-Anton

    2011-01-01

    Background: Chronic Lymphocytic Leukemia (CLL) is not curable in patients that are not eligible for allogeneic stem cell transplantation. Therefore, new treatment options are highly desirable. Chemically modified nonsteroidal anti-inflammatory drugs (NSAIDs), such as nitric-oxide-donating acetylsalicylic acid (NO-ASA), have been described to possess antineoplastic capacity. Recently, we could demonstrate a potent apoptosis induction in primary CLL cells in vitro and tumor growth inhibition by para-NO-ASA in a xenograft mouse model. However, little is known about the impact of positional isomerism of NO-ASA on its antineoplastic capacity in CLL. Methods: Primary CLL cells were treated with the meta-or para-isomer of NO-ASA at varying concentrations and durations. Viability was assessed flow cytometrically by annexin V-FITC/PI staining and by CellTiter-Glo luminescence cell viability assay. Caspase and PARP cleavage as well as involvement of β-catenin/Lef-1 signaling was determined by immunoblotting. For caspase inhibition, BD™ ApoBlock was used. Nude mice were xenografted with JVM3 cells and treated with meta-NO-ASA, para-NO-ASA or vehicle control. Results: The meta-isomer was entirely ineffective in inducing CLL cell apoptosis in concentrations up to 100 μM, while para-NO-ASA acted in the low micromolar range. meta-NO-ASA, in contrast to para-NO-ASA, did not alter caspase activity. While para-NO-ASA action involved inhibition of β-catenin/Lef-1 signaling, meta-NO-ASA did not show any impact on this signaling pathway. Further, meta-NO-ASA did not significantly reduce tumor growth in a CLL xenograft mouse model, while para-NO-ASA was highly potent. Conclusion: We conclude that positional isomerism is crucial for the antineoplastic effect of NO-ASA in CLL. It can be suggested that the para-isomer, but not the meta-isomer, generates a chemical structure which is essential for the neoplastic effect of NO-ASA. PMID:23556096

  12. Uncaria tomentosa exerts extensive anti-neoplastic effects against the Walker-256 tumour by modulating oxidative stress and not by alkaloid activity.

    Directory of Open Access Journals (Sweden)

    Arturo Alejandro Dreifuss

    Full Text Available This study aimed to compare the anti-neoplastic effects of an Uncaria tomentosa (UT brute hydroethanolic (BHE extract with those of two fractions derived from it. These fractions are choroformic (CHCl3 and n-butanolic (BuOH, rich in pentacyclic oxindole alkaloids (POA and antioxidant substances, respectively. The cancer model was the subcutaneous inoculation of Walker-256 tumour cells in the pelvic limb of male Wistar rat. Subsequently to the inoculation, gavage with BHE extract (50 mg.kg(-1 or its fractions (as per the yield of the fractioning process or vehicle (Control was performed during 14 days. Baseline values, corresponding to individuals without tumour or treatment with UT, were also included. After treatment, tumour volume and mass, plasma biochemistry, oxidative stress in liver and tumour, TNF-α level in liver and tumour homogenates, and survival rates were analysed. Both the BHE extract and its BuOH fraction successfully reduced tumour weight and volume, and modulated anti-oxidant systems. The hepatic TNF-α level indicated a greater effect from the BHE extract as compared to its BuOH fraction. Importantly, both the BHE extract and its BuOH fraction increased the survival time of the tumour-bearing animals. Inversely, the CHCl3 fraction was ineffective. These data represent an in vivo demonstration of the importance of the modulation of oxidative stress as part of the anti-neoplastic activity of UT, as well as constitute evidence of the lack of activity of isolated POAs in the primary tumour of this tumour lineage. These effects are possibly resulting from a synergic combination of substances, most of them with antioxidant properties.

  13. Uncaria tomentosa exerts extensive anti-neoplastic effects against the Walker-256 tumour by modulating oxidative stress and not by alkaloid activity.

    Science.gov (United States)

    Dreifuss, Arturo Alejandro; Bastos-Pereira, Amanda Leite; Fabossi, Isabella Aviles; Lívero, Francislaine Aparecida Dos Reis; Stolf, Aline Maria; Alves de Souza, Carlos Eduardo; Gomes, Liana de Oliveira; Constantin, Rodrigo Polimeni; Furman, Aline Emmer Ferreira; Strapasson, Regiane Lauriano Batista; Teixeira, Simone; Zampronio, Aleksander Roberto; Muscará, Marcelo Nicolás; Stefanello, Maria Elida Alves; Acco, Alexandra

    2013-01-01

    This study aimed to compare the anti-neoplastic effects of an Uncaria tomentosa (UT) brute hydroethanolic (BHE) extract with those of two fractions derived from it. These fractions are choroformic (CHCl3) and n-butanolic (BuOH), rich in pentacyclic oxindole alkaloids (POA) and antioxidant substances, respectively. The cancer model was the subcutaneous inoculation of Walker-256 tumour cells in the pelvic limb of male Wistar rat. Subsequently to the inoculation, gavage with BHE extract (50 mg.kg(-1)) or its fractions (as per the yield of the fractioning process) or vehicle (Control) was performed during 14 days. Baseline values, corresponding to individuals without tumour or treatment with UT, were also included. After treatment, tumour volume and mass, plasma biochemistry, oxidative stress in liver and tumour, TNF-α level in liver and tumour homogenates, and survival rates were analysed. Both the BHE extract and its BuOH fraction successfully reduced tumour weight and volume, and modulated anti-oxidant systems. The hepatic TNF-α level indicated a greater effect from the BHE extract as compared to its BuOH fraction. Importantly, both the BHE extract and its BuOH fraction increased the survival time of the tumour-bearing animals. Inversely, the CHCl3 fraction was ineffective. These data represent an in vivo demonstration of the importance of the modulation of oxidative stress as part of the anti-neoplastic activity of UT, as well as constitute evidence of the lack of activity of isolated POAs in the primary tumour of this tumour lineage. These effects are possibly resulting from a synergic combination of substances, most of them with antioxidant properties.

  14. A dose-ranging study of the pharmacokinetics and pharmacodynamics of the selective apoptotic antineoplastic drug (SAAND), OSI-461, in patients with advanced cancer, in the fasted and fed state.

    Science.gov (United States)

    O'Bryant, C L; Lieu, C H; Leong, S; Boinpally, R; Basche, M; Gore, L; Leonardi, K; Schultz, M K; Hariharan, S; Chow, L; Diab, S; Gibbs, A; Eckhardt, S G

    2009-02-01

    To evaluate the safety, pharmacokinetics and determine the recommended dose of the selective apoptotic antineoplastic drug, OSI-461 administered on a twice-daily regimen to patients with advanced solid malignancies. In this phase I trial, 33 patients were treated with OSI-461 doses ranging from 400 to 1,200 mg given twice daily in 4-week cycles. Pharmacokinetic studies were performed to characterize the plasma disposition of OSI-461 and the effect of food intake on OSI-461 absorption. Secondary biomarker studies were performed to assess the biologic activity of OSI-461 including the measurement of pGSK-3beta, a PKG substrate, and pharmacogenetic studies to identify polymorphisms of CYP3A that influence drug metabolism and of ABCG2, involved in drug resistance. Thirty-three patients were treated with 86 courses of OSI-461. The dose-limiting toxicities were grade 3 abdominal pain, found in one patient at the 1,000 mg BID fed dose level and all patients at the 1,200 mg BID fed dose level. There was also one episode each of grade 3 fatigue and grade 3 constipation at the 1,000 and 1,200 mg BID fed dose levels, respectively. Other common toxicities included mild to moderate fatigue, nausea, anorexia and mild elevation in bilirubin. Pharmacokinetic studies of OSI-461 revealed approximately a twofold increase in AUC(0-24) when OSI-461 was administered with food. An increase in pGSK-3beta post-dose was seen in the majority of patients and was greater at higher dose levels. No patients exhibited CYP3A4 polymorphisms, while 100% of patients were found to have the CYP3A5*3/CYP3A5*3 polymorphism. Two known polymorphisms of the ABCG2 gene, G34 --> A34 and C421 --> A421, occurred at frequencies of 11.76 and 29%, respectively. Toxicity and pharmacodynamic data show that the recommended oral dose of OSI-461 is 800 mg twice daily administered with food. The drug appears to be well-tolerated, and overall bioavailability appears to be markedly increased when the drug is administered

  15. Agility: Agent - Ility Architecture

    National Research Council Canada - National Science Library

    Thompson, Craig

    2002-01-01

    ...., object and web technologies). The objective of the Agility project is to develop an open agent grid architecture populated with scalable, deployable, industrial strength agent grid components, targeting the theme 'agents for the masses...

  16. Mobile Agent Security

    National Research Council Canada - National Science Library

    Jansen, Wayne

    1998-01-01

    Mobile agent technology offers a new computing paradigm in which a program, in the form of a software agent, can suspend its execution on a host computer, transfer itself to another agent-enabled host...

  17. Interacting agents in finance

    NARCIS (Netherlands)

    Hommes, C.; Durlauf, S.N.; Blume, L.E.

    2008-01-01

    Interacting agents in finance represent a behavioural, agent-based approach in which financial markets are viewed as complex adaptive systems consisting of many boundedly rational agents interacting through simple heterogeneous investment strategies, constantly adapting their behaviour in response

  18. The use of antioxidant agents for chemotherapy-induced peripheral neuropathy treatment in animal models.

    Science.gov (United States)

    Carvalho, Larissa F; Silva, Ana Maria F; Carvalho, Adriana A

    2017-10-01

    Antineoplastic drugs such as cisplatin, oxaliplatin, paclitaxel and vincristin are widely used in the treatment of several solid and blood tumours. However, the severity of peripheral neuropathy caused by these agents can affect the patient's quality of life. The major symptoms of chemotherapy-induced peripheral neuropathy (CIPN) involve: sensory loss, paresthesia, dysesthaesia, numbness, tingling, temperature sensitivity, allodynia and hyperalgesia, in a "stocking and glove" distribution. Why many different chemotherapeutic agents result in similar neuropathy profiles is unclear. Many drug classes such as antidepressants, anticonvulsants, antispastic agents and others have been used in clinical practice, but there is no scientific evidence to prove their effectiveness. But drugs as the antioxidant have shown a protective effect against free radical damage. In order to find out a successful treatment for CIPN, animal studies (ie pharmacological and mechanical tests and histopathological immunohistochemical analyses) have been developed to try to determinate the action of the antioxidant agents. This review provides an overview of the major antioxidant agents recently investigated to treat CIPN and the animal models used for this purpose. © 2017 John Wiley & Sons Australia, Ltd.

  19. Histone deacetylase inhibitors (HDACIs: multitargeted anticancer agents

    Directory of Open Access Journals (Sweden)

    Ververis K

    2013-02-01

    advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while discussing the safety and efficacy of these compounds in clinical studies to date.Keywords: chromatin modifications, histone acetylation, histone deacetylase inhibitor, suberoylanilide hydroxamic acid, depsipeptide, entinostat

  20. Active vitamin D potentiates the anti-neoplastic effects of calcium in the colon: A cross talk through the calcium-sensing receptor.

    Science.gov (United States)

    Aggarwal, Abhishek; Höbaus, Julia; Tennakoon, Samawansha; Prinz-Wohlgenannt, Maximilian; Graça, João; Price, Sally A; Heffeter, Petra; Berger, Walter; Baumgartner-Parzer, Sabina; Kállay, Enikö

    2016-01-01

    Epidemiological studies suggest an inverse correlation between dietary calcium (Ca(2+)) and vitamin D intake and the risk of colorectal cancer (CRC). It has been shown in vitro that the active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25-D3) can upregulate expression of the calcium-sensing receptor (CaSR). In the colon, CaSR has been suggested to regulate proliferation of colonocytes. However, during tumorigenesis colonic CaSR expression is downregulated and we hypothesized that the loss of CaSR could influence the anti-tumorigenic effects of Ca(2+) and vitamin D. Our aim was to assess the impact of CaSR expression and function on the anti-neoplastic effects of 1,25-D3 in colon cancer cell lines. We demonstrated that in the healthy colon of mice, high vitamin D diet (2500 IU/kg diet) increased expression of differentiation and apoptosis markers, decreased expression of proliferation markers and significantly upregulated CaSR mRNA expression, compared with low vitamin D diet (100 IU/kg diet). To determine the role of CaSR in this process, we transfected Caco2-15 and HT29 CRC cells with wild type CaSR (CaSR-WT) or a dominant negative CaSR mutant (CaSR-DN) and treated them with 1,25-D3 alone, or in combination with CaSR activators (Ca(2+) and NPS R-568). 1,25-D3 enhanced the anti-proliferative effects of Ca(2+) and induced differentiation and apoptosis only in cells with a functional CaSR, which were further enhanced in the presence of NPS R-568, a positive allosteric modulator of CaSR. The mutant CaSR inhibited the anti-tumorigenic effects of 1,25-D3 suggesting that the anti-neoplastic effects of 1,25-D3 are, at least in part, mediated by the CaSR. Taken together, our data provides molecular evidence to support the epidemiological observation that both, vitamin D and calcium are needed for protection against malignant transformation of the colon and that their effect is modulated by the presence of a functional CaSR. This article is part of a Special Issue

  1. Dexamethasone-(C21-phosphoramide)-[anti-EGFR]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency against pulmonary adenocarcinoma (A549).

    Science.gov (United States)

    Coyne, Cody P; Narayanan, Lakshmi

    2016-01-01

    Corticosteroids are effective in the management of a variety of disease states, such as several forms of neoplasia (leukemia and lymphoma), autoimmune conditions, and severe inflammatory responses. Molecular strategies that selectively "target" delivery of corticosteroids minimize or prevents large amounts of the pharmaceutical moiety from passively diffusing into normal healthy cell populations residing within tissues and organ systems. The covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR] was synthesized by reacting dexamethasone-21-monophosphate with a carbodiimide reagent to form a dexamethasone phosphate carbodiimide ester that was subsequently reacted with imidazole to create an amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate. Monoclonal anti-EGFR immunoglobulin was combined with the amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate, resulting in the synthesis of the covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR]. Following spectrophotometric analysis and validation of retained epidermal growth factor receptor type 1 (EGFR)-binding avidity by cell-ELISA, the selective anti-neoplasic cytotoxic potency of dexamethasone-(C21-phosphoramide)-[anti-EGFR] was established by MTT-based vitality stain methodology using adherent monolayer populations of human pulmonary adenocarcinoma (A549) known to overexpress the tropic membrane receptors EGFR and insulin-like growth factor receptor type 1. The dexamethasone:IgG molar-incorporation-index for dexamethasone-(C21-phosphoramide)-[anti-EGFR] was 6.95:1 following exhaustive serial microfiltration. Cytotoxicity analysis: covalent bonding of dexamethasone to monoclonal anti-EGFR immunoglobulin did not significantly modify the ex vivo antineoplastic cytotoxicity of dexamethasone against pulmonary adenocarcinoma at and between the standardized dexamethasone equivalent concentrations of 10(-9) M and 10(-5) M. Rapid increases in

  2. Toxicities of four anti-neoplastic drugs and their binary mixtures tested on the green alga Pseudokirchneriella subcapitata and the cyanobacterium Synechococcus leopoliensis.

    Science.gov (United States)

    Brezovšek, Polona; Eleršek, Tina; Filipič, Metka

    2014-04-01

    The residues of anti-neoplastic drugs are new and emerging pollutants in aquatic environments. This is not only because of their increasing use, but also because due to their mechanisms of action, they belong to a group of particularly dangerous compounds. However, information on their ecotoxicological properties is very limited. We tested the toxicities of four anti-neoplastic drugs with different mechanisms of action (5-fluorouracil [5-FU], cisplatin [CDDP], etoposide [ET], and imatinib mesylate [IM]), and some of their binary mixtures, against two phytoplankton species: the alga Pseudokirchneriella subcapitata, and the cyanobacterium Synechococcus leopoliensis. These four drugs showed different toxic potential, and the two species examined also showed differences in their susceptibilities towards the tested drugs and their mixtures. With P. subcapitata, the most toxic of these drugs was 5-FU (EC50, 0.13 mg/L), followed by CDDP (EC50, 1.52 mg/L), IM (EC50, 2.29 mg/L), and the least toxic, ET (EC50, 30.43 mg/L). With S. leopoliensis, the most toxic was CDDP (EC50, 0.67 mg/L), followed by 5-FU (EC50, 1.20 mg/L) and IM (EC50, 5.36 mg/L), while ET was not toxic up to 351 mg/L. The toxicities of the binary mixtures tested (5-FU + CDDP, 5-FU + IM, CDDP + ET) were predicted by the concepts of 'concentration addition' and 'independent action', and are compared to the experimentally determined toxicities. The measured toxicity of 5-FU + CDDP with P. subcapitata and S. leopoliensis was higher than that predicted, while the measured toxicity of CDDP + ET with both species was lower than that predicted. The measured toxicity of 5-FU + IM with P. subcapitata was higher, and with S. leopoliensis was lower, than that predicted. These data show that these mixtures can have compound-specific and species-specific synergistic or antagonistic effects, and they suggest that single compound toxicity data are not sufficient for the prediction of the aquatic

  3. Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel–cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Ye J

    2016-08-01

    Full Text Available Jun Ye,1,2 Xuejun Xia,1,2 Wujun Dong,1,2 Huazhen Hao,1,2 Luhua Meng,1,2 Yanfang Yang,1,2 Renyun Wang,1,2 Yuanfeng Lyu,3 Yuling Liu1,2 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 2Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 3School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: There is no effective clinical therapy for triple-negative breast cancers (TNBCs, which have high low-density lipoprotein (LDL requirements and express relatively high levels of LDL receptors (LDLRs on their membranes. In our previous study, a novel lipid emulsion based on a paclitaxel–cholesterol complex (PTX-CH Emul was developed, which exhibited improved safety and efficacy for the treatment of TNBC. To date, however, the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul have not been investigated. In order to offer powerful proof for the therapeutic effects of PTX-CH Emul, we systematically studied the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul and made a comparative evaluation of antineoplastic effects on TNBC (MDA-MB-231 and non-TNBC (MCF7 cell lines through in vitro and in vivo experiments. The in vitro antineoplastic effects and in vivo tumor-targeting efficiency of PTX-CH Emul were significantly more enhanced in MDA-MB-231-based models than those in MCF7-based models, which was associated with the more abundant expression profile of LDLR in MDA-MB-231 cells. The results of the cellular uptake mechanism indicated that PTX-CH Emul was internalized into breast cancer cells through the LDLR-mediated internalization pathway via clathrin-coated pits, localized in lysosomes, and then released into the cytoplasm, which was consistent with the internalization pathway and intracellular trafficking of native

  4. A literature update elucidating production of Panax ginsenosides with a special focus on strategies enriching the anti-neoplastic minor ginsenosides in ginseng preparations.

    Science.gov (United States)

    Biswas, Tanya; Mathur, A K; Mathur, Archana

    2017-05-01

    Ginseng, an oriental gift to the world of healthcare and preventive medicine, is among the top ten medicinal herbs globally. The constitutive triterpene saponins, ginsenosides, or panaxosides are attributed to ginseng's miraculous efficacy towards anti-aging, rejuvenating, and immune-potentiating benefits. The major ginsenosides such as Rb1, Rb2, Rc, Rd., Re, and Rg1, formed after extensive glycosylations of the aglycone "dammaranediol," dominate the chemical profile of this genus in vivo and in vitro. Elicitations have successfully led to appreciable enhancements in the production of these major ginsenosides. However, current research on ginseng biotechnology has been focusing on the enrichment or production of the minor ginsenosides (the less glycosylated precursors of the major ginsenosides) in ginseng preparations, which are either absent or are produced in very low amounts in nature or via cell cultures. The minor ginsenosides under current scientific scrutiny include diol ginsenosides such as Rg3, Rh2, compound K, and triol ginsenosides Rg2 and Rh1, which are being touted as the next "anti-neoplastic pharmacophores," with better bioavailability and potency as compared to the major ginsenosides. This review aims at describing the strategies for ginsenoside production with special attention towards production of the minor ginsenosides from the major ginsenosides via microbial biotransformation, elicitations, and from heterologous expression systems.

  5. Necroptosis mediates the antineoplastic effects of the soluble fraction of polysaccharide from red wine in Walker-256 tumor-bearing rats.

    Science.gov (United States)

    Stipp, Maria Carolina; Bezerra, Iglesias de Lacerda; Corso, Claudia Rita; Dos Reis Livero, Francislaine A; Lomba, Luiz Alexandre; Caillot, Adriana Rute Cordeiro; Zampronio, Aleksander Roberto; Queiroz-Telles, José Ederaldo; Klassen, Giseli; Ramos, Edneia A S; Sassaki, Guilherme Lanzi; Acco, Alexandra

    2017-03-15

    Polysaccharides are substances that modify the biological response to several stressors. The present study investigated the antitumor activity of the soluble fraction of polysaccharides (SFP), extracted from cabernet franc red wine, in Walker-256 tumor-bearing rats. The monosaccharide composition had a complex mixture, suggesting the presence of arabinoglactans, mannans, and pectins. Treatment with SFP (30 and 60mg/kg, oral) for 14days significantly reduced the tumor weight and volume compared with controls. Treatment with 60mg/kg SFP reduced blood monocytes and neutrophils, reduced the tumor activity of N-acetylglucosaminidase, myeloperoxidase, and nitric oxide, increased blood lymphocytes, and increased the levels of tumor necrosis factor α (TNF-α) in tumor tissue. Treatment with SFP also induced the expression of the cell necroptosis-related genes Rip1 and Rip3. The antineoplastic effect of SFP appears to be attributable to its action on the immune system by controlling the tumor microenvironment and stimulating TNF-α production, which may trigger the necroptosis pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Quantitative assessment of the relative antineoplastic potential of the n-butanolic leaf extract of Annona muricata Linn. in normal and immortalized human cell lines.

    Science.gov (United States)

    George, V Cijo; Kumar, D R Naveen; Rajkumar, V; Suresh, P K; Kumar, R Ashok

    2012-01-01

    Natural products have been the target for cancer therapy for several years but there is still a dearth of information on potent compounds that may protect normal cells and selectively destroy cancerous cells. The present study was aimed to evaluate the cytotoxic potential of n-butanolic leaf extract of Annona muricata L. on WRL-68 (normal human hepatic cells), MDA-MB-435S (human breast carcinoma cells) and HaCaT (human immortalized keratinocyte cells) lines by XTT assay. Prior to cytotoxicity testing, the extract was subjected to phytochemical screening for detecting the presence of compounds with therapeutic potential. Their relative antioxidant properties were evaluated using the reducing power and DPPH* radical scavenging assay. Since most of the observed chemo-preventive potential invariably correlated with the amount of total phenolics present in the extract, their levels were quantified and identified by HPLC analysis. Correlation studies indicated a strong and significant (Pcancerous cells (IC50 values of 29.2 μg for MDA-MB-435S and 30.1 μg for HaCaT respectively). The study confirms the presence of therapeutically active antineoplastic compounds in the n-butanolic leaf extract of Annona muricata. Isolation of the active metabolites from the extract is in prospect.

  7. Omega-3 PUFA Loaded in Resveratrol-Based Solid Lipid Nanoparticles: Physicochemical Properties and Antineoplastic Activities in Human Colorectal Cancer Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Simona Serini

    2018-02-01

    Full Text Available New strategies are being investigated to ameliorate the efficacy and reduce the toxicity of the drugs currently used in colorectal cancer (CRC, one of the most common malignancies in the Western world. Data have been accumulated demonstrating that the antineoplastic therapies with either conventional or single-targeted drugs could take advantage from a combined treatment with omega-3 polyunsaturated fatty acids (omega-3 PUFA. These nutrients, shown to be safe at the dosage generally used in human trials, are able to modulate molecules involved in colon cancer cell growth and survival. They have also the potential to act against inflammation, which plays a critical role in CRC development, and to increase the anti-cancer immune response. In the present study, omega-3 PUFA were encapsulated in solid lipid nanoparticles (SLN having a lipid matrix containing resveratrol esterified to stearic acid. Our aim was to increase the efficiency of the incorporation of these fatty acids into the cells and prevent their peroxidation and degradation. The Resveratrol-based SLN were characterized and investigated for their antioxidant activity. It was observed that the encapsulation of omega-3 PUFA into the SLN enhanced significantly their incorporation in human HT-29 CRC cells in vitro, and their growth inhibitory effects in these cancer cells, mainly by reducing cell proliferation.

  8. Radiopharmaceutical scanning agents

    International Nuclear Information System (INIS)

    1976-01-01

    This invention is directed to dispersions useful in preparing radiopharmaceutical scanning agents, to technetium labelled dispersions, to methods for preparing such dispersions and to their use as scanning agents

  9. Reasoning about emotional agents

    NARCIS (Netherlands)

    Meyer, J.-J.

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

  10. Asymptotically Optimal Agents

    OpenAIRE

    Lattimore, Tor; Hutter, Marcus

    2011-01-01

    Artificial general intelligence aims to create agents capable of learning to solve arbitrary interesting problems. We define two versions of asymptotic optimality and prove that no agent can satisfy the strong version while in some cases, depending on discounting, there does exist a non-computable weak asymptotically optimal agent.

  11. DEVELOPMENT OF ANTIVIRAL AGENTS

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. DEVELOPMENT OF ANTIVIRAL AGENTS. Chandipura virus can be regarded as a model system to design and develop antiviral agents. These agents could be small molecules or RNA/PNA aptamers or Antisense RNA to speicific gene sequence in the viral genome.

  12. Importance of cell cycle perturbations on the effectiveness of N-methylformamide and anti-neoplastic drugs in combination.

    Science.gov (United States)

    Cucco, C; D'Agnano, I; Marangolo, M; Candiloro, A; Zupi, G

    1991-05-01

    The effect of N-methylformamide (NMF) in combination with Adriamycin (ADM) and cis-diamminedichloroplatinum (DDP) on the cell survival and cell cycle kinetics of two human tumour lines was assessed: HT29 colon carcinoma and M14 melanoma cells were exposed to ADM and DDP alone or in combination with a non-cytotoxic dose of NMF, according to different schedules. The results demonstrate that NMF exposure sensitized both tumour cell lines to the lethal activity of ADM and DDP; however, reverse sequences had to be applied to reach an increase in the lethal activity of the two different drugs. The ADM-NMF combination determined a powerful decrease in the surviving fraction of the two cell lines when ADM was given as the first agent (ADM----NMF), while the reverse sequence did not increase the ADM cytotoxic effect. With respect to the DDP-NMF association, the sequence which accounted for a greater sensitizing effect was NMF administration followed by DDP treatment (NMF----DDP). This work demonstrates the importance of timing in combined treatments which involve NMF. A delay in cell proliferation elicited by NMF exposure could be responsible for the effectiveness of the combined treatment.

  13. A 25-Year Experience of Gastroenteropancreatic Neuroendocrine Tumors and Somatostatin (Congeners) Analogs: From Symptom Control to Antineoplastic Therapy.

    Science.gov (United States)

    O'Dorisio, Thomas M; Anthony, Lowell B

    2015-01-01

    Radioimmunoassay technology was utilized in the discovery of somatostatin and was quickly brought into therapeutics; however, it took the development of somatostatin congeners to solve its limitations of a short half-life. Therapeutic medical control of hyperhormonal states such as acromegaly, carcinoid syndrome and VIPoma significantly advanced from a nonspecific approach to one that specifically and effectively targeted the underlying pathophysiology. Clinical care was transformed from nonspecific symptom control to one of a significant improvement in not only quality of life, but also quantity of life. These data submitted to US and European regulatory authorities for approval included many investigative sites with no uniform protocol and multiple investigational new drugs, and have not been previously published. This review includes the original data demonstrating the transformational impact this class of agents had on specific disease subsets resulting in regulatory approval 25 years ago. Autoradiography techniques using somatostatin resulted in identifying, localizing and characterizing its receptor subtypes. Translating in vitro data to in vivo resulted in scintigraphic whole body and SPECT scans with (111)In-pentetreotide and was incorporated into standard clinical care 20 years ago. (68)Ga-octreotide congeners using PET scanning offers a major imaging advance. Peptide receptor radiotherapy has evolved over the last 2 decades and utilizes several therapeutic isotopes, including (90)Y and (177)Lu. © 2015 S. Karger AG, Basel.

  14. Radiographic scanning agent

    International Nuclear Information System (INIS)

    Bevan, J.A.

    1983-01-01

    This invention relates to radiodiagnostic agents and more particularly to a composition and method for preparing a highly effective technetium-99m-based bone scanning agent. One deficiency of x-ray examination is the inability of that technique to detect skeletal metastases in their incipient stages. It has been discovered that the methanehydroxydiphosphonate bone mineral-seeking agent is unique in that it provides the dual benefits of sharp radiographic imaging and excellent lesion detection when used with technetium-99m. This agent can also be used with technetium-99m for detecting soft tissue calcification in the manner of the inorganic phosphate radiodiagnostic agents

  15. Agente adaptable y aprendizaje

    Directory of Open Access Journals (Sweden)

    Arturo Angel Lara Rivero

    2013-05-01

    Full Text Available En este trabajo se contrasta el concepto de agente programado con el de agente complejo adaptable, se presenta una nueva visión ligada al aprendizaje y la estructura del agente. La imagen del agente se analiza considerando los modelos internos, la práctica, el concepto de rutina y la influencia en su comportamiento, y la importancia del aprendizaje ex ante y ex post. Por último se muestra que la resolución de problemas está sujeta a restricciones del agente y se describen las formas de explorar el espacio de soluciones mediante tres tipos de exploración: exhaustiva, aleatoria y selectiva.

