Intelligent Agents and Their Potential for Future Design and Synthesis Environment

NASA Technical Reports Server (NTRS)

Noor, Ahmed K. (Compiler); Malone, John B. (Compiler)

1999-01-01

This document contains the proceedings of the Workshop on Intelligent Agents and Their Potential for Future Design and Synthesis Environment, held at NASA Langley Research Center, Hampton, VA, September 16-17, 1998. The workshop was jointly sponsored by the University of Virginia's Center for Advanced Computational Technology and NASA. Workshop attendees came from NASA, industry and universities. The objectives of the workshop were to assess the status of intelligent agents technology and to identify the potential of software agents for use in future design and synthesis environment. The presentations covered the current status of agent technology and several applications of intelligent software agents. Certain materials and products are identified in this publication in order to specify adequately the materials and products that were investigated in the research effort. In no case does such identification imply recommendation or endorsement of products by NASA, nor does it imply that the materials and products are the only ones or the best ones available for this purpose. In many cases equivalent materials and products are available and would probably produce equivalent results.

Benzothiazole Derivatives as Potential Anti-Infective Agents.

PubMed

Sharma, Prabodh Chander; Bansal, Kushal Kumar; Deep, Aakash; Pathak, Meenakshi

2017-01-01

Severity of microbial infections and escalating resistance towards antibiotics has created a deep necessity for discovery of novel anti-infective agents. Heterocyclic chemistry of benzothiazole has become one of the most prolific areas in the field of drug discovery and development that has attracted great attention in recent time due to its increasing importance in the field of pharmaceuticals. The importance of benzothiazole and derivatives as potential antimicrobial agents has been well established and a large number of papers have been published in this regard. The present communication is an earnest attempt to review the chemistry, synthetic aspects including click chemistry and antimicrobial activities of benzothiazole derivatives reported in recent scientific literature. The scientific information of this manuscript may be worthwhile in encouraging the prospective researchers working on this heterocyclic scaffold.

The Structural Basis of Cryptosporidium-Specific IMP Dehydrogenase Inhibitor Selectivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacPherson, Iain S.; Kirubakaran, Sivapriya; Gorla, Suresh Kumar

2010-03-29

Cryptosporidium parvum is a potential biowarfare agent, an important AIDS pathogen, and a major cause of diarrhea and malnutrition. No vaccines or effective drug treatment exist to combat Cryptosporidium infection. This parasite relies on inosine 5{prime}-monophosphate dehydrogenase (IMPDH) to obtain guanine nucleotides, and inhibition of this enzyme blocks parasite proliferation. Here, we report the first crystal structures of CpIMPDH. These structures reveal the structural basis of inhibitor selectivity and suggest a strategy for further optimization. Using this information, we have synthesized low-nanomolar inhibitors that display 10{sup 3} selectivity for the parasite enzyme over human IMPDH2.

Imidacloprid as a Potential Agent for the Systemic Control of Sand Flies

DTIC Science & Technology

2011-03-01

Imidacloprid as a potential agent for the systemic control of sand flies Gideon Wasserberg1,4*, Richard... imidacloprid as a systemic control agent. First, to evaluate the blood-feeding effect, we fed adult female Phlebotomus papatasi with imidacloprid ...mortality was obtained with a dose of only 250 ppm. Overall, results support the feasibility of imidacloprid as a systemic control agent that

Vaccine Development for Biothreat Alpha Viruses

DTIC Science & Technology

2011-09-25

gaviridae, are causative agents of debilitative, acute, and sometimes fatal encephalitis in North, Central, and South America [1]. These viruses are...and can be lyophilized. VEEV was tested as a biowarfare agent during the U.S. offensive program in the 1950’s and 1960’s, and may have been...MD 21702, USA Abstract The majority of alpha virus is non-pathogenic to humans. However, select alpha viruses can cause severe disease in humans

Primary screen for potential sheep scab control agents.

PubMed

Dunn, J A; Prickett, J C; Collins, D A; Weaver, R J

2016-07-15

The efficacy of potential acaricidal agents were assessed against the sheep scab mite Psoroptes ovis using a series of in vitro assays in modified test arenas designed initially to maintain P. ovis off-host. The mortality effects of 45 control agents, including essential oils, detergents, desiccants, growth regulators, lipid synthesis inhibitors, nerve action/energy metabolism disruptors and ecdysteroids were assessed against adults and nymphs. The most effective candidates were the desiccants (diatomaceous earth, nanoclay and sorex), the growth regulators (buprofezin, hexythiazox and teflubenzuron), the lipid synthesis inhibitors (spirodiclofen, spirotetramat and spiromesifen) and the nerve action and energy metabolism inhibitors (fenpyroximate, spinosad, tolfenpyrad, and chlorantraniliprole). Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Advanced Development of the rF1V and rBV A/B Vaccines: Progress and Challenges

PubMed Central

Hart, Mary Kate; Saviolakis, George A.; Welkos, Susan L.; House, Robert V.

2012-01-01

The development of vaccines for microorganisms and bacterial toxins with the potential to be used as biowarfare and bioterrorism agents is an important component of the US biodefense program. DVC is developing two vaccines, one against inhalational exposure to botulinum neurotoxins A1 and B1 and a second for Yersinia pestis, with the ultimate goal of licensure by the FDA under the Animal Rule. Progress has been made in all technical areas, including manufacturing, nonclinical, and clinical development and testing of the vaccines, and in assay development. The current status of development of these vaccines, and remaining challenges are described in this chapter. PMID:22028978

Podophyllotoxin: a novel potential natural anticancer agent

PubMed Central

Ardalani, Hamidreza; Avan, Amir; Ghayour-Mobarhan, Majid

2017-01-01

Objective: The aim of the present review is to give an overview about the role, biosynthesis, and characteristics of Podophyllotoxin (PTOX) as a potential antitumor agent with particular emphasis on key biosynthesis processes, function of related enzymes and characterization of genes encoding the enzymes. Materials and Methods: Google scholar, PubMed and Scopus were searched for literatures which have studied identification, characterization, fermentation and therapeutic effects of PTOX and published in English language until end of 2016. Results: PTOX is an important plant-derived natural product, has derivatives such as etoposide and teniposide, which have been used as therapies for cancers and venereal wart. PTOX structure is closely related to the aryltetralin lactone lignans that have antineoplastic and antiviral activities. Podophyllum emodi Wall. (syn. P. hexandrum) and Podophyllum peltatum L. (Berberidaceae) are the major sources of PTOX. It has been shown that ferulic acid and methylenedioxy substituted cinnamic acid are the enzymes involved in PTOX synthesis. PTOX prevents cell growth via polymerization of tubulin, leading to cell cycle arrest and suppression of the formation of the mitotic-spindles microtubules. Conclusion: Several investigations have been performed in biosynthesis of PTOX such as cultivation of these plants, though they were unsuccessful. Thus, it is important to find alternative sources to satisfy the pharmaceutical demand for PTOX. Moreover, further preclinical studies are warranted to explore the molecular mechanisms of these agents in treatment of cancer and their possible potential to overcome chemoresistance of tumor cells. PMID:28884079

Rodents as potential couriers for bioterrorism agents.

PubMed

Lõhmus, Mare; Janse, Ingmar; van de Goot, Frank; van Rotterdam, Bart J

2013-09-01

Many pathogens that can cause major public health, economic, and social damage are relatively easily accessible and could be used as biological weapons. Wildlife is a natural reservoir for many potential bioterrorism agents, and, as history has shown, eliminating a pathogen that has dispersed among wild fauna can be extremely challenging. Since a number of wild rodent species live close to humans, rodents constitute a vector for pathogens to circulate among wildlife, domestic animals, and humans. This article reviews the possible consequences of a deliberate spread of rodentborne pathogens. It is relatively easy to infect wild rodents with certain pathogens or to release infected rodents, and the action would be difficult to trace. Rodents can also function as reservoirs for diseases that have been spread during a bioterrorism attack and cause recurring disease outbreaks. As rats and mice are common in both urban and rural settlements, deliberately released rodentborne infections have the capacity to spread very rapidly. The majority of pathogens that are listed as potential agents of bioterrorism by the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases exploit rodents as vectors or reservoirs. In addition to zoonotic diseases, deliberately released rodentborne epizootics can have serious economic consequences for society, for example, in the area of international trade restrictions. The ability to rapidly detect introduced diseases and effectively communicate with the public in crisis situations enables a quick response and is essential for successful and cost-effective disease control.

Plants' Metabolites as Potential Antiobesity Agents

PubMed Central

Gooda Sahib, Najla; Saari, Nazamid; Ismail, Amin; Khatib, Alfi; Mahomoodally, Fawzi; Abdul Hamid, Azizah

2012-01-01

Obesity and obesity-related complications are on the increase both in the developed and developing world. Since existing pharmaceuticals fail to come up with long-term solutions to address this issue, there is an ever-pressing need to find and develop new drugs and alternatives. Natural products, particularly medicinal plants, are believed to harbor potential antiobesity agents that can act through various mechanisms either by preventing weight gain or promoting weight loss amongst others. The inhibition of key lipid and carbohydrate hydrolyzing and metabolizing enzymes, disruption of adipogenesis, and modulation of its factors or appetite suppression are some of the plethora of targeted approaches to probe the antiobesity potential of medicinal plants. A new technology such as metabolomics, which deals with the study of the whole metabolome, has been identified to be a promising technique to probe the progression of diseases, elucidate their pathologies, and assess the effects of natural health products on certain pathological conditions. This has been applied to drug research, bone health, and to a limited extent to obesity research. This paper thus endeavors to give an overview of those plants, which have been reported to have antiobesity effects and highlight the potential and relevance of metabolomics in obesity research. PMID:22666121

Therapeutic options for diseases due to potential viral agents of bioterrorism.

PubMed

Bronze, Michael S; Greenfield, Ronald A

2003-02-01

The etiologic agents of smallpox and viral hemorrhagic fever have emerged as potential agents of bioterrorism due to their virulence, potential for human to human dissemination and limited strategies for treatment and prevention. Cidofovir has shown significant promise in animal models, and limited case reports in humans are encouraging. Ribavirin is the treatment of choice for certain hemorrhagic fever viral infections, but has no current application to Ebola and Marburg infections. Current vaccine strategies for smallpox are effective, but carry significant risk for complications. Licensed vaccines for hemorrhagic fever viruses are limited to yellow fever, but animal studies are promising. Genomic analysis of the viral pathogen and the animal model response to infection may provide valuable information enabling the development of novel treatment and prevention strategies. Current knowledge of these strategies is reviewed.

Xanthones from Mangosteen Extracts as Natural Chemopreventive Agents: Potential Anticancer Drugs

PubMed Central

Shan, T.; Ma, Q.; Guo, K.; Liu, J.; Li, W.; Wang, F.; Wu, E.

2011-01-01

Despite decades of research, the treatment and management of malignant tumors still remain a formidable challenge for public health. New strategies for cancer treatment are being developed, and one of the most promising treatment strategies involves the application of chemopreventive agents. The search for novel and effective cancer chemopreventive agents has led to the identification of various naturally occurring compounds. Xanthones, from the pericarp, whole fruit, heartwood, and leaf of mangosteen (Garcinia mangostana Linn., GML), are known to possess a wide spectrum of pharmacologic properties, including anti-oxidant, anti-tumor, anti-allergic, anti-inflammatory, anti-bacterial, anti-fungal, and anti-viral activities. The potential chemopreventive and chemotherapeutic activities of xanthones have been demonstrated in different stages of carcinogenesis (initiation, promotion, and progression) and are known to control cell division and growth, apoptosis, inflammation, and metastasis. Multiple lines of evidence from numerous in vitro and in vivo studies have confirmed that xanthones inhibit proliferation of a wide range of human tumor cell types by modulating various targets and signaling transduction pathways. Here we provide a concise and comprehensive review of preclinical data and assess the observed anticancer effects of xanthones, supporting its remarkable potential as an anticancer agent. PMID:21902651

Fate of Bacterial and Viral Bio-Warfare Agents in Disinfected Waters

DTIC Science & Technology

2010-10-01

600 nm; approximately 4 h). An aliquot of 0.4 mL bacterial culture is spread onto the surface of Sporulation Media A Medium (SMA) and incubated at...dishes containing Sporulation Medium Sterile distilled water at 4 °C 70% EtOH Crystal violet Stain 1.2 Sporulation media A: Nutrient broth 8g/L...phase (approximately 4 h). 2.2 Seeding the Sporulation Plates 1. Label 150 mm Petri dishes of SM A Medium. 2. Inoculate, by aseptically spreading

Stinging plants: as future bio-weapon.

PubMed

Gupta, Sanjay Mohan; Kumar, Kamal

2016-09-01

In the present opinion paper, we have been introducing for the first time the stinging plants and/or their biological toxins as novel bio-threat agents that may be used for the development of bio-weapons for self-defence purpose. The selected studied stinging plants are having dual role as nutraceutical and ethno-pharmacological uses apart from their less explored stinging property. However, future detailed work is required for identification and characterization of the precise stinging chemical components that will be used for the formulation of novel bio-warfare agents for self-defence purpose.

Synthetic Ni3S2/Ni hybrid architectures as potential contrast agents in MRI

NASA Astrophysics Data System (ADS)

Ma, J.; Chen, K.

2016-04-01

Traditional magnetic resonance imaging (MRI) contrast agents mainly include superparamagnetic (SPM) iron oxide nanoparticle as T 2 contrast agent for liver and paramagnetic Gd (III)-chelate as T 1 contrast agent for all organs. In this work, weak ferromagnetic kale-like and SPM cabbage-like Ni3S2@Ni hybrid architectures were synthesized and evaluated as potential T 1 MRI contrast agents. Their relatively small r 2/r 1 ratios of 2.59 and 2.38, and high r 1 values of 11.27 and 4.89 mmol-1 L s-1 (for the kale-like and cabbage-like Ni3S2@Ni, respectively) will shed some light on the development of new-type MRI contrast agents.

Potential drug-drug interactions between anti-cancer agents and community pharmacy dispensed drugs.

PubMed

Voll, Marsha L; Yap, Kim D; Terpstra, Wim E; Crul, Mirjam

2010-10-01

To identify the prevalence of potential drug-drug interactions between hospital pharmacy dispensed anti-cancer agents and community pharmacy dispensed drugs. A retrospective cohort study was conducted on the haematology/oncology department of the internal medicine ward in a large teaching hospital in Amsterdam, the Netherlands. Prescription data from the last 100 patients treated with anti-cancer agents were obtained from Paracelsus, the chemotherapy prescribing system in the hospital. The community pharmacy dispensed drugs of these patients were obtained by using OZIS, a system that allows regionally linked pharmacies to call up active medication on any patient. Both medication lists were manually screened for potential drug-drug interactions by using several information sources on interactions, e.g. Pubmed, the Flockhart P450 table, Micromedex and Dutch reference books. Prevalence of potential drug-drug interactions between anti-cancer agents provided by the hospital pharmacy and drugs dispensed by the community pharmacy. Ninety-one patients were included in the study. A total of 31 potential drug-drug interactions were found in 16 patients, of which 15 interactions were clinically relevant and would have required an intervention. Of these interactions 1 had a level of severity ≥ D, meaning the potential drug-drug interaction could lead to long lasting or permanent damage, or even death. The majority of the interactions requiring an intervention (67%) had a considerable level of evidence (≥ 2) and were based on well-documented case reports or controlled interaction studies. Most of the potential drug-drug interactions involved the antiretroviral drugs (40%), proton pump inhibitors (20%) and antibiotics (20%). The anti-cancer drug most involved in the drug-drug interactions is methotrexate (33%). This study reveals a high prevalence of potential drug-drug interactions between anti-cancer agents provided by the hospital pharmacy and drugs dispensed by the

The development of bis(hydroxymethyl)pyrrole analogs as bifunctional DNA cross-linking agents and their chemotherapeutic potential.

PubMed

Su, Tsann-Long; Lee, Te-Chang; Kakadiya, Rajesh

2013-11-01

Bifunctional DNA cross-linking agents are widely used as chemotherapeutic agents in clinics. The advance in the development of these agents as potential antitumor agents has generated various types of bis(hydroxymethyl)pyrrole analogs. In order to develop highly effective anticancer agents, it is necessary to understand the chemophysical properties, structure-activity relationships, therapeutic potency, toxicity/safety, and pharmacokinetics of these DNA cross-linking agents. This review presents an overview of the recent advances in developing various types of bis(hydroxymethyl)pyrrole analogs with potential antitumor activity to provide more information for future drug design and strategies for combination chemotherapy. The rational drug design, chemical syntheses, antitumor activity, mechanism of action, and development of combined chemotherapy regimens, including a DNA repair inhibitor, are discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Making vaccines "on demand": a potential solution for emerging pathogens and biodefense?

PubMed

De Groot, Anne S; Einck, Leo; Moise, Leonard; Chambers, Michael; Ballantyne, John; Malone, Robert W; Ardito, Matthew; Martin, William

2013-09-01

The integrated US Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) has made great strides in strategic preparedness and response capabilities. There have been numerous advances in planning, biothreat countermeasure development, licensure, manufacturing, stockpiling and deployment. Increased biodefense surveillance capability has dramatically improved, while new tools and increased awareness have fostered rapid identification of new potential public health pathogens. Unfortunately, structural delays in vaccine design, development, manufacture, clinical testing and licensure processes remain significant obstacles to an effective national biodefense rapid response capability. This is particularly true for the very real threat of "novel pathogens" such as the avian-origin influenzas H7N9 and H5N1, and new coronaviruses such as hCoV-EMC. Conventional approaches to vaccine development, production, clinical testing and licensure are incompatible with the prompt deployment needed for an effective public health response. An alternative approach, proposed here, is to apply computational vaccine design tools and rapid production technologies that now make it possible to engineer vaccines for novel emerging pathogen and WMD biowarfare agent countermeasures in record time. These new tools have the potential to significantly reduce the time needed to design string-of-epitope vaccines for previously unknown pathogens. The design process-from genome to gene sequence, ready to insert in a DNA plasmid-can now be accomplished in less than 24 h. While these vaccines are by no means "standard," the need for innovation in the vaccine design and production process is great. Should such vaccines be developed, their 60-d start-to-finish timeline would represent a 2-fold faster response than the current standard.

Anti-diabetic potential of peptides: Future prospects as therapeutic agents.

PubMed

Marya; Khan, Haroon; Nabavi, Seyed Mohammad; Habtemariam, Solomon

2018-01-15

Diabetes mellitus is a metabolic disorder in which the glucose level in blood exceeds beyond the normal level. Persistent hyperglycemia leads to diabetes late complication and obviously account for a large number of morbidity and mortality worldwide. Numerous therapeutic options are available for the treatment of diabetes including insulin for type I and oral tablets for type II, but its effective management is still a dream. To date, several options are under investigation in various research laboratories for efficacious and safer agents. Of them, peptides are currently amongst the most widely investigated potential therapeutic agents whose design and optimal uses are under development. A number of natural and synthetic peptides have so far been found with outstanding antidiabetic effect mediated through diverse mechanisms. The applications of new emerging techniques and drug delivery systems further offer opportunities to achieve the desired target outcomes. Some outstanding peptides in preclinical and clinical studies with better efficacy and safety profile have already been identified. Further detail studies on these peptides may therefore lead to significant clinically useful antidiabetic agents. Copyright © 2017. Published by Elsevier Inc.

Molecular effective coverage surface area of optical clearing agents for predicting optical clearing potential

NASA Astrophysics Data System (ADS)

Feng, Wei; Ma, Ning; Zhu, Dan

2015-03-01

The improvement of methods for optical clearing agent prediction exerts an important impact on tissue optical clearing technique. The molecular dynamic simulation is one of the most convincing and simplest approaches to predict the optical clearing potential of agents by analyzing the hydrogen bonds, hydrogen bridges and hydrogen bridges type forming between agents and collagen. However, the above analysis methods still suffer from some problem such as analysis of cyclic molecule by reason of molecular conformation. In this study, a molecular effective coverage surface area based on the molecular dynamic simulation was proposed to predict the potential of optical clearing agents. Several typical cyclic molecules, fructose, glucose and chain molecules, sorbitol, xylitol were analyzed by calculating their molecular effective coverage surface area, hydrogen bonds, hydrogen bridges and hydrogen bridges type, respectively. In order to verify this analysis methods, in vitro skin samples optical clearing efficacy were measured after 25 min immersing in the solutions, fructose, glucose, sorbitol and xylitol at concentration of 3.5 M using 1951 USAF resolution test target. The experimental results show accordance with prediction of molecular effective coverage surface area. Further to compare molecular effective coverage surface area with other parameters, it can show that molecular effective coverage surface area has a better performance in predicting OCP of agents.

Imaging of hemorrhagic fever with renal syndrome: a potential bioterrorism agent of military significance.

PubMed

Bui-Mansfield, Liem T; Cressler, Dana K

2011-11-01

Hemorrhagic fever with renal syndrome (HFRS) is a potentially fatal infectious disease with worldwide distribution. Its etiologic agents are viruses of the genus Hantavirus of the virus family Bunyaviridae. Hypothetical ease of production and distribution of these agents, with their propensity to incapacitate victims and overwhelm health care resources, lend themselves as significant potential biological agents of terrorism. HFRS has protean clinical manifestations, which may mimic upper respiratory tract infection, nephrolithiasis, and Hantavirus pulmonary syndrome and may delay proper treatment. Sequelae of HFRS, such as hemorrhage, acute renal failure, retroperitoneal edema, pancreatitis, pulmonary edema, and neurologic symptoms, can be detected by different imaging modalities. Medical providers caring for HFRS patients must be aware of its radiologic features, which may help to confirm its clinical diagnosis. In this article, the authors review the epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and complications of HFRS.

Potential of Three Ethnomedicinal Plants as Antisickling Agents.

PubMed

Nurain, Ismaila O; Bewaji, Clement O; Johnson, Jarrett S; Davenport, Robertson D; Zhang, Yang

2017-01-03

Sickle cell disease (SCD) is a genetic blood disorder that affects the shape and transportation of red blood cells (RBCs) in blood vessels, leading to various clinical complications. Many drugs that are available for treating the disease are insufficiently effective, toxic, or too expensive. Therefore, there is a pressing need for safe, effective, and inexpensive therapeutic agents from indigenous plants used in ethnomedicines. The potential of aqueous extracts of Cajanus cajan leaf and seed, Zanthoxylum zanthoxyloides leaf, and Carica papaya leaf in sickle cell disease management was investigated in vitro using freshly prepared 2% sodium metabisulfite for sickling induction. The results indicated that the percentage of sickled cells, which was initially 91.6% in the control, was reduced to 29.3%, 41.7%, 32.8%, 38.2%, 47.6%, in the presence of hydroxyurea, C. cajan seed, C. cajan leaf, Z. zanthoxyloides leaf, and C. papaya leaf extracts, respectively, where the rate of polymerization inhibition was 6.5, 5.9, 8.0, 6.6, and 6.0 (×10 -2 ) accordingly. It was also found that the RBC resistance to hemolysis was increased in the presence of the tested agents as indicated by the reduction of the percentage of hemolyzed cells from 100% to 0%. The phytochemical screening results indicated the presence of important phytochemicals including tannins, saponins, alkaloids, flavonoids, and glycosides in all the plant extracts. Finally, gas chromatography-mass spectrometry analysis showed the presence of important secondary metabolites in the plants. These results suggest that the plant extracts have some potential to be used as alternative antisickling therapy to hydroxyurea in SCD management.

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

PubMed Central

Thoppil, Roslin J; Bishayee, Anupam

2011-01-01

Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are currently available to patients with liver cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. Several naturally occurring dietary and non-dietary phytochemicals have shown enormous potential in the prevention and treatment of several cancers, especially those of the gastrointestinal tract. Terpenoids, the largest group of phytochemicals, traditionally used for medicinal purposes in India and China, are currently being explored as anticancer agents in clinical trials. Terpenoids (also called “isoprenoids”) are secondary metabolites occurring in most organisms, particularly plants. More than 40 000 individual terpenoids are known to exist in nature with new compounds being discovered every year. A large number of terpenoids exhibit cytotoxicity against a variety of tumor cells and cancer preventive as well as anticancer efficacy in preclinical animal models. This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors. Both in vitro and in vivo effects of these agents and related cellular and molecular mechanisms are highlighted. Potential challenges and future directions involved in the advancement of these promising natural compounds in the chemoprevention and therapy of human liver cancer are also discussed. PMID:21969877

Detection and identification of Variola virus in fixed human tissue after prolonged archival storage.

PubMed

Schoepp, Randal J; Morin, Michelle D; Martinez, Mark J; Kulesh, David A; Hensley, Lisa; Geisbert, Thomas W; Brady, Daniel R; Jahrling, Peter B

2004-01-01

Smallpox disease has been eradicated from the human population since 1979, but is again a concern because of its potential use as an agent of bioterrorism or biowarfare. World Health Organization-sanctioned repositories of infectious Variola virus are known to occur in both Russia and the United States, but many believe other undeclared and unregulated sources of the virus could exist. Thus, validation of improved methods for definitive identification of smallpox virus in diagnostic specimens is urgently needed. In this paper, we describe the discovery of suspected Variola infected human tissue, fixed and preserved for decades in largely unknown solutions, and the use of routine histology, electron microscopy, and ultimately DNA extraction and fluorogenic 5' nuclease (TaqMan) assays for its identification and confirmation.

Hypertension and vascular dementia in the elderly: the potential role of anti-hypertensive agents.

PubMed

Coca, Antonio

2013-09-01

Vascular dementia (VaD) - a severe form of vascular cognitive impairment - and cognitive decline are associated with hypertension and therefore it seems logical to consider that reducing BP with anti-hypertensive therapy may protect against the development/onset of cognitive function impairment or dementia. This narrative, non-systematic review discusses the available evidence on the potential correlation between the use of anti-hypertensive agents and the risk of VaD and cognitive decline. MEDLINE was searched for inclusion of relevant studies. No limitations in time were considered. A consensus on the potential effects of anti-hypertensive treatment in the reduction of VaD and associated cognitive decline has not been reached. A protective effect of anti-hypertensive agents has been observed in a number of studies although it is still unclear whether different classes of anti-hypertensive agents have a different effect on the development of VaD. The protective effect of anti-hypertensive agents appears to depend on the specific drug used - positive effects have been observed with calcium channel blockers (CCBs), such as lercanidipine and nitrendipine, the combination perindopril-indapamide and telmisartan.

Evaluation of FloSeal as a Potential Intracavitary Hemostatic Agent

DTIC Science & Technology

2006-02-01

Laws ER Jr. Use of FloSeal hemostatic sealant in transsphenoidal pituitary surgery : technical note. Neurosurgery. 2002;51:513–516. 14. Kheirabadi BS...of death in com- bat and civilian trauma. When surgery is unavailable, one potential solution to such hemorrhage might be the introduction of an agent...situations, including venous and arterial vascular surgery ,7,9 cardiac valve replacement or cardiopulmonary bypass grafting,6 partial nephrectomies,10

Real-Time Optical Detection of Single Nanoparticles and Viruses Using Heterodyne Interferometry

NASA Astrophysics Data System (ADS)

Mitra, Anirban; Novotny, Lukas

Nanoparticles play a significant role in various fields such as biomedical imaging and diagnostics [1-4], process control in semiconductor manufacturing [5], explosives [6], environmental monitoring and climate change [7, 8], and various other fields. Inhalation of ultrafine particulates in air has been shown to have adverse effects, such as inflammation of lungs or pulmonary and cardiovascular diseases [9, 10]. Nano-sized biological agents and pathogens such as viruses are known to be responsible for a wide variety of human diseases such as flu, AIDS and herpes, and have been used as biowarfare agents [11, 12].

Potential Bio-Control Agent from Rhodomyrtus tomentosa against Listeria monocytogenes

PubMed Central

Odedina, Grace Fiyinfoluwa; Vongkamjan, Kitiya; Voravuthikunchai, Supayang Piyawan

2015-01-01

Listeria monocytogenes is an important foodborne pathogen implicated in many outbreaks of listeriosis. This study aimed at screening for the potential use of Rhodomyrtus tomentosa ethanolic leaf extract as a bio-control agent against L. monocytogenes. Twenty-two L. monocytogenes isolates were checked with 16 commercial antibiotics and isolates displayed resistance to 10 antibiotics. All the tested isolates were sensitive to the extract with inhibition zones ranging from 14 to 16 mm. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranged from 16 to 32 µg/mL and 128 to 512 µg/mL, respectively. Time-kill assay showed that the extract had remarkable bactericidal effects on L. monocytogenes. The extract at a concentration of 16 µg/mL reduced tolerance to 10% NaCl in L. monocytogenes in 4 h. Stationary phase L. monocytogenes cells were rapidly inactivated by greater than 3-log units within 30 min of contact time with R. tomentosa extract at 128 µg/mL. Electron microscopy revealed fragmentary bacteria with changes in the physical and morphological properties. Our study demonstrates the potential of the extract for further development into a bio-control agent in food to prevent the incidence of L. monocytogenes contamination. PMID:26371033

Overview: cause and prevention in biowarfare and bioterrorism.

PubMed

Hilleman, Maurice R

2002-08-19

Bioweaponry is rooted in the ancient past. It became a science in the early 20th century following the breakthrough discoveries in microbiology and immunology of the late 1800s. The 20th century, with its major and minor wars, saw the research and development of biological weapons capable of immense destruction of life, which were used both by nations in preparation for military warfare and by individuals who engage in asymmetric warfare. Treaties, international agreements, and political pursuits have not been able either to control or to rid the world of bioweapons. The tools for specific defense against bioweapons consist of vaccines against both viruses and bacteria, and of antibiotics and drugs against bacteria. Vaccines and antimicrobials are of limited usefulness because of the large number of possible microbes that can be used for weapons, because of antimicrobial resistance to drugs and antibiotics, and because of limitations in technical feasibility for developing vaccines and antibacterials against certain of the agents. Induction of non-specific innate immunity by immunostimulatory vaccines (at one time licensed) needs to be explored for possible immunoprophylactic-therapeutic activity when administered immediately following exposure to bioweapon pathogens. The ideal solution to the bioweapons problem lies in measures to end their development and application throughout the world. Emphasis was made at the recent World Economic Forum of the need to end poverty and hunger in the world as a means to reduce the incentive to engage in warfare. Added to this is betterment of health, focused mainly on preventable diseases. A further solution to the problem may lie in the development of modern robotic systems for rapid forensic detection of development and production of bioweapons by "rogue" nations and even by individuals. This review deals with the specifics of the development of bioweapons and their control by vaccines, by therapy with antibacterials, by non

Anthrax vaccines: present status and future prospects.

PubMed

Kaur, Manpreet; Singh, Samer; Bhatnagar, Rakesh

2013-08-01

The management of anthrax remains a top priority among the biowarfare/bioterror agents. It was the Bacillus anthracis spore attack through the US mail system after the September 11, 2001, terrorist attacks in the USA that highlighted the potential of B. anthracis as a bioterrorism agent and the threat posed by its deliberate dissemination. These attacks invigorated the efforts toward understanding the anthrax pathogenesis and development of more comprehensive medical intervention strategies for its containment in case of both natural disease and manmade, accidental or deliberate infection of a non-suspecting population. Currently, efforts are directed toward the development of safe and efficacious vaccines as well as intervention tools for controlling the disease in the advanced fulminant stage when toxemia has already developed. This work presents an overview of the current understanding of anthrax pathogenesis and recent advances made, particularly after 2001, for the successful management of anthrax and outlines future perspectives.

Not so secret agents: Event-related potentials to semantic roles in visual event comprehension.

PubMed

Cohn, Neil; Paczynski, Martin; Kutas, Marta

2017-12-01

Research across domains has suggested that agents, the doers of actions, have a processing advantage over patients, the receivers of actions. We hypothesized that agents as "event builders" for discrete actions (e.g., throwing a ball, punching) build on cues embedded in their preparatory postures (e.g., reaching back an arm to throw or punch) that lead to (predictable) culminating actions, and that these cues afford frontloading of event structure processing. To test this hypothesis, we compared event-related brain potentials (ERPs) to averbal comic panels depicting preparatory agents (ex. reaching back an arm to punch) that cued specific actions with those to non-preparatory agents (ex. arm to the side) and patients that did not cue any specific actions. We also compared subsequent completed action panels (ex. agent punching patient) across conditions, where we expected an inverse pattern of ERPs indexing the differential costs of processing completed actions asa function of preparatory cues. Preparatory agents evoked a greater frontal positivity (600-900ms) relative to non-preparatory agents and patients, while subsequent completed actions panels following non-preparatory agents elicited a smaller frontal positivity (600-900ms). These results suggest that preparatory (vs. non-) postures may differentially impact the processing of agents and subsequent actions in real time. Copyright © 2017 Elsevier Inc. All rights reserved.

The poultry red mite (Dermanyssus gallinae): a potential vector of pathogenic agents.

PubMed

Valiente Moro, Claire; De Luna, Carlos J; Tod, Alexander; Guy, Jonathan H; Sparagano, Olivier A E; Zenner, Lionel

2009-06-01

The poultry red mite, D. gallinae has been involved in the transmission of many pathogenic agents, responsible for serious diseases both in animals and humans. Nowadays, few effective methods are available to control the ectoparasite in poultry farms. Consequently, this is an emerging problem which must be taken into account to maintain good health in commercial egg production. This paper addresses the vector capacity of the ectoparasite with special emphasis on salmonellae, pathogenic agents responsible for many of the most important outbreaks of food-borne diseases worlwide. It has been experimentally shown that D. gallinae could act as a biological vector of S. enteritidis and natural carriage of these bacteria by the mite on poultry premises has also been reported. It was also found that D. gallinae carried other pathogens such as E. coli, Shigella sp., and Staphylococcus, thus increasing the list of pathogenic agents potentially transmitted by the mite.

Nanoparticles as potential new generation broad spectrum antimicrobial agents.

PubMed

Yah, Clarence S; Simate, Geoffrey S

2015-09-02

The rapid emergence of antimicrobial resistant strains to conventional antimicrobial agents has complicated and prolonged infection treatment and increased mortality risk globally. Furthermore, some of the conventional antimicrobial agents are unable to cross certain cell membranes thus, restricting treatment of intracellular pathogens. Therefore, the disease-causing-organisms tend to persist in these cells. However, the emergence of nanoparticle (NP) technology has come with the promising broad spectrum NP-antimicrobial agents due to their vast physiochemical and functionalization properties. In fact, NP-antimicrobial agents are able to unlock the restrictions experienced by conventional antimicrobial agents. This review discusses the status quo of NP-antimicrobial agents as potent broad spectrum antimicrobial agents, sterilization and wound healing agents, and sustained inhibitors of intracellular pathogens. Indeed, the perspective of developing potent NP-antimicrobial agents that carry multiple-functionality will revolutionize clinical medicine and play a significant role in alleviating disease burden.

Potential production of palm oil-based foaming agent as fire extinguisher of peatlands in Indonesia: Literature review

NASA Astrophysics Data System (ADS)

Subekti, P.; Hambali, E.; Suryani, A.; Suryadarma, P.

2017-05-01

This study aims to analyze the potential aplication of of palm oil-based foaming agent as peat fires fighter in Indonesia. From literature review, it has been known that the foaming agent able to form foam to extinguish fire, wrap and refrigerate the burning peat. It is necessary to develop the production and application of foaming agent in Indonesia because peat fires occur almost every year that caused smoke haze. Potential raw material for the production of environmental friendly foaming agent as foam extinguishing for peat fires in Indonesia aong other is palm oil due to abundant availability, sustainable, and foam product easily degraded in the environment of the burnt areas. Production of foaming agent as fire-fighting in Indonesia is one alternative to reduce the time to control the fire and smog disaster impact. Application of palm oil as a raw material for fire-fighting is contribute to increase the value added and the development of palm oil downstream industry.

The use of marine-derived bioactive compounds as potential hepatoprotective agents

PubMed Central

Nair, Dileep G; Weiskirchen, Ralf; Al-Musharafi, Salma K

2015-01-01

The marine environment may be explored as a rich source for novel drugs. A number of marine-derived compounds have been isolated and identified, and their therapeutic effects and pharmacological profiles are characterized. In the present review, we highlight the recent studies using marine compounds as potential hepatoprotective agents for the treatment of liver fibrotic diseases and discuss the proposed mechanisms of their activities. In addition, we discuss the significance of similar studies in Oman, where the rich marine life provides a potential for the isolation of novel natural, bioactive products that display therapeutic effects on liver diseases. PMID:25500871

Discovery of antitubulin agents with antiangiogenic activity as single entities with multitarget chemotherapy potential.

PubMed

Gangjee, Aleem; Pavana, Roheeth Kumar; Ihnat, Michael A; Thorpe, Jessica E; Disch, Bryan C; Bastian, Anja; Bailey-Downs, Lora C; Hamel, Ernest; Bai, Rouli

2014-05-08

Antiangiogenic agents (AA) are cytostatic, and their utility in cancer chemotherapy lies in their combination with cytotoxic chemotherapeutic agents. Clinical combinations of vascular endothelial growth factor receptor-2 (VEGFR2) inhibitors with antitubulin agents have been particularly successful. We have discovered a novel, potentially important analogue, that combines potent VEGFR2 inhibitory activity (comparable to that of sunitinib) with potent antitubulin activity (comparable to that of combretastatin A-4 (CA)) in a single molecule, with GI50 values of 10(-7) M across the entire NCI 60 tumor cell panel. It potently inhibited tubulin assembly and circumvented the most clinically relevant tumor resistance mechanisms (P-glycoprotein and β-III tubulin expression) to antimicrotubule agents. The compound is freely water-soluble as its HCl salt and afforded excellent antitumor activity in vivo, superior to docetaxel, sunitinib, or Temozolomide, without any toxicity.

An Acoustic Plate Mode Sensor for Biowarfare Toxins, Phase II

DTIC Science & Technology

1997-10-01

Biological agents -- such as bacteria , bacterial toxins and viruses -- must be detected rapidly to allow their neutralization or the quick treatment of...Results were comparable. 16 * r Cyclic voltammetry (CV) studies indicate that the monolayers made with the thiodialkyne, D1, which have been photolyzed...Microprocessor system development is ahead of schedule. Preliminary biosensor data is offered using Y. Pestis. The data indi- cates marginal detection

Biology and preliminary host range assessment of two potential kudzu biological control agents

Treesearch

Matthew J. Fyre; Judith Hough-Goldstein; Jiang-Hua Sun

2007-01-01

Two insect species from China, Gonioctena tredecimmaclliata (Jacoby) (Coleoptera: Chrysomelidae) and Ornatalcides (Mesalcidodes) trifidus (Pascoe) (Coleoptera: Curculionidae), were studied in quarantine in the United States as potential biological control agents for kudzu, Pueraria nwntana variety Zobata (Willd.) Maesen and S. Almeida...

Metal-oxo containing polymer nanobeads as potential contrast agents for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Pablico, Michele Huelar

Magnetic resonance imaging (MRI) has greatly revolutionized the way diseases are detected and treated, as it is a non-invasive imaging modality solely based on the interaction of radiowaves and hydrogen nuclei in the presence of an external magnetic field. It is widely used today for the diagnosis of diseases as it offers an efficient method of mapping structure and function of soft tissues in the body. Most MRI examinations utilize paramagnetic materials known as contrast agents, which enhance the MR signal by decreasing the longitudinal (T1) and transverse (T2) relaxation times of the surrounding water protons in biological systems. This results into increased signal intensity differences thereby allowing better interpretation and analysis of pathological tissues. Contrast agents function by lowering the T1 or lowering the T2, resulting into bright and dark contrasts, respectively. The most common MRI contrast agents that are in clinical use today are gadolinium chelates and superparamagnetic iron oxide nanoparticles, both of which have their own advantages in terms of contrast enhancement properties. In the past few years, however, there has been interest in utilizing metal-containing clusters for MRI contrast enhancement as these materials bridge the gap between the constrained structure and magnetic properties of the gadolinium chelates with the superparamagnetic behavior of the iron oxide nanoparticles. Recently, metallic clusters containing Mn and Fe metal centers have received increased attention mainly because of their potential for high spin states and benign nature. In the quest to further develop novel imaging agents, this research has focused on investigating the use of metal-oxo clusters as potential contrast agents for MRI. The primary goal of this project is to identify clusters that meet the following criteria: high paramagnetic susceptibility, water-soluble, stable, cheap, contain environmentally benign metals, and easily derivatized. This work is

Advances in the Preclinical Study of Some Flavonoids as Potential Antidepressant Agents

PubMed Central

German-Ponciano, León Jesús; Rosas-Sánchez, Gilberto Uriel; Rivadeneyra-Domínguez, Eduardo

2018-01-01

Flavonoids are phenolic compounds found commonly in plants that protect them against the negative effects of environmental insults. These secondary metabolites have been widely studied in preclinical research because of their biological effects, particularly as antioxidant agents. Diverse flavonoids have been studied to explore their potential therapeutic effects in the treatment of disorders of the central nervous system, including anxiety and depression. The present review discusses advances in the study of some flavonoids as potential antidepressant agents. We describe their behavioral, physiological, and neurochemical effects and the apparent mechanism of action of their preclinical antidepressant-like effects. Natural flavonoids produce antidepressant-like effects in validated behavioral models of depression. The mechanism of action of these effects includes the activation of serotonergic, dopaminergic, noradrenergic, and γ-aminobutyric acid-ergic neurotransmitter systems and an increase in the production of neural factors, including brain-derived neurotrophic factor and nerve growth factor. Additionally, alterations in the function of tropomyosin receptor kinase B and activity of the enzyme monoamine oxidase A have been reported. In conclusion, preclinical research supports the potential antidepressant effects of some natural flavonoids, which opens new possibilities of evaluating these substances to develop complementary therapeutic alternatives that could ameliorate symptoms of depressive disorders in humans. PMID:29623232

The Potential of Streptomyces as Biocontrol Agents against the Rice Blast Fungus, Magnaporthe oryzae (Pyricularia oryzae).

PubMed

Law, Jodi Woan-Fei; Ser, Hooi-Leng; Khan, Tahir M; Chuah, Lay-Hong; Pusparajah, Priyia; Chan, Kok-Gan; Goh, Bey-Hing; Lee, Learn-Han

2017-01-01

Rice is a staple food source for more than three billion people worldwide. However, rice is vulnerable to diseases, the most destructive among them being rice blast, which is caused by the fungus Magnaporthe oryzae (anamorph Pyricularia oryzae ). This fungus attacks rice plants at all stages of development, causing annual losses of approximately 10-30% in various rice producing regions. Synthetic fungicides are often able to effectively control plant diseases, but some fungicides result in serious environmental and health problems. Therefore, there is growing interest in discovering and developing new, improved fungicides based on natural products as well as introducing alternative measures such as biocontrol agents to manage plant diseases. Streptomyce s bacteria appear to be promising biocontrol agents against a wide range of phytopathogenic fungi, which is not surprising given their ability to produce various bioactive compounds. This review provides insight into the biocontrol potential of Streptomyces against the rice blast fungus, M. oryzae . The ability of various S treptomyces spp. to act as biocontrol agents of rice blast disease has been studied by researchers under both laboratory and greenhouse/growth chamber conditions. Laboratory studies have shown that Streptomyces exhibit inhibitory activity against M. oryzae . In greenhouse studies, infected rice seedlings treated with Streptomyces resulted in up to 88.3% disease reduction of rice blast. Studies clearly show that Streptomyces spp. have the potential to be used as highly effective biocontrol agents against rice blast disease; however, the efficacy of any biocontrol agent may be affected by several factors including environmental conditions and methods of application. In order to fully exploit their potential, further studies on the isolation, formulation and application methods of Streptomyces along with field experiments are required to establish them as effective biocontrol agents.

The Potential of Streptomyces as Biocontrol Agents against the Rice Blast Fungus, Magnaporthe oryzae (Pyricularia oryzae)

PubMed Central

Law, Jodi Woan-Fei; Ser, Hooi-Leng; Khan, Tahir M.; Chuah, Lay-Hong; Pusparajah, Priyia; Chan, Kok-Gan; Goh, Bey-Hing; Lee, Learn-Han

2017-01-01

Rice is a staple food source for more than three billion people worldwide. However, rice is vulnerable to diseases, the most destructive among them being rice blast, which is caused by the fungus Magnaporthe oryzae (anamorph Pyricularia oryzae). This fungus attacks rice plants at all stages of development, causing annual losses of approximately 10–30% in various rice producing regions. Synthetic fungicides are often able to effectively control plant diseases, but some fungicides result in serious environmental and health problems. Therefore, there is growing interest in discovering and developing new, improved fungicides based on natural products as well as introducing alternative measures such as biocontrol agents to manage plant diseases. Streptomyces bacteria appear to be promising biocontrol agents against a wide range of phytopathogenic fungi, which is not surprising given their ability to produce various bioactive compounds. This review provides insight into the biocontrol potential of Streptomyces against the rice blast fungus, M. oryzae. The ability of various Streptomyces spp. to act as biocontrol agents of rice blast disease has been studied by researchers under both laboratory and greenhouse/growth chamber conditions. Laboratory studies have shown that Streptomyces exhibit inhibitory activity against M. oryzae. In greenhouse studies, infected rice seedlings treated with Streptomyces resulted in up to 88.3% disease reduction of rice blast. Studies clearly show that Streptomyces spp. have the potential to be used as highly effective biocontrol agents against rice blast disease; however, the efficacy of any biocontrol agent may be affected by several factors including environmental conditions and methods of application. In order to fully exploit their potential, further studies on the isolation, formulation and application methods of Streptomyces along with field experiments are required to establish them as effective biocontrol agents. PMID:28144236

The acquisition of dangerous biological materials: Technical facts sheets to assist risk assessments of 46 potential BW agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aceto, Donato Gonzalo; Astuto-Gribble, Lisa M.; Gaudioso, Jennifer M.

Numerous terrorist organizations have openly expressed interest in producing and deploying biological weapons. However, a limiting factor for many terrorists has been the acquisition of dangerous biological agents, as evidenced by the very few successful instances of biological weapons use compared to the number of documented hoaxes. Biological agents vary greatly in their ability to cause loss of life and economic damage. Some agents, if released properly, can kill many people and cause an extensive number of secondary infections; other agents will sicken only a small number of people for a short period of time. Consequently, several biological agents canmore » potentially be used to perpetrate a bioterrorism attack but few are likely capable of causing a high consequence event. It is crucial, from a US national security perspective, to more deeply understand the likelihood that terrorist organizations can acquire the range of these agents. Few studies have attempted to comprehensively compile the technical information directly relevant to the acquisition of dangerous bacteria, viruses and toxins. In this report, technical fact sheets were assembled for 46 potentially dangerous biological agents. Much of the information was taken from various research sources which could ultimately and significantly expedite and improve bioterrorism threat assessments. By systematically examining a number of specific agent characteristics included in these fact sheets, it may be possible to detect, target, and implement measures to thwart future terrorist acquisition attempts. In addition, the information in these fact sheets may be used as a tool to help laboratories gain a rudimentary understanding of how attractive a method laboratory theft is relative to other potential acquisition modes.« less

The emerging impact of genomics on the development of biological weapons. Threats and benefits posed by engineered extremophiles.

PubMed

Daly, M J

2001-09-01

During the past decades, representatives of Archaea, Bacteria, and Protista have been found thriving in many newly discovered extremely hostile habitats, which hitherto were regarded as too harsh to harbor life. To illustrate how an extremophile could be targeted for development as a biowarfare agent, an example is presented describing current advances in engineering Deinococcus radiodurans. Using a generally applicable combination of conventional genetic engineering and genomic informatics, this extremely radiation-resistant and environmentally robust bacterium is being developed for biotechnology.

Potential of Neoactinolaimus as a biological control agent of root-knot and reniform nematodes

USDA-ARS?s Scientific Manuscript database

The predatory nematode Neoactinolaimus spp. (family Actinolaimidae) was examined as a potential biological control agent against root-knot (Meloidogyne spp.) and reniform (Rotylenchulus reniformis) nematodes in laboratory conditions. Neoactinolaimus possesses a large odontostylet to puncture the cu...

Bioluminescent magnetic nanoparticles as potential imaging agents for mammalian spermatozoa.

PubMed

Vasquez, Erick S; Feugang, Jean M; Willard, Scott T; Ryan, Peter L; Walters, Keisha B

2016-03-17

Nanoparticles have emerged as key materials for developing applications in nanomedicine, nanobiotechnology, bioimaging and theranostics. Existing bioimaging technologies include bioluminescent resonance energy transfer-conjugated quantum dots (BRET-QDs). Despite the current use of BRET-QDs for bioimaging, there are strong concerns about QD nanocomposites containing cadmium which exhibits potential cellular toxicity. In this study, bioluminescent composites comprised of magnetic nanoparticles and firefly luciferase (Photinus pyralis) are examined as potential light-emitting agents for imaging, detection, and tracking mammalian spermatozoa. Characterization was carried out using infrared spectroscopy, TEM and cryo-TEM imaging, and ζ-potential measurements to demonstrate the successful preparation of these nanocomposites. Binding interactions between the synthesized nanoparticles and spermatozoon were characterized using confocal and atomic/magnetic force microscopy. Bioluminescence imaging and UV-visible-NIR microscopy results showed light emission from sperm samples incubated with the firefly luciferase-modified nanoparticles. Therefore, these newly synthesized luciferase-modified magnetic nanoparticles show promise as substitutes for QD labeling, and can potentially also be used for in vivo manipulation and tracking, as well as MRI techniques. These preliminary data indicate that luciferase-magnetic nanoparticle composites can potentially be used for spermatozoa detection and imaging. Their magnetic properties add additional functionality to allow for manipulation, sorting, or tracking of cells using magnetic techniques.

Marine Diterpenoids as Potential Anti-Inflammatory Agents

PubMed Central

González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E.; Fernandez, Patricia L.

2015-01-01

The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

A review of the possible mechanisms of action of tocotrienol - a potential antiosteoporotic agent.

PubMed

Chin, Kok-Yong; Mo, Huanbiao; Soelaiman, Ima-Nirwana

2013-12-01

Osteoporosis is posing a tremendous healthcare problem globally. Much effort has been invested in finding novel antiosteoporotic agents to stop the progression of this disease. Tocotrienol, one of the isoforms of vitamin E, is poised as a potential antiosteoporotic agent. Previous studies showed that tocotrienol as a single isomer or as a mixture demonstrated both anabolic and antiresorptive effects in various rodent models of osteoporosis. In vitro experiments further demonstrated that tocotrienol could up-regulate genes related to osteoblastogenesis and modify receptor activator of nuclear factor kappa B signaling against osteoclastogenesis. Additionally, tocotrienol was also shown to be a strong 3- hydroxy-3-methyl-glutaryl-CoA reductase down-regulator with a mechanism different from that of statins. Inhibition of the mevalonate pathway affects both osteoblast and osteoclast formation in favor of the former. Tocopherol, a more commonly used isoform of vitamin E does not possess similar effects. Tocotrienol is also a potent antioxidant. It can scavenge free radicals and prevent oxidative damage on osteoblast thus promoting its survival. It may also up-regulate the antioxidant defense network in osteoclast and indirectly act against free radical signaling essential in osteoclastogenesis. The effects of tocotrienol on Wnt/β-catenin signaling essential in osteoblastogenesis have not been determined. More mechanistic studies need to be conducted to illustrate the antiosteoporotic effects of tocotrienol. Clinical trials are also required to confirm its effects in humans. In conclusion, tocotrienol demonstrates great potential as an antiosteoporotic agent and much research effort should be invested to develop it as an agent to curb osteoporosis.

Plague.

PubMed

Lazarus, Angeline A; Decker, Catherine F

2004-03-01

In the United States, plague poses a threat to humans from the infected animals in the endemic areas of the Western states. Plague may also be used in the near future as an agent of warfare or terrorism. Although the presentation of bubonic plague may be less of a problem, the septicemic and pneumonic forms present challenges to early diagnosis and prompt treatment. The major threat of plague as an agent of terrorism will probably be through the inhalational route. which could result in many cases of the pneumonic form, requiring early recognition and initiation of appropriate therapy. In a mass-casualty scenario, the clinician should be aware of the potential agents of biowarfare and be familiar with the treatment and prophylaxis recommendations outlined by the CDC. It is also prudent to employ universal precautions and respiratory isolation when treating patients with any unknown exposure. In endemic areas, personal protective measures such as use of insecticides, insect repellants, and prompt prophylaxis in cases of exposure to plague are recommended for reducing the incidence of infection. The author also recommends review of CDC website on bioterrorism (http://www.bt.cdc.gov) to keep informed of plague updates.

Synthesis and mechanistic studies of curcumin analog-based oximes as potential anticancer agents.

PubMed

Qin, Hua-Li; Leng, Jing; Youssif, Bahaa G M; Amjad, Muhammad Wahab; Raja, Maria Abdul Ghafoor; Hussain, Muhammad Ajaz; Hussain, Zahid; Kazmi, Syeda Naveed; Bukhari, Syed Nasir Abbas

2017-09-01

The incidence of cancer can be decreased by chemoprevention using either natural or synthetic agents. Apart from synthetic compounds, numerous natural products have exhibited promising potential to inhibit carcinogenesis in vivo. In this study, α, β-unsaturated carbonyl-based anticancer compounds were used as starting materials to synthesize new oxime analogs. The findings from the antiproliferative assay using seven different human cancer cell lines provided a clear picture of structure-activity relationship. The oxime analogs namely 7a and 8a showed strong antiproliferative activity against the cell lines. The mechanistic effects of compounds on EGFR-TK kinases and tubulin polymerization and BRAF V 600E were investigated. In addition, the efficacy of compounds in reversing the efflux-mediated resistance developed by cancer cells was also studied. The compounds 5a and 6a displayed potent activity on various targets such as BRAF V 600E and EGFR-TK kinases and also exhibited strong antiproliferative activity against different cell lines hence showing potential of multifunctional anticancer agents. © 2017 John Wiley & Sons A/S.

Potential biological control agents for management of cogongrass (Cyperales: Poaceae) in the southeastern USA

USDA-ARS?s Scientific Manuscript database

Cogongrass, Imperata cylindrica (L.) Palisot de Beauvois (Cyperales: Poaceae), is a noxious invasive weed in the southeastern USA. Surveys for potential biological control agents of cogongrass were conducted in Asia and East Africa from 2013 to 2016. Several insect herbivores were found that may hav...

Discovery of wall teichoic acid inhibitors as potential anti-MRSA β-lactam combination agents.

PubMed

Wang, Hao; Gill, Charles J; Lee, Sang H; Mann, Paul; Zuck, Paul; Meredith, Timothy C; Murgolo, Nicholas; She, Xinwei; Kales, Susan; Liang, Lianzhu; Liu, Jenny; Wu, Jin; Santa Maria, John; Su, Jing; Pan, Jianping; Hailey, Judy; Mcguinness, Debra; Tan, Christopher M; Flattery, Amy; Walker, Suzanne; Black, Todd; Roemer, Terry

2013-02-21

Innovative strategies are needed to combat drug resistance associated with methicillin-resistant Staphylococcus aureus (MRSA). Here, we investigate the potential of wall teichoic acid (WTA) biosynthesis inhibitors as combination agents to restore β-lactam efficacy against MRSA. Performing a whole-cell pathway-based screen, we identified a series of WTA inhibitors (WTAIs) targeting the WTA transporter protein, TarG. Whole-genome sequencing of WTAI-resistant isolates across two methicillin-resistant Staphylococci spp. revealed TarG as their common target, as well as a broad assortment of drug-resistant bypass mutants mapping to earlier steps of WTA biosynthesis. Extensive in vitro microbiological analysis and animal infection studies provide strong genetic and pharmacological evidence of the potential effectiveness of WTAIs as anti-MRSA β-lactam combination agents. This work also highlights the emerging role of whole-genome sequencing in antibiotic mode-of-action and resistance studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Potentiation of the depression by adenosine of rat cerebral cortical neurones by progestational agents.

PubMed Central

Phillis, J. W.

1986-01-01

The effects of four progestational agents pregnenolone sulphate, cyproterone acetate, norethindrone acetate and progesterone, on adenosine-evoked depression of the firing of rat cerebral cortical neurones have been studied. When applied iontophoretically, pregnenolone sulphate, cyproterone, and norethindrone enhanced the actions of iontophoretically applied adenosine and failed to potentiate the depressant effects of adenosine 5'-N-ethylcarboxamide and gamma-aminobutyric acid. Cyproterone acetate (50 micrograms kg-1) and progesterone (200 micrograms kg-1) administered intravenously enhanced the depressant actions of iontophoretically applied adenosine. When applied by large currents, cyproterone, and less frequently norethindrone, depressed the firing of cerebral cortical neurones. The depressant effects of cyproterone were antagonized by caffeine. Pregnenolone sulphate tended to excite cortical neurones but neither this action, nor its potentiation of adenosine were reproduced by application of sulphate ions. It is hypothesized that some of the psychotropic actions of progestational agents may involve an enhancement of 'purinergic' tone in the central nervous system. PMID:3814905

Opportunities for Web-based Drug Repositioning: Searching for Potential Antihypertensive Agents with Hypotension Adverse Events.

PubMed

Wang, Kejian; Wan, Mei; Wang, Rui-Sheng; Weng, Zuquan

2016-04-01

Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning. We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents. We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs. Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning. We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning.

Plague Vaccines: Status and Future.

PubMed

Sun, Wei

2016-01-01

Three major plague pandemics caused by the gram-negative bacterium Yersinia pestis have killed nearly 200 million people in human history. Due to its extreme virulence and the ease of its transmission, Y. pestis has been used purposefully for biowarfare in the past. Currently, plague epidemics are still breaking out sporadically in most of parts of the world, including the United States. Approximately 2000 cases of plague are reported each year to the World Health Organization. However, the potential use of the bacteria in modern times as an agent of bioterrorism and the emergence of a Y. pestis strain resistant to eight antibiotics bring out severe public health concerns. Therefore, prophylactic vaccination against this disease holds the brightest prospect for its long-term prevention. Here, we summarize the progress of the current vaccine development for counteracting plague.

DNA detection on ultrahigh-density optical fiber-based nanoarrays.

PubMed

Tam, Jenny M; Song, Linan; Walt, David R

2009-04-15

Nanoarrays for DNA detection were fabricated on etched nanofiber bundles based on recently developed techniques for microscale arrays. Two different-sized nanoarrays were created: one with 700 nm feature sizes and a 1 microm center-to-center pitch (approximately 1x10(6) array elements/mm(2)) and one with 300 nm feature sizes and a 500 nm center-to-center pitch (4.6x10(6) array elements/mm(2)). A random, multiplexed array composed of oligonucleotide-functionalized nanospheres was constructed and used for parallel detection and analysis of fluorescently labeled DNA targets. We have used these arrays to detect a variety of target sequences including Bacillus thuringiensis kurstaki and vaccina virus sequences, two potential biowarfare agents, as well as interleukin-2 sequences, an immune system modulator that has been used for the diagnosis of HIV.

High-throughput screening technologies for botulinum neurotoxins.

PubMed

Bompiani, Kristin M; Dickerson, Tobin J

2014-01-01

Botulinum neurotoxins (BoNTs) are a class of bacterial neurotoxins that are the most potent toxic compounds reported to date. Exposure to relatively low concentrations of the toxin protein can result in major muscle paralysis, which may result in death in severe cases. In addition to their role in natural human disease, BoNTs are currently under close scrutiny because of their potential to be used as biowarfare agents. Clinical treatment options for botulism are currently limited, and finite stockpiles of antitoxin exist. In light of current bioterrorist threats, researchers have focused on identifying new molecules that can be applied to either sensitive toxin detection or improved clinical treatment. High-throughput screening (HTS) is a laboratory technique commonly employed to screen large libraries of diverse compounds based on specific compound binding capabilities or function. Here we review existing HTS platforms that have been applied to identify novel BoNT diagnostic or therapeutic agents. HTS platforms for screening antibodies, peptides, small molecules, and aptamers are described, as well as the screening results and current progress of the identified compounds.