  16. DNA damage induced in mouse peritoneal exudate cells after in vivo administration of chemical and physical agents as determined by alkaline elution

    International Nuclear Information System (INIS)

    Nishi, Yoshisuke; Miyanaga, Kumiko; Sato, Sei-ichi; Inui, Naomichi

    1990-01-01

    The alkaline elution technique for detecting DNA strand breaks has been applied to the study of DNA damage in mouse peritoneal exudate cells resulting from the in vivo administration of chemical and physical agents. The direct methylating agents methyl methanesulphonate and N-methyl-N-nitrosourea induced extensive breakage in samples taken 2 h after administration. The direct ethylating agents ethyl methanesulphonate and N-ethyl-N-nitrosourea also induced DNA strand breaks, but to a lesser extent than the methylating agents. The indirect methylating agent dimethylnitrosamine showed hardly any effect in this system. A weak but positive response was observed upon treatment with the anti-neoplastic alkylating agent procarbazine hydrochloride. The whole-body irradiation of mice with 60 Co γ-rays also induced DNA strand breaks. The elution profiles for γ-ray irradiation were different from those of alkylating agents, and indicate that alkylating agents produce many more secondary lesions leading to DNA strand breaks than γ-rays. N-methyl-N-nitrosourea produced slightly more DNA strand breaks in mutagen-sensitive mice, which are derived from the CD-1 strain, than in ICR mice. (Author)

  17. UbcH10 expression can predict prognosis and sensitivity to the antineoplastic treatment for colorectal cancer patients.

    Science.gov (United States)

    Cacciola, Nunzio Antonio; Calabrese, Chiara; Malapelle, Umberto; Pellino, Gianluca; De Stefano, Alfonso; Sepe, Romina; Sgariglia, Roberta; Quintavalle, Cristina; Federico, Antonella; Bianco, Antonio; Uchimura Bastos, André; Milone, Marco; Bellevicine, Claudio; Milone, Francesco; Carlomagno, Chiara; Selvaggi, Francesco; Troncone, Giancarlo; Fusco, Alfredo; Pallante, Pierlorenzo

    2016-05-01

    Colorectal cancer (CRC) is one of the most frequent and deadly malignancies worldwide. Despite the progresses made in diagnosis and treatment, the identification of tumor markers is still a strong clinical need, because current treatments are efficacious only in a subgroup of patients. UbcH10 represents a potential candidate biomarker, whose expression levels could be employed to predict response or resistance to chemotherapy or targeted agents. UbcH10 mRNA and protein expression levels have been evaluated in a large group of CRC patients and correlated with clinico-pathological characteristics, including KRAS mutations. Moreover, the endogenous levels of UbcH10 and its role on cell growth have been evaluated in CRC cells. Finally, to investigate the impact of UbcH10 protein expression on the response to irinotecan, its active metabolite SN-38 and cetuximab treatment, UbcH10 silencing experiments were carried-out on two colon carcinoma cell lines, Caco-2, and DLD1. Overexpression of UbcH10 mRNA and protein was observed in the vast majority of patients analyzed. UbcH10 suppression decreased CRC cell growth rate (at least in part through deregulation of Cyclin B and ERK1) and sensitized them to pharmacological treatments with irinotecan, SN-38 and cetuximab (at least in part through a down-regulation of AKT). Taken together, these findings indicate that UbcH10 expression regulates CRC growth and could play an important role in the personalization of the therapy of CRC patients. © 2015 Wiley Periodicals, Inc.

  18. Agent Programming Languages and Logics in Agent-Based Simulation

    DEFF Research Database (Denmark)

    Larsen, John

    2018-01-01

    and social behavior, and work on verification. Agent-based simulation is an approach for simulation that also uses the notion of agents. Although agent programming languages and logics are much less used in agent-based simulation, there are successful examples with agents designed according to the BDI......Research in multi-agent systems has resulted in agent programming languages and logics that are used as a foundation for engineering multi-agent systems. Research includes reusable agent programming platforms for engineering agent systems with environments, agent behavior, communication protocols...... paradigm, and work that combines agent-based simulation platforms with agent programming platforms. This paper analyzes and evaluates benefits of using agent programming languages and logics for agent-based simulation. In particular, the paper considers the use of agent programming languages and logics...

  19. Moral actor, selfish agent.

    Science.gov (United States)

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

    2014-05-01

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

  20. Design of novel antitumor DNA alkylating agents: the benzacronycine series.

    Science.gov (United States)

    David-Cordonnier, Marie-Hélène; Laine, William; Gaslonde, Thomas; Michel, Sylvie; Tillequin, Francois; Koch, Michel; Léonce, Stéphane; Pierré, Alain; Bailly, Christian

    2004-03-01

    Acronycine, a natural alkaloid originally extracted from the bark of the Australian ash scrub Acronychia baueri, has shown a significant antitumor activity in animal models. Acronycine has been tested against human cancers in the early 1980s, but the clinical trials showed modest therapeutic effects and its development was rapidly discontinued. In order to optimize the antineoplastic effect, different benzoacronycine derivatives were synthesized. Among those, the di-acetate compound S23906-1 was recently identified as a promising anticancer drug candidate and a novel alkylating agent specifically reacting with the exocylic 2-NH2 group of guanines in DNA. The study of DNA bonding capacity of acronycine derivatives leads to the identification of the structural requirements for DNA alkylation. In nearly all cases, the potent alkylating agents, such as S23906-1, were found to be much more cytotoxic than the unreactive analogs such as acronycine itself or diol derivatives. Alkylation of DNA by the monoacetate derivative S28687-1, which is a highly reactive hydrolysis metabolite of S23906-1, occurs with a marked preference for the N2 position of guanine. Other bionucleophiles can react with S23906-1. The benzacronycine derivatives, which efficiently alkylate DNA, also covalently bind to the tripeptide glutathione (GSH) but not to the oxidized product glutathione disulfide. Here we review the reactivity of S23906-1 and some derivatives toward DNA and GSH. The structure-activity relationships in the benzacronycine series validate the reaction mechanism implicating DNA as the main molecular target. S23906-1 stands as the most promising lead of a medicinal chemistry program aimed at discovering novel antitumor drugs based on the acronycine skeleton.

  1. Dexamethasone-(C21-phosphoramide-[anti-EGFR]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency against pulmonary adenocarcinoma (A549

    Directory of Open Access Journals (Sweden)

    Coyne CP

    2016-08-01

    did not significantly modify the ex vivo antineoplastic cytotoxicity of dexamethasone against pulmonary adenocarcinoma at and between the standardized dexamethasone equivalent concentrations of 10-9 M and 10-5 M. Rapid increases in antineoplastic cytotoxicity were observed at and between the dexamethasone equivalent concentrations of 10-9 M and 10-7 M where cancer cell death increased from 7.7% to a maximum of 64.9% (92.3%–35.1% residual survival, respectively, which closely paralleled values for “free” noncovalently bound dexamethasone. Discussion: Organic chemistry reaction regimens were optimized to develop a multiphase synthesis regimen for dexamethasone-(C21-phosphoramide-[anti-EGFR]. Attributes of dexamethasone-(C21-phosphoramide-[anti-EGFR] include a high dexamethasone molar incorporation-index, lack of extraneous chemical group introduction, retained EGFR-binding avidity (“targeted” delivery properties, and potential to enhance long-term pharmaceutical moiety effectiveness. Keywords: dexamethasone, anti-EGFR, organic chemistry reactions, synthesis, selective “targeted” delivery, covalent immunopharmaceuticals, EGFR 

  2. Apoptosis by antitumor agents and other factors in relation to cell cycle checkpoints

    International Nuclear Information System (INIS)

    Kondo, Sohei

    1995-01-01

    More than a cancer patients died in 1993 after treatment with antineoplastic derivatives of 5-fluorouracil and the antiherpes drug Sorivudine. This paper gives a short review of previous reports showing that killing of cells by 5-fluorouracil and other antitumor agents, including radiation at high doses, results from activation of apoptosis in the G2 phase. On the other hand, apoptosis of lymphocytes by radiation at low doses and treatment with other agents is known to occur in the G1 phase. The cells dying in the G1 or G2 phase could share the same final self-killing steps. For these common steps, I assume a mitotic catastrophe model, in which commitment to self-killing results from premature activation of the mitosis machinery, and propose a concept of a 'G1/G2 death circuit' for cells dying in the G1/G2 phase by short circuit to the M phase. Based on this model, reported modes of cell death, spontaneously occurring or after treatment with various agents, are classified by the phase of dying cells. The associations of incomplete apoptosis with production of chromosomal aberrations and prevention of tumorigenesis by complete apoptosis of carcinogen-treated cells are discussed. A presumptive rule for differentiation of G1 apoptosis and G2 apoptosis is proposed. (author)

  3. Prediction of drug distribution in subcutaneous xenografts of human tumor cell lines and healthy tissues in mouse: application of the tissue composition-based model to antineoplastic drugs.

    Science.gov (United States)

    Poulin, Patrick; Chen, Yung-Hsiang; Ding, Xiao; Gould, Stephen E; Hop, Cornelis Eca; Messick, Kirsten; Oeh, Jason; Liederer, Bianca M

    2015-04-01

    Advanced tissue composition-based models can predict the tissue-plasma partition coefficient (Kp ) values of drugs under in vivo conditions on the basis of in vitro and physiological input data. These models, however, focus on healthy tissues and do not incorporate data from tumors. The objective of this study was to apply a tissue composition-based model to six marketed antineoplastic drugs (docetaxel, DOC; doxorubicin, DOX; gemcitabine, GEM; methotrexate, MTX; topotecan, TOP; and fluorouracil, 5-FU) to predict their Kp values in three human tumor xenografts (HCT-116, H2122, and PC3) as well as in healthy tissues (brain, muscle, lung, and liver) under steady-state in vivo conditions in female NCR nude mice. The mechanisms considered in the tissue/tumor composition-based model are the binding to lipids and to plasma proteins, but the transporter effect was also investigated. The method consisted of analyzing tissue composition, performing the pharmacokinetics studies in mice, and calculating the corresponding in vivo Kp values. Analyses of tumor composition indicated that the tumor xenografts contained no or low amounts of common transporters by contrast to lipids. The predicted Kp values were within twofold and threefold of the measured values in 77% and 93% of cases, respectively. However, predictions for brain for each drug, for liver for MTX, and for each tumor xenograft for GEM were disparate from the observed values, and, therefore, not well served by the model. Overall, this study is the first step toward the mechanism-based prediction of Kp values of small molecules in healthy and tumor tissues in mouse when no transporter and permeation limitation effect is evident. This approach will be useful in selecting compounds based on their abilities to penetrate human cancer xenografts with a physiologically based pharmacokinetic (PBPK) model, thereby increasing therapeutic index for chemotherapy in oncology study. © 2015 Wiley Periodicals, Inc. and the American

  4. Stabilized radiographic scanning agents

    International Nuclear Information System (INIS)

    Fawzi, M.B.

    1982-01-01

    Stable compositions useful as technetium 99m-based scintigraphic agents comprise gentisic acid 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

  5. 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...

  6. Empathic Agent Technology (EAT)

    NARCIS (Netherlands)

    Johnson, L.; van den Broek, Egon; Richards, D.; Sklar, E.; Wilensky, U.

    2005-01-01

    A new view on empathic agents is introduced, named: Empathic Agent Technology (EAT). It incorporates a speech analysis, which provides an indication for the amount of tension present in people. It is founded on an indirect physiological measure for the amount of experienced stress, defined as the

  7. Agents in domestic environments

    NARCIS (Netherlands)

    Daniël Telgen; John-Jules Meyer; Glenn Meerstra; Franc Pape; Ing. Erik Puik; Leo van Moergestel; Niels van Nieuwenburg; Wouter Langerak

    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

  8. Change Agent Survival Guide

    Science.gov (United States)

    Dunbar, Folwell L.

    2011-01-01

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

  9. Travel Agent Course Outline.

    Science.gov (United States)

    British Columbia Dept. of Education, Victoria.

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

  10. Investigation of the interaction of radiation and cardiotoxic anticancer agents using a fetal mouse heart organ culture system

    International Nuclear Information System (INIS)

    Kimler, B.F.; Rethorst, R.D.; Cox, G.G.

    1985-01-01

    The fetal mouse heart organ culture was utilized in an attempt to predict the cardiotoxic effects of combinations of radiation, Adriamycin (ADR), and Dihydroxyanthraquinone (DHAQ), antineoplastic agents which have been shown to produce clinical cardiomyopathy. Seventeen-day fetal hearts were removed and placed in a culture system of micro-titer plates. A single heart was placed in each well on a piece of aluminum mesh to keep the heart above the culture medium but bathed by capillary action. The plates were then placed in a 100% oxygen environment at 37 0 C. Treatments were performed on day 1 after culture: radiation doses (Cs-137) of 10, 20, or 40 Gy; drug treatment with 10, 30, or 100 μg/ml of ADR; 5, 20, or 50 μg/ml of DHAQ; and combinations and sequences of drug and radiation. Hearts were checked every day for functional activity as evidenced by a continuous heart beat. Untreated hearts beat rhythmically for up to 9 days; treated hearts stopped beating earlier. Using an endpoint of functional retention time, dose response curves were obtained for all individual agents and for combinations of agents. This system may help to predict the cardiotoxic effects that result from the use of these drugs and radiation. It may also aid in the development of new anthracycline chemotherapeutic agents that lack cardiotoxicity

  11. 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.

  12. 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...

  13. Health care agents

    Science.gov (United States)

    ... do not want these treatments. Order sterilization or abortion. Choosing Your Health Care Agent Choose a person ... working well. A health care proxy is a legal paper that you fill out. You can get ...

  14. Robust Agent-Based Systems Incorporating Teams of Communicating Agents

    National Research Council Canada - National Science Library

    Cohen, Philip

    2004-01-01

    ... (AgentTalk). The A3 architecture supports human participation as agents, dynamic formation of agent teams, reorganization of teams based on network loads, and offers libraries for legacy code to be able...

  15. Targeting ferritin receptors for the selective delivery of imaging and therapeutic agents to breast cancer cells.

    Science.gov (United States)

    Geninatti Crich, S; Cadenazzi, M; Lanzardo, S; Conti, L; Ruiu, R; Alberti, D; Cavallo, F; Cutrin, J C; Aime, S

    2015-04-21

    In this work the selective uptake of native horse spleen ferritin and apoferritin loaded with MRI contrast agents has been assessed in human breast cancer cells (MCF-7 and MDA-MB-231). The higher expression of L-ferritin receptors (SCARA5) led to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent Gd-HPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin, it was possible to deliver a therapeutic dose of 167 μg ml(-1) (as calculated by MRI) of this natural drug to MCF-7 cells, thus obtaining a significant reduction of cell proliferation.

  16. 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.

  17. Monitoring volatile anaesthetic agents

    International Nuclear Information System (INIS)

    Russell, W.J.

    2000-01-01

    Full text: The methods that have been used for monitoring volatile anaesthetic agents depend on some physical property such as Density, Refractometry, Mass, Solubility, Raman scattering, or Infra-red absorption. Today, refractometry and infra-red techniques are the most common. Refractometry is used for the calibration of vaporizers. All anaesthetic agents increase the refractive index of the carrier gas. Provided the mixture is known then the refractive change measures the concentration of the volatile anaesthetic agent. Raman Scattering is when energy hits a molecule a very small fraction of the energy is absorbed and re-emitted at one or more lower frequencies. The shift in frequency is a function of the chemical bonds and is a fingerprint of the substance irradiated. Electromagnetic (Infra-red) has been the commonest method of detection of volatile agents. Most systems use a subtractive system, i.e. the agent in the sampling cell absorbed some of the infrared energy and the photo-detector therefore received less energy. A different approach is where the absorbed energy is converted into a pressure change and detected as sound (Acoustic monitor). This gives a more stable zero reference. More recently, the detector systems have used multiple narrow-band wavelengths in the infrared bands and by shape matching or matrix computing specific agent identification is achieved and the concentration calculated. In the early Datex AS3 monitors, a spectral sweep across the 3 micron infrared band was used to create spectral fingerprints. The recently released AS3 monitors use a different system with five very narrow band filters in the 8-10 micron region. The transmission through each of these filters is a value in a matrix which is solved by a micro computer to identify the agent and its concentration. These monitors can assist in improving the safety and efficiency of our anaesthetics but do not ensure that the patient is completely anaesthetized. Copyright (2000

  18. Teaching tourism change agents

    DEFF Research Database (Denmark)

    Blichfeldt, Bodil Stilling; Kvistgaard, Hans-Peter; Hird, John

    2017-01-01

    This article discuss es know ledge, competencies and skills Master’s students should obtain during their academic studies and particularly, the differences between teaching about a topic and teaching to do. This is ex emplified by experiential learning theory and the case of a change management...... course that is part of a Tourism Master’s program, where a major challenge is not only to teach students about change and change agents, but to teach them how change feels and ho w to become change agents. The c hange management course contains an experiment inspired by experiential teaching literature...... and methods. The experiment seeks to make students not only hear/learn about change agency and management, but to make them feel cha nge, hereby enabling them to develop the skills and competencies necessary for them to take on the role as change agent s and thus enable them to play key role s in implementing...

  19. 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

  20. Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) in vivo

    Czech Academy of Sciences Publication Activity Database

    Weber, T.; Lu, M.; Anděra, Ladislav; Lanm, H.; Gellert, N.; Fariss, M. W.; Kořínek, Vladimír; Sattler, W.; Ucker, D. S.; Terman, A.; Schroder, B.; Erl, W.; Brunk, U. T.; Coffey, R. J.; Weber, C.; Neužil, J.

    2002-01-01

    Roč. 8, č. 3 (2002), s. 863-869 ISSN 1078-0432 R&D Projects: GA AV ČR IAA5052001; GA ČR GA301/99/0350 Keywords : Vitamin E * TRAIL * apoptosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.991, year: 2002

  1. Developing Enculturated Agents

    DEFF Research Database (Denmark)

    Rehm, Matthias

    2010-01-01

    on our cultural profiles that provide us with heuristics of behavior and interpretation. Thus, integrating cultural aspects of communicative behaviors in virtual agents and thus enculturating such systems seems to be inevitable. But culture is a multi-defined domain and thus a number of pitfalls arise...... that have to be avoided in the endeavor. This chapter presents some of the pitfalls for enculturating interactive systems and presents strategies on how to avoid these pitfalls in relation to the standard development process of Embodied Conversational Agents....

  2. Teaching Tourism Change Agents

    DEFF Research Database (Denmark)

    Stilling Blichfeldt, Bodil; Kvistgaard, Hans-Peter; Hird, John

    2017-01-01

    This article discuss es know ledge, competencies and skills Master’s students should obtain during their academic studies and particularly, the differences between teaching about a topic and teaching to do. This is ex emplified by experiential learning theory and the case of a change management...... course that is part of a Tourism Master’s program, where a major challenge is not only to teach students about change and change agents, but to teach them how change feels and ho w to become change agents. The c hange management course contains an experiment inspired by experiential teaching literature...

  3. 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....

  4. Agent Persuasion Mechanism of Acquaintance

    Science.gov (United States)

    Jinghua, Wu; Wenguang, Lu; Hailiang, Meng

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

  5. 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...

  6. Fluoroquinolone antimicrobial agents.

    OpenAIRE

    Wolfson, J S; Hooper, D C

    1989-01-01

    The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The dr...

  7. Socially Intelligent Tutor Agents

    NARCIS (Netherlands)

    Heylen, Dirk K.J.; Nijholt, Antinus; op den Akker, Hendrikus J.A.; Vissers, M.; Aylett, R.; Ballin, D.; Rist, T.

    2003-01-01

    Emotions and personality have received quite a lot of attention the last few years in research on embodied conversational agents. Attention is also increasingly being paid to matters of social psychology and interpersonal aspects, for work of our group). Given the nature of an embodied

  8. Cell control with agents

    NARCIS (Netherlands)

    Ir Peter Boots; Ir. Dick van Schenk Brill

    2000-01-01

    A software system is described that uses the agent concept in the Cell Control layer. Important design goals are: the system continues as good as possible after a process crash, crashed processes are recreated whenever possible, and equivalent workstations are allocated dynamically. This project is

  9. 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...

  10. Multimodal training between agents

    DEFF Research Database (Denmark)

    Rehm, Matthias

    2003-01-01

    In the system Locator1, agents are treated as individual and autonomous subjects that are able to adapt to heterogenous user groups. Applying multimodal information from their surroundings (visual and linguistic), they acquire the necessary concepts for a successful interaction. This approach has...

  11. Attempts at the production of more selective antitumourals. Part I. The antineoplastic activity of cyclophosphazenes linked to the polyamines 1,3-diaminopropane and 1,4-diaminobutane (putrescine)

    Science.gov (United States)

    Labarre, Jean-François; Guerch, Guy; Sournies, François; Spreafico, Federico; Filippeschi, Stefania

    1984-06-01

    In an attempt to design antitumour cyclophosphazenes of improved specificity by linking them to some natural tumour finders, we studied the binding of gem-N 3P 3Az 4Cl 2 to 1,3-diaminopropane and 1,4-diaminobutane (putrescine). Synthesis, mass spectrum and NMR as well as X-ray crystal structures of the two spirocyclic N 3P 3Az 4 [HN(CH 2) 3,4NH] derivatives (in which the N 3P 3Az 4 active principle is linked to the diamine in a spiro configuration) are described. Results obtained with these compounds in 3 murine tumour systems (L1210 and P388 leukaemias and P815 mastocytoma), showing their potent antineoplastic activity in vivo obtainable at well-tolerated doses, are also described.

  12. Applying ligands profiling using multiple extended electron distribution based field templates and feature trees similarity searching in the discovery of new generation of urea-based antineoplastic kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Eman M Dokla

    Full Text Available This study provides a comprehensive computational procedure for the discovery of novel urea-based antineoplastic kinase inhibitors while focusing on diversification of both chemotype and selectivity pattern. It presents a systematic structural analysis of the different binding motifs of urea-based kinase inhibitors and the corresponding configurations of the kinase enzymes. The computational model depends on simultaneous application of two protocols. The first protocol applies multiple consecutive validated virtual screening filters including SMARTS, support vector-machine model (ROC = 0.98, Bayesian model (ROC = 0.86 and structure-based pharmacophore filters based on urea-based kinase inhibitors complexes retrieved from literature. This is followed by hits profiling against different extended electron distribution (XED based field templates representing different kinase targets. The second protocol enables cancericidal activity verification by using the algorithm of feature trees (Ftrees similarity searching against NCI database. Being a proof-of-concept study, this combined procedure was experimentally validated by its utilization in developing a novel series of urea-based derivatives of strong anticancer activity. This new series is based on 3-benzylbenzo[d]thiazol-2(3H-one scaffold which has interesting chemical feasibility and wide diversification capability. Antineoplastic activity of this series was assayed in vitro against NCI 60 tumor-cell lines showing very strong inhibition of GI(50 as low as 0.9 uM. Additionally, its mechanism was unleashed using KINEX™ protein kinase microarray-based small molecule inhibitor profiling platform and cell cycle analysis showing a peculiar selectivity pattern against Zap70, c-src, Mink1, csk and MeKK2 kinases. Interestingly, it showed activity on syk kinase confirming the recent studies finding of the high activity of diphenyl urea containing compounds against this kinase. Allover, the new series

  13. 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 Works hop 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

  14. Amphoteric surface active agents

    OpenAIRE

    Eissa, A.M. F.

    1995-01-01

    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 a...

  15. 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.

  16. Quantitative Analyses of Synergistic Responses between Cannabidiol and DNA-Damaging Agents on the Proliferation and Viability of Glioblastoma and Neural Progenitor Cells in Culture.

    Science.gov (United States)

    Deng, Liting; Ng, Lindsay; Ozawa, Tatsuya; Stella, Nephi

    2017-01-01

    Evidence suggests that the nonpsychotropic cannabis-derived compound, cannabidiol (CBD), has antineoplastic activity in multiple types of cancers, including glioblastoma multiforme (GBM). DNA-damaging agents remain the main standard of care treatment available for patients diagnosed with GBM. Here we studied the antiproliferative and cell-killing activity of CBD alone and in combination with DNA-damaging agents (temozolomide, carmustine, or cisplatin) in several human GBM cell lines and in mouse primary GBM cells in cultures. This activity was also studied in mouse neural progenitor cells (NPCs) in culture to assess for potential central nervous system toxicity. We found that CBD induced a dose-dependent reduction of both proliferation and viability of all cells with similar potencies, suggesting no preferential activity for cancer cells. Hill plot analysis indicates an allosteric mechanism of action triggered by CBD in all cells. Cotreatment regimens combining CBD and DNA-damaging agents produced synergistic antiproliferating and cell-killing responses over a limited range of concentrations in all human GBM cell lines and mouse GBM cells as well as in mouse NPCs. Remarkably, antagonistic responses occurred at low concentrations in select human GBM cell lines and in mouse GBM cells. Our study suggests limited synergistic activity when combining CBD and DNA-damaging agents in treating GBM cells, along with little to no therapeutic window when considering NPCs. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  17. Constructing Secure Mobile Agent Systems Using the Agent Operating System

    NARCIS (Netherlands)

    van t Noordende, G.J.; Overeinder, B.J.; Timmer, R.J.; Brazier, F.M.; Tanenbaum, A.S.

    2009-01-01

    Designing a secure and reliable mobile agent system is a difficult task. The agent operating system (AOS) is a building block that simplifies this task. AOS provides common primitives required by most mobile agent middleware systems, such as primitives for secure communication, secure and

  18. Logics for Intelligent Agents and Multi-Agent Systems

    NARCIS (Netherlands)

    Meyer, John-Jules Charles

    2014-01-01

    This chapter presents the history of the application of logic in a quite popular paradigm in contemporary computer science and artificial intelligence, viz. the area of intelligent agents and multi-agent systems. In particular we discuss the logics that have been used to specify single agents, the

  19. Holonic multi-agent systems

    OpenAIRE

    Gerber, Christian; Siekmann, Jörg; Vierke, Gero

    1999-01-01

    A holonic multi-agent paradigm is proposed, where agents give up parts of their autonomy and merge into a super-agent"(a holon), that acts - when seen from the outside - just as a single agent again. We explore the spectrum of this new paradigm, ranging from definitorial issues over classification of possible application domains, an algebraic characterization of the merge operation, to implementational aspects: We propose algorithms for holon formation and on-line re-configuration. Based on s...

  20. Respiratory agents: irritant gases, riot control agents, incapacitants, and caustics.

    Science.gov (United States)

    Warden, Craig R

    2005-10-01

    There are many chemical respiratory agents suitable for use by terrorists. They are the oldest chemical agents used and have caused the most casualties throughout the 20th century. Many are available in large quantities for industrial use and are susceptible to potential sabotage. This paper will concentrate on respiratory agents that are readily available and have the potential to cause a large number of casualties and panic. These agents have a lower rate of lethality when compared to other chemical agents but could produce many casualties that may overwhelm the emergency medical system.

  1. Chemical warfare agents

    Directory of Open Access Journals (Sweden)

    Vijayaraghavan R

    2010-01-01

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

  2. Toxorhynchites as biocontrol agents.

    Science.gov (United States)

    Focks, Dana A

    2007-01-01

    Toxorhynchites is an unusual and interesting genus of large, non-biting mosquitoes. In spite of their size, they are--like many species of mosquitoes--completely harmless to man. The larvae are predaceous on other mosquitoes and aquatic organisms that inhabit both natural and artificial containers. Because this habitat is the source of several medically important species of mosquitoes, there is warrant for evaluating the potential of Toxorhynchites as a biological control agent under various conditions. Toxorhynchites is not seen as a panacea for the control of all container-inhabiting mosquitoes. However, it has demonstrated practical potential in certain restricted but important situations.

  3. Product and Agent

    DEFF Research Database (Denmark)

    Montecino, Alex; Valero, Paola

    2015-01-01

    In this paper we will explore how the “mathematics teacher” becomes a subject and, at the same time, is subjected as part of diverse dispositive of power. We argue that the mathematics teacher becomes both a product and a social agent, which has been set, within current societies, from the ideas...... of globalization, social progress, and competitive logic. For our approximation, we use the concepts societies of control, dispositive, and discourses from a Foucault–Deleuze toolbox. Our purpose is to cast light on the social and cultural constitution of the ways of thinking about the mathematics teacher. Hence...

  4. Motivating agents in software tutorials

    NARCIS (Netherlands)

    van der Meij, Hans

    2013-01-01

    Pedagogical agents can provide important support for the user in human–computer interaction systems. This paper examines whether a supplementary, motivating agent in a print tutorial can enhance student motivation and learning in software training. The agent served the role of motivator, attending

  5. 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.

  6. [New agents for hypercholesterolemia].

    Science.gov (United States)

    Pintó, Xavier; García Gómez, María Carmen

    2016-02-19

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

  7. 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.

  8. Flexible, secure agent development framework

    Science.gov (United States)

    Goldsmith,; Steven, Y [Rochester, MN

    2009-04-07

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

  9. Anti-Neoplastic Cytotoxicity of Gemcitabine-(C4-amide)-[anti-EGFR] in Dual-combination with Epirubicin-(C3-amide)-[anti-HER2/neu] against Chemotherapeutic-Resistant Mammary Adenocarcinoma (SKBr-3) and the Complementary Effect of Mebendazole

    Science.gov (United States)

    Coyne, CP; Jones, Toni; Bear, Ryan

    2015-01-01

    Aims Delineate the feasibility of simultaneous, dual selective “targeted” chemotherapeutic delivery and determine if this molecular strategy can promote higher levels anti-neoplastic cytotoxicity than if only one covalent immunochemotherapeutic is selectively “targeted” for delivery at a single membrane associated receptor over-expressed by chemotherapeutic-resistant mammary adenocarcinoma. Methodology Gemcitabine and epirubicin were covalently bond to anti-EGFR and anti-HER2/neu utilizing a rapid multi-phase synthetic organic chemistry reaction scheme. Determination that 96% or greater gemcitabine or epirubicin content was covalently bond to immunoglobulin fractions following size separation by micro-scale column chromatography was established by methanol precipitation analysis. Residual binding-avidity of gemcitabine-(C4-amide)-[anti-EG-FR] applied in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu] was determined by cell-ELIZA utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) populations. Lack of fragmentation or polymerization was validated by SDS-PAGE/immunodetection/chemiluminescent autoradiography. Anti-neoplastic cytotoxic potency was determined by vitality stain analysis of chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) monolayers known to uniquely over-express EGFR (2 × 105/cell) and HER2/neu (1 × 106/cell) receptor complexes. The covalent immunochemotherapeutics gemcitabine-(C4-amide)-[anti-EGFR] and epirubicin-(C3-amide)-[anti-HER2/neu] were applied simultaneously in dual-combination to determine their capacity to collectively evoke elevated levels of anti-neoplastic cytotoxicity. Lastly, the tubulin/microtubule inhibitor mebendazole evaluated to determine if it’s potential to complemented the anti-neoplastic cytotoxic properties of gemcitabine-(C4-amide)-[anti-EGFR] in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu]. Results Dual-combination of gemcitabine-(C4-amide)-[anti-EGFR] with

  10. 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.