Impact of wine manufacturing practice on the occurrence of fining agents with allergenic potential.

PubMed

Deckwart, Marina; Carstens, Carsten; Webber-Witt, Manuella; Schäfer, Volker; Eichhorn, Lisa; Schröter, Franziska; Fischer, Markus; Brockow, Knut; Christmann, Monika; Paschke-Kratzin, Angelika

2014-01-01

Proteinogenic wine fining agents are hidden allergens and could present a risk for consumers with allergies. Therefore, the European Parliament adopted Directive 2003/89/EC amending Directive 2000/13/EC to declare ingredients, contaminations and processing aids that are known to trigger allergic reactions. The Amendment Regulation (EU) 1266/2010 excluded the labelling of wines which are processed with hen's egg and products thereof until 30 June 2012 to get more scientific findings. After 1 July 2012 wine fining agents have to be declared if above 0.25 mg l(-1) (Regulation (EU) 579/2012 in conjunction with article 120 g of Regulation (EU) 1234/2007). The Organisation International de la Vigne et du Vin (OIV) advises this limit of detection (LOD) for potential allergenic residues of proteins. Wine fining agents are processing aids and according to the wine producer's knowledge will be removed after coagulation by filtration or other production steps. Due to lack of scientific data, residues of fining agents in the final product could not be excluded. In this risk assessment, highly sensitive ELISA methods for ovalbumin of known origin for wine have been developed. The objective was to investigate the presence of allergen residues in wine after certain technological treatments were applied to remove the wine fining agents. For all developed ELISA methods the LODs are in the low µg l(-1) range between 5 and 10 µg l(-1) fining agent, whereas the LOQ varies between 5 and 80 µg l(-1) fining agent. The results of the investigation of well-known wines and fining agents demonstrate that white wines fined with white or ovalbumin from hen's egg could retain allergens. The use of certain technological procedures during wine processing leads to different results. In white wine, bentonite or sheet filtration followed by sterile filtration lead to wines containing no detectable amounts of ovalbumin. In red wine, especially the final sterile filtration removes the fining agents.

Mode of Infection of Metarhizium spp. Fungus and Their Potential as Biological Control Agents

PubMed Central

Aw, Kimberly Moon San; Hue, Seow Mun

2017-01-01

Chemical insecticides have been commonly used to control agricultural pests, termites, and biological vectors such as mosquitoes and ticks. However, the harmful impacts of toxic chemical insecticides on the environment, the development of resistance in pests and vectors towards chemical insecticides, and public concern have driven extensive research for alternatives, especially biological control agents such as fungus and bacteria. In this review, the mode of infection of Metarhizium fungus on both terrestrial and aquatic insect larvae and how these interactions have been widely employed will be outlined. The potential uses of Metarhizium anisopliae and Metarhizium acridum biological control agents and molecular approaches to increase their virulence will be discussed. PMID:29371548

PPARγ and Its Ligands: Potential Antitumor Agents in the Digestive System.

PubMed

Shu, Linjing; Huang, Renhuan; Wu, Songtao; Chen, Zhaozhao; Sun, Ke; Jiang, Yan; Cai, Xiaoxiao

2016-01-01

Peroxisome proliferator-activated receptor γ (PPARγ) is a versatile member of the ligand-activated nuclear hormone receptor superfamily of transcription factors, with expression in several different cell lines, especially in the digestive system. After being activated by its ligand, PPARγ can suppress the growth of oral, esophageal, gastric, colorectal, liver, biliary, and pancreatic tumor cells, suggesting that PPARγ ligand is a potential anticancer agent in PPARγ-expressing tumors. This review highlights key advances in understanding the effects of PPARγ ligands in the treatment of tumors in the digestive system.

The fabrication of novel nanobubble ultrasound contrast agent for potential tumor imaging

NASA Astrophysics Data System (ADS)

Xing, Zhanwen; Wang, Jinrui; Ke, Hengte; Zhao, Bo; Yue, Xiuli; Dai, Zhifei; Liu, Jibin

2010-04-01

Novel biocompatible nanobubbles were fabricated by ultrasonication of a mixture of Span 60 and polyoxyethylene 40 stearate (PEG40S) followed by differential centrifugation to isolate the relevant subpopulation from the parent suspensions. Particle sizing analysis and optical microscopy inspection indicated that the freshly generated micro/nanobubble suspension was polydisperse and the size distribution was bimodal with large amounts of nanobubbles. To develop a nano-sized contrast agent that is small enough to leak through tumor pores, a fractionation to extract smaller bubbles by variation in the time of centrifugation at 20g (relative centrifuge field, RCF) was suggested. The results showed that the population of nanobubbles with a precisely controlled mean diameter could be sorted from the initial polydisperse suspensions to meet the specified requirements. The isolated bubbles were stable over two weeks under the protection of perfluoropropane gas. The acoustic behavior of the nano-sized contrast agent was evaluated using power Doppler imaging in a normal rabbit model. An excellent power Doppler enhancement was found in vivo renal imaging after intravenous injection of the obtained nanobubbles. Given the broad spectrum of potential clinical applications, the nano-sized contrast agent may provide a versatile adjunct for ultrasonic imaging enhancement and/or treatment of tumors.

Toxicity potential of disinfection agent in tannery wastewater.

PubMed

Tisler, Tatjana; Zagorc-Koncan, Jana; Cotman, Magda; Drolc, Andreja

2004-09-01

Wastewater from a tannery was investigated using chemical-specific analyses and assessment of the acute toxicity of the whole effluent over a 2-year period. The wastewater samples were overloaded with organic and inorganic compounds, and measured concentrations of the chemical parameters as well as dilution factors estimating acute toxicity, frequently exceeded the permissible limits for the discharge of wastewater from a tannery into the receiving stream. In the later part of the monitoring programme, the toxicity of the samples was significantly increased in comparison to the previous samples. The agent for hide disinfection was assumed to be the reason for the increased toxicity of the wastewater samples, and the extremely high acute and chronic toxicity of the agent to bacteria, algae, daphnids, and fish confirmed this suspicion. The most sensitive species was Daphnia magna; the 48 h EC50 was 0.70 x 10(-5)v/v% and the 21d IC25 was 0.40 x 10(-6)v/v% of the agent. After withdrawal of this highly toxic agent for hide disinfection from the technological process in the tannery, the toxicity of the wastewater declined to the previous level.

Heterapoderopsis bicallosicollis (Coleoptera: Attelabidae): a potential biological control agent for Triadica sebifera.

PubMed

Wang, Yi; Ding, Jianqing; Wheeler, Gregory S; Purcell, Matthew F; Zhang, Guoan

2009-08-01

Native to China, Chinese tallow, Triadica sebifera L. Small (Euphorbiaceae), is an invasive plant in the southeastern United States. The leaf-rolling weevil, Heterapoderopsis bicallosicollis Voss, is a common herbivore attacking this plant in China. To evaluate its potential as a biological control agent of T. sebifera, biology and host specificity of this weevil were studied in China. H. bicallosicollis occurs over a wide, native, geographic range and its immatures successfully develop at 15-35 degrees C, indicating its physiological potential to establish and persist throughout the range of climatic conditions where the target plant grows in the United States. Adults make feeding holes on leaves. Before oviposition, the female makes a sealed leaf roll called a nidus and then lays one to two eggs inside. Eggs, larvae, and pupae develop within nidi, and larvae survive only when they develop inside the nidi. This requirement makes the weevil highly host specific to T. sebifera. In laboratory no-choice tests of 54 species from eight families, adults fed on only 3 plant species, T. sebifera, Sapium chihsinianum S. K. Lee, and Phyllanthus urinaria L. and only oviposited on T. sebifera. These results were confirmed where, in multiple-choice tests, adults only oviposited on T. sebifera. Given that T. sebifera is the only species in the genus Triadica in the United States, the results of this study suggest that H. bicallosicollis is a potential biological control agent of T. sebifera and should be considered to be imported into quarantine in the United States for further tests on native North American species.

[The plague, possible bioterrorist act].

PubMed

Bossi, Philippe; Bricaire, François

2003-05-17

PLAGUE AND BIOWARFARE: Plague is an infection caused by Yersinia pestis. This is a major agent that might be used as a biological weapon. If the bacteria is sprayed, the most frequent clinical form would be pneumonia. If contaminated fleas were used, the bubonic and septicaemic forms would be those observed. Suspicious context A biowarfare act by spraying Y pestis must be suspected when a patient without any risk factors presents with a primary pulmonary form of the disease in a non endemic area. All the patients presenting with a pulmonary form of plague must be hospitalised and isolated in de-pressurised room, at least for the first three days of antibiotherapy. For the other clinical forms, patients must isolated during the first 48 hours of treatment. Treatment must be initiated as rapidly as possible. Strains of Y. pestis are usually sensitive to many antibiotics (streptomycin, gentamicin, doxycycline, ciprofloxacin, chloramphenicol, sulfadiazin, trimethoprime-sulfamethoxazole...). In the case of contact with a spray suspected of containing the plague bacilla, doxycycline or ciprofloxacin can be prescribed. A dead cell vaccine exists, but its efficacy in terms of protection from primary pneumonia appears inadequate.

Chlamydia gallinacea: a widespread emerging Chlamydia agent with zoonotic potential in backyard poultry.

PubMed

Li, L; Luther, M; Macklin, K; Pugh, D; Li, J; Zhang, J; Roberts, J; Kaltenboeck, B; Wang, C

2017-10-01

Chlamydia gallinacea, a new chlamydial agent, has been reported in four European countries as well as Argentina and China. Experimentally infected chickens with C. gallinacea in previous study showed no clinical signs but had significantly reduced gains in body weight (6·5-11·4%). Slaughterhouse workers exposed to infected chickens have developed atypical pneumonia, indicating C. gallinacea is likely a zoonotic agent. In this study, FRET-PCR confirmed that C. gallinacea was present in 12·4% (66/531) of oral-pharyngeal samples from Alabama backyard poultry. Phylogenetic comparisons based on ompA variable domain showed that 16 sequenced samples represented 14 biotypes. We report for the first time the presence of C. gallinacea in North America, and this warrants further research on the organism's pathogenicity, hosts, transmission, and zoonotic potential.

Nitric oxide donors attenuate clongenic potential in rat C6 glioma cells treated with alkylating chemotherapeutic agents.

PubMed

Yang, Jir-Jei; Yin, Jiu-Haw; Yang, Ding-I

2007-05-11

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) kills tumor cells via multiple actions including alkylation and carbamoylation. Previously, we have reported that formation of S-nitrosoglutathione (GSNO) in glioma cells overexpressing inducible nitric oxide synthase (iNOS) contributed to nitric oxide (NO)-dependent carbamoylating chemoresistance against BCNU. To further characterize the effects of NO on alkylating cytotoxicity, colony formation assay was applied to evaluate the effects of various NO donors on rat C6 glioma cells challenged with alkylating agents. We demonstrate that NO donors including GSNO, diethylamine NONOate (DEA/NO), and sodium nitroprusside (SNP) substantially reduced the extent of colony formation in glioma cells treated with alkylating agents, namely methyl methanesulfonate (MMS), N-methyl-N-nitrosourea (MNU), and N-ethyl-N-nitrosourea (ENU). Without alkylating agents these NO-releasing agents alone had no effects on clongenic potential of rat C6 glioma cells. Among these three NO donors used, the effectiveness in potentiating alkylating cytotoxicity is in the order of "GSNO>DEA/NO>SNP" when applied at the same dosages. GSNO also exerted similar synergistic actions reducing the extents of colony formation when co-administrated with 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-hydrazine (compound #1), another alkylating agent that mimics the chloroethylating action of BCNU. Together with our previous findings, we propose that NO donors may be used as adjunct chemotherapy with alkylating agents for such malignant brain tumors as glioblastoma multiforme (GBM). In contrast, production of NO as a result of iNOS induction, such as that occurring after surgical resection of brain tumors, may compromise the efficacy of carbamoylating chemotherapy.

Antioxidants as potential medical countermeasures for chemical warfare agents and toxic industrial chemicals.

PubMed

McElroy, Cameron S; Day, Brian J

2016-01-15

The continuing horrors of military conflicts and terrorism often involve the use of chemical warfare agents (CWAs) and toxic industrial chemicals (TICs). Many CWA and TIC exposures are difficult to treat due to the danger they pose to first responders and their rapid onset that can produce death shortly after exposure. While the specific mechanism(s) of toxicity of these agents are diverse, many are associated either directly or indirectly with increased oxidative stress in affected tissues. This has led to the exploration of various antioxidants as potential medical countermeasures for CWA/TIC exposures. Studies have been performed across a wide array of agents, model organisms, exposure systems, and antioxidants, looking at an almost equally diverse set of endpoints. Attempts at treating CWAs/TICs with antioxidants have met with mixed results, ranging from no effect to nearly complete protection. The aim of this commentary is to summarize the literature in each category for evidence of oxidative stress and antioxidant efficacy against CWAs and TICs. While there is great disparity in the data concerning methods, models, and remedies, the outlook on antioxidants as medical countermeasures for CWA/TIC management appears promising. Copyright © 2015 Elsevier Inc. All rights reserved.

Temozolomide and other potential agents for the treatment of glioblastoma multiforme.

PubMed

Nagasawa, Daniel T; Chow, Frances; Yew, Andrew; Kim, Won; Cremer, Nicole; Yang, Isaac

2012-04-01

This article provides historical and recent perspectives related to the use of temozolomide for the treatment of glioblastoma multiforme. Temozolomide has quickly become part of the standard of care for the modern treatment of stage IV glioblastoma multiforme since its approval in 2005. Yet despite its improvements from previous therapies, median survival remains approximately 15 months, with a 2-year survival rate of 8% to 26%. The mechanism of action of this chemotherapeutic agent, conferred advantages and limitations, treatment resistance and rescue, and potential targets of future research are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Biology of Leptoypha hospita (Hemiptera: Tingidae), a Potential Biological Control Agent of Chinese Privet

Treesearch

Yanzhuo Zhang; James L. Hanula; Scott Horn; Kristine Braman; Jianghua Sun

2011-01-01

The biology of Leptoypha hospita Drake et Poor (Hemiptera: Tingidae), a potential biological control agent from China for Chinese privet, Ligustrum sinense Lour., was studied in quarantine in the United States. Both nymphs and adults feed on Chinese privet mesophyll cells that lead to a bleached appearance of leaves and dieback of branch tips. L. hospita has five...

Methods for neutralizing anthrax or anthrax spores

DOEpatents

Sloan, Mark A; Vivekandanda, Jeevalatha; Holwitt, Eric A; Kiel, Johnathan L

2013-02-26

The present invention concerns methods, compositions and apparatus for neutralizing bioagents, wherein bioagents comprise biowarfare agents, biohazardous agents, biological agents and/or infectious agents. The methods comprise exposing the bioagent to an organic semiconductor and exposing the bioagent and organic semiconductor to a source of energy. Although any source of energy is contemplated, in some embodiments the energy comprises visible light, ultraviolet, infrared, radiofrequency, microwave, laser radiation, pulsed corona discharge or electron beam radiation. Exemplary organic semiconductors include DAT and DALM. In certain embodiments, the organic semiconductor may be attached to one or more binding moieties, such as an antibody, antibody fragment, or nucleic acid ligand. Preferably, the binding moiety has a binding affinity for one or more bioagents to be neutralized. Other embodiments concern an apparatus comprising an organic semiconductor and an energy source. In preferred embodiments, the methods, compositions and apparatus are used for neutralizing anthrax spores.

Biomedical potentials of crown ethers: prospective antitumor agents.

PubMed

Kralj, Marijeta; Tusek-Bozić, Ljerka; Frkanec, Leo

2008-10-01

Crown ethers are of enormous interest and importance in chemistry, biochemistry, materials science, catalysis, separation, transport and encapsulated processes, as well as in the design and synthesis of various synthetic systems with specific properties, diverse capabilities, and programmable functions. Classical crown ethers are macrocyclic polyethers that contain 3-20 oxygen atoms separated from each other by two or more carbon atoms. They are exceptionally versatile in selectively binding a range of metal ions and a variety of organic neutral and ionic species. Crown ethers are currently being studied and used in a variety of applications beyond their traditional place in chemistry. This review presents additional applications and the ever-increasing biomedical potentials of these intriguing compounds, with particular emphasis on the prospects of their relevance as anticancer agents. We believe that further research in this direction should be encouraged, as crown compounds could either induce toxicities that are different from those of conventional antitumor drugs, or complement drugs in current use, thereby providing a valuable adjunct to therapy.

Activation of the chemosensing transient receptor potential channel A1 (TRPA1) by alkylating agents.

PubMed

Stenger, Bernhard; Zehfuss, Franziska; Mückter, Harald; Schmidt, Annette; Balszuweit, Frank; Schäfer, Eva; Büch, Thomas; Gudermann, Thomas; Thiermann, Horst; Steinritz, Dirk

2015-09-01

The transient receptor potential ankyrin 1 (TRPA1) cation channel is expressed in different tissues including skin, lung and neuronal tissue. Recent reports identified TRPA1 as a sensor for noxious substances, implicating a functional role in the molecular toxicology. TRPA1 is activated by various potentially harmful electrophilic substances. The chemical warfare agent sulfur mustard (SM) is a highly reactive alkylating agent that binds to numerous biological targets. Although SM is known for almost 200 years, detailed knowledge about the pathophysiology resulting from exposure is lacking. A specific therapy is not available. In this study, we investigated whether the alkylating agent 2-chloroethyl-ethylsulfide (CEES, a model substance for SM-promoted effects) and SM are able to activate TRPA1 channels. CEES induced a marked increase in the intracellular calcium concentration ([Ca(2+)]i) in TRPA1-expressing but not in TRPA1-negative cells. The TRP-channel blocker AP18 diminished the CEES-induced calcium influx. HEK293 cells permanently expressing TRPA1 were more sensitive toward cytotoxic effects of CEES compared with wild-type cells. At low CEES concentrations, CEES-induced cytotoxicity was prevented by AP18. Proof-of-concept experiments using SM resulted in a pronounced increase in [Ca(2+)]i in HEK293-A1-E cells. Human A549 lung epithelial cells, which express TRPA1 endogenously, reacted with a transient calcium influx in response to CEES exposure. The CEES-dependent calcium response was diminished by AP18. In summary, our results demonstrate that alkylating agents are able to activate TRPA1. Inhibition of TRPA1 counteracted cellular toxicity and could thus represent a feasible approach to mitigate SM-induced cell damage.

Chemical warfare agents.

PubMed

Kuca, Kamil; Pohanka, Miroslav

2010-01-01

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

Heparin Oligosaccharides as Potential Therapeutic Agents in Senile Dementia

PubMed Central

Ma, Qing; Cornelli, Umberto; Hanin, Israel; Jeske, Walter P.; Linhardt, Robert J.; Walenga, Jeanine M.; Fareed, Jawed; Lee, John M.

2014-01-01

Heparin is a glycosaminoglycan mixture currently used in prophylaxis and treatment of thrombosis. Heparin possesses non-anticoagulant properties, including modulation of various proteases, interactions with fibroblast growth factors, and anti-inflammatory actions. Senile dementia of Alzheimer’s type is accompanied by inflammatory responses contributing to irreversible changes in neuronal viability and brain function. Vascular factors are also involved in the pathogenesis of senile dementia. Inflammation, endogenous proteoglycans, and assembly of senile plagues and neurofibrillary tangles contribute directly and indirectly to further neuronal damage. Neuron salvage can be achieved by anti-inflammation and the competitive inhibition of proteoglycans accumulation. The complexity of the pathology of senile dementia provides numerous potential targets for therapeutic interventions designed to modulate inflammation and proteoglycan assembly. Heparin and related oligosaccharides are known to exhibit anti-inflammatory effects as well as inhibitory effects on proteoglycan assembly and may prove useful as neuroprotective agents. PMID:17504153

Pharmacokinetics of cotinine in rats: a potential therapeutic agent for disorders of cognitive function

PubMed Central

Li, Pei; Beck, Wayne D.; Callahan, Patrick M.; Terry, Alvin V.; Bartlett, Michael G.

2016-01-01

Background Attention has been paid to cotinine (COT), one of the major metabolites of nicotine (NIC), for its pro-cognitive effects and potential therapeutic activities against Alzheimer's Disease (AD) and other types of cognitive impairment. In order to facilitate pharmacological and toxicological studies on COT for its pro-cognitive activities, we conducted a pharmacokinetic (PK) study of COT in rats, providing important oral and intravenously (IV) PK information. Methods In this study, plasma samples were obtained up to 48 hours after COT was dosed to rats orally and IV at a dose of 3 mg/kg. Plasma samples were prepared and analyzed using a sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) bioanalytical method, providing concentration profiles of COT and metabolites after oral and IV administrations. Results The data were fitted into a one-compartment model and a two-compartment model for the oral and IV groups, respectively, providing important PK information for COT including PK profiles, half-life, clearance and bioavailability. The results suggested fast absorption, slow elimination and high bioavailability of COT in rats. Conclusions Several important facts about the PK properties in rats suggested COT could be a potential pro-cognitive agent. Information about the pharmacokinetics of COT in rats revealed in this study is of great importance for the future studies on COT or potential COT analogues as agents for improving cognition. PMID:25933960

A review of fungal antagonists of powdery mildews and their potential as biocontrol agents.

PubMed

Kiss, Levente

2003-04-01

There are approximately 40 fungal species that have so far been reported as natural antagonists of powdery mildews or have been tested as their potential biocontrol agents. This review summarizes the published data on their identification, taxonomy, ecology, modes of action and biocontrol efficacy. The results obtained with the two products already registered, AQ10 Biofungicide and Sporodex, are also discussed.

Development of a bacteriophage displayed peptide library and biosensor

NASA Astrophysics Data System (ADS)

Chin, Robert C.; Salazar, Noe; Mayo, Michael W.; Villavicencio, Victor I.; Taylor, Richard B.; Chambers, James P.; Valdes, James J.

1996-04-01

A miniaturized, handheld biosensor for identification of hazardous biowarfare agents with high specificity is being developed. An innovative biological recognition system based on bacteriophage displayed peptide receptors will be utilized in conjunction with the miniature biosensor technology being developed. A bacteriophage library has been constructed to provide the artificial receptors. The library can contain millions of bacteriophage with randomly displayed peptide sequences in the phage outer protein coat which act as binding sites for the agents of interest. This library will be used to 'bio-pan' for phages that bind to a number of toxins and infectious agents and can, thus, provide an endless supply of low cost, reliable, specific, and stable artificial receptors. The biosensor instrument will utilize evanescent wave, planar waveguide, far-red dyes, diode laser and miniature circuit technologies for performance and portability.

Sedaxicenes: potential new antifungal ferrocene-based agents?

PubMed

Rubbiani, R; Blacque, O; Gasser, G

2016-04-21

Fungal infections are a group of diseases spread all over the world with an extremely high morbidity. Worryingly, although several pathogenic fungi were found to develop resistance towards traditional therapy, research towards the discovery of novel antimycotic agents is very limited. Considering the promising results obtained with the ferrocene-based drug candidates Ferroquine and Ferrocifen as antimalarial and anticancer drug candidates, respectively, we envisaged derivatizing the organic scaffold of a new broad-spectrum fungicide, namely sedaxane, with a ferrocenyl moiety in order to obtain new metal-based antifungal agents. The new ferrocenyl sedaxane derivatives called herein Sedaxicenes (, and ) were characterized using different analytical techniques and the structures were confirmed by X-ray crystallography. As expected for antimycotic agents, , and were found to have a low or even no toxicity towards human cells (IC50 > 100 μM). Interestingly, while the parent drug did not display any mycotoxicity (EC50 > 100 μM), complex was found to have some antifungal activity with an IC50 value of 43 μM under the same experimental conditions. In order to investigate the possible redox-mediated mode of action of , we synthesized the ruthenocene analogue of , namely . Ruthenocene is known to have a completely different electrochemical behaviour from ferrocene although both the compounds are isostructural. As anticipated, complex was found to induce an increase of the reactive oxygen species level in S. cerevisiae, contrary to its analogue and to the parent compound sedaxane.

Xenon fluorides show potential as fluorinating agents

NASA Technical Reports Server (NTRS)

Chernick, C. L.; Shieh, T. C.; Yang, N. C.

1967-01-01

Xenon fluorides permit the controlled addition of fluorine across an olefinic double bond. They provide a series of fluorinating agents that permit ready separation from the product at a high purity. The reactions may be carried out in the vapor phase.

Rapid, Potentially Automatable, Method Extract Biomarkers for HPLC/ESI/MS/MS to Detect and Identify BW Agents

DTIC Science & Technology

1997-11-01

status can sometimes be reflected in the infectious potential or drug resistance of those pathogens. For example, in Mycobacterium tuberculosis ... Mycobacterium tuberculosis , its antibiotic resistance and prediction of pathogenicity amongst Mycobacterium spp. based on signature lipid biomarkers ...TITLE AND SUBTITLE Rapid, Potentially Automatable, Method Extract Biomarkers for HPLC/ESI/MS/MS to Detect and Identify BW Agents 5a. CONTRACT NUMBER 5b

Animal Venom Peptides: Potential for New Antimicrobial Agents.

PubMed

Primon-Barros, Muriel; José Macedo, Alexandre

2017-01-01

Microbial infections affect people worldwide, causing diseases with significant impact on public health, indicating the need for research and development of new antimicrobial agents. Animal venoms represent a vast and largely unexploited source of biologically active molecules with attractive candidates for the development of novel therapeutics. Venoms consist of complex mixtures of molecules, including antimicrobial peptides (AMPs). Since the discovery of AMPs, they have been studied as promising new antimicrobial drugs. Amongst the remarkable sources of AMPs with known antimicrobial activities are ants, bees, centipedes, cone snails, scorpions, snakes, spiders, and wasps. The antimicrobial tests against bacteria, protozoans, fungi and viruses using 170 different peptides isolated directly from crude venoms or cDNA libraries of venom glands are listed and discussed in this review, as well as hemolytic ativity. The potential of venoms as source of new compounds, including AMPs, is extensively discussed. Currently, there are six FDA-approved drugs and many others are undergoing preclinical and clinical trials. The search for antimicrobial "weapons" makes the AMPs from venoms promising candidates. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Astaxanthin: A Potential Therapeutic Agent in Cardiovascular Disease

PubMed Central

Fassett, Robert G.; Coombes, Jeff S.

2011-01-01

Astaxanthin is a xanthophyll carotenoid present in microalgae, fungi, complex plants, seafood, flamingos and quail. It is an antioxidant with anti-inflammatory properties and as such has potential as a therapeutic agent in atherosclerotic cardiovascular disease. Synthetic forms of astaxanthin have been manufactured. The safety, bioavailability and effects of astaxanthin on oxidative stress and inflammation that have relevance to the pathophysiology of atherosclerotic cardiovascular disease, have been assessed in a small number of clinical studies. No adverse events have been reported and there is evidence of a reduction in biomarkers of oxidative stress and inflammation with astaxanthin administration. Experimental studies in several species using an ischaemia-reperfusion myocardial model demonstrated that astaxanthin protects the myocardium when administered both orally or intravenously prior to the induction of the ischaemic event. At this stage we do not know whether astaxanthin is of benefit when administered after a cardiovascular event and no clinical cardiovascular studies in humans have been completed and/or reported. Cardiovascular clinical trials are warranted based on the physicochemical and antioxidant properties, the safety profile and preliminary experimental cardiovascular studies of astaxanthin. PMID:21556169

Synthesis and biological evaluation of sulfur-containing shikonin oxime derivatives as potential antineoplastic agents.

PubMed

Huang, Guang; Zhao, Hui-Ran; Meng, Qing-Qing; Zhang, Qi-Jing; Dong, Jin-Yun; Zhu, Bao-Quan; Li, Shao-Shun

2018-01-01

As a continuation of our research on developing potent and potentially safe antineoplastic agents, a set of forty five sulfur-containing shikonin oxime derivatives were synthesized and evaluated for their in vitro cytotoxic activity against human colon cancer (HCT-15), gastric carcinoma (MGC-803), liver (Bel7402), breast (MCF-7) cancer cells and human skin fibroblast (HSF) cells. All the synthesized compounds exhibited potent cytotoxic activity selectively towards HCT-15 cells and did not display apparent toxicity to the normal HSF cells, some of which were more or comparatively effective to the parent compound against HCT-15, MGC-803 and Bel7402 cells. The most active agent 9m displayed high potency against human cancer cells with IC 50 ranging from 0.27 ± 0.02 to 9.23 ± 0.12 μM. The structure-activity relationships (SARs) studies suggested that the nature of substituent group in the side chain is important for antitumor potency in vitro. Additionally, nitric oxide release studies revealed that the amount of nitric oxide generated from these oxime derivatives was relatively low. Furthermore, cellular mechanism investigations indicated that compound 9m could arrest cell cycle at G1 phase and induce a strong apoptotic response in HCT-15 cells. Moreover, western blot studies revealed that compound 9m induced apoptosis through the down-regulation of Bcl-2 and up-regulation of Bax, caspase 3 and 9. For all these reasons, compound 9m hold promising potential as antineoplastic agent. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

An albumin-based gold nanocomposites as potential dual mode CT/MRI contrast agent

NASA Astrophysics Data System (ADS)

Zhao, Wenjing; Chen, Lina; Wang, Zhiming; Huang, Yuankui; Jia, Nengqin

2018-02-01

In pursuit of the biological detection applications, recent years have witnessed the prosperity of novel multi-modal nanoprobes. In this study, biocompatible bovine serum albumin (BSA)-coated gold nanoparticles (Au NPs) containing Gd (III) as the contrast agent for both X-ray CT and T1-weighted MR imaging is reported. Firstly, the Au NPs with BSA coating (Au@BSA) was prepared through a moderate one-pot reduction route in the presence of hydrazine hydrate as reducer. Sequentially, the BSA coating enables modification of diethylenetriaminepentaacetic acid (DTPA) as well as targeting reagent hyaluronic acid (HA), and further chelation of Gd (III) ions led to the formation of biomimetic nanoagent HA-targeted Gd-Au NPs (HA-targeted Au@BSA-Gd-DTPA). Several techniques were used to thoroughly characterize the formed HA-targeted Gd-Au NPs. As expected, the as-prepared nanoagent with mean diameter of 13.82 nm exhibits not only good colloid stablility and water dispersibility, but also satisfying low cytotoxicity and hemocompatibility in the tested concentration range. Additionally, for the CT phantoms, the obtained nanocomplex shows an improved contrast in CT scanning than that of Au@BSA as well as small molecule iodine-based CT contrast agents such as iopromide. Meanwhile, for the T1-weighted MRI images, there is a linear increase of contrast with concentration of Gd for the two cases of HA-targeted Gd-Au NPs and Magnevist. Strikingly, the nanoagent we explored displays a relatively higher r1 relaxivity than that of commercial MR contrast agents. Therefore, this newly constructed nanoagent could be used as contrast agents for synergistically enhanced X-ray CT and MR phantoms, holding promising potential for future biomedical applications.

Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies.

PubMed

Ashraf, Zaman; Bais, Abdul; Manir, Md Maniruzzaman; Niazi, Umar

2015-01-01

A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.

Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies

PubMed Central

Ashraf, Zaman; Bais, Abdul; Manir, Md. Maniruzzaman; Niazi, Umar

2015-01-01

A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents. PMID:26267242

Proton Relaxivity and Magnetic Hyperthermia Evaluation of Gadolinium Doped Nickel Ferrite Nanoparticles as Potential Theranostic Agents.

PubMed

Yadavalli, Tejabhiram; Raja, Paradeep; Ramaswamy, Shivaraman; Chandrasekharan, Gopalakrishnan; Chennakesavulu, Ramasamy

2017-02-01

This paper outlines the preparation of gadolinium doped nickel ferrite nanoparticles as potential magnetic carriers and longitudinal magnetic resonance imaging contrast agents using hydrothermal method with gadolinium concentration varying from 10% to 40%. A concise effect on the crystal structure was observed at 10% and 20% gadolinium doping, while gadolinium oxide was observed to leach at concentrations exceeding 20%. Further, gadolinium doped nickel ferrites were analyzed for their morphological, magnetic, proton relaxation and magnetic hyperthermia heating properties to understand their potential role as magnetic carrier agents. Low temperature and room temperature magnetic studies conducted on the samples showed comparatively high magnetic saturation with low remanent magnetization. Further, relaxometry studies revealed a high relaxation rate of 6.63 s−1 at a concentration of 0.1 mg/mL. Magnetic hyperthermia studies of the samples at a concentration of 1 mg/mL, assessed that the samples attained a temperature of 68 °C in 240 seconds.

Fabricating PFPE Membranes for Microfluidic Valves and Pumps

NASA Technical Reports Server (NTRS)

Greer, Frank; White, Victor E.; Lee, Michael C.; Willis, Peter A.; Grunthaner, Frank J.; Rolland, Jason; Rolland, Jason

2009-01-01

A process has been developed for fabricating membranes of a perfluoropolyether (PFPE) and integrating them into valves and pumps in laboratory-on-achip microfluidic devices. Membranes of poly(tetrafluoroethylene) [PTFE] and poly(dimethylsilane) [PDMS] have been considered for this purpose and found wanting. By making it possible to use PFPE instead of PTFE or PDMS, the present process expands the array of options for further development of microfluidic devices for diverse applications that could include detection of biochemicals of interest, detection of toxins and biowarfare agents, synthesis and analysis of proteins, medical diagnosis, and synthesis of fuels.

ZMappTM Reinforces the Airway Mucosal Barrier Against Ebola Virus.

PubMed

Yang, Bing; Schaefer, Alison; Wang, Ying-Ying; McCallen, Justin; Lee, Phoebe; Newby, Jay M; Arora, Harendra; Kumar, Priya A; Zeitlin, Larry; Whaley, Kevin J; McKinley, Scott A; Fischer, William A; Harit, Dimple; Lai, Samuel K

2018-04-24

Filoviruses, including Ebola, have the potential to be transmitted via virus-laden droplets deposited onto mucus membranes. Protecting against such emerging pathogens will require understanding how they may transmit at mucosal surfaces and developing strategies to reinforce the airway mucus barrier.Here, we prepared Ebola pseudovirus (with Zaire strain glycoproteins) and employed high resolution multiple particle tracking to track the motions of hundreds of individual pseudoviruses in fresh and undiluted human airway mucus isolated from extubated endotracheal tubes.We found that Ebola pseudovirus readily penetrate human airway mucus. Addition of ZMappTM, a cocktail of Ebola-binding IgG antibodies, effectively reduced mobility of Ebola pseudovirus in the same mucus secretions. Topical delivery of ZMappTM to the mouse airways also facilitated rapid elimination of Ebola pseudovirus.Our work demonstrates that antibodies can immobilize virions in airway mucus and reduce access to the airway epithelium, highlighting topical delivery of pathogen-specific antibodies to the lungs as a potential prophylactic or therapeutic approach against emerging viruses or biowarfare agents.

Mustard vesicating agent-induced toxicity in the skin tissue and silibinin as a potential countermeasure.

PubMed

Tewari-Singh, Neera; Agarwal, Rajesh

2016-06-01

Exposure to the vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) causes severe skin injury with delayed blistering. Depending upon the dose and time of their exposure, edema and erythema develop into blisters, ulceration, necrosis, desquamation, and pigmentation changes, which persist weeks and even years after exposure. Research advances have generated data that have started to explain the probable mechanism of action of vesicant-induced skin toxicity; however, despite these advances, effective and targeted therapies are still deficient. This review highlights studies on two SM analogs, 2-chloroethyl ethyl sulfide (CEES) and NM, and CEES- and NM-induced skin injury mouse models that have substantially added to the knowledge on the complex pathways involved in mustard vesicating agent-induced skin injury. Furthermore, employing these mouse models, studies under the National Institutes of Health Countermeasures Against Chemical Threats program have identified the flavanone silibinin as a novel therapeutic intervention with the potential to be developed as an effective countermeasure against skin injury following exposure to mustard vesicating agents. © 2016 New York Academy of Sciences.

In vitro and In vivo Studies on Stilbene Analogs as Potential Treatment Agents for Colon Cancer

USDA-ARS?s Scientific Manuscript database

Based upon the potential of resveratrol as a cancer chemopreventive agent, 27 stilbenes analogs were synthesized and tested against colon cancer cell line HT-29. Among these compounds, amino derivative (Z)-4-(3,5-dimethoxystyryl) aniline (4), (Z)-methyl 4-(3,5-dimethoxystyryl) benzoate (6) and (Z)-1...

Macromolecular agents with antimicrobial potentialities: A drive to combat antimicrobial resistance.

PubMed

Bilal, Muhammad; Rasheed, Tahir; Iqbal, Hafiz M N; Hu, Hongbo; Wang, Wei; Zhang, Xuehong

2017-10-01

In recent years, the antimicrobial resistance (AMR) or multidrug resistance (MDR) has become a serious health concern and major challenging issue, worldwide. After decades of negligence, the AMR has now captured global attention. The increasing number of antibiotic-resistant strains has threatened the achievements of science and medicine since it inactivates conventional antimicrobial therapeutics. Scientists are trying to respond to AMR/MDR threat by exploring innovative platforms and new therapeutic strategies to tackle infections from these resistant strains and bypass treatment limitations related to these pathologies. The present review focuses on the utilization of bio-inspired novel constructs and their potential applications as novel antimicrobial agents. The first part of the review describes plant-based biological macromolecules containing an immense variety of secondary metabolites, which could be potentially used as alternative strategies to combat antimicrobial resistance. The second part discusses the potential of metal-based macromolecules as effective antimicrobial platforms for preventing infections from resistant strains. The third part comprehensively elucidates how nanoparticles, in particular, metal-integrated nanoparticles can overcome this AMR or MDR issue. Towards the end, information is given with critical concluding remarks, gaps, and finally envisioned with future considerations. Copyright © 2017 Elsevier B.V. All rights reserved.

Single Agents with Designed Combination Chemotherapy Potential: Synthesis and Evaluation of Substituted Pyrimido[4,5-b]indoles as Receptor Tyrosine Kinase and Thymidylate Synthase Inhibitors and as Antitumor Agents

PubMed Central

Gangjee, Aleem; Zaware, Nilesh; Raghavan, Sudhir; Ihnat, Michael; Shenoy, Satyendra; Kisliuk, Roy L.

2010-01-01

Combinations of antiangiogenic agents (AAs) with cytotoxic agents have shown significant promise and several such clinical trials are currently underway. We have designed, synthesized and evaluated two compounds that each inhibit vascular endothelial growth factor receptor-2 (VEGFR-2) and platelet derived growth factor receptor-beta (PDGFR-β) for antiangiogenic effects and also inhibit human thymidylate synthase (hTS) for cytotoxic effects in single agents. The synthesis of these compounds involved the nucleophilic displacement of the common intermediate 5-chloro-9H-pyrimido[4,5-b]indole-2,4-diamine with appropriate benzenethiols. The inhibitory potency of both these single agents against VEGFR-2, PDGFR-β and hTS is better than or close to standards. In a COLO-205 xenograft mouse model one of the analogs significantly decreased tumor growth (TGI = 76% at 35 mg/kg), liver metastases and tumor blood vessels compared to a standard drug and to control and thus demonstrated potent tumor growth inhibition, inhibition of metastasis and antiangiogenic effects in vivo. These compounds afford combination chemotherapeutic potential in single agents. PMID:20092323

[Alkylating agents].

PubMed

Pourquier, Philippe

2011-11-01

With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

Antimicrobial peptides as potential anti-biofilm agents against multidrug-resistant bacteria.

PubMed

Chung, Pooi Yin; Khanum, Ramona

2017-08-01

Bacterial resistance to commonly used drugs has become a global health problem, causing increased infection cases and mortality rate. One of the main virulence determinants in many bacterial infections is biofilm formation, which significantly increases bacterial resistance to antibiotics and innate host defence. In the search to address the chronic infections caused by biofilms, antimicrobial peptides (AMP) have been considered as potential alternative agents to conventional antibiotics. Although AMPs are commonly considered as the primitive mechanism of immunity and has been extensively studied in insects and non-vertebrate organisms, there is now increasing evidence that AMPs also play a crucial role in human immunity. AMPs have exhibited broad-spectrum activity against many strains of Gram-positive and Gram-negative bacteria, including drug-resistant strains, and fungi. In addition, AMPs also showed synergy with classical antibiotics, neutralize toxins and are active in animal models. In this review, the important mechanisms of action and potential of AMPs in the eradication of biofilm formation in multidrug-resistant pathogen, with the goal of designing novel antimicrobial therapeutics, are discussed. Copyright © 2017. Published by Elsevier B.V.

Complete Genome Sequence of Ralstonia solanacearum FJAT-1458, a Potential Biocontrol Agent for Tomato Wilt.

PubMed

Chen, Deju; Liu, Bo; Zhu, Yujing; Wang, Jieping; Chen, Zheng; Che, Jiamei; Zheng, Xuefang; Chen, Xiaoqiang

2017-04-06

An avirulent strain of Ralstonia solanacearum FJAT-1458 was isolated from a living tomato. Here, we report the complete R. solanacearum FJAT-1458 genome sequence of 6,059,899 bp and 5,241 genes. This bacterial strain is a potential candidate as a biocontrol agent in the form of a plant vaccine for bacterial wilt. Copyright © 2017 Chen et al.

A Potential Adjuvant Agent of Chemotherapy: Sepia Ink Polysaccharides

PubMed Central

Li, Fangping; Luo, Ping; Liu, Huazhong

2018-01-01

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. PMID:29597272

Glycosides from Medicinal Plants as Potential Anticancer Agents: Emerging Trends towards Future Drugs.

PubMed

Khan, Haroon; Saeedi, Mina; Nabavi, Seyed Mohammad; Mubarak, Mohammad S; Bishayee, Anupam

2018-04-03

Cancer continues to be a global burden, despite the advancement of various technological and pharmaceutical improvements over the past two decades. Methods for treating cancer include surgery, radiotherapy and chemotherapy in addition to other specialized techniques. On the other hand, medicinal plants have been traditionally employed either as the complementary medicine or dietary agents in the treatment and management of cancer. Medicinal plants are a rich source of secondary metabolites with interesting biological and pharmacological activities. Among these metabolites, glycosides are naturally occurring substances and have outstanding therapeutic potential and clinical utility. Different medical research engines such GoogleScholar, PubMed, SpringerLink, ScienceDirect were used to collect related literature on the subject matter. In this regard, only peer reviewed journals were considered. Emerging results showed that numerous glycosides isolated from various plants possessed marked anticancer activity against a variety of cancer cell lines. Accordingly, the aim of the present review is to shed light on the anticancer effects of glycosides, analyze possible mechanisms of action, and highlight the role of these natural agents as complementary and alternative medicine in combating and managing cancer. The glycosides isolated from different plants demonstrated potent cytotoxic effects against various cancer cell lines in initial preclinical studies. The anticancer effect was mediated through multiple mechanisms; however further detail studies are needed to understand the full potential of glycosides for clinical utility. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Small Scaffolds, Big Potential: Developing Miniature Proteins as Therapeutic Agents.

PubMed

Holub, Justin M

2017-09-01

Preclinical Research Miniature proteins are a class of oligopeptide characterized by their short sequence lengths and ability to adopt well-folded, three-dimensional structures. Because of their biomimetic nature and synthetic tractability, miniature proteins have been used to study a range of biochemical processes including fast protein folding, signal transduction, catalysis and molecular transport. Recently, miniature proteins have been gaining traction as potential therapeutic agents because their small size and ability to fold into defined tertiary structures facilitates their development as protein-based drugs. This research overview discusses emerging developments involving the use of miniature proteins as scaffolds to design novel therapeutics for the treatment and study of human disease. Specifically, this review will explore strategies to: (i) stabilize miniature protein tertiary structure; (ii) optimize biomolecular recognition by grafting functional epitopes onto miniature protein scaffolds; and (iii) enhance cytosolic delivery of miniature proteins through the use of cationic motifs that facilitate endosomal escape. These objectives are discussed not only to address challenges in developing effective miniature protein-based drugs, but also to highlight the tremendous potential miniature proteins hold for combating and understanding human disease. Drug Dev Res 78 : 268-282, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Potential of Biological Agents in Decontamination of Agricultural Soil

PubMed Central

Javaid, Muhammad Kashif; Ashiq, Mehrban; Tahir, Muhammad

2016-01-01

Pesticides are widely used for the control of weeds, diseases, and pests of cultivated plants all over the world, mainly since the period after the Second World War. The use of pesticides is very extensive to control harm of pests all over the globe. Persistent nature of most of the synthetic pesticides causes serious environmental concerns. Decontamination of these hazardous chemicals is very essential. This review paper elaborates the potential of various biological agents in decontamination of agricultural soils. The agricultural crop fields are contaminated by the periodic applications of pesticides. Biodegradation is an ecofriendly, cost-effective, highly efficient approach compared to the physical and chemical methods which are expensive as well as unfriendly towards environment. Biodegradation is sensitive to the concentration levels of hydrogen peroxide and nitrogen along with microbial community, temperature, and pH changes. Experimental work for optimum conditions at lab scale can provide very fruitful results about specific bacterial, fungal strains. This study revealed an upper hand of bioremediation over physicochemical approaches. Further studies should be carried out to understand mechanisms of biotransformation. PMID:27293964

Potential of Biological Agents in Decontamination of Agricultural Soil.

PubMed

Javaid, Muhammad Kashif; Ashiq, Mehrban; Tahir, Muhammad

2016-01-01

Pesticides are widely used for the control of weeds, diseases, and pests of cultivated plants all over the world, mainly since the period after the Second World War. The use of pesticides is very extensive to control harm of pests all over the globe. Persistent nature of most of the synthetic pesticides causes serious environmental concerns. Decontamination of these hazardous chemicals is very essential. This review paper elaborates the potential of various biological agents in decontamination of agricultural soils. The agricultural crop fields are contaminated by the periodic applications of pesticides. Biodegradation is an ecofriendly, cost-effective, highly efficient approach compared to the physical and chemical methods which are expensive as well as unfriendly towards environment. Biodegradation is sensitive to the concentration levels of hydrogen peroxide and nitrogen along with microbial community, temperature, and pH changes. Experimental work for optimum conditions at lab scale can provide very fruitful results about specific bacterial, fungal strains. This study revealed an upper hand of bioremediation over physicochemical approaches. Further studies should be carried out to understand mechanisms of biotransformation.

Technetium glucose complexes as potential cancer imaging agents.

PubMed

Dapueto, Rosina; Aguiar, Rodrigo B; Moreno, María; Machado, Camila M L; Marques, Fabio L N; Gambini, Juan P; Chammas, Roger; Cabral, Pablo; Porcal, Williams

2015-10-01

GLUT's (facilitative glucose transporters) over-expression in tumor cells has allowed the detection of several cancer types, using a glucose analogue ((18)F-FDG) with PET images, worldwide. New glucose analogs radiolabeled with (99m)Tc could be a less-expensive and more accessible alternative for diagnosis using SPECT imaging. d-Glucose ((99m)Tc-IDAG) and 2-d-deoxyglucose ((99m)Tc-AADG) organometallic complexes were proposed and studied as potential (18)F-FDG surrogates. The glucose complexes were prepared and evaluated as potential cancer imaging agents, in a melanoma tumor model. Iminodiacetic acid (IDA) and aminoacetate (AA) moieties were chosen as chelating system for radiolabeling with (99m)Tc. Tumor uptake of the formed complexes was evaluated in B16 murine cell line in vitro and in vivo in melanoma bearing C57BL/6 mice. In vitro and in vivo studies were conducted with (18)F-FDG in order to compare the uptake of (99m)Tc-glucose complexes in the tumor model. IDAG and AADG compounds were synthesized and radiolabeled with (99m)TcO4(-) to obtain the (99m)Tc-IDAG and (99m)Tc-AADG complexes in high yield and stability. In vitro cell studies showed maximum uptake at 60 min for complexes, (99m)Tc-IDAG and (99m)Tc-AADG, with 6% and 2%, respectively. Biodistribution studies showed high tumor uptake one hour post-injection, reaching tumor-to-muscle ratios of 12.1 ± 3.73 and 2.88 ± 1.40 for (99m)Tc-IDAG and (99m)Tc-AADG, respectively. SPECT and micro-SPECT-CT images acquired after the injection of (99m)Tc-IDAG showed accumulation in tumor sites, suggesting that this glucose complex would be a promising candidate for cancer imaging. Copyright © 2015 Elsevier Ltd. All rights reserved.

Protease inhibitors as potential therapeutic agents for AIDS.

PubMed

Jamjoom, G A

1991-09-01

A decade since the epidemic of the acquired immunodeficiency syndrome (AIDS) was first recognized, a wealth of information has accumulated on the molecular biology of the causative agents, the human immunodeficiency viruses (HIV). Of particular interest is knowledge of the viral enzymes involved in the formation of new virus particles. Such enzymes constitute attractive targets for efforts aimed at selecting agents that interfere with virus multiplication and subsequent spread and pathogenesis. Already, several agents that inhibit the viral reverse transcriptase (e.g., nucleoside analogs such as Zidovudine) have proved to have a beneficial effect on the course off the disease, but their prolonged use has been associated with significant toxicity and the emergence of resistant mutants. A second enzyme that has recently attracted attention is the virus-coded protease. This enzyme is involved in the cleavage of viral precursor polyproteins into the final products that constitute the mature virus particle. Protease inhibitors interfere with the process of virus maturation which is required for the formation of infective virus particles. Several custom-made inhibitors with a high selective action against HIV protease have been produced recently. They are nonhydrolyzable peptide analogs that mimic the cleavage sequences of the natural substrate of the enzyme during the transition state of the cleavage reaction. It is hoped that a similar selectivity in vivo may make protease inhibitors a promising new category of AIDS therapeutics.

Synthesis and evaluation of new 3-phenylcoumarin derivatives as potential antidepressant agents.

PubMed

Sashidhara, Koneni V; Rao, K Bhaskara; Singh, Seema; Modukuri, Ram K; Aruna Teja, G; Chandasana, Hardik; Shukla, Shubha; Bhatta, Rabi S

2014-10-15

A series of amine substituted 3-phenyl coumarin derivatives were designed and synthesized as potential antidepressant agents. In preliminary screening, all compounds were evaluated in forced swimming test (FST), a model to screen antidepressant activity in rodents. Among the series, compounds 5c and 6a potentially decreased the immobility time by 73.4% and 79.7% at a low dose of 0.5 mg/kg as compared to standard drug fluoxetine (FXT) which reduced the immobility time by 74% at a dose of 20 mg/kg, ip. Additionally, these active compounds also exhibited significant efficacy in tail suspension test (TST) (another model to screen antidepressant compounds). Interestingly, rotarod and locomotor activity tests confirmed that these two compounds do not have any motor impairment effect and neurotoxicity in mice. Our studies demonstrate that the new 3-phenylcoumarin derivatives may serve as a promising antidepressant lead and hence pave the way for further investigation around this chemical space. Copyright © 2014 Elsevier Ltd. All rights reserved.

Non-aflatoxigenic Aspergillus flavus as potential biocontrol agents to reduce aflatoxin contamination in peanuts harvested in Northern Argentina.

PubMed

Alaniz Zanon, María Silvina; Barros, Germán Gustavo; Chulze, Sofía Noemí

2016-08-16

Biological control is one of the most promising strategies for preventing aflatoxin contamination in peanuts at field stage. A population of 46 native Aspergillus flavus nonaflatoxin producers were analysed based on phenotypic, physiological and genetic characteristics. Thirty-three isolates were characterized as L strain morphotype, 3 isolates as S strain morphotype, and 10 isolates did not produce sclerotia. Only 11 of 46 non-aflatoxigenic isolates did not produce cyclopiazonic acid. The vegetative compatibility group (VCG) diversity index for the population was 0.37. For field trials we selected the non-aflatoxigenic A. flavus AR27, AR100G and AFCHG2 strains. The efficacy of single and mixed inocula as potential biocontrol agents in Northern Argentina was evaluated through a 2-year study (2014-2015). During the 2014 peanut growing season, most of the treatments reduced the incidence of aflatoxigenic strains in both soil and peanut kernel samples, and no aflatoxin was detected in kernels. During the 2015 growing season, there was a reduction of aflatoxigenic strains in kernel samples from the plots treated with the potential biocontrol agents. Reductions of aflatoxin contamination between 78.36% and 89.55% were observed in treated plots in comparison with the un-inoculated control plots. This study provides the first data on aflatoxin biocontrol based on competitive exclusion in the peanut growing region of Northern Argentina, and proposes bioproducts with potential use as biocontrol agents. Copyright © 2016. Published by Elsevier B.V.

Synthetic chalcones as potential anti-inflammatory and cancer chemopreventive agents.

PubMed

Won, Shen-Jeu; Liu, Cheng-Tsung; Tsao, Lo-Ti; Weng, Jing-Ru; Ko, Horng-Huey; Wang, Jih-Pyang; Lin, Chun-Nan

2005-01-01

In an effort to develop potent anti-inflammatory and cancer chemopreventive agents, a series of chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with suitable aromatic aldehyde or prepared with appropriate dihydrochalcone reacted with appropriate alkyl bromide or prepared in one-pot procedure involving acetophenone and convenient aromatic aldehyde using ultrasonic agitation on basic alumina. The synthesized products were tested for their inhibitory effects on the activation of mast cells, neutrophils, macrophages, and microglial cells. The potent inhibitors of NO production in macrophages and microglial cells were further evaluated for their in vitro cytotoxic effects against several human cancer cell lines. 2'-Hydroxychalcones 1-3, and 2',5'-dihydroxychalcone 7 exhibited potent inhibitory effects on the release of beta-glucuronidase or lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB). Two 2'-hydroxychalcones (1 and 3) showed potent inhibitory effects on superoxide anion generation in rat neutrophils in response to fMLP/CB. The previously reported chalcone, 5, 6, and 12, exhibited potent inhibitory effect on NO production in lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma)-activated N9 microglial cells or in LPS-activated RAW 264.7 macrophage-like cells. The potent inhibitors 5, 6, and 12 of NO production in macrophages or microglial cells revealed significant or marginal cytotoxic effects against several human cancer lines. Compound 12 manifested potent selective cytotoxicity against human MCF-7 cells and caused cell death by apoptosis. The present results demonstrated that 1-3, and 7 have anti-inflammatory effects and 5, 6, and 12 are potential anti-inflammatory and cancer chemopreventive agents.

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tewari-Singh, Neera, E-mail: Neera.Tewari-Singh@ucdenver.edu; Jain, Anil K., E-mail: Anil.Jain@ucdenver.edu; Inturi, Swetha, E-mail: Swetha.Inturi@ucdenver.edu

There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and everymore » 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost

Synthesis of C-Pseudonucleosides Bearing Thiazolidin-4-one as a Novel Potential Immunostimulating Agent

PubMed Central

2011-01-01

Several novel C-pseudonucleosides bearing thiazolidin-4-one were synthesized by one-pot three-component condensation using unprotected sugar aldehyde at room temperature, and their effects on T cells, B cells, the cytokine secretion of IL-2, IL-4, and IFN-γ, T cell-associated molecules (CD3, CD4, CD8), and B cell-associated molecules (CD19) were first evaluated. The experimental data demonstrated that such thiazolidin-4-one C-pseudonucleosides hold potential as immunostimulating agents. PMID:24900274

Synthesis of DTPA analogues derived from piperidine and azepane: potential contrast enhancement agents for magnetic resonance imaging.

PubMed

Chong, H S; Garmestani, K; Bryant, L H; Brechbiel, M W

2001-11-16

Two DTPA derivatives (PIP-DTPA and AZEP-DTPA) as potential contrast enhancement agents in MRI are synthesized. The T1 and T2 relaxivities of their corresponding Gd(III) complexes are reported. At clinically relevant field strengths, the relaxivities of the complexes are comparable to that of the contrast agent, Gd(DTPA) which is in clinical use. The serum stability of the (153)Gd-labeled complexes is assessed by measuring the release of (153)Gd from the ligands. The radiolabeled Gd chelates are found to be kinetically stable in human serum for up to at least 14 days without any measurable loss of radioactivity.

Design, synthesis and evaluation of 4-dimethylamine flavonoid derivatives as potential multifunctional anti-Alzheimer agents.

PubMed

Luo, Wen; Wang, Ting; Hong, Chen; Yang, Ya-Chen; Chen, Ying; Cen, Juan; Xie, Song-Qiang; Wang, Chao-Jie

2016-10-21

A new series of 4-dimethylamine flavonoid derivatives were designed and synthesized as potential multifunctional anti-Alzheimer agents. The inhibition of cholinesterase activity, self-induced β-amyloid (Aβ) aggregation, and antioxidant activity by these derivatives was investigated. Most of the compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. A Lineweaver-Burk plot and molecular modeling study showed that these compounds targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. The derivatives showed potent self-induced Aβ aggregation inhibition and peroxyl radical absorbance activity. Moreover, compound 6d significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. Thus, these compounds could become multifunctional agents for further development for the treatment of AD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Comparative evaluation of enamel remineralization potential of processed cheese, calcium phosphate-based synthetic agent, and a fluoride-containing toothpaste: An in situ study.

PubMed

Grewal, Navneet; Gumber, Samita; Kaur, Nirapjeet

2017-01-01

Enamel remineralization potential of variety of products has been established, but there is a lack of evidence of comparison of remineralization potential of natural versus synthetic products. The aim of this study was to compare the enamel remineralization potential of saliva, cheese, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP)-based synthetic agent, and fluoride toothpaste. In situ study was carried out on sixty individuals who wore an intraoral appliance containing demineralized enamel slabs for each agent. One out of six slabs was kept as a control so as to record the baseline values (neither subjected to demineralization nor remineralization). Experimental agents were applied on the designated enamel slabs on day 1, 4, 7, and 10 with a crossover wash out period of 7 days. Quantitative values of mineral content of slab were measured using energy dispersive X-ray and qualitative changes in surface topography of slab were seen under scanning electron microscope at ×20K magnification. Highly significant changes from baseline values were seen in calcium and phosphorus content of slabs treated with cheese and CPP-ACP-based agent whereas levels of fluoride were significantly higher in enamel slabs treated with fluoride-containing toothpaste. Cheese is an organic, economical, and user-friendly option over prescribed synthetic agents. A synergistic effect of fluoride-containing toothpaste with intake of cheese could be a good enamel remineralization protocol.

Screening for potential anti-infective agents towards Burkholderia pseudomallei infection

NASA Astrophysics Data System (ADS)

Eng, Su Anne; Nathan, Sheila

2014-09-01

The established treatment for melioidosis is antibiotic therapy. However, a constant threat to this form of treatment is resistance development of the causative agent, Burkholderia pseudomallei, towards antibiotics. One option to circumvent this threat of antibiotic resistance is to search for new alternative anti-infectives which target the host innate immune system and/or bacterial virulence. In this study, 29 synthetic compounds were evaluated for their potential to increase the lifespan of an infected host. The nematode Caenorhabditis elegans was adopted as the infection model as its innate immune pathways are homologous to humans. Screens were performed in a liquid-based survival assay containing infected worms exposed to individual compounds and survival of untreated and compound-treated worms were compared. A primary screen identified nine synthetic compounds that extended the lifespan of B. pseudomallei-infected worms. Subsequently, a disc diffusion test was performed on these selected compounds to delineate compounds into those that enhanced the survival of worms via antimicrobial activity i.e. reducing the number of infecting bacteria, or into those that did not target pathogen viability. Out of the nine hits selected, two demonstrated antimicrobial effects on B. pseudomallei. Therefore, the findings from this study suggest that the other seven identified compounds are potential anti-infectives which could protect a host against B. pseudomallei infection without developing the risk of drug resistance.

Potential of Pest and Host Phenological Data in the Attribution of Regional Forest Disturbance Detection Maps According to Causal Agent

NASA Technical Reports Server (NTRS)

Spruce, Joseph; Hargrove, William; Norman Steve; Christie, William

2014-01-01

Near real time forest disturbance detection maps from MODIS NDVI phenology data have been produced since 2010 for the conterminous U.S., as part of the on-line ForWarn national forest threat early warning system. The latter has been used by the forest health community to identify and track many regional forest disturbances caused by multiple biotic and abiotic damage agents. Attribution of causal agents for detected disturbances has been a goal since project initiation in 2006. Combined with detailed cover type maps, geospatial pest phenology data offer a potential means for narrowing the candidate causal agents responsible for a given biotic disturbance. U.S. Aerial Detection Surveys (ADS) employ such phenology data. Historic ADS products provide general locational data on recent insect-induced forest type specific disturbances that may help in determining candidate causal agents for MODIS-based disturbance maps, especially when combined with other historic geospatial disturbance data (e.g., wildfire burn scars and drought maps). Historic ADS disturbance detection polygons can show severe and extensive regional forest disturbances, though they also can show polygons with sparsely scattered or infrequent disturbances. Examples will be discussed that use various historic disturbance data to help determine potential causes of MODIS-detected regional forest disturbance anomalies.

Recent progress in the development of anthrax vaccines.

PubMed

Kaur, Manpreet; Bhatnagar, Rakesh

2011-12-01

Bacillus anthracis is the etiological agent of anthrax. Although anthrax is primarily an epizootic disease; humans are at risk for contracting anthrax. The potential use of B. anthracis spores as biowarfare agent has led to immense attention. Prolonged vaccination schedule of current anthrax vaccine and variable protection conferred; often leading to failure of therapy. This highlights the need for alternative anthrax countermeasures. A number of approaches are being investigated to substitute or supplement the existing anthrax vaccines. These relied on expression of Protective antigen (PA), the key protective immunogen; in bacterial or plant systems; or utilization of attenuated strains of B. anthracis for immunization. Few studies have established potential of domain IV of PA for immunization. Other targets including the spore, capsule, S-layer and anthrax toxin components have been investigated for imparting protective immunity. It has been shown that co-immunization of PA with domain I of lethal factor that binds PA resulted in higher antibody responses. Of the epitope based vaccines, the loop neutralizing determinant, in particular; elicited robust neutralizing antibody response and conferred 97% protection upon challenge. DNA vaccination resulted in varying degree of protection and seems a promising approach. Additionally, the applicability of monoclonal and therapeutic antibodies in the treatment of anthrax has also been demonstrated. The recent progress in the direction of anthrax prophylaxis has been evaluated in this review.

Dietary Antioxidants: Potential Anticancer Agents.

PubMed

Wu, Xiayu; Cheng, Jiaoni; Wang, Xu

2017-01-01

There are several extrinsic and intrinsic factors involving reactive oxygen species that play critical roles in tumor development and progression by inducing DNA mutations, genomic instability, and aberrant pro-tumorigenic signaling. There are various essential micronutrients including minerals and vitamins in the diet, which play pivotal roles in maintaining and reinforcing antioxidant performance, affecting the complex network of genes (nutrigenomic approach) and encoding proteins for carcinogenesis. A lot of these antioxidant agents are available as dietary supplements and are predominant worldwide. However, the best antioxidant micronutrient (or a combination of micronutrients) for reducing cancer risks is unknown. The purpose of this review is to survey the literature on modern biological theories of cancer and the roles of dietary antioxidants in cancer. The roles and functions of antioxidant micronutrients, such as vitamin C (ascorbate), vitamin E (alpha-tocopherol), selenium, and vitamin A, provided through diet for the prevention of cancer are discussed in the present work.

Antitumoral, antioxidant, and antimelanogenesis potencies of Hawthorn, a potential natural agent in the treatment of melanoma.

PubMed

Mustapha, Nadia; Mokdad-Bzéouich, Imèn; Maatouk, Mouna; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

2016-06-01

The lack of an efficient agent that does not have the disadvantage of low activity (kojic acid), high cytotoxicity, and mutagenicity (hydroquinone), poor skin penetration (arbutin), or low stability in formulation (glabridin) led us to continue our research on new antipigmentation/skin-lightening agents. Therefore, research of natural products that can modulate the metabolism of pigmentation is of great interest. Otherwise, malignant melanoma is one of the most aggressive forms of skin cancer, with high metastatic potential, and currently, there is no effective chemotherapy against invasive melanoma. Therefore, it is necessary to develop new drugs with potent activity and weak side effects against melanoma. The in-vitro anticancer effect of hawthorn was analyzed against B16F10 melanoma cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of isolated compounds from hawthorn on melanogenesis in B16F10 melanoma cells was investigated by measuring the amounts of melanin and tyrosinase spectrophotometrically at 475 nm. Balb/c mice models inoculated with B16F10 mouse tumor cells were used to evaluate the in-vivo antitumoral potential of hawthorn by assessing its effect on the growth of transplanted tumors. The antioxidant potential of tested samples was evaluated in B16F10 and primary human keratinocyte cells using a cellular antioxidant activity assay. Hawthorn tested samples inhibited effectively the growth of melanoma cells in vitro. Furthermore, it appears that tested samples from hawthorn reduced melanogenesis by inhibiting the tyrosinase activity of B16F10 cells in a dose-dependent manner. In-vivo studies showed that hawthorn total oligomer flavonoids extract treatment at a dose of 150 mg/kg body weight for 21 days in implanted tumor mice resulted in significant inhibition of the tumor growth volume and weight. In addition, tested samples showed significant cellular antioxidant capacity against the reactive oxygen species

Quinazoline derivatives as potential anticancer agents: a patent review (2007 - 2010).

PubMed

Marzaro, Giovanni; Guiotto, Adriano; Chilin, Adriana

2012-03-01

Due to the increase in knowledge about cancer pathways, there is a growing interest in finding novel potential drugs. Quinazoline is one of the most widespread scaffolds amongst bioactive compounds. A number of patents and papers appear in the literature regarding the discovery and development of novel promising quinazoline compounds for cancer chemotherapy. Although there is a progressive decrease in the number of patents filed, there is an increasing number of biochemical targets for quinazoline compounds. This paper provides a comprehensive review of the quinazolines patented in 2007 - 2010 as potential anticancer agents. Information from articles published in international peer-reviewed journals was also included, to give a more exhaustive overview. From about 1995 to 2006, the anticancer quinazolines panorama has been dominated by the 4-anilinoquinazolines as tyrosine kinase inhibitors. The extensive researches conducted in this period could have caused the progressive reduction in the ability to file novel patents as shown in the 2007 - 2010 period. However, the growing knowledge of cancer-related pathways has recently highlighted some novel potential targets for therapy, with quinazolines receiving increasing attention. This is well demonstrated by the number of different targets of the patents considered in this review. The structural heterogeneity in the patented compounds makes it difficult to derive general pharmacophores and make comparisons among claimed compounds. On the other hand, the identification of multi-target compounds seems a reliable goal. Thus, it is reasonable that quinazoline compounds will be studied and developed for multi-target therapies.

Design, synthesis, and biological evaluation of the first podophyllotoxin analogues as potential vascular-disrupting agents.

PubMed

Labruère, Raphaël; Gautier, Benoît; Testud, Marlène; Seguin, Johanne; Lenoir, Christine; Desbène-Finck, Stéphanie; Helissey, Philippe; Garbay, Christiane; Chabot, Guy G; Vidal, Michel; Giorgi-Renault, Sylviane

2010-12-03

We designed and synthesized two novel series of azapodophyllotoxin analogues as potential antivascular agents. A linker was inserted between the trimethoxyphenyl ring E and the tetracyclic ABCD moiety of the 4-aza-1,2-didehydropodophyllotoxins. In the first series, the linker enables free rotation between the two moieties; in the second series, conformational restriction of the E nucleus was considered. We have identified several new compounds with inhibitory activity toward tubulin polymerization similar to that of CA-4 and colchicine, while displaying low cytotoxic activity against normal and/or cancer cells. An aminologue and a methylenic analogue were shown to disrupt endothelial cell cords on Matrigel at subtoxic concentrations, and an original assay of drug washout allowed us to demonstrate the rapid reversibility of this effect. These two new analogues are promising leads for the development of vascular-disrupting agents in the podophyllotoxin series.

Smart phones: platform enabling modular, chemical, biological, and explosives sensing

NASA Astrophysics Data System (ADS)

Finch, Amethist S.; Coppock, Matthew; Bickford, Justin R.; Conn, Marvin A.; Proctor, Thomas J.; Stratis-Cullum, Dimitra N.

2013-05-01

Reliable, robust, and portable technologies are needed for the rapid identification and detection of chemical, biological, and explosive (CBE) materials. A key to addressing the persistent threat to U.S. troops in the current war on terror is the rapid detection and identification of the precursor materials used in development of improvised explosive devices, homemade explosives, and bio-warfare agents. However, a universal methodology for detection and prevention of CBE materials in the use of these devices has proven difficult. Herein, we discuss our efforts towards the development of a modular, robust, inexpensive, pervasive, archival, and compact platform (android based smart phone) enabling the rapid detection of these materials.

Discovery of a Phosphodiesterase 9A Inhibitor as a Potential Hypoglycemic Agent

PubMed Central

2015-01-01

Phosphodiesterase 9 (PDE9) inhibitors have been studied as potential therapeutics for treatment of diabetes and Alzheimer’s disease. Here we report a potent PDE9 inhibitor 3r that has an IC50 of 0.6 nM and >150-fold selectivity over other PDEs. The HepG2 cell-based assay shows that 3r inhibits the mRNA expression of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase. These activities of 3r, together with the reasonable pharmacokinetic properties and no acute toxicity at 1200 mg/kg dosage, suggest its potential as a hypoglycemic agent. The crystal structure of PDE9-3r reveals significantly different conformation and hydrogen bonding pattern of 3r from those of previously published 28s. Both 3r and 28s form a hydrogen bond with Tyr424, a unique PDE9 residue (except for PDE8), but 3r shows an additional hydrogen bond with Ala452. This structure information might be useful for design of PDE9 inhibitors. PMID:25432025

Recent developments in L-asparaginase discovery and its potential as anticancer agent.

PubMed

Shrivastava, Abhinav; Khan, Abdul Arif; Khurshid, Mohsin; Kalam, Mohd Abul; Jain, Sudhir K; Singhal, Pradeep K

2016-04-01

L-Asparaginase (EC3.5.1.1) is an enzyme, which is used for treatment of acute lymphoblastic leukaemia (ALL) and other related blood cancers from a long time. This enzyme selectively hydrolyzes the extracellular amino acid L-asparagine into L-aspartate and ammonia, leading to nutritional deficiencies, protein synthesis inhibition, and ultimately death of lymphoblastic cells by apoptosis. Currently, bacterial asparaginases are used for treatment purpose but offers scepticism due to a number of toxicities, including thrombosis, pancreatitis, hyperglycemia, and hepatotoxicity. Resistance towards bacterial asparaginase is another major disadvantage during cancer management. This situation attracted attention of researchers towards alternative sources of L-asparaginase, including plants and fungi. Present article discusses about potential of L-asparaginase as an anticancer agent, its mechanism of action, and adverse effects related to current asparaginase formulations. This article also provides an outlook for recent developments in L-asparaginase discovery from alternative sources and their potential as a less toxic alternative to current formulations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Triterpenoids as potential agents for the chemoprevention and therapy of breast cancer

PubMed Central

Bishayee, Anupam; Ahmed, Shamima; Brankov, Nikoleta; Perloff, Marjorie

2010-01-01

Breast cancer remains a major cause of death in the United States as well as the rest of the world. In view of the limited treatment options for patients with advanced breast cancer, preventive and novel therapeutic approaches play an important role in combating this disease. The plant-derived triterpenoids, commonly used for medicinal purposes in many Asian countries, posses various pharmacological properties. A large number of triterpenoids are known to exhibit cytotoxicity against a variety of tumor cells as well as anticancer efficacy in preclinical animal models. Numerous triterpenoids have been synthesized by structural modification of natural compounds. Some of these analogs are considered to be the most potent antiinflammatory and anticarcinogenic triterpenoids known. This review examines the potential role of natural triterpenoids and their derivatives in the chemoprevention and treatment of mammary tumors. Both in vitro and in vivo effects of these agents and related molecular mechanisms are presented. Potential challenges and future directions involved in the advancement of these promising compounds in the prevention and therapy of human breast cancer are also identified. PMID:21196213

Rational Discovery of (+) (S) Abscisic Acid as a Potential Antifungal Agent: a Repurposing Approach.

PubMed

Khedr, Mohammed A; Massarotti, Alberto; Mohamed, Maged E

2018-06-04

Fungal infections are spreading widely worldwide, and the types of treatment are limited due to the lack of diverse therapeutic agents and their associated side effects and toxicity. The discovery of new antifungal classes is vital and critical. We discovered the antifungal activity of abscisic acid through a rational drug design methodology that included the building of homology models for fungal chorismate mutases and a pharmacophore model derived from a transition state inhibitor. Ligand-based virtual screening resulted in some hits that were filtered using molecular docking and molecular dynamic simulations studies. Both in silico methods and in vitro antifungal assays were used as tools to select and validate the abscisic acid repurposing. Abscisic acid inhibition assays confirmed the inhibitory effect of abscisic acid on chorismate mutase through the inhibition of phenylpyruvate production. The repositioning of abscisic acid, the well-known and naturally occurring plant growth regulator, as a potential antifungal agent because of its suggested action as an inhibitor to several fungal chorismate mutases was the main result of this work.

Potential of Microbispora sp. V2 as biocontrol agent against Sclerotium rolfsii, the causative agent of southern blight of Zea mays L (Baby corn)--in vitro studies.

PubMed

Patil, N N; Waghmode, M S; Gaikwad, P S; Gajbhiye, M H; Gunjal, A B; Nawani, N N; Kapadnis, B P

2014-11-01

The study was undertaken with the aim of exploring novel and beneficial agro activities of rare actinomycetes like Microbispora sp. V2. The antagonistic activity of Microbispora sp. V2 was evaluated as a biocontrol agents against Sclerotium rolfsii, a soil-borne fungal plant pathogen. The methodology performed for evaluation of biocontrol agent was in vitro evaluation assay which comprised of three tests viz., cellophane overlay technique, seed germination test and Thiram (fungicide) tolerance of Microbispora sp. V2. The isolate was found to inhibit the fungal pathogen Sclerotium rolfsii to 91.43% in cellophane assay. In seed germination assay, Microbispora sp. V2 treated seeds resulted in 25.75% increased germination efficiency, as compared to seeds infected by Sclerotium rolfsii. The isolate Microbispora sp. V2 could tolerate 1000 microg mL(-1) of Thiram (fungicide). The in vitro assay studies proved that Microbispora sp. V2 can be used as antifungal antagonist and thus posses' great potential as biocontrol agent against southern blight caused by Sclerotium rolfsii in Zea mays L (Baby corn) which causes large economical losses.

Novel dual-mode nanobubbles as potential targeted contrast agents for female tumors exploration.

PubMed

Yang, Hengli; Zhou, Tian; Cai, Wenbin; Yi, Xiaomin; Liu, Xi; Wang, Yixiao; Zhang, Li; Duan, Yunyou

2016-10-01

The purpose of this study was to prepare tumor-specific dual-mode nanobubbles as both ultrasound contrast agents (UCAs) and near-infrared fluorescence (NIRF) imaging agents for female tumors. Recent studies have demonstrated the conjugation of anti-tumor ligands on the surface of nanobubbles for use as molecule-targeting ultrasound contrast agents for tumor visualization. However, this complicated procedure has also posed a challenge to nanobubble stability. Thus, in the present study, we combined the fluorescent dye, NIRF IR-780 iodide, which has lipid solubility and tumor-targeting characteristics, with the phospholipid film of nanobubbles that we constructed. We then characterized the physical features of the IR-780-nanobubbles, observed their tumor-targeting capacity in multiple female tumor cell types in vitro, and verified their capability for use in tumor-specific ultrasound contrast imaging and NIRF imaging in vivo. The results showed that the new IR-780-nanobubbles had a uniform nano-size (442.5 ± 48.6 nm) and stability and that they were safe and effective at NIRF imaging and ultrasound imaging in vitro. The IR-780-nanobubbles were found to automatically accumulate on different female tumor cells in vitro with a considerable targeting rate (close to 40 %) but did not accumulate on cardiac muscle cells used as a negative control. Importantly, the IR-780-nanobubbles can detect female tumors precisely via dual-mode imaging in vivo. In conclusion, the new dual-mode IR-780-nanobubbles are stable and have potential advantages in non-invasive tumor-specific detection for female tumors via contrast-enhanced ultrasound and NIRF imaging.

Anabolic agents and bone quality.

PubMed

Sibai, Tarek; Morgan, Elise F; Einhorn, Thomas A

2011-08-01

The definition of bone quality is evolving particularly from the perspective of anabolic agents that can enhance not only bone mineral density but also bone microarchitecture, composition, morphology, amount of microdamage, and remodeling dynamics. This review summarizes the molecular pathways and physiologic effects of current and potential anabolic drugs. From a MEDLINE search (1996-2010), articles were identified by the search terms "bone quality" (1851 articles), "anabolic agent" (5044 articles), "PTH or parathyroid hormone" (32,229 articles), "strontium" or "strontium ranelate" (283 articles), "prostaglandin" (77,539 articles), and "statin" or "statins" (14,233 articles). The search strategy included combining each with the phrase "bone quality." Another more limited search aimed at finding more novel potential agents. Parathyroid hormone is the only US Food and Drug Administration-approved bone anabolic agent in the United States and has been the most extensively studied in in vitro animal and human trials. Strontium ranelate is approved in Europe but has not undergone Food and Drug Administration trials in the United States. All the studies on prostaglandin agonists have used in vivo animal models and there are no human trials examining prostaglandin agonist effects. The advantages of statins include the long-established advantages and safety profile, but they are limited by their bioavailability in bone. Other potential pathways include proline-rich tyrosine kinase 2 (PYK2) and sclerostin (SOST) inhibition, among others. The ongoing research to enhance the anabolic potential of current agents, identify new agents, and develop better delivery systems will greatly enhance the management of bone quality-related injuries and diseases in the future.

Active oligonucleotides incorporating alkylating an agent as potential sequence- and base selective modifier of gene expression.

PubMed

Sasaki, S

2001-04-01

A number of cross-linking (alkylating) agents have been developed and incorporated into the oligonulceotides for sequence selective control of gene expression. Recently, potential application of such active oligonucleotides has been expanding from use for improvement of inhibition efficiency to new biotechnology that may enable chemical alteration of genetic information. These interests in active oligonucleotides have encouraged the generation of new cross-linking agents that exhibit high efficiency for application of either in vitro or in vivo. This mini review summarizes structures of alkylating agents, in particular, a new basic skeleton for cross-linking, a 2'-deoxyribose derivative of 2-amino-6-vinylpurine that has been recently developed by the author's group. The 2-amino-6-vinylpurine has been shown to form a complex with cytidine under acidic conditions, and brings the vinyl and the amino reactive groups into proximity to achieve efficient alkylation. A new strategy was designed so that the reactivity of 2-amino-6-vinylpurine can be induced from the corresponding phenylsulfoxide derivative within a duplex with the complementary strand. The validity of the new strategy has been proven by achievement of cytidine-selective cross-linking with remarkably efficiency.

VIP as a potential therapeutic agent in gram negative sepsis.

PubMed

Ibrahim, Hiba; Barrow, Paul; Foster, Neil

2012-12-01

Gram negative sepsis remains a high cause of mortality and places a great burden on public health finance in both the developed and developing world. Treatment of sepsis, using antibiotics, is often ineffective since pathology associated with the disease occurs due to dysregulation of the immune system (failure to return to steady state conditions) which continues after the bacteria, which induced the immune response, have been cleared. Immune modulation is therefore a rational approach to the treatment of sepsis but to date no drug has been developed which is highly effective, cheap and completely safe to use. One potential therapeutic agent is VIP, which is a natural peptide and is highly homologous in all vertebrates. In this review we will discuss the effect of VIP on components of the immune system, relevant to gram negative sepsis, and present data from animal models. Furthermore we will hypothesise on how these studies could be improved in future and speculate on the possible different ways in which VIP could be used in clinical medicine.

Quercetin and rutin as potential agents antifungal against Cryptococcus spp.

PubMed

Oliveira, V M; Carraro, E; Auler, M E; Khalil, N M

2016-01-01

Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting as cryptococcosis the immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with quercetin or rutin and as a protective of citotoxic effect. The antifungal activity to amphotericin B, quercetin and rutin alone and in combination was determined in Candida sp and Cryptococcus neoformans strains. Cytotoxicity test on erythrocytes was performed by spectrophotometric absorbance of hemoglobin. The amphotericin B MIC was reduced when used in combination with quercetin or rutin to C. neoformans ATCC strain and reduced when combined with rutin to a clinical isolate of C. neoformans. In addition, the combination of quercetin with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that quercetin and rutin are potential agents to combine with amphotericin B in order to reduce the amphotericin dose to lessen side effects and improve antifungal efficacy.

Potential Use of Phenolic Acids as Anti-Candida Agents: A Review

PubMed Central

Teodoro, Guilherme R.; Ellepola, Kassapa; Seneviratne, Chaminda J.; Koga-Ito, Cristiane Y.

2015-01-01

There has been a sharp rise in the occurrence of Candida infections and associated mortality over the last few years, due to the growing body of immunocompromised population. Limited number of currently available antifungal agents, undesirable side effects and toxicity, as well as emergence of resistant strains pose a considerable clinical challenge for the treatment of candidiasis. Therefore, molecules that derived from natural sources exhibiting considerable antifungal properties are a promising source for the development of novel anti-candidal therapy. Phenolic compounds isolated from natural sources possess antifungal properties of interest. Particularly, phenolic acids have shown promising in vitro and in vivo activity against Candida species. However, studies on their mechanism of action alone or in synergism with known antifungals are still scarce. This review attempts to discuss the potential use, proposed mechanisms of action and limitations of the phenolic acids in anti-candidal therapy. PMID:26733965

Honey: A Potential Therapeutic Agent for Managing Diabetic Wounds

PubMed Central

Islam, Md. Asiful; Gan, Siew Hua; Khalil, Md. Ibrahim

2014-01-01

Diabetic wounds are unlike typical wounds in that they are slower to heal, making treatment with conventional topical medications an uphill process. Among several different alternative therapies, honey is an effective choice because it provides comparatively rapid wound healing. Although honey has been used as an alternative medicine for wound healing since ancient times, the application of honey to diabetic wounds has only recently been revived. Because honey has some unique natural features as a wound healer, it works even more effectively on diabetic wounds than on normal wounds. In addition, honey is known as an “all in one” remedy for diabetic wound healing because it can combat many microorganisms that are involved in the wound process and because it possesses antioxidant activity and controls inflammation. In this review, the potential role of honey's antibacterial activity on diabetic wound-related microorganisms and honey's clinical effectiveness in treating diabetic wounds based on the most recent studies is described. Additionally, ways in which honey can be used as a safer, faster, and effective healing agent for diabetic wounds in comparison with other synthetic medications in terms of microbial resistance and treatment costs are also described to support its traditional claims. PMID:25386217

Exposure of hospital operating room personnel to potentially harmful environmental agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sass-Kortsak, A.M.; Purdham, J.T.; Bozek, P.R.

1992-03-01

Epidemiologic studies of risk to reproductive health arising from the operating room environment have been inconclusive and lack quantitative exposure information. This study was undertaken to quantify exposure of operating room (OR) personnel to anesthetic agents, x-radiation, methyl methacrylate, and ethylene oxide and to determine how exposure varies with different operating room factors. Exposures of anesthetists and nurses to these agents were determined in selected operating rooms over three consecutive days. Each subject was asked to wear an x-radiation dosimeter for 1 month. Exposure to anesthetic agents was found to be influenced by the age of the OR facility, typemore » of surgical service, number of procedures carried out during the day, type of anesthetic circuitry, and method of anesthesia delivery. Anesthetists were found to have significantly greater exposures than OR nurses. Exposure of OR personnel to ethylene oxide, methyl methacrylate, and x-radiation were well within existing standards. Exposure of anesthetists and nurses to anesthetic agents, at times, was in excess of Ontario exposure guidelines, despite improvements in the control of anesthetic pollution.« less

Bismuth@US-tubes as a Potential Contrast Agent for X-ray Imaging Applications

PubMed Central

Rivera, Eladio J.; Tran, Lesa A.; Hernández-Rivera, Mayra; Yoon, Diana; Mikos, Antonios G.; Rusakova, Irene A.; Cheong, Benjamin Y.; Cabreira-Hansen, Maria da Graça; Willerson, James T.; Perin, Emerson C.; Wilson, Lon J.

2013-01-01

The encapsulation of bismuth as BiOCl/Bi2O3 within ultra-short (ca. 50 nm) single-walled carbon nanocapsules (US-tubes) has been achieved. The Bi@US-tubes have been characterized by high-resolution transmission electron microscopy (HR-TEM), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Bi@US-tubes have been used for intracellular labeling of pig bone marrow-derived mesenchymal stem cells (MSCs) to show high X-ray contrast in computed tomography (CT) cellular imaging for the first time. The relatively high contrast is achieved with low bismuth loading (2.66% by weight) within the US-tubes and without compromising cell viability. X-ray CT imaging of Bi@US-tubes-labeled MSCs showed a nearly two-fold increase in contrast enhancement when compared to unlabeled MSCs in a 100 kV CT clinical scanner. The CT signal enhancement from the Bi@US-tubes is 500 times greater than polymer-coated Bi2S3 nanoparticles and several-fold that of any clinical iodinated contrast agent (CA) at the same concentration. Our findings suggest that the Bi@US-tubes can be used as a potential new class of X-ray CT agent for stem cell labeling and possibly in vivo tracking. PMID:24288589

Preparation and Evaluation of Multiple Nanoemulsions Containing Gadolinium (III) Chelate as a Potential Magnetic Resonance Imaging (MRI) Contrast Agent.

PubMed

Sigward, Estelle; Corvis, Yohann; Doan, Bich-Thuy; Kindsiko, Kadri; Seguin, Johanne; Scherman, Daniel; Brossard, Denis; Mignet, Nathalie; Espeau, Philippe; Crauste-Manciet, Sylvie

2015-09-01

The objective was to develop, characterize and assess the potentiality of W1/O/W2 self-emulsifying multiple nanoemulsions to enhance signal/noise ratio for Magnetic Resonance Imaging (MRI). For this purpose, a new formulation, was designed for encapsulation efficiency and stability. Various methods were used to characterize encapsulation efficiency ,in particular calorimetric methods (Differential Scanning Calorimetry (DSC), thermogravimetry analysis) and ultrafiltration. MRI in vitro relaxivities were assessed on loaded DTPA-Gd multiple nanoemulsions. Characterization of the formulation, in particular of encapsulation efficiency was a challenge due to interactions found with ultrafiltration method. Thanks to the specifically developed DSC protocol, we were able to confirm the formation of multiple nanoemulsions, differentiate loaded from unloaded nanoemulsions and measure the encapsulation efficiency which was found to be quite high with a 68% of drug loaded. Relaxivity studies showed that the self-emulsifying W/O/W nanoemulsions were positive contrast agents, exhibiting higher relaxivities than those of the DTPA-Gd solution taken as a reference. New self-emulsifying multiple nanoemulsions that were able to load satisfactory amounts of contrasting agent were successfully developed as potential MRI contrasting agents. A specific DSC protocol was needed to be developed to characterize these complex systems as it would be useful to develop these self-formation formulations.

01-ERD-111 - The Development of Synthetic High Affinity Ligands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perkins, J; Balhorn, R; Cosman, M

2004-02-05

The aim of this project was to develop Synthetic High-Affinity Ligands (SHALs), which bind with high affinity and specificity to proteins of interest for national security and cancer therapy applications. The aim of producing synthetic ligands for sensory devices as an alternative to antibody-based detection assays and therapeutic agents is to overcome the drawbacks associated with antibody-based in next-generation sensors and systems. The focus area of the project was the chemical synthesis of the SHALs. The project concentrated on two different protein targets. (a) The C fragment of tetanus and botulinum toxin, potential biowarfare agents. A SHAL for tetanus ormore » botulinum toxin would be incorporated into a sensory device for the toxins. (b) HLA-DR10, a protein found in high abundance on the surface of Non-Hodgkins Lymphoma. A SHAL specific to a tumor marker, labeled with a radionuclide, would enable the targeted delivery of radiation therapy to metastatic disease. The technical approach used to develop a SHAL for each protein target will be described in more detail below. However, in general, the development of a SHAL requires a combination of computational modeling techniques, modern nuclear magnetic resonance spectroscopy (NMR) and synthetic chemistry.« less

Multigeneration Cross-Contamination of Mail with Bacillus anthracis Spores

PubMed Central

Edmonds, Jason; Lindquist, H. D. Alan; Sabol, Jonathan; Martinez, Kenneth; Shadomy, Sean; Cymet, Tyler; Emanuel, Peter

2016-01-01

The release of biological agents, including those which could be used in biowarfare or bioterrorism in large urban areas, has been a concern for governments for nearly three decades. Previous incidents from Sverdlosk and the postal anthrax attack of 2001 have raised questions on the mechanism of spread of Bacillus anthracis spores as an aerosol or contaminant. Prior studies have demonstrated that Bacillus atrophaeus is easily transferred through simulated mail handing, but no reports have demonstrated this ability with Bacillus anthracis spores, which have morphological differences that may affect adhesion properties between spore and formite. In this study, equipment developed to simulate interactions across three generations of envelopes subjected to tumbling and mixing was used to evaluate the potential for cross-contamination of B. anthracis spores in simulated mail handling. In these experiments, we found that the potential for cross-contamination through letter tumbling from one generation to the next varied between generations while the presence of a fluidizer had no statistical impact on the transfer of material. Likewise, the presence or absence of a fluidizer had no statistically significant impact on cross-contamination levels or reaerosolization from letter opening. PMID:27123934

Prevention and treatment of cancer targeting chronic inflammation: research progress, potential agents, clinical studies and mechanisms.

PubMed

Zhang, Yong; Kong, Weijia; Jiang, Jiandong

2017-06-01

Numerous experimental and clinical studies indicate that chronic inflammation is closely related to the initiation, progression, and spread of cancer, in which proinflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α), and transcription factors, such as nuclear factor-κB (NF-κB), and signal transducer and activator of transcription 3 (STAT3), play pivotal roles. Stimulated by proinflammatory cytokines, NF-κB and STAT3 can modulate the expression of target genes, most of which are oncogenic ones, and promote the survival, proliferation, invasion, and metastasis of cancer cells. Now it is generally accepted that inflammation-related molecules and pathways are useful targets for the prevention and treatment of cancer. In this review, we summarize the relationship between chronic inflammation and cancer and describe some potentially useful agents including aspirin, meformin, statins, and some natural products (green tea catechins, andrographolide, curcumin) for their cancer prevention and treatment activities targeting chronic inflammation. The results of typical clinical studies are included, and the influences of these agents on the proinflammatory cytokines and inflammation-related pathways are discussed. Data from the present review support that agents targeting chronic inflammation may have a broad application prospect for the prevention and treatment of cancer in the future.

Theoretical Studies Applied to the Evaluation of the DFPase Bioremediation Potential against Chemical Warfare Agents Intoxication

PubMed Central

Soares, Flávia V.; de Castro, Alexandre A.; Pereira, Ander F.; Leal, Daniel H. S.; Mancini, Daiana T.; da Cunha, Elaine F. F.; Kuca, Kamil

2018-01-01

Organophosphorus compounds (OP) are part of a group of compounds that may be hazardous to health. They are called neurotoxic agents because of their action on the nervous system, inhibiting the acetylcholinesterase (AChE) enzyme and resulting in a cholinergic crisis. Their high toxicity and rapid action lead to irreversible damage to the nervous system, drawing attention to developing new treatment methods. The diisopropyl fluorophosphatase (DFPase) enzyme has been considered as a potent biocatalyst for the hydrolysis of toxic OP and has potential for bioremediation of this kind of intoxication. In order to investigate the degradation process of the nerve agents Tabun, Cyclosarin and Soman through the wild-type DFPase, and taking into account their stereochemistry, theoretical studies were carried out. The intermolecular interaction energy and other parameters obtained from the molecular docking calculations were used to construct a data matrix, which were posteriorly treated by statistical analyzes of chemometrics, using the PCA (Principal Components Analysis) multivariate analysis. The analyzed parameters seem to be quite important for the reaction mechanisms simulation (QM/MM). Our findings showed that the wild-type DFPase enzyme is stereoselective in hydrolysis, showing promising results for the catalytic degradation of the neurotoxic agents under study, with the degradation mechanism performed through two proposed pathways. PMID:29690585

Theoretical Studies Applied to the Evaluation of the DFPase Bioremediation Potential against Chemical Warfare Agents Intoxication.

PubMed

Soares, Flávia V; de Castro, Alexandre A; Pereira, Ander F; Leal, Daniel H S; Mancini, Daiana T; Krejcar, Ondrej; Ramalho, Teodorico C; da Cunha, Elaine F F; Kuca, Kamil

2018-04-23

Organophosphorus compounds (OP) are part of a group of compounds that may be hazardous to health. They are called neurotoxic agents because of their action on the nervous system, inhibiting the acetylcholinesterase (AChE) enzyme and resulting in a cholinergic crisis. Their high toxicity and rapid action lead to irreversible damage to the nervous system, drawing attention to developing new treatment methods. The diisopropyl fluorophosphatase (DFPase) enzyme has been considered as a potent biocatalyst for the hydrolysis of toxic OP and has potential for bioremediation of this kind of intoxication. In order to investigate the degradation process of the nerve agents Tabun, Cyclosarin and Soman through the wild-type DFPase, and taking into account their stereochemistry, theoretical studies were carried out. The intermolecular interaction energy and other parameters obtained from the molecular docking calculations were used to construct a data matrix, which were posteriorly treated by statistical analyzes of chemometrics, using the PCA (Principal Components Analysis) multivariate analysis. The analyzed parameters seem to be quite important for the reaction mechanisms simulation (QM/MM). Our findings showed that the wild-type DFPase enzyme is stereoselective in hydrolysis, showing promising results for the catalytic degradation of the neurotoxic agents under study, with the degradation mechanism performed through two proposed pathways.

Streptomyces globosus UAE1, a Potential Effective Biocontrol Agent for Black Scorch Disease in Date Palm Plantations.

PubMed

Saeed, Esam E; Sham, Arjun; Salmin, Zeinab; Abdelmowla, Yasmeen; Iratni, Rabah; El-Tarabily, Khaled; AbuQamar, Synan

2017-01-01

Many fungal diseases affect date palm causing considerable losses in date production worldwide. We found that the fungicide Cidely ® Top inhibited the mycelial growth of the soil-borne pathogenic fungus Thielaviopsis punctulata , the causal agent of black scorch disease of date palm, both in vitro and in vivo . Because the use of biocontrol agents (BCAs) can minimize the impact of pathogen control on economic and environmental concerns related to chemical control, we aimed at testing local actinomycete strains isolated from the rhizosphere soil of healthy date palm cultivated in the United Arab Emirates (UAE) against T. punctulata . The selected isolate can thus be used as a potential agent for integrated disease management programs. In general, the BCA showed antagonism in vitro and in greenhouse experiments against this pathogen. The most promising actinomycete isolate screened showed the highest efficacy against the black scorch disease when applied before or at the same time of inoculation with T. punctulata , compared with BCA or fungicide application after inoculation. The nucleotide sequence and phylogenetic analyses using the 16 S ribosomal RNA gene with other Streptomyces spp. in addition to morphological and cultural characteristics revealed that the isolated UAE strain belongs to Streptomyces globosus UAE1. The antagonistic activity of S. globosus against T. punctulata , was associated with the production by this strain of diffusible antifungal metabolites i.e., metabolites that can inhibit mycelial growth of the pathogen. This was evident in the responses of the vegetative growth of pure cultures of the pathogen when exposed to the culture filtrates of the BCA. Altogether, the pathogenicity tests, disease severity indices and mode of action tests confirmed that the BCA was not only capable of suppressing black scorch disease symptoms, but also could prevent the spread of the pathogen, as a potential practical method to improve disease management in the

Synthesis and evaluation of novel triazolyl quinoline derivatives as potential antileishmanial agents.

PubMed

Upadhyay, Akanksha; Kushwaha, Pragati; Gupta, Sampa; Dodda, Ranga Prasad; Ramalingam, Karthik; Kant, Ruchir; Goyal, Neena; Sashidhara, Koneni V

2018-05-12

The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover novel series of 25 compounds for the development of new antileishmanial agents. A series of triazolyl 2-methyl-4-phenylquinoline-3-carboxylate derivatives has been synthesized via click chemistry inspired molecular hybridization approach and evaluated against Leishmania donovani. Most of the screened derivatives exhibited significant in vitro anti-leishmanial activity against promastigote (IC 50 ranging from 2.43 to 45.75 μM) and intracellular amastigotes (IC 50 ranging from 7.06 to 34.9 μM) than the control, miltefosine (IC 50  = 8.4 μM), with less cytotoxicity in comparison to the standard drugs. Overall results revealed that prototype signify a new structural lead for antileishmanial chemotherapy. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity--an update.

PubMed

Grunberg, Steven M; Osoba, David; Hesketh, Paul J; Gralla, Richard J; Borjeson, Sussanne; Rapoport, Bernardo L; du Bois, Andreas; Tonato, Maurizio

2005-02-01

Development of effective antiemetic therapy depends upon an understanding of both the antiemetic agents and the emetogenic challenges these agents are designed to address. New potential antiemetic agents should be studied in an orderly manner, proceeding from phase I to phase II open-label trials and then to randomized double-blind phase III trials comparing new agents and regimens to best standard therapy. Use of placebos in place of antiemetic therapy against highly or moderately emetogenic chemotherapy is unacceptable. Nausea and vomiting should be evaluated separately and for both the acute and delayed periods. Defining the emetogenicity of new antineoplastic agents is a challenge, since such data are often not reliably recorded during early drug development. A four-level classification system is proposed for emetogenicity of intravenous antineoplastic agents. A separate four-level classification system for emetogenicity of oral antineoplastic agents, which are often given over an extended period of time, is also proposed.

Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata.

PubMed

Rajagopal, Sriram; Kumar, R Ajaya; Deevi, Dhanvanthri S; Satyanarayana, Chitkala; Rajagopalan, R

2003-01-01

Andrographis paniculata plant extract is known to possess a variety of pharmacological activities. Andrographolide, the major constituent of the extract is implicated towards its pharmacological activity. We studied the cellular processes and targets modulated by andrographolide treatment in human cancer and immune cells. Andrographolide treatment inhibited the in vitro proliferation of different tumor cell lines, representing various types of cancers. The compound exerts direct anticancer activity on cancer cells by cell-cycle arrest at G0/G1 phase through induction of cell-cycle inhibitory protein p27 and decreased expression of cyclin-dependent kinase 4 (CDK4). Immunostimulatory activity of andrographolide is evidenced by increased proliferation of lymphocytes and production of interleukin-2. Andrographolide also enhanced the tumor necrosis factor-alpha production and CD marker expression, resulting in increased cytotoxic activity of lymphocytes against cancer cells, which may contribute for its indirect anticancer activity. The in vivo anticancer activity of the compound is further substantiated against B16F0 melanoma syngenic and HT-29 xenograft models. These results suggest that andrographolide is an interesting pharmacophore with anticancer and immunomodulatory activities and hence has the potential for being developed as a cancer therapeutic agent.

Hyperglycaemia Induced by Novel Anticancer Agents: An Undesirable Complication or a Potential Therapeutic Opportunity?

PubMed

Shah, Rashmi R

2017-03-01

Signalling pathways involving protein kinase, insulin-like growth factor 1, insulin receptors and the phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) system are critical in promoting oncogenesis. The use of anticancer agents that inhibit these pathways frequently results in hyperglycaemia, an on-target effect of these drugs. Hyperglycaemia induced by these agents denotes optimal inhibition of the desired pharmacological target. As hyperglycaemia can be treated successfully and effectively with metformin, managing this complication by reducing the dose of or discontinuing the anticancer drug may be counterproductive, especially if it is otherwise effective and clinically tolerated. The use of metformin to treat hyperglycaemia induced by anticancer drugs provides a valuable therapeutic opportunity of potentiating their clinical anticancer effects. Although evidence from randomised controlled trials is awaited, extensive preclinical evidence and clinical observational studies suggest that metformin has anticancer properties that improve overall survival in patients with diabetes and a variety of cancers. Metformin has also been reported to reverse resistance to epidermal growth factor receptor (EGFR)-inhibiting tyrosine kinase inhibitors. This review summarises briefly the role of the above signalling pathways in oncogenesis, the causal association between inhibition of these pathways and hyperglycaemia, and the effect of metformin on clinical outcomes resulting from its anticancer properties. The evidence reviewed herein, albeit almost exclusively from observational studies, provides support for a greater use of metformin not only in patients with cancer and diabetes or drug-induced hyperglycaemia but also potentially as an anticancer drug. However, prospective randomised controlled studies are needed in all these settings to better assess the effect on clinical outcomes of adding metformin to ongoing anticancer therapy.

Potential therapeutic applications of multifunctional host-defense peptides from frog skin as anti-cancer, anti-viral, immunomodulatory, and anti-diabetic agents.

PubMed

Conlon, J Michael; Mechkarska, Milena; Lukic, Miodrag L; Flatt, Peter R

2014-07-01

Frog skin constitutes a rich source of peptides with a wide range of biological properties. These include host-defense peptides with cytotoxic activities against bacteria, fungi, protozoa, viruses, and mammalian cells. Several hundred such peptides from diverse species have been described. Although attention has been focused mainly on antimicrobial activity, the therapeutic potential of frog skin peptides as anti-infective agents remains to be realized and no compound based upon their structures has yet been adopted in clinical practice. Consequently, alternative applications are being explored. Certain naturally occurring frog skin peptides, and analogs with improved therapeutic properties, show selective cytotoxicity against tumor cells and viruses and so have potential for development into anti-cancer and anti-viral agents. Some peptides display complex cytokine-mediated immunomodulatory properties. Effects on the production of both pro-inflammatory and anti-inflammatory cytokines by peritoneal macrophages and peripheral blood mononuclear cells have been observed so that clinical applications as anti-inflammatory, immunosuppressive, and immunostimulatory agents are possible. Several frog skin peptides, first identified on the basis of antimicrobial activity, have been shown to stimulate insulin release both in vitro and in vivo and so show potential as incretin-based therapies for treatment of patients with Type 2 diabetes mellitus. This review assesses the therapeutic possibilities of peptides from frogs belonging to the Ascaphidae, Alytidae, Pipidae, Dicroglossidae, Leptodactylidae, Hylidae, and Ranidae families that complement their potential role as anti-infectives for use against multidrug-resistant microorganisms. Copyright © 2014 Elsevier Inc. All rights reserved.

Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors.

PubMed

Delgado-Goñi, T; Martín-Sitjar, J; Simões, R V; Acosta, M; Lope-Piedrafita, S; Arús, C

2013-02-01

Dimethyl sulfoxide (DMSO) is commonly used in preclinical studies of animal models of high-grade glioma as a solvent for chemotherapeutic agents. A strong DMSO signal was detected by single-voxel MRS in the brain of three C57BL/6 control mice during a pilot study of DMSO tolerance after intragastric administration. This led us to investigate the accumulation and wash-out kinetics of DMSO in both normal brain parenchyma (n=3 control mice) by single-voxel MRS, and in 12 GL261 glioblastomas (GBMs) by single-voxel MRS (n=3) and MRSI (n=9). DMSO accumulated differently in each tissue type, reaching its highest concentration in tumors: 6.18 ± 0.85 µmol/g water, 1.5-fold higher than in control mouse brain (p<0.05). A faster wash-out was detected in normal brain parenchyma with respect to GBM tissue: half-lives of 2.06 ± 0.58 and 4.57 ± 1.15 h, respectively. MRSI maps of time-course DMSO changes revealed clear hotspots of differential spatial accumulation in GL261 tumors. Additional MRSI studies with four mice bearing oligodendrogliomas (ODs) revealed similar results as in GBM tumors. The lack of T(1) contrast enhancement post-gadolinium (gadopentetate dimeglumine, Gd-DTPA) in control mouse brain and mice with ODs suggested that DMSO was fully able to cross the intact blood-brain barrier in both normal brain parenchyma and in low-grade tumors. Our results indicate a potential role for DMSO as a contrast agent for brain tumor detection, even in those tumors 'invisible' to standard gadolinium-enhanced MRI, and possibly for monitoring heterogeneities associated with progression or with therapeutic response. Copyright © 2012 John Wiley & Sons, Ltd.

Induction of brain tumor stem cell apoptosis by FTY720: a potential therapeutic agent for glioblastoma.

PubMed

Estrada-Bernal, Adriana; Palanichamy, Kamalakannan; Ray Chaudhury, Abhik; Van Brocklyn, James R

2012-04-01

FTY720 is a sphingosine analogue that down regulates expression of sphingosine-1-phosphate receptors and causes apoptosis of multiple tumor cell types, including glioma cells. This study examined the effect of FTY720 on brain tumor stem cells (BTSCs) derived from human glioblastoma (GBM) tissue. FTY720 treatment of BTSCs led to rapid inactivation of ERK MAP kinase, leading to upregulation of the BH3-only protein Bim and apoptosis. In combination with temozolomide (TMZ), the current standard chemotherapeutic agent for GBM, FTY720 synergistically induced BTSC apoptosis. FTY720 also slowed growth of intracranial xenograft tumors in nude mice and augmented the therapeutic effect of TMZ, leading to enhanced survival. Furthermore, the combination of FTY720 and TMZ decreased the invasiveness of BTSCs in mouse brains. FTY720 is known to cross the blood-brain barrier and recently received Food and Drug Administration approval for treatment of relapsing multiple sclerosis. Thus, FTY720 is an excellent potential therapeutic agent for treatment of GBM.

DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease.

PubMed

Larkin, Benjamin P; Glastras, Sarah J; Chen, Hui; Pollock, Carol A; Saad, Sonia

2018-04-24

Chronic kidney disease (CKD) is a global epidemic, and its major risk factors include obesity and type 2 diabetes. Obesity not only promotes metabolic dysregulation and the development of diabetic kidney disease but also may independently lead to CKD by a variety of mechanisms, including endocrine and metabolic dysfunction, inflammation, oxidative stress, altered renal hemodynamics, and lipotoxicity. Deleterious renal effects of obesity can also be transmitted from one generation to the next, and it is increasingly recognized that offspring of obese mothers are predisposed to CKD. Epigenetic modifications are changes that regulate gene expression without altering the DNA sequence. Of these, DNA methylation is the most studied. Epigenetic imprints, particularly DNA methylation, are laid down during critical periods of fetal development, and they may provide a mechanism by which maternal-fetal transmission of chronic disease occurs. Our current review explores the evidence for the role of DNA methylation in the development of CKD, diabetic kidney disease, diabetes, and obesity. DNA methylation has been implicated in renal fibrosis-the final pathophysiologic pathway in the development of end-stage kidney disease-which supports the notion that demethylating agents may play a potential therapeutic role in preventing development and progression of CKD.-Larkin, B. P., Glastras, S. J., Chen, H., Pollock, C. A., Saad, S. DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease.

Host Specificity of Epiplema albida: A Potential Biological Control Agent for Sri Lankan Privet in the Mascarene Islands

PubMed Central

Shaw, Richard H.

2017-01-01

Epiplema albida (Hampson) (Lepidoptera: Uraniidae, Epipleminae) from Sri Lanka, was studied to assess its safety for use as a biological control agent for Sri Lankan privet, Ligustrum robustum subsp. walkeri (Oleaceae) in La Réunion and other Mascarene Islands. Larval no-choice feeding tests using newly hatched larvae, larval development tests, and multiple choice oviposition tests were used. Adult females of E. albida are shown to have highly selective oviposition behaviour and the species is physiologically restricted to very few hosts for feeding and development. The risk to key test plants in La Réunion is minimal, so this species can be considered for use as a biological control agent there, but would need further evaluation for potential use elsewhere. PMID:28788086

Cyprinid herpesvirus 3 as a potential biological control agent for carp (Cyprinus carpio) in Australia: susceptibility of non-target species.

PubMed

McColl, K A; Sunarto, A; Slater, J; Bell, K; Asmus, M; Fulton, W; Hall, K; Brown, P; Gilligan, D; Hoad, J; Williams, L M; Crane, M St J

2017-09-01

Carp (Cyprinus carpio L.) is a pest species in Australian waterways, and cyprinid herpesvirus 3 (CyHV-3) is being considered as a potential biological control (biocontrol) agent. An important consideration for any such agent is its target specificity. In this study, the susceptibility to CyHV-3 of a range of non-target species (NTS) was tested. The NTS were as follows: 13 native Australian, and one introduced, fish species; a lamprey species; a crustacean; two native amphibian species (tadpole and mature stages); two native reptilian species; chickens; and laboratory mice. Animals were exposed to 100-1000 times the approximate minimum amount of CyHV-3 required to cause disease in carp by intraperitoneal and/or bath challenge, and then examined clinically each day over the course of 28 days post-challenge. There were no clinical signs, mortalities or histological evidence consistent with a viral infection in a wide taxonomic range of NTS. Furthermore, there was no molecular evidence of infection with CyHV-3, and, in particular, all RT-PCRs for viral mRNA were negative. As a consequence, the results encourage further investigation of CyHV-3 as a potential biocontrol agent that is specific for carp. © 2016 John Wiley & Sons Ltd.

Biothreat agents and pathology laboratories.

PubMed

Nelson, Ann; Wilson, Michael L

2007-11-01

Pathologists and laboratory staff are likely to be among the first health care workers to be aware that a potential bioterrorism attack has occurred. To prepare for such an event, it is necessary to be familiar with 1) the characteristics of bioterrorism attacks versus natural disease outbreaks, 2) which pathogens are potential bioterrorism agents; 3) the types of lesions that each causes; 4) the microbiological characteristics of each agent; 5) the Laboratory Response Network and reporting requirements, and 6) what resources are available.

Joint Chemical Agent Detector (JCAD): the future of chemical agent detection

NASA Astrophysics Data System (ADS)

Laljer, Charles E.; Owen, Jeffery L.

2002-06-01

The Joint Chemical Agent Detector (JCAD) will provide state of the art chemical warfare agent detection capability to ground vehicle operators. Intelligence sources estimate that over twenty counties have active chemical weapons programs. The spread of chemical weapons to third world nations, coupled with the potential for US involvement in these areas in an operational or support capacity, increases the probability that the Joint Services may encounter chemical agents and toxic industrial materials anywhere in the world. Currently, fielded chemical agent detectors are bulky, labor intensive, and subject to false readings. No legacy detector is sensitive enough to provide detection and warning of the low dose hazards associated with miosis contamination. The JCAD will provide a small, lightweight chemical agent detector for vehicle interiors, aircraft, individual personnel, shipboard, and fixed site locations. The system provides a common detection components across multi-service platforms. This common detector system will allow the Joint Services to use the same operational and support concept for more efficient utilization of resources. The JCAD will detect, identify, quantify, and warn of the presence of chemical agents prior to onset of miosis. Upon detection of chemical agents, the detector will provide local and remote audible and visual alarms to the operators. Advance warning will provide the vehicle crew with the time necessary to protect themselves from the lethal effects of chemical agents. The JCAD will also be capable of being upgraded to protect against future chemical agent threats. The JCAD will provide the vehicle operators with the warning necessary to survive and fight in a chemical warfare agent threat environment.

The potential of tetrandrine as a protective agent for ischemic stroke.

PubMed

Chen, Yun; Tsai, Ya-Hui; Tseng, Sheng-Hong

2011-09-16

Stroke is one of the leading causes of mortality, with a high incidence of severe morbidity in survivors. The treatment to minimize tissue injury after stroke is still unsatisfactory and it is mandatory to develop effective treatment strategies for stroke. The pathophysiology of ischemic stroke is complex and involves many processes including energy failure, loss of ion homeostasis, increased intracellular calcium level, platelet aggregation, production of reactive oxygen species, disruption of blood brain barrier, and inflammation and leukocyte infiltration, etc. Tetrandrine, a bisbenzylisoquinoline alkaloid, has many pharmacologic effects including anti-inflammatory and cytoprotective effects. In addition, tetrandrine has been found to protect the liver, heart, small bowel and brain from ischemia/reperfusion injury. It is a calcium channel blocker, and can inhibit lipid peroxidation, reduce generation of reactive oxygen species, suppress the production of cytokines and inflammatory mediators, inhibit neutrophil recruitment and platelet aggregation, which are all devastating factors during ischemia/reperfusion injury of the brain. Because tetrandrine can counteract these important pathophysiological processes of ischemic stroke, it has the potential to be a protective agent for ischemic stroke.

Species-Specific Standard Redox Potential of Thiol-Disulfide Systems: A Key Parameter to Develop Agents against Oxidative Stress

NASA Astrophysics Data System (ADS)

Mirzahosseini, Arash; Noszál, Béla

2016-11-01

Microscopic standard redox potential, a new physico-chemical parameter was introduced and determined to quantify thiol-disulfide equilibria of biological significance. The highly composite, codependent acid-base and redox equilibria of thiols could so far be converted into pH-dependent, apparent redox potentials (E’°) only. Since the formation of stable metal-thiolate complexes precludes the direct thiol-disulfide redox potential measurements by usual electrochemical techniques, an indirect method had to be elaborated. In this work, the species-specific, pH-independent standard redox potentials of glutathione were determined primarily by comparing it to 1-methylnicotinamide, the simplest NAD+ analogue. Secondarily, the species-specific standard redox potentials of the two-electron redox transitions of cysteamine, cysteine, homocysteine, penicillamine, and ovothiol were determined using their microscopic redox equilibrium constants with glutathione. The 30 different, microscopic standard redox potential values show close correlation with the respective thiolate basicities and provide sound means for the development of potent agents against oxidative stress.

Cold tolerance of Trissolcus japonicus and T. cultratus, potential biological control agents of Halyomorpha halys, the brown marmorated stink bug

Treesearch

Erica Nystrom Santacruz; Robert C. Venette; Christine Dieckhoff; Kim Hoelmer; Robert L. Koch

2017-01-01

Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) is native to Asia and has become a severe agricultural and nuisance pest in the U.S. Therefore, foreign exploration was conducted in Asia to identify potential classical biological control agents. Several Trissolcus spp. (Hymenoptera: Scelionidae) parasitize H. halys...

Gadolinium heteropoly complex K 17[Gd(P 2W 17O 61) 2] as a potential MRI contrast agent

NASA Astrophysics Data System (ADS)

Sun, Guoying; Feng, Jianghua; Wu, Huifeng; Pei, Fengkui; Fang, Ke; Lei, Hao

2004-10-01

Gadolinium heteropoly complex K17[Gd(P2W17O61)2] has been evaluated by in vitro and in vivo experiments as a potential contrast agent for magnetic resonance imaging (MRI). The thermal analysis and conductivity study indicate that this complex has good thermal stability and wide pH stability range. The T1 relaxivity is 7.59 mM-1 s-1 in aqueous solution and 7.97 mM-1 s-1 in 0.725 mmol l-1 bovine serum albumin (BSA) solution at 25 °C and 9.39 T, respectively. MR imaging of three male Sprague-Dawley rats showed remarkable enhancement in rat liver after intravenous injection, which persisted longer than with Gd-DTPA. The signal intensity increased by 57.1±16.9% during the whole imaging period at 0.082 mmol kg-1dose. Our preliminary in vitro and in vivo studies indicate that K17[Gd(P2W17O61)2] is a potential liver-specific MRI contrast agent.

Genomic characterization of key bacteriophages to formulate the potential biocontrol agent to combat enteric pathogenic bacteria.

PubMed

Parmar, Krupa M; Dafale, Nishant A; Tikariha, Hitesh; Purohit, Hemant J

2018-05-01

Combating bacterial pathogens has become a global concern especially when the antibiotics and chemical agents are failing to control the spread due to its resistance. Bacteriophages act as a safe biocontrol agent by selectively lysing the bacterial pathogens without affecting the natural beneficial microflora. The present study describes the screening of prominent enteric pathogens NDK1, NDK2, NDK3, and NDK4 (Escherichia, Klebsiella, Enterobacter, and Serratia) mostly observed in domestic wastewater; against which KNP1, KNP2, KNP3, and KNP4 phages were isolated. To analyze their potential role in eradicating enteric pathogens and toxicity issue, these bacteriophages were sequenced using next-generation sequencing and characterized based on its genomic content. The isolated bacteriophages were homologous to Escherichia phage (KNP1), Klebsiella phage (KNP2), Enterobacter phage (KNP3), Serratia phage (KNP4), and belonged to Myoviridae family of Caudovirales except for the unclassified KNP4 phage. Draft genome analysis revealed the presence of lytic enzymes such as holing and lysozyme in KNP1 phage, endolysin in KNP2 phage, and endopeptidase with holin in KNP3 phage. The absence of any lysogenic and virulent genes makes this bacteriophage suitable candidate for preparation of phage cocktail to combat the pathogens present in wastewater. However, KNP4 contained a virulent gene rendering it unsuitable to be used as a biocontrol agent. These findings make the phages (KNP1-KNP3) as a promising alternative for the biocontrol of pathogens in wastewater which is the main culprit to spread these dominated pathogens in different natural water bodies. This study also necessitates for genomic screening of bacteriophages for lysogenic and virulence genes prior to its use as a biocontrol agent.

Whole-Genome Sequence of Pseudomonas graminis Strain UASWS1507, a Potential Biological Control Agent and Biofertilizer Isolated in Switzerland.

PubMed

Crovadore, Julien; Calmin, Gautier; Chablais, Romain; Cochard, Bastien; Schulz, Torsten; Lefort, François

2016-10-06

We report here the whole-genome shotgun sequence of the strain UASWS1507 of the species Pseudomonas graminis, isolated in Switzerland from an apple tree. This is the first genome registered for this species, which is considered as a potential and valuable resource of biological control agents and biofertilizers for agriculture. Copyright © 2016 Crovadore et al.

THIRD-GENERATION FOAM BLOWING AGENTS FOR FOAM INSULATION

EPA Science Inventory

The report gives results of a study of third-generation blowing agents for foam insulation. (NOTE: the search for third-generation foam blowing agents has led to the realization that, as the number of potential substitutes increases, new concerns, such as their potential to act a...

Joint chemical agent detector (JCAD): the future of chemical agent detection

NASA Astrophysics Data System (ADS)

Laljer, Charles E.

2003-08-01

The Joint Chemical Agent Detector (JCAD) has continued development through 2002. The JCAD has completed Contractor Validation Testing (CVT) that included chemical warfare agent testing, environmental testing, electromagnetic interferent testing, and platform integration validation. The JCAD provides state of the art chemical warfare agent detection capability to military and homeland security operators. Intelligence sources estimate that over twenty countries have active chemical weapons programs. The spread of weapons of mass destruction (and the industrial capability for manufacture of these weapons) to third world nations and terrorist organizations has greatly increased the chemical agent threat to U.S. interests. Coupled with the potential for U.S. involvement in localized conflicts in an operational or support capacity, increases the probability that the military Joint Services may encounter chemical agents anywhere in the world. The JCAD is a small (45 in3), lightweight (2 lb.) chemical agent detector for vehicle interiors, aircraft, individual personnel, shipboard, and fixed site locations. The system provides a common detection component across multi-service platforms. This common detector system will allow the Joint Services to use the same operational and support concept for more efficient utilization of resources. The JCAD detects, identifies, quantifies, and warns of the presence of chemical agents prior to onset of miosis. Upon detection of chemical agents, the detector provides local and remote audible and visual alarms to the operators. Advance warning will provide the vehicle crew and other personnel in the local area with the time necessary to protect themselves from the lethal effects of chemical agents. The JCAD is capable of being upgraded to protect against future chemical agent threats. The JCAD provides the operator with the warning necessary to survive and fight in a chemical warfare agent threat environment.