  11. Microencapsulation of chemotherapeutic agents

    International Nuclear Information System (INIS)

    Byun, Hong Sik

    1993-01-01

    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)

  12. New MR contrast agent

    International Nuclear Information System (INIS)

    Grossman, C.D.; Subramanian, G.; Schneider, R.; Szeverenyi, N.E.; Rosenbaum, A.M.; Gagne, G.; Tillapaugh-Fay, G.; Berlin, R.; Ritter-Hrncirik, C.; Yu, S.

    1990-01-01

    This paper evaluates an MR contrast agent-meglumine tris-(2,6-dicarboxypyridine) gadolinium (III) or gadolinium dipicolinate (Gd-DPC)-produced in-house. Rats were anesthetized with pentobarbital. For renal imaging, bowel motion artifact was minimized with glucagon (0.014 mg/kg, intravenous (IV)). Enhanced images were generated on a 2-T chemical shift imaging system with a 31-cm horizontal bore magnet after IV injection of Gd-DPC (100 μM/kg). Coronal sections of the kidneys and sagittal sections of the brain, 2 mm thick, were made. Six to eight excitations and 128 or 356 phase-encoding steps were used for each image. Control animals were injected with equivalent doses of gadopentetate dimeglumine

  13. A Composite Agent Architecture for Multi-Agent Simulations

    OpenAIRE

    VanPutte, Michael; Osborn, Brian; Hiles, John

    2002-01-01

    CGF Computer Generated Forces and Behavioral Representation The MOVES Institute’s Computer-Generated Autonomy Group has focused on a research goal of modeling complex and adaptive behavior while at the same time making the behavior easier to create and control. This research has led to several techniques for agent construction, that includes a social and organization relationship management engine, a composite agent architecture, an agent goal apparatus, a structure for capturi...

  14. Targeting Histone Deacetylases in Malignant Melanoma: A Future Therapeutic Agent or Just Great Expectations?

    Science.gov (United States)

    Garmpis, Nikolaos; Damaskos, Christos; Garmpi, Anna; Dimitroulis, Dimitrios; Spartalis, Eleftherios; Margonis, Georgios-Antonios; Schizas, Dimitrios; Deskou, Irini; Doula, Chrysoula; Magkouti, Eleni; Andreatos, Nikolaos; Antoniou, Efstathios A; Nonni, Afroditi; Kontzoglou, Konstantinos; Mantas, Dimitrios

    2017-10-01

    Malignant melanoma is the most aggressive type of skin cancer, with increasing frequency and mortality. Melanoma is characterized by rapid proliferation and metastases. Malignant transformation of normal melanocytes is associated with imbalance between oncogenes' action and tumor suppressor genes. Mutations or inactivation of these genes plays an important role in the pathogenesis of malignant melanoma. Many target-specific agents improved progression-free survival but unfortunately metastatic melanoma remains incurable, so new therapeutic strategies are needed. The balance of histones' acetylation affects cell cycle progression, differentiation and apoptosis. Histone deacetylases (HDAC) are associated with different types of cancer. Histone deacetylase inhibitors (HDACI) are enzymes that inhibit the action of HDAC, resulting in block of tumor cell proliferation. A small number of these enzymes has been studied regarding their anticancer effects in melanoma. The purpose of this article was to review the therapeutic effect of HDACI against malignant melanoma, enlightening the molecular mechanisms of their action. The MEDLINE database was used. The keywords/ phrases were; HDACI, melanoma, targeted therapies for melanoma. Our final conclusions were based on studies that didn't refer solely to melanoma due to their wider experimental data. Thirty-two articles were selected from the total number of the search's results. Only English articles published until March 2017 were used. Molecules, such as valproid acid (VPA), LBH589, LAQ824 (dacinostat), vorinostat, tubacin, sirtinol and tx-527, suberoyl bis-hydroxamic acid (SBHA), depsipeptide and Trichostatin A (TSA) have shown promising antineoplastic effects against melanoma. HDACI represent a promising agent for targeted therapy. More trials are required. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. 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.

  16. 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.

  17. Radioactive scanning agents with stabilizer

    International Nuclear Information System (INIS)

    Fawzi, M.B.

    1982-01-01

    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

  18. Believable Social and Emotional Agents.

    Science.gov (United States)

    1996-05-01

    generation). Our agent is now also capable of talking about its emo- tions. Emotions might also affect how the agent speaks, such as stuttering when the...he will eventually tell the teacher and get the user in trouble1. Sluggo goes into the trade with an impatient and aggressive attitude and quickly...personality resulted in a more interesting character. 1. There is no teacher agent in the simulation, but the simulation can end with a message to the user

  19. Towards Information-Seeking Agents

    OpenAIRE

    Bachman, Philip; Sordoni, Alessandro; Trischler, Adam

    2016-01-01

    We develop a general problem setting for training and testing the ability of agents to gather information efficiently. Specifically, we present a collection of tasks in which success requires searching through a partially-observed environment, for fragments of information which can be pieced together to accomplish various goals. We combine deep architectures with techniques from reinforcement learning to develop agents that solve our tasks. We shape the behavior of these agents by combining e...

  20. Choice a real estate agent

    OpenAIRE

    Pantelic, Marija

    2014-01-01

    Every year a hundreds of new Estate agents is examined, and new agency comes to, which increase the competition for estate agents. Property sellers have the option to choose the estate agent which they think is the best one that will best mediate their property at a flexible and a correct way. It has been common that property sellers choose and compare estate agents in the city, the competition is today equal outside the city as in the city. Possibly, these are other criteria that values high...

  1. Judicial supervision of enforcement agents

    Directory of Open Access Journals (Sweden)

    Bodiroga Nikola

    2015-01-01

    Full Text Available The main focus of this paper is the supervision of enforcement agents conducted by enforcement courts. Law on Enforcement and Security recognizes three levels of control of enforcement agents. Certain monitoring powers are delegated to the Ministry of Justice and to Chamber of Enforcement Agents. However, for parties and other participants to enforcement proceedings control of enforcement agents implemented by enforcement courts seems to be the most important one. The strongest powers of enforcement agents are related to the special procedure for collection of claims for utilities and other similar services (exclusive competence of enforcement agents and for carrying out the enforcement (if enforcement creditor has requested it. When it comes to special procedure for collection of claims for utilities and other similar services objection can be used in order to control legality of decisions rendered by enforcements agents. However, many procedural issues related to the objection procedure remain unsolved. Motion for correction of irregularities is the only legal remedy that can be used when enforcement is being carried out by enforcement agents. This legal remedy cannot be considered an effective one in the sense of Article 13 European Convention for Protection of Human Rights and Fundamental Liberties. The new proposed Law on Enforcement and Security expected to come into force on July 1, 2016, will delegate the exclusive competence for carrying out the enforcement to enforcement agents (except cases related to family relations and reinstatement, but it will not improve the court supervision of their work.

  2. GOAL Agents Instantiate Intention Logic

    OpenAIRE

    Hindriks, Koen; van der Hoek, Wiebe

    2008-01-01

    It is commonly believed there is a big gap between agent logics and computational agent frameworks. In this paper, we show that this gap is not as big as believed by showing that GOAL agents instantiate Intention Logic of Cohen and Levesque. That is, we show that GOAL agent programs can be formally related to Intention Logic.We do so by proving that the GOAL Verification Logic can be embedded into Intention Logic. It follows that (a fragment of) Intention Logic can be used t...

  3. Business Intelligence using Software Agents

    Directory of Open Access Journals (Sweden)

    Ana-Ramona BOLOGA

    2011-12-01

    Full Text Available 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 propose some basic ideas for developing real-time agent-based software system for business intelligence in supply chain management, using Case Base Reasoning Agents.

  4. Stable agents for imaging investigations

    International Nuclear Information System (INIS)

    Tofe, A.J.

    1976-01-01

    This invention concerns highly stable compounds useful in preparing technetium 99m based scintiscanning exploration agents. The compounds of this invention include a pertechnetate reducing agent or a solution of oxidized pertechnetate and an efficient proportion, sufficient to stabilize the compounds in the presence of oxygen and of radiolysis products, of ascorbic acid or a pharmaceutically acceptable salt or ester of this acid. The invention also concerns a perfected process for preparing a technetium based exploration agent, consisting in codissolving the ascorbic acid or a pharmaceutically acceptable salt or ester of such an acid and a pertechnetate reducing agent in a solution of oxidized pertechnetate [fr

  5. Gastrointestinal scanning agent

    International Nuclear Information System (INIS)

    Francis, M.D.

    1980-01-01

    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)TcO 4 and SnCl 2 . 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)

  6. 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.

  7. The Agent of Change: The Agent of Conflict.

    Science.gov (United States)

    Hatfield, C. R., Jr.

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

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

    Science.gov (United States)

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

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

  9. Players' agents worldwide: legal aspects

    NARCIS (Netherlands)

    Siekmann, R.C.R.; Parrish, R.; Branco Martins, R.; Soek, J.W.

    2007-01-01

    Publicly, at least, there appears to be a strong collective will within football to clean up the game, to make the work of players’ agents more transparent and to allow a greater share of the game’s profits to stay within the game. Privately, there seems to be unease that current agent regulation is

  10. Overview of shoreline cleaning agents

    International Nuclear Information System (INIS)

    Clayton, J.

    1992-01-01

    Chemical cleaning agents may be used to promote release of stranded oil from shorelines for reasons including biological sensitivity of indigenous fauna and flora to the oil, amenity considerations of the shoreline, or concern about refloating of the oil and subsequent stranding on adjacent shorelines. While use of chemical cleaning agents may be appropriate under proper toxic responses in circumstances, certain limitations should be recognized. The potential for toxic responses in indigenous fauna and flora to the cleaning agents must be considered. Enhanced penetration of oil into permeable shorelines following treatment with chemical cleaning agents also is not desirable. However, if conditions related to toxicity and substrate permeability are determined to be acceptable, the use of chemical cleaning agents for treatment of stranded oil can be considered. Chemical agents for cleaning oiled shorelines can be grouped into three categories: (1) non-surfactant-based solvents, (2) chemical dispersants, and (3) formulations especially designed to release stranded oil from shoreline substrates (i.e., shoreline-cleaning-agents). Depending on the specific circumstances present on an oiled shoreline, it is generally desirable that chemical agents used for cleaning will release oil from shoreline substrate(s) to surface waters. Recovery of the oil can then be accomplished by mechanical procedures such as booming and skimming operations

  11. Dialogue Games for Agent Argumentation

    Science.gov (United States)

    McBurney, Peter; Parsons, Simon

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

  12. A Verification Logic for GOAL Agents

    Science.gov (United States)

    Hindriks, K. V.

    Although there has been a growing body of literature on verification of agents programs, it has been difficult to design a verification logic for agent programs that fully characterizes such programs and to connect agent programs to agent theory. The challenge is to define an agent programming language that defines a computational framework but also allows for a logical characterization useful for verification. The agent programming language GOAL has been originally designed to connect agent programming to agent theory and we present additional results here that GOAL agents can be fully represented by a logical theory. GOAL agents can thus be said to execute the corresponding logical theory.

  13. New agents for cancer chemoprevention.

    Science.gov (United States)

    Kelloff, G J; Boone, C W; Crowell, J A; Steele, V E; Lubet, R A; Doody, L A; Malone, W F; Hawk, E T; Sigman, C C

    1996-01-01

    Clinical chemoprevention trials of more than 30 agents and agent combinations are now in progress or being planned. The most advanced agents are well known and are in large Phase III chemoprevention intervention trials or epidemiological studies. These drugs include several retinoids [e.g., retinol, retinyl palmitate, all-trans-retinoic acid, and 13-cis-retinoic acid], calcium, Beta carotene, vitamin E, tamoxifen, and finasteride. Other newer agents are currently being evaluated in or being considered for Phase II and early Phase III chemoprevention trials. Prominent in this group are all-trans-N-(4-hydroxy phenyl)retinamide (4-HPR) (alone and in combination with tamoxifen), 2-difluoromethylornithine (DFMO), nonsteroidal antiinflammatory drugs (aspirin, piroxicam, sulindac), oltipraz, and dehydroepiandrostenedione (DHEA). A third group is new agents showing chemopreventive activity in animal models, epidemiological studies, or in pilot clinical intervention studies. They are now in preclinical toxicology testing or Phase I safety and pharmacokinetics trials preparatory to chemoprevention efficacy trials. These agents include S-allyl-l-cysteine, curcumin, DHEA analog 8354 (fluasterone), genistein, ibuprofen, indole-3-carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, sulindac sulfone, tea extracts, ursodiol, vitamin D analogs, and p-xylyl selenocyanate. A new generation of agents and agent combinations will soon enter clinical chemoprevention studies based primarily on promising chemopreventive activity in animal models and in mechanistic studies. Among these agents are more efficacious analogs of known chemopreventive drugs including novel carotenoids (e.g., alpha-carotene and lutein). Also included are safer analogs which retain the chemopreventive efficacy of the parent drug such as vitamin D3 analogs. Other agents of high interest are aromatase inhibitors (e.g., (+)-vorozole), and protease inhibitors (e.g., Bowman-Birk soybean trypsin

  14. Smart Agents and Sentiment in the Heterogeneous Agent Model

    Czech Academy of Sciences Publication Activity Database

    Vácha, Lukáš; Baruník, Jozef; Vošvrda, Miloslav

    2009-01-01

    Roč. 18, č. 3 (2009), s. 209-219 ISSN 1210-0455 R&D Projects: GA MŠk(CZ) LC06075; GA ČR GP402/08/P207; GA ČR(CZ) GA402/09/0965 Institutional research plan: CEZ:AV0Z10750506 Keywords : heterogeneous agent model * market structure * smart traders * Hurst exponent Subject RIV: AH - Economics http://library.utia.cas.cz/separaty/2009/E/vacha- smart agents and sentiment in the heterogeneous agent model.pdf

  15. Immunological effects of hypomethylating agents.

    Science.gov (United States)

    Lindblad, Katherine E; Goswami, Meghali; Hourigan, Christopher S; Oetjen, Karolyn A

    2017-08-01

    Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets. We summarized the effects of hypomethylating agents on the frequency and function of natural killer cells, T cells, and dendritic cells. In particular, we highlight the effects of hypomethylating agents on expression of immune checkpoint inhibitors, leukemia-associated antigens, and endogenous retroviral elements. Expert commentary: In vitro and ex vivo studies indicate mixed effects on the function of natural killer, dendritic cells and T cells following treatment with hypomethylating agents. Clinical correlates of immune function have suggested that hypomethylating agents have immunomodulatory functions with the potential to synergize with immune checkpoint therapy for the treatment of hematologic malignancy, and has become an active area of clinical research.

  16. Rollover Cyclometalated Bipyridine Platinum Complexes as Potent Anticancer Agents: Impact of the Ancillary Ligands on the Mode of Action.

    Science.gov (United States)

    Babak, Maria V; Pfaffeneder-Kmen, Martin; Meier-Menches, Samuel M; Legina, Maria S; Theiner, Sarah; Licona, Cynthia; Orvain, Christophe; Hejl, Michaela; Hanif, Muhammad; Jakupec, Michael A; Keppler, Bernhard K; Gaiddon, Christian; Hartinger, Christian G

    2018-03-05

    Platinum-based anticancer coordination compounds are widely used in the treatment of many tumor types, where they are very effective but also cause severe side effects. Organoplatinum compounds are significantly less investigated than the analogous coordination compounds. We report here rollover cyclometalated Pt compounds based on 2,2'-bipyridine which are demonstrated to be potent antitumor agents both in vitro and in vivo. Variation of the co-ligands on the Pt(2,2'-bipyridine) backbone resulted in the establishment of structure-activity relationships. They showed that the biological activity was in general inversely correlated with the reaction kinetics to biomolecules as shown for amino acids, proteins, and DNA. The less stable compounds caused higher reactivity with biomolecules and were shown to induce p53-dependent DNA damage. In contrast, the presence of bulky PTA and PPh 3 ligands was demonstrated to cause lower reactivity and increased antineoplastic activity. Such compounds were devoid of DNA-damaging activity and induced ATF4, a component of the endoplasmic reticulum (ER) stress pathway. The lead complex inhibited tumor growth similar to oxaliplatin while showing no signs of toxicity in test mice. Therefore, we demonstrated that it is possible to fine-tune rollover-cyclometalated Pt(II) compounds to target different cancer pathways and be a means to overcome the side effects associated with cisplatin and analogous compounds in cancer chemotherapy.

  17. Antioxidant agents: a future alternative approach in the prevention and treatment of radiation-induced oral mucositis?

    Science.gov (United States)

    de Freitas Cuba, Letícia; Salum, Fernanda Gonçalves; Cherubini, Karen; de Figueiredo, Maria Antonia Zancanaro

    2015-01-01

    Radiotherapy is a therapeutic modality frequently employed for patients with head and neck cancer (HNC). It destroys tumor cells, but it is not selective, also affecting healthy tissues and producing adverse effects. One that stands out is oral mucositis because of the morbidity that it is capable of causing. This lesion is characterized by the presence of erythema, ulcerations, pain, opportunistic infections, and weight loss. These side effects can lead to serious situations that require the interruption of the antineoplastic treatment and can result in hospitalization and even death. The complex mechanisms linked to the pathogenesis of oral mucositis were recently established, and since then, the control of oxidative stress (OS) has been tied to the prevention and management of this disease. The authors have carried out a review of the literature about the use of antioxidant agents in the prevention and treatment of radiation-induced oral mucositis, using the PubMed database. This review has shown that the research on use of antioxidants (AOX) has proved insufficient to justify suggesting the products in treatment protocols. Results are promising, however, and AOX may represent a future alternative in the prevention and treatment of oral mucositis.

  18. Riproximin: A type II ribosome inactivating protein with anti-neoplastic potential induces IL24/MDA-7 and GADD genes in colorectal cancer cell lines.

    Science.gov (United States)

    Pervaiz, Asim; Adwan, Hassan; Berger, Martin R

    2015-09-01

    Riproximin (Rpx) is a type II ribosome inactivating protein, which was extracted and purified from the seeds of Ximenia americana. Previous studies demonstrated cytotoxicity of Rpx against a variety of cell lines originating from solid and non-solid cancers. In this study, we investigated the mechanistic aspects of Rpx in selected human and rat colorectal cancer (CRC) cell lines. Cytotoxic levels of Rpx were determined by MTT assay, while cytostatic and apoptotic effects were investigated by flow cytometry and nuclear staining procedures. Effects of Rpx exposure on colony formation/migration of CRC cells and expressional modulations in anticancer/stress-related genes were also studied. Rpx showed significant and comparable levels of cytotoxicity in CRC cells as determined by inhibitory concentration (IC) values. Similar inhibitory effects were found for clonogenicity, while more pronounced inhibition of migration was observed in response to Rpx exposure. Profound arrest in S phases of the cell cycle was noted especially in primary CRC cells. Apoptotic effects were more prominent in rat CRC cells as indicated by Annexin V-FITC assay and Hoechst 33342 nuclear staining. Rpx exposure induced significantly increased levels of the IL24/MDA-7, a well characterized anticancer gene, in all CRC cells. In addition, following Rpx treatment, high expression levels of growth arrest and DNA damage (GADD family) genes were also observed. Increased expression of two additional GADD genes (34 and 153) only in rat CRC cells (CC531) conferred higher sensitivity towards Rpx and subsequent anti-proliferative/apoptotic effects as compared to human CRC cells (SW480 and SW620). The present investigation indicates the anticancer potential of Rpx in CRC and favor further evaluation of this natural compound as therapeutic agent.

  19. Complex responses to alkylating agents

    International Nuclear Information System (INIS)

    Samson, L.D.

    2003-01-01

    Using Affymetrix oligonucleotide GeneChip analysis, we previously found that, upon exposure to the simple alkylating agent methylmethane sulfonate, the transcript levels for about one third of the Saccharomyces cerevisiae genome (∼2,000 transcripts) are induced or repressed during the first hour or two after exposure. In order to determine whether the responsiveness of these genes has any relevance to the protection of cells against alkylating agents we have undertaken several follow-up studies. First, we explored the specificity of this global transcriptional response to MMS by measuring the global response of S. cerevisiae to a broad range of agents that are known to induce DNA damage. We found that each agent produced a very different mRNA transcript profile, even though the exposure doses produced similar levels of toxicity. We also found that the selection of genes that respond to MMS is highly dependent upon what cell cycle phase the cells are in at the time of exposure. Computational clustering analysis of the dataset derived from a large number of exposures identified several promoter motifs that are likely to control some of the regulons that comprise this large set of genes that are responsive to DNA damaging agents. However, it should be noted that these agents damage cellular components other than DNA, and that the responsiveness of each gene need not be in response to DNA damage per se. We have also begun to study the response of other organisms to alkylating agents, and these include E. coli, cultured mouse and human cells, and mice. Finally, we have developed a high throughput phenotypic screening method to interrogate the role of all non-essential S. cerevisiae genes (about 4,800) in protecting S. cerevisiae against the deleterious effects of alkylating agents; we have termed this analysis 'genomic phenotyping'. This study has uncovered a plethora of new pathways that play a role in the recovery of eukaryotic cells after exposure to toxic

  20. Industrial Agents: Emerging Applications of Software Agents in Industry

    OpenAIRE

    Leitão P.; Leitão, Paulo; Karnouskos, Stamatis

    2015-01-01

    The objective of this book is to address both industry practitioners and academia, providing the vision, on-going efforts, example applications, assessments, and roadmaps associated with industrial agents used in multiple industries. Such a book provides an introduction to the “industrial agents” domain by discussing up-to-date examples of their applications in industry, and it offers a view of future challenges with an accompanying roadmap. Part I introduces industrial agents,...

  1. Nuclear magnetic resonance contrast agents

    Science.gov (United States)

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

    1997-12-30

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

  2. Cytotoxicity of dentin bonding agents.

    Science.gov (United States)

    Cal, Ebru; Guneri, Pelin; Atay, Ayse; Cetintas, Vildan Bozok

    2014-01-01

    This study sought to evaluate the cytotoxicity of 5 dentin bonding agents (Admira Bond, Adper Single Bond Plus, Clearfil SE Bond, Clearfil S3 Bond, and Heliobond) by XTT assay using human gingival fibroblast cells. Samples of dentin bonding agents were prepared on a black 96-well microplate, and the cytotoxicity of each bonding material was measured every 24 hours for 7 days, then on Days 14, 21, and 28. One-way ANOVA and Bonferroni post hoc tests were used for statistical analyses. All 5 materials were evaluated as severely cytotoxic (P agents showed severe cytotoxicity with viability results exception of Adper Single Bond Plus, toxicity continued to Day 28 for all compounds. The utmost care must be considered during the clinical utilization of dentin bonding agents to keep them within the area of restoration and prevent their contact with adjacent tissues.

  3. Chemical Agents: Facts about Evacuation

    Science.gov (United States)

    ... What CDC is Doing Blog: Public Health Matters 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 ...

  4. Relational agents: A critical review

    DEFF Research Database (Denmark)

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

    2009-01-01

    Relationships between people who meet in virtual worlds are common and these relationships can be long term, in some cases lasting a life-time. Although relationships formed in virtual worlds have invited a lot of recent interest, surprisingly little work has been done on developing computer agen...... 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....... 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...

  5. Antisense Treatments for Biothreat Agents

    National Research Council Canada - National Science Library

    Warfield, Kelly L; Panchal, Rekha G; Aman, M J; Bavari, Sina

    2006-01-01

    ... a variety of pathogens in cell culture studies and nonhuman primate models of infection. For these reasons, antisense technologies are being pursued as treatments against biothreat agents such as Ebola virus, dengue virus and Bacillus anthracis...

  6. 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...

  7. Mobile Objects and Agents (MOA)

    Science.gov (United States)

    Milojicic, Dejan S.; LaForge, William; Chauhan, Deepika

    1998-12-01

    This paper describes the design and implementation of the Mobile Objects and Agents (MOA) project at the Open Group Research Institute. MOA was designed to support migration, communication and control of agents. It was implemented on top of the Java Virtual Machine, without any modifications to it. The initial project goals were to support communication across agent migration, as a means for collaborative work; and to provide extensive resource control, as a basic support for countering denial of service attacks. In the course of the project we added two further goals: compliance with the Java Beans component model, which provides for additional configurability and customization of agent system and agent applications; and interoperability, which allows cooperation with other agent systems. This paper analyses the architecture of MOA, in particular the support for mobility, naming and locating, communication, and resource management. Object and component models of MOA are discussed and some implementation details described. We summarize the lessons learned while developing and implementing MOA and compare it with related work.

  8. Oral hypoglycemic agents in pregnancy.

    Science.gov (United States)

    Tran, Nam D; Hunter, Stephen K; Yankowitz, Jerome

    2004-06-01

    Pregnancies in diabetic women are associated with increased risk of spontaneous abortion, congenital malformations, preeclampsia, preterm labor, macrosomia, shoulder dystocia, and cesarean section. Advances in antepartum cares and strict adherence to dietary and insulin regimens have been shown to significantly reduce the rate of maternal morbidity as well as perinatal morbidity and mortality. Historically, reports of potential fetal teratogenicity and hypoglycemic effects on the fetus contraindicated the use of oral hypoglycemic agents in pregnancies complicated with either type II diabetes mellitus (DM) or gestational diabetes mellitus (GDM). Recently, physicians increasingly prescribe newer generations of oral hypoglycemic agents to treat GDM and type II DM to pregnant patients. This review addresses the safety, current recommendations, and controversies surrounding use of the available oral hypoglycemic agents during pregnancy. Obstetricians & Gynecologists, Family Physicians After completion of this article, the reader should be able to describe the mechanisms of actions of the various oral hypoglycemic agents, to list the known side effects of these agents, and to summarize the data on the use of these agents during pregnancy.

  9. Bacterial biosynthesis and maturation of the didemnin anti-cancer agents

    KAUST Repository

    Xü, Ying

    2012-05-23

    The anti-neoplastic agent didemnin B from the Caribbean tunicate Trididemnum solidum was the first marine drug to be clinically tested in humans. Because of its limited supply and its complex cyclic depsipeptide structure, considerable challenges were encountered during didemnin B\\'s development that continue to limit aplidine (dehydrodidemnin B), which is currently being evaluated in numerous clinical trials. Herein we show that the didemnins are bacterial products produced by the marine α-proteobacteria Tistrella mobilis and Tistrella bauzanensis via a unique post-assembly line maturation process. Complete genome sequence analysis of the 6,513,401 bp T. mobilis strain KA081020-065 with its five circular replicons revealed the putative didemnin biosynthetic gene cluster (did) on the 1,126,962 bp megaplasmid pTM3. The did locus encodes a 13-module hybrid non-ribosomal peptide synthetase-polyketide synthase enzyme complex organized in a collinear arrangement for the synthesis of the fatty acylglutamine ester derivatives didemnins X and Y rather than didemnin B as first anticipated. Imaging mass spectrometry of T. mobilis bacterial colonies captured the time-dependent extracellular conversion of the didemnin X and Y precursors to didemnin B, in support of an unusual post-synthetase activation mechanism. Significantly, the discovery of the didemnin biosynthetic gene cluster may provide a long-term solution to the supply problem that presently hinders this group of marine natural products and pave the way for the genetic engineering of new didemnin congeners. © 2012 American Chemical Society.

  10. 13 CFR 120.952 - Fiscal agent.

    Science.gov (United States)

    2010-01-01

    ... Loan Program (504) Debenture Sales and Service Agents § 120.952 Fiscal agent. SBA shall appoint a Fiscal Agent to assess the financial markets, minimize the cost of sales, arrange for the production of...

  11. Homeostatic Agent for General Environment

    Science.gov (United States)

    Yoshida, Naoto

    2018-03-01

    One of the essential aspect in biological agents is dynamic stability. This aspect, called homeostasis, is widely discussed in ethology, neuroscience and during the early stages of artificial intelligence. Ashby's homeostats are general-purpose learning machines for stabilizing essential variables of the agent in the face of general environments. However, despite their generality, the original homeostats couldn't be scaled because they searched their parameters randomly. In this paper, first we re-define the objective of homeostats as the maximization of a multi-step survival probability from the view point of sequential decision theory and probabilistic theory. Then we show that this optimization problem can be treated by using reinforcement learning algorithms with special agent architectures and theoretically-derived intrinsic reward functions. Finally we empirically demonstrate that agents with our architecture automatically learn to survive in a given environment, including environments with visual stimuli. Our survival agents can learn to eat food, avoid poison and stabilize essential variables through theoretically-derived single intrinsic reward formulations.

  12. 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...... evolutionary step for the in-vehicle route planners is the introduction of two-way communication. We presume that the agent is capable of exactly this. Based on this presumption we discuss the possibilities and define a taxonomy and use this to discuss the ABIT system. Based on a set of scenarios we conclude...... 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...

  13. 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.

  14. Dual Rationality and Deliberative Agents

    Science.gov (United States)

    Debenham, John; Sierra, Carles

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

  15. Monitoring presence of chemical agents

    International Nuclear Information System (INIS)

    Preston, J.M.

    1984-01-01

    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. Solidifying agent for radioactive waste

    International Nuclear Information System (INIS)

    Kida, Tsutomu; Sakai, Etsuro.

    1988-01-01

    Purpose: To increase the processing performance even when the iodine content is great and obtain solidification products of excellent durability. Constitution: The solidifying agent mainly comprises waterhardenable material, calcium aluminate (CA), gypsum, ultrafine powder and high performance water reducer. As the water hardenable material, mixed cement incorporated with portland cement, for example, is used. CA with CAO/Al 2 O 3 molar ratio of about 1.5 - 4 is used. Gypsum dihydrate is used as the gypsum in an amount of about 2 to 19 parts by weight based on 29 to 93 parts by weight of water-hardenable materials. The average grain size of the ultrafine powder is lower by about one digit than that of water-hardenable material, CA and gypsum and, for example, silica dust is used. The high performance water reducing agent is a surface active agent, for example, mainly comprising naphthalene sulfonate, etc. (Yoshio, Y.)