Integrating virtual screening and biochemical experimental approach to identify potential anti-cancer agents from drug databank.

PubMed

Deka, Suman Jyoti; Roy, Ashalata; Manna, Debasis; Trivedi, Vishal

2018-06-01

Chemical libraries constitute a reservoir of pharmacophoric molecules to identify potent anti-cancer agents. Virtual screening of heterocyclic compound library in conjugation with the agonist-competition assay, toxicity-carcinogenicity analysis, and string-based structural searches enabled us to identify several drugs as potential anti-cancer agents targeting protein kinase C (PKC) as a target. Molecular modeling study indicates that Cinnarizine fits well within the PKC C2 domain and exhibits extensive interaction with the protein residues. Molecular dynamics simulation of PKC-Cinnarizine complex at different temperatures (300, 325, 350, 375, and 400[Formula: see text]K) confirms that Cinnarizine fits nicely into the C2 domain and forms a stable complex. The drug Cinnarizine was found to bind PKC with a dissociation constant Kd of [Formula: see text]M. The breast cancer cells stimulated with Cinnarizine causes translocation of PKC-[Formula: see text] to the plasma membrane as revealed by immunoblotting and immunofluorescence studies. Cinnarizine also dose dependently reduced the viability of MDAMB-231 and MCF-7 breast cancer cells with an IC[Formula: see text] of [Formula: see text] and [Formula: see text]g/mL, respectively. It is due to the disturbance of cell cycle of breast cancer cells with reduction of S-phase and accumulation of cells in G1-phase. It disturbs mitochondrial membrane potentials to release cytochrome C into the cytosol and activates caspase-3 to induce apoptosis in cancer cells. The cell death was due to induction of apoptosis involving mitochondrial pathway. Hence, the current study has assigned an additional role to Cinnarizine as an activator of PKC and potentials of the approach to identify new molecules for anti-cancer therapy. Thus, in silico screening along with biochemical experimentation is a robust approach to assign additional roles to the drugs present in the databank for anti-cancer therapy.

Adaptivity in Agent-Based Routing for Data Networks

NASA Technical Reports Server (NTRS)

Wolpert, David H.; Kirshner, Sergey; Merz, Chris J.; Turner, Kagan

2000-01-01

Adaptivity, both of the individual agents and of the interaction structure among the agents, seems indispensable for scaling up multi-agent systems (MAS s) in noisy environments. One important consideration in designing adaptive agents is choosing their action spaces to be as amenable as possible to machine learning techniques, especially to reinforcement learning (RL) techniques. One important way to have the interaction structure connecting agents itself be adaptive is to have the intentions and/or actions of the agents be in the input spaces of the other agents, much as in Stackelberg games. We consider both kinds of adaptivity in the design of a MAS to control network packet routing. We demonstrate on the OPNET event-driven network simulator the perhaps surprising fact that simply changing the action space of the agents to be better suited to RL can result in very large improvements in their potential performance: at their best settings, our learning-amenable router agents achieve throughputs up to three and one half times better than that of the standard Bellman-Ford routing algorithm, even when the Bellman-Ford protocol traffic is maintained. We then demonstrate that much of that potential improvement can be realized by having the agents learn their settings when the agent interaction structure is itself adaptive.

Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

PubMed

Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

2013-01-01

Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

Electrophysiological mechanisms of sophocarpine as a potential antiarrhythmic agent.

PubMed

Yang, Zhi-fang; Li, Ci-zhen; Wang, Wei; Chen, Ying-min; Zhang, Ying; Liu, Yuan-mou; Wang, Hong-wei

2011-03-01

To examine the electrophysiological effects of sophocarpine on action potentials (AP) and ionic currents of cardiac myocytes and to compare some of these effects with those of amiodarone. Langendorff perfusion set-up was used in isolated guinea pig heart, and responses to sophocarpine were monitored using electrocardiograph. Conventional microelectrode, voltage clamp technique and perforated patch were employed to record fast response AP (fAP), slow response AP (sAP) and ionic currents in guinea pig papillary muscle or rabbit sinus node cells. Tachyarrhythmia produced by isoprenaline (15 μmol/L) could be reversed by sophocarpine (300 μmol/L). Sophocarpine (10 μmol/L) decreased the amplitude by 4.0%, maximal depolarization velocity (V(max)) of the fAP by 24.4%, and Na(+) current (I(Na)) by 18.0%, while it prolonged the effective refractory period (ERP) by 21.1%. The same concentration of sophocarpine could also decrease the amplitude and V(max) of the sAP, by 26.8% and 25.7%, respectively, and attenuated the Ca(2+) current (I(CaL)) and the K(+) tail current substantially. Comparison of sophocarpine with amiodarone demonstrated that both prolonged the duration and the ERP of fAP and sAP, both decreased the amplitude and V(max) of the fAP and sAP, and both slowed the automatic heart rate. Sophocarpine could reverse isoprenaline-induced arrhythmia and inhibit I(Na), I(CaL), and I(Kr) currents. The electrophysiological effects of sophocarpine are similar to those of amiodarone, which might be regarded as a prospective antiarrhythmic agent.

A Novel Bacteriophage Targeting Cronobacter sakazakii Is a Potential Biocontrol Agent in Foods

PubMed Central

Lee, Ju-Hoon; Bai, Jaewoo; Shin, Hakdong; Kim, Yeran; Park, Bookyung; Heu, Sunggi

2015-01-01

Cronobacter sakazakii is an important pathogen that causes high mortality in infants. Due to its occasional antibiotic resistance, a bacteriophage approach might be an alternative effective method for the control of this pathogen. To develop a novel biocontrol agent using bacteriophages, the C. sakazakii-infecting phage CR5 was newly isolated and characterized. Interestingly, this phage exhibited efficient and relatively durable host lysis activity. In addition, a specific gene knockout study and subsequent complementation experiment revealed that this phage infected the host strain using the bacterial flagella. The complete genome sequence analysis of phage CR5 showed that its genome contains 223,989 bp of DNA, including 231 predicted open reading frames (ORFs), and it has a G+C content of 50.06%. The annotated ORFs were classified into six functional groups (structure, packaging, host lysis, DNA manipulation, transcription, and additional functions); no gene was found to be related to virulence or toxin or lysogen formation, but >80% of the predicted ORFs are unknown. In addition, a phage proteomic analysis using SDS-PAGE and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) revealed that seven phage structural proteins are indeed present, supporting the ORF predictions. To verify the potential of this phage as a biocontrol agent against C. sakazakii, it was added to infant formula milk contaminated with a C. sakazakii clinical isolate or food isolate, revealing complete growth inhibition of the isolates by the addition of phage CR5 when the multiplicity of infection (MOI) was 105. PMID:26497465

Screening of proteins based on macro-algae from West Java coast in Indonesian marine as a potential anti-aging agent

NASA Astrophysics Data System (ADS)

Putri, Arlina Prima; Dewi, Rizna Triana; Handayani, Aniek Sri; Harjanto, Sri; Chalid, Mochamad

2018-02-01

Algae has been known as one of the potential marine bio-resources that have been used in many fields such as bio-energy, food, pharmaceutical and medical applications. Study of macro-algae or seaweed for medicine application, in particular, highlights to empower their ingredients as a promising antioxidant like anti-aging agent due to their diversity in biological activity. The tropical climate of Indonesia with the highest marine biodiversity puts this country an auspicious source of numerous alga species as a novel antioxidant source. A Sample of 29 species of macroalgae has been collected from Coast of Pari Island as a part of Seribu Islands, Indonesia. Screening and extracting of aqueous tropical marine alga protein as a potential source for an antioxidant agent has been done by using 2,2-diphenyl-1-picrylhydrazyl scavenging method, and protein contents have been determined by Lowry method. Sample number 26 of the phylum Rhodophyta have 9.00±0.03 % protein content, which is potential for nutritional food in form of nutraceutical. That sample demonstrated the maximum DPPH scavenging activity 79.27±1.81 %. Moreover, crude extract from another species from phylum Rhodophyta had the very lower IC50 (3.4333±0.29 mg/ml) followed by Chlorophyta species (7.1069±1.78 mg/ml). In general, this study found that algae from phylum Rhodophyta possess a high content of protein, high activity towards free radical. Nevertheless, algae acquire the lowest IC50 value not only dominated by Rhodophyta but also from phylum Chlorophyta. The conclusion of this study leads to empowering high antioxidant activity algae as an anti-aging agent, which can be used in pharmaceutical applications. Therefore, the next study should be concerned on the properties of the algae which has been known to be suitable for pharmaceutical fields.

THE BIOTERRORISM THREAT: TECHNOLOGICAL AND POLITICAL CONSIDERATIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

J. F. PILAT

2000-03-01

Bioterrorism--along with biowarfare, from which it may not always be distinguishable in practice--will be a feature of the strategic landscape in the 21st century and is high on the US national security agenda. Bioterrorism poses a potential threat to the US population, agriculture, interests, friends and allies, and military forces (asymmetric threats). Yet these possibilities have not been widely pursued or realized by terrorists. The perceived threat is far worse than anything experienced to date, and is largely technologically driven.

Prevalence of acid-reducing agents (ARA) in cancer populations and ARA drug-drug interaction potential for molecular targeted agents in clinical development.

PubMed

Smelick, Gillian S; Heffron, Timothy P; Chu, Laura; Dean, Brian; West, David A; Duvall, Scott L; Lum, Bert L; Budha, Nageshwar; Holden, Scott N; Benet, Leslie Z; Frymoyer, Adam; Dresser, Mark J; Ware, Joseph A

2013-11-04

Acid-reducing agents (ARAs) are the most commonly prescribed medications in North America and Western Europe. There are currently no data describing the prevalence of their use among cancer patients. However, this is a paramount question due to the potential for significant drug-drug interactions (DDIs) between ARAs, most commonly proton pump inhibitors (PPIs), and orally administered cancer therapeutics that display pH-dependent solubility, which may lead to decreased drug absorption and decreased therapeutic benefit. Of recently approved orally administered cancer therapeutics, >50% are characterized as having pH-dependent solubility, but there are currently no data describing the potential for this ARA-DDI liability among targeted agents currently in clinical development. The objectives of this study were to (1) determine the prevalence of ARA use among different cancer populations and (2) investigate the prevalence of orally administered cancer therapeutics currently in development that may be liable for an ARA-DDI. To address the question of ARA use among cancer patients, a retrospective cross-sectional analysis was performed using two large healthcare databases: Thomson Reuters MarketScan (N = 1,776,443) and the U.S. Department of Veterans Affairs (VA, N = 1,171,833). Among all cancer patients, the total prevalence proportion of ARA use (no. of cancer patients receiving an ARA/total no. of cancer patients) was 20% and 33% for the MarketScan and VA databases, respectively. PPIs were the most commonly prescribed agent, comprising 79% and 65% of all cancer patients receiving a prescription for an ARA (no. of cancer patients receiving a PPI /no. of cancer patients receiving an ARA) for the MarketScan and VA databases, respectively. To estimate the ARA-DDI liability of orally administered molecular targeted cancer therapeutics currently in development, two publicly available databases, (1) Kinase SARfari and (2) canSAR, were examined. For those orally administered

Anti-Clotting Agents Explained

MedlinePlus

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

Agents Within our Midst

DTIC Science & Technology

2012-03-14

agents; and the development of bio -monitoring protocols for civilian and service personnel during a chemical attack. These efforts have resulted in greater...produced by staphylococcal bacteria that is and is classified as a CDC select agent which has the potential to be used as a biological weapon .1...NMR chemical shift perturbation titrations with Fab (fragment, antigen binding regions) domains of 20B1, 14G8, and 6D3 using deuterated (2H) SEB

Molecular basis of toxicity of Clostridium perfringens epsilon toxin.

PubMed

Bokori-Brown, Monika; Savva, Christos G; Fernandes da Costa, Sérgio P; Naylor, Claire E; Basak, Ajit K; Titball, Richard W

2011-12-01

Clostridium perfringens ε-toxin is produced by toxinotypes B and D strains. The toxin is the aetiological agent of dysentery in newborn lambs but is also associated with enteritis and enterotoxaemia in goats, calves and foals. It is considered to be a potential biowarfare or bioterrorism agent by the US Government Centers for Disease Control and Prevention. The relatively inactive 32.9 kDa prototoxin is converted to active mature toxin by proteolytic cleavage, either by digestive proteases of the host, such as trypsin and chymotrypsin, or by C. perfringens λ-protease. In vivo, the toxin appears to target the brain and kidneys, but relatively few cell lines are susceptible to the toxin, and most work has been carried out using Madin-Darby canine kidney (MDCK) cells. The binding of ε-toxin to MDCK cells and rat synaptosomal membranes is associated with the formation of a stable, high molecular weight complex. The crystal structure of ε-toxin reveals similarity to aerolysin from Aeromonas hydrophila, parasporin-2 from Bacillus thuringiensis and a lectin from Laetiporus sulphureus. Like these toxins, ε-toxin appears to form heptameric pores in target cell membranes. The exquisite specificity of the toxin for specific cell types suggests that it binds to a receptor found only on these cells. © 2011 The Authors Journal compilation © 2011 FEBS.

Balancing stealth and echogenic properties in an ultrasound contrast agent with drug delivery potential.

PubMed

Jablonowski, Lauren J; Alfego, David; Andorko, James I; Eisenbrey, John R; Teraphongphom, Nutte; Wheatley, Margaret A

2016-10-01

Contrast agents are currently being modified to combine diagnostic and therapeutic capabilities. For ultrasound (US) imaging with polymeric contrast agents, it is necessary to modify the shell to create "stealth" microbubbles but without these modifications sacrificing the agent's ability to interact with the focused US beam. We hypothesize that addition of the classic immune shielding molecule polyethylene glycol (PEG) to a polylactide (PLA) microbubble shell will affect the acoustic and physical properties of the resulting agents. In an effort to determine the best formulation to achieve a balance between stealth and acoustic activity, we compared two PEGylation techniques; addition of increasing amounts of PEG-PLA copolymer and employing incorporation of a PEG lipid (LipidPEG) into the shell. Loss of acoustic enhancement occurred in a dose-dependent manner for both types of PEGylated agents (loss of signal occurred at >5 wt% PEG-PLA and >1 wt% LipidPEG), while immune activation was also reduced in a dose-dependent manner for the PEG-PLA agents. This study shows that the balance between acoustic behavior and improved immune avoidance was scalable and successful to different degrees with both PEGylation methods, and was best achieved using for PEG-PLA at 5 wt% and for LipidPEG at 1 wt%. Studies are ongoing to evaluate the best method for the targeting and drug delivery capabilities of these agents for applications in cancer treatment. This study represents the basis for understanding the consequences of making modifications to the native polymeric shell. Copyright © 2016 Elsevier Ltd. All rights reserved.

Conflict resolution in multi-agent hybrid systems

DOT National Transportation Integrated Search

1996-12-01

A conflict resolution architecture for multi-agent hybrid systems with emphasis on Air Traffic Management Systems (ATMS) is presented. In such systems, conflicts arise in the form of potential collisions which are resolved locally by inter-agent coor...

Social scaling of extrapersonal space: target objects are judged as closer when the reference frame is a human agent with available movement potentialities.

PubMed

Fini, C; Brass, M; Committeri, G

2015-01-01

Space perception depends on our motion potentialities and our intended actions are affected by space perception. Research on peripersonal space (the space in reaching distance) shows that we perceive an object as being closer when we (Witt, Proffitt, & Epstein, 2005; Witt & Proffitt, 2008) or another actor (Costantini, Ambrosini, Sinigaglia, & Gallese, 2011; Bloesch, Davoli, Roth, Brockmole, & Abrams, 2012) can interact with it. Similarly, an object only triggers specific movements when it is placed in our peripersonal space (Costantini, Ambrosini, Tieri, Sinigaglia, & Committeri, 2010) or in the other's peripersonal space (Costantini, Committeri, & Sinigaglia, 2011; Cardellicchio, Sinigaglia, & Costantini, 2013). Moreover, also the extrapersonal space (the space outside reaching distance) seems to be perceived in relation to our movement capabilities: the more effort it takes to cover a distance, the greater we perceive the distance to be (Proffitt, Stefanucci, Banton, & Epstein, 2003; Sugovic & Witt, 2013). However, not much is known about the influence of the other's movement potentialities on our extrapersonal space perception. Three experiments were carried out investigating the categorization of distance in extrapersonal space using human or non-human allocentric reference frames (RF). Subjects were asked to judge the distance ("Near" or "Far") of a target object (a beach umbrella) placed at progressively increasing or decreasing distances until a change from near to far or vice versa was reported. In the first experiment we found a significant "Near space extension" when the allocentric RF was a human virtual agent instead of a static, inanimate object. In the second experiment we tested whether the "Near space extension" depended on the anatomical structure of the RF or its movement potentialities by adding a wooden dummy. The "Near space extension" was only observed for the human agent but not for the dummy. Finally, to rule out the possibility that the

A spontaneous mutation in kdsD, a biosynthesis gene for 3 Deoxy-D-manno-Octulosonic Acid, occurred in a ciprofloxacin resistant strain of Francisella tularensis and caused a high level of attenuation in murine models of tularemia

PubMed Central

Chance, Taylor; Toothman, Ronald G.; Nuss, Jonathan E.; Raymond, Jo Lynne; Biot, Fabrice V.; Demons, Samandra; Miller, Lynda; Halasohoris, Stephanie; Mou, Sherry; Koroleva, Galina; Lovett, Sean; Palacios, Gustavo; Vietri, Nicholas J.; Worsham, Patricia L.; Cote, Christopher K.; Kijek, Todd M.; Bozue, Joel A.

2017-01-01

Francisella tularensis, a gram–negative facultative intracellular bacterial pathogen, is the causative agent of tularemia and able to infect many mammalian species, including humans. Because of its ability to cause a lethal infection, low infectious dose, and aerosolizable nature, F. tularensis subspecies tularensis is considered a potential biowarfare agent. Due to its in vitro efficacy, ciprofloxacin is one of the antibiotics recommended for post-exposure prophylaxis of tularemia. In order to identify therapeutics that will be efficacious against infections caused by drug resistant select-agents and to better understand the threat, we sought to characterize an existing ciprofloxacin resistant (CipR) mutant in the Schu S4 strain of F. tularensis by determining its phenotypic characteristics and sequencing the chromosome to identify additional genetic alterations that may have occurred during the selection process. In addition to the previously described genetic alterations, the sequence of the CipR mutant strain revealed several additional mutations. Of particular interest was a frameshift mutation within kdsD which encodes for an enzyme necessary for the production of 3-Deoxy-D-manno-Octulosonic Acid (KDO), an integral component of the lipopolysaccharide (LPS). A kdsD mutant was constructed in the Schu S4 strain. Although it was not resistant to ciprofloxacin, the kdsD mutant shared many phenotypic characteristics with the CipR mutant, including growth defects under different conditions, sensitivity to hydrophobic agents, altered LPS profiles, and attenuation in multiple models of murine tularemia. This study demonstrates that the KdsD enzyme is essential for Francisella virulence and may be an attractive therapeutic target for developing novel medical countermeasures. PMID:28328947

Animals living in polluted environments are potential source of antimicrobials against infectious agents

PubMed Central

Lee, Simon; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

2012-01-01

The antimicrobials crisis is a ticking time bomb which could lead to millions of people dying from untreatable infections. With the worsening trends of antimicrobial resistance, we are heading towards a pre-antibiotic era. Thus, there is a need for newer and more powerful antibiotic agents. The search for new antibiotic compounds originating from natural resources is a promising research area. Animals living in germ-infested environments are a potent source of antimicrobials. Under polluted milieus, organisms such as cockroaches encounter different types of bacteria, including superbugs. Such creatures survive the onslaught of superbugs and are able to ward off disease by producing antimicrobial substances which show potent activity in the nervous system. We hope that the discovery of antimicrobial activity in the cockroach brain will stimulate research in finding antimicrobials from unusual sources, and has potential for the development of novel antibiotics. Nevertheless, intensive research in the next few years will be required to approach or realize these expectations. PMID:23265422

Structure-based drug discovery for botulinum neurotoxins.

PubMed

Swaminathan, Subramanyam

2013-01-01

Clostridium botulinum neurotoxin is the most poisonous substance known to humans. It is a potential biowarfare threat and a public health hazard. The only therapeutics available is antibody treatment which will not be effective for post-exposure therapy. There are no drugs available for post-intoxication treatment. Accordingly, it is imperative to develop effective drugs to counter botulism. Available structural information on botulinum neurotoxins both alone and in complex with their substrates offers an efficient method for designing structure-based drugs to treat botulism.

Understanding Virulence in the Brucellae and Francisellae: Towards Efficacious Treatments for Two Potential Biothreat Agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rasley, A; Parsons, D A; El-Etr, S

2009-12-30

Francisella tularensis, Yersinia pestis and Brucellae species are highly infectious pathogens classified as select agents by the Centers for Disease Control and Prevention (CDC) with the potential for use in bioterrorism attacks. These organisms are known to be facultative intracellular pathogens that preferentially infect human monocytes. As such, understanding how the host responds to infection with these organisms is paramount in detecting and combating human disease. We have compared the ability of fully virulent strains of each pathogen and their non-pathogenic near neighbors to enter and survive inside the human monocytic cell line THP-1 and have quantified the cellular responsemore » to infection with the goal of identifying both unique and common host response patterns. We expanded the scope of these studies to include experiments with pathogenic and non-pathogenic strains of Y. pestis, the causative agent of plague. Nonpathogenic strains of each organism were impaired in their ability to survive intracellularly compared with their pathogenic counterparts. Furthermore, infection of THP-1 cells with pathogenic strains of Y. pestis and F. tularensis resulted in marked increases in the secretion of the inflammatory chemokines IL-8, RANTES, and MIP-1{beta}. In contrast, B. melitensis infection failed to elicit any significant increases in a panel of cytokines tested. These differences may underscore distinct strategies in pathogenic mechanisms employed by these pathogens.« less

BSL-3 laboratory practices in the United States: comparison of select agent and non-select agent facilities.

PubMed

Richards, Stephanie L; Pompei, Victoria C; Anderson, Alice

2014-01-01

New construction of biosafety level 3 (BSL-3) laboratories in the United States has increased in the past decade to facilitate research on potential bioterrorism agents. The Centers for Disease Control and Prevention inspect BSL-3 facilities and review commissioning documentation, but no single agency has oversight over all BSL-3 facilities. This article explores the extent to which standard operating procedures in US BSL-3 facilities vary between laboratories with select agent or non-select agent status. Comparisons are made for the following variables: personnel training, decontamination, personal protective equipment (PPE), medical surveillance, security access, laboratory structure and maintenance, funding, and pest management. Facilities working with select agents had more complex training programs and decontamination procedures than non-select agent facilities. Personnel working in select agent laboratories were likely to use powered air purifying respirators, while non-select agent laboratories primarily used N95 respirators. More rigorous medical surveillance was carried out in select agent workers (although not required by the select agent program) and a higher level of restrictive access to laboratories was found. Most select agent and non-select agent laboratories reported adequate structural integrity in facilities; however, differences were observed in personnel perception of funding for repairs. Pest management was carried out by select agent personnel more frequently than non-select agent personnel. Our findings support the need to promote high quality biosafety training and standard operating procedures in both select agent and non-select agent laboratories to improve occupational health and safety.

Synthesis and biological activity of acetyl-protected hydroxybenzyl diethyl phosphates (EHBP) as potential chemotherapeutic agents.

PubMed

Kodela, Ravinder; Chattopadhyay, Mitali; Nath, Niharika; Cieciura, Lucyna Z; Pospishill, Liliya; Boring, Daniel; Crowell, James A; Kashfi, Khosrow

2011-12-01

Several acetyl-protected hydroxybenzyl diethyl phosphates (EHBPs) that are capable of forming quinone methide intermediates were synthesized and their cell growth inhibitory properties were evaluated in four different human cancer cell lines. Compounds 1, 1a, and 1b, corresponding to (4-acetyloxybenzyl diethylphosphate), (3-methyl-4-acetyloxybenzyl diethylphosphate), and (3-chloro-4-acetyloxybenzyl diethylphosphate), were significantly more potent than compounds 2 and 3, (2-acetyloxybenzyl diethylphosphate) and (3-acetyloxybenzyl diethylphosphate), respectively. Using HT-29 human colon cancer cells, compounds 1 and 3 increased apoptosis, inhibited proliferation, and caused a G(2)/M block in the cell cycle. Our data suggest that these compounds merit further investigation as potential anti-cancer agents. Copyright © 2011 Elsevier Ltd. All rights reserved.

Do Low Molecular Weight Agents Cause More Severe Asthma than High Molecular Weight Agents?

PubMed

Meca, Olga; Cruz, María-Jesús; Sánchez-Ortiz, Mónica; González-Barcala, Francisco-Javier; Ojanguren, Iñigo; Munoz, Xavier

2016-01-01

The aim of this study was to analyse whether patients with occupational asthma (OA) caused by low molecular weight (LMW) agents differed from patients with OA caused by high molecular weight (HMW) with regard to risk factors, asthma presentation and severity, and response to various diagnostic tests. Seventy-eight patients with OA diagnosed by positive specific inhalation challenge (SIC) were included. Anthropometric characteristics, atopic status, occupation, latency periods, asthma severity according to the Global Initiative for Asthma (GINA) control classification, lung function tests and SIC results were analysed. OA was induced by an HMW agent in 23 patients (29%) and by an LMW agent in 55 (71%). A logistic regression analysis confirmed that patients with OA caused by LMW agents had a significantly higher risk of severity according to the GINA classification after adjusting for potential confounders (OR = 3.579, 95% CI 1.136-11.280; p = 0.029). During the SIC, most patients with OA caused by HMW agents presented an early reaction (82%), while in patients with OA caused by LMW agents the response was mainly late (73%) (p = 0.0001). Similarly, patients with OA caused by LMW agents experienced a greater degree of bronchial hyperresponsiveness, measured as the difference in the methacholine dose-response ratio (DRR) before and after SIC (1.77, range 0-16), compared with patients with OA caused by HMW agents (0.87, range 0-72), (p = 0.024). OA caused by LMW agents may be more severe than that caused by HMW agents. The severity of the condition may be determined by the different mechanisms of action of these agents.

Honey - A Novel Antidiabetic Agent

PubMed Central

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

2012-01-01

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

The anorexic agents, sibutramine and fenfluramine, depress GABAB-induced inhibitory postsynaptic potentials in rat mesencephalic dopaminergic cells

PubMed Central

Ledonne, Ada; Sebastianelli, Luca; Federici, Mauro; Bernardi, Giorgio; Mercuri, Nicola Biagio

2009-01-01

Background and purpose Nutrition is the result of a complex interaction among environmental, homeostatic and reward-related processes. Accumulating evidence supports key roles for the dopaminergic neurons of the ventral midbrain in regulating feeding behaviour. For this reason, in the present study, we have investigated the electrophysiological effects of two centrally acting anorexic agents, fenfluramine and sibutramine, on these cells. Experimental approach Rat midbrain slices were used to make intracellular recordings from dopaminergic neurons of the substantia nigra and the ventral tegmental area. Gamma-aminobutyric acid (GABA)-mediated synaptic transmission was assessed from the inhibitory postsynaptic potentials (IPSPs) mediated by GABAA and GABAB receptors. Key results Fenfluramine and sibutramine reduced, concentration-dependently, the GABAB IPSPs, without affecting the GABAA-mediated potentials. This effect is presynaptic, as postsynaptic membrane responses induced by application of a GABAB receptor agonist, baclofen, were not affected by the two drugs. Furthermore, the selective 5-hydroxytriptamine 1B (5-HT1B) receptor antagonist, SB216641, blocked the reduction of GABAB IPSPs caused by fenfluramine and sibutramine, indicating that the receptor mediating this effect is 5-HT1B. Conclusions and implications Two anorexic agents, fenfluramine and sibutramine, induced the activation of 5-HT1B receptors located on presynaptic GABAergic terminals, thus reducing the release of GABA. This action can alter the strength of synaptic afferents that modify the activity of dopaminergic neurons, inducing neuronal excitation. Our results reveal an additional mechanism of action for fenfluramine and sibutramine that might contribute to reducing food intake, by influencing the pleasurable and motor aspects of feeding behaviour. PMID:19298257

Induction of defense responses against Magnaporthe oryzae in rice seedling by a new potential biocontrol agent Streptomyces JD211.

PubMed

Shao, Zhengying; Li, Zhang; Fu, Yanhui; Wen, Yangping; Wei, Saijin

2018-06-14

The induced resistance against plant pathogens via biocontrol agents is considered as an eco-friendly and promising strategy. In this study, the induced resistance against Magnaporthe oryzae (M. oryzae) in rice seedling by a new potential biocontrol agent Streptomyces JD211 (JD211) was evaluated. The effects of JD211 on defense-related enzymes activities and defense genes expression were investigated. The biocontrol efficacy of different JD211 concentrations was different, and the treatment of 10 g kg -1 JD211 achieved the highest biocontrol efficacy. Activities of catalase, phenylalanine ammonia-lyase (PAL) and β-1,3-glucanase significantly increased in the presence of JD211. The gene expression level of both PAL and pathogenesis related protein 1 increased when rice seedlings were inoculated with JD211 alone or co-inoculated with M. oryzae, and the expression level of chitinase gene was enhanced by JD211 in the later stage. All results suggested that JD211 could increase the rice resistance by stimulating a series of defense responses, which was the result of induced systemic resistance by JD211. This work will provide a new biocontrol agent against Magnaporthe oryzae in rice seedling. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhancing Potentially Plant-Available Lead Concentrations in Contaminated Residential Soils Using a Biodegradable Chelating Agent

NASA Astrophysics Data System (ADS)

Andra, S.; Datta, R.; Sarkar, D.; Saminathan, S.

2007-12-01

Chelation of heavy metals is an important factor in enhancing metal solubility and, hence, metal availability to plants to promote phytoremediation. In the present study, we compared the effects of application of a biodegradable chelating agent, namely, ethylenediaminedisuccinic acid (EDDS) on enhancing plant available form of lead (Pb) in Pb-based paint contaminated residential soils compared to that of a more commonly used, but non-biodegradable chelate, i.e., ethylenediaminetetraacetic acid (EDTA). Development of a successful phytoremediation model for metals such as Pb depends on a thorough understanding of the physical and chemical properties of the soil, along with the optimization of a chelate treatment to mobilize Pb from `unavailable' pools to potentially plant available fraction. In this context, we set out to perform batch incubation experiments to investigate the effectiveness of the two aforementioned chelates in enhancing plant available Pb at four different concentrations (0, 5, 10 and 15 mM/kg soil) and three treatment durations (0, 10 and 30 days). We selected 12 contaminated residential soils from two major metropolitan areas (San Antonio, TX and Baltimore, MD) with varying soil physico-chemical properties - the soils from San Antonio were primarily alkaline and those from Baltimore were typically acidic. Total soil Pb concentrations ranged between 256 mg/kg and 4,182 mg/kg. Our results show that both chelates increased the solubility of Pb, otherwise occluded in the complex soil matrix. For both EDTA and EDDS, the exchangeable concentrations of soil Pb also increased with increase in chelate concentration and incubation time. The most effective treatment was 15 mM chelate kg-1 soil incubated for 30 days, which caused many fold increase in potentially plant available Pb (a combination of the soluble and exchangeable fractions) relative to the unamended controls. Step wise multiple linear regression analysis using chelate-extractable Pb and soil

Triggered pore-forming agents

DOEpatents

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

1998-01-01

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

12 CFR 612.2260 - Standards of conduct for agents.

Code of Federal Regulations, 2012 CFR

2012-01-01

... agents. (a) Agents of System institutions shall maintain high standards of honesty, integrity, and... business practices, to avoid or control situations that have inherent potential for sensitivity, either...

12 CFR 612.2260 - Standards of conduct for agents.

Code of Federal Regulations, 2014 CFR

2014-01-01

... agents. (a) Agents of System institutions shall maintain high standards of honesty, integrity, and... business practices, to avoid or control situations that have inherent potential for sensitivity, either...

12 CFR 612.2260 - Standards of conduct for agents.

Code of Federal Regulations, 2013 CFR

2013-01-01

... agents. (a) Agents of System institutions shall maintain high standards of honesty, integrity, and... business practices, to avoid or control situations that have inherent potential for sensitivity, either...

An Embodied Agent Helps Anxious Students in Mathematics Learning

ERIC Educational Resources Information Center

Kim, Yanghee; Thayne, Jeffrey; Wei, Quan

2017-01-01

Mathematics anxiety is known to be detrimental to mathematics learning. This study explored if an embodied agent could be used to help alleviate student anxiety in classrooms. To examine this potential, agent-guided algebra lessons were developed, in which an animated agent was equipped with prescriptive instructional guidance and anxiety treating…

BSL-3 Laboratory Practices in the United States: Comparison of Select Agent and Non–Select Agent Facilities

PubMed Central

Pompei, Victoria C.; Anderson, Alice

2014-01-01

New construction of biosafety level 3 (BSL-3) laboratories in the United States has increased in the past decade to facilitate research on potential bioterrorism agents. The Centers for Disease Control and Prevention inspect BSL-3 facilities and review commissioning documentation, but no single agency has oversight over all BSL-3 facilities. This article explores the extent to which standard operating procedures in US BSL-3 facilities vary between laboratories with select agent or non–select agent status. Comparisons are made for the following variables: personnel training, decontamination, personal protective equipment (PPE), medical surveillance, security access, laboratory structure and maintenance, funding, and pest management. Facilities working with select agents had more complex training programs and decontamination procedures than non–select agent facilities. Personnel working in select agent laboratories were likely to use powered air purifying respirators, while non–select agent laboratories primarily used N95 respirators. More rigorous medical surveillance was carried out in select agent workers (although not required by the select agent program) and a higher level of restrictive access to laboratories was found. Most select agent and non–select agent laboratories reported adequate structural integrity in facilities; however, differences were observed in personnel perception of funding for repairs. Pest management was carried out by select agent personnel more frequently than non–select agent personnel. Our findings support the need to promote high quality biosafety training and standard operating procedures in both select agent and non–select agent laboratories to improve occupational health and safety. PMID:24552359

Marine Isolates of Trichoderma spp. as Potential Halotolerant Agents of Biological Control for Arid-Zone Agriculture ▿ †

PubMed Central

Gal-Hemed, Inbal; Atanasova, Lea; Komon-Zelazowska, Monika; Druzhinina, Irina S.; Viterbo, Ada; Yarden, Oded

2011-01-01

The scarcity of fresh water in the Mediterranean region necessitates the search for halotolerant agents of biological control of plant diseases that can be applied in arid-zone agriculture irrigated with saline water. Among 29 Trichoderma strains previously isolated from Mediterranean Psammocinia sp. sponges, the greatest number of isolates belong to the Trichoderma longibrachiatum-Hypocrea orientalis species pair (9), H. atroviridis/T. atroviride (9), and T. harzianum species complex (7), all of which are known for high mycoparasitic potential. In addition, one isolate of T. asperelloides and two putative new species, Trichoderma sp. O.Y. 14707 and O.Y. 2407, from Longibrachiatum and Strictipilosa clades, respectively, have been identified. In vitro salinity assays showed that the ability to tolerate increasing osmotic pressure (halotolerance) is a strain- or clade-specific property rather than a feature of a species. Only a few isolates were found to be sensitive to increased salinity, while others either were halotolerant or even demonstrated improved growth in increasingly saline conditions. In vitro antibiosis assays revealed strong antagonistic activity toward phytopathogens due to the production of both soluble and volatile metabolites. Two marine-derived Trichoderma isolates, identified as T. atroviride and T. asperelloides, respectively, effectively reduced Rhizoctonia solani damping-off disease on beans and also induced defense responses in cucumber seedlings against Pseudomonas syringae pv. lachrimans. This is the first inclusive evaluation of marine fungi as potential biocontrol agents. PMID:21666030

Hydroxy double salts intercalated with Mn(II) complexes as potential contrast agents

NASA Astrophysics Data System (ADS)

Jin, Miao; Li, Wanjing; Spillane, Dominic E. M.; Geraldes, Carlos F. G. C.; Williams, Gareth R.; Bligh, S. W. Annie

2016-03-01

A series of Mn(II) aminophosphonate complexes were successfully synthesized and intercalated into the hydroxy double salt [Zn5(OH)8]Cl2·yH2O. Complex incorporation led to an increase in the interlayer spacing from 7.8 to 10-12 Å. Infrared spectroscopy showed the presence of the characteristic vibration peaks of the Mn(II) complexes in the intercalates' spectra, indicating successful incorporation. The complex-loaded composites had somewhat lower proton relaxivities than the pure complexes. Nevertheless, these intercalates may have use as MRI contrast agents for patients with poor kidney function, where traditional Gd(III)-based contrast agents cause severe renal failure.

An evaluation of the sonoporation potential of low-boiling point phase-change ultrasound contrast agents in vitro.

PubMed

Fix, Samantha M; Novell, Anthony; Yun, Yeoheung; Dayton, Paul A; Arena, Christopher B

2017-01-01

Phase-change ultrasound contrast agents (PCCAs) offer a solution to the inherent limitations associated with using microbubbles for sonoporation; they are characterized by prolonged circulation lifetimes, and their nanometer-scale sizes may allow for passive accumulation in solid tumors. As a first step towards the goal of extravascular cell permeabilization, we aim to characterize the sonoporation potential of a low-boiling point formulation of PCCAs in vitro. Parameters to induce acoustic droplet vaporization and subsequent microbubble cavitation were optimized in vitro using high-speed optical microscopy. Sonoporation of pancreatic cancer cells in suspension was then characterized at a range of pressures (125-600 kPa) and pulse lengths (5-50 cycles) using propidium iodide as an indicator molecule. We achieved sonoporation efficiencies ranging from 8 ± 1% to 36 ± 4% (percent of viable cells), as evidenced by flow cytometry. Increasing sonoporation efficiency trended with increasing pulse length and peak negative pressure. We conclude that PCCAs can be used to induce the sonoporation of cells in vitro, and our results warrant further investigation into the use of PCCAs as extravascular sonoporation agents in vivo.

Rapid screening of potential autophagic inductor agents using mammalian cell lines.

PubMed

Martins, Waleska K; Severino, Divinomar; Souza, Cleidiane; Stolf, Beatriz S; Baptista, Maurício S

2013-06-01

Recent progress in understanding the molecular basis of autophagy has demonstrated its importance in several areas of human health. Affordable screening techniques with higher sensitivity and specificity to identify autophagy are, however, needed to move the field forward. In fact, only laborious and/or expensive methodologies such as electron microscopy, dye-staining of autophagic vesicles, and LC3-II immunoblotting or immunoassaying are available for autophagy identification. Aiming to fulfill this technical gap, we describe here the association of three widely used assays to determine cell viability - Crystal Violet staining (CVS), 3-[4, 5-dimethylthiaolyl]-2, 5-diphenyl-tetrazolium bromide (MTT) reduction, and neutral red uptake (NRU) - to predict autophagic cell death in vitro. The conceptual framework of the method is the superior uptake of NR in cells engaging in autophagy. NRU was then weighted by the average of MTT reduction and CVS allowing the calculation of autophagic arbitrary units (AAU), a numeric variable that correlated specifically with the autophagic cell death. The proposed strategy is very useful for drug discovery, allowing the investigation of potential autophagic inductor agents through a rapid screening using mammalian cell lines B16-F10, HaCaT, HeLa, MES-SA, and MES-SA/Dx5 in a unique single microplate. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nitric oxide inhibitory daphnane diterpenoids as potential anti-neuroinflammatory agents for AD from the twigs of Trigonostemon thyrsoideus.

PubMed

Liu, Feng; Yang, Xueyuan; Ma, Jun; Yang, Yuling; Xie, Chunfeng; Tuerhong, Muhetaer; Jin, Da-Qing; Xu, Jing; Lee, Dongho; Ohizumi, Yasushi; Guo, Yuanqiang

2017-12-01

The extensive pathology studies revealed that Alzheimer's disease (AD) is closely related to neuroinflammation and anti-neuroinflammatory agents may be potentially useful for the treatment of AD. A continuous search for new nitric oxide (NO) inhibitory compounds as anti-neuroinflammatory agents for AD resulted in the isolation of four new (1-4) and eight known (5-12) daphnane diterpenoids from the twigs of Trigonostemon thyrsoideus. Their structures were elucidated on the basis of extensive nuclear magnetic resonance (NMR) spectroscopic data analysis and the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Compounds 1-4 represent new examples of daphnane diterpenoid orthoesters and 4 features a rare and complex macroring diterpenoid structure. The anti-neuroinflammatory effects were examined by inhibiting NO release in lipopolysaccharide (LPS)-induced murine microglial BV-2 cells. The possible mechanism of NO inhibition of some bioactive compounds was also investigated using molecular docking, which revealed the interactions of bioactive compounds with the inducible nitric oxide synthase (iNOS) protein. Copyright © 2017 Elsevier Inc. All rights reserved.

Triggered pore-forming agents

DOEpatents

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

1998-07-07

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

Gancidin W, a potential low-toxicity antimalarial agent isolated from an endophytic Streptomyces SUK10

PubMed Central

Zin, Noraziah Mohamad; Baba, Mohd Shukri; Zainal-Abidin, Abu Hassan; Latip, Jalifah; Mazlan, Noor Wini; Edrada-Ebel, RuAngelie

2017-01-01

Endophytic Streptomyces strains are potential sources for novel bioactive molecules. In this study, the diketopiperazine gancidin W (GW) was isolated from the endophytic actinobacterial genus Streptomyces, SUK10, obtained from the bark of Shorea ovalis tree, and it was tested in vivo against Plasmodium berghei PZZ1/100. GW exhibited an inhibition rate of nearly 80% at 6.25 and 3.125 μg kg−1 body weight on day four using the 4-day suppression test method on male ICR strain mice. Comparing GW at both concentrations with quinine hydrochloride and normal saline as positive and negative controls, respectively, 50% of the mice treated with 3.125 μg kg−1 body weight managed to survive for more than 11 months after infection, which almost reached the life span of normal mice. Biochemical tests of selected enzymes and proteins in blood samples of mice treated with GW were also within normal levels; in addition, no abnormalities or injuries were found on internal vital organs. These findings indicated that this isolated bioactive compound from Streptomyces SUK10 exhibits very low toxicity and is a good candidate for potential use as an antimalarial agent in an animal model. PMID:28223778

Characterization and competitive ability of non-aflatoxigenic Aspergillus flavus isolated from the maize agro-ecosystem in Argentina as potential aflatoxin biocontrol agents.

PubMed

Alaniz Zanon, María Silvina; Clemente, María Paz; Chulze, Sofía Noemí

2018-07-20

Aspergillus flavus is an opportunistic pathogen and may produce aflatoxins in maize, one of the most important crops in Argentina. A promising strategy to reduce aflatoxin accumulation is the biological control based on competitive exclusion. In order to select potential biocontrol agents among isolates from the maize growing region in Argentina, a total of 512 A. flavus strains were isolated from maize kernels and soil samples. Thirty-six per cent of the isolates from maize kernels did not produce detectable levels of aflatoxins, while 73% of the isolates from soil were characterized as non-aflatoxin producers. Forty percent and 49% of the isolates from maize kernels and soil samples, respectively, were not producers of cyclopiazonic acid (CPA). Sclerotia morphology was evaluated using Czapek Dox media. Eighty-six per cent of the isolates from maize kernels and 85% of the isolates from soil samples were L sclerotia morphotype (average diameter > 400 μm). The remaining isolates did not produce sclerotia. All isolates had MAT 1-1 idiomorph. The competitive ability of 9 non aflatoxigenic strains, 4 CPA(+) and 5 CPA(-), was evaluated in co-inoculations of maize kernels with an aflatoxigenic strain. All evaluated strains significantly (p < 0.05) reduced aflatoxin contamination in maize kernels. The aflatoxin B 1 (AFB 1 ) reduction ranged from 6 to 60%. The strain A. flavus ARG5/30 isolated from maize kernels would be a good candidate as a potential biocontrol agent to be used in maize, since it was characterized as neither aflatoxin nor CPA producer, morphotype L, MAT 1-1 idiomorph, and reduced AFB 1 content in maize kernels by 59%. This study showed the competitive ability of potential aflatoxin biocontrol agents to be evaluated under field trials in a maize agro-ecosystem in Argentina. Copyright © 2018 Elsevier B.V. All rights reserved.

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

PubMed Central

Lefranc, Florence; Carbone, Marianna; Mollo, Ernesto; Gavagnin, Margherita; Betancourt, Tania; Dasari, Ramesh

2016-01-01

Abstract The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity. PMID:27925266

Quantification of the biocontrol agent Trichoderma harzianum with real-time TaqMan PCR and its potential extrapolation to the hyphal biomass.

PubMed

López-Mondéjar, Rubén; Antón, Anabel; Raidl, Stefan; Ros, Margarita; Pascual, José Antonio

2010-04-01

The species of the genus Trichoderma are used successfully as biocontrol agents against a wide range of phytopathogenic fungi. Among them, Trichoderma harzianum is especially effective. However, to develop more effective fungal biocontrol strategies in organic substrates and soil, tools for monitoring the control agents are required. Real-time PCR is potentially an effective tool for the quantification of fungi in environmental samples. The aim of this study consisted of the development and application of a real-time PCR-based method to the quantification of T. harzianum, and the extrapolation of these data to fungal biomass values. A set of primers and a TaqMan probe for the ITS region of the fungal genome were designed and tested, and amplification was correlated to biomass measurements obtained with optical microscopy and image analysis, of the hyphal length of the mycelium of the colony. A correlation of 0.76 between ITS copies and biomass was obtained. The extrapolation of the quantity of ITS copies, calculated based on real-time PCR data, into quantities of fungal biomass provides potentially a more accurate value of the quantity of soil fungi. Copyright 2009 Elsevier Ltd. All rights reserved.

How Long Does the Benefit of Biologics Last? An Update on Time To Relapse and Potential for Rebound of Biologic Agents for Psoriasis.

PubMed

Kamaria, Monique; Liao, Wilson; Koo, J Y

2010-01-01

The biologic agents vary considerably in terms of their long-term duration of effect. Using the definitions provided by the National Psoriasis Foundation Medical Board, the objective of this review was to compare all biologic agents with respect to time to relapse and potential for rebound. Overall, alefacept had the longest off-treatment benefit (29.9 weeks in Psoriasis Area and Severity Index [PASI] 75 responders), followed by ustekinumab (22 weeks), infliximab (19.5 weeks), adalimumab (18 weeks), etanercept (12.1 weeks in PASI 50 responders), and, lastly, efalizumab (9.6 weeks). Rebound was reported commonly for efalizumab (14%) and, extremely rarely, for etanercept (0.002%).

Redox-active compounds with a history of human use: antistaphylococcal action and potential for repurposing as topical antibiofilm agents.

PubMed

Ooi, N; Eady, E A; Cove, J H; O'Neill, A J

2015-02-01

To investigate the antistaphylococcal/antibiofilm activity and mode of action (MOA) of a panel of redox-active (RA) compounds with a history of human use and to provide a preliminary preclinical assessment of their potential for topical treatment of staphylococcal infections, including those involving a biofilm component. Antistaphylococcal activity was evaluated by broth microdilution and by time-kill studies with growing and slow- or non-growing cells. The antibiofilm activity of RA compounds, alone and in combination with established antibacterial agents, was assessed using the Calgary Biofilm Device. Established assays were used to examine the membrane-perturbing effects of RA compounds, to measure penetration into biofilms and physical disruption of biofilms and to assess resistance potential. A living skin equivalent model was used to assess the effects of RA compounds on human skin. All 15 RA compounds tested displayed antistaphylococcal activity against planktonic cultures (MIC 0.25-128 mg/L) and 7 eradicated staphylococcal biofilms (minimum biofilm eradication concentration 4-256 mg/L). The MOA of all compounds involved perturbation of the bacterial membrane, whilst selected compounds with antibiofilm activity caused destructuring of the biofilm matrix. The two most promising agents [celastrol and nordihydroguaiaretic acid (NDGA)] in respect of antibacterial potency and selective toxicity against bacterial membranes acted synergistically with gentamicin against biofilms, did not damage artificial skin following topical application and exhibited low resistance potential. In contrast to established antibacterial drugs, some RA compounds are capable of eradicating staphylococcal biofilms. Of these, celastrol and NDGA represent particularly attractive candidates for development as topical antistaphylococcal biofilm treatments. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

In Vitro Evaluation of Gd(3+)-Anionic Linear Globular Dendrimer-Monoclonal Antibody: Potential Magnetic Resonance Imaging Contrast Agents for Prostate Cancer Cell Imaging.

PubMed

Mirzaei, Mehdi; Mehravi, Bita; Ardestani, Mehdi Shafiee; Ziaee, Seyed Amir Mohsen; Pourghasem, Peyman

2015-12-01

Early stage prostate cancer diagnosis is of high global interest. Magnetic resonance imaging (MRI) is a non-invasive modality for early cancer diagnosis, in particular for prostate cancer detection. The research aim is to synthesize a nanodendrimer and its conjugate with C595 monoclonal antibody (mAb C595), against prostate cancer, followed by its chelating with Gd(3+). Anti-MUC-1 mAb C595 was conjugated to an anionic linear globular dendrimer (ALGDG2). The polyethylene glycol core and citric acid shell were synthesized followed by loading with Gd(3+) to make novel contrast agents for functional MRI. The in vitro behavior and MRI parameters of the nanoconjugate were investigated performing several studies such as cell toxicity and TNF-alpha evaluations. The investigation of magnetic resonance imaging parameters indicated how well nanoconjugate performs in (1)H-NMR and (17)O-NMR in vitro. Results showed a potential specific MRI activity by improving the swelling responses cell binding. The MTT (2-(4,5-dimethyl-2-thiazolyl)-3,5-diphenyl-2H-tetrazolium bromide) assay demonstrated that this contrast agent had significant cytotoxicity on prostate cancer cells. These results showed that Gd(3+)-ALGDG2-C595 is a potential prostate molecular imaging agent and could be considered as an ideal functional nanoprobe. Additionally, further investigations by clinical trials are in the pipeline.

The Design of Motivational Agents and Avatars

ERIC Educational Resources Information Center

Baylor, Amy L.

2011-01-01

While the addition of an anthropomorphic interface agent to a learning system generally has little direct impact on learning, it potentially has a huge impact on learner motivation. As such agents become increasingly ubiquitous on the Internet, in virtual worlds, and as interfaces for learning and gaming systems, it is important to design them to…

1α,25-Dihydroxyvitamin D3-3β-bromoacetate, a potential cancer therapeutic agent: synthesis and molecular mechanism of action

PubMed Central

Ray, Rahul; Lambert, James R.

2011-01-01

Synthesis of 1α,25-dihydroxyvitamin D3-3β-bromoacetate (1,25(OH)2D3-3-BE), a potential anti-cancer agent is presented. We also report that mechanism of action of 1,25(OH)2D3-3-BE may involve reduction of its catabolism, as evidenced by the reduced and delayed expression of 1α,25-dihydroxyvitamin D3-24-hydroxylase (CYP24) gene in cellular assays. PMID:21392983

STATINS MORE THAN CHOLESTEROL LOWERING AGENTS IN ALZHEIMER DISEASE: THEIR PLEIOTROPIC FUNCTIONS AS POTENTIAL THERAPEUTIC TARGETS

PubMed Central

Barone, Eugenio; Domenico, Fabio Di; Butterfield, D. Allan

2013-01-01

Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive impairment, inability to perform activities of daily living and mood changes. Statins, long known to be beneficial in conditions where dyslipidemia occurs by lowering serum cholesterol levels, also have been proposed for use in neurodegenerative conditions, including AD. However, it is not clear that the purported effectiveness of statins in neurodegenerative disorders is directly related to cholesterol-lowering effects of these agents; rather, the pleiotropic functions of statins likely play critical roles. The aim of this review is to provide an overview on the new discoveries about the effects of statin therapy on the oxidative ad nitrosative stress levels as well as on the modulation of the heme oxygenase/biliverdin reductase (HO/BVR) system in the brain. We propose a novel mechanism of action for atorvastatin which, through the activation of HO/BVR-A system, may contribute to the neuroprotective effects thus suggesting a potential therapeutic role in AD and potentially accounting for the observation of decreased AD incidence with persons on statin. PMID:24231510

wFlu: Characterization and Evaluation of a Native Wolbachia from the Mosquito Aedes fluviatilis as a Potential Vector Control Agent

PubMed Central

Gonçalves, Daniela da Silva; Moreira, Luciano Andrade

2013-01-01

There is currently considerable interest and practical progress in using the endosymbiotic bacteria Wolbachia as a vector control agent for human vector-borne diseases. Such vector control strategies may require the introduction of multiple, different Wolbachia strains into target vector populations, necessitating the identification and characterization of appropriate endosymbiont variants. Here, we report preliminary characterization of wFlu, a native Wolbachia from the neotropical mosquito Aedes fluviatilis, and evaluate its potential as a vector control agent by confirming its ability to cause cytoplasmic incompatibility, and measuring its effect on three parameters determining host fitness (survival, fecundity and fertility), as well as vector competence (susceptibility) for pathogen infection. Using an aposymbiotic strain of Ae. fluviatilis cured of its native Wolbachia by antibiotic treatment, we show that in its natural host wFlu causes incomplete, but high levels of, unidirectional cytoplasmic incompatibility, has high rates of maternal transmission, and no detectable fitness costs, indicating a high capacity to rapidly spread through host populations. However, wFlu does not inhibit, and even enhances, oocyst infection with the avian malaria parasite Plasmodium gallinaceum. The stage- and sex-specific density of wFlu was relatively low, and with limited tissue distribution, consistent with the lack of virulence and pathogen interference/symbiont-mediated protection observed. Unexpectedly, the density of wFlu was also shown to be specifically-reduced in the ovaries after bloodfeeding Ae. fluviatilis. Overall, our observations indicate that the Wolbachia strain wFlu has the potential to be used as a vector control agent, and suggests that appreciable mutualistic coevolution has occurred between this endosymbiont and its natural host. Future work will be needed to determine whether wFlu has virulent host effects and/or exhibits pathogen interference when

Extravasation of antineoplastic agents: prevention and treatments.

PubMed

Boschi, Rita; Rostagno, Elena

2012-07-31

The extravasation of antineoplastic agents is an unwanted and distressing situation that can easily occur. It may cause severe and irreversible local injuries. Left untreated, vesicant chemotherapy extravasation can potentially cause tissue necrosis, functional impairment and permanent disfigurement. This article provides a review of current literature regarding recommendations on the prevention and treatment of extravasation of antineoplastic agents.

Design and synthesis of some new 2,3'-bipyridine-5-carbonitriles as potential anti-inflammatory/antimicrobial agents.

PubMed

Elzahhar, Perihan A; Elkazaz, Salwa; Soliman, Raafat; El-Tombary, Alaa A; Shaltout, Hossam A; El-Ashmawy, Ibrahim M; Abdel Wahab, Abeer E; El-Hawash, Soad A

2017-08-01

Inflammation may cause accumulation of fluid in the injured area, which may promote bacterial growth. Other reports disclosed that non-steroidal anti-inflammatory drugs may enhance progression of bacterial infection. This work describes synthesis of new series of 2,3'-bipyridine-5-carbonitriles as structural analogs of etoricoxib, linked at position-6 to variously substituted thio or oxo moieties. Biological screening results revealed that compounds 2b, 4b, 7e and 8 showed significant acute and chronic AI activities and broad spectrum of antimicrobial activity. In addition, similarity ensemble approach was applied to predict potential biological targets of the tested compounds. Then, pharmacophore modeling study was employed to determine the most important structural parameters controlling bioactivity. Moreover, title compounds showed physicochemical properties within those considered adequate for drug candidates. This study explored the potential of such series of compounds as structural leads for further modification to develop a new class of dual AI-antimicrobial agents.

Gregarines (Apicomplexa, Gregarinasina) in psocids (Insecta, Psocoptera) including a new species description and their potential use as pest control agents.

PubMed

Rueckert, Sonja; Devetak, Dušan

2017-08-01

Gregarine apicomplexans are unicellular organisms that infect invertebrate hosts in marine, freshwater and terrestrial habitats. The largest group of invertebrates infested on land is the insects. The insect order Psocoptera (booklice) has recently gained wider interest due to specimens occurring in stored food products and therefore being considered pest organisms. Biological control agents are often used to eliminate pest organisms. In this study we examined the psocid Dorypteryx domestica, an invasive psocid species that is spreading all over the world. We were able to isolate and describe a new gregarine species (Enterocystis dorypterygis sp. n.) infecting D. domestica. The trophozoites are panduri- or pyriform and their association/syzygy is caudo-frontal. The surface is inscribed by longitudinal epicytic folds covering the complete cell. Phylogenetic analyses of the SSU rDNA gene revealed an only weakly supported relationship with two Gregarina species G. ormieri and G. basiconstrictonea, both from tenebrionid beetles. Gregarines have been proposed to have some potential as biological control agents for several insects. Identifying the gregarine species infecting pest organisms like psocids is a first step and prerequisite for the probable utilization of these parasites as biological control agents in the future. Copyright © 2017 Elsevier GmbH. All rights reserved.

Biology, behavior, and larval morphology of Salbia lotanalis (Lepidoptera: Crambidae), a potential biological control agent of Miconia calvescens (Myrtales: Melastomataceae) from Costa Rica

Treesearch

Alexander Castillo; M. Tracy Johnson; Francisco R. Badenes-Pérez

2014-01-01

The leaf roller Salbia lotanalis Druce (Lepidoptera: Crambidae), a potential biological control agent of Miconia calvescens de Candolle (Melastomataceae), was studied in Costa Rica. Larvae were collected from a field site near San Jose and the insect was reared in the laboratory to study its biology and behavior. Chaetotaxy and...

Pedagogical Agents as Learning Companions: The Impact of Agent Emotion and Gender

ERIC Educational Resources Information Center

Kim, Yanghee; Baylor, A. L.; Shen, E.

2007-01-01

The potential of emotional interaction between human and computer has recently interested researchers in human-computer interaction. The instructional impact of this interaction in learning environments has not been established, however. This study examined the impact of emotion and gender of a pedagogical agent as a learning companion (PAL) on…

Biological agents for controlling excessive scarring.

PubMed

Berman, Brian

2010-01-01

The potential of various biological agents to reduce or prevent excessive scar formation has now been evaluated in numerous in-vitro studies, experimental animal models and preliminary clinical trials, in some cases with particularly promising results. Perhaps prominent among this group of biological agents, and, to some degree, possibly representing marketed compounds already being used 'off label' to manage excessive scarring, are the tumor necrosis factor alpha antagonist etanercept, and immune-response modifiers such as IFNalpha2b and imiquimod. Additional assessment of these novel agents is now justified with a view to reducing or preventing hypertrophic scars, keloid scars and the recurrence of post-excision keloid lesions.

On the Basicity of 8-Phenylsulfanyl Quipazine Derivatives: New Potential Serotonergic Agents.

PubMed

Pieńko, T; Taciak, P P; Mazurek, A P

2015-07-09

A protonation state of serotonergic ligands plays a crucial role in their pharmacological activity. In this research, the basicity of 8-phenylsulfanyl quipazine derivatives as new potential serotonergic agents was studied. The most favorable protonation sites were determined in the gas and aqueous phases. In water, a solvation effect promoting the protonation of the N3 atom overcomes a positive charge delocalization phenomenon favoring a N1 atom protonation. The most stable conformations of neutral and protonated molecules in gas and water were found. It was demonstrated that a diprotonation reaction may occur. The most favorable among the diprotonated structures is the molecule with the N1 and N3 atoms protonated. A calculation of the pKa and pKa2 in water of a set of monosubstituted 8-phenylsulfanyl quipazine derivatives was performed using B3LYP/6-31G(d) and the SMD continuum solvation model. Enthalpic and entropic contributions to the pKa and pKa2 in gas and water were separated for a rationalization of a substituent effect on values of the pKa and pKa2. The relationship of the proton affinity and the solvation enthalpy in water with some reactivity descriptors, such as the Fukui function, the molecular electrostatic potential (MEP), and the global softness, was investigated. The order of the pKa values is the most controlled by the entropy. The diprotonation reaction, despite having an unfavorable enthalpy in water, is driven entropically. Final state effects in the diprotonated species were analyzed with the triadic formula. Results of a calculation of the theoretical basicity of the 8-phenylsulfanyl quipazines indicate that they should be monoprotonated on the N3 atom in the CNS environment. Diprotonation of the studied compounds may occur in very acidic body fluids such as the gastric juice.