  17. Intelligent agent software for medicine.

    Science.gov (United States)

    Lieberman, Henry; Mason, Cindy

    2002-01-01

    An important trend for the future of health technology will be the increasing use of intelligent agent software for medical applications. As the complexity of situations faced by both patients and health care providers grows, conventional interfaces that rely on users to manually transfer data and manually perform each problem-solving step, won't be able to keep up. This article describes how software agents that incorporate learning, personalization, proactivity, context-sensitivity and collaboration will lead to a new generation of medical applications that will streamline user interfaces and enable more sophisticated communication and problem-solving.

  18. 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.

  19. Clustering recommendations to compute agent reputation

    Science.gov (United States)

    Bedi, Punam; Kaur, Harmeet

    2005-03-01

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

  20. 2APL: a practical agent programming language

    NARCIS (Netherlands)

    Dastani, M.M.

    2008-01-01

    This article presents a BDI-based agent-oriented programming language, called 2APL (A Practical Agent Programming Language). This programming language facilitates the implementation ofmulti-agent systems consisting of individual agents thatmay share and access external environments. It realizes

  1. Fundamental studies of oral contrast agents for MR. Comparison of manganese agent and iron agent

    International Nuclear Information System (INIS)

    Fujita, Osamu; Hiraishi, Kumiko; Suginobu, Yoshito; Takeuchi, Masayasu; Narabayashi, Isamu

    1996-01-01

    We investigated and compared signal intensity and the effect of imaging the upper abdomen with blueberry juice (B.J.), a Mn agent utilizing the properties of paramagnetic metals, and FerriSeltz (F.S.), an iron agent. Since the relaxation effect was much stronger with B.J. than with F.S., the signal intensity required of a peroral contrast agent was able to be obtained at a much lower concentration of B.J. In imaging the upper abdomen, B.J. had a positive effect on imaging in T1-weighted images, and a negative effect in T2-weighted images. F.S. had a positive imaging effect in both, and because it showed extremely high signals in T2-weighted images, motion artifact arose. (author)

  2. 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...

  3. Agent Supported Serious Game Environment

    Science.gov (United States)

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

    2016-01-01

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

  4. 13 CFR 108.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Science.gov (United States)

    2010-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM SBA Financial Assistance for NMVC Companies (Leverage) Funding Leverage by Use of Sba Guaranteed Trust Certificates (âtcsâ... Debenture, SBA may cause each NMVC Company to appoint a Selling Agent to perform functions that include, but...

  5. Design of Collaborative Information Agents

    NARCIS (Netherlands)

    Jonker, C.M.; Klusch, M.; Treur, J.; Klusch, M.; Kerschberg, L.

    2000-01-01

    Effective development of nontrivial systems of collaborative information agents requires that an in-depth analysis is made resulting in (1) specification of requirements at different levels of the system, (2) specification of design structures, and (3) a systematic verification. To support a

  6. 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.

  7. Voice in the Agentic Assemblage

    Science.gov (United States)

    Mazzei, Lisa A.; Jackson, Alecia Y.

    2017-01-01

    In this article, we explore how a posthumanist stance has enabled us to work a different consideration of the way in which "voice" is constituted and constituting in educational inquiry; that is, we position voice in a posthuman ontology that is understood as attributable to a complex network of human and nonhuman agents that exceed the…

  8. Strategic management of biotechnology agents.

    Science.gov (United States)

    Huber, S L

    1993-07-01

    The use of biologic response modifiers to demonstrate a value-driven approach to strategic management by pharmacists is described. To participate in decisions on the use of technology in their institutions, pharmacists must practice strategic management. This process includes environmental scanning, analysis of clinical and pharmacoeconomic data, and development of clinical management approaches. It is ideal for analyzing biologic response modifiers such as filgrastim and sargramostim. Emphasis must be placed on maximizing the fit among the products, the institution, and the health care environment. Pharmacists will find plentiful opportunities for clinical management with biotechnology agents. Practitioners who specialize in determining the total cost of care by using pharmacoeconomic methods are needed, as are practitioners trained to monitor the complicated biotechnology agents. Also, the institution needs to forecast accurately the impact of emerging biotechnology agents. If pharmacists can develop and control clinical, pharmacoeconomic, and reimbursement information databases for biotechnology agents, the pharmacy profession will be in a strong position to meet the challenges of biotechnology and realize the inherent opportunities.

  9. Bridging humans via agent networks

    International Nuclear Information System (INIS)

    Ishida, Toru

    1994-01-01

    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.)

  10. Hyperthermia as a teratogenic agent

    Science.gov (United States)

    Poswillo, David; Nunnerley, Heather; Sopher, Dinah; Keith, John

    1974-01-01

    The common cotton-eared marmoset, a nonhuman primate with a narrow zone of thermoneutrality, was used in an experiment to assess the effects of hyperthermia as a teratogenic agent. Mild heat stress conditions were used. The results of this preliminary study justify further investigation of the effect of hyperthermia on the primate embryo during morphogenesis. Imagesp173-a PMID:4214348

  11. Real Estate Agent Commission Disputes

    Directory of Open Access Journals (Sweden)

    Anida Duarte

    2015-06-01

    Full Text Available The purpose of this study was to examine the relationship among Procuring Cause Law, real estate agent years of experience, and real estate commission disputes. A pilot survey was conducted in the southwestern United States among real estate agents, realtor(s, and brokers. After testing the hypothesis, the decision was made to fail to reject the hypothesis and conclude that real estate agent experience and not Procuring Cause Law produced favorable outcomes in disputes. As a result, the following recommendations were made: (a Agency seller and buyer’s agreements should be used in each transaction to avoid disputes, (b proper expectations and guidelines should be reviewed prior to starting any real estate transaction, (c a checklist may assist in the assurance that all valuable information is reviewed, (d agents could benefit from fully understanding Procuring Cause Law and sharing this information with their clients, (e state and national regulatory requirements of the law could be modified for easier understanding and use, and (f consumers who willfully violate the law could be subject to monetary penalties.

  12. The DARPA agent markup language

    NARCIS (Netherlands)

    Lassila, O; van Harmelen, F; Horrocks, I.; Hendler, J.; McGuinness, DL

    2000-01-01

    The DARPA Agent Markup Language (DAML) program is a United States government sponsored endeavor aimed at providing the foundation for the next web evolution – the semantic web. The program is funding critical research to develop languages, tools and techniques for making considerably more of the

  13. 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

  14. Biocontrol agents in signalling resistance

    NARCIS (Netherlands)

    Loon, L.C. van; 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

  15. The Power Trading Agent Competition

    NARCIS (Netherlands)

    W. Ketter (Wolfgang); J. Collins (John); P. Reddy (Prashant); C. Flath (Christoph); M.M. de Weerdt (Mathijs)

    2011-01-01

    textabstractThis is the specification for the Power Trading Agent Competition for 2012 (Power TAC 2012). Power TAC is a competitive simulation that models a “liberalized” retail electrical energy market, where competing business entities or “brokers” offer energy services to customers through tariff

  16. The Power Trading Agent Competition

    NARCIS (Netherlands)

    Ketter, W.; Collins, J.; Reddy, P.; Flath, C.; De Weerdt, M.M.

    2011-01-01

    This is the specification for the Power Trading Agent Competition for 2012 (Power TAC 2012). Power TAC is a competitive simulation that models a “liberalized” retail electrical energy market, where competing business entities or “brokers” offer energy services to customers through tariff contracts,

  17. Agents containing chlorhexidine in dentistry

    Directory of Open Access Journals (Sweden)

    Lebedeva S.N.

    2011-03-01

    Full Text Available 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

  18. Humor and Embodied Conversational Agents

    NARCIS (Netherlands)

    Nijholt, Antinus

    This report surveys the role of humor in human-to-human interaction and the possible role of humor in human-computer interaction. The aim is to see whether it is useful for embodied conversational agents to integrate humor capabilities in their internal model of intelligence, emotions and

  19. Tc-99m imaging agents

    International Nuclear Information System (INIS)

    Weininger, J.; Trumper, J.

    1984-01-01

    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

  20. Travel Agent. Occupational Simulation Kit.

    Science.gov (United States)

    Peterson, Wayne

    This career exploration instructional booklet on the travel agent's occupation is one of several resulting from the rural southwestern Colorado CEPAC Project (Career Education Process of Attitude Change). Based on a job analysis and utilizing a programed instructional format, the following content is included: A brief description of what a travel…

  1. SEM: A Cultural Change Agent

    Science.gov (United States)

    Barnes, Bradley; Bourke, Brian

    2015-01-01

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

  2. Vitamina D y cáncer: acción antineoplásica de la 1α, 25(OH2 -vitamina D3 Vitamin D and cancer: antineoplastic effects of 1α,25(OH2-vitamin D3

    Directory of Open Access Journals (Sweden)

    Verónica González Pardo

    2012-04-01

    Full Text Available La forma hormonalmente activa de la vitamina D, 1α,25(OH2-vitamina D3 (1α,25(OH2D3, además de desempeñar un rol crucial en el mantenimiento de la homeostasis de calcio en el cuerpo, también regula el crecimiento y la diferenciación de diferentes tipos celulares, incluyendo células cancerosas. Actualmente hay numerosos estudios que investigan los efectos de la hormona en estas células, debido al interés en el uso terapéutico del 1α,25(OH2D3 y de análogos con menor actividad calcémica para el tratamiento o prevención del cáncer. En este trabajo de revisión se describe el sistema endocrino de la vitamina D, su mecanismo de acción, su acción antineoplásica y se provee información sobre los últimos avances en el estudio de nuevos análogos de la hormona con menos actividad calcémica para el tratamiento del cáncer.The hormonal form of vitamin D, 1α,25(OH2-vitamin D3 (1α,25(OH2D3, in addition of playing a central role in the control of calcium homeostasis in the body, regulates the growth and differentiation of different cell types, including cancer cells. At present several epidemiologic and clinical studies investigate the effect of the hormone in these cells due to the interest in the therapeutic use of 1α,25(OH2D3 and analogues with less calcemic activity for prevention or treatment of cancer. This review describes vitamin D endocrine system, its mechanism of action, its antineoplastic activity and provides information about the latest advances in the study of new hormone analogues with less calcemic activity for cancer treatment.

  3. 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.

  4. Limonene and tetrahydrofurfurly alcohol cleaning agent

    Science.gov (United States)

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

    1997-10-21

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

  5. Limonene and tetrahydrofurfuryl alcohol cleaning agent

    Science.gov (United States)

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

    1996-05-07

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

  6. Limonene and tetrahydrofurfuryl alcohol cleaning agent

    Science.gov (United States)

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

    1997-10-21

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

  7. Innovative agents in cancer prevention.

    Science.gov (United States)

    Manson, Margaret M; Farmer, Peter B; Gescher, Andreas; Steward, William P

    2005-01-01

    There are many facets to cancer prevention: a good diet, weight control and physical activity, a healthy environment, avoidance of carcinogens such as those in tobacco smoke, and screening of populations at risk to allow early detection. But there is also the possibility of using drugs or naturally occurring compounds to prevent initiation of, or to suppress, tumour growth. Only a few such agents have been used to date in the clinic with any success, and these include non-steroidal anti-inflammatory drugs for colon, finasteride for prostate and tamoxifen or raloxifene for breast tumours. An ideal chemopreventive agent would restore normal growth control to a preneoplastic or cancerous cell population by modifying aberrant signalling pathways or inducing apoptosis (or both) in cells beyond repair. Characteristics for such an agent include selectivity for damaged or transformed cells, good bioavailability and more than one mechanism of action to foil redundancy or crosstalk in signalling pathways. As more research effort is being targeted towards this area, the distinction between chemotherapeutic and chemopreventive agents is blurring. Chemotherapeutic drugs are now being designed to target over- or under-active signalling molecules within cancer cells, a philosophy which is just as relevant in chemoprevention. Development of dietary agents is particularly attractive because of our long-standing exposure to them, their relative lack of toxicity, and encouraging indications from epidemiology. The carcinogenic process relies on the cell's ability to proliferate abnormally, evade apoptosis, induce angiogenesis and metastasise to distant sites. In vitro studies with a number of different diet-derived compounds suggest that there are molecules capable of modulating each of these aspects of tumour growth. However, on the negative side many of them have rather poor bioavailability. The challenge is to uncover their multiple mechanisms of action in order to predict their

  8. Does an Agent Matter? The Effects of Animated Pedagogical Agents on Multimedia Environments.

    Science.gov (United States)

    Craig, Scotty D.; Gholson, Barry

    Data are presented on the effects of Animated Agents on multimedia learning environments with specific concerns of split attention and modality effects. The study was a 3 (agent properties: agent only, agent with gestures, no agent) x 3 (picture features: static picture, sudden onset, animation) factorial design with outcome measures of mental…

  9. 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.

  10. Software agents in molecular computational biology.

    Science.gov (United States)

    Keele, John W; Wray, James E

    2005-12-01

    Progress made in applying agent systems to molecular computational biology is reviewed and strategies by which to exploit agent technology to greater advantage are investigated. Communities of software agents could play an important role in helping genome scientists design reagents for future research. The advent of genome sequencing in cattle and swine increases the complexity of data analysis required to conduct research in livestock genomics. Databases are always expanding and semantic differences among data are common. Agent platforms have been developed to deal with generic issues such as agent communication, life cycle management and advertisement of services (white and yellow pages). This frees computational biologists from the drudgery of having to re-invent the wheel on these common chores, giving them more time to focus on biology and bioinformatics. Agent platforms that comply with the Foundation for Intelligent Physical Agents (FIPA) standards are able to interoperate. In other words, agents developed on different platforms can communicate and cooperate with one another if domain-specific higher-level communication protocol details are agreed upon between different agent developers. Many software agent platforms are peer-to-peer, which means that even if some of the agents and data repositories are temporarily unavailable, a subset of the goals of the system can still be met. Past use of software agents in bioinformatics indicates that an agent approach should prove fruitful. Examination of current problems in bioinformatics indicates that existing agent platforms should be adaptable to novel situations.

  11. Children as digital rights agents

    DEFF Research Database (Denmark)

    Stald, Gitte Bang

    2016-01-01

    the role of the “adult world” is. We need to focus more on the active role that children and adolescents play, according to age, skills and various capacities, in identifying, reflecting upon and acting according to opportunities and challenges in relation to digital media and digital rights (Hartman et al...... 2007). The paper presents a model for analyzing the intersecting levels of children as agents in relation to digital risks and rights: Children as peer-to-peer agents. Children provide mutual practical guidance; experience sharing; advice. re. to risk and harm. Children as advocates/ politicians....... Children participate in youth parliaments; media councils; Safer Internet day; IGF; NGOs, Children as informants. Children contribute to research; media coverage; content providers; reporters (of negative content/ behavior The model is primarily supported by empirical data from the Net Children Go Mobile...

  12. Extension agents and conflict narratives

    DEFF Research Database (Denmark)

    Bond, Jennifer Lauren

    2016-01-01

    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 subjective......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 elicit the conflict narratives present among extension professionals. A concourse of 221 statements were devised from interviews and group discussions with key informants and a final sample of 49 statements was used for the sorting. Thirteen Q-sorts were undertaken with among rural extension...

  13. 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...... 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...... by developments within semantics for logic programming within computational logic and formal theories of truth within philosophical logic. The thesis provides a number of examples showing how the developed theories can be used as reasoning frameworks for agents with introspective abilities. In Danish...

  14. Solidifying agent for radioactive waste

    International Nuclear Information System (INIS)

    Sakai, Etsuro; Kida, Tsutomu; Sasagawa, Yukio.

    1988-01-01

    Purpose: To apply solidifying treatment to boron-containing radioactive wastes while improving the durability, rapid hardening property and processing performance, as well as reducing the leaching property. Constitution: A solidifying agent comprising calcium aluminate having CaO and Al 2 O 3 at 1.5 - 4 molar ratio, super fine powder and high performance moderator is used. As the super fine powder, those having a grain size smaller by 1 - 2 orders than that of the calcium aluminate are preferred. Specifically, there can be used silica dust, calcium carbonate, silica gel, titanium oxide, aluminum oxide, etc. As the moderator, there are used those surface active agents of great dispersing performance not causing excess delay for coagulation or excess air entrainment when added in a great amount to cements. Specifically, there can be mentioned those mainly composed of salts of naphthalene sulfonic acid-formaldehyde condensates, salts of melamine sulfonic acid formaldehyde condensates, etc. (Ikeda, J.)

  15. Antineoplastic therapy by radioactive cisplatin in experiment

    International Nuclear Information System (INIS)

    Dikiy, N.P.; Dovbnya, A.N.; Lyashko, Yu.V.; Medvedeva, E.P.; Medvedev, D.V.; Uvarov, V.L.

    2007-01-01

    The method of 195m Pt production on linear electron accelerators and cyclotron of NSC KIPT are described. The method of 195m Pt separation from the irradiated samples are developed. The methods of cisplatin synthesis with use of a radioactive isotope of 195m Pt are realized. Results of biological tests of radioactive cisplatin on animals are described. Our preliminary results demonstrate the feasibility of radioactive cisplatin for treatment of cancer diseases

  16. Antineoplastic And Antiviral Properties Of Merocyanine 540

    Science.gov (United States)

    Sieber, Fritz

    1989-03-01

    Simultaneous exposure to the lipophilic photosensitizer, merocyanine 540, and light in the presence of serum (or certain serum components) and oxygen kills leukemia cells, lymphoma cells, neuroblastoma cells, cell-free enveloped viruses, cell-associated enveloped viruses, and virus-infected cells. The same treatment spares pluripotent hematopoietic stem cells, mature erythrocytes, factor VIII, von Willebrand factor, and probably other blood components. Merocyanine 540-mediated photosensitization is now being evaluated clinically as a means to eliminate residual tumor cells from autologous remission bone marrow grafts and preclinically as a means to inactivate pathogenic viruses in blood products.

  17. Strategic Design of Mobile Agents

    OpenAIRE

    Vulkan, Nir

    2002-01-01

    Much of the economic value of electronic commerce comes from the automation of interactions between businesses and individuals. Game theory is a useful set of tools that can be used by designers of electronic-commerce applications in analyzing and engineering of automated agents and communication protocols. The central theoretical concept used in game theory is the Nash equilibrium. In this article, I show how the outcomes supported by a Nash equilibrium can positively be enlarged using autom...

  18. Needs, Pains, and Motivations in Autonomous Agents.

    Science.gov (United States)

    Starzyk, Janusz A; Graham, James; Puzio, Leszek

    This paper presents the development of a motivated learning (ML) agent with symbolic I/O. Our earlier work on the ML agent was enhanced, giving it autonomy for interaction with other agents. Specifically, we equipped the agent with drives and pains that establish its motivations to learn how to respond to desired and undesired events and create related abstract goals. The purpose of this paper is to explore the autonomous development of motivations and memory in agents within a simulated environment. The ML agent has been implemented in a virtual environment created within the NeoAxis game engine. Additionally, to illustrate the benefits of an ML-based agent, we compared the performance of our algorithm against various reinforcement learning (RL) algorithms in a dynamic test scenario, and demonstrated that our ML agent learns better than any of the tested RL agents.This paper presents the development of a motivated learning (ML) agent with symbolic I/O. Our earlier work on the ML agent was enhanced, giving it autonomy for interaction with other agents. Specifically, we equipped the agent with drives and pains that establish its motivations to learn how to respond to desired and undesired events and create related abstract goals. The purpose of this paper is to explore the autonomous development of motivations and memory in agents within a simulated environment. The ML agent has been implemented in a virtual environment created within the NeoAxis game engine. Additionally, to illustrate the benefits of an ML-based agent, we compared the performance of our algorithm against various reinforcement learning (RL) algorithms in a dynamic test scenario, and demonstrated that our ML agent learns better than any of the tested RL agents.

  19. Preponderant agent, what is that?

    Directory of Open Access Journals (Sweden)

    Clara Luz Álvarez

    2015-05-01

    Full Text Available Purpose – Preponderant agent is a new instrument for preventing and reverting adverse impact in competition due to highly concentrated markets. Therefore, this paper's objective is to present and analyze the preponderant agent concept in Mexico with emphasis on the broadcast sector, the telecommunication regulator decisions and the courts' interpretation. Methodology/approach/design – The objectives were achieved by researching and analyzing the main legal documents, the Congress reports and debates, the regulator's decisions and other relevant regulator's documents, as well as final decisions by the courts in connection with broadcast sector. Findings – Among the findings are that certain topics were not duly addressed by the Mexican regulator, or by the Congress, whereas the courts were more willing to hold decisions in favor of public interest based on constitutional intent and deference to the regulator's decision. Originality/value – This paper will be valuable for persons interested in telecommunications, broadcast and antitrust. Although the preponderant agent concept created in Mexico is not necessarily a “best practice”, it does provide an alternative instrument in antitrust. Moreover, the courts decisions also provide criteria regarding regulatory deference for the regulator.

  20. Solidification agent for radioactive waste

    International Nuclear Information System (INIS)

    Sakai, Etsuro; Shibayama, Yukio.

    1986-01-01

    Purpose: In low and medium level radioactive waste processing, to obtain superior solidified blocks by mixing cement, super-fine dusts and high-performance water-reducing agent and water to radioactive waste materials for solidification. Constitution: The various types of portland cements available are used for solidification. Silica dust is used as the super-fine dust and has an average article size of one order smaller than that of the cement used for solidification. Napthalene, sulfonic acid formalydehyde condensation salts etc. are used as the water-reducing agents. For example, for hundred units, by weight, of cement and super-fine dust 10 units (by solid content) are added. Furthermore, smaller quantities of water are desirable. By mixing the radioactive wastes with cement, super-fine dust, water-reducing agents, and water, the solidified material shows superior chemical resistance and durability. The processing capacity is also increased. Furthermore, a more leach resistant solid can be obtained for storage. (Takahashi, M.)

  1. Overprescribing of lipid lowering agents.

    Science.gov (United States)

    Smith, M A; Cox, E D; Bartell, J M

    2006-08-01

    Undertreatment of hyperlipidemia has received considerable attention. However, little is known about trends in overprescribing of lipid lowering agents. We examined these trends and their associations with physician, practice, and organisational factors. 2034 physicians were surveyed twice: baseline (1996-7) and follow up (1998-9). On each occasion they were asked: "For what percentage of 50 year old men without other cardiac risk factors would you recommend an oral agent for total cholesterol of 240, LDL 150, and HDL 50 after 6 months on a low cholesterol diet?" During the survey period the National Cholesterol Education Program guidelines did not recommend prescribing for these patients. Binomial and multinomial logistic regressions assessed baseline overprescribing and longitudinal changes in overprescribing, accounting for complex sampling. 39% of physicians recommended prescribing at baseline (round 1), increasing at follow up (round 2) to 51% (p overprescribe at baseline were less likely to be board certified (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.38 to 0.63; p overprescribing to be international medical graduates (OR 2.09, 95% CI 1.20 to 3.64; p = 0.011) and to spend more hours in patient care (OR 1.14, 95% CI 1.03 to 1.26; p = 0.016). Overprescribing of lipid lowering agents is commonplace and increased. At baseline and longitudinally, overprescribing was primarily associated with physician and practice characteristics and not with organisational factors.

  2. Commission of the commercial agent

    Directory of Open Access Journals (Sweden)

    Radović Mirjana

    2015-01-01

    Full Text Available In this paper the author analyses the commercial agent's commission as the most important type of remuneration for commercial agency. In the European Union the issue of commercial agent's commission is regulated in the Directive 86/653/EEC on self-employed commercial agents, whereas the Serbian Law on Obligations has still not been harmonised with those rules. Such state of law would change if and when the new Serbian Civil Code is enacted, since its latest Draft contains numerous new solutions, which were inspired by the Directive. The first part of the paper is dedicated to defining the term 'commission' and its distinguishing from the wider term 'remuneration'. Thereafter, the main types of commission are explained. The following part investigates whether the commission or its specific type constitutes essentialia or naturalia negotii of the contract on commercial agency. Finally, the last part of the paper deals with the amount and the extent of covering costs by the commission, in the absence of any agreement on that matter.

  3. 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 ...

  4. 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.

  5. 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.

  6. Validation of Agent Based Distillation Movement Algorithms

    National Research Council Canada - National Science Library

    Gill, Andrew

    2003-01-01

    Agent based distillations (ABD) are low-resolution abstract models, which can be used to explore questions associated with land combat operations in a short period of time Movement of agents within the EINSTein and MANA ABDs...

  7. Surface modification agents for lithium batteries

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zonghai; Amine, Khalil; Belharouak, Ilias

    2017-11-21

    An active material for an electrochemical device wherein a surface of the active material is modified by a surface modification agent, wherein the surface modification agent is an organometallic compound.

  8. 2APL: a practical agent programming language

    OpenAIRE

    Dastani, M.M.

    2008-01-01

    This article presents a BDI-based agent-oriented programming language, called 2APL (A Practical Agent Programming Language). This programming language facilitates the implementation ofmulti-agent systems consisting of individual agents thatmay share and access external environments. It realizes an effective integration of declarative and imperative style programming by introducing and integrating declarative beliefs and goals with events and plans. It also provides practical programming const...

  9. An overview of agents in knowledge management

    OpenAIRE

    Dignum, M.V.

    2006-01-01

    Current developments in Knowledge Management concern the sharing and usage of knowledge in dynamic environments. The need for systems that both react to and anticipate the needs and expectations of users calls for flexible and adaptable development and implementation frameworks. These are exactly the characteristics that identify software agents and agent societies, which make natural the application of the agent paradigm in KM. This paper attempts to identify both the advantages of agents fo...

  10. Honey - A Novel Antidiabetic Agent

    Science.gov (United States)

    Erejuwa, Omotayo O.; Sulaiman, Siti A.; Wahab, Mohd S. Ab

    2012-01-01

    Diabetes mellitus remains a burden worldwide in spite of the availability of numerous antidiabetic drugs. Honey is a natural substance produced by bees from nectar. Several evidence-based health benefits have been ascribed to honey in the recent years. In this review article, we highlight findings which demonstrate the beneficial or potential effects of honey in the gastrointestinal tract (GIT), on the gut microbiota, in the liver, in the pancreas and how these effects could improve glycemic control and metabolic derangements. In healthy subjects or patients with impaired glucose tolerance or diabetes mellitus, various studies revealed that honey reduced blood glucose or was more tolerable than most common sugars or sweeteners. Pre-clinical studies provided more convincing evidence in support of honey as a potential antidiabetic agent than clinical studies did. The not-too-impressive clinical data could mainly be attributed to poor study designs or due to the fact that the clinical studies were preliminary. Based on the key constituents of honey, the possible mechanisms of action of antidiabetic effect of honey are proposed. The paper also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. It makes recommendations for further clinical studies on the potential antidiabetic effect of honey. This review provides insight on the potential use of honey, especially as a complementary agent, in the management of diabetes mellitus. Hence, it is very important to have well-designed, randomized controlled clinical trials that investigate the reproducibility (or otherwise) of these experimental data in diabetic human subjects. PMID:22811614

  11. Agent based energy management systems

    Energy Technology Data Exchange (ETDEWEB)

    Wolter, Martin

    2012-07-01

    In liberalized, regulated energy markets, the different participants - namely producers and consumers of energy, transmission and distribution system operators as well as regulatory authorities - have partly divergent and partly convergent interests. Loads, power plants and grid operators try to maximize their own benefit in this highly complex environment accepting to act detrimentally to others. Although the relationship between the participants is mostly competitive, there are some fundamental shared interests, e.g. voltage stability, a constant system frequency or efficient energy production, transmission and distribution, which are endangered e.g. by increased injection of volatile sources in low and medium voltage grids, displacement of stabilizing bulk generation and the slowly progressing extension of the electric grid. There is a global consensus, that the resulting challenges can efficiently be faced using information and communication technologies to coordinate grid utilization and operation. The basic idea is to benefit from unused reserves by participating in deployment of system services e.g. reactive power supply to keep the voltage within certain bounds. The coordination can best be done by the grid operator. All activities of that kind are summarized under the umbrella term ''Smart Grid''. To simultaneously model the behavior and interests of different types of market participants and their convergent and divergent interests, multi-agent systems are used. They offer a perfectly fitting framework for this sort of game theory and can easily be adapted to all kinds of new challenges of electricity markets. In this work, multi-agent systems are used to either cooperatively or competitively solve problems in distribution and transmission systems. Therefore, conventional algorithms have to be modified to converge into multiple local optima using only small pieces of the entire system information. It is clearly stated, that personal

  12. 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.

  13. 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...... to 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....

  14. Protein binding of psychotropic agents

    International Nuclear Information System (INIS)

    Hassan, H.A.

    1990-01-01

    Based upon fluorescence measurements, protein binding of some psychotropic agents (chlorpromazine, promethazine, and trifluoperazine) to human IgG and HSA was studied in aqueous cacodylate buffer, PH7. The interaction parameters determined from emission quenching of the proteins. The interaction parameters determined include the equilibrium constant (K), calculated from equations derived by Borazan and coworkers, the number of binding sites (n) available to the monomer molecules on a single protein molecule. The results revealed a high level of affinity, as reflected by high values of K, and the existence of specific binding sites, since a limited number of n values are obtained. 39 tabs.; 37 figs.; 83 refs

  15. Multi agent gathering waste system

    Directory of Open Access Journals (Sweden)

    Álvaro LOZANO MURCIEGO

    2016-07-01

    Full Text Available Along this paper, we present a new multi agent-based system to gather waste on cities and villages. We have developed a low cost wireless sensor prototype to measure the volume level of the containers. Furthermore a route system is developed to optimize the routes of the trucks and a mobile application has been developed to help drivers in their working days. In order to evaluate and validate the proposed system a practical case study in a real city environment is modeled using open data available and with the purpose of identifying limitations of the system.