High level expression and immunochemical characterization of botulinum neurotoxin type F light chain.

PubMed

Chauhan, Ritika; Chauhan, Vinita; Rao, Mula Kameshwar; Chaudhary, Dilip; Bhagyawant, Sameer; Dhaked, Ram Kumar

2018-06-01

Botulinum neurotoxins (BoNTs) are the most toxic biological substances known. Their potential use as biological warfare agent results in their classification as category A biowarfare agent by Centers for Disease Control and Prevention (CDC), USA. Presently, there are no approved detection system and pharmacological treatments for BoNT intoxication. Although a toxoid vaccine is available for immuno-prophylaxis, vaccines cannot reverse the effect of pre-translocated toxin. Direct handling of the live BoNTs for developing detection and therapeutics may pose fatal danger. This concern was addressed by purifying the recombinant catalytically active light chain of BoNT/F. BoNT/F-LC gene was amplified from the genomic DNA using specifically designed primers and expressed in Escherichia coli. Expression and purification profile were optimized under different conditions for biologically active light chain production. Specific polyclonal antibodies generated against type F illustrates in vivo neutralization in mice and rabbit. These antibodies play key role in conceiving the development of high throughput SPR based detection system which is a highly precise label free technique for protein interaction analysis. The presented work is first of its kind, signifying the production of highly stable and active rBoNT/F-LC and its immunochemical characterization. The study aids in paving the path towards developing a persistent detection system as well as in presenting comprehended scheme for in vitro small molecule therapeutics analysis. Copyright © 2018 Elsevier Inc. All rights reserved.

Potential use of cucumber (Cucumis sativus L.) endophytic fungi as seed treatment agents against root-knot nematode Meloidogyne incognita.

PubMed

Yan, Xiao-ning; Sikora, Richard A; Zheng, Jing-wu

2011-03-01

Seed treatment with endophytic fungi has been regarded as an effective method for plant parasitic nematode control. Endophytic fungi from cucumber seedlings were isolated and screened for their potential to be used as seed treatment agents against Meloidogyne incognita. Among the 294 isolates screened, 23 significantly reduced galls formed by M. incognita in greenhouse test. The 10 most effective isolates were Fusarium (5), Trichoderma (1), Chaetomium (1), Acremonium (1), Paecilomyces (1), and Phyllosticta (1). Their control efficacies were repeatedly tested and their colonizations as well as in vitro activity against M. incognita were studied. They reduced the number of galls by 24.0%-58.4% in the first screening and 15.6%-44.3% in the repeated test, respectively. Phyllosticta Ph511 and Chaetomium Ch1001 had high colonizations on both the roots and the aboveground parts of cucumber seedlings. Fusarium isolates had colonization preference on the roots, their root colonizations ranging from 20.1% to 47.3% of the total root area. Trichoderma Tr882, Paecilomyces Pa972, and Acremonium Ac985 had low colonizations on both the roots and the aboveground parts. Acremonium Ac985, Chaetomium Ch1001, Paecilomyces Pa972, and Phyllosticta Ph511 produced compounds affecting motility of the second stage juveniles of M. incognita. Based on these results, Chaetomium Ch1001 was considered to have the highest potential as a seed treatment agent for M. incognita biocontrol.

Potential use of cucumber (Cucumis sativus L.) endophytic fungi as seed treatment agents against root-knot nematode Meloidogyne incognita *

PubMed Central

Yan, Xiao-ning; Sikora, Richard A.; Zheng, Jing-wu

2011-01-01

Seed treatment with endophytic fungi has been regarded as an effective method for plant parasitic nematode control. Endophytic fungi from cucumber seedlings were isolated and screened for their potential to be used as seed treatment agents against Meloidogyne incognita. Among the 294 isolates screened, 23 significantly reduced galls formed by M. incognita in greenhouse test. The 10 most effective isolates were Fusarium (5), Trichoderma (1), Chaetomium (1), Acremonium (1), Paecilomyces (1), and Phyllosticta (1). Their control efficacies were repeatedly tested and their colonizations as well as in vitro activity against M. incognita were studied. They reduced the number of galls by 24.0%–58.4% in the first screening and 15.6%–44.3% in the repeated test, respectively. Phyllosticta Ph511 and Chaetomium Ch1001 had high colonizations on both the roots and the aboveground parts of cucumber seedlings. Fusarium isolates had colonization preference on the roots, their root colonizations ranging from 20.1% to 47.3% of the total root area. Trichoderma Tr882, Paecilomyces Pa972, and Acremonium Ac985 had low colonizations on both the roots and the aboveground parts. Acremonium Ac985, Chaetomium Ch1001, Paecilomyces Pa972, and Phyllosticta Ph511 produced compounds affecting motility of the second stage juveniles of M. incognita. Based on these results, Chaetomium Ch1001 was considered to have the highest potential as a seed treatment agent for M. incognita biocontrol. PMID:21370507

Α-aryl-N-alkyl nitrones, as potential agents for stroke treatment: synthesis, theoretical calculations, antioxidant, anti-inflammatory, neuroprotective, and brain-blood barrier permeability properties.

PubMed

Chioua, Mourad; Sucunza, David; Soriano, Elena; Hadjipavlou-Litina, Dimitra; Alcázar, Alberto; Ayuso, Irene; Oset-Gasque, María Jesús; González, María Pilar; Monjas, Leticia; Rodríguez-Franco, María Isabel; Marco-Contelles, José; Samadi, Abdelouahid

2012-01-12

We report the synthesis, theoretical calculations, the antioxidant, anti-inflammatory, and neuroprotective properties, and the ability to cross the blood-brain barrier (BBB) of (Z)-α-aryl and heteroaryl-N-alkyl nitrones as potential agents for stroke treatment. The majority of nitrones compete with DMSO for hydroxyl radicals, and most of them are potent lipoxygenase inhibitors. Cell viability-related (MTT assay) studies clearly showed that nitrones 1-3 and 10 give rise to significant neuroprotection. When compounds 1-11 were tested for necrotic cell death (LDH release test) nitrones 1-3, 6, 7, and 9 proved to be neuroprotective agents. In vitro evaluation of the BBB penetration of selected nitrones 1, 2, 10, and 11 using the PAMPA-BBB assay showed that all of them cross the BBB. Permeable quinoline nitrones 2 and 3 show potent combined antioxidant and neuroprotective properties and, therefore, can be considered as new lead compounds for further development in specific tests for potential stroke treatment.

Agent based modeling of the effects of potential treatments over the blood-brain barrier in multiple sclerosis.

PubMed

Pennisi, Marzio; Russo, Giulia; Motta, Santo; Pappalardo, Francesco

2015-12-01

Multiple sclerosis is a disease of the central nervous system that involves the destruction of the insulating sheath of axons, causing severe disabilities. Since the etiology of the disease is not yet fully understood, the use of novel techniques that may help to understand the disease, to suggest potential therapies and to test the effects of candidate treatments is highly advisable. To this end we developed an agent based model that demonstrated its ability to reproduce the typical oscillatory behavior observed in the most common form of multiple sclerosis, relapsing-remitting multiple sclerosis. The model has then been used to test the potential beneficial effects of vitamin D over the disease. Many scientific studies underlined the importance of the blood-brain barrier and of the mechanisms that influence its permeability on the development of the disease. In the present paper we further extend our previously developed model with a mechanism that mimics the blood-brain barrier behavior. The goal of our work is to suggest the best strategies to follow for developing new potential treatments that intervene in the blood-brain barrier. Results suggest that the best treatments should potentially prevent the opening of the blood-brain barrier, as treatments that help in recovering the blood-brain barrier functionality could be less effective. Copyright © 2015 Elsevier B.V. All rights reserved.

Complete Host Testing with a Potential Biological Control Agent on Common Reed in View of Submitting a Petition for Field Release in Winter 2014/15

DTIC Science & Technology

2014-12-01

natural field setting. Leaf sheaths of native reed are looser and tend to fall off before winter. Ovipositing females might notice the difference and...Interim Report August-December 2014 Contract No. W911NF-14-1-0510 Project title: Complete host testing with a potential ...4. TITLE AND SUBTITLE Complete host testing with a potential biological control agent on common reed in view of submitting a petition for field

An Agent-Based Data Mining System for Ontology Evolution

NASA Astrophysics Data System (ADS)

Hadzic, Maja; Dillon, Darshan

We have developed an evidence-based mental health ontological model that represents mental health in multiple dimensions. The ongoing addition of new mental health knowledge requires a continual update of the Mental Health Ontology. In this paper, we describe how the ontology evolution can be realized using a multi-agent system in combination with data mining algorithms. We use the TICSA methodology to design this multi-agent system which is composed of four different types of agents: Information agent, Data Warehouse agent, Data Mining agents and Ontology agent. We use UML 2.1 sequence diagrams to model the collaborative nature of the agents and a UML 2.1 composite structure diagram to model the structure of individual agents. The Mental Heath Ontology has the potential to underpin various mental health research experiments of a collaborative nature which are greatly needed in times of increasing mental distress and illness.

Agent-based assessment of stormwater re-use potential of low-impact development control facilities at the site of Vlasina Lake, Serbia.

PubMed

Blagojević, Borislava; Milićević, Dragan; Potić, Olivera

2013-01-01

Vlasina Lake in south-east Serbia is classified as an Area of Distinct Land Use and, as such, is subject to high environmental protection standards applied in the Master Plan. Two open channels for stormwater and sediment transportation to two large detention basins with pumping stations for water evacuation into the lake were envisaged in the Master Plan. In the preliminary design, the stormwater system was quite different: wherever possible, on-site natural features were used for allocation of ponds, and drainage channels were led through existing road culverts. The applied design concept has been low impact development (LID), which led to potential blue-green corridors, recognized by project stakeholders. The paper studies the possibility of using ponds as a key element of both the LID concept and the blue-green corridors approach. For that purpose, an initial Vlasina Lake site agent-based simulation model has been created. A realistic physical model is included, and simulation results for two hypothetical climatic and socio-economic scenarios are presented. From the experience in creating the agent-based model, and based on the simulation results, recommendations are given for further work. It is shown that ponds have potential for the investigated water re-use purposes.

Reliable Prescreening of Candidate NerveAgent Prophylaxes via 3D QSAR

DTIC Science & Technology

2005-12-31

recognize and predict prospective toxicity among covalent -binding AChE inhibitors of potential application to nerve agent prophylaxis and...is below since many authors do not follow the 200 word limit 14. SUBJECT TERMS nerve agents , acetylcholinesterase, prophylaxis, QSAR, virtual...Report: Reliable Prescreening of Candidate NerveAgent Prophylaxes via 3D QSAR Report Title ABSTRACT Organophosphorus (OP) nerve agents are among the

Cranial nerve contrast using nerve-specific fluorophores improved by paired-agent imaging with indocyanine green as a control agent

NASA Astrophysics Data System (ADS)

Torres, Veronica C.; Vuong, Victoria D.; Wilson, Todd; Wewel, Joshua; Byrne, Richard W.; Tichauer, Kenneth M.

2017-09-01

Nerve preservation during surgery is critical because damage can result in significant morbidity. This remains a challenge especially for skull base surgeries where cranial nerves (CNs) are involved because visualization and access are particularly poor in that location. We present a paired-agent imaging method to enhance identification of CNs using nerve-specific fluorophores. Two myelin-targeting imaging agents were evaluated, Oxazine 4 and Rhodamine 800, and coadministered with a control agent, indocyanine green, either intravenously or topically in rats. Fluorescence imaging was performed on excised brains ex vivo, and nerve contrast was evaluated via paired-agent ratiometric data analysis. Although contrast was improved among all experimental groups using paired-agent imaging compared to conventional, solely targeted imaging, Oxazine 4 applied directly exhibited the greatest enhancement, with a minimum 3 times improvement in CNs delineation. This work highlights the importance of accounting for nonspecific signal of targeted agents, and demonstrates that paired-agent imaging is one method capable of doing so. Although staining, rinsing, and imaging protocols need to be optimized, these findings serve as a demonstration for the potential use of paired-agent imaging to improve contrast of CNs, and consequently, surgical outcome.

Immunotherapeutics in Pediatric Autoimmune Central Nervous System Disease: Agents and Mechanisms.

PubMed

Nosadini, Margherita; Sartori, Stefano; Sharma, Suvasini; Dale, Russell C

2017-08-01

Beyond the major advances produced by careful clinical-radiological phenotyping and biomarker development in autoimmune central nervous system disorders, a comprehensive knowledge of the range of available immune therapies and a deeper understanding of their action should benefit therapeutic decision-making. This review discusses the agents used in neuroimmunology and their mechanisms of action. First-line treatments typically include corticosteroids, intravenous immunoglobulin, and plasmapheresis, while for severe disease second-line "induction" agents such as rituximab or cyclophosphamide are used. Steroid-sparing agents such as mycophenolate, azathioprine, or methotrexate are often used in potentially relapsing or corticosteroid-dependent diseases. Lessons from adult neuroimmunology and rheumatology could be translated into pediatric autoimmune central nervous system disease in the future, including the potential utility of monoclonal antibodies targeting lymphocytes, adhesion molecules for lymphocytic migration, cytokines or their receptors, or complement. Finally, many agents used in other fields have multiple mechanisms of action, including immunomodulation, with potential usefulness in neuroimmunology, such as antibiotics, psychotropic drugs, probiotics, gut health, and ketogenic diet. All currently accepted and future potential agents have adverse effects, which can be severe; therefore, a "risk-versus-benefit" determination should guide therapeutic decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of tumor related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma.

PubMed

Xu, Song; Liu, Renwang; Da, Yurong

2018-06-05

This study compared tumor-related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma (LUAD) treatment. Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses were performed based on LUAD differentially expressed genes from The Cancer Genome Atlas (TCGA) project and genotype-tissue expression controls. These results were compared to various known compounds using the Connectivity Mapping dataset. The clinical significance of the hub genes identified by overlapping pathway enrichment analysis was further investigated using data mining from multiple sources. A drug-pathway network for LUAD was constructed, and molecular docking was carried out. After the integration of 57 LUAD-related pathways and 35 pathways affected by small molecules, five overlapping pathways were revealed. Among these five pathways, the p53 signaling pathway was the most significant, with CCNB1, CCNB2, CDK1, CDKN2A, and CHEK1 being identified as hub genes. The p53 signaling pathway is implicated as a risk factor for LUAD tumorigenesis and survival. A total of 88 molecules significantly inhibiting the five LUAD-related oncogenic pathways were involved in the LUAD drug-pathway network. Daunorubicin, mycophenolic acid, and pyrvinium could potentially target the hub gene CHEK1 directly. Our study highlights the critical pathways that should be targeted in the search for potential LUAD treatments, most importantly, the p53 signaling pathway. Some compounds, such as ciclopirox and AG-028671, may have potential roles for LUAD treatment but require further experimental verification. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Understanding the properties of chitosan aryl substituted thioureas in their role and potential as antibacterial agents

NASA Astrophysics Data System (ADS)

Khairul, Wan M.; Daud, Adibah Izzati; Ismail, Noraznawati

2018-02-01

In this study, the effort was to design and synthesize a series of thiourea-chitosan derivatives featuring five aryl substituted members namely N-chitosan-N'-(4-nitrobenzoyl) thiourea (1), N-chitosan-N'-(4-chlorobenzoyl) thiourea (2), N-chitosan-N'-(4-methylbenzoyl) thiourea (3), N-chitosan-N'-(2-iodobenzoyl) thiourea (4), and N-chitosan-N'-(2-methylbenzoyl) thiourea (5) via SN2 reaction pathway having different donating and withdrawing groups. Their molecular structures were then characterised by FT-IR, UV-Vis, and thermogravimetric analysis (TGA). The antimicrobial activities of these derivatives against four species bacteria Bacillus cereus, Staphylococcus aureus, Salmonella typhi, and Escherichia coli of both Gram-positive and Gram-negative type bacteria at minimum concentration 6mg/ml were carried out to investigate their potential as antibacterial agents. Compound 1 exhibited specific activity as it can only inhibit Gram-positive bacteria while other compounds 2-5 showed broad range spectrum activity as they were able to inhibit both Gram-positive and Gram-negative bacteria. Therefore, 1-5 showed good antibacterial activity and have high potential to be further developed as active materials in pharmaceutical interests.

Heat shock protein 27 is a potential indicator for response to YangZheng XiaoJi and chemotherapy agents in cancer cells.

PubMed

Owen, Sioned; Zhao, Huishan; Dart, Alwyn; Wang, Yamei; Ruge, Fiona; Gao, Yong; Wei, Cong; Wu, Yiling; Jiang, Wen G

2016-11-01

Heat shock protein 27 (HSP27) is a member of the heat shock protein family which has been linked to tumour progression and, most interestingly, to chemotherapy resistance in cancer patients. The present study examined the potential interplay between HSP27 and YangZheng XiaoJi, a traditional Chinese medicine used in cancer treatment. A range of cell lines from different tumour types including pancreatic, lung, gastric, colorectal, breast, prostate and ovarian cancer (both wild-type and resistant) were used. Levels and activation of HSP27 and its potential associated signalling pathways were evaluated by protein array and western blotting. Knockdown of HSP27 in cancer cells was achieved using siRNA. Localisation and co-localisation of HSP27 and other proteins were carried out by immunofluorescence. Cell growth and migration were evaluated in their response to a range of chemotherapeutic agents. The present study first identified, by way of protein array, that YangZheng XiaoJi was able to inhibit the phosphorylation of HSP27 protein in cancer cells. We further demonstrated that HSP27, which is co-localised with caspase-9, can be blocked from localising in focal adhesions and co-localising with caspase-9 by YangZheng XiaoJi. The study also demonstrated that YangZheng XiaoJi was able to sensitise cancer cells including those cells that were resistant to chemotherapy, to chemotherapeutic agents. Finally, knocking down HSP27 markedly reduced the migration of cancer cells and increased the sensitivity of cancer cells to the inhibitory effect on cellular migration by YangZheng XiaoJi. YangZheng XiaoJi can act as an agent in first sensitising cancer cells to chemotherapy and secondly to overcome, to some degree, chemoresistance when used in an appropriate fashion in patients who have active HSP27.

Bioprospecting the Curculigoside-Cinnamic Acid-Rich Fraction from Molineria latifolia Rhizome as a Potential Antioxidant Therapeutic Agent.

PubMed

Ooi, Der Jiun; Chan, Kim Wei; Sarega, Nadarajan; Alitheen, Noorjahan Banu; Ithnin, Hairuszah; Ismail, Maznah

2016-06-17

Increasing evidence from both experimental and clinical studies depicts the involvement of oxidative stress in the pathogenesis of various diseases. Specifically, disruption of homeostatic redox balance in accumulated body fat mass leads to obesity-associated metabolic syndrome. Strategies for the restoration of redox balance, potentially by exploring potent plant bioactives, have thus become the focus of therapeutic intervention. The present study aimed to bioprospect the potential use of the curculigoside-cinnamic acid-rich fraction from Molineria latifolia rhizome as an antioxidant therapeutic agent. The ethyl acetate fraction (EAF) isolated from M. latifolia rhizome methanolic extract (RME) contained the highest amount of phenolic compounds, particularly curculigoside and cinnamic acid. EAF demonstrated glycation inhibitory activities in both glucose- and fructose-mediated glycation models. In addition, in vitro chemical-based and cellular-based antioxidant assays showed that EAF exhibited high antioxidant activities and a protective effect against oxidative damage in 3T3-L1 preadipocytes. Although the efficacies of individual phenolics differed depending on the structure and concentration, a correlational study revealed strong correlations between total phenolic contents and antioxidant capacities. The results concluded that enriched phenolic contents in EAF (curculigoside-cinnamic acid-rich fraction) contributed to the overall better reactivity. Our data suggest that this bioactive-rich fraction warrants therapeutic potential against oxidative stress-related disorders.

Biomaterials for mediation of chemical and biological warfare agents.

PubMed

Russell, Alan J; Berberich, Jason A; Drevon, Geraldine F; Koepsel, Richard R

2003-01-01

Recent events have emphasized the threat from chemical and biological warfare agents. Within the efforts to counter this threat, the biocatalytic destruction and sensing of chemical and biological weapons has become an important area of focus. The specificity and high catalytic rates of biological catalysts make them appropriate for decommissioning nerve agent stockpiles, counteracting nerve agent attacks, and remediation of organophosphate spills. A number of materials have been prepared containing enzymes for the destruction of and protection against organophosphate nerve agents and biological warfare agents. This review discusses the major chemical and biological warfare agents, decontamination methods, and biomaterials that have potential for the preparation of decontamination wipes, gas filters, column packings, protective wear, and self-decontaminating paints and coatings.

Carbonyl Compounds Produced by Vaporizing Cannabis Oil Thinning Agents.

PubMed

Troutt, William D; DiDonato, Matthew D

2017-11-01

Cannabis use has increased in the United States, particularly the use of vaporized cannabis oil, which is often mixed with thinning agents for use in vaporizing devices. E-cigarette research shows that heated thinning agents produce potentially harmful carbonyls; however, similar studies have not been conducted (1) with agents that are commonly used in the cannabis industry and (2) at temperatures that are appropriate for cannabis oil vaporization. The goal of this study was to determine whether thinning agents used in the cannabis industry produce potentially harmful carbonyls when heated to a temperature that is appropriate for cannabis oil vaporization. Four thinning agents (propylene glycol [PG], vegetable glycerin [VG], polyethylene glycol 400 [PEG 400], and medium chain triglycerides [MCT]) were heated to 230°C and the resulting vapors were tested for acetaldehyde, acrolein, and formaldehyde. Each agent was tested three times. Testing was conducted in a smoking laboratory. Carbonyl levels were measured in micrograms per puff block. Analyses showed that PEG 400 produced significantly higher levels of acetaldehyde and formaldehyde than PG, MCT, and VG. Formaldehyde production was also significantly greater in PG compared with MCT and VG. Acrolein production did not differ significantly across the agents. PG and PEG 400 produced high levels of acetaldehyde and formaldehyde when heated to 230°C. Formaldehyde production from PEG 400 isolate was particularly high, with one inhalation accounting for 1.12% of the daily exposure limit, nearly the same exposure as smoking one cigarette. Because PG and PEG 400 are often mixed with cannabis oil, individuals who vaporize cannabis oil products may risk exposure to harmful formaldehyde levels. Although more research is needed, consumers and policy makers should consider these potential health effects before use and when drafting cannabis-related legislation.

Organic molecule-based photothermal agents: an expanding photothermal therapy universe.

PubMed

Jung, Hyo Sung; Verwilst, Peter; Sharma, Amit; Shin, Jinwoo; Sessler, Jonathan L; Kim, Jong Seung

2018-04-03

Over the last decade, organic photothermal therapy (PTT) agents have attracted increasing attention as a potential complement for, or alternative to, classical drugs and sensitizers involving inorganic nanomaterials. In this tutorial review, we provide a structured description of the main classes of organic photothermal agents and their characteristics. Representative agents that have been studied in the context of photothermal therapy since 2000 are summarized and recent advances in using PTT agents to address various cancers indications are highlighted.

Phyllanthus wightianus Müll. Arg.: A Potential Source for Natural Antimicrobial Agents

PubMed Central

Natarajan, D.; Srinivasan, R.; Shivakumar, M. S.

2014-01-01

Phyllanthus wightianus belongs to Euphorbiaceae family having ethnobotanical importance. The present study deals with validating the antimicrobial potential of solvent leaf extracts of P. wightianus. 11 human bacterial pathogens (Bacillus subtilis, Streptococcus pneumoniae, Staphylococcus epidermidis, Proteus vulgaris, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhimurium, Escherichia coli, Shigella flexneri, Proteus vulgaris, and Serratia marcescens) and 4 fungal pathogens (Candida albicans, Cryptococcus neoformans, Mucor racemosus, and Aspergillus niger) were also challenged with solvent leaf extracts usingagar well and disc diffusion methods. Further, identification of the active component present in the bioactive extract was done using GC-MS analysis. Results show that all extracts exhibited broad spectrum (6–29 mm) of antibacterial activity on most of the tested organisms. The results highlight the fact that the well in agar method was more effective than disc diffusion method. Significant antimicrobial activity was detected in methanol extract against S. pneumoniae (29 mm) with MIC and MBC values of 15.62 μg/mL. GC-MS analysis revealed that 29 bioactive constituents were present in methanolic extract of P. wightianus, of which 9,12-octadecaenioic acid (peak area 22.82%; RT-23.97) and N-hexadecanoic acid (peak area 21.55% RT-21.796) are the major compounds. The findings of this study show that P. wightianus extracts may be used as an anti-infective agent in folklore medicine. PMID:24883301

Epigallocatechin Gallate (EGCG) Inhibits Alpha-Synuclein Aggregation: A Potential Agent for Parkinson's Disease.

PubMed

Xu, Yan; Zhang, Yanyan; Quan, Zhenzhen; Wong, Winnie; Guo, Jianping; Zhang, Rongkai; Yang, Qinghu; Dai, Rongji; McGeer, Patrick L; Qing, Hong

2016-10-01

Protein aggregation is a prominent feature of many neurodegenerative disorders including Parkinson's disease (PD). Aggregation of alpha-synuclein (SNCA) may underlie the pathology of PD. They are the main components of Lewy bodies and dystrophic neurites that are the intraneuronal inclusions characteristic of the disease. We have demonstrated that the polyphenol (-)-epi-gallocatechine gallate (EGCG) inhibited SNCA aggregation, which made it a candidate for therapeutic intervention in PD. Three methods were used: SNCA fibril formation inhibition by EGCG in incubates; inhibition of the SNCA fluorophore A-Syn-HiLyte488 binding to plated SNCA in microwells; and inhibition of the A-Syn-HiLyte488 probe binding to aggregated SNCA in postmortem PD tissue. Recombinant human SNCA was incubated under conditions that result in fibril formation. The aggregation was blocked by 100 nM EGCG in a concentration-dependent manner, as shown by an absence of thioflavin T binding. In the microplate assay system, the ED 50 of EGCG inhibition of A-Syn-HiLyte488 binding to coated SNCA was 250 nM. In the PD tissue based assay, SNCA aggregates were recognized by incubation with 7 nM of A-Syn-HiLyte488. This binding was blocked by EGCG in a concentration dependent manner. The SNCA amino acid sites, which potentially interacted with EGCG, were detected on peptide membranes. It was implicated that EGCG binds to SNCA by instable hydrophobic interactions. In this study, we suggested that EGCG could be a potent remodeling agent of SNCA aggregates and a potential disease modifying drug for the treatment of PD and other α-synucleinopathies.

Potential Role of Natural Compounds as Anti-Angiogenic Agents in Cancer.

PubMed

Shanmugam, Muthu K; Warrier, Sudha; Kumar, Alan P; Sethi, Gautam; Arfuso, Frank

2017-01-01

Neovascularization, also known as angiogenesis, is the process of capillary sprouting from pre-existing blood vessels. This physiological process is a hallmark event in normal embryonic development as blood vessels generally supply both oxygen and nutrients to the cells of the body. Any disruption in this process can lead to the development of various chronic diseases, including cancer. In cancer, aberrant angiogenesis plays a prominent role in maintaining sustained tumor growth to malignant phenotypes and promoting metastasis. The leakiness in the tumor microvasculature is attributed to the tumor cells migrating to distal site organs and forming colonies. In this article, we briefly review the various mediators involved in the angiogenic process and the anti-angiogenic potential of selected natural compounds against various malignancies. Several growth factors and their receptors such as vascular endothelial growth factor and receptor (VEGF/VEGFR), basic fibroblast growth factor and receptor (bFGF/FGFR), angiopoietins, and hypoxia inducible factors facilitate the development of angiogenesis and are attractive anti-cancer targets. Natural products represent a rich diversity of compounds for drug discovery and are currently being actively exploited to target tumor angiogenesis. Agents such as curcumin, artemisinin, EGCG, resveratrol, emodin, celastrol, thymoquinone and tocotrienols all have shown prominent anti-angiogenic effects in the preclinical models of tumor angiogenesis. Several semi-synthetic derivatives and novel nano-formulations of these natural compounds have also exhibited excellent anti-angiogenic activity by increasing bioavailability and delivering the drugs to the sites of tumor angiogenesis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Antibacterial Potential of an Antimicrobial Agent Inspired by Peroxidase-Catalyzed Systems

PubMed Central

Tonoyan, Lilit; Fleming, Gerard T. A.; Mc Cay, Paul H.; Friel, Ruairi; O'Flaherty, Vincent

2017-01-01

Antibiotic resistance is an increasingly serious threat to global health. Consequently, the development of non-antibiotic based therapies and disinfectants, which avoid induction of resistance, or cross-resistance, is of high priority. We report the synthesis of a biocidal complex, which is produced by the reaction between ionic oxidizable salts—iodide and thiocyanate—in the presence of hydrogen peroxide as an oxidation source. The reaction generates bactericidal reactive oxygen and iodine species. In this study, we report that the iodo-thiocyanate complex (ITC) is an effective bactericidal agent with activity against planktonic and biofilm cells of Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and methicillin-resistant S. aureus) bacteria. The minimum bactericidal concentrations and the minimum biofilm eradication concentrations of the biocidal composite were in the range of 7.8–31.3 and 31.3–250 μg ml−1, respectively. As a result, the complex was capable to cause a rapid cell death of planktonic test cultures at between 0.5 and 2 h, and complete eradication of dual and mono-species biofilms between 30 s and 10 min. Furthermore, the test bacteria, including a MRSA strain, exposed to the cocktail failed to develop resistance after serial passages. The antimicrobial activity of the ITC appears to derive from the combinational effect of the powerful species capable of oxidizing the essential biomolecules of bacteria. The use of this composition may provide an effective and efficient method for killing potential pathogens, as well as for disinfecting and removing biofilm contamination. PMID:28512449

Platinum(II)-gadolinium(III) complexes as potential single-molecular theranostic agents for cancer treatment.

PubMed

Zhu, Zhenzhu; Wang, Xiaoyong; Li, Tuanjie; Aime, Silvio; Sadler, Peter J; Guo, Zijian

2014-11-24

Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)-gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt-Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd-DTPA. T1-weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt-Gd complexes promising theranostic agents for cancer treatment. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Keeping pace with ACE: are ACE inhibitors and angiotensin II type 1 receptor antagonists potential doping agents?

PubMed

Wang, Pei; Fedoruk, Matthew N; Rupert, Jim L

2008-01-01

activity or block the action of angiotensin II, the question is relevant to the study of ergogenic agents and to the efforts to rid sports of 'doping'. This article discusses the possibility that ACE inhibitors and ARBs, by virtue of their effects on ACE or angiotensin II function, respectively, have performance-enhancing capabilities; it also reviews the data on the effects of these medications on VO2max, muscle composition and endurance capacity in patient and non-patient populations. We conclude that, while the direct evidence supporting the hypothesis that ACE-related medications are potential doping agents is not compelling, there are insufficient data on young, athletic populations to exclude the possibility, and there is ample, albeit indirect, support from genetic studies to suggest that they should be. Unfortunately, given the history of drug experimentation in athletes and the rapid appropriation of therapeutic agents into the doping arsenal, this indirect evidence, coupled with the availability of ACE-inhibiting and ACE-receptor blocking medications may be sufficiently tempting to unscrupulous competitors looking for a shortcut to the finish line.

Evolutionary game theory using agent-based methods.

PubMed

Adami, Christoph; Schossau, Jory; Hintze, Arend

2016-12-01

Evolutionary game theory is a successful mathematical framework geared towards understanding the selective pressures that affect the evolution of the strategies of agents engaged in interactions with potential conflicts. While a mathematical treatment of the costs and benefits of decisions can predict the optimal strategy in simple settings, more realistic settings such as finite populations, non-vanishing mutations rates, stochastic decisions, communication between agents, and spatial interactions, require agent-based methods where each agent is modeled as an individual, carries its own genes that determine its decisions, and where the evolutionary outcome can only be ascertained by evolving the population of agents forward in time. While highlighting standard mathematical results, we compare those to agent-based methods that can go beyond the limitations of equations and simulate the complexity of heterogeneous populations and an ever-changing set of interactors. We conclude that agent-based methods can predict evolutionary outcomes where purely mathematical treatments cannot tread (for example in the weak selection-strong mutation limit), but that mathematics is crucial to validate the computational simulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis and mechanisms of action of novel harmine derivatives as potential antitumor agents

PubMed Central

Zhang, Xiao-Fei; Sun, Rong-qin; Jia, Yi-fan; Chen, Qing; Tu, Rong-Fu; Li, Ke-ke; Zhang, Xiao-Dong; Du, Run-Lei; Cao, Ri-hui

2016-01-01

A series of novel harmine derivatives bearing a benzylindine substituent in position-1 of β-carboline ring were synthesized and evaluated as antitumor agents. The N2-benzylated β-carboline derivatives 3a–g represented the most interesting anticancer activities and compound 3c was found to be the most active agent to diverse cancer cell lines such as gastric carcinoma, melanoma and colorectal cancer. Notably, compound 3c showed low toxicity to normal cells. The treatment significantly induced cell apoptosis. Mechanistically, PI3K/AKT signaling pathway mediated compound 3c-induced apoptosis. Compound 3c inhibited phosphorylation of AKT and promoted the production of reactive oxygen species (ROS). The ROS scavenger, LNAC and GSH, could disturb the effect of compound 3c induced apoptosis and PI3K activity inhibitor LY294002 synergistically enhanced compound 3c efficacy. Moreover, the results from nude mice xenograft model showed that compound 3c treatment effectively inhibited tumor growth and decreased tumor weight. Collectively, our results demonstrated that compound 3c exerts apoptotic effect in cancer cells via suppression of phosphorylated AKT and evocation of ROS generation, which suggested that compound 3c might be served as a promising therapeutic agent for cancer treatment. PMID:27625151

Measure Landscape Diversity with Logical Scout Agents

NASA Astrophysics Data System (ADS)

Wirth, E.; Szabó, G.; Czinkóczky, A.

2016-06-01

The Common Agricultural Policy reform of the EU focuses on three long-term objectives: viable food production, sustainable management of natural resources and climate action with balanced territorial development. To achieve these goals, the EU farming and subsidizing policies (EEA, 2014) support landscape heterogeneity and diversity. Current paper introduces an agent-based method to calculate the potential of landscape diversity. The method tries to catch the nature of heterogeneity using logic and modelling as opposed to the traditional statistical reasoning. The outlined Random Walk Scouting algorithm registers the land cover crossings of the scout agents to a Monte Carlo integral. The potential is proportional with the composition and the configuration (spatial character) of the landscape. Based on the measured points a potential map is derived to give an objective and quantitative basis to the stakeholders (policy makers, farmers).

Evolution of hemostatic agents in surgical practice

PubMed Central

Sundaram, Chandru P.; Keenan, Alison C.

2010-01-01

Objective: Topical hemostatic agents are used in a wide variety of surgical settings, and the evolution of this class of surgical tools is an interesting topic. We reviewed and outlined the historical progress of topical hemostats into present day surgery and urology, and highlight opportunities for future research. Materials and Methods: A MEDLINE search of all available literature concerning several classes of topical hemostatic agents was performed. Fibrins sealants, Gelatin sponge hemostatics, cyanoacrylate adhesives, oxidized regenerated cellulose, and microfibrillar collagen were included. References were chosen from a broad range of surgical literature. Results: Topical hemostatic agents have historically taken advantage of a wide variety of mechanisms for hemostasis. Fibrin sealants have a rich history and large potential for further applications. Gelatin sponge hemostatics have been widely used since their introduction, but have changed little. Cyanoacrylate adhesives have a unique mechanism and opportunity for novel applications of existing products. Oxidized cellulose was original in the use of plant-based components. Microfibrillar collagen hemostats have evolved to a wide variety of formats. 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. PMID:21116358

New multifunctional ligands for potential use in the design therapeutic or diagnostic radiopharmaceutical imaging agents

DOEpatents

Katti, Kattesh V.; Volkert, Wynn A.; Ketring, Alan R.; Singh, Prahlad R.

1997-01-01

A class of diagnostic and therapeutic compounds derived from phosphinimines that include ligands containing either a single phosphinimine functionality or both a phosphinimine group and a phosphine or arsine group, or an aminato group, or a second phosphinimine moiety. These phosphinimine ligands are complexed to early transition metal radionuclides (e.g. .sup.99m Tc or .sup.186 Re/.sup.188 Re) or late transition metals (e.g., .sup.105 Rh or .sup.109 Pd). The complexes with these metals .sup.186 Re/.sup.188 Re, .sup.99m Tc and .sup.109 Pd exhibit a high in vitro and high in vivo stability. The complexes are formed in high yields and can be neutral or charged. These ligands can also be used to form stable compounds with paramagnetic transition metals (e.g. Fe and Mn) for potential use as MRI contrast agents. Applications for the use of ligands and making the ligands are also disclosed.

New multifunctional ligands for potential use in the design therapeutic or diagnostic radiopharmaceutical imaging agents

DOEpatents

Katti, K.V.; Volkert, W.A.; Ketring, A.R.; Singh, P.R.

1997-02-11

A class of diagnostic and therapeutic compounds are derived from phosphinimines that include ligands containing either a single phosphinimine functionality or both a phosphinimine group and a phosphine or arsine group, or an aminato group, or a second phosphinimine moiety. These phosphinimine ligands are complexed to early transition metal radionuclides (e.g., {sup 99m}Tc or {sup 186}Re/{sup 188}Re) or late transition metals (e.g., {sup 105}Rh or {sup 109}Pd). The complexes with these metals {sup 186}Re/{sup 188}Re, {sup 99m}Tc and {sup 109}Pd exhibit a high in vitro and high in vivo stability. The complexes are formed in high yields and can be neutral or charged. These ligands can also be used to form stable compounds with paramagnetic transition metals (e.g., Fe and Mn) for potential use as MRI contrast agents. Applications for the use of ligands and making the ligands are also disclosed.

Multifunctional agents for concurrent imaging and therapy in cardiovascular disease

PubMed Central

McCarthy, Jason R.

2010-01-01

The development of agents for the simultaneous detection and treatment of disease has recently gained significant attention. These multifunctional theranostic agents posses a number of advantages over their monofunctional counterparts, as they potentially allow for the concomitant determination of agent localization, release, and efficacy. Whereas the development of these agents for use in cancers has received the majority of the attention, their use in cardiovascular disease is steadily increasing. As such, this review summarized some of the most poignant recent advances in the development of theranostic agents for the treatment of this class of diseases. PMID:20654664

Discovery of direct inhibitors of Keap1-Nrf2 protein-protein interaction as potential therapeutic and preventive agents.

PubMed

Abed, Dhulfiqar Ali; Goldstein, Melanie; Albanyan, Haifa; Jin, Huijuan; Hu, Longqin

2015-07-01

The Keap1-Nrf2-ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1-Nrf2 protein-protein interaction (PPI) has become an important drug target to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes in the development of therapeutic and preventive agents for a number of diseases and conditions. However, most known Nrf2 activators/ARE inducers are indirect inhibitors of Keap1-Nrf2 PPI and they are electrophilic species that act by modifying the sulfhydryl groups of Keap1׳s cysteine residues. The electrophilicity of these indirect inhibitors may cause "off-target" side effects by reacting with cysteine residues of other important cellular proteins. Efforts have recently been focused on the development of direct inhibitors of Keap1-Nrf2 PPI. This article reviews these recent research efforts including the development of high throughput screening assays, the discovery of peptide and small molecule direct inhibitors, and the biophysical characterization of the binding of these inhibitors to the target Keap1 Kelch domain protein. These non-covalent direct inhibitors of Keap1-Nrf2 PPI could potentially be developed into effective therapeutic or preventive agents for a variety of diseases and conditions.

Contrast agent-free sonoporation: The use of an ultrasonic standing wave microfluidic system for the delivery of pharmaceutical agents

PubMed Central

Carugo, Dario; Ankrett, Dyan N.; Glynne-Jones, Peter; Capretto, Lorenzo; Boltryk, Rosemary J.; Zhang, Xunli; Townsend, Paul A.; Hill, Martyn

2011-01-01

Sonoporation is a useful biophysical mechanism for facilitating the transmembrane delivery of therapeutic agents from the extracellular to the intracellular milieu. Conventionally, sonoporation is carried out in the presence of ultrasound contrast agents, which are known to greatly enhance transient poration of biological cell membranes. However, in vivo contrast agents have been observed to induce capillary rupture and haemorrhage due to endothelial cell damage and to greatly increase the potential for cell lysis in vitro. Here, we demonstrate sonoporation of cardiac myoblasts in the absence of contrast agent (CA-free sonoporation) using a low-cost ultrasound-microfluidic device. Within this device an ultrasonic standing wave was generated, allowing control over the position of the cells and the strength of the acoustic radiation forces. Real-time single-cell analysis and retrospective post-sonication analysis of insonated cardiac myoblasts showed that CA-free sonoporation induced transmembrane transfer of fluorescent probes (CMFDA and FITC-dextran) and that different mechanisms potentially contribute to membrane poration in the presence of an ultrasonic wave. Additionally, to the best of our knowledge, we have shown for the first time that sonoporation induces increased cell cytotoxicity as a consequence of CA-free ultrasound-facilitated uptake of pharmaceutical agents (doxorubicin, luteolin, and apigenin). The US-microfluidic device designed here provides an in vitro alternative to expensive and controversial in vivo models used for early stage drug discovery, and drug delivery programs and toxicity measurements. PMID:22662060

Putative neuroprotective agents in neuropsychiatric disorders.

PubMed

Dodd, Seetal; Maes, Michael; Anderson, George; Dean, Olivia M; Moylan, Steven; Berk, Michael

2013-04-05

In many individuals with major neuropsychiatric disorders including depression, bipolar disorder and schizophrenia, their disease characteristics are consistent with a neuroprogressive illness. This includes progressive structural brain changes, cognitive and functional decline, poorer treatment response and an increasing vulnerability to relapse with chronicity. The underlying molecular mechanisms of neuroprogression are thought to include neurotrophins and regulation of neurogenesis and apoptosis, neurotransmitters, inflammatory, oxidative and nitrosative stress, mitochondrial dysfunction, cortisol and the hypothalamic-pituitary-adrenal axis, and epigenetic influences. Knowledge of the involvement of each of these pathways implies that specific agents that act on some or multiple of these pathways may thus block this cascade and have neuroprotective properties. This paper reviews the potential of the most promising of these agents, including lithium and other known psychotropics, aspirin, minocycline, statins, N-acetylcysteine, leptin and melatonin. These agents are putative neuroprotective agents for schizophrenia and mood disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

About the Chemopreventive Agent Development Research Group | Division of Cancer Prevention

Cancer.gov

The Chemopreventive Agent Development Research Group promotes and supports research on early chemopreventive agent development, from preclinical studies to phase I clinical trials. The group’s projects aim to identify and develop prevention agents with the potential to block, reverse, or delay the early stages of cancer. The overarching goal is to determine positive and

A review of Agent Orange and its associated oncologic risk of genitourinary cancers.

PubMed

Chang, Chrystal; Benson, Michael; Fam, Mina M

2017-11-01

Agent Orange is an herbicide sprayed widely in Vietnam that is linked to a variety of malignancies in as early as 1991.Since then, there has been concern for, and subsequent interest in studying, the potential connection between Agent Orange and other malignancies. In the past 2 decades, there have been significant changes in the opinion of the National Academy of Science regarding Agent Orange and certain genitourinary malignancies. Herein, we review the literature regarding the potential link between Agent Orange and various urological cancers, including prostate, bladder, testicular, and renal cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

Systemic use of tumor necrosis factor alpha as an anticancer agent

PubMed Central

Roberts, Nicholas J.; Zhou, Shibin; Diaz, Luis A.; Holdhoff, Matthias

2011-01-01

Tumor necrosis factor-α (TNF-α) has been discussed as a potential anticancer agent for many years, however initial enthusiasm about its clinical use as a systemic agent was curbed due to significant toxicities and lack of efficacy. Combination of TNF-α with chemotherapy in the setting of hyperthermic isolated limb perfusion (ILP), has provided new insights into a potential therapeutic role of this agent. The therapeutic benefit from TNF-α in ILP is thought to be not only due to its direct anti-proliferative effect, but also due to its ability to increase penetration of the chemotherapeutic agents into the tumor tissue. New concepts for the use of TNF-α as a facilitator rather than as a direct actor are currently being explored with the goal to exploit the ability of this agent to increase drug delivery and to simultaneously reduce systemic toxicity. This review article provides a comprehensive overview on the published previous experience with systemic TNF-α. Data from 18 phase I and 10 phase II single agent as well as 18 combination therapy studies illustrate previously used treatment and dose schedules, response data as well as the most prominently observed adverse effects. Also discussed, based on recent preclinical data, is a potential future role of systemic TNF-α in combination with liposomal chemotherapy to facilitate increased drug uptake into tumors. PMID:22036896

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

Treesearch

Deborah J. Chavez; Joanne F. Tynon

2007-01-01

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

A newly developed silymarin nanoformulation as a potential antidiabetic agent in experimental diabetes.

PubMed

El-Far, Yousra M; Zakaria, Mahmoud M; Gabr, Mahmoud M; El Gayar, Amal M; El-Sherbiny, Ibrahim M; Eissa, Laila A

2016-10-01

This study aimed to develop a new stable nanoformulation of silymarin (SM) with optimum enhanced oral bioavailability and to evaluate its effect as well as mechanism of action as a superior antidiabetic agent over native SM using streptozotocin-induced diabetic rats. SM-loaded pluronic nanomicelles (SMnp) were prepared and fully characterized. Biochemical parameters were performed as well as histological, confocal and reverse-transcription polymerase chain reaction studies on pancreatic target tissues. SMnp were found to improve significantly the antihyperglycemic, antioxidant and antihyperlipidemic properties as compared with native SM. In addition, SMnp was found to be a more efficient agent over SM in the management of diabetes and its associated complications due to its superior bioavailability in vivo, and the controlled release profile of SM. [Formula: see text].

Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer—Part 1

PubMed Central

Sagar, S.M.; Yance, D.; Wong, R.K.

2006-01-01

An integrative approach for managing a patient with cancer should target the multiple biochemical and physiologic pathways that support tumour development and minimize normal-tissue toxicity. Angiogenesis is a key process in the promotion of cancer. Many natural health products that inhibit angiogenesis also manifest other anticancer activities. The present article focuses on products that have a high degree of anti-angiogenic activity, but it also describes some of the many other actions of these agents that can inhibit tumour progression and reduce the risk of metastasis. Natural health products target molecular pathways other than angiogenesis, including epidermal growth factor receptor, the HER2/neu gene, the cyclooxygenase-2 enzyme, the nuclear factor kappa-B transcription factor, the protein kinases, the Bcl-2 protein, and coagulation pathways. The herbs that are traditionally used for anticancer treatment and that are anti-angiogenic through multiple interdependent processes (including effects on gene expression, signal processing, and enzyme activities) include Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (curcumin), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinalis (ginger), Panax ginseng, Rabdosia rubescens hora (Rabdosia), and Chinese destagnation herbs. Quality assurance of appropriate extracts is essential prior to embarking upon clinical trials. More data are required on dose–response, appropriate combinations, and potential toxicities. Given the multiple effects of these agents, their future use for cancer therapy probably lies in synergistic combinations. During active cancer therapy, they should generally be evaluated in combination with chemotherapy and radiation. In this role, they act as modifiers of biologic response or

Functionality study of santalin as tyrosinase inhibitor: A potential depigmentation agent.

PubMed

Hridya, Hemachandran; Amrita, Anantharaman; Mohan, Sankari; Gopalakrishnan, Mohan; Dakshinamurthy, Thirumal Kumar; Doss, George Priya; Siva, Ramamoorthy

2016-05-01

Excessive melanin production leads to hyperpigmentation disorders which results in distressing aesthetic values. Though there are some synthetic depigmentation agents available it has been reported to possess cytotoxic and mutagenic effects. Hence there is a need for the development of safe and non toxic natural tyrosinase inhibitors. Here we report the role of santalin, the chief constituent of Pterocarpus santalinus in inhibition of tyrosinase and melanin synthesis. Santalin inhibited tyrosinase activity dose dependently. Inhibitory kinetic studies revealed mixed type of inhibition with reversible mechanism. Santalin was found to interact with the fluorophore amino acid residue of tyrosinase. Analysis of circular dichroism spectra showed the binding of santalin to tyrosinase which induced the loss of secondary helical structure. Molecular docking result suggested that santalin interact with the catalytic core of tyrosinase through strong hydrogen and hydrophobic bonding. The results of in vitro studies showed santalin inhibited melanogenesis through down regulation of MITF, tyrosinase, TRP-1 and TRP-2 without any cytotoxic effects towards B16F0 melanoma cells. Therefore, our results suggested that santalin possesses anti-tyrosinase activity, which could be utilized as a safe depigmentation agent in the cosmetic field for the treatment of hyperpigmentation disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

Curcumin derivatives as metal-chelating agents with potential multifunctional activity for pharmaceutical applications.

PubMed

Ferrari, Erika; Benassi, Rois; Sacchi, Stefania; Pignedoli, Francesca; Asti, Mattia; Saladini, Monica

2014-10-01

Curcuminoids represent new perspectives for the development of novel therapeutics for Alzheimer's disease (AD), one probable mechanism of action is related to their metal complexing ability. In this work we examined the metal complexing ability of substituted curcuminoids to propose new chelating molecules with biological properties comparable with curcumin but with improved stability as new potential AD therapeutic agents. The K2T derivatives originate from the insertion of a -CH2COOC(CH3)3 group on the central atom of the diketonic moiety of curcumin. They retain the diketo-ketoenol tautomerism which is solvent dependent. In aqueous solution the prevalent form is the diketo one but the addition of metal ion (Ga(3+), Cu(2+)) causes the dissociation of the enolic proton creating chelate complexes and shifting the tautomeric equilibrium towards the keto-enol form. The formation of metal complexes is followed by both NMR and UV-vis spectroscopy. The density functional theory (DFT) calculations on K2T21 complexes with Ga(3+) and Cu(2+) are performed and compared with those on curcumin complexes. [Ga(K2T21)2(H2O)2](+) was found more stable than curcumin one. Good agreement is detected between calculated and experimental (1)H and (13)C NMR data. The calculated OH bond dissociation energy (BDE) and the OH proton dissociation enthalpy (PDE), allowed to predict the radical scavenging ability of the metal ion complexed with K2T21, while the calculated electronic affinity (EA) and ionization potential (IP) represent yardsticks of antioxidant properties. Eventually theoretical calculations suggest that the proton-transfer-associated superoxide-scavenging activity is enhanced after binding metal ions, and that Ga(3+) complexes display possible superoxide dismutase (SOD)-like activity. Copyright © 2014 Elsevier Inc. All rights reserved.

Hydroxychalcone inhibitors of Streptococcus mutans glucosyl transferases and biofilms as potential anticaries agents.

PubMed

Nijampatnam, Bhavitavya; Casals, Luke; Zheng, Ruowen; Wu, Hui; Velu, Sadanandan E

2016-08-01

Streptococcus mutans has been implicated as the major etiological agent in the initiation and the development of dental caries due to its robust capacity to form tenacious biofilms. Ideal therapeutics for this disease will aim to selectively inhibit the biofilm formation process while preserving the natural bacterial flora of the mouth. Several studies have demonstrated the efficacies of flavonols on S. mutans biofilms and have suggested the mechanism of action through their effect on S. mutans glucosyltransferases (Gtfs). These enzymes metabolize sucrose into water insoluble and soluble glucans, which are an integral measure of the dental caries pathogenesis. Numerous studies have shown that flavonols and polyphenols can inhibit Gtf and biofilm formation at millimolar concentrations. We have screened a group of 14 hydroxychalcones, synthetic precursors of flavonols, in an S. mutans biofilm assay. Several of these compounds emerged to be biofilm inhibitors at low micro-molar concentrations. Chalcones that contained a 3-OH group on ring A exhibited selectivity for biofilm inhibition. Moreover, we synthesized 6 additional analogs of the lead compound and evaluated their potential activity and selectivity against S. mutans biofilms. The most active compound identified from these studies had an IC50 value of 44μM against biofilm and MIC50 value of 468μM against growth displaying >10-fold selectivity inhibition towards biofilm. The lead compound displayed a dose dependent inhibition of S. mutans Gtfs. The lead compound also did not affect the growth of two commensal species (Streptococcus sanguinis and Streptococcus gordonii) at least up to 200μM, indicating that it can selectively inhibit cariogenic biofilms, while leaving commensal and/or beneficial microbes intact. Thus non-toxic compounds have the potential utility in public oral health regimes. Copyright © 2016. Published by Elsevier Ltd.

An ergonomic evaluation of a call center performed by disabled agents.

PubMed

Chi, Chia-Fen; Lin, Yen-Hui

2008-08-01

Potential ergonomic hazards for 27 disabled call center agents engaged in computer-telephone interactive tasks were evaluated for possible associations between the task behaviors and work-related disorders. Data included task description, 300 samples of performance, a questionnaire on workstation design, body-part discomfort rating, perceived stress, potential job stressors, and direct measurement of environmental factors. Analysis indicated agents were frequently exposed to prolonged static sitting and repetitive movements, together with unsupported back and flexed neck, causing musculoskeletal discomforts. Visual fatigue (85.2% of agents), discomfort of ears (66.7%), and musculoskeletal discomforts (59.3%) were the most pronounced and prevalent complaints after prolonged working. 17 of 27 agents described job pressure as high or very high, and dealing with difficult customers and trying to fulfill the customers' needs within the time standard were main stressors. Further work on surrounding noise, earphone use, possible hearing loss of experienced agents, training programs, feasible solutions for visual fatigue, musculoskeletal symptoms, and psychosocial stress should be conducted.

Protecting software agents from malicious hosts using quantum computing

NASA Astrophysics Data System (ADS)

Reisner, John; Donkor, Eric

2000-07-01

We evaluate how quantum computing can be applied to security problems for software agents. Agent-based computing, which merges technological advances in artificial intelligence and mobile computing, is a rapidly growing domain, especially in applications such as electronic commerce, network management, information retrieval, and mission planning. System security is one of the more eminent research areas in agent-based computing, and the specific problem of protecting a mobile agent from a potentially hostile host is one of the most difficult of these challenges. In this work, we describe our agent model, and discuss the capabilities and limitations of classical solutions to the malicious host problem. Quantum computing may be extremely helpful in addressing the limitations of classical solutions to this problem. This paper highlights some of the areas where quantum computing could be applied to agent security.

Novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents: Design, synthesis and biological evaluation.

PubMed

Liu, Han-Bo; Gao, Wei-Wei; Tangadanchu, Vijai Kumar Reddy; Zhou, Cheng-He; Geng, Rong-Xia

2018-01-01

A series of novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents were designed, synthesized and characterized by IR, NMR and HRMS spectra. The biological evaluation in vitro revealed that some of the target compounds exerted good antibacterial and antifungal activity in comparison with the reference drugs. Noticeably, compound 7d could effectively inhibit the growth of A. flavus, E. coli DH52 and MRSA with MIC values of 1, 1 and 8 μg/mL, respectively. Further studies revealed that pyrimidine derivative 7d could exhibit bactericidal mode of action against both Gram positive (S. aureus and MRSA) and Gram negative (P. aeruginosa) bacteria. The active molecule 7d showed low cell toxicity and did not obviously trigger the development of resistance in bacteria even after 16 passages. Furthermore, compound 7d was able to beneficially regulate reactive oxygen species (ROS) generation for an excellent safety profile. Molecular docking study revealed that compound 7d could bind with DNA gyrase by the formation of hydrogen bonds. The preliminary exploration for antimicrobial mechanism disclosed that compound 7d could effectively intercalate into calf thymus DNA to form a steady supramolecular complex, which might further block DNA replication to exert the powerful bioactivities. The binding investigation of compound 7d with human serum albumins (HSA) revealed that this molecule could be effectively transported by HSA. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Biological activity of N(4)-boronated derivatives of 2'-deoxycytidine, potential agents for boron-neutron capture therapy.

PubMed

Nizioł, Joanna; Uram, Łukasz; Szuster, Magdalena; Sekuła, Justyna; Ruman, Tomasz

2015-10-01

Boron-neutron capture therapy (BNCT) is a binary anticancer therapy that requires boron compound for nuclear reaction during which high energy alpha particles and lithium nuclei are formed. Unnatural, boron-containing nucleoside with hydrophobic pinacol moiety was investigated as a potential BNCT boron delivery agent. Biological properties of this compound are presented for the first time and prove that boron nucleoside has low cytotoxicity and that observed apoptotic effects suggest alteration of important functions of cancer cells. Mass spectrometry analysis of DNA from cancer cells proved that boron nucleoside is inserted into nucleic acids as a functional nucleotide derivative. NMR studies present very high degree of similarity of natural dG-dC base pair with dG-boron nucleoside system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thyroid Dysfunction from Antineoplastic Agents

PubMed Central

Larsen, P. Reed; Marqusee, Ellen

2011-01-01

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

Development of high temperature resistant graphite fiber coupling agents

NASA Technical Reports Server (NTRS)

Griffin, R. N.

1975-01-01

Surface treatments were investigated as potential coupling agents to improve the elevated temperature shear strength retention of polyimide/graphite and polyphenylquinoxaline/graphite composites. The potential coupling agents were evaluated by fiber strand tensile tests, fiber and composite weight losses at 533 and 588K, and by interlaminar shear strength retention at 533 and 588K. The two surface treatments selected for more extensive evaluation were a coating of Ventromer T-1, a complex organometallic reaction product of titanium tetrachloride and trimethyl borate, and a polyphenylquinoxaline (PPQ) sizing which was pyrolyzed in nitrogen to form a carbonaceous layer on the fiber. Pyrolyzed polyphenylquinoxaline is a satisfactory coupling agent for polyimide/Thornel 300 graphite fiber composites. During 1000 hours aging at 588K such composites lose a little over half their transverse tensile strength, and suffer a slight loss in flexural modulus. No degradation of flexural strength or interlaminar shear strength occured during 1000 hours aging at 588K. None of the coupling agents examined had a markedly beneficial effect with polyphenylquinoxaline composites.

Evaluation of carrier agents for hyperpolarized xenon MRI

NASA Technical Reports Server (NTRS)

Venkatesh, A. K.; Zhao, L.; Balamore, D.; Jolesz, F. A.; Albert, M. S.

2000-01-01

Several biocompatible carrier agents, in which xenon is highly soluble and has a long T(1), were tested, and injected in living rats. These included saline, Intralipid suspension, perfluorocarbon emulsion and (129)Xe gas-filled liposomes. The T(1) of (129)Xe in these compounds ranged from 47 to 116 s. Vascular injection of these carrier agents was tolerated well, encouraging their use for further experiments in live animals. In vivo spectra, obtained from gas-filled liposomes and perfluorocarbon solutions, suggest that these carrier agents have potential for use in angiography and perfusion imaging. Copyright 2000 John Wiley & Sons, Ltd.

Quinine conjugates and quinine analogues as potential antimalarial agents.

PubMed

Jones, Rachel A; Panda, Siva S; Hall, C Dennis

2015-06-05

Malaria is a tropical disease, prevalent in Southeast Asia and Africa, resulting in over half a million deaths annually; efforts to develop new antimalarial agents are therefore particularly important. Quinine continues to play a role in the fight against malaria, but quinoline derivatives are more widely used. Drugs based on the quinoline scaffold include chloroquine and primaquine, which are able to act against the blood and liver stages of the parasite's life cycle. The purpose of this review is to discuss reported biologically active compounds based on either the quinine or quinoline scaffold that may have enhanced antimalarial activity. The review emphasises hybrid molecules, and covers advances made in the last five years. The review is divided into three sections: modifications to the quinine scaffold, modifications to aminoquinolines and finally metal-containing antimalarial compounds. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Using Animated Agents in Learner-Controlled Training: The Effects of Design Control

ERIC Educational Resources Information Center

Behrend, Tara S.; Thompson, Lori Foster

2012-01-01

Animated agents have the potential to increase engagement and learning during online training by acting as personalized tutors. However, little is known about the conditions that make these agents most effective. In this study, 183 e-learners completed a Microsoft Excel training course. Approximately half were assigned an agent with predetermined…

NMR-based metabonomic analysis of MnO-embedded iron oxide nanoparticles as potential dual-modal contrast agents

NASA Astrophysics Data System (ADS)

Li, Jinquan; Zhou, Zijian; Feng, Jianghua; Cai, Shuhui; Gao, Jinhao; Chen, Zhong

2014-05-01

MnO-embedded iron oxide nanoparticles (MnIO-NPs) can be treated as potential dual-modal contrast agents. However, their overall bio-effects and potential toxicity remain unknown. In this study, the metabolic effects of MnIO-NPs (dosed at 1 and 5 mg Fe/kg) on Sprague-Dawley rats were investigated using metabonomic analysis, histopathological examination, and conventional biochemical analysis. The histological changes included a focal inflammation in the liver at high-dose and a slightly enlarged area of splenic white pulp after 48 h post-dose. Blood biochemical analysis showed that albumin, globulins, aspartate aminotransferase, lactate dehydrogenase, blood urea nitrogen, and glucose changed distinctly compared to the control. The metabonomic analysis of body fluids (serum and urine) and tissues (liver, kidney, and spleen) indicated that MnIO-NPs induced metabolic perturbation in rats including energy, nucleotides, amino acids and phospholipid metabolisms. Besides, the variations of supportive nutrients: valine, leucine, isoleucine, nicotinamide adenine dinucleotide (phosphate), and nicotinamide, and the conjugation substrates: glycine, taurine, glutamine, glutathione, and methyl donors (formate, sarcosine, dimethylglycine, choline, and betaine) were involved in detoxification reaction of MnIO-NPs. The obtained information would provide identifiable ground for the candidate selection and optimization.

Systematic review of herbals as potential anti-inflammatory agents: Recent advances, current clinical status and future perspectives

PubMed Central

Beg, Sarwar; Swain, Suryakanta; Hasan, Hameed; Barkat, M Abul; Hussain, Md Sarfaraz

2011-01-01

Many synthetic drugs reported to be used for the treatment of inflammatory disorders are of least interest now a days due to their potential side effects and serious adverse effects and as they are found to be highly unsafe for human assistance. Since the last few decades, herbal drugs have regained their popularity in treatment against several human ailments. Herbals containing anti-inflammatory activity (AIA) are topics of immense interest due to the absence of several problems in them, which are associated with synthetic preparations. The primary objective of this review is to provide a deep overview of the recently explored anti-inflammatory agents belonging to various classes of phytoconstituents like alkaloids, glycosides, terpenoids, steroids, polyphenolic compounds, and also the compounds isolated from plants of marine origin, algae and fungi. Also, it enlists a distended view on potential interactions between herbals and synthetic preparations, related adverse effects and clinical trials done on herbals for exploring their AIA. The basic aim of this review is to give updated knowledge regarding plants which will be valuable for the scientists working in the field of anti-inflammatory natural chemistry. PMID:22279370

Assessment of the risk of antiangiogenic agents before and after surgery.

PubMed

Bailey, Christina E; Parikh, Alexander A

2018-05-08

Angiogenesis plays a critical role in the growth, progression, and metastasis of numerous solid tumor types, and thus, antiangiogenic agents have been studied for many years as potential therapeutic agents. Many different antiangiogenic agents, including monoclonal antibodies and multi-targeted tyrosine kinase inhibitors (TKIs), have been approved for various oncology indications, and promising clinical activity has been demonstrated. However, some of these agents have also been associated with serious safety concerns. Because angiogenesis is an important step in the wound healing process, agents targeting the angiogenesis pathway may interfere with wound healing, thus increasing the risk of surgical wound complications, such as dehiscence, surgical site bleeding, and wound infection. Nevertheless, antiangiogenic agents can be safely used in the perioperative setting if oncologists and surgeons are educated on the biology and pharmacokinetics of these agents. This review discusses the available published literature regarding surgical complications associated with the use of antiangiogenic agents and provides updated clinical recommendations on the optimal timing between surgery and antiangiogenic therapy. Due to the paucity of data surrounding this topic, current and future clinical trials need to evaluate prospectively the potential risks for surgical complications associated with antiangiogenic therapies to establish specific guidelines for their safe and effective use within the surgical oncology community. Copyright © 2018 Elsevier Ltd. All rights reserved.

[New agents for hypercholesterolemia].

PubMed

Pintó, Xavier; García Gómez, María Carmen

2016-02-19

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

Synthesis of nοvel artemisinin dimers with polyamine linkers and evaluation of their potential as anticancer agents.

PubMed

Magoulas, George E; Tsigkou, Tzoanna; Skondra, Lina; Lamprou, Margarita; Tsoukala, Panagiota; Kokkinogouli, Vassiliki; Pantazaka, Evangelia; Papaioannou, Dionissios; Athanassopoulos, Constantinos M; Papadimitriou, Evangelia

2017-07-15

The natural product artemisinin and derivatives thereof are currently considered as the drugs of choice for the treatment of malaria. At the same time, a significant number of such drugs have also shown interesting anticancer activity. In the context of the present research work, artemisinin was structurally modified and anchored to naturally occurring polyamines to afford new artemisinin dimeric conjugates whose potential anticancer activity was evaluated. All artemisinin conjugates tested were more effective than artemisinin itself in decreasing the number of MCF7 breast cancer cells. The effect required conjugation and was not due to the artemisinin analogue or the polyamine, alone or in combination. To elucidate potential mechanism of action, we used the most effective conjugates 6, 7, 9 and 12 and found that they decreased expression and secretion of the angiogenic growth factor pleiotrophin by the cancer cells themselves, and inhibited angiogenesis in vivo and endothelial cell growth in vitro. These data suggest that the new artemisinin dimers are good candidates for the development of effective anticancer agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

An overview of cytokines and cytokine antagonists as therapeutic agents.

PubMed

Donnelly, Raymond P; Young, Howard A; Rosenberg, Amy S

2009-12-01

Cytokine-based therapies have the potential to provide novel treatments for cancer, autoimmune diseases, and many types of infectious disease. However, to date, the full clinical potential of cytokines as drugs has been limited by a number of factors. To discuss these limitations and explore ways to overcome them, the FDA partnered with the New York Academy of Sciences in March 2009 to host a two-day forum to discuss more effective ways to harness the clinical potential of cytokines and cytokine antagonists as therapeutic agents. The first day was focused primarily on the use of recombinant cytokines as therapeutic agents for treatment of human diseases. The second day focused largely on the use of cytokine antagonists as therapeutic agents for treatment of human diseases. This issue of the Annals includes more than a dozen papers that summarize much of the information that was presented during this very informative two-day conference.

Redox-activated MRI contrast agents based on lanthanide and transition metal ions.

PubMed

Tsitovich, Pavel B; Burns, Patrick J; McKay, Adam M; Morrow, Janet R

2014-04-01

The reduction/oxidation (redox) potential of tissue is tightly regulated in order to maintain normal physiological processes, but is disrupted in disease states. Thus, the development of new tools to map tissue redox potential may be clinically important for the diagnosis of diseases that lead to redox imbalances. One promising area of chemical research is the development of redox-activated probes for mapping tissue through magnetic resonance imaging (MRI). In this review, we summarize several strategies for the design of redox-responsive MRI contrast agents. Our emphasis is on both lanthanide(III) and transition metal(II/III) ion complexes that provide contrast either as T1 relaxivity MRI contrast agents or as paramagnetic chemical exchange saturation transfer (PARACEST) contrast agents. These agents are redox-triggered by a variety of chemical reactions or switches including redox-activated thiol groups, and heterocyclic groups that interact with the metal ion or influence properties of other ancillary ligands. Metal ion centered redox is an approach which is ripe for development by coordination chemists. Redox-triggered metal ion approaches have great potential for creating large differences in magnetic properties that lead to changes in contrast. An attractive feature of these agents is the ease of fine-tuning the metal ion redox potential over a biologically relevant range. Copyright © 2014 Elsevier Inc. All rights reserved.

Genomic identification of potential targets unique to Candida albicans for the discovery of antifungal agents.

PubMed

Tripathi, Himanshu; Luqman, Suaib; Meena, Abha; Khan, Feroz

2014-01-01

Despite of modern antifungal therapy, the mortality rates of invasive infection with human fungal pathogen Candida albicans are up to 40%. Studies suggest that drug resistance in the three most common species of human fungal pathogens viz., C. albicans, Aspergillus fumigatus (causing mortality rate up to 90%) and Cryptococcus neoformans (causing mortality rate up to 70%) is due to mutations in the target enzymes or high expression of drug transporter genes. Drug resistance in human fungal pathogens has led to an imperative need for the identification of new targets unique to fungal pathogens. In the present study, we have used a comparative genomics approach to find out potential target proteins unique to C. albicans, an opportunistic fungus responsible for severe infection in immune-compromised human. Interestingly, many target proteins of existing antifungal agents showed orthologs in human cells. To identify unique proteins, we have compared proteome of C. albicans [SC5314] i.e., 14,633 total proteins retrieved from the RefSeq database of NCBI, USA with proteome of human and non-pathogenic yeast Saccharomyces cerevisiae. Results showed that 4,568 proteins were identified unique to C. albicans as compared to those of human and later when these unique proteins were compared with S. cerevisiae proteome, finally 2,161 proteins were identified as unique proteins and after removing repeats total 1,618 unique proteins (42 functionally known, 1,566 hypothetical and 10 unknown) were selected as potential antifungal drug targets unique to C. albicans.

Sonorensin: A new bacteriocin with potential of an anti-biofilm agent and a food biopreservative

PubMed Central

Chopra, Lipsy; Singh, Gurdeep; Kumar Jena, Kautilya; Sahoo, Debendra K.

2015-01-01

The emergence of antibiotic resistant bacteria has led to exploration of alternative therapeutic agents such as ribosomally synthesized bacterial peptides known as bacteriocins. Biofilms, which are microbial communities that cause serious chronic infections, form environments that enhance antimicrobial resistance. Bacteria in biofilm can be upto thousand times more resistant to antibiotics than the same bacteria circulating in a planktonic state. In this study, sonorensin, predicted to belong to the heterocycloanthracin subfamily of bacteriocins, was found to be effectively killing active and non-multiplying cells of both Gram-positive and Gram-negative bacteria. Sonorensin showed marked inhibition activity against biofilm of Staphylococcus aureus. Fluorescence and electron microscopy suggested that growth inhibition occurred because of increased membrane permeability. Low density polyethylene film coated with sonorensin was found to effectively control the growth of food spoilage bacteria like Listeria monocytogenes and S. aureus. The biopreservative effect of sonorensin coated film showing growth inhibition of spoilage bacteria in chicken meat and tomato samples demonstrated the potential of sonorensin as an alternative to current antibiotics/ preservatives. PMID:26292786

Gold-Containing Indoles as Anti-Cancer Agents that Potentiate the Cytotoxic Effects of Ionizing Radiation

PubMed Central

Craig, Sandra; Gao, Lei; Lee, Irene; Gray, Thomas; Berdis, Anthony J.

2012-01-01

This report describes the design and application of several distinct gold-containing indoles as anti-cancer agents. When used individually, all gold-bearing compounds display cytostatic effects against leukemia and adherent cancer cell lines. However, two gold-bearing indoles show unique behavior by increasing the cytotoxic effects of clinically relevant levels of ionizing radiation. Quantifying the amount of DNA damage demonstrates that each gold-indole enhances apoptosis by inhibiting DNA repair. Both Au(I)-indoles were tested for inhibitory effects against various cellular targets including thioredoxin reductase, a known target of several gold compounds, and various ATP-dependent kinases. While neither compound significantly inhibits the activity of thioreoxin reductase, both showed inhibitory effects against several kinases associated with cancer initiation and progression. The inhibition of these kinases provides a possible mechanism for the ability of these Au(I)-indoles potentiate the cytotoxic effects of ionizing radiation. Clinical applications of combining Au(I)-indoles with ionizing radiation are discussed as a new strategy to achieve chemosensitization of cancer cells. PMID:22289037

Curcumin: a promising agent targeting cancer stem cells.

PubMed

Zang, Shufei; Liu, Tao; Shi, Junping; Qiao, Liang

2014-01-01

Cancer stem cells are a subset of cells that are responsible for cancer initiation and relapse. They are generally resistant to the current anticancer agents. Successful anticancer therapy must consist of approaches that can target not only the differentiated cancer cells, but also cancer stem cells. Emerging evidence suggested that the dietary agent curcumin exerted its anti-cancer activities via targeting cancer stem cells of various origins such as those of colorectal cancer, pancreatic cancer, breast cancer, brain cancer, and head and neck cancer. In order to enhance the therapeutic potential of curcumin, this agent has been modified or used in combination with other agents in the experimental therapy for many cancers. In this mini-review, we discussed the effect of curcumin and its derivatives in eliminating cancer stem cells and the possible underlying mechanisms.

Potential applications of venom peptides as anti-thrombotic agents in arterial & deep-vein thrombosis.

PubMed

Khan, Samiullah; Gul, Aqsa; Noreen, Rabia; Ashraf, Muhammad; Ahmad, Sohail; Awan, Sattar Bakhsh

2018-06-13

Thrombus is composed of two main substances i.e. red blood cells and aggregated platelets which make a web of inter-connected fibrin proteins. During injury it prevents bleeding, so it is very useful but it can be very dangerous if it is produced in healthy blood vessels and block the blood flow through it. Mural thrombi attaches with the blood vessels but in most cases do not block it completely. Venoms are an incredible source of peptides having amazing bioactivities with varying number of amino acid residues. Anticoagulant venom peptides however inhibit the enzyme taking part in coagulation like factor Xa and thrombin. The anticoagulant potential of venom peptides have also been reported by the degradation of the fibrin or fibrinogen related to serine or metalloproteases. Designing and development of numerous therapeutic agents or lead molecules mostly for cardiovascular diseases have been motivated from toxins/proteins from snake venoms. For example, disintegrins, a large family of platelet aggregation inhibitors found in viperid and crotalid snake venoms were the basis for designing of platelet aggregation inhibitors such as eptifibatide and tirofiban. Ancrod isolated from Malayan pit viper venom can cause reduction in level of blood fibrinogen and has been effectively tried in various ischemic conditions, including stroke. In order to search for novel lead molecules, the emphasis should be on isolation and characterization of pharmacologically active snake venoms proteins affecting blood coagulation and platelet aggregation. In this review an attempt has been made to recapitulates and discuss venoms of different animals and arthropod having anticoagulant peptides for their potential use in therapeutics and diagnostics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

School-Based Decision Making: A Principal-Agent Perspective.

ERIC Educational Resources Information Center

Ferris, James M.

1992-01-01

A principal-agent framework is used to examine potential gains in educational performance and potential threats to public accountability that school-based decision-making proposals pose. Analysis underscores the need to tailor the design of decentralized decision making to the sources of poor educational performance and threats to school…

The potential of compounds isolated from Xylaria spp. as antifungal agents against anthracnose.

PubMed

Elias, Luciana M; Fortkamp, Diana; Sartori, Sérgio B; Ferreira, Marília C; Gomes, Luiz H; Azevedo, João L; Montoya, Quimi V; Rodrigues, André; Ferreira, Antonio G; Lira, Simone P

2018-03-31

Anthracnose is a crop disease usually caused by fungi in the genus Colletotrichum or Gloeosporium. These are considered one of the main pathogens, causing significant economic losses, such as in peppers and guarana. The current forms of control include the use of resistant cultivars, sanitary pruning and fungicides. However, even with the use of some methods of controlling these cultures, the crops are not free of anthracnose. Additionally, excessive application of fungicides increases the resistance of pathogens to agrochemicals and cause harm to human health and the environment. In order to find natural antifungal agents against guarana anthracnose, endophytic fungi were isolated from Amazon guarana. The compounds piliformic acid and cytochalasin D were isolated by chromatographic techniques from two Xylaria spp., guided by assays with Colletotrichum gloeosporioides. The isolated compounds were identified by spectrometric techniques, as NMR and mass spectrometry. This is the first report that piliformic acid and cytochalasin D have antifungal activity against C. gloeosporioides with MIC 2.92 and 2.46μmolmL -1 respectively. Captan and difenoconazole were included as positive controls (MIC 16.63 and 0.02μmolmL -1 , respectively). Thus, Xylaria species presented a biotechnological potential and production of different active compounds which might be promising against anthracnose disease. Copyright © 2018 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Potential of Submergedly Cultivated Mycelia of Ganoderma spp. as Antioxidant and Antimicrobial Agents.

PubMed

Ćilerdžić, Jasmina; Stajic, Mirjana; Vukojevic, Jelena

2016-01-01

The study aimed to evaluate the antiradical and antimicrobial (antibacterial and antifungal) potentials of ethanol mycelial extracts of selected Ganoderma species and strains and to define interand intraspecies diversity among Ganoderma species and strains. Ganoderma lucidum strains were good DPPH• scavengers (neutralizing up to 57.12% radicals), contrary to G. applanatum (20.35%) and G. carnosum (17.04%). High correlations between the activities and contents of total phenols in the extracts showed that these compounds were carriers of the activity. Results obtained by both discdiffusion and microdilution methods indicated that the extract of G. lucidum BEOFB 433 was the most potent antibacterial agent that inhibited growth of almost all bacterial species at a concentration of 1.0 mg/mL. Salmonella typhimurium was the most sensitive species to the mycelium extracts. Extracts of G. lucidum BEOFB 431 and BEOFB 434 showed the best antifungal activity since in concentration of 0.5 mg/mL inhibited the growth of Aspergillus glaucus (BEOFB 431) and the growth of A. glaucus and Trichoderma viride (BEOFB 434). Extracts of G. applanatum and G. lucidum BEOFB 431 had the strongest fungicidal effects, with lethal outcomes for A. glaucus and T. viride, respectively, being noted at a concentration of 1.17 mg/mL. Aspergillus niger was proved as the most resistant species.

A technology path to tactical agent-based modeling

NASA Astrophysics Data System (ADS)

James, Alex; Hanratty, Timothy P.

2017-05-01

Wargaming is a process of thinking through and visualizing events that could occur during a possible course of action. Over the past 200 years, wargaming has matured into a set of formalized processes. One area of growing interest is the application of agent-based modeling. Agent-based modeling and its additional supporting technologies has potential to introduce a third-generation wargaming capability to the Army, creating a positive overmatch decision-making capability. In its simplest form, agent-based modeling is a computational technique that helps the modeler understand and simulate how the "whole of a system" responds to change over time. It provides a decentralized method of looking at situations where individual agents are instantiated within an environment, interact with each other, and empowered to make their own decisions. However, this technology is not without its own risks and limitations. This paper explores a technology roadmap, identifying research topics that could realize agent-based modeling within a tactical wargaming context.

Pre-release efficacy assessment of the leaf-mining moth Digitivalva delaireae (Lepidoptera: Glyphipterigidae), a potential biological control agent for Cape-ivy, Delairea odorata (Asteraceae), in western North America

USDA-ARS?s Scientific Manuscript database

The leaf-mining moth Digitivalva delaireae Gaedike & Kruger (Lepidoptera: Glyphipterigidae) is a potential biological control agent for the invasive vine Cape-ivy, Delairea odorata Lemaire (Asteraceae), in western North America, where two morphological varieties (stipulate and exstipulate) of Cape-i...

Potential therapeutic agents for circulatory diseases from Bauhinia glauca Benth.subsp. pernervosa. (Da Ye Guan Men).

PubMed

Tang, Yingzhan; Ling, Junhong; Zhang, Peng; Zhang, Xiangrong; Zhang, Na; Wang, Wenli; Li, Jiayuan; Li, Ning

2015-08-15

Because of platelets as critical factor in the formation of pathogenic thrombi, anti-platelet activities have been selected as therapeutic target for various circulatory diseases. In order to find potential therapeutic agents, bioassay-directed separation of Bauhinia glauca Benth.subsp. pernervosa. (called Da Ye Guan Men as a traditional Chinese medicine) was performed to get 29 main components (compounds 1-29) from the bioactive part of this herbal. It was the first time to focus on the composition with anti-platelet aggregation activities for this traditional Chinese medicine. The constituents, characterized from the effective extract, were established on the basis of extensive spectral data analysis. Then their anti-platelet aggregation effects were evaluated systematically. On the basis of the chemical profile and biological assay, it was suggested that the flavonoid composition (5 and 18) should be responsible for the anti-platelet aggregation of the herbal because of their significant activities. The primary structure and activity relationship was also discussed briefly. Copyright © 2015. Published by Elsevier Ltd.

Antidotes and treatments for chemical warfare/terrorism agents: an evidence-based review.

PubMed

Rodgers, G C; Condurache, C T

2010-09-01

This article reviews the evidence supporting the efficacy of antidotes used or recommended for the potential chemical warfare agents of most concern. Chemical warfare agents considered include cyanide, vesicants, pulmonary irritants such as chlorine and phosgene, and nerve agents. The strength of evidence for most antidotes is weak, highlighting the need for additional research in this area.

Two decades of dendrimers as versatile MRI agents: a tale with and without metals.

PubMed

McMahon, Michael T; Bulte, Jeff W M

2018-05-01

Dendrimers or dendritic polymers are a class of compounds with great potential for nanomedical use. Some of their properties, including their rigidity, low polydispersity and the ease with which their surfaces can be modified make them particularly well suited for use as MRI diagnostic or theranostic agents. For the past 20 years, researchers have recognized this potential and refined dendrimer formulations to optimize these nanocarriers for a host of MRI applications, including blood pool imaging agents, lymph node imaging agents, tumor-targeted theranostic agents and cell tracking agents. This review summarizes the various types of dendrimers according to the type of MR contrast they can provide. This includes the metallic T 1 , T 2 and paraCEST imaging agents, and the non-metallic diaCEST and fluorinated ( 19 F) heteronuclear imaging agents. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanomaterials and Implants. © 2017 Wiley Periodicals, Inc.

Preparing Change Agents for Change Agent Roles.

ERIC Educational Resources Information Center

Sedlacek, James R.

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

Evaluation of Market Design Agents: The Mertacor Perspective

NASA Astrophysics Data System (ADS)

Stavrogiannis, Lampros C.; Mitkas, Pericles A.

The annual Trading Agent Competition for Market Design, CAT, provides a testbed to study the mechanisms that modern stock exchanges use in their effort to attract potential traders while maximizing their profit. This paper presents an evaluation of the agents that participated in the 2008 competition. The evaluation is based on the analysis of the CAT finals as well as on the results obtained from post-tournament experiments. We present Mertacor, our entrant for 2008, and compare it with the other available agents. In addition, we introduce a simple yet effective way of computing the global competitive equilibrium that Mertacor utilizes and discuss its importance for the game.

Radioiodine Labeled Anti-MIF McAb: A Potential Agent for Inflammation Imaging

PubMed Central

Zhang, Chao; Hou, Gui-hua; Han, Jian-kui; Song, Jing; Liang, Ting

2007-01-01

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that may play a role in the pathogenesis of inflammation. Radiolabeled anti-MIF McAb can be used to detect in vivo inflammatory changes. The objective of this study was to investigate in vivo biology of radioiodinated anti-MIF McAb using the inflammation model mice. Anti-MIF McAb was radioiodinated with NaI125 by Iodogen method. Animal models were induced in the mice by intramuscular injection of S. aureus, E. coli, and turpentine oil. The biodistribution studies with radioiodinated anti-MIF McAb were performed on inflammation mice. The relationship between inflammatory lesions and anti-MIF McAb binding was investigated using the percent of injected dose per gram tissue (% ID/g) of tissue samples and whole-body autoradiography. The radioactivity of I125-anti-MIF McAb in the inflammatory tissue increased gradually for three inflammation models. The highest uptake was found in S. aureus group and the lowest was in E. coli group. The uptake in turpentine oil group was average. Whole-body autoradiography showed that all inflammation foci could be visualized clearly from 24 hours after injection, but 48 hours images were much clearer in accordance with the high T/NT ratio. These results demonstrate the ability of radioiodinated anti-MIF McAb to measure in vivo inflammatory events represented by high expression of MIF and suggests that radiolabeled anti-MIF McAb warrants further investigation as a potential inflammation-seeking agent for imaging to detect inflammatory disorders. PMID:18317509

Bioinformatics prediction of siRNAs as potential antiviral agents against dengue viruses

PubMed Central

Villegas-Rosales, Paula M; Méndez-Tenorio, Alfonso; Ortega-Soto, Elizabeth; Barrón, Blanca L

2012-01-01

Dengue virus (DENV 1-4) represents the major emerging arthropod-borne viral infection in the world. Currently, there is neither an available vaccine nor a specific treatment. Hence, there is a need of antiviral drugs for these viral infections; we describe the prediction of short interfering RNA (siRNA) as potential therapeutic agents against the four DENV serotypes. Our strategy was to carry out a series of multiple alignments using ClustalX program to find conserved sequences among the four DENV serotype genomes to obtain a consensus sequence for siRNAs design. A highly conserved sequence among the four DENV serotypes, located in the encoding sequence for NS4B and NS5 proteins was found. A total of 2,893 complete DENV genomes were downloaded from the NCBI, and after a depuration procedure to identify identical sequences, 220 complete DENV genomes were left. They were edited to select the NS4B and NS5 sequences, which were aligned to obtain a consensus sequence. Three different servers were used for siRNA design, and the resulting siRNAs were aligned to identify the most prevalent sequences. Three siRNAs were chosen, one targeted the genome region that codifies for NS4B protein and the other two; the region for NS5 protein. Predicted secondary structure for DENV genomes was used to demonstrate that the siRNAs were able to target the viral genome forming double stranded structures, necessary to activate the RNA silencing machinery. PMID:22829722

Inosine 5'-Monophosphate Dehydrogenase (IMPDH) as a Potential Target for the Development of a New Generation of Antiprotozoan Agents.

PubMed

Fotie, Jean

2018-01-01

Inosine-5'-monophosphate dehydrogenase (IMPDH) is a metabolic enzyme that catalyzes the critical step in guanine nucleotide biosynthesis, and thus is at the center of cell growth and proliferation. However, although this enzyme has been exploited as potential target for the development of immunosuppressive, anticancer, and antiviral agents, the functional importance of IMPDH as a promising antiprotozoan drug target is still in its infancy mainly because of the availability of alternative nucleotides metabolic pathways in many of these parasites. This situation suggests that the inhibition of IMPDH might have little to no effect on the survival of protozoan parasites. As a result, no IMPDH inhibitor is currently commercially available or has advanced to clinical trials as a potential antiprotozoan drug. Nevertheless, recent advances toward the development of selective inhibitors of the IMPDH enzyme from Crystosporidium parvum as potential drug candidates against cryptosporidiosis should revive further investigations of this drug target in other protozoa parasites. The current review examines the chemical structures and biological activities of reported protozoan's IMPDH inhibitors. SciFinder was used to broadly pinpoint reports published on the topic in the chemical literature, with no specific time frame. Opportunities and challenges towards the development of inhibitors of IMPDH enzymes from protozoa parasites as potential chemotherapies toward the respective diseases they cause are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Caspase-3 short hairpin RNAs: a potential therapeutic agent in neurodegeneration of aluminum-exposed animal model.

PubMed

Zhang, Qinli; Li, Na; Jiao, Xia; Qin, Xiujun; Kaur, Ramanjit; Lu, Xiaoting; Song, Jing; Wang, Linping; Wang, Junming; Niu, Qiao

2014-01-01

There is abundant evidence supporting the role of caspases in the development of neurodegenerative disease, including Alzheimer's disease (AD). Therefore, regulating the activity of caspases has been considered as a therapeutic target. However, all the efforts on AD therapy using pan-caspase inhibitors have failed because of uncontrolled adverse effects. Alternatively, the specific knockdown of caspase-3 gene through RNA interference (RNAi) could serve as a future potential therapeutic strategy. The aim of the present study is to down-regulate the expression of caspase-3 gene using lentiviral vector-mediated caspase-3 short hairpin RNA (LV-Caspase-3 shRNA). The effect of LV-Caspase-3 shRNA on apoptosis induced by aluminum (Al) was investigated in primary cultured cortical neurons and validated in C57BL/6J mice. The results indicated an increase in apoptosis and caspase-3 expression in primary cultured neurons and the cortex ofmice exposed to Al, which could be down-regulated by LV-Caspase-3 shRNA. Furthermore, LV-Caspase-3 shRNA reduced neural cell death and improved learning and memory in C57BL/6J mice treated with Al. Our results suggest that LV-caspase-3 shRNA is a potential therapeutic agent to prevent neurodegeneration and cognitive dysfunction in aluminum- exposed animal models. The findings provide a rational gene therapy strategy for AD.

New Potential Antimalarial Agents: Design, Synthesis and Biological Evaluation of Some Novel Quinoline Derivatives as Antimalarial Agents.

PubMed

Radini, Ibrahim Ali M; Elsheikh, Tarek M Y; El-Telbani, Emad M; Khidre, Rizk E

2016-07-14

A novel series of dihydropyrimidines (DHPMs) 4a-j; 2-oxopyran-3-carboxylate 7a,b; 1-amino-1,2-dihydropyridine-3-carboxylate 8; and 1,3,4-oxadiazole derivatives 12 with quinolinyl residues have been synthesized in fairly good yields. The structure of the newly synthesized compounds was elucidated on the basis of analytical and spectral analyses. In vitro antimalarial evaluation of the synthesized quinoline derivatives against Plasmodium falciparum revealed them to possess moderate to high antimalarial activities, with IC50 values ranging from 0.014-5.87 μg/mL. Compounds 4b,g,i and 12 showed excellent antimalarial activity against to Plasmodium falciparum compared with the antimalarial agent chloroquine (CQ).

Agent-based modeling as a tool for program design and evaluation.

PubMed

Lawlor, Jennifer A; McGirr, Sara

2017-12-01

Recently, systems thinking and systems science approaches have gained popularity in the field of evaluation; however, there has been relatively little exploration of how evaluators could use quantitative tools to assist in the implementation of systems approaches therein. The purpose of this paper is to explore potential uses of one such quantitative tool, agent-based modeling, in evaluation practice. To this end, we define agent-based modeling and offer potential uses for it in typical evaluation activities, including: engaging stakeholders, selecting an intervention, modeling program theory, setting performance targets, and interpreting evaluation results. We provide demonstrative examples from published agent-based modeling efforts both inside and outside the field of evaluation for each of the evaluative activities discussed. We further describe potential pitfalls of this tool and offer cautions for evaluators who may chose to implement it in their practice. Finally, the article concludes with a discussion of the future of agent-based modeling in evaluation practice and a call for more formal exploration of this tool as well as other approaches to simulation modeling in the field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recent perspectives on the role of nutraceuticals as cholesterol-lowering agents.

PubMed

Ward, Natalie; Sahebkar, Amirhossein; Banach, Maciej; Watts, Gerald

2017-12-01

Reduction in circulating cholesterol is an important step in lowering cardiovascular risk. Although statins are the most frequently prescribed cholesterol-lowering medication, there remains a significant portion of patients who require alternative treatment options. Nutraceuticals are increasingly popular as cholesterol-lowering agents. Despite the lack of long-term trials evaluating their use on cardiovascular endpoints and mortality, several studies have demonstrated their potential cholesterol-lowering effects. The purpose of this review is to provide an update on the role of nutraceuticals as cholesterol-lowering agents. The present review will focus on individual nutraceutical compounds, which have shown modest cholesterol-lowering abilities, as well as combination nutraceuticals, which may offer potential additive and/or synergistic effects. Berberine, red yeast rice, and plant sterols have moderate potential as cholesterol-lowering agents. Combination nutraceuticals, including the proprietary formulation, Armolipid Plus, appear to confer additional benefit on plasma lipid profiles, even when taken with statins and other agents. Although robust, long-term clinical trials to examine the effects of nutraceuticals on clinical outcomes are still required, their cholesterol-lowering ability, together with their reported tolerance and safety, offer a pragmatic option for lowering plasma cholesterol levels.

Biological control agents elevate hantavirus by subsidizing deer mouse populations

Treesearch

Dean E. Pearson; Ragan M. Callaway

2006-01-01

Biological control of exotic invasive plants using exotic insects is practiced under the assumption that biological control agents are safe if they do not directly attack non-target species. We tested this assumption by evaluating the potential for two host-specific biological control agents (Urophora spp.), widely established in North America for spotted...

PAXIP1 potentiates the combination of WEE1 inhibitor AZD1775 and platinum agents in lung cancer

PubMed Central

Jhuraney, Ankita; Woods, Nicholas T.; Wright, Gabriela; Rix, Lily; Kinose, Fumi; Kroeger, Jodi L.; Remily-Wood, Elizabeth; Cress, W. Douglas; Koomen, John M.; Brantley, Stephen G.; Gray, Jhanelle E.; Haura, Eric B.; Rix, Uwe; Monteiro, Alvaro N.

2016-01-01

The DNA damage response (DDR) involves a complex network of signaling events mediated by modular protein domains such as the BRCT (BRCA1 C-terminal) domain. Thus, proteins that interact with BRCT domains and are a part of the DDR constitute potential targets for sensitization to DNA damaging chemotherapy agents. We performed a pharmacological screen to evaluate seventeen kinases, identified in a BRCT-mediated interaction network as targets to enhance platinum-based chemotherapy in lung cancer. Inhibition of mitotic kinase WEE1 was found to have the most effective response in combination with platinum compounds in lung cancer cell lines. In the BRCT-mediated interaction network, WEE1 was found in complex with PAXIP1, a protein containing six BRCT domains involved in transcription and in the cellular response to DNA damage. We show that PAXIP1 BRCT domains regulate WEE1-mediated phosphorylation of CDK1. Further, ectopic expression of PAXIP1 promotes enhanced caspase 3-mediated apoptosis in cells treated with WEE1 inhibitor AZD1775 (formerly, MK-1775) and cisplatin compared with cells treated with AZD1775 alone. Cell lines and patient-derived xenograft models expressing both PAXIP1 and WEE1 exhibited synergistic effects of AZD1775 and cisplatin. In summary, PAXIP1 is involved in sensitizing lung cancer cells to the WEE1 inhibitor AZD1775 in combination with platinum-based treatment. We propose that WEE1 and PAXIP1 levels may be used as mechanism-based biomarkers of response when WEE1 inhibitor AZD1775 is combined with DNA damaging agents. PMID:27196765

Efficacy of a novel mucolytic agent on pseudomyxoma peritonei mucin, with potential for treatment through peritoneal catheters

PubMed Central

Akhter, Javed; Pillai, Krishna; Chua, Terence C; Alzarin, Naeef; Morris, David Lawson

2014-01-01

Compared to current treatment for pseudomyxoma peritonei (PMP), the extraction of solubilised mucin through peritoneal catheter can be minimally invasive. However, mucin has variable appearance that may influence mucolysis. Hence, we investigated the mucolysis of 36 mucin samples with a novel agent. Using visual inspection and hardness index, PMP mucin was classified into three grades. The mucin pathological category was identified from patient record. Subsequently, the dissolution of the samples was tested. For in vitro, 1 g of mucin was treated to the mucolytic agent in 10 ml TRIS buffer at 37 deg. Celsius for 3 hours, with weighing of residual mucin. Control treatment was similar but received TRIS buffer. For in vivo, 2 g of implanted intra-peritoneal mucin in nude rats was treated to mucolytic (2 X 500 ul/24 hr, over 48 hours, plus another treatment before sacrifice at 56 hours, with weighing of residual mucin. Controls were treated but only with TRIS buffer. Six animals were used for each mucin grade (3 mucolytic treated & and 3 controls). Grades of mucin were soft mucin (62%), semi hard (20%) and hard mucin (18%). Diffuse peritoneal adenomucinosis had 50% of soft mucin and peritoneal mucinous carcinoma had 11% (P = 0.0382). In vitro and in vivo absolute disintegration was 100% for soft, 57.38% and 48.67% for semi hard, 50% and 28.67% for hard mucin. Majority of mucin were soft with complete disintegration, the rest showed variable disintegration, suggesting that the mucolytic has potential for treating PMP. PMID:25232491

Enhanced degradation of chitosan by applying plasma treatment in combination with oxidizing agents for potential use as an anticancer agent.

PubMed

Chokradjaroen, Chayanaphat; Rujiravanit, Ratana; Watthanaphanit, Anyarat; Theeramunkong, Sewan; Saito, Nagahiro; Yamashita, Kazuko; Arakawa, Ryuichi

2017-07-01

Solution plasma (SP) treatment in combination with oxidizing agents, i.e., hydrogen peroxide (H 2 O 2 ), potassium persulfate (K 2 S 2 O 8 ) and sodium nitrite (NaNO 2 ) were adopted to chitosan degradation in order to achieve fast degradation rate, low chemicals used and high yield of low-molecular-weight chitosan and chitooligosaccharide (COS). Among the studied oxidizing agents, H 2 O 2 was found to be the best choice in terms of appreciable molecular weight reduction without major change in chemical structure of the degraded products of chitosan. By the combination with SP treatment, dilute solution of H 2 O 2 (4-60mM) was required for effective degradation of chitosan. The combination of SP treatment and dilute solution of H 2 O 2 (60mM) resulted in the great reduction of molecular weight of chitosan and water-soluble chitosan was obtained as a major product. The resulting water-soluble chitosan was precipitated to obtain COS. An inhibitory effect against cervical cancer cell line (HeLa cells) of COS was also examined. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biology and host range of Tecmessa elegans (Lepidoptera:Notodontidae) a leaf-feeding moth evaluated as a potential biological control agent for Schinus terebinthifolius (Sapindales: Anacardiaceae) in the USA

USDA-ARS?s Scientific Manuscript database

During surveys for natural enemies that could potentially be used as classical biological control agents of Schinus terebinthifolius Raddi (Brazilian pepper) which is invasive in the USA, the caterpillar, Tecmessa elegans Schaus (Lepidoptera: Notodontidae), was recorded feeding on the leaves of the ...

Multi-Targeted Agents in Cancer Cell Chemosensitization: What We Learnt from Curcumin Thus Far.

PubMed

Bordoloi, Devivasha; Roy, Nand K; Monisha, Javadi; Padmavathi, Ganesan; Kunnumakkara, Ajaikumar B

2016-01-01

Research over the past several years has developed many mono-targeted therapies for the prevention and treatment of cancer, but it still remains one of the fatal diseases in the world killing 8.2 million people annually. It has been well-established that development of chemoresistance in cancer cells against mono-targeted chemotherapeutic agents by modulation of multiple survival pathways is the major cause of failure of cancer chemotherapy. Therefore, inhibition of these pathways by non-toxic multi-targeted agents may have profoundly high potential in preventing drug resistance and sensitizing cancer cells to chemotherapeutic agents. To study the potential of curcumin, a multi-targeted natural compound, obtained from the plant Turmeric (Curcuma longa) in combination with standard chemotherapeutic agents to inhibit drug resistance and sensitize cancer cells to these agents based on available literature and patents. An extensive literature survey was performed in PubMed and Google for the chemosensitizing potential of curcumin in different cancers published so far and the patents published during 2014-2015. Our search resulted in many in vitro, in vivo and clinical reports signifying the chemosensitizing potential of curcumin in diverse cancers. There were 160 in vitro studies, 62 in vivo studies and 5 clinical studies. Moreover, 11 studies reported on hybrid curcumin: the next generation of curcumin based therapeutics. Also, 34 patents on curcumin's biological activity have been retrieved. Altogether, the present study reveals the enormous potential of curcumin, a natural, non-toxic, multi-targeted agent in overcoming drug resistance in cancer cells and sensitizing them to chemotherapeutic drugs.

Fatty acid is a potential agent for bone tissue induction: In vitro and in vivo approach.

PubMed

Cardoso, Guinea Bc; Chacon, Erivelto; Chacon, Priscila Gl; Bordeaux-Rego, Pedro; Duarte, Adriana Ss; Saad, Sara T Olalla; Zavaglia, Cecilia Ac; Cunha, Marcelo R

2017-12-01

Our hypothesis was to investigate the fatty acid potential as a bone induction factor. In vitro and in vivo studies were performed to evaluate this approach. Oleic acid was used in a 0.5 wt.% concentration. Polycaprolactone was used as the polymeric matrix by combining solvent-casting and particulate-leaching techniques, with a final porosity of 70 wt.%, investigated by SEM images. Contact angle measurements were produced to investigate the influence of oleic acid on polycaprolactone chains. Cell culture was performed using adipocyte-derived stem cells to evaluate biocompatibility and bioactivity properties. In addition, in vivo studies were performed to evaluate the induction potential of oleic acid addition. Adipocyte-derived stem cells were used to provide differentiation after 21 days of culture. Likewise, information were obtained with in vivo data and cellular invagination was observed on both scaffolds (polycaprolactone and polycaprolactone /oleic acid); interestingly, the scaffold with oleic acid addition demonstrated that cellular migrations are not related to the surrounding tissue, indicating bioactive potential. Our hypothesis is that fatty acid may be used as a potential induction factor for bone tissue engineering. The study's findings indicate oleic acid as a possible agent for bone induction, according to data on cell differentiation, proliferation, and migration. Impact statement The biomaterial combined in this study on bone regeneration is innovative and shows promising results in the treatment of bone lesions. Polycaprolactone (PCL) and oleic acid have been studied separately. In this research, we combined biomaterials to assess the stimulus and the speed of bone healing.

Foaming Betadine Spray as a potential agent for non-labor-intensive preoperative surgical site preparation.

PubMed

Kargupta, Roli; Hull, Garret J; Rood, Kyle D; Galloway, James; Matthews, Clinton F; Dale, Paul S; Sengupta, Shramik

2015-04-02

could potentially serve as a non-labor intensive antimicrobial agent for surgical site preparation.

Distribution and Identification of Endophytic Streptomyces Species from Schima wallichii as Potential Biocontrol Agents against Fungal Plant Pathogens.

PubMed

Passari, Ajit K; Mishra, Vineet K; Gupta, Vijai K; Saikia, Ratul; Singh, Bhim P

2016-08-26

The prospective of endophytic microorganisms allied with medicinal plants is disproportionally large compared to those in other biomes. The use of antagonistic microorganisms to control devastating fungal pathogens is an attractive and eco-friendly substitute for chemical pesticides. Many species of actinomycetes, especially the genus Streptomyces, are well known as biocontrol agents. We investigated the culturable community composition and biological control ability of endophytic Streptomyces sp. associated with an ethanobotanical plant Schima wallichi. A total of 22 actinobacterial strains were isolated from different organs of selected medicinal plants and screened for their biocontrol ability against seven fungal phytopathogens. Seven isolates showed significant inhibition activity against most of the selected pathogens. Their identification based on 16S rRNA gene sequence analysis, strongly indicated that all strains belonged to the genus Streptomyces. An endophytic strain BPSAC70 isolated from root tissues showed highest percentage of inhibition (98.3 %) against Fusarium culmorum with significant activity against other tested fungal pathogens. Phylogenetic analysis based on 16S rRNA gene sequences revealed that all seven strains shared 100 % similarity with the genus Streptomyces. In addition, the isolates were subjected to the amplification of antimicrobial genes encoding polyketide synthase type I (PKS-I) and nonribosomal peptide synthetase (NRPS) and found to be present in most of the potent strains. Our results identified some potential endophytic Streptomyces species having antagonistic activity against multiple fungal phytopathogens that could be used as an effective biocontrol agent against pathogenic fungi.

Chemosensitization as a Means to Augment Commercial Antifungal Agents

PubMed Central

Campbell, Bruce C.; Chan, Kathleen L.; Kim, Jong H.

2012-01-01

Antimycotic chemosensitization and its mode of action are of growing interest. Currently, use of antifungal agents in agriculture and medicine has a number of obstacles. Foremost of these is development of resistance or cross-resistance to one or more antifungal agents. The generally high expense and negative impact, or side effects, associated with antifungal agents are two further issues of concern. Collectively, these problems are exacerbated by efforts to control resistant strains, which can evolve into a treadmill of higher dosages for longer periods. This cycle in turn, inflates cost of treatment, dramatically. A further problem is stagnation in development of new and effective antifungal agents, especially for treatment of human mycoses. Efforts to overcome some of these issues have involved using combinations of available antimycotics (e.g., combination therapy for invasive mycoses). However, this approach has had inconsistent success and is often associated with a marked increase in negative side effects. Chemosensitization by natural compounds to increase effectiveness of commercial antimycotics is a somewhat new approach to dealing with the aforementioned problems. The potential for safe natural products to improve antifungal activity has been observed for over three decades. Chemosensitizing agents possess antifungal activity, but at insufficient levels to serve as antimycotics, alone. Their main function is to disrupt fungal stress response, destabilize the structural integrity of cellular and vacuolar membranes or stimulate production of reactive oxygen species, augmenting oxidative stress and apoptosis. Use of safe chemosensitizing agents has potential benefit to both agriculture and medicine. When co-applied with a commercial antifungal agent, an additive or synergistic interaction may occur, augmenting antifungal efficacy. This augmentation, in turn, lowers effective dosages, costs, negative side effects and, in some cases, countermands resistance

Incorporating BDI Agents into Human-Agent Decision Making Research

NASA Astrophysics Data System (ADS)

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

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

Doxorubicin Delivery into Tumor Cells by Stable Cavitation without Contrast Agents.

PubMed

Chettab, Kamel; Mestas, Jean-Louis; Lafond, Maxime; Saadna, Djamel Eddine; Lafon, Cyril; Dumontet, Charles

2017-02-06

Doxorubicin, alone or in combination with other anticancer agents, is one of the most widely used chemotherapeutic agents and is administered in a wide range of cancers. However, the use of doxorubicin is limited due to its potential serious adverse reactions. Previous studies have established the ability of high intensity focused ultrasound (HIFU) in combination with various contrast agents to increase intracellular doxorubicin delivery in a targeted and noninvasive manner. In this study, we developed a new sonoporation device generating and monitoring acoustic cavitation bubbles without any addition of contrast agents. The device was used to potentiate the delivery of active doxorubicin into both adherent and suspended cell lines. Combining doxorubicin with ultrasound resulted in a significant enhancement of doxorubicin intracellular delivery and a decrease in cell viability at 48 and 72 h, in comparison to doxorubicin alone. More importantly and unlike previous investigations, our procedure does not require the addition of contrast agents to generate acoustic cavitation and to achieve high levels of doxorubicin delivery. The successful translation of this approach for an in vivo application may allow a significant reduction in the dosage and the adverse effects of doxorubicin therapy in patients.

Scaffold Hopping Toward Agomelatine: Novel 3, 4-Dihydroisoquinoline Compounds as Potential Antidepressant Agents

NASA Astrophysics Data System (ADS)

Yang, Yang; Ang, Wei; Long, Haiyue; Chang, Ying; Li, Zicheng; Zhou, Liangxue; Yang, Tao; Deng, Yong; Luo, Youfu

2016-10-01

A scaffold-hopping strategy toward Agomelatine based on in silico screening and knowledge analysis was employed to design novel antidepressant agents. A series of 3, 4-dihydroisoquinoline compounds were selected for chemical synthesis and biological assessment. Three compounds (6a-1, 6a-2, 6a-9) demonstrated protective effects on corticosterone-induced lesion of PC12 cells. Compound 6a-1 also displayed low inhibitory effects on the growth of HEK293 and L02 normal cells and it was further evaluated for its potential antidepressant effects in vivo. The forced swim test (FST) results revealed that compound 6a-1 remarkably reduced the immobility time of rats and the open field test (OFT) results indicated a better general locomotor activity of the rats treated with compound 6a-1 than those with Agomelatine or Fluoxetine. Mechanism studies implied that compound 6a-1 can significantly reduce PC12 cell apoptosis by up-regulation of GSH and down-regulation of ROS in corticosterone-induced lesion of PC12 cells. Meanwhile, the down-regulation of calcium ion concentration and up-regulation of BDNF level in PC12 cells may account for the neuroprotective effects. Furthermore, compound 6a-1 can increase cell survival and cell proliferation, promote cell maturation in the rat hippocampus after chronic treatment. The acute toxicity data in vivo indicated compound 6a-1 exhibited less hepatotoxicity than Agomelatine.

In Vivo Assessment of the Potential for Renal Bio-Effects from the Vaporization of Perfluorocarbon Phase-Change Contrast Agents.

PubMed

Nyankima, A Gloria; Rojas, Juan D; Cianciolo, Rachel; Johnson, Kennita A; Dayton, Paul A

2018-02-01

Low-boiling-point perfluorocarbon phase-change contrast agents (PCCAs) provide an alternative to microbubble contrast agents. Although parameter ranges related to in vivo bio-effects of microbubbles are fairly well characterized, few studies have been done to evaluate the potential of bio-effects related to PCCAs. To bridge this gap, we present an assessment of biological effects (e.g., hemorrhage) related to acoustically excited PCCAs in the rodent kidney. The presence or absence of bio-effects was observed after sonication with various perfluorocarbon core PCCAs (decafluorobutane, octafluoropropane or a 1:1 mixture) and as a function of activation pulse mechanical index (MI; minimum activation threshold, which was a moderate MI of 0.81-1.35 vs. a clinical maximum of 1.9). Bio-effects on renal tissue were assessed through hematology and histology including measurement of blood creatinine levels and the quantity of red blood cell (RBC) casts present in hematoxylin and eosin-stained kidney tissue sections after sonication. Short-term (24 h) and long-term (2 and 4 wk) analyses were performed after treatment. Results indicated that bio-effects from PCCA vaporization were not observed at lower mechanical indices. At higher mechanical indices, bio-effects were observed at 24 h, although these were not observable 2 wk after treatment. Copyright © 2018. Published by Elsevier Inc.

Potentiation activity of multiple antibacterial agents by Salvianolate from the Chinese medicine Danshen against methicillin-resistant Staphylococcus aureus (MRSA).

PubMed

Liu, Qing-Qing; Han, Jun; Zuo, Guo-Ying; Wang, Gen-Chun; Tang, Hua-Shu

2016-05-01

Salvianolate (SAL) is a prescribed medicine from the Chinese herb Danshen (Salvia miltiorrhiza Bunge). It has been widely used in treatment of coronary and other diseases with significant effects. The in vitro antimicrobial activities of SAL against infectious pathogens were assayed and its combined effects on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA) with ten antibiotics were evaluated. Susceptibility to each agent alone was tested using a broth microdilution method, and the chequerboard and time-kill experiments were used for the combined activities. The results showed MIC was 128-256 mg/L for SAL used alone against MRSA. Significant synergies were observed for SAL/Ampicillin (Fosfomycin, Erythromycin, Piperacillin-tazobactam or Clindamycin) combination against over half of the isolates, with their MICs reduced by times of dilution (TOD) to 4-32 (FICIs 0.375-0.5), respectively. SAL/AMP combination showed the best combined effect of synergy on bacteriostatic and bactericidal activities, while SAL/AMK combination reversed the resistance of MRSA to AMK. The results demonstrated that SAL enhanced widely the in vitro anti-MRSA efficacy of the ten antibacterial agents, which had potential for combinatory therapy of patients infected with MRSA and warrants further investigations. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Extinguishment and Burnback Testing of Fire Fighting Agents

DTIC Science & Technology

2005-09-26

resisting burnback for hydrocarbon fuel fires. Potential Aqueous Film Forming Foam ( AFFF ) replacements are required to exhibit an...simple, reliable test to evaluate the effectiveness of new foams being introduced into the market as potential Aqueous Film Forming Foam ( AFFF ...normal concentrations. Reference: Military Specification MIL-F-24385F, Fire Extinguishing Agent, Aqueous Film - Forming Foam

Biological Agents

MedlinePlus

... E-Tools Safety and Health Topics / Biological Agents Biological Agents This page requires that javascript be enabled ... 202) 693-2300 if additional assistance is required. Biological Agents Menu Overview In Focus: Ebola Frederick A. ...

Biological warfare agents as threats to potable water.

PubMed Central

Burrows, W D; Renner, S E

1999-01-01

Nearly all known biological warfare agents are intended for aerosol application. Although less effective as potable water threats, many are potentially capable of inflicting heavy casualties when ingested. Significant loss of mission capability can be anticipated even when complete recovery is possible. Properly maintained field army water purification equipment can counter this threat, but personnel responsible for the operation and maintenance of the equipment may be most at risk of exposure. Municipal water treatment facilities would be measurably less effective. Some replicating (infectious) agents and a few biotoxins are inactivated by chlorine disinfection; for others chlorine is ineffective or of unknown efficacy. This report assesses the state of our knowledge of agents as potable water threats and contemplates the consequences of intentional or collateral contamination of potable water supplies by 18 replicating agents and 9 biotoxins known or likely to be weaponized or otherwise used as threats. PMID:10585901

Pharmacotherapeutic agents in the treatment of methamphetamine dependence.

PubMed

Morley, Kirsten C; Cornish, Jennifer L; Faingold, Alon; Wood, Katie; Haber, Paul S

2017-05-01

Methamphetamine use is a serious public health concern in many countries and is second to cannabis as the most widely abused illicit drug in the world. Effective management for methamphetamine dependence remains elusive and the large majority of methamphetamine users relapse following treatment. Areas covered: Progression in the understanding of the pharmacological basis of methamphetamine use has provided us with innovative opportunities to develop agents to treat dependence. The current review summarizes relevant literature on the neurobiological and clinical correlates associated with methamphetamine use. We then outline agents that have been explored for potential treatments in preclinical studies, human laboratory phase I and phase II trials over the last ten years. Expert opinion: No agent has demonstrated a broad and strong effect in achieving MA abstinence in Phase II trials. Agents with novel therapeutic targets appear promising. Advancement in MA treatment, including translation into practice, faces several clinical challenges.

Detoxification of organophosphate nerve agents by bacterial phosphotriesterase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghanem, Eman; Raushel, Frank M.

2005-09-01

Organophosphates have been widely used as insecticides and chemical warfare agents. The health risks associated with these agents have necessitated the need for better detoxification and bioremediation tools. Bacterial enzymes capable of hydrolyzing the lethal organophosphate nerve agents are of special interest. Phosphotriesterase (PTE) isolated from the soil bacteria Pseudomonas diminuta displays a significant rate enhancement and substrate promiscuity for the hydrolysis of organophosphate triesters. Directed evolution and rational redesign of the active site of PTE have led to the identification of new variants with enhanced catalytic efficiency and stereoselectivity toward the hydrolysis of organophosphate neurotoxins. PTE has been utilizedmore » to protect against organophosphate poisoning in vivo. Biotechnological applications of PTE for detection and decontamination of insecticides and chemical warfare agents are developing into useful tools. In this review, the catalytic properties and potential applications of this remarkable enzyme are discussed.« less

Synthesis of (+)-Antroquinonol: An Antihyperglycemic Agent.

PubMed

Sulake, Rohidas S; Lin, Hsiao-Han; Hsu, Chia-Yu; Weng, Ching-Feng; Chen, Chinpiao

2015-06-19

The total synthesis of antroquinonol has been accomplished through Suzuki-Miyaura cross-coupling and Barton-McCombie reaction, and the α,β-unsaturation was achieved through selenylation and oxidation protocols. In vitro and in vivo studies on the glucose-lowering properties of antroquinonol indicate that it is a potential antidiabetic agent.

Agent-based services for B2B electronic commerce

NASA Astrophysics Data System (ADS)

Fong, Elizabeth; Ivezic, Nenad; Rhodes, Tom; Peng, Yun

2000-12-01

The potential of agent-based systems has not been realized yet, in part, because of the lack of understanding of how the agent technology supports industrial needs and emerging standards. The area of business-to-business electronic commerce (b2b e-commerce) is one of the most rapidly developing sectors of industry with huge impact on manufacturing practices. In this paper, we investigate the current state of agent technology and the feasibility of applying agent-based computing to b2b e-commerce in the circuit board manufacturing sector. We identify critical tasks and opportunities in the b2b e-commerce area where agent-based services can best be deployed. We describe an implemented agent-based prototype system to facilitate the bidding process for printed circuit board manufacturing and assembly. These activities are taking place within the Internet Commerce for Manufacturing (ICM) project, the NIST- sponsored project working with industry to create an environment where small manufacturers of mechanical and electronic components may participate competitively in virtual enterprises that manufacture printed circuit assemblies.

Military chemical warfare agent human subjects testing: part 1--history of six-decades of military experiments with chemical warfare agents.

PubMed

Brown, Mark

2009-10-01

Military chemical warfare agent testing from World War I to 1975 produced thousands of veterans with concerns of possible long-term health consequences. Clinical and research evaluation of potential long-term health effects has been difficult because the exposures occurred decades ago, the identity of troops exposed and exposure magnitudes are uncertain, and acute effects during experiments poorly documented. In contrast, a companion article describes the large amount of information available about the specific agents tested and their long-term health effects. This short history describes U.S. military chemical-agent experiments with human subjects and identifies tested agents. Finally, the demonstrated need to anticipate future health concerns from military personnel involved in such military testing suggests current and future military researchers should be required, by law and regulation, to fully record the identity of those exposed, relevant exposure magnitude, and complete medical information for all subjects. New study protocols and institutional review board approvals for research involving military personnel should reflect this need.

Synthesis of 5-thiodidehydropyranylcytosine derivatives as potential anti-HIV agents.

PubMed

Yoshimura, Yuichi; Yamazaki, Yoshiko; Saito, Yukako; Natori, Yoshihiro; Imamichi, Tomozumi; Takahata, Hiroki

2011-06-01

As a part of our ongoing efforts to identify new anti-HIV agents, a 5'-thiopyrano-nucleoside derivative 4, designed based on 4'-thioD4C 1 and cyclohexenylnucleoside 3, was synthesized. The dihydrothiopyran skeleton of 4 was constructed by the ring closing metathesis of 21 which was synthesized from but-2-yne-1,4-diol. After converting the protecting group from MOM to TBS followed by oxidation, a Pummerer-type thioglycosylation reaction of 24 with persilylated uracil gave the desired 5-thiodihydrothiopyranyluracils 25 and 26 as a mixture of anomers. The conversion of 25 to a cytosine derivative and subsequent deprotection gave a 5-thiodidehydropyranosylcytosine derivative 4 in good yield. The anti-HIV activity of 4 was also evaluated. Copyright © 2011 Elsevier Ltd. All rights reserved.

Demeter, persephone, and the search for emergence in agent-based models.

DOE Office of Scientific and Technical Information (OSTI.GOV)

North, M. J.; Howe, T. R.; Collier, N. T.