  16. Diarrhea caused by circulating agents.

    Science.gov (United States)

    Fabian, Elisabeth; Kump, Patrizia; Krejs, Guenter J

    2012-09-01

    Circulating agents cause intestinal secretion or changes in motility with decreased intestinal transit time, resulting in secretory-type diarrhea. Secretory diarrhea as opposed to osmotic diarrhea is characterized by large-volume, watery stools, often more than 1 L per day; by persistence of diarrhea when patients fast; and by the fact that on analysis of stool-water, measured osmolarity is identical to that calculated from the electrolytes present. Although sodium plays the main role in water and electrolyte absorption, chloride is the major ion involved in secretion. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. A principal-agent Model of corruption

    NARCIS (Netherlands)

    Groenendijk, Nico

    1997-01-01

    One of the new avenues in the study of political corruption is that of neo-institutional economics, of which the principal-agent theory is a part. In this article a principal-agent model of corruption is presented, in which there are two principals (one of which is corrupting), and one agent (who is

  18. Do pedagogical agents enhance software training?

    NARCIS (Netherlands)

    van der Meij, Hans

    2013-01-01

    This study investigates whether a tutorial for software training can be enhanced by adding a pedagogical agent, and whether the type of agent matters (i.e., cognitive, motivational, or mixed). The cognitive agent was designed to stimulate students to process their experiences actively. The

  19. Animated BDP agents in virtual environments

    NARCIS (Netherlands)

    Nijholt, Antinus; Egges, A.; op den Akker, Hendrikus J.A.; Zwiers, Jakob; Krose, B.; de Rijke, M.; Schreiber, G.; van Someren, M.

    2001-01-01

    We introduce a Believes, Desires and Plans (BDP) agent that acts in a virtual environment using multi-modal interaction with the user. The environment is our virtual theatre environment. In this environment different agents have been introduced. In order to obtain a more uniform framework for agent

  20. Group Formation Among Decentralized Autonomous Agents

    NARCIS (Netherlands)

    Ogston, E.F.Y.L.; van Steen, M.R.; Brazier, F.M.

    2004-01-01

    This paper examines a method of clustering within a fully decentralized multi-agent system. Our goal is to group agents with similar objectives or data, as is done in traditional clustering. However, we add the additional constraint that agents must remain in place on a network, instead of first

  1. Individualism and Collectivism in Trade Agents

    NARCIS (Netherlands)

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

    2008-01-01

    Agent-Based Modeling can contribute to the understanding of international trade processes. Models for the effects of culture and cultural differences on agent behavior are required for realistic agent-based simulation of international trade. This paper makes a step toward modeling of culture in

  2. A Framework for Organization-Aware Agents

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt; Dignum, Virginia; Villadsen, Jørgen

    2016-01-01

    This short paper introduces and summarizes the AORTA reasoning framework that can be integrated into BDI-agents to enable organizational decision-making. This work has recently been published in the Journal of Autonomous Agents and Multi-Agent Systems (JAAMAS), as [3]....

  3. Radioactive scanning agents with hydroquinone stabilizer

    International Nuclear Information System (INIS)

    Whitehouse, H.S.

    1982-01-01

    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

  4. 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...

  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

  6. IRANIAN MEDICINAL PLANTS AS ANTIMICROBIAL AGENTS

    OpenAIRE

    Mohaddese Mahboubi

    2013-01-01

    Resistance of human and food spoilage pathogens to antimicrobial agents and the side effects of chemical agents or preservative for human is caused for finding natural new antimicrobial agents, especially among the medicinal plants. This review introduces the methods that are used for antimicrobial evaluations and synergistic activities and the antimicrobial potential of some Iranian medicinal plants.

  7. 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.

  8. 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.

  9. Agent modelling in METATEM and DESIRE

    NARCIS (Netherlands)

    Mulder, Marco; Treur, Jan; Fisher, Michael

    1998-01-01

    In spite of the rapid spread of agent technology, there is, as yet, little evidence of an engineering approach to the development of multi-agent systems. For example, both development methods and verification techniques for multi-agent systems are rare. In this paper, we describe a case study aimed

  10. Using Intelligent Agents To Assist Educators.

    Science.gov (United States)

    Knode, Steve; Knode, Jon-David W.

    This paper begins with background on intelligent agents (software programs built to perform certain specific tasks for the user). A taxonomy that categorizes intelligent agents by the degree of intelligence embedded in the software is presented. Applications of today's intelligent agents are discussed, including specific examples of the following:…

  11. Information brokering agents in intelligent Websites

    NARCIS (Netherlands)

    Jonker, Catholijn M.; Treur, J.

    1999-01-01

    In this paper a generic information broker agent for intelligent Websites is introduced. The agent architecture has been designed using the compositional development method for multi-agent systems Desire. The use of the architecture is illustrated in an Electronic Commerce application for a

  12. Modelling an Agent's Mind and Matter

    NARCIS (Netherlands)

    Jonker, C.M.; Treur, J.; Boman, M.

    1997-01-01

    In agent models often it is assumed that the agent maintains internal representations of the material world (e.g., its beliefs). An overall model of the agent and the material world necessarily incorporates sub-models for physical simulation and symbolic simulation, and a formalisation of the

  13. Making Agents Gaze Naturally. Does it work?

    NARCIS (Netherlands)

    van Es, Ivo; De Marsico, M.; Levialdi, S.; Heylen, Dirk K.J.; Panizzi, E.; van Dijk, Elisabeth M.A.G.; Nijholt, Antinus

    2002-01-01

    We investigated the effects of varying eye gaze behavior of an embodied conversational agent on the quality of human-agent dialogues. In an experiment we compared three versions of an agent: one with gaze behavior that is typically found to occur in human-human dialogues, one with gaze that is fixed

  14. Effectiveness testing of spill-treating agents

    International Nuclear Information System (INIS)

    Fingas, M.F.; Stoodley, R.; Laroche, N.

    1990-01-01

    Laboratory effectiveness tests are described for four classes of spill-treating agents: solidifiers, demulsifying agents, surface-washing agents and dispersants. Many treating agents in these four categories have been tested for effectiveness and the results are presented. Solidifiers or gelling agents solidify oil, requiring a large amount of agent to solidify oil-ranging between 16% by weight, to over 200%. Emulsion breakers prevent or reverse the formation of water-in-oil emulsions. A newly-developed effectiveness test shows that only one product is highly effective; however, many products will work, but require large amounts of spill-treating agent. Surfactant--containing materials are of two types, surface-washing agents and dispersants. Testing has shown that an agent that is a good dispersant is conversely a poor surface-washing agent, and vice versa. Tests of surface-washing agents show that only a few agents have effectiveness of 25-40%, where this effectiveness is the percentage of heavy oil removed from a test surface. Results using the 'swirling flask' test for dispersant effectiveness are reported. Heavy oils show effectiveness values of about 1%, medium crudes of about 10%, light crude oils of about 30% and very light oils of about 90%. (author)

  15. Exposição ocupacional a medicamentos antineoplásicos em clínicas veterinárias no município do Rio de Janeiro / Occupational risks in the manipulation of antineoplastic in clinical veterinarians in the of Rio de Janeiro city

    Directory of Open Access Journals (Sweden)

    Mônica Faria da Silva

    2013-02-01

    Full Text Available Médicos veterinários estão expostos constantemente a riscos químicos, físicos e biológicos durante a prática de sua profissão. Médicos veterinários, de 78 dos 88estabelecimentos registrados no Conselho Regional de Medicina Veterinária do Rio de Janeiro e com mais de cinco anos de funcionamento, foram entrevistados sobre o uso de medicamentos antineoplásicos, medidas de proteção individual e efeitos tóxicos associados. A vincristina (100% é o antineoplásico mais utilizado, seguido da ciclofosfamida (27,02%. Nenhuma das clínicas visitadas possuía capela de fluxo laminar; 58,10% dos profissionais não utilizavam máscaras, 16,20% não usavam luvas e 14,85% nenhum tipo de Equipamento de Proteção Individual (EPI; 30% relataram não conhecer os efeitos tóxicos decorrentes da exposição aos antineoplásicos. A maioria dos entrevistados relatou que, durante a graduação, não recebeu orientação adequada sobre riscos químicos ocupacionais. Ações de vigilância sanitária devem ser tomadas para diminuir os riscos decorrentes da manipulação de medicamentos antineoplásicos em clínicas veterinárias. -------------------------------------------------------------------------------- Veterinarians are constantly exposed to chemical physical and biological risks during professional practice. Veterinarians from 78 out of 88 fi ve-year functioning establishments in the city of Rio de Janeiro were interviewed about antineoplastics usage and individual protective measures and the associated toxic effects. As informed, vincristine (100% is the most widely used anticancer, followed by cyclophosphamide (27.02%. None of the clinics visited had any laminar fl ow chamber; 58.10% of professionals weren’t using masks to manipulate anticancers; 16.20% weren’t using gloves and 14.85% weren’t using any type of IEP; 30% reported not to be aware of antineoplastics toxicity. Most veterinarians related that during graduation course no proper

  16. Mobile agent location in distributed environments

    Science.gov (United States)

    Fountoukis, S. G.; Argyropoulos, I. P.

    2012-12-01

    An agent is a small program acting on behalf of a user or an application which plays the role of a user. Artificial intelligence can be encapsulated in agents so that they can be capable of both behaving autonomously and showing an elementary decision ability regarding movement and some specific actions. Therefore they are often called autonomous mobile agents. In a distributed system, they can move themselves from one processing node to another through the interconnecting network infrastructure. Their purpose is to collect useful information and to carry it back to their user. Also, agents are used to start, monitor and stop processes running on the individual interconnected processing nodes of computer cluster systems. An agent has a unique id to discriminate itself from other agents and a current position. The position can be expressed as the address of the processing node which currently hosts the agent. Very often, it is necessary for a user, a processing node or another agent to know the current position of an agent in a distributed system. Several procedures and algorithms have been proposed for the purpose of position location of mobile agents. The most basic of all employs a fixed computing node, which acts as agent position repository, receiving messages from all the moving agents and keeping records of their current positions. The fixed node, responds to position queries and informs users, other nodes and other agents about the position of an agent. Herein, a model is proposed that considers pairs and triples of agents instead of single ones. A location method, which is investigated in this paper, attempts to exploit this model.

  17. Nonsteroid anti-inflammatory agents.

    Science.gov (United States)

    Paulus, H E; Whitehouse, M W

    1973-01-01

    Nonsteroidal antiinflammatory agents (NSAID) are reviewed. Aspirin, indomethacin, and salicylate have all been shown to interfere or prevent the synthesis of prostaglandins (PGs), a main tissue inflammatory substance. However, an exception to the correlation of PG-synthetase inhibition with antiinflammatory activity has been noted with certain arylacetic acids. Studies on the role of lysosomes in the inflammation are criticized in this review, mainly because of improper understanding of the role of lysosomes in a physiological system. Since lysosomes are not a specific body, but an activator, attempts to isolate lysosomes to study functions are doomed to failure; i.e., a lysosome has no definition without the rest of its self-regulating system. NSAIDs work in 2 main ways; either via antiaggregation or antiinflammation. This may result in drug interactions between various types of NSAIDs. For example, simultaneous administration of aspirin with indomethacine did not produce an additive effect; rather they produced no effect in the rat paw edema test dissimilar to the action of either drug separately. However, hydrocortisone combined with another NSAID enhanced its antiinflammatory effects. Albumin binding theories of NSAID mechanism of action state that drugs are active only when albumin-bound because it has displaced tryptophane, or urate, or some other normally bound substance. The only way to discover an efficient antiinflammatory agent is to obviate the need for it by discovering the actual mechanism of inflammation, for when specific anti-etiologic therapy is developed, the need for treatment with NSAIDs is irrelevant.

  18. A Review of Luting Agents

    Directory of Open Access Journals (Sweden)

    Cornelis H. Pameijer

    2012-01-01

    Full Text Available Due to the availability of a large number of luting agents (dental cements proper selection can be a daunting task and is usually based on a practitioner’s reliance on experience and preference and less on in depth knowledge of materials that are used for the restoration and luting agent properties. This review aims at presenting an overview of current cements and discusses physical properties, biocompatibility and other properties that make a particular cement the preferred choice depending on the clinical indication. Tables are provided that outline the different properties of the generic classification of cements. It should be noted that no recommendations are made to use a particular commercial cement for a hypothetical clinical situation. The choice is solely the responsibility of the practitioner. The appendix is intended as a guide for the practitioner towards a recommended choice under commonly encountered clinical scenarios. Again, no commercial brands are recommended although the author recognizes that some have better properties than others. Please note that this flowchart strictly presents the author’s opinion and is based on research, clinical experience and the literature.

  19. Animal venoms as antimicrobial agents.

    Science.gov (United States)

    Perumal Samy, Ramar; Stiles, Bradley G; Franco, Octavio L; Sethi, Gautam; Lim, Lina H K

    2017-06-15

    Hospitals are breeding grounds for many life-threatening bacteria worldwide. Clinically associated gram-positive bacteria such as Staphylococcus aureus/methicillin-resistant S. aureus and many others increase the risk of severe mortality and morbidity. The failure of antibiotics to kill various pathogens due to bacterial resistance highlights the urgent need to develop novel, potent, and less toxic agents from natural sources against various infectious agents. Currently, several promising classes of natural molecules from snake (terrestrial and sea), scorpion, spider, honey bee and wasp venoms hold promise as rich sources of chemotherapeutics against infectious pathogens. Interestingly, snake venom-derived synthetic peptide/snake cathelicidin not only has potent antimicrobial and wound-repair activity but is highly stable and safe. Such molecules are promising candidates for novel venom-based drugs against S. aureus infections. The structure of animal venom proteins/peptides (cysteine rich) consists of hydrophobic α-helices or β-sheets that produce lethal pores and membrane-damaging effects on bacteria. All these antimicrobial peptides are under early experimental or pre-clinical stages of development. It is therefore important to employ novel tools for the design and the development of new antibiotics from the untapped animal venoms of snake, scorpion, and spider for treating resistant pathogens. To date, snail venom toxins have shown little antibiotic potency against human pathogens. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Ruthenium complexes as antimicrobial agents.

    Science.gov (United States)

    Li, Fangfei; Collins, J Grant; Keene, F Richard

    2015-04-21

    One of the major advances in medical science has been the development of antimicrobials; however, a consequence of their widespread use has been the emergence of drug-resistant populations of microorganisms. There is clearly a need for the development of new antimicrobials--but more importantly, there is the need for the development of new classes of antimicrobials, rather than drugs based upon analogues of known scaffolds. Due to the success of the platinum anticancer agents, there has been considerable interest in the development of therapeutic agents based upon other transition metals--and in particular ruthenium(II/III) complexes, due to their well known interaction with DNA. There have been many studies of the anticancer properties and cellular localisation of a range of ruthenium complexes in eukaryotic cells over the last decade. However, only very recently has there been significant interest in their antimicrobial properties. This review highlights the types of ruthenium complexes that have exhibited significant antimicrobial activity and discusses the relationship between chemical structure and biological processing--including site(s) of intracellular accumulation--of the ruthenium complexes in both bacterial and eukaryotic cells.

  1. Surfactants as blackbird stressing agents

    Science.gov (United States)

    Lefebvre, P.W.; Seubert, J.L.

    1970-01-01

    Applications of wetting-agent solutions produce mortality in birds. The exact cause of death is undetermined but it is believed that destruction of the insulating qualities of the plumage permits ambient cold temperatures and evaporation to lower the body temperature to a lethal level. The original concept of using these materials as bird-control tools was developed in 1958 at the Patuxent Wildlife Research Center, Bureau of Sport Fisheries and Wildlife Laurel, Maryland. Early field trials by personnel of the Division of Wildlife Services and the Denver Wildlife Research Center indicated that ground-application techniques had promise but limitations of the equipment precluded successful large-scale roost treatments. In 1966, Patuxent Center personnel began using tanker-type aircraft to evaluate high-volume aerial applications of wetting agents. The success of these tests led to the use of small aircraft to make low-volume, high-concentration aerial applications just prior to expected rainfall. Recent trials of the low-volume method show that, with some limitations, it is effective, inexpensive, and safe to the environment. Current research emphasizes the screening of new candidate materials for efficacy, biodegradability, and toxicity to plants and non-target animals, as well as basic investigations of the avian physiological mechanisms involved. Field trials to develop more effective application techniques will continue.

  2. Building Multi-Agent Systems Using Jason

    DEFF Research Database (Denmark)

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

    2010-01-01

    We provide a detailed description of the Jason-DTU system, including the used methodology, tools as well as team strategy. We also discuss the experience gathered in the contest. In spring 2009 the course “Artificial Intelligence and Multi- Agent Systems” was held for the first time...... on the 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...

  3. Reversal agents in anaesthesia and critical care

    Directory of Open Access Journals (Sweden)

    Nibedita Pani

    2015-01-01

    Full Text Available Despite the advent of short and ultra-short acting drugs, an in-depth knowledge of the reversal agents used is a necessity for any anaesthesiologist. Reversal agents are defined as any drug used to reverse the effects of anaesthetics, narcotics or potentially toxic agents. The controversy on the routine reversal of neuromuscular blockade still exists. The advent of newer reversal agents like sugammadex have made the use of steroidal neuromuscular blockers like rocuronium feasible in rapid sequence induction situations. We made a review of the older reversal agents and those still under investigation for drugs that are regularly used in our anaesthesia practice.

  4. Variations on agent-oriented programming

    Directory of Open Access Journals (Sweden)

    Dalia Baziukė

    2017-12-01

    Full Text Available Occurrence of the agent paradigm and its further applications have stimulated the emergence of new concepts and methodologies in computer science. Today terms like multi-agent system, agent-oriented methodology, and agent-oriented programming (AOP are widely used. The aim of this paper is to clarify the validity of usage of the terms AOP and AOP language. This is disclosed in two phases of an analysis process. Determining to which concepts, terms like agent, programming, object-oriented analysis and design, object-oriented programming, and agent-oriented analysis and design correspond is accomplished in the first phase. Analysis of several known agent system engineering methodologies in terms of key concepts used, final resulting artifacts, and their relationship with known programming paradigms and modern tools for agent system development is performed in the second phase. The research shows that in most cases in the final phase of agent system design and in the coding stage, the main artifact is an object, defined according to the rules of the object-oriented paradigm. Hence, we say that the computing society still does not have AOP owing to the lack of an AOP language. Thus, the term AOP is very often incorrectly assigned to agent system development frameworks that in most cases, transform agents into objects.DOI: 10.15181/csat.v5i1.1361

  5. Introduction to Agent Mining Interaction and Integration

    Science.gov (United States)

    Cao, Longbing

    In recent years, more and more researchers have been involved in research on both agent technology and data mining. A clear disciplinary effort has been activated toward removing the boundary between them, that is the interaction and integration between agent technology and data mining. We refer this to agent mining as a new area. The marriage of agents and data mining is driven by challenges faced by both communities, and the need of developing more advanced intelligence, information processing and systems. This chapter presents an overall picture of agent mining from the perspective of positioning it as an emerging area. We summarize the main driving forces, complementary essence, disciplinary framework, applications, case studies, and trends and directions, as well as brief observation on agent-driven data mining, data mining-driven agents, and mutual issues in agent mining. Arguably, we draw the following conclusions: (1) agent mining emerges as a new area in the scientific family, (2) both agent technology and data mining can greatly benefit from agent mining, (3) it is very promising to result in additional advancement in intelligent information processing and systems. However, as a new open area, there are many issues waiting for research and development from theoretical, technological and practical perspectives.

  6. A SURVEY OF THE PROPERTIES OF AGENTS

    Directory of Open Access Journals (Sweden)

    Kornelije Rabuzin

    2006-06-01

    Full Text Available In the past decade agent systems were considered to be as one of the major fields of study in Artificial Intelligence (AI field. Many different definitions of agents were presented and several different approaches describing agency can be distinguished. While some authors have tried to define “what” an agent really is, others have tried to identify agents by means of properties which they should possess. Most authors agree on these properties (at least basic set of properties which are intrinsic to agents. Since agent's definitions are not consistent, we are going to give an overview and list the properties intrinsic to an agent. Many different adjectives were attached to the term agent as well and many different kinds of agents and different architectures emerged too. The aim of this paper it go give an overview of what was going on in the field while taking into consideration main streams and projects. We will also present some guidelines important when modelling agent systems and say something about security issues. Also, some existing problems which restrict the wider usage of agents will be mentioned too.

  7. A Framework for Organization-Aware Agents

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt; Dignum, Virginia; Villadsen, Jørgen

    2017-01-01

    Open systems are characterized by the presence of a diversity of heterogeneous and autonomous agents that act according to private goals. Organizations, such as those used in real-life to structure human activities such as task allocation, coordination and supervision, can regulate the agents...... boundaries and work towards the objectives of the organization. In this paper, we present the AORTA reasoning framework and show how it can be integrated into typical BDI-agents. We provide operational semantics that enables agents to make organizational decisions in order to coordinate and cooperate without...... explicit coordination mechanisms within the agents. The organizational model is independent of that of the agents, and the approach is not tied to a specific organizational model, but uses an organizational metamodel. We show how AORTA helps agents work together in a system with an organization...

  8. An Agent Framework of Tourism Recommender System

    Directory of Open Access Journals (Sweden)

    Jia Zhi Yang

    2016-01-01

    Full Text Available This paper proposes the development of an Agent framework for tourism recommender system. The recommender system can be featured as an online web application which is capable of generating a personalized list of preference attractions for tourists. Traditional technologies of classical recommender system application domains, such as collaborative filtering, content-based filtering and content-based filtering are effectively adopted in the framework. In the framework they are constructed as Agents that can generate recommendations respectively. Recommender Agent can generate recommender information by integrating the recommendations of Content-based Agent, collaborative filtering-based Agent and constraint-based Agent. In order to make the performance more effective, linear combination method of data fusion is applied. User interface is provided by the tourist Agent in form of webpages and mobile app.

  9. Multi-agent for manufacturing systems optimization

    Science.gov (United States)

    Ciortea, E. M.; Tulbure, A.; Huţanu, C.-tin

    2016-08-01

    The paper is meant to be a dynamic approach to optimize manufacturing systems based on multi-agent systems. Multi-agent systems are semiautonomous decision makers and cooperate to optimize the manufacturing process. Increasing production the capacity is achieved by developing, implementing efficient and effective systems from control based on current manufacturing process. The model multi-agent proposed in this paper is based on communication between agents who, based on their mechanisms drive to autonomous decision making. Methods based on multi-agent programming are applied between flexible manufacturing processes and cooperation with agents. Based on multi-agent technology and architecture of intelligent manufacturing can lead to development of strategies for control and optimization of scheduled production resulting from the simulation.

  10. 10th International Conference on Practical Applications of Agents and Multi-Agent Systems

    CERN Document Server

    Pérez, Javier; Golinska, Paulina; Giroux, Sylvain; Corchuelo, Rafael; Trends in Practical Applications of Agents and Multiagent Systems

    2012-01-01

    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 2012 in the workshops: Workshop on Agents for Ambient Assisted Living, Workshop on Agent-Based Solutions for Manufacturing and Supply Chain and Workshop on Agents and Multi-agent systems for Enterprise Integration.

  11. Survey of agent for intelligent information retrieval; Chiteki kensaku no tame no agent no chosa

    Energy Technology Data Exchange (ETDEWEB)

    Yazawa, T. [Central Research Institute of Electric Power Industry, Tokyo (Japan)

    1996-09-01

    Development of agent systems has been surveyed, to classify and arrange characteristic functions of the agents, and to grasp the realization situation of these agents in their development. In addition, prospective functions of information retrieval systems using the agents at maximum and functions to be developed among these in the future are clarified. The agents are characterized by the expression function, communication function, planning function, adaptive function, and learning function. The agents are desired to be classified into interface agents whose works are to respond to individual workers, coordinator agents which conduct works with high pervasion, such as assignment of works and their control, and task agents which conduct specialized works for individual examples. Thus, design and configuration of the agent system, and improvement and expansion of system functions can be effectively and easily conducted. 52 refs., 5 figs., 3 tabs.

  12. Bioprotective agents in safety control

    Directory of Open Access Journals (Sweden)

    Dimitrijević-Branković Suzana I.

    2003-01-01

    Full Text Available Food poisoning is the one of the main health hazards even today. More than 200 known diseases are transmitted through food. The causes of foodborne illness include viruses, bacteria, parasites, toxins, metals, and prions and the symptoms of foodborne illness range from mild gastroenteritis to life-threatening neurological, hepatic and renal syndromes.The prevention of food poisonings represents very serious task for food manufacturers. Beside food control according to the concept "from the farm to the table" there is increased need for the development of new technology for longer shelf lifes of food. Food fermented by lactic acid bacteria (LAB and traditionally considered to be safe. There are many substances produced by LAB that affect the shelf life of fermented food, by active suppression of poisoning microorganisms growth. Because of that, the LAB is recently considered as bioprotective agents that have important role in food safety.

  13. Il libro agente della socializzazione

    Directory of Open Access Journals (Sweden)

    Daniela Sideri

    2017-06-01

    Full Text Available Il saggio indaga il ruolo del libro come agente di socializzazione, con particolare riferimento al pubblico dei lettori ragazzi e bambini e alle specifiche funzioni formative della “lettura della letteratura” in età pre-scolare e scolare fino ai 14 anni. La ricerca di matrice socio-culturale si è occupata per lo più del libro in qualità di prodotto eminentemente sociale (sociologia della letteratura, contenitore di testi significanti (semiotica, e bene di consumo dell’industria culturale (cultural studies: lo studio proposto richiama le conclusioni fondamentali di decenni di studi intorno al libro, con l’intento di rintracciare i criteri adeguati (tema, target, identità visiva, funzione pratica e utopica a guidare una classificazione dei generi 0-14 che evidenzi il valore socializzante di ciascuno, proponendo così una originale tipologia, che giustifica l’inserimento del libro tra quelle definite “agenzie testuali” della socializzazione.

  14. Host modulation by therapeutic agents

    Directory of Open Access Journals (Sweden)

    Sugumari Elavarasu

    2012-01-01

    Full Text Available Periodontal disease susceptible group present advanced periodontal breakdown even though they achieve a high standard of oral hygiene. Various destructive enzymes and inflammatory mediators are involved in destruction. These are elevated in case of periodontal destruction. Host modulation aims at bringing these enzymes and mediators to normal level. Doxycycline, nonsteroidal anti-inflammatory drugs (NSAIDs, bisphosphonates, nitrous oxide (NO synthase inhibitors, recombinant human interleukin-11 (rhIL-11, omega-3 fatty acid, mouse anti-human interleukin-6 receptor antibody (MRA, mitogen-activated protein kinase (MAPK inhibitors, nuclear factor-kappa B (NF-kb inhibitors, osteoprotegerin, and tumor necrosis factor antagonist (TNF-α are some of the therapeutic agents that have host modulation properties.

  15. DNA minor groove alkylating agents.

    Science.gov (United States)

    Denny, W A

    2001-04-01

    Recent work on a number of different classes of anticancer agents that alkylate DNA in the minor groove is reviewed. There has been much work with nitrogen mustards, where attachment of the mustard unit to carrier molecules can change the normal patterns of both regio- and sequence-selectivity, from reaction primarily at most guanine N7 sites in the major groove to a few adenine N3 sites at the 3'-end of poly(A/T) sequences in the minor groove. Carrier molecules discussed for mustards are intercalators, polypyrroles, polyimidazoles, bis(benzimidazoles), polybenzamides and anilinoquinolinium salts. In contrast, similar targeting of pyrrolizidine alkylators by a variety of carriers has little effect of their patterns of alkylation (at the 2-amino group of guanine). Recent work on the pyrrolobenzodiazepine and cyclopropaindolone classes of natural product minor groove binders is also reviewed.

  16. Blasting agents and initiation systems

    Energy Technology Data Exchange (ETDEWEB)

    Fiscor, S.

    2000-01-01

    Although blasting differs between and within each industry, as a whole, the mines and quarries are making a shift from a purely ammonium nitrate/fuel oil (ANFO) mixture to a blend of emulsion and ANFO on a straight emulsion. Non-electric (shock tube) initiation systems have provided a viable alternative to the electric detonator (blasting cap). Explosives manufacturers are seeing their roles changes to being blasting contractors or consultants rather than just suppliers. The article discusses these trends and gives examples of typical blasting techniques and amounts of blasting agent used at large USA surface coal mines. Electric caps are still used in blasting underground coal. The Ensign Bickford Co. (EBCo) is developing electronic detonators and has been field testing an electronic initiator, the DIGIDET detonator, for the last four years. When commercially available, electronic detonators will be accurate but will come with a hefty price tag. 2 photos.

  17. Loss of expression of a new member of the DNAJ protein family confers resistance to chemotherapeutic agents used in the treatment of ovarian cancer.

    Science.gov (United States)

    Shridhar, V; Bible, K C; Staub, J; Avula, R; Lee, Y K; Kalli, K; Huang, H; Hartmann, L C; Kaufmann, S H; Smith, D I

    2001-05-15

    Differential display-PCR between ovarian tumor cell lines and short-term cultures of normal ovarian epithelial cell brushings was used to isolate a differentially expressed transcript and its corresponding gene. The gene, which mapped to 13q14.1, has partial homology in the DNAJ domain to a number of proteins with a similar domain and was designated as methylation-controlled J protein (MCJ). MCJ has the highest similarity to a functionally undefined protein from Caenorhabditis elegans. MCJ is expressed as a 1.2-kb transcript in several adult tissues, with testis showing the highest level of expression. Expression of MCJ was absent in three of seven ovarian cancer cell lines. Similarly, expression analysis using semiquantitative reverse transcription-PCR indicated that 12 of 18 primary ovarian tumors examined had either a complete absence or lower levels of expression of this gene. 5-Aza-2'-deoxycytidine treatment of the OV202 cell line induced MCJ expression in a dose-dependent manner, implicating methylation in this induction. Loss of heterozygosity and methylation-specific PCR analysis revealed that the loss of MCJ expression in primary tumors and cell lines was attributable to deletion of one allele and methylation of the other. To assess the potential functional significance of MCJ down-regulation, the sensitivity of parental (MCJ-nonexpressing) and MCJ-transfected OV167 cells to antineoplastic agents was evaluated. MCJ expression was associated with enhanced sensitivity to paclitaxel, topotecan, and cisplatin, suggesting that MCJ loss may play a role in de novo chemoresistance in ovarian carcinoma. These observations raise the possibility that MCJ loss may: (a) have potential prognostic significance in ovarian cancer; and (b) contribute to the malignant phenotype by conferring resistance to the most commonly used chemotherapeutic agents for ovarian cancer.

  18. Effects of cytochalasin congeners, microtubule-directed agents, and doxorubicin alone or in combination against human ovarian carcinoma cell lines in vitro

    International Nuclear Information System (INIS)

    Trendowski, Matthew; Christen, Timothy D.; Acquafondata, Christopher; Fondy, Thomas P.