2006-01-01

In Greek mythology, the earth goddess Demeter was unable to find her daughter Persephone after Persephone was abducted by Hades, the god of the underworld. Demeter is said to have embarked on a long and frustrating, but ultimately successful, search to find her daughter. Unfortunately, long and frustrating searches are not confined to Greek mythology. In modern times, agent-based modelers often face similar troubles when searching for agents that are to be to be connected to one another and when seeking appropriate target agents while defining agent behaviors. The result is a 'search for emergence' in that many emergent ormore » potentially emergent behaviors in agent-based models of complex adaptive systems either implicitly or explicitly require search functions. This paper considers a new nested querying approach to simplifying such agent-based modeling and multi-agent simulation search problems.« less

Potential Use of Essential Oil Isolated from Cleistocalyx operculatus Leaves as a Topical Dermatological Agent for Treatment of Burn Wound

PubMed Central

Le, Nghia-Thu Tram; Dam, Sao-Mai

2018-01-01

Several herbal remedies have been used as topical agents to cure burn wound, one of the most common injuries in worldwide. In this study, we investigated the potential use of Cleistocalyx operculatus essential oil to treat the burn wound. We identified a total of 13 bioactive compounds of essential oil, several of which exhibited the anti-inflammatory and antimicrobial activities. Furthermore, the essential oil showed the antibacterial effect against S. aureus but not with P. aeruginosa. The supportive effect of essential oil on burn wound healing process also has been proven. Among three groups of mice, wound contraction rate of essential oil treated group (100%) was significantly higher than tamanu oil treated (79%) and control mice (71%) after 20 days (0.22 ± 0.03 versus 0.31 ± 0.02 cm2, resp., p < 0.05). Histological studies revealed that burn wounds treated with essential oil formed a complete epidermal structure, thick and neatly arranged fibers, and scattered immune cells in burn wound. On the contrary, saline treated burn wound formed uneven epidermal layer with necrotic ulcer, infiltration of immune cells, and existence of granulation tissue. This finding demonstrated Cleistocalyx operculatus essential oil as promising topical dermatological agent to treat burn wound. PMID:29692805

Potential Use of Essential Oil Isolated from Cleistocalyx operculatus Leaves as a Topical Dermatological Agent for Treatment of Burn Wound.

PubMed

Tran, Gia-Buu; Le, Nghia-Thu Tram; Dam, Sao-Mai

2018-01-01

Several herbal remedies have been used as topical agents to cure burn wound, one of the most common injuries in worldwide. In this study, we investigated the potential use of Cleistocalyx operculatus essential oil to treat the burn wound. We identified a total of 13 bioactive compounds of essential oil, several of which exhibited the anti-inflammatory and antimicrobial activities. Furthermore, the essential oil showed the antibacterial effect against S. aureus but not with P. aeruginosa. The supportive effect of essential oil on burn wound healing process also has been proven. Among three groups of mice, wound contraction rate of essential oil treated group (100%) was significantly higher than tamanu oil treated (79%) and control mice (71%) after 20 days (0.22 ± 0.03 versus 0.31 ± 0.02 cm 2 , resp., p < 0.05). Histological studies revealed that burn wounds treated with essential oil formed a complete epidermal structure, thick and neatly arranged fibers, and scattered immune cells in burn wound. On the contrary, saline treated burn wound formed uneven epidermal layer with necrotic ulcer, infiltration of immune cells, and existence of granulation tissue. This finding demonstrated Cleistocalyx operculatus essential oil as promising topical dermatological agent to treat burn wound.

Agricultural Bioterrorism What Challenges and Actions Remain

DTIC Science & Technology

2006-03-10

African milk bush.29 In 1966, Bacillus subtilis was released in the New York City subway system to test the vulnerability of biowarfare.30 In 1984...These diseases include: Foot and Mouth Disease (FMD), Rift Valley Fever ( RVF ), Nipah Virus, Avian Influenza, Exotic Newcastle Disease, Classical Swine

Designing Agent Utilities for Coordinated, Scalable and Robust Multi-Agent Systems

NASA Technical Reports Server (NTRS)

Tumer, Kagan

2005-01-01

Coordinating the behavior of a large number of agents to achieve a system level goal poses unique design challenges. In particular, problems of scaling (number of agents in the thousands to tens of thousands), observability (agents have limited sensing capabilities), and robustness (the agents are unreliable) make it impossible to simply apply methods developed for small multi-agent systems composed of reliable agents. To address these problems, we present an approach based on deriving agent goals that are aligned with the overall system goal, and can be computed using information readily available to the agents. Then, each agent uses a simple reinforcement learning algorithm to pursue its own goals. Because of the way in which those goals are derived, there is no need to use difficult to scale external mechanisms to force collaboration or coordination among the agents, or to ensure that agents actively attempt to appropriate the tasks of agents that suffered failures. To present these results in a concrete setting, we focus on the problem of finding the sub-set of a set of imperfect devices that results in the best aggregate device. This is a large distributed agent coordination problem where each agent (e.g., device) needs to determine whether to be part of the aggregate device. Our results show that the approach proposed in this work provides improvements of over an order of magnitude over both traditional search methods and traditional multi-agent methods. Furthermore, the results show that even in extreme cases of agent failures (i.e., half the agents failed midway through the simulation) the system's performance degrades gracefully and still outperforms a failure-free and centralized search algorithm. The results also show that the gains increase as the size of the system (e.g., number of agents) increases. This latter result is particularly encouraging and suggests that this method is ideally suited for domains where the number of agents is currently in the

Toxicogenomic identification of biomarkers of acute respiratory exposure sensitizing agents

EPA Science Inventory

Allergy induction requires multiple exposures to an agent. Therefore the development of high-throughput or in vitro assays for effective screening of potential sensitizers will require the identification of biomarkers. The goal of this preliminary study was to identify potential ...

"A Child Is Also a Teacher": Exploring the Potential for Children as Change Agents in the Context of a School-Based WASH Intervention in Rural Eastern Zambia

ERIC Educational Resources Information Center

Bresee, S.; Caruso, B. A.; Sales, J.; Lupele, J.; Freeman, M. C.

2016-01-01

As part of water, sanitation and hygiene interventions in low-income settings, it is frequently assumed that pupils can disseminate information and catalyze change at home, yet this assumption has not been rigorously assessed. We employed qualitative research methods in two phases to assess the potential for children to be change agents in five…

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Wen-wen; Yu, Jia-ying; Xu, Huai-long

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.more » 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.« less

Silicon-zinc-glycerol hydrogel, a potential immunotropic agent for topical application.

PubMed

Khonina, Tat'yana G; Ivanenko, Maria V; Chupakhin, Oleg N; Safronov, Alexander P; Bogdanova, Ekaterina A; Karabanalov, Maxim S; Permikin, Vasily V; Larionov, Leonid P; Drozdova, Lyudmila I

2017-09-30

Nanoparticles synthesized using sol-gel method are promising agents for biomedical applications, in particular for the therapy and diagnosis of various diseases. Using silicon and zinc glycerolates as biocompatible precursors we synthesized by the sol-gel method a new bioactive silicon-zinc-containing glycerohydrogel combining the positive pharmacological properties of the precursors. In the present work the structural features of silicon-zinc-containing glycerohydrogel and its immunotropic properties were studied. The advanced physical methods, including XRD, TEM, dynamic and electrophoretic light scattering, were used for studying the structural features of the gel. Hydrolysis of zinc monoglycerolate was investigated under gelation conditions. Evaluation of the efficiency of silicon-zinc-containing glycerohydrogel in providing immune functions was carried out using a model of the complicated wound process behind immunosuppression induced by hydrocortisone administration in the Wistar rats. It has been shown that zinc monoglycerolate exists in the state of amorphous nanoparticles in the cells of 3D-network formed due to incomplete hydrolysis of silicon glycerolates and subsequent silanol condensation. Zinc monoglycerolate is not hydrolyzed and does not enter 3D-network of the gel with the formation of Zn-O-Si groups, but it forms a separate phase. Immunotropic action of silicon-zinc-containing glycerohydrogel was revealed by the histology and immunohistochemistry methods. Amorphous nanoparticles of zinc monoglycerolate, water-soluble silicon glycerolates, and products of their hydrolytic transformations, which are present in a aqueous-glycerol medium, are in the first place responsible for the pharmacological activity of hydrogel. The results obtained allow us to consider silicon-zinc-containing glycerohydrogel as a promising immunotropic agent for topical application. Copyright © 2017 Elsevier B.V. All rights reserved.

Design, synthesis and biological evaluation of 5-fluorouracil-derived benzimidazoles as novel type of potential antimicrobial agents.

PubMed

Fang, Xue-Jie; Jeyakkumar, Ponmani; Avula, Srinivasa Rao; Zhou, Qian; Zhou, Cheng-He

2016-06-01

A series of 5-fluorouracil benzimidazoles as novel type of potential antimicrobial agents were designed and synthesized for the first time. Bioactive assay manifested that some of the prepared compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains in comparison with reference drugs norfloxacin, chloromycin and fluconazole. Noticeably, 3-fluorobenzyl benzimidazole derivative 5c gave remarkable antimicrobial activities against Saccharomyces cerevisiae, MRSA and Bacillus proteus with MIC values of 1, 2 and 4μg/mL, respectively. Experimental research revealed that compound 5c could effectively intercalate into calf thymus DNA to form compound 5c-DNA complex which might block DNA replication and thus exert antimicrobial activities. Molecular docking indicated that compound 5c should bind with DNA topoisomerase IA through three hydrogen bonds by the use of fluorine atom and oxygen atoms in 5-fluorouracil with the residue Lys 423. Copyright © 2016 Elsevier Ltd. All rights reserved.

An investigation into the potential of phenothiazinium-based photo-sensitisers to act as PDT agents.

PubMed

Harris, F; Sayed, Z; Hussain, S; Phoenix, D A

2004-11-01

There is an urgent need for effective cancer treatments and increasingly, photo-dynamic therapy (PDT) is being used to fulfil this need as it offers a number of advantages over traditional cancer treatments. Here, the potential of a series of phenothiazinium-based photo-sensitisers (PhBPs) as PDT agents is tested. PhBPs were incubated with EMT-6 tumour cells and erythrocytes respectively under dark and light conditions (3.15Jcm(-2) over 30min). "Comet assay" and haemolytic assay were then used to assess cellular photo-damage induced by these PhBPs. Additionally, in vitro assays were used to determine light adsorption characteristics, singlet oxygen yields (ΦΔPhBP) and lipophilicity (logP) of these PhBPs. "Comet assay" showed EMT-6 incubation with PhBPs under light conditions to produce DNA "tails", which were circa 35μm long, indicating the presence of DNA photo-damage. Corresponding incubations under dark conditions led to no such damage. The majority of the PhBPs tested possessed significant singlet oxygen yields (ΦΔPhBP>0.7), suggesting the general use of type II mechanisms for photo-sensitization, and were generally lipophilic (logP>0). Incubation of erythrocytes with these PhBPs in the dark produced between 6% and 19% haemolysis. These levels were generally unaffected by illumination except in the case of DMMB, which showed haemolytic levels increasing from 11% to 61%. It is suggested that DNA may be the primary target for the photo-dynamic anti-tumour activity of the PhBPs tested with the exception of DMMB, which may potentially also target tumour cell membranes.

22 CFR 51.22 - Passport agents and passport acceptance agents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the...

22 CFR 51.22 - Passport agents and passport acceptance agents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the...

22 CFR 51.22 - Passport agents and passport acceptance agents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the...

22 CFR 51.22 - Passport agents and passport acceptance agents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the...

22 CFR 51.22 - Passport agents and passport acceptance agents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the...

Corneal toxicity induced by vesicating agents and effective treatment options

PubMed Central

Goswami, Dinesh G.; Tewari-Singh, Neera; Agarwal, Rajesh

2016-01-01

The vesicating agents sulfur mustard (SM) and lewisite (LEW) are potent chemical warfare agents that primarily cause damage to the ocular, skin, and respiratory systems. However, ocular tissue is the most sensitive organ, and vesicant exposure results in a biphasic injury response, including photophobia, corneal lesions, corneal edema, ulceration, and neovascularization, and may cause loss of vision. There are several reports on ocular injury from exposure to SM, which has been frequently used in warfare. However, there are very few reports on ocular injury by LEW, which indicate that injury symptoms appear instantly after exposure and faster than SM. In spite of extensive research efforts, effective therapies for vesicant-induced ocular injuries, mainly to the most affected corneal tissue, are not available. Hence, we have established primary human corneal epithelial (HCE) cells and rabbit corneal organ culture models with the SM analog nitrogen mustard (NM), which have helped to test the efficacy of potential therapeutic agents. These agents will then be further evaluated against in vivo SM- and LEW-induced corneal injury models, which will assist in the development of potential broad-spectrum therapies against vesicant-induced ocular injuries. PMID:27327041

Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents.

PubMed

Ma, Brigette B Y; Bristow, Robert G; Kim, John; Siu, Lillian L

2003-07-15

Molecular targeted agents have been combined with radiotherapy (RT) in recent clinical trials in an effort to optimize the therapeutic index of RT. The appeal of this strategy lies in their potential target specificity and clinically acceptable toxicity. This article integrates the salient, published research findings into the underlying molecular mechanisms, preclinical efficacy, and clinical applicability of combining RT with molecular targeted agents. These agents include inhibitors of intracellular signal transduction molecules, modulators of apoptosis, inhibitors of cell cycle checkpoints control, antiangiogenic agents, and cyclo-oxygenase-2 inhibitors. Molecular targeted agents can have direct effects on the cytoprotective and cytotoxic pathways implicated in the cellular response to ionizing radiation (IR). These pathways involve cellular proliferation, DNA repair, cell cycle progression, nuclear transcription, tumor angiogenesis, and prostanoid-associated inflammation. These pathways can also converge to alter RT-induced apoptosis, terminal growth arrest, and reproductive cell death. Pharmacologic modulation of these pathways may potentially enhance tumor response to RT though inhibition of tumor repopulation, improvement of tumor oxygenation, redistribution during the cell cycle, and alteration of intrinsic tumor radiosensitivity. Combining RT and molecular targeted agents is a rational approach in the treatment of solid tumors. Translation of this approach from promising preclinical data to clinical trials is actively underway.

Candida lipolytica UCP0988 Biosurfactant: Potential as a Bioremediation Agent and in Formulating a Commercial Related Product

PubMed Central

Santos, Danyelle K. F.; Resende, Ana H. M.; de Almeida, Darne G.; Soares da Silva, Rita de Cássia F.; Rufino, Raquel D.; Luna, Juliana M.; Banat, Ibrahim M.; Sarubbo, Leonie A.

2017-01-01

The aim of the present study was to investigate the potential application of the biosurfactant from Candida lipolytica grown in low-cost substrates, which has previously been produced and characterized under optimized conditions as an adjunct material to enhance the remediation processes of hydrophobic pollutants and heavy metals generated by the oil industry and propose the formulation of a safe and stable remediation agent. In tests carried out with seawater, the crude biosurfactant demonstrated 80% oil spreading efficiency. The dispersion rate was 50% for the biosurfactant at a concentration twice that of the CMC. The biosurfactant removed 70% of motor oil from contaminated cotton cloth in detergency tests. The crude biosurfactant also removed 30–40% of Cu and Pb from standard sand, while the isolated biosurfactant removed ~30% of the heavy metals. The conductivity of solutions containing Cd and Pb was sharply reduced after biosurfactants' addition. A product was prepared through adding 0.2% potassium sorbate as preservative and tested over 120 days. The formulated biosurfactant was analyzed for emulsification and surface tension under different pH values, temperatures, and salt concentrations and tested for toxicity against the fish Poecilia vivipara. The results showed that the formulation had no toxicity and did not cause significant changes in the tensoactive capacity of the biomolecule while maintaining activity demonstrating suitability for potential future commercial product formulation. PMID:28507538

Radiation countermeasure agents: an update (2011 – 2014)

PubMed Central

Newman, Victoria L; Romaine, Patricia LP; Wise, Stephen Y; Seed, Thomas M

2014-01-01

Introduction Despite significant scientific advances over the past 60 years towards the development of a safe, nontoxic and effective radiation countermeasure for the acute radiation syndrome (ARS), no drug has been approved by the US FDA. A radiation countermeasure to protect the population at large from the effects of lethal radiation exposure remains a significant unmet medical need of the US citizenry and, thus, has been recognized as a high priority area by the government. Area covered This article reviews relevant publications and patents for recent developments and progress for potential ARS treatments in the area of radiation countermeasures. Emphasis is placed on the advanced development of existing agents since 2011 and new agents identified as radiation countermeasure for ARS during this period. Expert opinion A number of promising radiation countermeasures are currently under development, seven of which have received US FDA investigational new drug status for clinical investigation. Four of these agents, CBLB502, Ex-RAD, HemaMax and OrbeShield, are progressing with large animal studies and clinical trials. G-CSF has high potential and well-documented therapeutic effects in countering myelosuppression and may receive full licensing approval by the US FDA in the future. PMID:25315070

Benefits of a European project on diagnostics of highly pathogenic agents and assessment of potential "dual use" issues.

PubMed

Grunow, Roland; Ippolito, G; Jacob, D; Sauer, U; Rohleder, A; Di Caro, A; Iacovino, R

2014-01-01

Quality assurance exercises and networking on the detection of highly infectious pathogens (QUANDHIP) is a joint action initiative set up in 2011 that has successfully unified the primary objectives of the European Network on Highly Pathogenic Bacteria (ENHPB) and of P4-laboratories (ENP4-Lab) both of which aimed to improve the efficiency, effectiveness, and response capabilities of laboratories directed at protecting the health of European citizens against high consequence bacteria and viruses of significant public health concern. Both networks have established a common collaborative consortium of 37 nationally and internationally recognized institutions with laboratory facilities from 22 European countries. The specific objectives and achievements include the initiation and establishment of a recognized and acceptable quality assurance scheme, including practical external quality assurance exercises, comprising living agents, that aims to improve laboratory performance, accuracy, and detection capabilities in support of patient management and public health responses; recognized training schemes for diagnostics and handling of highly pathogenic agents; international repositories comprising highly pathogenic bacteria and viruses for the development of standardized reference material; a standardized and transparent Biosafety and Biosecurity strategy protecting healthcare personnel and the community in dealing with high consequence pathogens; the design and organization of response capabilities dealing with cross-border events with highly infectious pathogens including the consideration of diagnostic capabilities of individual European laboratories. The project tackled several sensitive issues regarding Biosafety, Biosecurity and "dual use" concerns. The article will give an overview of the project outcomes and discuss the assessment of potential "dual use" issues.

Visual Stereotypes and Virtual Pedagogical Agents

ERIC Educational Resources Information Center

Haake, Magnus; Gulz, Agneta

2008-01-01

The paper deals with the use of visual stereotypes in virtual pedagogical agents and its potential impact in digital learning environments. An analysis of the concept of visual stereotypes is followed by a discussion of affordances and drawbacks as to their use in the context of traditional media. Next, the paper explores whether virtual…

Quinol derivatives as potential trypanocidal agents

PubMed Central

Capes, Amy; Patterson, Stephen; Wyllie, Susan; Hallyburton, Irene; Collie, Iain T.; McCarroll, Andrew J.; Stevens, Malcolm F.G.; Frearson, Julie A.; Wyatt, Paul G.; Fairlamb, Alan H.; Gilbert, Ian H.

2012-01-01

Quinols have been developed as a class of potential anti-cancer compounds. They are thought to act as double Michael acceptors, forming two covalent bonds to their target protein(s). Quinols have also been shown to have activity against the parasite Trypanosoma brucei, the causative organism of human African trypanosomiasis, but they demonstrated little selectivity over mammalian MRC5 cells in a counter-screen. In this paper, we report screening of further examples of quinols against T. brucei. We were able to derive an SAR, but the compounds demonstrated little selectivity over MRC5 cells. In an approach to increase selectivity, we attached melamine and benzamidine motifs to the quinols, because these moieties are known to be selectively concentrated in the parasite by transporter proteins. In general these transporter motif-containing analogues showed increased selectivity; however they also showed reduced levels of potency against T. brucei. PMID:22264753

Newer cytotoxic agents: attacking cancer broadly.

PubMed

Teicher, Beverly A

2008-03-15

The plasticity and instability of the cancer genome is impressive and is characterized by gene amplifications and deletions, rearrangements, and many silent and active mutations. Although targeted therapeutics have had effect in some diseases, there remains a large role for new cytotoxic agents that have the potential to be broadly active across multiple cancers. Platinum-based regimens are the basis for treatment of several common tumors. Satraplatin and picoplatin are newer platinum complexes that form bulkier lesions in DNA than their forerunners. Microtubules are a key target for anticancer agents. Vinca alkaloid and similar compounds fragment these critical structures, whereas taxanes stabilize them. Vinflunine is a new fluorinated Vinca alkaloid derivative with vascular disrupting effects, as well as antitumor effects. Epothilones are a new class of microtubule stabilizers. Mitosis has been targeted directly and indirectly by many anticancer agents. The aurora kinases are new targets in this class. Inhibitors of aurora kinases are likely to be cytotoxic. Finally, protein regulation is essential for cellular integrity. With the approval of bortezomib (Velcade, PS-341), the proteosome, a master protein regulator, has been validated as an anticancer target. The five articles in this issue of CCR Focus present the current status of these next generation cytotoxic agents.

Towards non- and minimally instrumented, microfluidics-based diagnostic devices†

PubMed Central

Weigl, Bernhard; Domingo, Gonzalo; LaBarre, Paul; Gerlach, Jay

2009-01-01

In many health care settings, it is uneconomical, impractical, or unaffordable to maintain and access a fully equipped diagnostics laboratory. Examples include home health care, developing-country health care, and emergency situations in which first responders are dealing with pandemics or biowarfare agent release. In those settings, fully disposable diagnostic devices that require no instrument support, reagent, or significant training are well suited. Although the only such technology to have found widespread adoption so far is the immunochromatographic rapid assay strip test, microfluidics holds promise to expand the range of assay technologies that can be performed in formats similar to that of a strip test. In this paper, we review progress toward development of disposable, low-cost, easy-to-use microfluidics-based diagnostics that require no instrument at all. We also present examples of microfluidic functional elements—including mixers, separators, and detectors—as well as complete microfluidic devices that function entirely without any moving parts and external power sources. PMID:19023463

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehboob, Shahila; Hevener, Kirk E.; Truong, Kent

Because of structural and mechanistic differences between eukaryotic and prokaryotic fatty acid synthesis enzymes, the bacterial pathway, FAS-II, is an attractive target for the design of antimicrobial agents. We have previously reported the identification of a novel series of benzimidazole compounds with particularly good antibacterial effect against Francisella tularensis, a Category A biowarfare pathogen. Herein we report the crystal structure of the F. tularensis FabI enzyme in complex with our most active benzimidazole compound bound with NADH. The structure reveals that the benzimidazole compounds bind to the substrate site in a unique conformation that is distinct from the binding motifmore » of other known FabI inhibitors. Detailed inhibition kinetics have confirmed that the compounds possess a novel inhibitory mechanism that is unique among known FabI inhibitors. These studies could have a strong impact on future antimicrobial design efforts and may reveal new avenues for the design of FAS-II active antibacterial compounds.« less

Potential New Pharmacological Agents Derived From Medicinal Plants for the Treatment of Pancreatic Cancer.

PubMed

Azimi, Haniye; Khakshur, Ali Asghar; Abdollahi, Mohammad; Rahimi, Roja

2015-01-01

In the present article, we reviewed plants and phytochemical compounds demonstrating beneficial effects in pancreatic cancer to find new sources of pharmaceutical agents. For this purpose, Scopus, PubMed, Web of Science, and Google scholar were searched for plants or herbal components with beneficial effects in the treatment of pancreatic cancer. Data were collected up to January 2013. The search terms were "plant," "herb," "herbal therapy," or "phytotherapy" and "pancreatic cancer" or "pancreas." All of the human in vivo and in vitro studies were included. According to studies, among diverse plants and phytochemicals, 12 compounds including apigenin, genistein, quercetin, resveratrol, epigallocatechin gallate, benzyl isothiocyanate, sulforaphane, curcumin, thymoquinone, dihydroartemisinin, cucurbitacin B, and perillyl alcohol have beneficial action against pancreatic cancer cells through 4 or more mechanisms. Applying their plausible synergistic effects can be an imperative approach for finding new efficient pharmacological agents in the treatment of pancreatic cancer.

Pyrazole and imidazo[1,2-b]pyrazole derivatives as new potential anti-tuberculosis agents.

PubMed

Meta, Elda; Brullo, Chiara; Tonelli, Michele; Franzblau, Scott G; Wang, Yuehong; Ma, Rui; Baojie, Wan; Orena, Beatrice Silvia; Pasca, Maria Rosalia; Bruno, Olga

2018-05-23

We screened a large library of differently decorated imidazo-pyrazole and pyrazole derivatives as possible new antitubercular agents and this preliminary screening showed that many compounds are able to totally inhibit Mycobacterium growth (>90 %). Among the most active compounds, we selected some new possible hits based on their similarities and, at the same time, their novelty respect to the pipeline drugs. In order to increase the potency and obtain more information about structure activity relationship (SAR), we design and synthesized three new series of compounds (2a-e, 3a-e, and 4a-l). Performed tests confirmed that both new pyrazoles and imidazo-pyrazoles could represent a new starting point to obtain more potent compounds and further work is now underway to identify the protein targets of this new class of anti-TB agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents

NASA Astrophysics Data System (ADS)

Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Hervault, Aziliz; Mertz, Damien; Begin-Colin, Sylvie; Thanh, Nguy&Ecirtil; N. Thi&Cmb. B. Dot; Kim

2016-02-01

Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high saturation magnetization value (84.5 emu g-1). The surface of the IONPs could be tailored post synthesis with two different ligands which provided functionality and stability in water and phosphate buffer saline (PBS). Their potential as a magnetic resonance imaging (MRI) contrast agent was confirmed as they exhibited high r1 and r2 relaxivities of 7.95 mM-1 s-1 and 185.58 mM-1 s-1 respectively at 1.4 T. Biocompatibility and viability of IONPs in primary human mesenchymal stem cells (hMSCs) was studied and confirmed.Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high

"Lactoferrin and Peptide-derivatives: Antimicrobial Agents with Potential Use in Nonspecific Immunity Modulation".

PubMed

Drago-Serrano, Maria Elisa; Campos-Rodriguez, Rafael; Carrero, Julio Cesar; de la Garza, Mireya

2018-03-27

Lactoferrin (Lf) is a conserved cationic non-heme glycoprotein that is part of the innate immune defense system of mammals. Lf is present in colostrum, milk and mucosal sites, and it is also produced by polymorphonuclear neutrophils and secreted at infection sites. Lf and Lf N-terminus peptide-derivatives named lactoferricins (Lfcins) are molecules with microbiostatic and microbicidal action in a wide array of pathogens. In addition, they display regulatory properties on components of nonspecific immunity, including toll-like receptors, pro- and anti-inflammatory cytokines, and reactive oxygen species. Mechanisms explaining the ability of Lf and Lfcins to display both up- and down-modulatory properties on cells are not fully understood but result, in part, from their interactions with membrane receptors that elicit biochemical signal pathways, whereas other receptors enable the nuclear translocation of these molecules for the modulation of target genes. The dual role of Lf and Lfcins as antimicrobials and immunomodulators is of biotechnological and pharmaceutical interest. Native Lf and its peptide-derivatives from human and bovine sources, the recombinant versions of the human protein, and their synthetic peptides have potential application as adjunctive agents in therapies to combat infections caused by multi-resistant bacteria and those caused by fungi, protozoa and viruses, as well as in the prevention and reduction of several types of cancer and response to LPS-shock, among other effects. In this review, we summarize the immunomodulatory properties of the unique multifunctional protein Lf and its N-terminus peptides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mitochondrial Agents for Bipolar Disorder.

PubMed

Pereira, Círia; Chavarria, Victor; Vian, João; Ashton, Melanie Maree; Berk, Michael; Marx, Wolfgang; Dean, Olivia May

2018-03-27

Bipolar disorder is a chronic and often debilitating illness. Current treatment options (both pharmaco- and psychotherapy) have shown efficacy, but for many leave a shortfall in recovery. Advances in the understanding of the pathophysiology of bipolar disorder suggest that interventions that target mitochondrial dysfunction may provide a therapeutic benefit. This review explores the current and growing theoretical rationale as well as existing preclinical and clinical data for those therapies aiming to target the mitochondrion in bipolar disorder. A Clinicaltrials.gov and ANZCTR search was conducted for complete and ongoing trials on mitochondrial agents used in psychiatric disorders. A PubMed search was also conducted for literature published between January 1981 and July 2017. Systematic reviews, randomized controlled trials, observational studies, case series, and animal studies with an emphasis on agents affecting mitochondrial function and its role in bipolar disorder were included. The search was augmented by manually searching the references of key papers and related literature. The results were presented as a narrative review. Mitochondrial agents offer new horizons in mood disorder treatment. While some negative effects have been reported, most compounds are overall well tolerated and have generally benign side-effect profiles. The study of neuroinflammation, neurodegeneration, and mitochondrial function has contributed the understanding of bipolar disorder's pathophysiology. Agents targeting these pathways could be a potential therapeutic strategy. Future directions include identification of novel candidate mitochondrial modulators as well as rigorous and well-powered clinical trials.

Computational Investigations of Potential Energy Function Development for Metal--Organic Framework Simulations, Metal Carbenes, and Chemical Warfare Agents

NASA Astrophysics Data System (ADS)

Cioce, Christian R.

Metal-Organic Frameworks (MOFs) are three-dimensional porous nanomaterials with a variety of applications, including catalysis, gas storage and separation, and sustainable energy. Their potential as air filtration systems is of interest for designer carbon capture materials. The chemical constituents (i.e. organic ligands) can be functionalized to create rationally designed CO2 sequestration platforms, for example. Hardware and software alike at the bleeding edge of supercomputing are utilized for designing first principles-based molecular models for the simulation of gas sorption in these frameworks. The classical potentials developed herein are named PHAST --- Potentials with High Accuracy, Speed, and Transferability, and thus are designed via a "bottom-up" approach. Specifically, models for N2 and CH4 are constructed and presented. Extensive verification and validation leads to insights and range of applicability. Through this experience, the PHAST models are improved upon further to be more applicable in heterogeneous environments. Given this, the models are applied to reproducing high level ab initio energies for gas sorption trajectories of helium atoms in a variety of rare-gas clusters, the geometries of which being representative of sorption-like environments commonly encountered in a porous nanomaterial. This work seeks to push forward the state of classical and first principles materials modeling. Additionally, the characterization of a new type of tunable radical metal---carbene is presented. Here, a cobalt(II)---porphyrin complex, [Co(Por)], was investigated to understand its role as an effective catalyst in stereoselective cyclopropanation of a diazoacetate reagent. Density functional theory along with natural bond order analysis and charge decomposition analysis gave insight into the electronics of the catalytic intermediate. The bonding pattern unveiled a new class of radical metal---carbene complex, with a doublet cobalt into which a triplet carbene

Agent-based Modeling with MATSim for Hazards Evacuation Planning

NASA Astrophysics Data System (ADS)

Jones, J. M.; Ng, P.; Henry, K.; Peters, J.; Wood, N. J.

2015-12-01

Hazard evacuation planning requires robust modeling tools and techniques, such as least cost distance or agent-based modeling, to gain an understanding of a community's potential to reach safety before event (e.g. tsunami) arrival. Least cost distance modeling provides a static view of the evacuation landscape with an estimate of travel times to safety from each location in the hazard space. With this information, practitioners can assess a community's overall ability for timely evacuation. More information may be needed if evacuee congestion creates bottlenecks in the flow patterns. Dynamic movement patterns are best explored with agent-based models that simulate movement of and interaction between individual agents as evacuees through the hazard space, reacting to potential congestion areas along the evacuation route. The multi-agent transport simulation model MATSim is an agent-based modeling framework that can be applied to hazard evacuation planning. Developed jointly by universities in Switzerland and Germany, MATSim is open-source software written in Java and freely available for modification or enhancement. We successfully used MATSim to illustrate tsunami evacuation challenges in two island communities in California, USA, that are impacted by limited escape routes. However, working with MATSim's data preparation, simulation, and visualization modules in an integrated development environment requires a significant investment of time to develop the software expertise to link the modules and run a simulation. To facilitate our evacuation research, we packaged the MATSim modules into a single application tailored to the needs of the hazards community. By exposing the modeling parameters of interest to researchers in an intuitive user interface and hiding the software complexities, we bring agent-based modeling closer to practitioners and provide access to the powerful visual and analytic information that this modeling can provide.

Further development of high temperature-resistant graphite fiber coupling agents

NASA Technical Reports Server (NTRS)

Griffin, R. N.

1976-01-01

Potential coupling agents for graphite fibers were screened by their effect on the weight losses of Thornel 300, HMS, and HTS fibers at 588K for 200 and 400 hours. Unidirectional laminates were made from HMS and HTS fibers, untreated, and treated with each of the seven coupling agents. The matrix of all laminates was PMR polyimide (PMR-PR). On the basis of the best overall retention of elevated temperature interlaminar shear strength after 200 hours at 588K, composite weight after 200 hours at 588K, and fiber weight after 400 hours at 588K, ventromer T-1 applied from aqueous solution and pyrolyzed PPQ were selected for further evaluation as coupling agents for HTS fiber while ventromer T-2 and pyrolyzed PPQ were selected as coupling agents for HMS fiber. It was shown that pyrolyzed PPQ as a coupling agent improves the oxidative stability of HTS/PMR-PI composites.

Halloysite clay nanotubes for controlled release of protective agents.

PubMed

Abdullayev, Elshad; Lvov, Yuri

2011-11-01

Halloysite is a naturally occurring clay mineral with submicron sized hollow cylindrical morphology. Halloysite morphology, structure and properties were characterized by using SEM, TEM, XRD, FT-IR spectroscopy, surface electrokinetic (zeta) potential and nitrogen adsorption isotherms. Comparison of the halloysite structure with imogolite was also provided. Halloysite toxicological studies revealed that it is environmentally friendly and biocompatible material. Due to its unique tubular shape and availability in thousands of tons halloysite has potential to be applied as nanocontainers for encapsulation of chemically and biologically active agents such as medicines, pharmaceuticals, antiseptics, corrosion inhibitors, antifouling agents, and doped with them plastics producing smart polymeric nanocomposites with improved mechanical strength. Finally possibility to synthesize metal nanorods within the halloysite lumen was demonstrated.

Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents

DOE PAGES

Rees, Julian A.; Deblonde, Gauthier J. -P.; An, Dahlia D.; ...

2018-03-13

Several MRI contrast agent clinical formulations are now known to leave deposits of the heavy metal gadolinium in the brain, bones, and other organs of patients. This persistent biological accumulation of gadolinium has been recently recognized as a deleterious outcome in patients administered Gd-based contrast agents (GBCAs) for MRI, prompting the European Medicines Agency to recommend discontinuing the use of over half of the GBCAs currently approved for clinical applications. Here, to address this problem, we find that the orally-available metal decorporation agent 3,4,3-LI(1,2-HOPO) demonstrates superior efficacy at chelating and removing Gd from the body compared to diethylenetriaminepentaacetic acid, amore » ligand commonly used in the United States in the GBCA Gadopentetate (Magnevist). Using the radiotracer 153Gd to obtain precise biodistribution data, the results herein, supported by speciation simulations, suggest that the prophylactic or post-hoc therapeutic use of 3,4,3-LI(1,2-HOPO) may provide a means to mitigate Gd retention in patients requiring contrast-enhanced MRI.« less

Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rees, Julian A.; Deblonde, Gauthier J. -P.; An, Dahlia D.

Several MRI contrast agent clinical formulations are now known to leave deposits of the heavy metal gadolinium in the brain, bones, and other organs of patients. This persistent biological accumulation of gadolinium has been recently recognized as a deleterious outcome in patients administered Gd-based contrast agents (GBCAs) for MRI, prompting the European Medicines Agency to recommend discontinuing the use of over half of the GBCAs currently approved for clinical applications. Here, to address this problem, we find that the orally-available metal decorporation agent 3,4,3-LI(1,2-HOPO) demonstrates superior efficacy at chelating and removing Gd from the body compared to diethylenetriaminepentaacetic acid, amore » ligand commonly used in the United States in the GBCA Gadopentetate (Magnevist). Using the radiotracer 153Gd to obtain precise biodistribution data, the results herein, supported by speciation simulations, suggest that the prophylactic or post-hoc therapeutic use of 3,4,3-LI(1,2-HOPO) may provide a means to mitigate Gd retention in patients requiring contrast-enhanced MRI.« less

Increasing nerve agent treatment efficacy by P-glycoprotein inhibition.

PubMed

Joosen, Marloes J A; Vester, Stefanie M; Hamelink, Jouk; Klaassen, Steven D; van den Berg, Roland M

2016-11-25

One of the shortcomings of current treatment of nerve agent poisoning is that not all drugs effectively penetrate the blood-brain barrier (BBB), whereas most nerve agents easily do. P-glycoprotein (Pgp) efflux transporters at the BBB may contribute to this aspect. It was previously shown that Pgp inhibition by tariquidar enhanced the efficacy of nerve agent treatment when administered as a pretreatment. In the present study soman-induced seizures were also substantially prevented when the animals were intravenously treated with tariquidar post-poisoning, in addition to HI-6 and atropine. In these animals, approximately twice as much AChE activity was present in their brain as compared to control rats. The finding that tariquidar did not affect distribution of soman to the brain indicates that the potentiating effects were a result of interactions of Pgp inhibition with drug distribution. In line with this, atropine appeared to be a substrate for Pgp in in vitro studies in a MDR1/MDCK cell model. This indicates that tariquidar might induce brain region specific effects on atropine distribution, which could contribute to the therapeutic efficacy increase found. Furthermore, the therapeutic enhancement by tariquidar was compared to that of the less specific and less potent Pgp inhibitor cyclosporine A. This compound appeared to induce a protective effect similar to tariquidar. In conclusion, treatment with a Pgp inhibitor resulted in enhanced therapeutic efficacy of HI-6 and atropine in a soman-induced seizure model in the rat. The mechanism underlying these effects should be further investigated. To that end, the potentiating effect of nerve agent treatment should be addressed against a broader range of nerve agents, for oximes and atropine separately, and for those at lower doses. In particular when efficacy against more nerve agents is shown, a Pgp inhibitor such as tariquidar might be a valid addition to nerve agent antidotes. Copyright © 2016 Elsevier Ireland

Skin-derived dendritic cells acquire and degrade the scrapie agent following in vitro exposure

PubMed Central

Mohan, Joanne; Hopkins, John; Mabbott, Neil A

2005-01-01

The accumulation of the scrapie agent in lymphoid tissues following inoculation via the skin is critical for efficient neuroinvasion, but how the agent is initially transported from the skin to the draining lymph node is not known. Langerhans cells (LCs) are specialized antigen-presenting cells that continually sample their microenvironment within the epidermis and transport captured antigens to draining lymph nodes. We considered LCs probable candidates to acquire and transport the scrapie agent after inoculation via the skin. XS106 cells are dendritic cells (DCs) isolated from mouse epidermis with characteristics of mature LC cells. To investigate the potential interaction of LCs with the scrapie agent XS106 cells were exposed to the scrapie agent in vitro. We show that XS106 cells rapidly acquire the scrapie agent following in vitro exposure. In addition, XS106 cells partially degrade the scrapie agent following extended cultivation. These data suggest that LCs might acquire and degrade the scrapie agent after inoculation via the skin, but data from additional experiments demonstrate that this ability could be lost in the presence of lipopolysaccharide or other immunostimulatory molecules. Our studies also imply that LCs would not undergo maturation following uptake of the scrapie agent in the skin, as the expression of surface antigens associated with LC maturation were unaltered following exposure. In conclusion, although LCs or DCs have the potential to acquire the scrapie agent within the epidermis our data suggest it is unlikely that they become activated and stimulated to transport the agent to the draining lymph node. PMID:16108824

TACtic- A Multi Behavioral Agent for Trading Agent Competition

NASA Astrophysics Data System (ADS)

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

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

Examining multi-component DNA-templated nanostructures as imaging agents

NASA Astrophysics Data System (ADS)

Jaganathan, Hamsa

2011-12-01

Magnetic resonance imaging (MRI) is the leading non-invasive tool for disease imaging and diagnosis. Although MRI exhibits high spatial resolution for anatomical features, the contrast resolution is low. Imaging agents serve as an aid to distinguish different types of tissues within images. Gadolinium chelates, which are considered first generation designs, can be toxic to health, while ultra-small, superparamagnetic nanoparticles (NPs) have low tissue-targeting efficiency and rapid bio-distribution, resulting to an inadequate detection of the MRI signal and enhancement of image contrast. In order to improve the utility of MRI agents, the challenge in composition and structure needs to be addressed. One-dimensional (1D), superparamagnetic nanostructures have been reported to enhance magnetic and in vivo properties and therefore has a potential to improve contrast enhancement in MRI images. In this dissertation, the structure of 1D, multi-component NP chains, scaffolded on DNA, were pre-clinically examined as potential MRI agents. First, research was focused on characterizing and understanding the mechanism of proton relaxation for DNA-templated NP chains using nuclear magnetic resonance (NMR) spectrometry. Proton relaxation and transverse relaxivity were higher in multi-component NP chains compared to disperse NPs, indicating the arrangement of NPs on a 1D structure improved proton relaxation sensitivity. Second, in vitro evaluation for potential issues in toxicity and contrast efficiency in tissue environments using a 3 Tesla clinical MRI scanner was performed. Cell uptake of DNA-templated NP chains was enhanced after encapsulating the nanostructure with layers of polyelectrolytes and targeting ligands. Compared to dispersed NPs, DNA-templated NP chains improved MRI contrast in both the epithelial basement membrane and colon cancer tumors scaffolds. The last part of the project was focused on developing a novel MRI agent that detects changes in DNA methylation

Multi-agent integrated password management (MIPM) application secured with encryption

NASA Astrophysics Data System (ADS)

Awang, Norkhushaini; Zukri, Nurul Hidayah Ahmad; Rashid, Nor Aimuni Md; Zulkifli, Zuhri Arafah; Nazri, Nor Afifah Mohd

2017-10-01

Users use weak passwords and reuse them on different websites and applications. Password managers are a solution to store login information for websites and help users log in automatically. This project developed a system that acts as an agent managing passwords. Multi-Agent Integrated Password Management (MIPM) is an application using encryption that provides users with secure storage of their login account information such as their username, emails and passwords. This project was developed on an Android platform with an encryption agent using Java Agent Development Environment (JADE). The purpose of the embedded agents is to act as a third-party software to ease the encryption process, and in the future, the developed encryption agents can form part of the security system. This application can be used by the computer and mobile users. Currently, users log into many applications causing them to use unique passwords to prevent password leaking. The crypto agent handles the encryption process using an Advanced Encryption Standard (AES) 128-bit encryption algorithm. As a whole, MIPM is developed on the Android application to provide a secure platform to store passwords and has high potential to be commercialised for public use.

Nanoparticle Contrast Agents for Computed Tomography: A Focus on Micelles

PubMed Central

Cormode, David P.; Naha, Pratap C.; Fayad, Zahi A.

2014-01-01

Computed tomography (CT) is an X-ray based whole body imaging technique that is widely used in medicine. Clinically approved contrast agents for CT are iodinated small molecules or barium suspensions. Over the past seven years there has been a great increase in the development of nanoparticles as CT contrast agents. Nanoparticles have several advantages over small molecule CT contrast agents, such as long blood-pool residence times, and the potential for cell tracking and targeted imaging applications. Furthermore, there is a need for novel CT contrast agents, due to the growing population of renally impaired patients and patients hypersensitive to iodinated contrast. Micelles and lipoproteins, a micelle-related class of nanoparticle, have notably been adapted as CT contrast agents. In this review we discuss the principles of CT image formation and the generation of CT contrast. We discuss the progress in developing non-targeted, targeted and cell tracking nanoparticle CT contrast agents. We feature agents based on micelles and used in conjunction with spectral CT. The large contrast agent doses needed will necessitate careful toxicology studies prior to clinical translation. However, the field has seen tremendous advances in the past decade and we expect many more advances to come in the next decade. PMID:24470293

Passive Standoff Detection of Chemical Warfare Agents on Surfaces

NASA Astrophysics Data System (ADS)

Thériault, Jean-Marc; Puckrin, Eldon; Hancock, Jim; Lecavalier, Pierre; Lepage, Carmela Jackson; Jensen, James O.

2004-11-01

Results are presented on the passive standoff detection and identification of chemical warfare (CW) liquid agents on surfaces by the Fourier-transform IR radiometry. This study was performed during surface contamination trials at Defence Research and Development Canada-Suffield in September 2002. The goal was to verify that passive long-wave IR spectrometric sensors can potentially remotely detect surfaces contaminated with CW agents. The passive sensor, the Compact Atmospheric Sounding Interferometer, was used in the trial to obtain laboratory and field measurements of CW liquid agents, HD and VX. The agents were applied to high-reflectivity surfaces of aluminum, low-reflectivity surfaces of Mylar, and several other materials including an armored personnel carrier. The field measurements were obtained at a standoff distance of 60 m from the target surfaces. Results indicate that liquid contaminant agents deposited on high-reflectivity surfaces can be detected, identified, and possibly quantified with passive sensors. For low-reflectivity surfaces the presence of the contaminants can usually be detected; however, their identification based on simple correlations with the absorption spectrum of the pure contaminant is not possible.

Dembo polymerase chain reaction technique for detection of bovine abortion, diarrhea, and respiratory disease complex infectious agents in potential vectors and reservoirs.

PubMed

Rahpaya, Sayed Samim; Tsuchiaka, Shinobu; Kishimoto, Mai; Oba, Mami; Katayama, Yukie; Nunomura, Yuka; Kokawa, Saki; Kimura, Takashi; Kobayashi, Atsushi; Kirino, Yumi; Okabayashi, Tamaki; Nonaka, Nariaki; Mekata, Hirohisa; Aoki, Hiroshi; Shiokawa, Mai; Umetsu, Moeko; Morita, Tatsushi; Hasebe, Ayako; Otsu, Keiko; Asai, Tetsuo; Yamaguchi, Tomohiro; Makino, Shinji; Murata, Yoshiteru; Abi, Ahmad Jan; Omatsu, Tsutomu; Mizutani, Tetsuya

2018-05-31

Bovine abortion, diarrhea, and respiratory disease complexes, caused by infectious agents, result in high and significant economic losses for the cattle industry. These pathogens are likely transmitted by various vectors and reservoirs including insects, birds, and rodents. However, experimental data supporting this possibility are scarce. We collected 117 samples and screened them for 44 bovine abortive, diarrheal, and respiratory disease complex pathogens by using Dembo polymerase chain reaction (PCR), which is based on TaqMan real-time PCR. Fifty-seven samples were positive for at least one pathogen, including bovine viral diarrhea virus, bovine enterovirus, Salmonella enterica ser. Dublin, Salmonella enterica ser. Typhimurium, and Neospora caninum ; some samples were positive for multiple pathogens. Bovine viral diarrhea virus and bovine enterovirus were the most frequently detected pathogens, especially in flies, suggesting an important role of flies in the transmission of these viruses. Additionally, we detected the N. caninum genome from a cockroach sample for the first time. Our data suggest that insects (particularly flies), birds, and rodents are potential vectors and reservoirs of abortion, diarrhea, and respiratory infectious agents, and that they may transmit more than one pathogen at the same time.

Ursolic acid derivatives as potential antidiabetic agents: In vitro, in vivo, and in silico studies.

PubMed

Guzmán-Ávila, Ricardo; Flores-Morales, Virginia; Paoli, Paolo; Camici, Guido; Ramírez-Espinosa, Juan José; Cerón-Romero, Litzia; Navarrete-Vázquez, Gabriel; Hidalgo-Figueroa, Sergio; Yolanda Rios, Maria; Villalobos-Molina, Rafael; Estrada-Soto, Samuel

2018-03-01

Hit, Lead & Candidate Discovery Protein tyrosine phosphatase 1B (PTP-1B) has attracted interest as a novel target for the treatment of type 2 diabetes, this because its role in the insulin-signaling pathway as a negative regulator. Thus, the aim of current work was to obtain seven ursolic acid derivatives as potential antidiabetic agents with PTP-1B inhibition as main mechanism of action. Furthermore, derivatives 1-7 were submitted in vitro to enzymatic PTP-1B inhibition being 3, 5, and 7 the most active compounds (IC 50  = 5.6, 4.7, and 4.6 μM, respectively). In addition, results were corroborated with in silico docking studies with PTP-1B orthosteric site A and extended binding site B, showed that 3 had polar and Van der Waals interactions in both sites with Lys120, Tyr46, Ser216, Ala217, Ile219, Asp181, Phe182, Gln262, Val49, Met258, and Gly259, showing a docking score value of -7.48 Kcal/mol, being more specific for site A. Moreover, compound 7 showed polar interaction with Gln262 and Van der Waals interactions with Ala217, Phe182, Ile219, Arg45, Tyr46, Arg47, Asp48, and Val49 with a predictive docking score of -6.43 kcal/mol, suggesting that the potential binding site could be localized in the site B adjacent to the catalytic site A. Finally, derivatives 2 and 7 (50 mg/kg) were selected to establish their in vivo antidiabetic effect using a noninsulin-dependent diabetes mice model, showing significant blood glucose lowering compared with control group (p < .05). © 2018 Wiley Periodicals, Inc.

Kinase inhibitors of the IGF-1R as a potential therapeutic agent for rheumatoid arthritis.

PubMed

Tsushima, Hiroshi; Morimoto, Shinji; Fujishiro, Maki; Yoshida, Yuko; Hayakawa, Kunihiro; Hirai, Takuya; Miyashita, Tomoko; Ikeda, Keigo; Yamaji, Ken; Takamori, Kenji; Takasaki, Yoshinari; Sekigawa, Iwao; Tamura, Naoto

2017-08-01

We have previously shown that the inhibition of connective tissue growth factor (CTGF) is a potential therapeutic strategy against rheumatoid arthritis (RA). CTGF consists of four distinct modules, including the insulin-like growth factor binding protein (IGFBP). In serum, insulin-like growth factors (IGFs) bind IGFBPs, interact with the IGF-1 receptor (IGF-1 R), and regulate anabolic effects and bone metabolism. We investigated the correlation between IGF-1 and the pathogenesis of RA, and the inhibitory effect on osteoclastogenesis and angiogenesis of the small molecular weight kinase inhibitor of the IGF-1 R, NVP-AEW541, against pathogenesis of RA in vitro. Cell proliferation was evaluated by cell count and immunoblotting. The expression of IGF-1 and IGF-1 R was evaluated by RT-PCR. Osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase staining, a bone resorption assay, and osteoclast-specific enzyme production. Angiogenesis was evaluated by a tube formation assay using human umbilical vein endothelial cells (HUVECs). The proliferation of MH7A cells was found to be inhibited in the presence of NVP-AEW541, and the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt was downregulated in MH7A cells. IGF-1 and IGF-1 R mRNA expression levels were upregulated during formation of M-colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL)-mediated osteoclast formation. Moreover, osteoclastogenesis was suppressed in the presence of NVP-AEW541. The formation of the tubular network was enhanced by IGF-1, and this effect was neutralized by NVP-ARE541. Our findings suggest that NVP-AEW541 may be utilized as a potential therapeutic agent in the treatment of RA.

Technological advancements for the detection of and protection against biological and chemical warfare agents.

PubMed

Eubanks, Lisa M; Dickerson, Tobin J; Janda, Kim D

2007-03-01

There is a growing need for technological advancements to combat agents of chemical and biological warfare, particularly in the context of the deliberate use of a chemical and/or biological warfare agent by a terrorist organization. In this tutorial review, we describe methods that have been developed both for the specific detection of biological and chemical warfare agents in a field setting, as well as potential therapeutic approaches for treating exposure to these toxic species. In particular, nerve agents are described as a typical chemical warfare agent, and the two potent biothreat agents, anthrax and botulinum neurotoxin, are used as illustrative examples of potent weapons for which countermeasures are urgently needed.

Toxicogenomic identification of biomarkers of acute respiratory expsoure to sensitizing agents

EPA Science Inventory

Allergy induction requires multiple exposures to an agent. Therefore the development of high-throughput or in vitro assays for effective screening of potential sensitizers will require the identification of biomarkers. The goal of this preliminary study was to identify potential ...

Validating agent oriented methodology (AOM) for netlogo modelling and simulation

NASA Astrophysics Data System (ADS)

WaiShiang, Cheah; Nissom, Shane; YeeWai, Sim; Sharbini, Hamizan

2017-10-01

AOM (Agent Oriented Modeling) is a comprehensive and unified agent methodology for agent oriented software development. AOM methodology was proposed to aid developers with the introduction of technique, terminology, notation and guideline during agent systems development. Although AOM methodology is claimed to be capable of developing a complex real world system, its potential is yet to be realized and recognized by the mainstream software community and the adoption of AOM is still at its infancy. Among the reason is that there are not much case studies or success story of AOM. This paper presents two case studies on the adoption of AOM for individual based modelling and simulation. It demonstrate how the AOM is useful for epidemiology study and ecological study. Hence, it further validate the AOM in a qualitative manner.

Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent

PubMed Central

Heinrich, Tobias K.; Gottumukkala, Vijay; Snay, Erin; Dunning, Patricia; Fahey, Frederic H; Treves, S. Ted; Packard, Alan B.

2009-01-01

There is considerable interest in developing an 18F-labeled PET myocardial perfusion agent. Rhodamine dyes share several properties with 99mTc-MIBI, the most commonly used single-photon myocardial perfusion agent, suggesting that an 18F-labeled rhodamine dye might prove useful for this application. In addition to being lipophilic cations, like 99mTc-MIBI, rhodamine dyes are known to accumulate in the myocardium and are substrates for Pgp, the protein implicated in MDR1 multidrug resistance. As the first step in determining whether 18F-labeled rhodamines might be useful as myocardial perfusion agents for PET, our objective was to develop synthetic methods for preparing the 18F-labeled compounds so that they could be evaluated in vivo. Rhodamine B was chosen as the prototype compound for development of the synthesis because the ethyl substituents on the amine moieties of rhodamine B protect them from side reactions, thus eliminating the need to include (and subsequently remove) protecting groups. The 2′-[18F]fluoroethyl ester of rhodamine B was synthesized by heating rhodamine B lactone with [18F]fluoroethyltosylate in acetonitrile at 165°C for 30 min.using [18F]fluoroethyl tosylate, which was prepared by the reaction of ethyleneglycol ditosylate with Kryptofix 2.2.2, K2CO3, and [18F]NaF in acetonitrile for 10 min. at 90°C. The product was purified by semi-preparative HPLC to produce the 2′-[18F]-fluoroethylester in >97% radiochemical purity with a specific activity of 1.3 GBq/μmol, an isolated decay corrected yield of 35%, and a total synthesis time of 90 min. PMID:19783150

Pharmacoeconomics of inhaled anesthetic agents: considerations for the pharmacist.

PubMed

Chernin, Eric L

2004-10-15

Types of economic analyses used for inhaled anesthetic agents, factors to consider in calculating the cost of inhaled anesthetics, limitations of pharmacoeconomic studies of these agents, and strategies for controlling inhaled anesthetic costs are discussed. Inhaled anesthetic agents comprise a substantial component of drug budgets. Calculation of the cost of administering an inhaled anesthetic should take into consideration the cost per mL, potency, waste, concentration and duration of gas delivery, fresh gas flow rate, molecular weight, and density. The use of newer inhaled anesthetic agents with low solubility in blood and tissue provides a more rapid recovery from anesthesia than older, more soluble agents, and also provides the same level of control of depth of anesthesia at a lower fresh gas flow rate and possibly a lower cost than older agents at a higher fresh gas flow rate. A more rapid recovery may facilitate fast-track recovery and yield cost savings if it allows the completion of additional surgical cases or allows a reduction in personnel overtime expenses. Interpretation of pharmacoeconomic studies of inhaled anesthetics requires an appreciation of the limitations in methodology and ability to extrapolate results from one setting to another. Pharmacists' efforts to reduce anesthetic waste and collaborate with anesthesiologists to improve the use of these agents can help contain costs, but improving scheduling and efficiency in the operating room has a greater potential to reduce operating room costs. Much can be done to control costs of anesthetic agents without compromising availability of these agents and patient care.

Modeling marine oily wastewater treatment by a probabilistic agent-based approach.

PubMed

Jing, Liang; Chen, Bing; Zhang, Baiyu; Ye, Xudong

2018-02-01

This study developed a novel probabilistic agent-based approach for modeling of marine oily wastewater treatment processes. It begins first by constructing a probability-based agent simulation model, followed by a global sensitivity analysis and a genetic algorithm-based calibration. The proposed modeling approach was tested through a case study of the removal of naphthalene from marine oily wastewater using UV irradiation. The removal of naphthalene was described by an agent-based simulation model using 8 types of agents and 11 reactions. Each reaction was governed by a probability parameter to determine its occurrence. The modeling results showed that the root mean square errors between modeled and observed removal rates were 8.73 and 11.03% for calibration and validation runs, respectively. Reaction competition was analyzed by comparing agent-based reaction probabilities, while agents' heterogeneity was visualized by plotting their real-time spatial distribution, showing a strong potential for reactor design and process optimization. Copyright © 2017 Elsevier Ltd. All rights reserved.

AFFECTIVE GUIDANCE OF INTELLIGENT AGENTS: How Emotion Controls Cognition1

PubMed Central

Clore, Gerald L.; Palmer, Janet E.

2008-01-01

Emotions and moods color cognition. In this article, we outline how emotions affect judgments and cognitive performance of human agents. We argue that affective influences are due, not to the affective reactions themselves, but to the information they carry about value, a potentially useful finding for creators of artificial agents. The kind of influence that occurs depends on the focus of the agent at the time. When making evaluative judgments, for example, agents may experience positive affect as a positive attitude toward a person or object. But when an agent focuses on a cognitive task, positive affect may act like performance feedback, with positive affect giving a green light to cognitive, relational processes. By contrast, negative affect tends to inhibit relational processing, resulting in a more perceptual, stimulus-specific processing. One result is that many textbook phenomena from cognitive psychology occur readily in happy moods, but are inhibited in sad moods. PMID:19255620

Apparent competition can compromise the safety of highly specific biocontrol agents.

PubMed

Carvalheiro, Luisa G; Buckley, Yvonne M; Ventim, Rita; Fowler, Simon V; Memmott, Jane

2008-07-01

Despite current concern about the safety of biological control of weeds, assessing the indirect impacts of introduced agents is not common practice. Using 17 replicate food webs, we demonstrate that the use of a highly host-plant specific weed biocontrol agent, recently introduced into Australia, is associated with declines of local insect communities. The agent shares natural enemies (predators and parasitoids) with seed herbivore species from native plants, so apparent competition is the most likely cause for these losses. Both species richness and abundance in insect communities (seed herbivores and their parasitoids) were negatively correlated with the abundance of the biocontrol agent. Local losses of up to 11 species (dipteran seed herbivores and parasitoids) took place as the biocontrol agent abundance increased. Ineffective biocontrol agents that remain highly abundant in the community are most likely to have persistent, indirect negative effects. Our findings suggest that more investment is required in pre-release studies on the effectiveness of biocontrol agents, as well as in post-release studies assessing indirect impacts, to avoid or minimize the release of potentially damaging species.

Evaluation of Degradation Properties of Polyglycolide and Its Potential as Delivery Vehicle for Anticancer Agents

NASA Astrophysics Data System (ADS)

Noorsal, K.; Ghani, S. M.; Yunos, D. M.; Mohamed, M. S. W.; Yahya, A. F.

2010-03-01

Biodegradable polymers offer a unique combination of properties that can be tailored to suit nearly any controlled drug delivery application. The most common biodegradable polymers used for biomedical applications are semicrystalline polyesters and polyethers which possess good mechanical properties and have been used in many controlled release applications. Drug release from these polymers may be controlled by several mechanisms and these include diffusion of drug through a matrix, dissolution of polymer matrix and degradation of the polymer. This study aims to investigate the degradation and drug release properties of polyglycolide (1.03 dL/g), in which, cis platin, an anticancer agent was used as the model drug. The degradation behaviour of the chosen polymer is thought to largely govern the release of the anticancer agent in vitro.

Behavioral biometrics for verification and recognition of malicious software agents

NASA Astrophysics Data System (ADS)

Yampolskiy, Roman V.; Govindaraju, Venu

2008-04-01

Homeland security requires technologies capable of positive and reliable identification of humans for law enforcement, government, and commercial applications. As artificially intelligent agents improve in their abilities and become a part of our everyday life, the possibility of using such programs for undermining homeland security increases. Virtual assistants, shopping bots, and game playing programs are used daily by millions of people. We propose applying statistical behavior modeling techniques developed by us for recognition of humans to the identification and verification of intelligent and potentially malicious software agents. Our experimental results demonstrate feasibility of such methods for both artificial agent verification and even for recognition purposes.