    2015-01-01

    Although the actin cytoskeleton is vital for carcinogenesis and subsequent pathology, no microfilament-directed agent has been approved for cancer chemotherapy. One of the most studied classes of microfilament-directed agents has been the cytochalasins, mycotoxins known to disrupt the formation of actin polymers. In the present study, we sought to determine the effects of cytochalasin congeners toward human drug sensitive and multidrug resistant cell lines. SKOV3 human ovarian carcinoma and several multidrug resistant derivatives were tested for sensitivity against a panel of nine cytochalasin congeners, as well as three clinically approved chemotherapeutic agents (doxorubicin, paclitaxel, and vinblastine). In addition, verapamil, a calcium ion channel blocker known to reverse P-glycoprotein (P-gp) mediated drug resistance, was used in combination with multiple cytochalasin congeners to determine whether drug sensitivity could be increased. While multidrug resistant SKVLB1 had increased drug tolerance (was more resistant) to most cytochalasin congeners in comparison to drug sensitive SKOV3, the level of resistance was 10 to 1000-fold less for the cytochalasins than for any of the clinically approved agents. While cytochalasins did not appear to alter the expression of ATP binding cassette (ABC) transporters, several cytochalasins appeared to inhibit the activity of ABC transporter-mediated efflux of rhodamine 123 (Rh123), suggesting that these congeners do have affinity for drug efflux pumps. Cytochalasins also appeared to significantly decrease the F/G-actin ratio in both drug sensitive and drug resistant cells, indicative of marked microfilament inhibition. The cytotoxicity of most cytochalasin congeners could be increased with the addition of verapamil, and the drug sensitivity of resistant SKVLB1 to the clinically approved antineoplastic agents could be increased with the addition of cytochalasins. As assessed by isobolographic analysis and Chou

  19. An Important Chemical Weapon Group: Nerve Agents

    Directory of Open Access Journals (Sweden)

    Hakan Yaren

    2007-12-01

    Full Text Available As a result of developing modern chemistry, nerve agents, which are one of the most important group of efficient chemical warfare agents, were developed just before Second World War. They generate toxic and clinical effects via inhibiting acetylcholinesterase irreversibly and causing excessive amounts of acetylcholine at cholinergic synapses in the body. Clinical symptoms are occurred as a result of affected muscarinic (stimulation of secretuar glands, miosis, breathing problems etc., nicotinic (stimulation of skeletal muscles, paralyse, tremors etc. and central nerve system (convulsions, loss of consciousness, coma etc. areas. In case of a nerve agent exposure, treatment includes the steps of ventilation, decontamination, antidotal treatment (atropine, oximes, diazepam and pyridostigmine bromide and supportive theraphy. Because of arising possibility of using chemical warfare agents due to current conjuncture of the world, medical staff should know about nerve agents, their effects and how to treat the casualties exposured to nerve agents. [TAF Prev Med Bull 2007; 6(6.000: 491-500

  20. An Important Chemical Weapon Group: Nerve Agents

    Directory of Open Access Journals (Sweden)

    Hakan Yaren

    2007-12-01

    Full Text Available As a result of developing modern chemistry, nerve agents, which are one of the most important group of efficient chemical warfare agents, were developed just before Second World War. They generate toxic and clinical effects via inhibiting acetylcholinesterase irreversibly and causing excessive amounts of acetylcholine at cholinergic synapses in the body. Clinical symptoms are occurred as a result of affected muscarinic (stimulation of secretuar glands, miosis, breathing problems etc., nicotinic (stimulation of skeletal muscles, paralyse, tremors etc. and central nerve system (convulsions, loss of consciousness, coma etc. areas. In case of a nerve agent exposure, treatment includes the steps of ventilation, decontamination, antidotal treatment (atropine, oximes, diazepam and pyridostigmine bromide and supportive theraphy. Because of arising possibility of using chemical warfare agents due to current conjuncture of the world, medical staff should know about nerve agents, their effects and how to treat the casualties exposured to nerve agents. [TAF Prev Med Bull. 2007; 6(6: 491-500

  1. Supporting a Learner Community with Software Agents

    Directory of Open Access Journals (Sweden)

    Pierre Tchounikine

    2004-04-01

    Full Text Available This paper describes a multi- agent approach that aims at supporting learners involved in a collective activity. We consider pedagogical situations where students have to explicitly define the articulation of their collective work and then achieve the different tasks they have defined. Our objective is to support these students by taking some of these tasks in charge whilst making them work out such organisation features. For this purpose, we propose to consider that the group of students forms a multi- agent system and to introduce software agents that can achieve some of the tasks within this group. This conducts students to tackle the problem in terms of human and software agent coordination. We present how this approach can be conceptualized and modelled using Engeström’s triangle, how task delegation can be used as a means to enable students to define the software agents’ behaviour and the multi-agent implementation we propose.

  2. Persuasive Conversational Agent with Persuasion Tactics

    Science.gov (United States)

    Narita, Tatsuya; Kitamura, Yasuhiko

    Persuasive conversational agents persuade people to change their attitudes or behaviors through conversation, and are expected to be applied as virtual sales clerks in e-shopping sites. As an approach to create such an agent, we have developed a learning agent with the Wizard of Oz method in which a person called Wizard talks to the user pretending to be the agent. The agent observes the conversations between the Wizard and the user, and learns how to persuade people. In this method, the Wizard has to reply to most of the user's inputs at the beginning, but the burden gradually falls because the agent learns how to reply as the conversation model grows.

  3. Radioiodine: the classic theranostic agent.

    Science.gov (United States)

    Silberstein, Edward B

    2012-05-01

    Radioiodine has the distinction of being the first theranostic agent in our armamentarium. Millennia were required to discover that the agent in orally administered seaweed and its extracts, which had been shown to cure neck swelling due to thyromegaly, was iodine, first demonstrated to be a new element in 1813. Treatment of goiter with iodine began at once, but its prophylactic value to prevent a common form of goiter took another century. After Enrico Fermi produced the first radioiodine, (128)I, in 1934, active experimentation in the United States and France delineated the crucial role of iodine in thyroid metabolism and disease. (130)I and (131)I were first employed to treat thyrotoxicosis by 1941, and thyroid cancer in 1943. After World War II, (131)I became widely available at a reasonable price for diagnostic testing and therapy. The rectilinear scanner of Cassen and Curtis (Science 1949;110:94-95), and a dedicated gamma camera invented by Anger (Nature 1952;170:200-201), finally permitted the diagnostic imaging of thyroid disease, with (131)I again the radioisotope of choice, although there were short-lived attempts to employ (125)I and (132)I for this purpose. (123)I was first produced in 1949 but did not become widely available until about 1982, 10 years after a production technique eliminated high-energy (124)I contamination. I continues to be the radioiodine of choice for the diagnosis of benign thyroid disease, whereas (123)I and (131)I are employed in the staging and detection of functioning thyroid cancer. (124)I, a positron emitter, can produce excellent anatomically correlated images employing positron emission tomography/computed tomography equipment and has the potential to enhance heretofore imperfect dosimetric studies in determining the appropriate administered activity to ablate/treat thyroid cancer. Issues of acceptable measuring error in thyroid cancer dosimetry and the role in (131)I therapy of tumor heterogeneity, tumor hypoxia, and

  4. Inaccessibility in Multi-Agent Systems

    Science.gov (United States)

    2004-03-08

    Mař́ık, D. McFarlane, and P. Valckenaers (eds.): Holonic and Multi-Agent Systems for Manufacturing , No. 2744 in LNAI. Springer-Verlag, Heidelberg. 17...in Multi-Agent Systems 5c. PROGRAM ELEMENT NUMBER 5d. PROJECT NUMBER 5d. TASK NUMBER 6. AUTHOR(S) Professor Vladimir Marik 5e. WORK UNIT NUMBER...short term inaccessibility, (3) long term inaccessibility, and (4) testing and validation. 15. SUBJECT TERMS EOARD, Multi Agent Systems , Behavior

  5. Different Views of Software Agent Paradigm

    OpenAIRE

    Anand Kumar Pandey; Rashmi Pandey

    2012-01-01

    Agent modelling in software engineering is a relatively young area, and there are, as yet, no standard methodologies, development tools, or software architectures. Although our work is emphasized on to represent the agent specifications using different views, they are not oriented for software engineering in terms of providing a modeling notation that directly supports software development. There are, however, some software frameworks using different views of software agents, that are beginni...

  6. Running agent-based simulations. Unternehmensmodell / Computersimulation.

    OpenAIRE

    Meyer, David; Karatzoglou, Alexandros; Buchta, Christian; Leisch, Friedrich; Hornik, Kurt

    2001-01-01

    When running agent-based simulations using ready-made components, one usually faces heterogenity problems both for the agents' implementation and for the underlying platform. To circumvent these kind of hindrances, we introduce a wrapper technique for mapping the functionality of agents living in an interpreter-based environment to a standardized CORBA interface, thus facilitating the task for any control mechanism (like a simulation manager) which just will need to handle one set of commands...

  7. Glutamic acid as anticancer agent: An overview

    OpenAIRE

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K.

    2013-01-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. I...

  8. Rule Value Reinforcement Learning for Cognitive Agents

    OpenAIRE

    Child, C. H. T.; Stathis, K.

    2006-01-01

    RVRL (Rule Value Reinforcement Learning) is a new algorithm which extends an existing learning framework that models the environment of a situated agent using a probabilistic rule representation. The algorithm attaches values to learned rules by adapting reinforcement learning. Structure captured by the rules is used to form a policy. The resulting rule values represent the utility of taking an action if the rule`s conditions are present in the agent`s current percept. Advantages of the new f...

  9. Intelligent Agents in E-Commerce

    Directory of Open Access Journals (Sweden)

    Valentin LITOIU

    2006-01-01

    Full Text Available This paper emphasizes the importance of intelligent agents in e-commerce, with a particular focus on the B2C and B2B context. From the consumer buying behaviour perspective, agents can be used to assist the following stages: need identification, product brokering, buyer coalition formation, merchant brokering and negotiation. Related to B2B commerce, intelligent agents are involved in partnership formation, brokering and negotiation.

  10. Conversational Agents in E-Learning

    Science.gov (United States)

    Kerry, Alice; Ellis, Richard; Bull, Susan

    This paper discusses the use of natural language or 'conversational' agents in e-learning environments. We describe and contrast the various applications of conversational agent technology represented in the e-learning literature, including tutors, learning companions, language practice and systems to encourage reflection. We offer two more detailed examples of conversational agents, one which provides learning support, and the other support for self-assessment. Issues and challenges for developers of conversational agent systems for e-learning are identified and discussed.

  11. Multi-agent and complex systems

    CERN Document Server

    Ren, Fenghui; Fujita, Katsuhide; Zhang, Minjie; Ito, Takayuki

    2017-01-01

    This book provides a description of advanced multi-agent and artificial intelligence technologies for the modeling and simulation of complex systems, as well as an overview of the latest scientific efforts in this field. A complex system features a large number of interacting components, whose aggregate activities are nonlinear and self-organized. A multi-agent system is a group or society of agents which interact with others cooperatively and/or competitively in order to reach their individual or common goals. Multi-agent systems are suitable for modeling and simulation of complex systems, which is difficult to accomplish using traditional computational approaches.

  12. Multi-agent systems simulation and applications

    CERN Document Server

    Uhrmacher, Adelinde M

    2009-01-01

    Methodological Guidelines for Modeling and Developing MAS-Based SimulationsThe intersection of agents, modeling, simulation, and application domains has been the subject of active research for over two decades. Although agents and simulation have been used effectively in a variety of application domains, much of the supporting research remains scattered in the literature, too often leaving scientists to develop multi-agent system (MAS) models and simulations from scratch. Multi-Agent Systems: Simulation and Applications provides an overdue review of the wide ranging facets of MAS simulation, i

  13. Agent-Based Negotiation in Uncertain Environments

    Science.gov (United States)

    Debenham, John; Sierra, Carles

    An agent aims to secure his projected needs by attempting to build a set of (business) relationships with other agents. A relationship is built by exchanging private information, and is characterised by its intimacy — degree of closeness — and balance — degree of fairness. Each argumentative interaction between two agents then has two goals: to satisfy some immediate need, and to do so in a way that develops the relationship in a desired direction. An agent's desire to develop each relationship in a particular way then places constraints on the argumentative utterances. The form of negotiation described is argumentative interaction constrained by a desire to develop such relationships.

  14. Toddlers Selectively Help Fair Agents

    Directory of Open Access Journals (Sweden)

    Luca Surian

    2017-06-01

    Full Text Available Previous research showed that infants and toddlers are inclined to help prosocial agents and assign a positive valence to fair distributions. Also, they expect that positive and negative actions directed toward distributors will conform to reciprocity principles. This study investigates whether toddlers are selective in helping others, as a function of others’ previous distributive actions. Toddlers were presented with real-life events in which two actresses distributed resources either equally or unequally between two puppets. Then, they played together with a ball that accidentally fell to the ground and asked participants to help them to retrieve it. Participants preferred to help the actress who performed equal distributions. This finding suggests that by the second year children’s prosocial actions are modulated by their emerging sense of fairness.HighlightsToddlers (mean age = 25 months are selective in helping distributors.Toddlers prefer helping a fair rather than an unfair distributor.Toddlers’ selective helping provides evidence for an early sense of fairness.

  15. Viruses: agents of coral disease?

    Science.gov (United States)

    Davy, S K; Burchett, S G; Dale, A L; Davies, P; Davy, J E; Muncke, C; Hoegh-Guldberg, O; Wilson, W H

    2006-03-23

    The potential role of viruses in coral disease has only recently begun to receive attention. Here we describe our attempts to determine whether viruses are present in thermally stressed corals Pavona danai, Acropora formosa and Stylophora pistillata and zoanthids Zoanthus sp., and their zooxanthellae. Heat-shocked P. danai, A. formosa and Zoanthus sp. all produced numerous virus-like particles (VLPs) that were evident in the animal tissue, zooxanthellae and the surrounding seawater; VLPs were also seen around heat-shocked freshly isolated zooxanthellae (FIZ) from P. danai and S. pistillata. The most commonly seen VLPs were tail-less, hexagonal and about 40 to 50 nm in diameter, though a diverse range of other VLP morphotypes (e.g. rounded, rod-shaped, droplet-shaped, filamentous) were also present around corals. When VLPs around heat-shocked FIZ from S. pistillata were added to non-stressed FIZ from this coral, they resulted in cell lysis, suggesting that an infectious agent was present; however, analysis with transmission electron microscopy provided no clear evidence of viral infection. The release of diverse VLPs was again apparent when flow cytometry was used to enumerate release by heat-stressed A. formosa nubbins. Our data support the infection of reef corals by viruses, though we cannot yet determine the precise origin (i.e. coral, zooxanthellae and/or surface microbes) of the VLPs seen. Furthermore, genome sequence data are required to establish the presence of viruses unequivocally.

  16. Novel Methylselenoesters as Antiproliferative Agents.

    Science.gov (United States)

    Díaz-Argelich, Nuria; Encío, Ignacio; Plano, Daniel; Fernandes, Aristi P; Palop, Juan Antonio; Sanmartín, Carmen

    2017-08-02

    Selenium (Se) compounds are potential therapeutic agents in cancer. Importantly, the biological effects of Se compounds are exerted by their metabolites, with methylselenol (CH₃SeH) being one of the key executors. In this study, we developed a new series of methylselenoesters with different scaffolds aiming to modulate the release of CH₃SeH. The fifteen compounds follow Lipinski's Rule of Five and with exception of compounds 1 and 14 , present better drug-likeness values than the positive control methylseleninic acid. The compounds were evaluated to determine their radical scavenging activity. Compound 11 reduced both DPPH and ABTS radicals. The cytotoxicity of the compounds was evaluated in a panel of five cancer cell lines (prostate, colon and lung carcinoma, mammary adenocarcinoma and chronic myelogenous leukemia) and two non-malignant (lung and mammary epithelial) cell lines. Ten compounds had GI 50 values below 10 μM at 72 h in four cancer cell lines. Compounds 5 and 15 were chosen for further characterization of their mechanism of action in the mammary adenocarcinoma cell line due to their similarity with methylseleninic acid. Both compounds induced G₂/M arrest whereas cell death was partially executed by caspases. The reduction and metabolism were also investigated, and both compounds were shown to be substrates for redox active enzyme thioredoxin reductase.

  17. Novel Methylselenoesters as Antiproliferative Agents

    Directory of Open Access Journals (Sweden)

    Nuria Díaz-Argelich

    2017-08-01

    Full Text Available Selenium (Se compounds are potential therapeutic agents in cancer. Importantly, the biological effects of Se compounds are exerted by their metabolites, with methylselenol (CH3SeH being one of the key executors. In this study, we developed a new series of methylselenoesters with different scaffolds aiming to modulate the release of CH3SeH. The fifteen compounds follow Lipinski’s Rule of Five and with exception of compounds 1 and 14, present better drug-likeness values than the positive control methylseleninic acid. The compounds were evaluated to determine their radical scavenging activity. Compound 11 reduced both DPPH and ABTS radicals. The cytotoxicity of the compounds was evaluated in a panel of five cancer cell lines (prostate, colon and lung carcinoma, mammary adenocarcinoma and chronic myelogenous leukemia and two non-malignant (lung and mammary epithelial cell lines. Ten compounds had GI50 values below 10 μM at 72 h in four cancer cell lines. Compounds 5 and 15 were chosen for further characterization of their mechanism of action in the mammary adenocarcinoma cell line due to their similarity with methylseleninic acid. Both compounds induced G2/M arrest whereas cell death was partially executed by caspases. The reduction and metabolism were also investigated, and both compounds were shown to be substrates for redox active enzyme thioredoxin reductase.

  18. Direct anti-HCV agents

    Directory of Open Access Journals (Sweden)

    Xingquan Zhang

    2016-01-01

    Full Text Available Unlike human immunodeficiency virus (HIV and hepatitis B virus (HBV, hepatitis C virus (HCV infection is a curable disease. Current direct antiviral agent (DAA targets are focused on HCV NS3/4A protein (protease, NS5B protein (polymerase and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi, simeprevir (Olysio, and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the “cure HCV” goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others.

  19. Departments as Agents of Change

    Science.gov (United States)

    Lagowski, J. J.

    1996-07-01

    Higher education is changing because it has no choice. And, for the most part, outside influences are dictating the processes of change. The more fortunate institutions have had a flat budget during this period, but most have been forced to deal with a declining revenue stream as well. Legislators seem bent on micromanaging state-supported institutions, even as they cut their support. Regulators demand greater institutional accountability. Students and their parents expect more service at lower prices and increased flexibility. Technological advances have dramatically affected the availability and accessibility of extant knowledge. It is no longer a question of whether institutions will change, but rather, who will control the change. Most institutions possess long-standing academic traditions, but these are placed at risk in an increasingly competitive market that holds little sympathy for such traditions and may even see them as obstacles or barriers. As a result, the change agents will undoubtedly have a profound effect on the very nature of academic institutions. From the academic point of view, it would seem prudent to attempt to manage the changes that will inevitably occur. A number of concerned observers, notably the Pew Higher Education Roundtable and the American Association for Higher Education, argue persuasively that the academic department is the logical focus for responding to the current winds of change. Using a marketing metaphor, the academic department has been likened to a "producers' cooperative" of services that consumers seek. Thus, the department should be held accountable for the quality of teaching delivered by its members, for the coherence of its major, for its contributions to the general education curriculum, and for supervising and rewarding its individual faculty members. If departments are to be held accountable, it is surely in their best interest to act in such a way that they are accountable. Expecting academic departments to be

  20. Novel infectious agents causing uveitis.

    Science.gov (United States)

    Khairallah, Moncef; Chee, Soon Phaik; Rathinam, Sivakumar R; Attia, Sonia; Nadella, Venu

    2010-10-01

    In any patient with uveitis, an infectious cause should be ruled out first. The differential diagnosis includes multiple well-known diseases including herpes, syphilis, toxoplasmosis, tuberculosis, bartonellosis, Lyme disease, and others. However, clinician should be aware of emerging infectious agents as potential causes of systemic illness and also intraocular inflammation. Air travel, immigration, and globalization of business have overturned traditional pattern of geographic distribution of infectious diseases, and therefore one should work locally but think globally. This review recapitulates the systemic and ocular manifestations of several emergent infectious diseases relevant to the ophthalmologist including Rickettsioses, West Nile virus infection, Rift valley fever, Dengue fever, and Chikungunya. Retinitis, chorioretinitis, retinal vasculitis, and optic nerve involvement have been associated with these emergent infectious diseases. The diagnosis of any of these infections is usually based on pattern of uveitis, systemic symptoms and signs, and specific epidemiological data and confirmed by detection of specific antibody in serum. A systematic ocular examination, showing fairly typical fundus findings, may help establish an early clinical diagnosis, which allows prompt, appropriate management.

  1. Application Framework with Abstractions for Protocol and Agent Role

    DEFF Research Database (Denmark)

    Kristensen, Bent Bruun

    2016-01-01

    In multi-agent systems, agents interact by sending and receiving messages and the actual sequences of message form interaction structures between agents. Protocols and agents organized internally by agent roles support these interaction structures. Description and use of protocols based on agent ...... roles are supported by a simple and expressive application framework....

  2. Ultrasound contrast agents: An overview

    International Nuclear Information System (INIS)

    Cosgrove, David

    2006-01-01

    With the introduction of microbubble contrast agents, diagnostic ultrasound has entered a new era that allows the dynamic detection of tissue flow of both the macro and microvasculature. Underpinning this development is the fact that gases are compressible, and thus the microbubbles expand and contract in the alternating pressure waves of the ultrasound beam, while tissue is almost incompressible. Special software using multiple pulse sequences separates these signals from those of tissue and displays them as an overlay or on a split screen. This can be done at low acoustic pressures (MI < 0.3) so that the microbubbles are not destroyed and scanning can continue in real time. The clinical roles of contrast enhanced ultrasound scanning are expanding rapidly. They are established in echocardiography to improve endocardial border detection and are being developed for myocardial perfusion. In radiology, the most important application is the liver, especially for focal disease. The approach parallels that of dynamic CT or MRI but ultrasound has the advantages of high spatial and temporal resolution. Thus, small lesions that can be indeterminate on CT can often be studied with ultrasound, and situations where the flow is very rapid (e.g., focal nodular hyperplasia where the first few seconds of arterial perfusion may be critical to making the diagnosis) are readily studied. Microbubbles linger in the extensive sinusoidal space of normal liver for several minutes whereas they wash out rapidly from metastases, which have a low vascular volume and thus appear as filling defects. The method has been shown to be as sensitive as three-phase CT. Microbubbles have clinical uses in many other applications where knowledge of the microcirculation is important (the macrocirculation can usually be assessed adequately using conventional Doppler though there are a few important situations where the signal boost given by microbubbles is useful, e.g., transcranial Doppler for evaluating

  3. Ultrasound contrast agents: an overview.

    Science.gov (United States)

    Cosgrove, David

    2006-12-01

    With the introduction of microbubble contrast agents, diagnostic ultrasound has entered a new era that allows the dynamic detection of tissue flow of both the macro and microvasculature. Underpinning this development is the fact that gases are compressible, and thus the microbubbles expand and contract in the alternating pressure waves of the ultrasound beam, while tissue is almost incompressible. Special software using multiple pulse sequences separates these signals from those of tissue and displays them as an overlay or on a split screen. This can be done at low acoustic pressures (MI<0.3) so that the microbubbles are not destroyed and scanning can continue in real time. The clinical roles of contrast enhanced ultrasound scanning are expanding rapidly. They are established in echocardiography to improve endocardial border detection and are being developed for myocardial perfusion. In radiology, the most important application is the liver, especially for focal disease. The approach parallels that of dynamic CT or MRI but ultrasound has the advantages of high spatial and temporal resolution. Thus, small lesions that can be indeterminate on CT can often be studied with ultrasound, and situations where the flow is very rapid (e.g., focal nodular hyperplasia where the first few seconds of arterial perfusion may be critical to making the diagnosis) are readily studied. Microbubbles linger in the extensive sinusoidal space of normal liver for several minutes whereas they wash out rapidly from metastases, which have a low vascular volume and thus appear as filling defects. The method has been shown to be as sensitive as three-phase CT. Microbubbles have clinical uses in many other applications where knowledge of the microcirculation is important (the macrocirculation can usually be assessed adequately using conventional Doppler though there are a few important situations where the signal boost given by microbubbles is useful, e.g., transcranial Doppler for evaluating

  4. Evolution of hemostatic agents in surgical practice

    Directory of Open Access Journals (Sweden)

    Chandru P Sundaram

    2010-01-01

    Conclusions : A review of the evolution of topical hemostatic agents highlights opportunities for potential novel research. Fibrin sealants may have the most opportunity for advancement, and understanding the history of these products is useful. With the drive in urology for minimally invasive surgical techniques, adaptation of topical hemostatic agents to this surgical approach would be valuable and offers an opportunity for novel contributions.

  5. Computational Intelligence Agent-Oriented Modelling

    Czech Academy of Sciences Publication Activity Database

    Neruda, Roman

    2006-01-01

    Roč. 5, č. 2 (2006), s. 430-433 ISSN 1109-2777 R&D Projects: GA MŠk 1M0567 Institutional research plan: CEZ:AV0Z10300504 Keywords : multi-agent systems * adaptive agents * computational intelligence Subject RIV: IN - Informatics, Computer Science

  6. Agent Based Reasoning in Multilevel Flow Modeling

    DEFF Research Database (Denmark)

    Lind, Morten; Zhang, Xinxin

    2012-01-01

    to launch the MFM Workbench into an agent based environment, which can complement disadvantages of the original software. The agent-based MFM Workbench is centered on a concept called “Blackboard System” and use an event based mechanism to arrange the reasoning tasks. This design will support the new...

  7. Anonymity and Software Agents: An Interdiscplinary Challenge

    NARCIS (Netherlands)

    Brazier, F.M.; Oskamp, A.; Prins, J.M.; Schellekens, M.H.M.; Wijngaards, N.J.E.

    2004-01-01

    Software agents that play a role in E-commerce and E-government applications involving the Internet often contain information about the identity of their human user such as credit cards and bank accounts. This paper discusses whether this is necessary: whether human users and software agents are

  8. Anonymity and Software Agents: An Interdisciplinary Challenge

    NARCIS (Netherlands)

    Oskamp, A.; Brazier, F.M.; Prins, J.E.J.; Schellekens, M.H.M.; Wijngaards, N.J.E.

    2004-01-01

    Software agents that play a role in E-commerce and E-government applications involving the Internet often contain information about the identity of their human user such as credit cards and bank accounts. This paper discusses whether this is necessary: whether human users and software agents are

  9. Dynamics of three-agent games

    International Nuclear Information System (INIS)

    Mungan, Muhittin; Rador, Tonguc

    2008-01-01

    We study the dynamics and resulting score distribution of three-agent games where after each competition a single agent wins and scores a point. A single competition is described by a triplet of numbers p, t and q denoting the probabilities that the team with the highest, middle or lowest accumulated score wins. The three-agent game can be regarded as a social model where a player can be favored or disfavored for advancement, based on his/her accumulated score. We study the full family of solutions in the regime, where the number of agents and competitions is large, which can be regarded as a hydrodynamic limit. Depending on the parameter values (p, q, t), we find six qualitatively different asymptotic score distributions and we provide a qualitative explanation of these results. We also compare our analytical results against numerical simulations of the microscopic model and find these to be in excellent agreement. It is possible to decide the outcome of a three-agent game through a mini-tournament of two-agent competitions among the participating players and it turns out that the resulting possible score distributions are a subset of those obtained for the general three-agent games. We discuss how one can add a steady and democratic decline rate to the model and present a simple geometric construction that allows one to obtain the score evolution equations for n-agent games

  10. On conversational agents with mental states

    NARCIS (Netherlands)

    Bosse, T.; Provoost, S.

    2015-01-01

    Embodied conversational agents (ECAs) have been put forward as a promising means for the training of social skills. The traditional approach to drive the behaviour of ECAs during human-agent dialogues is to use conversation trees. Although this approach is easy to use and very transparent, an

  11. Explanation in human-agent teamwork

    NARCIS (Netherlands)

    Harbers, M.; Bradshaw, J.M.; Johnson, M.; Feltovich, P.; Bosch, K. van den; Meyer, J.J.C.

    2012-01-01

    There are several applications in which humans and agents jointly perform a task. If the task involves interdependence among the team members, coordination is required to achieve good team performance. This paper discusses the role of explanation in coordination in human-agent teams. Explanations

  12. assessment of extension agents' communication methods

    African Journals Online (AJOL)

    USER

    ABSTRACT. The need to improve aquaculture production through enhanced technology transfer necessitated this study to assess extension agents' use of communication methods and its impact on linkage. A structured questionnaire was administered to 44 extension agents who were randomly selected from Lagos State ...

  13. Mansion, A Distributed Multi-Agent System

    NARCIS (Netherlands)

    van t Noordende, G.; Brazier, F.M.; Tanenbaum, A.S.

    2001-01-01

    In this position summary we present work in progress on a worldwide, scalable multi-agent system, based on a paradigm of hyperlinked rooms. The framework offers facilities for managing distribution, security and mobility aspects for both active elements (agents) and passive elements (objects) in the

  14. Some Pitfalls for Developing Enculturated Conversational Agents

    DEFF Research Database (Denmark)

    Rehm, Matthias; André, Elisabeth; Nakano, Yukiko

    2009-01-01

    A review of current agent-based systems exemplifies that a Western perspective is predominant in the field. But as conversational agents focus on rich multimodal interactive behaviors that underlie face-to-face encounters, it is indispensable to incorporate cultural heuristics of such behaviors...

  15. Security of Mobile Agents on the Internet.

    Science.gov (United States)

    Corradi, Antonio; Montanari, Rebecca; Stefanelli, Cesare

    2001-01-01

    Discussion of the Internet focuses on new programming paradigms based on mobile agents. Considers the security issues associated with mobile agents and proposes a security architecture composed of a wide set of services and components capable of adapting to a variety of applications, particularly electronic commerce. (Author/LRW)

  16. Inhabited interfaces : Attentive conversational agents that help

    NARCIS (Netherlands)

    Nijholt, Antinus; Heylen, Dirk K.J.; Vertegaal, R.P.H.; Sharkey, P.; Cesarani, A.; Pugnetti, L.; Rizzo, A.

    2000-01-01

    We discuss the role of attentive agents in virtual reality interfaces. This discussion is guided by experiences and experiments with a virtual reality environment we designed and implemented. In this environment we have introduced agents, sometimes embodied, with which the users can communicate

  17. Biomonitoring of exposure to chemical warfare agents

    NARCIS (Netherlands)

    Noort, D.; Schans, M.J. van der; Benschop, H.P.

    2006-01-01

    An overview is presented of the major methods that are presently available for biomonitoring of exposure to chemical warfare agents, i.e., nerve agents and sulfur mustard. These methods can be applied for a variety of purposes such as diagnosis and dosimetry of exposure of casualties, verification

  18. Deliberate Evolution in Multi-Agent Systems

    NARCIS (Netherlands)

    Brazier, F.M.; Jonker, C.M.; Treur, J.; Wijngaards, N.J.E.; Gabbay, D.

    2001-01-01

    Evolution in societies of agents is a challenging phenomenon, both from a fundamental perspective and from an applied perspective. In the literature often genetic programming approaches are used and relatively simple agents are considered, which have no deliberate influence on the direction of the

  19. AGENT: Awareness Game Environment for Natural Training

    NARCIS (Netherlands)

    Linssen, Johannes Maria; de Groot, Thomas

    We propose AGENT, the Awareness Game Environment for Natural Training, as a virtual environment in which serious games can be enacted. AGENT combines research on interactive storytelling, game design, turn-taking and social signal processing with a multi-modal UI in a modular fashion. Current work

  20. Assurance in Agent-Based Systems

    Energy Technology Data Exchange (ETDEWEB)

    Gilliom, Laura R.; Goldsmith, Steven Y.

    1999-05-10

    Our vision of the future of information systems is one that includes engineered collectives of software agents which are situated in an environment over years and which increasingly improve the performance of the overall system of which they are a part. At a minimum, the movement of agent and multi-agent technology into National Security applications, including their use in information assurance, is apparent today. The use of deliberative, autonomous agents in high-consequence/high-security applications will require a commensurate level of protection and confidence in the predictability of system-level behavior. At Sandia National Laboratories, we have defined and are addressing a research agenda that integrates the surety (safety, security, and reliability) into agent-based systems at a deep level. Surety is addressed at multiple levels: The integrity of individual agents must be protected by addressing potential failure modes and vulnerabilities to malevolent threats. Providing for the surety of the collective requires attention to communications surety issues and mechanisms for identifying and working with trusted collaborators. At the highest level, using agent-based collectives within a large-scale distributed system requires the development of principled design methods to deliver the desired emergent performance or surety characteristics. This position paper will outline the research directions underway at Sandia, will discuss relevant work being performed elsewhere, and will report progress to date toward assurance in agent-based systems.

  1. Assurance in Agent-Based Systems

    International Nuclear Information System (INIS)

    Gilliom, Laura R.; Goldsmith, Steven Y.

    1999-01-01

    Our vision of the future of information systems is one that includes engineered collectives of software agents which are situated in an environment over years and which increasingly improve the performance of the overall system of which they are a part. At a minimum, the movement of agent and multi-agent technology into National Security applications, including their use in information assurance, is apparent today. The use of deliberative, autonomous agents in high-consequence/high-security applications will require a commensurate level of protection and confidence in the predictability of system-level behavior. At Sandia National Laboratories, we have defined and are addressing a research agenda that integrates the surety (safety, security, and reliability) into agent-based systems at a deep level. Surety is addressed at multiple levels: The integrity of individual agents must be protected by addressing potential failure modes and vulnerabilities to malevolent threats. Providing for the surety of the collective requires attention to communications surety issues and mechanisms for identifying and working with trusted collaborators. At the highest level, using agent-based collectives within a large-scale distributed system requires the development of principled design methods to deliver the desired emergent performance or surety characteristics. This position paper will outline the research directions underway at Sandia, will discuss relevant work being performed elsewhere, and will report progress to date toward assurance in agent-based systems

  2. Giving advice to agents with hidden goals

    CSIR Research Space (South Africa)

    Rosman, Benjamin S

    2014-05-01

    Full Text Available on an approximation of the trade-off in utility between potential benefits to the exploring agent and the costs incurred in giving this advice. This model is evaluated on a maze world domain by providing advice to different types of agents, and we show that this leads...

  3. Sanguinarine: A Novel Agent Against Prostate Cancer

    National Research Council Canada - National Science Library

    Ahmad, Nihal

    2005-01-01

    .... Therefore, the search for novel agents and approaches for the treatment of CaP continues. Natural plant-based products have shown promise as anticancer agents. Sanguinarine (13-methyl[ 1,3]benzodioxolo[5,6-c]- 1,3-dioxolo[4,5-i]phenanthridinium...

  4. Marine Natural Products as Prototype Agrochemical Agents

    Science.gov (United States)

    Peng, Jiangnan; Shen, Xiaoyu; El Sayed, Khalid A.; Dunbar, D. C Harles; Perry, Tony L.; Wilkins, Scott P.; Hamann, Mark T.; Bobzin, Steve; Huesing, Joseph; Camp, Robin; Prinsen, Mike; Krupa, Dan; Wideman, Margaret A.

    2016-01-01

    In the interest of identifying new leads that could serve as prototype agrochemical agents, 18 structurally diverse marine-derived compounds were examined for insecticidal, herbicidal, and fungicidal activities. Several new classes of compounds have been shown to be insecticidal, herbicidal, and fungicidal, which suggests that marine natural products represent an intriguing source for the discovery of new agrochemical agents. PMID:12670165

  5. 21 CFR 181.28 - Release agents.

    Science.gov (United States)

    2010-04-01

    ... Release agents. Substances classified as release agents, when migrating from food-packaging material shall...). Linoleamide (linoleic acid amide). Oleamide (oleic acid amide). Palmitamide (palmitic acid amide). Stearamide (stearic acid amide). [42 FR 14638, Mar. 15, 1977; 42 FR 56728, Oct. 28, 1977] ...

  6. BOA: A cognitive tactical picture compilation agent

    NARCIS (Netherlands)

    Heuvelink, A.; Both, F.

    2007-01-01

    Simulation-based training in complex decision-making can be made more effective by using intelligent software agents to play key roles, such as teammates, opponents and instructors. This paper presents a cognitive software agent that is capable of compiling a tactical picture in the domain of Naval

  7. Cognitive agent programming : A semantic approach

    NARCIS (Netherlands)

    Riemsdijk, M.B. van

    2006-01-01

    In this thesis we are concerned with the design and investigation of dedicated programming languages for programming agents. We focus in particular on programming languages for rational agents, i.e., flexibly behaving computing entities that are able to make "good" decisions about what to do. An

  8. Mechanisms of bacterial resistance to antimicrobial agents.

    NARCIS (Netherlands)

    van Duijkeren, Engeline; Schink, Anne-Kathrin; Roberts, Marilyn C; Wang, Yang; Schwarz, Stefan

    During the past decades resistance to virtually all antimicrobial agents has been observed in bacteria of animal origin. This chapter describes in detail the mechanisms so far encountered for the various classes of antimicrobial agents. The main mechanisms include enzymatic inactivation by either

  9. Moral conflicts between groups of agents

    NARCIS (Netherlands)

    Kooi, Barteld; Tamminga, A.

    Two groups of agents, G1 and G2, face a *moral conflict* if G1 has a moral obligation and G2 has a moral obligation, such that these obligations cannot both be fulfilled. We study moral conflicts using a multi-agent deontic logic devised to represent reasoning about sentences like 'In the interest

  10. 7 CFR 983.86 - Agents.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Agents. 983.86 Section 983.86 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... NEW MEXICO Miscellaneous Provisions § 983.86 Agents. The Secretary may, by a designation in writing...

  11. Econophysics of agent-based models

    CERN Document Server

    Aoyama, Hideaki; Chakrabarti, Bikas; Chakraborti, Anirban; Ghosh, Asim

    2014-01-01

    The primary goal of this book is to present the research findings and conclusions of physicists, economists, mathematicians and financial engineers working in the field of "Econophysics" who have undertaken agent-based modelling, comparison with empirical studies and related investigations. Most standard economic models assume the existence of the representative agent, who is “perfectly rational” and applies the utility maximization principle when taking action. One reason for this is the desire to keep models mathematically tractable: no tools are available to economists for solving non-linear models of heterogeneous adaptive agents without explicit optimization. In contrast, multi-agent models, which originated from statistical physics considerations, allow us to go beyond the prototype theories of traditional economics involving the representative agent. This book is based on the Econophys-Kolkata VII Workshop, at which many such modelling efforts were presented. In the book, leading researchers in the...

  12. Agent-based models of cellular systems.

    Science.gov (United States)

    Cannata, Nicola; Corradini, Flavio; Merelli, Emanuela; Tesei, Luca

    2013-01-01

    Software agents are particularly suitable for engineering models and simulations of cellular systems. In a very natural and intuitive manner, individual software components are therein delegated to reproduce "in silico" the behavior of individual components of alive systems at a given level of resolution. Individuals' actions and interactions among individuals allow complex collective behavior to emerge. In this chapter we first introduce the readers to software agents and multi-agent systems, reviewing the evolution of agent-based modeling of biomolecular systems in the last decade. We then describe the main tools, platforms, and methodologies available for programming societies of agents, possibly profiting also of toolkits that do not require advanced programming skills.

  13. Fault Reconnaissance Agent for Sensor Networks

    Directory of Open Access Journals (Sweden)

    Elhadi M. Shakshuki

    2010-01-01

    Full Text Available One of the key prerequisite for a scalable, effective and efficient sensor network is the utilization of low-cost, low-overhead and high-resilient fault-inference techniques. To this end, we propose an intelligent agent system with a problem solving capability to address the issue of fault inference in sensor network environments. The intelligent agent system is designed and implemented at base-station side. The core of the agent system – problem solver – implements a fault-detection inference engine which harnesses Expectation Maximization (EM algorithm to estimate fault probabilities of sensor nodes. To validate the correctness and effectiveness of the intelligent agent system, a set of experiments in a wireless sensor testbed are conducted. The experimental results show that our intelligent agent system is able to precisely estimate the fault probability of sensor nodes.

  14. Advances on Practical Applications of Agents and Multi-Agent Systems 10th International Conference on Practical Applications of Agents and Multi-Agent Systems

    CERN Document Server

    Müller, Jörg; Rodríguez, Juan; Pérez, Javier

    2012-01-01

    Research on Agents and Multi-Agent Systems has matured during the last decade and many effective applications of this technology are now deployed. PAAMS provides an international forum to present and discuss the latest scientific developments and their effective applications, to assess the impact of the approach, and to facilitate technology transfer. PAAMS started as a local initiative, but has since grown to become THE international yearly platform 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 and deployment of Agents and Multi-Agent Systems. PAAMS intends to bring together researchers and developers from industry and the academic world to report on the latest scientific and technical advances on the application of multi-agent systems, to discuss and debate the major ...

  15. Highlights on Practical Applications of Agents and Multi-Agent Systems 10th International Conference on Practical Applications of Agents and Multi-Agent Systems

    CERN Document Server

    Sánchez, Miguel; Mathieu, Philippe; Rodríguez, Juan; Adam, Emmanuel; Ortega, Alfonso; Moreno, María; Navarro, Elena; Hirsch, Benjamin; Lopes-Cardoso, Henrique; Julián, Vicente

    2012-01-01

    Research on Agents and Multi-Agent Systems has matured during the last decade and many effective applications of this technology are now deployed. PAAMS provides an international forum to present and discuss the latest scientific developments and their effective applications, to assess the impact of the approach, and to facilitate technology transfer. PAAMS started as a local initiative, but has since grown to become THE international yearly platform 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 and deployment of Agents and Multi-Agent Systems. PAAMS intends to bring together researchers and developers from industry and the academic world to report on the latest scientific and technical advances on the application of multi-agent systems, to discuss and debate the major ...

  16. In vitro testing of plaque control agents.

    Science.gov (United States)

    Coburn, R A

    1979-12-01

    The development of a number of in vitro techniques for the evaluation of antiplaque effects of test agents has followed the characterization and culturing of plaque-forming microorganisms. Studies of the mechanism of action of chlorhexidine and clinical observations have assisted in defining critical aspects of these in vitro techniques. Such assays may play an increasingly important role in screening potential new agents as well as in the optimization of properties by chemical modification of new lead agents. In addition, data generated in the in vitro assay may assist the design of in vivo evaluations of new agents. Proper selection of in vitro techniques for these various functions in the pre-clinical development process may reduce the time and cost involved in the development of new antiplaque agents.

  17. Biological agents in polyarticular juvenile idiopathic arthritis

    DEFF Research Database (Denmark)

    Amarilyo, Gil; Tarp, Simon; Foeldvari, Ivan

    2016-01-01

    (nearly all exceptions were in agreement with the original study data). Serious AEs occurred very infrequently (0-8%) and an analysis was not possible. There were no differences for AEs when compared among biological agents or to placebo. CONCLUSION: There were no statistical differences among biological......BACKGROUND AND OBJECTIVE: Although various biological agents are in use for polyarticular juvenile idiopathic arthritis (pJIA), head-to-head trials comparing the efficacy and safety among them are lacking. We aimed to compare the efficacy and safety of biological agents in pJIA using all currently...... available randomized withdrawal trials (wRCTs). METHODS: A systematic search of MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov was performed. Eligible wRCTs: patients with pJIA where a biological agent was compared with another biological agent or placebo. Efficacy was evaluated using disease flare...

  18. CEST and PARACEST MR contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Hancu, Ileana; Dixon, W. Thomas (GE Global Research Center, Niskayuna, NY (United States)); Woods, Mark; Sherry, A. Dean (Univ. of Texas at Dallas, Dallas, TX (United States)); Vinogradov, Elena; Lenkinski, Robert E. (Beth Israel Deaconess Medical Center, Boston, MA (United States)), e-mail: rlenkins@bidmc.harvard.edu

    2010-10-15

    In this review we describe the status of development for a new class of magnetic resonance (MR) contrast agents, based on chemical exchange saturation transfer (CEST). The mathematics and physics relevant to the description of the CEST effect in MR are presented in an appendix published in the online version only. We discuss the issues arising when translating in vitro results obtained with CEST agents to using these MR agents in in vivo model studies and in humans. Examples are given on how these agents are imaged in vivo. We summarize the status of development of these CEST agents, and speculate about the next steps that may be taken towards the demonstration of CEST MR imaging in clinical applications

  19. The agent-relative/agent-neutral distinction: my two sense(s) | Lerm ...

    African Journals Online (AJOL)

    -relative in the dependence sense but agent-neutral in the homogeneous sense, and – perhaps surprisingly – of Utilitarianism, according to which reasons are agent-neutral in the independence sense but agent-relative in the heterogeneous ...

  20. Human-agent experience sharing : Creating social agents for elderly people with dementia

    NARCIS (Netherlands)

    Peeters, M.M.M.; Neerincx, M.A.

    2016-01-01

    As intelligent technology steadily becomes a part of modern societies, people collaborate with agents more frequently, and so agents need to be socially intelligent, i.e. personalised and context-sensitive. This paper introduces a context-sensitive personalisation framework for social agents that

  1. 9th KES Conference on Agent and Multi-Agent Systems : Technologies and Applications

    CERN Document Server

    Howlett, Robert; Jain, Lakhmi

    2015-01-01

    Agents and multi-agent systems are related to a modern software paradigm which has long been recognized as a promising technology for constructing autonomous, complex and intelligent systems. The topics covered in this volume include agent-oriented software engineering, agent co-operation, co-ordination, negotiation, organization and communication, distributed problem solving, specification of agent communication languages, agent privacy, safety and security, formalization of ontologies and conversational agents. The volume highlights new trends and challenges in agent and multi-agent research and includes 38 papers classified in the following specific topics: learning paradigms, agent-based modeling and simulation, business model innovation and disruptive technologies, anthropic-oriented computing, serious games and business intelligence, design and implementation of intelligent agents and multi-agent systems, digital economy, and advances in networked virtual enterprises. Published p...

  2. For whom will the Bayesian agents vote?

    Science.gov (United States)

    Caticha, Nestor; Cesar, Jonatas; Vicente, Renato

    2015-04-01

    Within an agent-based model where moral classifications are socially learned, we ask if a population of agents behaves in a way that may be compared with conservative or liberal positions in the real political spectrum. We assume that agents first experience a formative period, in which they adjust their learning style acting as supervised Bayesian adaptive learners. The formative phase is followed by a period of social influence by reinforcement learning. By comparing data generated by the agents with data from a sample of 15000 Moral Foundation questionnaires we found the following. 1. The number of information exchanges in the formative phase correlates positively with statistics identifying liberals in the social influence phase. This is consistent with recent evidence that connects the dopamine receptor D4-7R gene, political orientation and early age social clique size. 2. The learning algorithms that result from the formative phase vary in the way they treat novelty and corroborative information with more conservative-like agents treating it more equally than liberal-like agents. This is consistent with the correlation between political affiliation and the Openness personality trait reported in the literature. 3. Under the increase of a model parameter interpreted as an external pressure, the statistics of liberal agents resemble more those of conservative agents, consistent with reports on the consequences of external threats on measures of conservatism. We also show that in the social influence phase liberal-like agents readapt much faster than conservative-like agents when subjected to changes on the relevant set of moral issues. This suggests a verifiable dynamical criterium for attaching liberal or conservative labels to groups.

  3. For whom will the Bayesian agents vote?

    Directory of Open Access Journals (Sweden)

    Nestor eCaticha

    2015-04-01

    Full Text Available Within an agent-based model where moral classifications are socially learned, we ask if a population of agents behaves in a way that may be compared with conservative or liberal positions in the real political spectrum. We assume that agents first experience a formative period, in which they adjust their learning style acting as supervised Bayesian adaptive learners. The formative phase is followed by a period of social influence by reinforcement learning. By comparing data generated by the agents with data from a sample of 15000 Moral Foundation questionnaires we found the following. 1. The number of information exchanges in the formative phase correlates positively with statistics identifying liberals in the social influence phase. This is consistent with recent evidence that connects the dopamine receptor D4-7R gene, political orientation and early age social clique size. 2. The learning algorithms that result from the formative phase vary in the way they treat novelty and corroborative information with more conservative-like agents treating it more equally than liberal-like agents. This is consistent with the correlation between political affiliation and the Openness personality trait reported in the literature. 3. Under the increase of a model parameter interpreted as an external pressure, the statistics of liberal agents resemble more those of conservative agents, consistent with reports on the consequences of external threats on measures of conservatism. We also show that in the social influence phase liberal-like agents readapt much faster than conservative-like agents when subjected to changes on the relevant set of moral issues. This suggests a verifiable dynamical criterium for attaching liberal or conservative labels to groups.

  4. Multi-Agent Systems for E-Commerce

    OpenAIRE

    Solodukha, T. V.; Sosnovskiy, O. A.; Zhelezko, B. A.

    2009-01-01

    The article focuses on multi-agent systems (MAS) and domains that can benefit from multi-agent technology. In the last few years, the agent based modeling (ABM) community has developed several practical agent based modeling toolkits that enable individuals to develop agent-based applications. The comparison of agent-based modeling toolkits is given. Multi-agent systems are designed to handle changing and dynamic business processes. Any organization with complex and distributed busine...

  5. Chemical Warfare Agent Decontaminant Solution Using Quaternary Ammonium Complexes

    Science.gov (United States)

    1997-12-11

    warfare agents, which include a variety of organophosphorus and organosulfur compounds, are known in the art. 15 However, these known methods use...chemical warfare agents, and works particularly well for neutralization of organosulfur agents such as mustard gas (HD), and organophosphorus agents such...detoxifying/neutralizing a variety of chemical warfare agents, including organosulfur agents such as mustard gas (HD), and organophosphorus agents such as

  6. Traitement de l'hétérogénéité sémantique dans les interactions humain-agent et agent-agent

    OpenAIRE

    Mazuel , Laurent

    2008-01-01

    The main purpose of this thesis is the management of semantic heterogeneity in human-agent and agent-agent interaction. We especially focus on the situation where a software agent, supplied with a knowledge representation model, has to understand requests coming from different interlocutors; either it is a human user or another software agent.Most work in this domain either focus on human-agent interaction or agent-agent interaction. On the contrary, we suggest that it is possible to use a co...

  7. Human butyrylcholinesterase efficacy against nerve agent exposure.

    Science.gov (United States)

    Reed, Beth A; Sabourin, Carol L; Lenz, David E

    2017-05-01

    Acetylcholinesterase is vital for normal operation of many processes in the body. Following exposure to organophosphorus (OP) nerve agents, death can ensue without immediate medical intervention. Current therapies mitigate the cholinergic crisis caused by nerve agents but do not fully prevent long-term health concerns, for example, brain damage following seizures. Human butyrylcholinesterase (HuBChE) is a stoichiometric bioscavenger being investigated as an antidote for OP nerve agent poisoning. HuBChE sequesters OP nerve agent in the bloodstream preventing the nerve agent from reaching critical target organ systems. HuBChE was effective when used as both a pre-treatment and as a post-exposure therapy. HuBChE has potential for use in both military settings and to protect civilian first responders in situations where nerve agent usage is suspected. We reviewed various animal models studies evaluating the efficacy of HuBChE against nerve agent exposure, pursuant to its submission for approval under the FDA Animal Rule. © 2017 Wiley Periodicals, Inc.

  8. Persistent agents in Axelrod's social dynamics model

    Science.gov (United States)

    Reia, Sandro M.; Neves, Ubiraci P. C.

    2016-01-01

    Axelrod's model of social dynamics has been studied under the effect of external media. Here we study the formation of cultural domains in the model by introducing persistent agents. These are agents whose cultural traits are not allowed to change but may be spread through local neighborhood. In the absence of persistent agents, the system is known to present a transition from a monocultural to a multicultural regime at some critical Q (number of traits). Our results reveal a dependence of critical Q on the occupation probability p of persistent agents and we obtain the phase diagram of the model in the (p,Q) -plane. The critical locus is explained by the competition of two opposite forces named here barrier and bonding effects. Such forces are verified to be caused by non-persistent agents which adhere (adherent agents) to the set of traits of persistent ones. The adherence (concentration of adherent agents) as a function of p is found to decay for constant Q. Furthermore, adherence as a function of Q is found to decay as a power law with constant p.

  9. Agent-Supported Mission Operations Teamwork

    Science.gov (United States)

    Malin, Jane T.

    2003-01-01

    This slide presentation reviews the development of software agents to support of mission operations teamwork. The goals of the work was to make automation by agents easy to use, supervise and direct, manage information and communication to decrease distraction, interruptions, workload and errors, reduce mission impact of off-nominal situations and increase morale and decrease turnover. The accomplishments or the project are: 1. Collaborative agents - mixed initiative and creation of instructions for mediating agent 2. Methods for prototyping, evaluating and evolving socio-technical systems 3. Technology infusion: teamwork tools in mISSIons 4. Demonstrations in simulation testbed An example of the use of agent is given, the use of an agent to monitor a N2 tank leak. An incomplete instruction to the agent is handled with mediating assistants, or Intelligent Briefing and Response Assistant (IBRA). The IBRA Engine also watches data stream for triggers and executes Act-Whenever actions. There is also a Briefing and Response Instruction (BRI) which is easy for a discipline specialist to create through a BRI editor.

  10. Continuum deformation of multi-agent systems

    CERN Document Server

    Rastgoftar, Hossein

    2016-01-01

    This monograph presents new algorithms for formation control of multi-agent systems (MAS) based on principles of continuum mechanics. Beginning with an overview of traditional methods, the author then introduces an innovative new approach whereby agents of an MAS are considered as particles in a continuum evolving in ℝn whose desired configuration is required to satisfy an admissible deformation function. The necessary theory and its validation on a mobile-agent-based swarm test bed are considered for two primary tasks: homogeneous transformation of the MAS and deployment of a random distribution of agents on a desired configuration. The framework for this model is based on homogeneous transformations for the evolution of an MAS under no inter-agent communication, local inter-agent communication, and intelligent perception by agents. Different communication protocols for MAS evolution, the robustness of tracking of a desired motion by an MAS evolving in ℝn, and the effect of communication delays in an MAS...

  11. Relay tracking control for second-order multi-agent systems with damaged agents.

    Science.gov (United States)

    Dong, Lijing; Li, Jing; Liu, Qin

    2017-11-01

    This paper investigates a situation where smart agents capable of sensory and mobility are deployed to monitor a designated area. A preset number of agents start tracking when a target intrudes this area. Some of the tracking agents are possible to be out of order over the tracking course. Thus, we propose a cooperative relay tracking strategy to ensure the successful tracking with existence of damaged agents. Relay means that, when a tracking agent quits tracking due to malfunction, one of the near deployed agents replaces it to continue the tracking task. This results in jump of tracking errors and dynamic switching of topology of the multi-agent system. Switched system technique is employed to solve this specific problem. Finally, the effectiveness of proposed tracking strategy and validity of the theoretical results are verified by conducting a numerical simulation. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  12. Agent and multi-Agent systems in distributed systems digital economy and e-commerce

    CERN Document Server

    Hartung, Ronald

    2013-01-01

    Information and communication technology, in particular artificial intelligence, can be used to support economy and commerce using digital means. This book is about agents and multi-agent distributed systems applied to digital economy and e-commerce to meet, improve, and overcome challenges in the digital economy and e-commerce sphere. Agent and multi-agent solutions are applied in implementing real-life, exciting developments associated with the need to eliminate problems of distributed systems.   The book presents solutions for both technology and applications, illustrating the possible uses of agents in the enterprise domain, covering design and analytic methods, needed to provide a solid foundation required for practical systems. More specifically, the book provides solutions for the digital economy, e-sourcing clusters in network economy, and knowledge exchange between agents applicable to online trading agents, and security solutions to both digital economy and e-commerce. Furthermore, it offers soluti...

  13. Multi-Agent Pathfinding with n Agents on Graphs with n Vertices

    DEFF Research Database (Denmark)

    Förster, Klaus-Tycho; Groner, Linus; Hoefler, Torsten

    2017-01-01

    We investigate the multi-agent pathfinding (MAPF) problem with $n$ agents on graphs with $n$ vertices: Each agent has a unique start and goal vertex, with the objective of moving all agents in parallel movements to their goal s.t.~each vertex and each edge may only be used by one agent at a time....... We give a combinatorial classification of all graphs where this problem is solvable in general, including cases where the solvability depends on the initial agent placement. Furthermore, we present an algorithm solving the MAPF problem in our setting, requiring O(n²) rounds, or O(n³) moves...... of individual agents. Complementing these results, we show that there are graphs where Omega(n²) rounds and Omega(n³) moves are required for any algorithm....

  14. Topical antimicrobial agents in ophthalmology. A review

    Directory of Open Access Journals (Sweden)

    E. V. Dovgan’

    2014-01-01

    Full Text Available The data on different antimicrobial agents (fluoroquinolones, minoglycosides, macrolides, fusidic acid, chloramphenicol and their activity against various microorganisms are reviewed. The findings from different researchers are analyzed. Considerable attention is devoted to the problem of antimicrobial resistance in ophthalmology. Pharmacokinetics of topical antimicrobial agents applied in ophthalmology, their safety and tolerability are described. The indications for topical antimicrobial agents use in ophthalmology approved in Russian Federation are presented. With regard for pharmacokinetics and pharmacodynamics, safety profile and good tolerability, it is concluded that fluoroquinolones are medication of choice for empirical antimicrobial treatment in ophthalmology.

  15. Process for preparation of MR contrast agents

    DEFF Research Database (Denmark)

    2002-01-01

    The present invention provides a process for the preparation of an MR contrast agent, said process comprising: i) obtaining a solution in a solvent of a hydrogenatable, unsaturated substrate compound and a catalyst for the hydrogenation of said substrate compound; ii) introducing said solution...... in droplet form into a chamber containing hydrogen gas (H2) enriched in para-hydrogen (p-1H2) and/or ortho-deuterium (o-2H2) whereby to hydrogenate said substrate to form a hydrogenated imaging agent; iii) optionally subjecting said hydrogenated imaging agent to a magnetic field having a field strength below...

  16. Mechanisms of resistance to alkylating agents

    OpenAIRE

    Damia, G.; D‘Incalci, M.

    1998-01-01

    Alkylating agents are the most widely used anticancer drugs whose main target is the DNA, although how exactly the DNA lesions cause cell death is still not clear. The emergence of resistance to this class of drugs as well as to other antitumor agents is one of the major causes of failure of cancer treatment. This paper reviews some of the best characterized mechanisms of resistance to alkylating agents. Pre- and post-target mechanisms are recognized, the former able to limit the formation of...

  17. AORTA: Adding Organizational Reasoning to Agents

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt; Dignum, Virginia

    2014-01-01

    the expected behavior of the agents. Agents need to be able to reason about the regulations, so that they can act within the expected boundaries and work towards the objectives of the organization. This extended abstract introduces AORTA, a component that can be integrated into agents’ reasoning mechanism......, allowing them to reason about (and act upon) regulations specified by an organizational model using simple reasoning rules. The added value is that the organizational model is independent of that of the agents, and that the approach is not tied to a specific organizational model....

  18. Francisella tularensis - potential biological agent

    International Nuclear Information System (INIS)

    Taleski, V.

    2009-01-01

    Francisella tularensis is a small, nonmotile, aerobic, gram-negative coccobacillus capable of surviving for weeks at low temperatures in water, moist soil, hay, straw, or decaying animal carcasses. F. tularensis is the causative of the zoonotic disease tularemia. This bacterium was first identified in ground squirrels in Tulare County, California (1912). The human disease was recognized and described by Edward Francis (1922) as tularemia, and the agent was renamed Francisella tularensis in his honor. F. tularensis is one of the most infectious bacterial pathogens known, as few as 10-50 organisms can cause disease. Humans can become incidentally infected through diverse environmental exposures: bites by infected arthropods; handling infectious animal tissues or fluids; direct contact with or ingestion of contaminated food, water, or soil and inhalation of infective aerosols. Humans can develop severe and sometimes fatal illness, but do not transmit the disease to others. F. tularensis have few subspecies: 1) F. tularensis subsp. tularensis (type A), highly virulent, found only in North America. The bacterium is transmitted among animals and from animals to humans by ticks, occasionally deerfly, or by aerosols; 2) F. tularensis subsp. holarctica (type B), moderately virulent, occurs in Euroasia and North America, mainly associated with streams, lakes, ponds, rivers and semi-aquatic animals such as muskrats and beavers (water-borne disease). Type B tularemia has been observed during war times (during Second World War 100 000 cases occurred each year, in Kosovo in 2000 and 2003 over 300 cases each year); 3) F. tularensis subsp. mediasiatica, rarely reported, isolated only in Kazahstan and Turkmenistan; 4) F. tularensis subsp. novicida is of low virulence, isolated in USA, Canada, Spain and Australia; 5) F. tularensis subsp. philomiragia, is of low virulence, associated with salt water (Atlantic, Mediterranean). Tularemia is very rear in Macedonia, but in 1996 an

  19. Panel: Methodologies for multi-agent systems

    NARCIS (Netherlands)

    Kinny, David; Treur, Jan; Gasser, Les; Clark, Steve; Müller, Jörg

    1998-01-01

    Multi-Agent Systems technologies are migrating from research labs to software engineering centres. If these technologies are to realize their potential, it will become increasingly important to develop and employ methodologies, accessible to software engineers, for specifying, analysing, designing,

  20. A Highly Secure Mobile Agent System Architecture

    Science.gov (United States)

    Okataku, Yasukuni; Okutomi, Hidetoshi; Yoshioka, Nobukazu; Ohgishi, Nobuyuki; Honiden, Shinichi

    We propose a system architecture for mobile agents to improve their security in the environments of insecure networks and non-sophisticated terminals such as PDAs. As mobile agents freely migrate onto their favorite terminals through insecure networks or terminals, it is not appropriate for them to store some secret information for authentication and encryption/decryption. We introduce one and more secure nodes(OASIS NODE) for securely generating and verifying authentication codes. The each agent’s data are encrypted by a pseudo-chaos cipher mechanism which doesn’t need any floating processing co-processor. We’ve constructed a prototype system on a Java mobile agent framework, “Bee-gent" which implements the proposed authentication and cipher mechanisms, and evaluated their performances and their applicability to business fields such as an auction system by mobile agents.

  1. Agent-based modeling of sustainable behaviors

    CERN Document Server

    Sánchez-Maroño, Noelia; Fontenla-Romero, Oscar; Polhill, J; Craig, Tony; Bajo, Javier; Corchado, Juan

    2017-01-01

    Using the O.D.D. (Overview, Design concepts, Detail) protocol, this title explores the role of agent-based modeling in predicting the feasibility of various approaches to sustainability. The chapters incorporated in this volume consist of real case studies to illustrate the utility of agent-based modeling and complexity theory in discovering a path to more efficient and sustainable lifestyles. The topics covered within include: households' attitudes toward recycling, designing decision trees for representing sustainable behaviors, negotiation-based parking allocation, auction-based traffic signal control, and others. This selection of papers will be of interest to social scientists who wish to learn more about agent-based modeling as well as experts in the field of agent-based modeling.

  2. Trial of a New Antirheumatic Agent

    African Journals Online (AJOL)

    1974-05-04

    aspirin) and placebo in 10 outpatients with active rheumatoid arthritis, is reported. Both fenoprofen and aspirin were found to be similarly effective agents in rheumatoid arthritis with an average daily dose of 2,1 g fenoprofen ...

  3. Intelligent agents in data-intensive computing

    CERN Document Server

    Correia, Luís; Molina, José

    2016-01-01

    This book presents new approaches that advance research in all aspects of agent-based models, technologies, simulations and implementations for data intensive applications. The nine chapters contain a review of recent cross-disciplinary approaches in cloud environments and multi-agent systems, and important formulations of data intensive problems in distributed computational environments together with the presentation of new agent-based tools to handle those problems and Big Data in general. This volume can serve as a reference for students, researchers and industry practitioners working in or interested in joining interdisciplinary work in the areas of data intensive computing and Big Data systems using emergent large-scale distributed computing paradigms. It will also allow newcomers to grasp key concepts and potential solutions on advanced topics of theory, models, technologies, system architectures and implementation of applications in Multi-Agent systems and data intensive computing. .

  4. Matching Conflicts: Functional Validation of Agents

    National Research Council Canada - National Science Library

    Cybenko, George; Jiang, Guofei

    1999-01-01

    .... A broker or matchmaker service is often proposed as a solution. These systems use keywords drawn from application domain ontologies to specify agent services, usually framed within some sort of knowledge representation language...

  5. Competing intelligent search agents in global optimization

    Energy Technology Data Exchange (ETDEWEB)

    Streltsov, S.; Vakili, P. [Boston Univ., MA (United States); Muchnik, I. [Rutgers Univ., Piscataway, NJ (United States)

    1996-12-31

    In this paper we present a new search methodology that we view as a development of intelligent agent approach to the analysis of complex system. The main idea is to consider search process as a competition mechanism between concurrent adaptive intelligent agents. Agents cooperate in achieving a common search goal and at the same time compete with each other for computational resources. We propose a statistical selection approach to resource allocation between agents that leads to simple and efficient on average index allocation policies. We use global optimization as the most general setting that encompasses many types of search problems, and show how proposed selection policies can be used to improve and combine various global optimization methods.

  6. Penetratin and derivatives acting as antifungal agents

    NARCIS (Netherlands)

    Masman, Marcelo F.; Rodriguez, Ana M.; Raimondi, Marcela; Zacchino, Susana A.; Luiten, Paul G. M.; Somlai, Csaba; Kortvelyesi, Tamas; Penke, Botond; Enriz, Ricardo D.

    The synthesis, in vitro evaluation, and conformational study of RQIKTWFQNRRMKWKK-NH(2) (penetratin) and related derivatives acting as antifungal agents are reported. Penetratin and some of its derivatives displayed antifungal activity against the human opportunistic pathogenic standardized ATCC

  7. Agendas for Multi-Agent Learning

    National Research Council Canada - National Science Library

    Gordon, Geoffrey J

    2006-01-01

    .... Finally, we conclude with an example: starting from an informally-specified multi-agent learning problem, we illustrate how one might formalize and solve it by stepping through the tasks of modelling, design, and learning...

  8. AORTA: Adding Organizational Reasoning to Agents

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt; Dignum, Virginia

    2014-01-01

    Open systems are characterized by a diversity of heterogeneous and autonomous agents that act according to private goals, and with a behavior that is hard to predict. They can be regulated through organizations similar to human organizations, which regulate the agents’ behavior space and describe...... the expected behavior of the agents. Agents need to be able to reason about the regulations, so that they can act within the expected boundaries and work towards the objectives of the organization. This extended abstract introduces AORTA, a component that can be integrated into agents’ reasoning mechanism......, allowing them to reason about (and act upon) regulations specified by an organizational model using simple reasoning rules. The added value is that the organizational model is independent of that of the agents, and that the approach is not tied to a specific organizational model....

  9. BODIPY derivatives as molecular photoacoustic contrast agents

    Science.gov (United States)

    Laoui, Samir; Bag, Seema; Dantiste, Olivier; Frenette, Mathieu; Hatamimoslehabadi, Maryam; Bellinger-Buckley, Stephanie; Tseng, Jen-Chieh; Rochford, Jonathan; Yelleswarapu, Chandra

    2014-03-01

    Photoacoustic imaging (PAI) is emerging as a key in vivo imaging technique. Endogenous contrast agents alone are insufficient to obtain high contrast images necessitating a need for synthetic exogenous contrast agents. In recent years a great deal of research has been devoted to the development of nanoparticle based contrast agents with little effort on molecular systems. Here we report on the design and evaluation of BODIPY inspired molecular photoacoustic contrast agents (MPACs). Through chemical modification of the established BODIPY fluorophore, increasing its vibrational freedom and appending with non-emissive functionalities, it is demonstrated that the S0-S1 absorbed excitation energy is redirected towards a nonradiative excited-state decay pathway. Optical and photoacoustic characterization of the modified BODIPY MPACs demonstrates a stronger photoacoustic signal compared to the corresponding fluorescent BODIPY probes.

  10. Paramecium tetraurelia: prescreen for hazardous agents

    Energy Technology Data Exchange (ETDEWEB)

    Smith-Sonneborn, J.; Herr, C.; VanKirk, E.

    1979-01-01

    The ciliated protozoan, paramecia, is proposed as a eukaryote model system for use in short-term screening assays for detection of mutagenic/carcinogenic and hazardous agents. The approach utilizes two assays: the mutagenic and photodynamic systems.

  11. Veterans and agent orange: update 2000

    National Research Council Canada - National Science Library

    Division of Health Promotion and Disease Prevention Staff; Institute of Medicine, Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides

    2001-01-01

    Veterans and Agent Orange: Update 2000 examines the state of the scientific evidence regarding associations between diseases and exposure to dioxin and other chemical compounds in herbicides used in Vietnam...

  12. Ulipristal acetate as an emergency contraceptive agent.

    Science.gov (United States)

    Martinez, Alan M; Thomas, Michael A

    2012-09-01

    Emergency contraceptive agents play a crucial role in preventing unplanned pregnancy. These agents and devices have been studied since the 1960s and have had varied results in terms of side effects and efficacy. A new oral tablet for emergency contraception (EC), ulipristal acetate (UPA) , is a selective progesterone receptor modulator and can be used up to 120 h following unprotected intercourse, without an increase in adverse effects or a decrease in efficacy. This article reviews studies that evaluate the pharmacodynamics, pharmacokinetics, clinical efficacy, and safety profile of UPA as an emergency contraceptive agent. UPA, a selective progesterone receptor modulator, is administered as a single 30 mg dose for EC. This agent provides a comparable, if not better, efficacy and side effect profile than seen with levonorgestrel or mifepristone. Because it has both agonistic and antagonistic effects on the progesterone receptor, ongoing clinical trials are documenting UPA's use for patients with endometriosis and as an extended use contraceptive.

  13. Spions as nano-theranostics agents

    CERN Document Server

    Zarepour, Atefeh; Khosravi, Arezoo

    2017-01-01

    This Brief introduces SuperParamagnetic Iron Oxide Nanoparticles (SPIONs), the different synthesis approaches, their applications in the field of diagnostics and treatment and finally as theranostic agents in cancer.

  14. Argumentation and Multi-Agent Decision Making

    OpenAIRE

    Parsons, S; Jennings, NR

    1998-01-01

    This paper summarises our on-going work on mixed- initiative decision making which extends both classical decision theory and a symbolic theory of decision making based on argumentation to a multi-agent domain.

  15. Sanguinarine: A Novel Agent Against Prostate Cancer

    National Research Council Canada - National Science Library

    Ahmad, Nihal

    2007-01-01

    ..., has been shown to possess anti-microbial, antioxidant and anti-inflammatory properties. Our earlier studies suggested that sanguinarine may be developed as an agent for the management of prostate cancer...

  16. Sanguinarine: A Novel Agent Against Prostate Cancer

    National Research Council Canada - National Science Library

    Ahmad, Nihal

    2008-01-01

    ..., has been shown to possess anti-microbial, antioxidant and anti-inflammatory properties. Our earlier studies suggested that sanguinarine may be developed as an agent for the management of prostate cancer...

  17. Nominaliseeritud protsessi agent meediauudistes / Reet Kasik

    Index Scriptorium Estoniae

    Kasik, Reet, 1946-

    2006-01-01

    Ajalehe "Postimees" 2005. aasta materjalile toetudes vaadeldakse, mis tüüpi on nominalisatsioonides representeeritavad protsessid ja mis kujul on esitatud protsessi agent ehk tegija. Aluseks on võetud funktsionaalse grammatika põhimõtted.

  18. Radioiodination of methoxsalen using different iodinating agents

    International Nuclear Information System (INIS)

    Ayyoub, S.M.; Farah, K.

    2007-01-01

    Different iodinating agents such as chloramine-T (Ch-T), iodogen, H 2 O 2 and N-bromosuccinimide (NBS) were used for the labelling of methoxsalen via electrophilic substitution reaction. These iodinating agents oxidize NaI to produce the iodonium ions which attacked the active position in methoxsalen. These iodinating agents successfully iodinate the methoxsalen with a reasonable radiochemical yield and purity. The factors affecting both chemical yield and purity, such as the concentration of the iodinating agent, the methoxsalen concentration and the reaction time, were studied. Different developing solvents were used for the identification of the products using TLC technique. It was found that the most suitable solvent for the identification of methoxsalen using TLC was n-butanol : acetic acid : water (4:1:1). Radiochemical yields of 80% and 84% , with purity 99%, were achieved in case of NBS and H 2 O 2 , respectively

  19. Contrast Agent in Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Vu-Quang, Hieu

    2015-01-01

    Nanoparticles have been employed as contrast agent in magnetic resonance imaging (MRI) in order to improve sensitivity and accuracy in diagnosis. In addition, these contrast agents are potentially combined with other therapeutic compounds or near infrared bio-imaging (NIR) fluorophores to obtain...... theranostic or dual imaging purposes, respectively. There were two main types of MRI contrast agent that were synthesized during this PhD project including fluorine containing nanoparticles and magnetic nanoparticles. In regard of fluorine containing nanoparticles, there were two types contrast agent...... that were synthesized in project I and II. In project I, Poly (lactic-co-glycolic acid)-block-poly (ethylene glycol)-Folate Pefluorooctyl Bromide/Indocyanine green/ Doxorubicin (PLGA-PEG-Folate PFOB/ICG/Dox) has been formulated for the dual imaging NIR and 19F MRI as well as in the combination of Dox...

  20. Behavioural domain knowledge transfer for autonomous agents

    CSIR Research Space (South Africa)

    Rosman, Benjamin S

    2014-11-01

    Full Text Available , and Behavior Transfer in Autonomous Robots, AAAI 2014 Fall Symposium Series, 13-15 November 2014 Behavioural Domain Knowledge Transfer for Autonomous Agents Benjamin Rosman Mobile Intelligent Autonomous Systems Modelling and Digital Science Council...

  1. Agent chameleons: moving minds from robots to digital information spaces

    OpenAIRE

    O'Hare, G. M. P. (Greg M. P.); Duffy, Brian R.; Bradley, John F.; Martin, A. (Alan)

    2003-01-01

    Agent Chameleons investigates the motivation, desire and possibility of agent migration and mutation between real and artificial spaces. The agent must be able to mutate and change its form and function depending upon the environment within which it is situated. The form inextricably dictates or constrains its behaviour and capabilities. This paper introduces the Agent Chameleon Architecture which supports agent migration and mutation.

  2. inventory management, VMI, software agents, MDV model

    Directory of Open Access Journals (Sweden)

    Waldemar Wieczerzycki

    2012-03-01

    Full Text Available Background: As it is well know, the implementation of instruments of logistics management is only possible with the use of the latest information technology. So-called agent technology is one of the most promising solutions in this area. Its essence consists in an entirely new way of software distribution on the computer network platform, in which computer exchange among themselves not only data, but also software modules, called just agents. The first aim is to propose the alternative method of the implementation of the concept of the inventory management by the supplier with the use of intelligent software agents, which are able not only to transfer the information but also to make the autonomous decisions based on the privileges given to them. The second aim of this research was to propose a new model of a software agent, which will be both of a high mobility and a high intelligence. Methods: After a brief discussion of the nature of agent technology, the most important benefits of using it to build platforms to support business are given. Then the original model of polymorphic software agent, called Multi-Dimensionally Versioned Software Agent (MDV is presented, which is oriented on the specificity of IT applications in business. MDV agent is polymorphic, which allows the transmission through the network only the most relevant parts of its code, and only when necessary. Consequently, the network nodes exchange small amounts of software code, which ensures high mobility of software agents, and thus highly efficient operation of IT platforms built on the proposed model. Next, the adaptation of MDV software agents to implementation of well-known logistics management instrument - VMI (Vendor Managed Inventory is illustrated. Results: The key benefits of this approach are identified, among which one can distinguish: reduced costs, higher flexibility and efficiency, new functionality - especially addressed to business negotiation, full automation

  3. Agent tracking: a psycho-historical theory of the identification of living and social agents.

    Science.gov (United States)

    Bullot, Nicolas J

    To explain agent-identification behaviours, universalist theories in the biological and cognitive sciences have posited mental mechanisms thought to be universal to all humans, such as agent detection and face recognition mechanisms. These universalist theories have paid little attention to how particular sociocultural or historical contexts interact with the psychobiological processes of agent-identification. In contrast to universalist theories, contextualist theories appeal to particular historical and sociocultural contexts for explaining agent-identification. Contextualist theories tend to adopt idiographic methods aimed at recording the heterogeneity of human behaviours across history, space, and cultures. Defenders of the universalist approach tend to criticise idiographic methods because such methods can lead to relativism or may lack generality. To overcome explanatory limitations of proposals that adopt either universalist or contextualist approaches in isolation, I propose a philosophical model that integrates contributions from both traditions: the psycho-historical theory of agent-identification. This theory investigates how the tracking processes that humans use for identifying agents interact with the unique socio-historical contexts that support agent-identification practices. In integrating hypotheses about the history of agents with psychological and epistemological principles regarding agent-identification, the theory can generate novel hypotheses regarding the distinction between recognition-based, heuristic-based, and explanation-based agent-identification.

  4. Disease Modifying Agents for Multiple Sclerosis

    OpenAIRE

    Hilas, Olga; Patel, Priti N; Lam, Sum

    2010-01-01

    Objective: To summarize major clinical trials which evaluate the efficacy and safety data of approved disease modifying agents for the treatment of various types of multiple sclerosis. Data Sources: A MEDLINE (1966 to August 2008) search of clinical trials using the terms multiple sclerosis, interferon, glatiramer, mitoxantrone and natalizumab was performed. A manual bibliographic search was also conducted. English-language articles identified from the searches were evaluated. New agents unde...

  5. New Safety rule for Chemical Agents

    CERN Multimedia

    Safety Commission

    2010-01-01

    The following Safety rule has been issued on 08-01-2010: Safety Regulation SR-C Chemical Agents This document applies to all persons under the Director General’s authority. It sets out the minimal requirements for the protection of persons from risks to their safety and health arising, or likely to arise, from the effects of hazardous chemical agents used in any CERN activity. All Safety rules are available on the web pages.

  6. Non-toxic brominated perfluorocarbons radiopaque agents

    International Nuclear Information System (INIS)

    Long, D.M. Jr.

    1976-01-01

    Non-toxic bromofluorocarbon radiopaque agents are disclosed. Certain monobrominated acyclic fluorocarbons, e.g., CF 3 (CF 2 ) 6 CF 2 Br, are improved non-toxic radiopaque agents useful in diagnostic roentgenology, for example in visualizing the gastrointestinal tract, the tracheobronchial tree, the alveolar spaces or parenchyma of the lung, the spleen, the urinary bladder and ureters, the common bile duct and its radicals, the pancreatic ducts, the blood vessels, etc. 13 claims, no drawings

  7. Institutions, Behavior of Agents and Efficiency

    Directory of Open Access Journals (Sweden)

    Sukharev Oleg, S.

    2016-03-01

    Full Text Available We study the efficiency criterion, describing the behavior and choices of agents, the influence of moral norms on the model of behavior, as well as the criterion of efficiency as an institution to assess the behavior and development of the economic system. Curve proposed institutional compromise that allows to determine the possibility of changes in the welfare of interacting agents and their compliance with ethical standards when welfare increases due to violation or compliance with these standards. For the purposes of this demonstration of the influence of the model of chart-based dilemmas Holmes-Moriarty. Incentives in determining the agents behaviors play a key role in their formation due to the moral principles of behavior. However, in economics there are situations when moral principles are derived certain behaviors or interactions agents. Holmes and Moriarty there is an alternative interaction, which they can not take advantage of, and there is a full range of alternatives that actually programs the strategic outcomes of interactions that reflect the curves of "institutional compromise." Choosing an agent of moral standards as a potential model determines its behavior and, most importantly, interaction with other agents, adhering to certain moral principles. Assess the condition and the possibility of using a static criterion of Pareto efficiency for the analysis of situations where it is important to measure the economic efficiency. Showing institutional aspects that must be considered in the application or formulation of new performance criteria. It is proved that there is a connection microeconomic efficiency / inefficiency and parameters of behavior of agents that actualizes the need to impact on the behavior of agents incentives to solve the task of changing the structure.

  8. Multiobjective Genetic Programming of Agent Decision Strategies

    OpenAIRE

    Šlapák, M.; Neruda, R. (Roman)

    2014-01-01

    This work describes a method to control a behaviour of intelligent data mining agent We developed an adaptive decision making system that utilizes genetic programming technique to evolve an agent’s decision strategy. The parameters of data mining task and current state of an agent are taken into account by tree structures evolved by genetic programming. Efficiency of decision strategies is compared from the perspectives of single and multi criteria optimization.

  9. Bacteriophages as recognition and identification agents

    International Nuclear Information System (INIS)

    Teodorescu, M.C.; Gaspar, Alexandre.

    1987-01-01

    Bacteriophages are employed as agents for recognition and identification of molecules and cellular materials, using their ability to recognize their bacterial host, by coating them with antibodies or by selecting them to perform in a manner analogous to antibodies. Visibility for identification is effected by incorporating a fluorescent agent, a radioisotope, a metal, an enzyme, or other staining material. The method of this invention may be utilized in selected clinical procedures, and is adaptable to use in an assay kit. (author)

  10. Quantum decision making by social agents

    OpenAIRE

    V. I. Yukalov; D. Sornette

    2012-01-01

    The influence of additional information on the decision making of agents, who are interacting members of a society, is analyzed within the mathematical framework based on the use of quantum probabilities. The introduction of social interactions, which influence the decisions of individual agents, leads to a generalization of the quantum decision theory developed earlier by the authors for separate individuals. The generalized approach is free of the standard paradoxes of classical decision th...

  11. A Estreptozootocina Como Agente Diabetogênico

    OpenAIRE

    Furlan, Maria Montserrat Diaz Pedrosa

    2008-01-01

    Os quadros experimentais de diabetes mellitus permitem observar as diversas variáveis envolvidas na fisiopatologia desta doença sob condições controladas. Entretanto, conhecer as características do agente químico usado na indução do diabetes é importante para uma análise coerente dos resultados obtidos. Esta revisão apresenta aspectos relacionados à estreptozootocina, um agente diabetogênico amplamente u...

  12. Towards Culturally-Aware Virtual Agent Systems

    DEFF Research Database (Denmark)

    Endrass, Birgit; André, Elisabeth; Rehm, Matthias

    2010-01-01

    Globalization leads to an increase in intercultural encounters with a risk of misunderstandings due to different patterns of behavior and understanding. Learning applications have been proposed that employ virtual agents as their primary tool. Through their embodiment, learning can be done in a g...... of the art that integrates culture in multiagent systems. In addition, an approach of simulating culture-specific behavior using such a multiagent system is introduced and future trends in enculturating virtual agent systems are outlined....

  13. Tissue-specific MR contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Weinmann, Hanns-Joachim E-mail: hannsjoachim.weinmann@schering.de; Ebert, Wolfgang; Misselwitz, Bernd; Schmitt-Willich, Heribert

    2003-04-01

    The purpose of this review is to outline recent trends in contrast agent development for magnetic resonance imaging. Up to now, small molecular weight gadolinium chelates are the workhorse in contrast enhanced MRI. These first generation MR contrast agents distribute into the intravascular and interstitial space, thus allowing the evaluation of physiological parameters, such as the status or existence of the blood-brain-barrier or the renal function. Shortly after the first clinical use of paramagnetic metallochelates in 1983, compounds were suggested for liver imaging and enhancing a cardiac infarct. Meanwhile, liver specific contrast agents based on gadolinium, manganese or iron become reality. Dedicated blood pool agents will be available within the next years. These gadolinium or iron agents will be beneficial for longer lasting MRA procedures, such as cardiac imaging. Contrast enhanced lymphography after interstitial or intravenous injection will be another major step forward in diagnostic imaging. Metastatic involvement will be seen either after the injection of ultrasmall superparamagnetic iron oxides or dedicated gadolinium chelates. The accumulation of both compound classes is triggered by an uptake into macrophages. It is likely that similar agents will augment MRI of atheriosclerotic plaques, a systemic inflammatory disease of the arterial wall. Thrombus-specific agents based on small gadolinium labeled peptides are on the horizon. It is very obvious that the future of cardiovascular MRI will benefit from the development of new paramagnetic and superparamagnetic substances. The expectations for new tumor-, pathology- or receptor-specific agents are high. However, is not likely that such a compound will be available for daily routine MRI within the next decade.

  14. Agent Argumentation with Opinions and Advice

    Science.gov (United States)

    Debenham, John; Sierra, Carles

    In argumentation-based negotiation the rhetorical illocutionary particles Appeals, Rewards and Threats have implications for the players that extend beyond a single negotiation and are concerned with building (business) relationships. This paper extends an agent's relationship-building argumentative repertoire with Opinions and Advice. A framework is described that enables agents to model their relationships and to use argumentative dialogue strategically both to achieve good negotiation outcomes and to build and sustain valuable relationships.

  15. A multi-agent based cell controller

    OpenAIRE

    Paulo Leitão; Francisco José de Oliveira Restivo; Goran Putnik

    2001-01-01

    This paper discusses the opportunity to use multi-agents technology in automation and distributed manufacturing systems and the expected improvements. To support the discussion, it is described a manufacturing cell control application developed using the multi-agent technology, and the results are compared with other control application developed in the past by some of the authors, using a traditional approach, for the same flexible manufacturing cell.

  16. Ontologies, Agents and the Grid: An Overview

    OpenAIRE

    Drozdowicz, Michal; Ganzha, Maria; Paprzycki, Marcin; Olejnik, Richard; Lirkov, Ivan; Telegin, P.; Senobari, M.

    2009-01-01

    23 pages; One of the important claims that permeate the current view of information management is that ontological demarcation of data and semantic information processing are going to allow us to infuse "intelligence" into information systems. Separately, it is claimed that software agents, combined with ontologies will be the foundation ofWeb 4.0. In our work we are developing an agent-team-based resource management and brokering infrastructure for computational grids. The proposed meta-leve...

  17. Reaching High Interactive Levels with Situated Agents

    Directory of Open Access Journals (Sweden)

    Guzmán-Obando J.

    2013-01-01

    Full Text Available El documento presenta un proceso coordinado a través del cual los agentes situados son capaces de trabajar en forma conjunta con el conocimiento de sus habilidades para interactuar con otras entidades similares. Una buena coordinación se deriva de que cada agente situado es capaz de representar sus tasas de idoneidad para llevar a cabo cualquier acción de una manera eficaz. Además de utilizar dichas tasas, un agente puede coordinar sus acciones con otros agentes. En este sentido, cada agente situado trata de seleccionar y realizar sólo las acciones con los mayores índices de ejecución. Algunos experimentos en un verdadero fútbol robótico banco de pruebas están diseñadas para poner en práctica el enfoque coordinado propuesto. Observaciones finales concluir la eficacia y las ventajas de la obra presentada con el fin de aumentar el rendimiento de un equipo integrado por agentes situados cuando tienen que resolver tareas complejas en un escenario dinámico, competitivo e impredecible.

  18. CHI: A General Agent Communication Framework

    Energy Technology Data Exchange (ETDEWEB)

    Goldsmith, S.Y.; Phillips, L.R.; Spires, S.V.

    1998-12-17

    We have completed and exercised a communication framework called CHI (CLOS to HTML Interface) by which agents can communicate with humans. CHI follows HTTP (HyperText Transfer Protocol) and produces HTML (HyperText Markup Language) for use by WWW (World-Wide Web) browsers. CHI enables the rapid and dynamic construction of interface mechanisms. The essence of CHI is automatic registration of dynamically generated interface elements to named objects in the agent's internal environment. The agent can access information in these objects at will. State is preserved, so an agent can pursue branching interaction sequences, activate failure recovery behaviors, and otherwise act opportunistically to maintain a conversation. The CHI mechanism remains transparent in multi-agent, multi-user environments because of automatically generated unique identifiers built into the CHI mechanism. In this paper we discuss design, language, implementation, and extension issues, and, by way of illustration, examine the use of the general CHI/HCHI mechanism in a specific international electronic commerce system. We conclude that the CHI mechanism is an effective, efficient, and extensible means of the agent/human communication.

  19. History of chemical and biological warfare agents

    International Nuclear Information System (INIS)

    Szinicz, L.

    2005-01-01

    Chemical and biological warfare agents constitute a low-probability, but high-impact risk both to the military and to the civilian population. The use of hazardous materials of chemical or biological origin as weapons and for homicide has been documented since ancient times. The first use of chemicals in terms of weapons of mass destruction goes back to World War I, when on April 22, 1915 large amounts of chlorine were released by German military forces at Ypres, Belgium. Until around the 1970s of the 20th century, the awareness of the threat by chemical and biological agents had been mainly confined to the military sector. In the following time, the development of increasing range delivery systems by chemical and biological agents possessors sensitised public attention to the threat emanating from these agents. Their proliferation to the terrorists field during the 1990s with the expanding scale and globalisation of terrorist attacks suggested that these agents are becoming an increasing threat to the whole world community. The following article gives a condensed overview on the history of use and development of the more prominent chemical and biological warfare agents

  20. History of chemical and biological warfare agents.

    Science.gov (United States)

    Szinicz, L

    2005-10-30

    Chemical and biological warfare agents constitute a low-probability, but high-impact risk both to the military and to the civilian population. The use of hazardous materials of chemical or biological origin as weapons and for homicide has been documented since ancient times. The first use of chemicals in terms of weapons of mass destruction goes back to World War I, when on April 22, 1915 large amounts of chlorine were released by German military forces at Ypres, Belgium. Until around the 1970s of the 20th century, the awareness of the threat by chemical and biological agents had been mainly confined to the military sector. In the following time, the development of increasing range delivery systems by chemical and biological agents possessors sensitised public attention to the threat emanating from these agents. Their proliferation to the terrorists field during the 1990s with the expanding scale and globalisation of terrorist attacks suggested that these agents are becoming an increasing threat to the whole world community. The following article gives a condensed overview on the history of use and development of the more prominent chemical and biological warfare agents.