Novel sarsasapogenin-triazolyl hybrids as potential anti-Alzheimer's agents: Design, synthesis and biological evaluation.

PubMed

Wang, Wenbao; Wang, Wei; Yao, Guodong; Ren, Qiang; Wang, Di; Wang, Zedan; Liu, Peng; Gao, Pinyi; Zhang, Yan; Wang, Shaojie; Song, Shaojiang

2018-05-10

Sarsasapogenin, an active ingredient in Rhizoma anemarrhenae, is a promising bioactive lead compound in the treatment of Alzheimer's disease. To search for more efficient anti-Alzheimer agents, a series of novel sarsasapogenin-triazolyl hybrids were designed, synthesized, and evaluated for their Aβ 1-42 aggregation inhibitory activities. Most of these new hybrids displayed potent Aβ 1-42 aggregation inhibition. In particular, the promising compounds 6j and 6o displayed a better ability to interrupt the formation of Aβ 1-42 fibrils than curcumin. Moreover, 6j and 6o exhibited moderate neuroprotective effects against H 2 O 2 -induced neurotoxicity in SH-SY5Y cells. To investigate whether 6j and 6o could improve cognitive deficits, we performed behavioral tests to examine the learning and memory impairments induced by intracerebroventricular injection of Aβ 1-42 (ICV-Aβ 1-42 ) in mice and TUNEL staining to observe neuronal apoptosis in the hippocampus. The results obtained indicated that oral treatment with 6j and 6o significantly ameliorated cognitive impairments in behavioral tests and TUNEL staining showed that 6j and 6o attenuated neuronal loss in the brain. Taken together, the results we obtained showed that the sarsasapogenin skeleton could be a promising structural template for the development of new anti-Alzheimer drug candidates, and compounds 6j and 6o have the potential to be important lead compounds for further research. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Flocking with connectivity preservation for disturbed nonlinear multi-agent systems by output feedback

NASA Astrophysics Data System (ADS)

Li, Ping; Zhang, Baoyong; Ma, Qian; Xu, Shengyuan; Chen, Weimin; Zhang, Zhengqiang

2018-05-01

This paper considers the problem of flocking with connectivity preservation for a class of disturbed nonlinear multi-agent systems. In order to deal with the nonlinearities in the dynamic of all agents, some auxiliary variables are introduced into the state observer for stability analysis. By proposing a bounded potential function and using adaptive theory, a novel output feedback consensus algorithm is developed to guarantee that the states of all agents achieve flocking with connectivity preservation.

Riot Control Agents

MedlinePlus

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[Utilization of polymeric micelle magnetic resonance imaging (MRI) contrast agent for theranostic system].

PubMed

Shiraishi, Kouichi

2013-01-01

We applied a polymeric micelle carrier system for the targeting of a magnetic resonance imaging (MRI) contrast agent. Prepared polymeric micelle MRI contrast agent exhibited a long circulation characteristic in blood, and considerable amount of the contrast agent was found to accumulate in colon 26 solid tumor by the EPR effect. The signal intensities of tumor area showed 2-folds increase in T1-weighted images at 24 h after i.v. injection. To observe enhancement of the EPR effect by Cderiv pretreatment on tumor targeting, we used the contrast agent for the evaluation by means of MRI. Cderiv pretreatment significantly enhanced tumor accumulation of the contrast agent. Interestingly, very high signal intensity in tumor region was found at 24 h after the contrast agent injection in Cderiv pretreated mice. The contrast agent visualized a microenvironmental change in tumor. These results indicate that the contrast agent exhibits potential use for tumor diagnostic agent. To combine with a polymeric micelle carrier system for therapeutic agent, the usage of the combination makes a new concept of "theranostic" for a better cancer treatment.

The potential of a fluorescent-based approach for bioassay of antifungal agents against chili anthracnose disease in Thailand.

PubMed

Chutrakul, Chanikul; Khaokhajorn, Pratoomporn; Auncharoen, Patchanee; Boonruengprapa, Tanapong; Mongkolporn, Orarat

2013-01-01

Severe chili anthracnose disease in Thailand is caused by Colletotrichum gloeosporioides and C. capsici. To discover anti-anthracnose substances we developed an efficient dual-fluorescent labeling bioassay based on a microdilution approach. Indicator strains used in the assay were constructed by integrating synthetic green fluorescent protein (sGFP) and Discosoma sp. red fluorescent protein (DsRedExp) genes into the genomes of C. gloeosporioides or C. capsici respectively. Survival of co-spore cultures in the presence of inhibitors was determined by the expression levels of these fluorescent proteins. This developed assay has high potential for utilization in the investigation of selective inhibition activity to either one of the pathogens as well as the broad-range inhibitory effect against both pathogens. The value of using the dual-fluorescent assay is rapid, reliable, and consistent identification of anti-anthracnose agents. Most of all, the assay enables the identification of specific inhibitors under the co-cultivation condition.

Nanomaterials incorporated ultrasound contrast agents for cancer theranostics

PubMed Central

Fu, Lei; Ke, Heng-Te

2016-01-01

Nanotechnology provides various nanomaterials with tremendous functionalities for cancer diagnostics and therapeutics. Recently, theranostics has been developed as an alternative strategy for efficient cancer treatment through combination of imaging diagnosis and therapeutic interventions under the guidance of diagnostic results. Ultrasound (US) imaging shows unique advantages with excellent features of real-time imaging, low cost, high safety and portability, making US contrast agents (UCAs) an ideal platform for construction of cancer theranostic agents. This review focuses on the development of nanomaterials incorporated multifunctional UCAs serving as theranostic agents for cancer diagnostics and therapeutics, via conjugation of superparamagnetic iron oxide nanoparticles (SPIOs), CuS nanoparticles, DNA, siRNA, gold nanoparticles (GNPs), gold nanorods (GNRs), gold nanoshell (GNS), graphene oxides (GOs), polypyrrole (PPy) nanocapsules, Prussian blue (PB) nanoparticles and so on to different types of UCAs. The cancer treatment could be more effectively and accurately carried out under the guidance and monitoring with the help of the achieved theranostic agents. Furthermore, nanomaterials incorporated theranostic agents based on UCAs can be designed and constructed by demand for personalized and accurate treatment of cancer, demonstrating their great potential to address the challenges of cancer heterogeneity and adaptation, which can provide alternative strategies for cancer diagnosis and therapeutics. PMID:27807499

A water market simulator considering pair-wise trades between agents

NASA Astrophysics Data System (ADS)

Huskova, I.; Erfani, T.; Harou, J. J.

2012-04-01

In many basins in England no further water abstraction licences are available. Trading water between water rights holders has been recognized as a potentially effective and economically efficient strategy to mitigate increasing scarcity. A screening tool that could assess the potential for trade through realistic simulation of individual water rights holders would help assess the solution's potential contribution to local water management. We propose an optimisation-driven water market simulator that predicts pair-wise trade in a catchment and represents its interaction with natural hydrology and engineered infrastructure. A model is used to emulate licence-holders' willingness to engage in short-term trade transactions. In their simplest form agents are represented using an economic benefit function. The working hypothesis is that trading behaviour can be partially predicted based on differences in marginal values of water over space and time and estimates of transaction costs on pair-wise trades. We discuss the further possibility of embedding rules, norms and preferences of the different water user sectors to more realistically represent the behaviours, motives and constraints of individual licence holders. The potential benefits and limitations of such a social simulation (agent-based) approach is contrasted with our simulator where agents are driven by economic optimization. A case study based on the Dove River Basin (UK) demonstrates model inputs and outputs. The ability of the model to suggest impacts of water rights policy reforms on trading is discussed.

Biocompatible blood pool MRI contrast agents based on hyaluronan

PubMed Central

Zhu, Wenlian; Artemov, Dmitri

2010-01-01

Biocompatible gadolinium blood pool contrast agents based on a biopolymer, hyaluronan, were investigated for magnetic resonance angiography application. Hyaluronan, a non-sulfated linear glucosaminoglycan composed of 2000–25,000 repeating disaccharide subunits of D-glucuronic acid and N-acetylglucosamine with molecular weight up to 20 MDa, is a major component of the extracellular matrix. Two gadolinium contrast agents based on 16 and 74 kDa hyaluronan were synthesized, both with R1 relaxivity around 5 mM−1 s−1 per gadolinium at 9.4 T at 25°C. These two hyaluronan based agents show significant enhancement of the vasculature for an extended period of time. Initial excretion was primarily through the renal system. Later uptake was observed in the stomach and lower gastrointestinal tract. Macromolecular hyaluronan-based gadolinium agents have a high clinical translation potential as hyaluronan is already approved by FDA for a variety of medical applications. PMID:21504061

Nondestructive Intervention to Multi-Agent Systems through an Intelligent Agent

PubMed Central

Han, Jing; Wang, Lin

2013-01-01

For a given multi-agent system where the local interaction rule of the existing agents can not be re-designed, one way to intervene the collective behavior of the system is to add one or a few special agents into the group which are still treated as normal agents by the existing ones. We study how to lead a Vicsek-like flocking model to reach synchronization by adding special agents. A popular method is to add some simple leaders (fixed-headings agents). However, we add one intelligent agent, called ‘shill’, which uses online feedback information of the group to decide the shill's moving direction at each step. A novel strategy for the shill to coordinate the group is proposed. It is strictly proved that a shill with this strategy and a limited speed can synchronize every agent in the group. The computer simulations show the effectiveness of this strategy in different scenarios, including different group sizes, shill speed, and with or without noise. Compared to the method of adding some fixed-heading leaders, our method can guarantee synchronization for any initial configuration in the deterministic scenario and improve the synchronization level significantly in low density groups, or model with noise. This suggests the advantage and power of feedback information in intervention of collective behavior. PMID:23658695

Ultrasound Contrast Agents

NASA Astrophysics Data System (ADS)

Cachard, Christian; Basset, Olivier

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

Remote Agent Demonstration

NASA Technical Reports Server (NTRS)

Dorais, Gregory A.; Kurien, James; Rajan, Kanna

1999-01-01

We describe the computer demonstration of the Remote Agent Experiment (RAX). The Remote Agent is a high-level, model-based, autonomous control agent being validated on the NASA Deep Space 1 spacecraft.

Climate variability and change in the United States: potential impacts on water- and foodborne diseases caused by microbiologic agents.

PubMed

Rose, J B; Epstein, P R; Lipp, E K; Sherman, B H; Bernard, S M; Patz, J A

2001-05-01

Exposure to waterborne and foodborne pathogens can occur via drinking water (associated with fecal contamination), seafood (due to natural microbial hazards, toxins, or wastewater disposal) or fresh produce (irrigated or processed with contaminated water). Weather influences the transport and dissemination of these microbial agents via rainfall and runoff and the survival and/or growth through such factors as temperature. Federal and state laws and regulatory programs protect much of the U.S. population from waterborne disease; however, if climate variability increases, current and future deficiencies in areas such as watershed protection, infrastructure, and storm drainage systems will probably increase the risk of contamination events. Knowledge about transport processes and the fate of microbial pollutants associated with rainfall and snowmelt is key to predicting risks from a change in weather variability. Although recent studies identified links between climate variability and occurrence of microbial agents in water, the relationships need further quantification in the context of other stresses. In the marine environment as well, there are few studies that adequately address the potential health effects of climate variability in combination with other stresses such as overfishing, introduced species, and rise in sea level. Advances in monitoring are necessary to enhance early-warning and prevention capabilities. Application of existing technologies, such as molecular fingerprinting to track contaminant sources or satellite remote sensing to detect coastal algal blooms, could be expanded. This assessment recommends incorporating a range of future scenarios of improvement plans for current deficiencies in the public health infrastructure to achieve more realistic risk assessments.

Climate variability and change in the United States: potential impacts on water- and foodborne diseases caused by microbiologic agents.

PubMed Central

Rose, J B; Epstein, P R; Lipp, E K; Sherman, B H; Bernard, S M; Patz, J A

2001-01-01

Exposure to waterborne and foodborne pathogens can occur via drinking water (associated with fecal contamination), seafood (due to natural microbial hazards, toxins, or wastewater disposal) or fresh produce (irrigated or processed with contaminated water). Weather influences the transport and dissemination of these microbial agents via rainfall and runoff and the survival and/or growth through such factors as temperature. Federal and state laws and regulatory programs protect much of the U.S. population from waterborne disease; however, if climate variability increases, current and future deficiencies in areas such as watershed protection, infrastructure, and storm drainage systems will probably increase the risk of contamination events. Knowledge about transport processes and the fate of microbial pollutants associated with rainfall and snowmelt is key to predicting risks from a change in weather variability. Although recent studies identified links between climate variability and occurrence of microbial agents in water, the relationships need further quantification in the context of other stresses. In the marine environment as well, there are few studies that adequately address the potential health effects of climate variability in combination with other stresses such as overfishing, introduced species, and rise in sea level. Advances in monitoring are necessary to enhance early-warning and prevention capabilities. Application of existing technologies, such as molecular fingerprinting to track contaminant sources or satellite remote sensing to detect coastal algal blooms, could be expanded. This assessment recommends incorporating a range of future scenarios of improvement plans for current deficiencies in the public health infrastructure to achieve more realistic risk assessments. PMID:11359688

Benefits of a European Project on Diagnostics of Highly Pathogenic Agents and Assessment of Potential “Dual Use” Issues

PubMed Central

Grunow, Roland; Ippolito, G.; Jacob, D.; Sauer, U.; Rohleder, A.; Di Caro, A.; Iacovino, R.

2014-01-01

Quality assurance exercises and networking on the detection of highly infectious pathogens (QUANDHIP) is a joint action initiative set up in 2011 that has successfully unified the primary objectives of the European Network on Highly Pathogenic Bacteria (ENHPB) and of P4-laboratories (ENP4-Lab) both of which aimed to improve the efficiency, effectiveness, and response capabilities of laboratories directed at protecting the health of European citizens against high consequence bacteria and viruses of significant public health concern. Both networks have established a common collaborative consortium of 37 nationally and internationally recognized institutions with laboratory facilities from 22 European countries. The specific objectives and achievements include the initiation and establishment of a recognized and acceptable quality assurance scheme, including practical external quality assurance exercises, comprising living agents, that aims to improve laboratory performance, accuracy, and detection capabilities in support of patient management and public health responses; recognized training schemes for diagnostics and handling of highly pathogenic agents; international repositories comprising highly pathogenic bacteria and viruses for the development of standardized reference material; a standardized and transparent Biosafety and Biosecurity strategy protecting healthcare personnel and the community in dealing with high consequence pathogens; the design and organization of response capabilities dealing with cross-border events with highly infectious pathogens including the consideration of diagnostic capabilities of individual European laboratories. The project tackled several sensitive issues regarding Biosafety, Biosecurity and “dual use” concerns. The article will give an overview of the project outcomes and discuss the assessment of potential “dual use” issues. PMID:25426479

Measuring the remineralization potential of different agents with quantitative light-induced fluorescence digital Biluminator.

PubMed

Kucukyilmaz, Ebru; Savas, Selcuk

2017-01-26

The aim of this study was to investigate the effectiveness of different remineralization agents by quantitative light-induced fluorescence digital BiluminatorTM (QLF-D). Artificial caries lesions were created, and the teeth were divided according to the tested materials: (i) distilled water, (ii) acidulated phosphate fluoride (APF), (iii) Curodont Repair (CR), (iv) ammonium hexafluorosilicate (SiF) and (v) ammonium hexafluorosilicate plus cetylpyridinium chloride (SiF + CPC). After treatment procedures, each of the samples was placed in artificial saliva. After demineralization and 1 and 4 weeks of remineralization procedures, fluorescence loss and lesion areas were measured with QLF-D. Data were statistically analyzed (α = 0.05). The fluorescence values of the demineralized enamel specimens treated with the various agents differed significantly compared with pretreatment values for both 1 and 4 weeks (p<0.05). At 4 weeks, the highest fluorescence gain was calculated in the CR, APF and SiF groups compared with the control (p<0.05). APF, SiF and CR groups yielded greater remineralization ability than SiF + CPC and control groups.

Synthesis and cytotoxic evaluation of novel symmetrical taspine derivatives as anticancer agents.

PubMed

Zhang, Jie; Zhang, Yanmin; Pan, Xiaoyan; Wang, Sicen; He, Langchon

2011-07-01

It has been demonstrated that taspine derivatives act as anticancer agents, thus we designed and synthesized a novel class of symmetrical biphenyl derivatives. We evaluated the cytotoxicity and antitumor activity of biphenyls against five human tumor and normal cell lines. The results indicated that the majority of the compounds exhibited anticancer activity equivalent to or greater than the positive control. Compounds (11) and (12) demonstrated the most potent cytotoxic activity with IC₅₀ values between 19.41 µM and 29.27 µM. The potent antiproliferative capabilities of these compounds against ECV304 human transformed endothelial cells indicated that these biphenyls could potentially serve as antiangiogenic agents. We also reviewed the relationship between structure and activity based on the experimental results. Our findings provide a good starting point for further development of symmetrical biphenyl derivatives as potential novel anticancer agents.

Efficacy of aprotinin with various anticoagulant agents in cardiopulmonary bypass.

PubMed

Terrell, M R; Walenga, J M; Koza, M J; Pifarré, R

1996-08-01

Aprotinin has recently been approved for clinical use in cardiopulmonary bypass. Although unfractionated heparin has been the only anticoagulant widely used for cardiopulmonary bypass, disadvantages involving heparin have led to ongoing investigations of alternative anticoagulant agents. The objective of this study was to evaluate the efficacy of aprotinin in combination with other anticoagulant agents, specifically low molecular weight heparin and recombinant hirudin, using a dog model of cardiopulmonary bypass. The blood conservation resulting from the use of aprotinin was observed only with unfractionated heparin. Efficacy of anticoagulation as measured by protein deposits in the bypass circuit filter revealed an unexpected reduction in the quantity of deposits when aprotinin was used in combination with low molecular weight heparin. As alternative anticoagulant agents are sought, the potential benefits of aprotinin in the reduction of operative blood loss must be evaluated independently for each anticoagulant agent.

CATS-based Air Traffic Controller Agents

NASA Technical Reports Server (NTRS)

Callantine, Todd J.

2002-01-01

This report describes intelligent agents that function as air traffic controllers. Each agent controls traffic in a single sector in real time; agents controlling traffic in adjoining sectors can coordinate to manage an arrival flow across a given meter fix. The purpose of this research is threefold. First, it seeks to study the design of agents for controlling complex systems. In particular, it investigates agent planning and reactive control functionality in a dynamic environment in which a variety perceptual and decision making skills play a central role. It examines how heuristic rules can be applied to model planning and decision making skills, rather than attempting to apply optimization methods. Thus, the research attempts to develop intelligent agents that provide an approximation of human air traffic controller behavior that, while not based on an explicit cognitive model, does produce task performance consistent with the way human air traffic controllers operate. Second, this research sought to extend previous research on using the Crew Activity Tracking System (CATS) as the basis for intelligent agents. The agents use a high-level model of air traffic controller activities to structure the control task. To execute an activity in the CATS model, according to the current task context, the agents reference a 'skill library' and 'control rules' that in turn execute the pattern recognition, planning, and decision-making required to perform the activity. Applying the skills enables the agents to modify their representation of the current control situation (i.e., the 'flick' or 'picture'). The updated representation supports the next activity in a cycle of action that, taken as a whole, simulates air traffic controller behavior. A third, practical motivation for this research is to use intelligent agents to support evaluation of new air traffic control (ATC) methods to support new Air Traffic Management (ATM) concepts. Current approaches that use large, human

Effects of antihypertensive agents on sexual function.

PubMed

Weiss, R J

1991-12-01

Patient compliance with antihypertensive therapy can be improved by minimizing drug-induced sexual dysfunction. Impotence, decreased libido, impaired ejaculation and gynecomastia are potential side effects, depending on the agent prescribed. Centrally acting antihypertensive agents such as methyldopa and clonidine, nonselective beta-adrenergic blockers and potassium-sparing diuretics are the drugs most often associated with sexual dysfunction. Thiazide diuretics cause impotence but may otherwise play a minimal role in sexual dysfunction. Alpha-adrenergic blockers, angiotensin converting enzyme inhibitors and calcium channel blockers have little adverse effect on sexual function. It is important to obtain an adequate history before and after initiating therapy. If sexual dysfunction develops in a patient, a different class of medication can be tried.

Targeting tumor glycolysis by a mitotropic agent.

PubMed

Ganapathy-Kanniappan, Shanmugasundaram

2016-01-01

Metabolic reprogramming is one of the hallmarks of cancer. Altered metabolism in cancer cells is exemplified by enhanced glucose utilization, a biochemical signature that is clinically exploited for cancer diagnosis using positron-emission tomography and computed tomography imaging. Accordingly, disrupting the glucose metabolism of cancer cells has been contemplated as a potential therapeutic strategy against cancer. Experimental evidences indicate that targeting glucose metabolism by inhibition of glycolysis or oxidative phosphorylation promotes anticancer effects. Yet, successful clinical translation of antimetabolites or energy blockers to treat cancer remains a challenge, primarily due to lack of efficacy and/or systemic toxicity. Recently, using nanotechnology, Marrache and Dhar have documented the feasibility of delivering a glycolytic inhibitor through triphenylphosphonium (TPP), a mitotropic agent that selectively targets mitochondria based on membrane potential. Furthermore, by utilizing gold nanoparticles the investigators also demonstrated the potential for simultaneous induction of photothermal therapy, thus facilitating an additional line of attack on cancer cells. The report establishes that specific inhibition of tumor glycolysis is achievable through TPP-dependent selective targeting of cancer cells. This nanotechnological approach involving TPP-guided selective delivery of an antiglycolytic agent complemented with photothermal therapy provides a new window of opportunity for effective and specific targeting of tumor glycolysis.

Excellent approach to modeling urban expansion by fuzzy cellular automata: agent base model

NASA Astrophysics Data System (ADS)

Khajavigodellou, Yousef; Alesheikh, Ali A.; Mohammed, Abdulrazak A. S.; Chapi, Kamran

2014-09-01

Recently, the interaction between humans and their environment is the one of important challenges in the world. Landuse/ cover change (LUCC) is a complex process that includes actors and factors at different social and spatial levels. The complexity and dynamics of urban systems make the applicable practice of urban modeling very difficult. With the increased computational power and the greater availability of spatial data, micro-simulation such as the agent based and cellular automata simulation methods, has been developed by geographers, planners, and scholars, and it has shown great potential for representing and simulating the complexity of the dynamic processes involved in urban growth and land use change. This paper presents Fuzzy Cellular Automata in Geospatial Information System and remote Sensing to simulated and predicted urban expansion pattern. These FCA-based dynamic spatial urban models provide an improved ability to forecast and assess future urban growth and to create planning scenarios, allowing us to explore the potential impacts of simulations that correspond to urban planning and management policies. A fuzzy inference guided cellular automata approach. Semantic or linguistic knowledge on Land use change is expressed as fuzzy rules, based on which fuzzy inference is applied to determine the urban development potential for each pixel. The model integrates an ABM (agent-based model) and FCA (Fuzzy Cellular Automata) to investigate a complex decision-making process and future urban dynamic processes. Based on this model rapid development and green land protection under the influences of the behaviors and decision modes of regional authority agents, real estate developer agents, resident agents and non- resident agents and their interactions have been applied to predict the future development patterns of the Erbil metropolitan region.

Cyclic peptides as potential therapeutic agents for skin disorders.

PubMed

Namjoshi, Sarika; Benson, Heather A E

2010-01-01

There is an increasing understanding of the role of peptides in normal skin function and skin disease. With this knowledge, there is significant interest in the application of peptides as therapeutics in skin disease or as cosmeceuticals to enhance skin appearance. In particular, antimicrobial peptides and those involved in inflammatory processes provide options for the development of new therapeutic directions in chronic skin conditions such as psoriasis and dermatitis. To exploit their potential, it is essential that these peptides are delivered to their site of action in active form and in sufficient quantity to provide the desired effect. Many polymers permeate the skin poorly and are vulnerable to enzymatic degradation. Synthesis of cyclic peptide derivatives can substantially alter the physicochemical characteristics of the peptide with the potential to improve its skin permeation. In addition, cyclization can stabilize the peptide structure and thereby increase its stability. This review describes the role of cyclic peptides in the skin, examples of current cyclic peptide therapeutic products, and the potential for cyclic peptides as dermatological therapeutics and cosmeceuticals.

Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

NASA Astrophysics Data System (ADS)

Chen, Zhijin; Yu, Dexin; Wang, Shaojie; Zhang, Na; Ma, Chunhong; Lu, Zaijun

2009-07-01

Accurate diagnosis in early stage is vital for the treatment of Hepatocellular carcinoma. The aim of this study was to investigate the potential of poly lactic acid-polyethylene glycol/gadolinium-diethylenetriamine-pentaacetic acid (PLA-PEG/Gd-DTPA) nanocomplexes using as biocompatible molecular magnetic resonance imaging (MRI) contrast agent. The PLA-PEG/Gd-DTPA nanocomplexes were obtained using self-assembly nanotechnology by incubation of PLA-PEG nanoparticles and the commercial contrast agent, Gd-DTPA. The physicochemical properties of nanocomplexes were measured by atomic force microscopy and photon correlation spectroscopy. The T1-weighted MR images of the nanocomplexes were obtained in a 3.0 T clinical MR imager. The stability study was carried out in human plasma and the distribution in vivo was investigated in rats. The mean size of the PLA-PEG/Gd-DTPA nanocomplexes was 187.9 ± 2.30 nm, and the polydispersity index was 0.108, and the zeta potential was -12.36 ± 3.58 mV. The results of MRI test confirmed that the PLA-PEG/Gd-DTPA nanocomplexes possessed the ability of MRI, and the direct correlation between the MRI imaging intensities and the nano-complex concentrations was observed ( r = 0.987). The signal intensity was still stable within 2 h after incubation of the nanocomplexes in human plasma. The nanocomplexes gave much better image contrast effects and longer stagnation time than that of commercial contrast agent in rat liver. A dose of 0.04 mmol of gadolinium per kilogram of body weight was sufficient to increase the MRI imaging intensities in rat livers by five-fold compared with the commercial Gd-DTPA. PLA-PEG/Gd-DTPA nanocomplexes could be prepared easily with small particle sizes. The nanocomplexes had high plasma stability, better image contrast effect, and liver targeting property. These results indicated that the PLA-PEG/Gd-DTPA nanocomplexes might be potential as molecular targeted imaging contrast agent.

Evolutionary Agent-based Models to design distributed water management strategies

NASA Astrophysics Data System (ADS)

Giuliani, M.; Castelletti, A.; Reed, P. M.

2012-12-01

There is growing awareness in the scientific community that the traditional centralized approach to water resources management, as described in much of the water resources literature, provides an ideal optimal solution, which is certainly useful to quantify the best physically achievable performance, but is generally inapplicable. Most real world water resources management problems are indeed characterized by the presence of multiple, distributed and institutionally-independent decision-makers. Multi-Agent Systems provide a potentially more realistic alternative framework to model multiple and self-interested decision-makers in a credible context. Each decision-maker can be represented by an agent who, being self-interested, acts according to local objective functions and produces negative externalities on system level objectives. Different levels of coordination can potentially be included in the framework by designing coordination mechanisms to drive the current decision-making structure toward the global system efficiency. Yet, the identification of effective coordination strategies can be particularly complex in modern institutional contexts and current practice is dependent on largely ad-hoc coordination strategies. In this work we propose a novel Evolutionary Agent-based Modeling (EAM) framework that enables a mapping of fully uncoordinated and centrally coordinated solutions into their relative "many-objective" tradeoffs using multiobjective evolutionary algorithms. Then, by analysing the conflicts between local individual agent and global system level objectives it is possible to more fully understand the causes, consequences, and potential solution strategies for coordination failures. Game-theoretic criteria have value for identifying the most interesting alternatives from a policy making point of view as well as the coordination mechanisms that can be applied to obtain these interesting solutions. The proposed approach is numerically tested on a

Neuroprotective "agents" in surgery. Secret "agent" man, or common "agent" machine?

NASA Technical Reports Server (NTRS)

Andrews, R. J.

1999-01-01

The search for clinically-effective neuroprotective agents has received enormous support in recent years--an estimated $200 million by pharmaceutical companies on clinical trials for traumatic brain injury alone. At the same time, the pathophysiology of brain injury has proved increasingly complex, rendering the likelihood of a single agent "magic bullet" even more remote. On the other hand, great progress continues with technology that makes surgery less invasive and less risky. One example is the application of endovascular techniques to treat coronary artery stenosis, where both the invasiveness of sternotomy and the significant neurological complication rate (due to microemboli showering the cerebral vasculature) can be eliminated. In this paper we review aspects of intraoperative neuroprotection both present and future. Explanations for the slow progress on pharmacologic neuroprotection during surgery are presented. Examples of technical advances that have had great impact on neuroprotection during surgery are given both from coronary artery stenosis surgery and from surgery for Parkinson's disease. To date, the progress in neuroprotection resulting from such technical advances is an order of magnitude greater than that resulting from pharmacologic agents used during surgery. The progress over the last 20 years in guidance during surgery (CT and MRI image-guidance) and in surgical access (endoscopic and endovascular techniques) will soon be complemented by advances in our ability to evaluate biological tissue intraoperatively in real-time. As an example of such technology, the NASA Smart Probe project is considered. In the long run (i.e., in 10 years or more), pharmacologic "agents" aimed at the complex pathophysiology of nervous system injury in man will be the key to true intraoperative neuroprotection. In the near term, however, it is more likely that mundane "agents" based on computers, microsensors, and microeffectors will be the major impetus to improved

Comparison of the Lonidamine Potentiated Effect of Nitrogen Mustard Alkylating Agents on the Systemic Treatment of DB-1 Human Melanoma Xenografts in Mice.

PubMed

Nath, Kavindra; Nelson, David S; Putt, Mary E; Leeper, Dennis B; Garman, Bradley; Nathanson, Katherine L; Glickson, Jerry D

2016-01-01

Previous NMR studies demonstrated that lonidamine (LND) selectively diminishes the intracellular pH (pHi) of DB-1 melanoma and mouse xenografts of a variety of other prevalent human cancers while decreasing their bioenergetic status (tumor βNTP/Pi ratio) and enhancing the activities of melphalan and doxorubicin in these cancer models. Since melphalan and doxorubicin are highly toxic agents, we have examined three other nitrogen (N)-mustards, chlorambucil, cyclophosphamide and bendamustine, to determine if they exhibit similar potentiation by LND. As single agents LND, melphalan and these N-mustards exhibited the following activities in DB-1 melanoma xenografts; LND: 100% tumor surviving fraction (SF); chlorambucil: 100% SF; cyclophosphamide: 100% SF; bendamustine: 79% SF; melphalan: 41% SF. When combined with LND administered 40 min prior to administration of the N-mustard (to maximize intracellular acidification) the following responses were obtained; chlorambucil: 62% SF; cyclophosphamide: 42% SF; bendamustine: 36% SF; melphalan: 10% SF. The effect of LND on the activities of these N-mustards is generally attributed to acid stabilization of the aziridinium active intermediate, acid inhibition of glutathione-S-transferase, which acts as a scavenger of aziridinium, and acid inhibition of DNA repair by O6-alkyltransferase. Depletion of ATP by LND may also decrease multidrug resistance and increase tumor response. At similar maximum tolerated doses, our data indicate that melphalan is the most effective N-mustard in combination with LND when treating DB-1 melanoma in mice, but the choice of N-mustard for coadministration with LND will also depend on the relative toxicities of these agents, and remains to be determined.

Identification of black market products and potential doping agents in Germany 2010-2013.

PubMed

Krug, Oliver; Thomas, Andreas; Walpurgis, Katja; Piper, Thomas; Sigmund, Gerd; Schänzer, Wilhelm; Laussmann, Tim; Thevis, Mario

2014-11-01

The desire to increase the athletic performance, to 'optimize' an individual's appearance, and to complement but also to arguably substitute exercise by means of drugs and drug candidates has generated a considerable (illicit) market for compounds such as anabolic-androgenic steroids, stimulants, growth promoting peptide hormones, and so on. Genuinely developed for therapeutic use, their abuse/misuse generates enormous health risks, which has necessitated comprehensive controls of compound trafficking by customs and anti-doping authorities. From 2012 to 2013, the Bureau of Customs Investigation confiscated products containing anabolic-androgenic steroids (AAS; 259 kg), stimulants (13 kg), selective estrogen receptor modulators (SERMs; 24 kg), and human growth hormone (hGH; 3500 ampules). In cooperation with the Bureau and under the umbrella of the European Monitoring Center for Emerging Doping Agents (EuMoCEDA), the Cologne Anti-Doping Laboratory analyzed an additional 337 (black market) products between 2010 and 2013, allowing to monitor developments in drug use and, hence, the anticipation of new challenges in sports drug testing. Main tools utilized in characterizing confiscated materials were liquid chromatography-high resolution mass spectrometry (LC-HRMS), gas chromatography-high resolution mass spectrometry (GC-HRMS), and polyacrylamide gel electrophoresis (PAGE) with subsequent bottom-up identification of peptidic compounds using nano liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS). Among the 337 substances analyzed in the doping control laboratory in Cologne, 67 active ingredients were found, 49 of which being categorized as doping agents by the World Anti-Doping Agency (WADA). A total of 83.7 % accounted for steroidal substances (predominantly testosterone, trenbolone, and nandrolone and corresponding esters), 12.8 % accounted for peptide hormones and growth factors (predominantly hGH and growth hormone releasing peptides (GHRPs)), 3.2 % of

Elemental selenium at nano size (Nano-Se) as a potential chemopreventive agent with reduced risk of selenium toxicity: comparison with se-methylselenocysteine in mice.

PubMed

Zhang, Jinsong; Wang, Xufang; Xu, Tongwen

2008-01-01

Selenium (Se) is an essential trace element with a narrow margin between beneficial and toxic effects. As a promising chemopreventive agent, its use requires consumption over the long term, so the toxicity of Se is always a crucial concern. Based on clinical findings and recent studies in selenoprotein gene-modified mice, it is likely that the antioxidant function of one or more selenoproteins is responsible for the chemopreventive effect of Se. Furthermore, upregulation of phase 2 enzymes by Se has been implicated as a possible chemopreventive mechanism at supranutritional dietary levels. Se-methylselenocysteine (SeMSC), a naturally occurring organic Se product, is considered as one of the most effective chemopreventive selenocompounds. The present study revealed that, as compared with SeMSC, elemental Se at nano size (Nano-Se) possessed equal efficacy in increasing the activities of glutathione peroxidase, thioredoxin reductase, and glutathione S-transferase, but had much lower toxicity as indicated by median lethal dose, acute liver injury, survival rate, and short-term toxicity. Our results suggest that Nano-Se can serve as a potential chemopreventive agent with reduced risk of Se toxicity.

Paramagnetic liposomes as innovative contrast agents for magnetic resonance (MR) molecular imaging applications.

PubMed

Terreno, Enzo; Delli Castelli, Daniela; Cabella, Claudia; Dastrù, Walter; Sanino, Alberto; Stancanello, Joseph; Tei, Lorenzo; Aime, Silvio

2008-10-01

This article illustrates some innovative applications of liposomes loaded with paramagnetic lanthanide-based complexes in MR molecular imaging field. When a relatively high amount of a Gd(III) chelate is encapsulated in the vesicle, the nanosystem can simultaneously affect both the longitudinal (R(1)) and the transverse (R(2)) relaxation rate of the bulk H2O H-atoms, and this finding can be exploited to design improved thermosensitive liposomes whose MRI response is not longer dependent on the concentration of the probe. The observation that the liposome compartmentalization of a paramagnetic Ln(III) complex induce a significant R(2) enhancement, primarily caused by magnetic susceptibility effects, prompted us to test the potential of such agents in cell-targeting MR experiments. The results obtained indicated that these nanoprobes may have a great potential for the MR visualization of cellular targets (like the glutamine membrane transporters) overexpressing in tumor cells. Liposomes loaded with paramagnetic complexes acting as NMR shift reagents have been recently proposed as highly sensitive CEST MRI agents. The main peculiarity of CEST probes is to allow the MR visualization of different agents present in the same region of interest, and this article provides an illustrative example of the in vivo potential of liposome-based CEST agents.

Nootropic agents stimulate neurogenesis. Brain Cells, Inc.: WO2007104035.

PubMed

Taupin, Philippe

2009-05-01

The application is in the field of adult neurogenesis, neural stem cells and cellular therapy. It aims to characterize the activity of nootropic agents on adult neurogenesis in vitro. Nootropic agents are substances improving cognitive and mental abilities. AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) and nootropic agents were assessed for the potential to differentiate human neural progenitor and stem cells into neuronal cells in vitro. They were also tested for their behavioural activity on the novel object recognition task. AMPA, piracetam, FK-960 and SGS-111 induce and stimulate neuronal differentiation of human-derived neural progenitor and stem cells. SGS-111 increases the number of visits to the novel object. The neurogenic activity of piracetam and SGS-111 is mediated through AMPA receptor. The neurogenic activity of SGS-111 may contribute and play a role in its nootropic activity. These results suggest that nootropic agents may elicit some of their effects through their neurogenic activity. The application claims the use of nootropic agents for their neurogenic activity and for the treatment of neurological diseases, disorders and injuries, by stimulating or increasing the generation of neuronal cells in the adult brain.

Superhydrophobic silica nanoparticles as ultrasound contrast agents.

PubMed

Jin, Qiaofeng; Lin, Chih-Yu; Kang, Shih-Tsung; Chang, Yuan-Chih; Zheng, Hairong; Yang, Chia-Min; Yeh, Chih-Kuang

2017-05-01

Microbubbles have been widely studied as ultrasound contrast agents for diagnosis and as drug/gene carriers for therapy. However, their size and stability (lifetime of 5-12min) limited their applications. The development of stable nanoscale ultrasound contrast agents would therefore benefit both. Generating bubbles persistently in situ would be one of the promising solutions to the problem of short lifetime. We hypothesized that bubbles could be generated in situ by providing stable air nuclei since it has been found that the interfacial nanobubbles on a hydrophobic surface have a much longer lifetime (orders of days). Mesoporous silica nanoparticles (MSNs) with large surface areas and different levels of hydrophobicity were prepared to test our hypothesis. It is clear that the superhydrophobic and porous nanoparticles exhibited a significant and strong contrast intensity compared with other nanoparticles. The bubbles generated from superhydrophobic nanoparticles sustained for at least 30min at a MI of 1.0, while lipid microbubble lasted for about 5min at the same settings. In summary MSNs have been transformed into reliable bubble precursors by making simple superhydrophobic modification, and made into a promising contrast agent with the potentials to serve as theranostic agents that are sensitive to ultrasound stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Diversity and Community: The Role of Agent-Based Modeling.

PubMed

Stivala, Alex

2017-06-01

Community psychology involves several dialectics between potentially opposing ideals, such as theory and practice, rights and needs, and respect for human diversity and sense of community. Some recent papers in the American Journal of Community Psychology have examined the diversity-community dialectic, some with the aid of agent-based modeling and concepts from network science. This paper further elucidates these concepts and suggests that research in community psychology can benefit from a useful dialectic between agent-based modeling and the real-world concerns of community psychology. © Society for Community Research and Action 2017.

Evaluation of atoxigenic isolates of Aspergillus flavus as potential biocontrol agents for aflatoxin in maize.

PubMed

Atehnkeng, J; Ojiambo, P S; Ikotun, T; Sikora, R A; Cotty, P J; Bandyopadhyay, R

2008-10-01

Aflatoxin contamination resulting from maize infection by Aspergillus flavus is both an economic and a public health concern. Therefore, strategies for controlling aflatoxin contamination in maize are being investigated. The abilities of eleven naturally occurring atoxigenic isolates in Nigeria to reduce aflatoxin contamination in maize were evaluated in grain competition experiments and in field studies during the 2005 and 2006 growing seasons. Treatments consisted of inoculation of either grains in vials or ears at mid-silking stage in field plots, with the toxigenic isolate (La3228) or atoxigenic isolate alone and co-inoculation of each atoxigenic isolate and La3328. Aflatoxin B(1) + B(2) concentrations were significantly (p < 0.05) lower in the co-inoculation treatments compared with the treatment in which the aflatoxin-producing isolate La3228 was inoculated alone. Relative levels of aflatoxin B(1) + B(2) reduction ranged from 70.1% to 99.9%. Among the atoxigenics, two isolates from Lafia, La3279 and La3303, were most effective at reducing aflatoxin B(1) + B(2) concentrations in both laboratory and field trials. These two isolates have potential value as agents for the biocontrol of aflatoxin contamination in maize. Because these isolates are endemic to West Africa, they are both more likely than introduced isolates to be well adapted to West African environments and to meet regulatory concerns over their use throughout that region.

Viruses as potential pathogenic agents in systemic lupus erythematosus.

PubMed

Nelson, P; Rylance, P; Roden, D; Trela, M; Tugnet, N

2014-05-01

Genetic and environmental factors appear to contribute to the pathogenesis of systemic lupus erythematosus (SLE). Viral infections have been reported to be associated with the disease. A number of exogenous viruses have been linked to the pathogenesis of SLE, of which Epstein-Barr virus (EBV) has the most evidence of an aetiological candidate. In addition, human endogenous retroviruses (HERV), HRES-1, ERV-3, HERV-E 4-1, HERV-K10 and HERV-K18 have also been implicated in SLE. HERVs are incorporated into human DNA, and thus can be inherited. HERVs may trigger an autoimmune reaction through molecular mimicry, since homology of amino acid sequences between HERV proteins and SLE autoantigens has been demonstrated. These viruses can also be influenced by oestrogen, DNA hypomethylation, and ultraviolet light (UVB) exposure which have been shown to enhance HERV activation or expression. Viral infection, or other environmental factors, could induce defective apoptosis, resulting in loss of immune tolerance. Further studies in SLE and other autoimmune diseases are needed to elucidate the contribution of both exogenous and endogenous viruses in the development of autoimmunity. If key peptide sequences could be identified as molecular mimics between viruses and autoantigens, then this might offer the possibility of the development of blocking peptides or antibodies as therapeutic agents in SLE and other autoimmune conditions.

Strategies for the synthesis of the novel antitumor agent peloruside A

PubMed Central

Williams, David R; Nag, Partha P; Zorn, Nicolas

2009-01-01

The microtubule-stabilizing agent (+)-peloruside A has emerged as a potential therapeutic agent for the treatment of cancer. Two total syntheses have been published and these reports have stimulated additional studies to advance the methodology and strategies for accessing this molecular architecture. This review details the biological data, modeling and conformation analyses, and synthetic studies toward the synthesis of (+)-peloruside A, that were reported prior to December 2007. PMID:18283613

Sunscreening Agents

PubMed Central

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

2013-01-01

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

Cyclodextrins as new formulation entities and therapeutic agents.

PubMed

Sikharam, Sreevalli; Egan, Talmage D; Kern, Steven E

2005-08-01

This review is focused on recent advances in the application of cyclodextrins to new drug formulations, with emphasis on the field of anesthesia. Cyclodextrins are well-known excipients in the pharmaceutical industry. Their recent application to the anesthetic induction agent propofol as a means of creating a non-lipid formulation may lead to their introduction into anesthesia pharmacology. The development of a novel cyclodextrin as specific reversal agent for the neuromuscular blocker rocuronium (that acts as an in-vivo scavenging system to bind free rocuronium in the circulation) will also increase the likelihood that cyclodextrins will have a greater clinical presence in anesthesiology in the future. Cyclodextrin-containing polymers are also finding a role in the delivery of nucleic acids and protein therapeutic agents. Recent developments in cyclodextrins as excipients for anesthetics may soon culminate in their introduction into anesthesiology, although more research is necessary to better define their potential.

Cladosporium cladosporioides and Cladosporium pseudocladosporioides as potential new fungal antagonists of Puccinia horiana Henn., the causal agent of chrysanthemum white rust.

PubMed

Torres, David Eduardo; Rojas-Martínez, Reyna Isabel; Zavaleta-Mejía, Emma; Guevara-Fefer, Patricia; Márquez-Guzmán, G Judith; Pérez-Martínez, Carolina

2017-01-01

Puccinia horiana Hennings, the causal agent of chrysanthemum white rust, is a worldwide quarantine organism and one of the most important fungal pathogens of Chrysanthemum × morifolium cultivars, which are used for cut flowers and as potted plants in commercial production regions of the world. It was previously reported to be controlled by Lecanicillium lecanii, Cladosporium sphaerospermum, C. uredinicola and Aphanocladium album, due to their antagonistic and hyperparasitic effects. We report novel antagonist species on Puccinia horiana. Fungi isolated from rust pustules in a commercial greenhouse from Villa Guerrero, México, were identified as Cladosporium cladosporioides and Cladosporium pseudocladosporioides based upon molecular analysis and morphological characters. The antagonism of C. cladosporioides and C. pseudocladosporioides on chrysanthemum white rust was studied using light and electron microscopy in vitro at the host/parasite interface. Cladosporium cladosporioides and C. pseudocladosporioides grew towards the white rust teliospores and colonized the sporogenous cells, but no direct penetration of teliospores was observed; however, the structure and cytoplasm of teliospores were altered. The two Cladosporium spp. were able to grow on media containing laminarin, but not when chitin was used as the sole carbon source; these results suggest that they are able to produce glucanases. Results from the study indicate that both Cladosporium species had potential as biological control agents of chrysanthemum white rust.

Cladosporium cladosporioides and Cladosporium pseudocladosporioides as potential new fungal antagonists of Puccinia horiana Henn., the causal agent of chrysanthemum white rust

PubMed Central

Guevara-Fefer, Patricia; Márquez-Guzmán, G. Judith; Pérez-Martínez, Carolina

2017-01-01

Puccinia horiana Hennings, the causal agent of chrysanthemum white rust, is a worldwide quarantine organism and one of the most important fungal pathogens of Chrysanthemum × morifolium cultivars, which are used for cut flowers and as potted plants in commercial production regions of the world. It was previously reported to be controlled by Lecanicillium lecanii, Cladosporium sphaerospermum, C. uredinicola and Aphanocladium album, due to their antagonistic and hyperparasitic effects. We report novel antagonist species on Puccinia horiana. Fungi isolated from rust pustules in a commercial greenhouse from Villa Guerrero, México, were identified as Cladosporium cladosporioides and Cladosporium pseudocladosporioides based upon molecular analysis and morphological characters. The antagonism of C. cladosporioides and C. pseudocladosporioides on chrysanthemum white rust was studied using light and electron microscopy in vitro at the host/parasite interface. Cladosporium cladosporioides and C. pseudocladosporioides grew towards the white rust teliospores and colonized the sporogenous cells, but no direct penetration of teliospores was observed; however, the structure and cytoplasm of teliospores were altered. The two Cladosporium spp. were able to grow on media containing laminarin, but not when chitin was used as the sole carbon source; these results suggest that they are able to produce glucanases. Results from the study indicate that both Cladosporium species had potential as biological control agents of chrysanthemum white rust. PMID:28141830

Viral Vectors for Use in the Development of Biodefense Vaccines

DTIC Science & Technology

2005-06-17

vaccinia virus, and Venezuelan equine encephalitis virus, as vaccine vectors has enabled researchers to develop effective means for countering the...biowarfare. The use of viruses, for example adenovirus, vaccinia virus, and Venezuelan equine encephalitis virus, as vaccine -vectors has enabled researchers to... vaccines . . . . . . . . . . . . . . . . . . . 1298 2.1.3. Vaccinia virus-vectored Venezuelan equine encephalitis vaccines

A gadolinium(III) complex of a carboxylic-phosphorus acid derivative of diethylenetriamine covalently bound to inulin, a potential macromolecular MRI contrast agent.

PubMed

Lebdusková, Petra; Kotek, Jan; Hermann, Petr; Vander Elst, Luce; Muller, Robert N; Lukes, Ivan; Peters, Joop A

2004-01-01

A novel conjugate of a polysaccharide and a Gd(III) chelate with potential as contrast agent for magnetic resonance imaging (MRI) was synthesized. The structure of the chelate was derived from H5DTPA by replacing the central pendant arm by a phosphinic acid functional group, which was covalently bound to the polysaccharide inulin. On the average, each monosaccharide unit of the inulin was attached to approximately one (0.9) chelate moiety. The average molecular weight is 23110 and the average number of Gd3+ ions per molecule is 24. The ligand binds the Gd3+ ion in an octadentate fashion via three nitrogen atoms, four carboxylate oxygen atoms, and one P-O oxygen atom, and its first coordination sphere is completed by a water molecule. This compound shows promising properties for application as a contrast agent for MRI thanks to a favorable residence lifetime of this water molecule (170 ns at 298 K), a relatively long rotational correlation time (866 ps at 298 K), and the presence of two water molecules in the second coordination sphere of the Gd3+ ion. Furthermore, its stability toward transmetalation with Zn(II) is as high as that of the clinically used [Gd(DTPA)(H2O)]2-.

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

ERIC Educational Resources Information Center

Baker, Lauri M.; Hadley, Gregg

2014-01-01

The qualitative study reported here assessed the needs of agents related to new agent professional development to improve the current model. Agents who participated in new agent professional development within the last 5 years were selected to participate in focus groups to determine concerns and continued needs. Agents enjoyed networking and…

Pathobiology and management of laboratory rodents administered CDC category A agents.

PubMed

He, Yongqun; Rush, Howard G; Liepman, Rachel S; Xiang, Zuoshuang; Colby, Lesley A

2007-02-01

The Centers for Disease Control and Prevention Category A infectious agents include Bacillus anthracis (anthrax), Clostridium botulinum toxin (botulism), Yersinia pestis (plague), variola major virus (smallpox), Francisella tularensis (tularemia), and the filoviruses and arenaviruses that induce viral hemorrhagic fevers. These agents are regarded as having the greatest potential for adverse impact on public health and therefore are a focus of renewed attention in infectious disease research. Frequently rodent models are used to study the pathobiology of these agents. Although much is known regarding naturally occurring infections in humans, less is documented on the sources of exposures and potential risks of infection to researchers and animal care personnel after the administration of these hazardous substances to laboratory animals. Failure to appropriately manage the animals can result both in the creation of workplace hazards if human exposures occur and in disruption of the research if unintended animal exposures occur. Here we review representative Category A agents, with a focus on comparing the biologic effects in naturally infected humans and rodent models and on considerations specific to the management of infected rodent subjects. The information reviewed for each agent has been curated manually and stored in a unique Internet-based database system called HazARD (Hazards in Animal Research Database, http://helab.bioinformatics.med.umich.edu/hazard/) that is designed to assist researchers, administrators, safety officials, Institutional Biosafety Committees, and veterinary personnel seeking information on the management of risks associated with animal studies involving hazardous substances.

Aptamer-Targeted Gold Nanoparticles As Molecular-Specific Contrast Agents for Reflectance Imaging

PubMed Central

2008-01-01

Targeted metallic nanoparticles have shown potential as a platform for development of molecular-specific contrast agents. Aptamers have recently been demonstrated as ideal candidates for molecular targeting applications. In this study, we investigated the development of aptamer-based gold nanoparticles as contrast agents, using aptamers as targeting agents and gold nanoparticles as imaging agents. We devised a novel conjugation approach using an extended aptamer design where the extension is complementary to an oligonucleotide sequence attached to the surface of the gold nanoparticles. The chemical and optical properties of the aptamer−gold conjugates were characterized using size measurements and oligonucleotide quantitation assays. We demonstrate this conjugation approach to create a contrast agent designed for detection of prostate-specific membrane antigen (PSMA), obtaining reflectance images of PSMA(+) and PSMA(−) cell lines treated with the anti-PSMA aptamer−gold conjugates. This design strategy can easily be modified to incorporate multifunctional agents as part of a multimodal platform for reflectance imaging applications. PMID:18512972

Blechnum Orientale Linn - a fern with potential as antioxidant, anticancer and antibacterial agent

PubMed Central

2010-01-01

Background Blechnum orientale Linn. (Blechnaceae) is used ethnomedicinally for the treatment of various skin diseases, stomach pain, urinary bladder complaints and sterilization of women. The aim of the study was to evaluate antioxidant, anticancer and antibacterial activity of five solvent fractions obtained from the methanol extract of the leaves of Blechnum orientale Linn. Methods Five solvent fractions were obtained from the methanol extract of B. orientale through successive partitioning with petroleum ether, chloroform, ethyl acetate, butanol and water. Total phenolic content was assessed using Folin-Ciocalteu's method. The antioxidant activity was determined by measuring the scavenging activity of DPPH radicals. Cytotoxic activity was tested against four cancer cell lines and a non-malignant cell using MTT assay. Antibacterial activity was assessed using the disc diffusion and broth microdilution assays. Standard phytochemical screening tests for saponins, tannins, terpenoids, flavonoids and alkaloids were also conducted. Results The ethyl acetate, butanol and water fractions possessed strong radical scavenging activity (IC50 8.6-13.0 μg/ml) and cytotoxic activity towards human colon cancer cell HT-29 (IC50 27.5-42.8 μg/ml). The three extracts were also effective against all Gram-positive bacteria tested: Bacillus cereus, Micrococcus luteus, methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and Stapylococcus epidermidis(minimum inhibitory concentration MIC 15.6-250 μg/ml; minimum bactericidal concentration MBC 15.6-250 μg/ml). Phytochemical analysis revealed the presence of flavonoids, terpenoids and tannins. Ethyl acetate and butanol fractions showed highest total phenolic content (675-804 mg gallic acid equivalent/g). Conclusions The results indicate that this fern is a potential candidate to be used as an antioxidant agent, for colon cancer therapy and for treatment of MRSA infections and other

Dragonflies are biocontrol agents in Wisconsin cranberry marshes

USDA-ARS?s Scientific Manuscript database

Dragonflies (Order Odonata) are abundant predators that emerge in large hatch events each summer in Wisconsin cranberry marshes. They seem to be a potential group of biocontrol agents for pest management that may be influenced by the diversity found on the marsh. In fact, our evidence shows that dra...

Melanin-Based Contrast Agents for Biomedical Optoacoustic Imaging and Theranostic Applications.

PubMed

Longo, Dario Livio; Stefania, Rachele; Aime, Silvio; Oraevsky, Alexander

2017-08-07

Optoacoustic imaging emerged in early 1990s as a new biomedical imaging technology that generates images by illuminating tissues with short laser pulses and detecting resulting ultrasound waves. This technique takes advantage of the spectroscopic approach to molecular imaging, and delivers high-resolution images in the depth of tissue. Resolution of the optoacoustic imaging is scalable, so that biomedical systems from cellular organelles to large organs can be visualized and, more importantly, characterized based on their optical absorption coefficient, which is proportional to the concentration of absorbing chromophores. Optoacoustic imaging was shown to be useful in both preclinical research using small animal models and in clinical applications. Applications in the field of molecular imaging offer abundant opportunities for the development of highly specific and effective contrast agents for quantitative optoacoustic imaging. Recent efforts are being made in the direction of nontoxic biodegradable contrast agents (such as nanoparticles made of melanin) that are potentially applicable in clinical optoacoustic imaging. In order to increase the efficiency and specificity of contrast agents and probes, they need to be made smart and capable of controlled accumulation in the target cells. This review was written in recognition of the potential breakthroughs in medical optoacoustic imaging that can be enabled by efficient and nontoxic melanin-based optoacoustic contrast agents.

Melanin-Based Contrast Agents for Biomedical Optoacoustic Imaging and Theranostic Applications

PubMed Central

Longo, Dario Livio; Aime, Silvio

2017-01-01

Optoacoustic imaging emerged in early 1990s as a new biomedical imaging technology that generates images by illuminating tissues with short laser pulses and detecting resulting ultrasound waves. This technique takes advantage of the spectroscopic approach to molecular imaging, and delivers high-resolution images in the depth of tissue. Resolution of the optoacoustic imaging is scalable, so that biomedical systems from cellular organelles to large organs can be visualized and, more importantly, characterized based on their optical absorption coefficient, which is proportional to the concentration of absorbing chromophores. Optoacoustic imaging was shown to be useful in both preclinical research using small animal models and in clinical applications. Applications in the field of molecular imaging offer abundant opportunities for the development of highly specific and effective contrast agents for quantitative optoacoustic imaging. Recent efforts are being made in the direction of nontoxic biodegradable contrast agents (such as nanoparticles made of melanin) that are potentially applicable in clinical optoacoustic imaging. In order to increase the efficiency and specificity of contrast agents and probes, they need to be made smart and capable of controlled accumulation in the target cells. This review was written in recognition of the potential breakthroughs in medical optoacoustic imaging that can be enabled by efficient and nontoxic melanin-based optoacoustic contrast agents. PMID:28783106

Aptamer delivery of siRNA, radiopharmaceutics and chemotherapy agents in cancer.

PubMed

de Almeida, Carlos E B; Alves, Lais Nascimento; Rocha, Henrique F; Cabral-Neto, Januário Bispo; Missailidis, Sotiris

2017-06-20

Aptamers are oligonucleotide reagents with high affinity and specificity, which among other therapeutic and diagnostic applications have the capability of acting as delivery agents. Thus, aptamers are capable of carrying small molecules, nanoparticles, radiopharmaceuticals or fluorescent agents as well as nucleic acid therapeutics specifically to their target cells. In most cases, the molecules may possess interesting therapeutic properties, but their lack of specificity for a particular cell type, or ability to internalise in such a cell, hinders their clinical development, or cause unwanted side effects. Thus, chemotherapy or radiotherapy agents, famous for their side effects, can be coupled to aptamers for specific delivery. Equally, siRNA have great therapeutic potential and specificity, but one of their shortcomings remain the delivery and internalisation into cells. Various methodologies have been proposed to date, including aptamers, to resolve this problem. Therapeutic or imaging reagents benefit from the adaptability and ease of chemical manipulation of aptamers, their high affinity for the specific marker of a cell type, and their internalisation ability via cell mediated endocytosis. In this review paper, we explore the potential of the aptamers as delivery agents and offer an update on current status and latest advancements. Copyright © 2017 Elsevier B.V. All rights reserved.

Agent-specific learning signals for self-other distinction during mentalising.

PubMed

Ereira, Sam; Dolan, Raymond J; Kurth-Nelson, Zeb

2018-04-01

Humans have a remarkable ability to simulate the minds of others. How the brain distinguishes between mental states attributed to self and mental states attributed to someone else is unknown. Here, we investigated how fundamental neural learning signals are selectively attributed to different agents. Specifically, we asked whether learning signals are encoded in agent-specific neural patterns or whether a self-other distinction depends on encoding agent identity separately from this learning signal. To examine this, we tasked subjects to learn continuously 2 models of the same environment, such that one was selectively attributed to self and the other was selectively attributed to another agent. Combining computational modelling with magnetoencephalography (MEG) enabled us to track neural representations of prediction errors (PEs) and beliefs attributed to self, and of simulated PEs and beliefs attributed to another agent. We found that the representational pattern of a PE reliably predicts the identity of the agent to whom the signal is attributed, consistent with a neural self-other distinction implemented via agent-specific learning signals. Strikingly, subjects exhibiting a weaker neural self-other distinction also had a reduced behavioural capacity for self-other distinction and displayed more marked subclinical psychopathological traits. The neural self-other distinction was also modulated by social context, evidenced in a significantly reduced decoding of agent identity in a nonsocial control task. Thus, we show that self-other distinction is realised through an encoding of agent identity intrinsic to fundamental learning signals. The observation that the fidelity of this encoding predicts psychopathological traits is of interest as a potential neurocomputational psychiatric biomarker.

Discovery of Clinically Approved Agents That Promote Suppression of Cystic Fibrosis Transmembrane Conductance Regulator Nonsense Mutations.

PubMed

Mutyam, Venkateshwar; Du, Ming; Xue, Xiaojiao; Keeling, Kim M; White, E Lucile; Bostwick, J Robert; Rasmussen, Lynn; Liu, Bo; Mazur, Marina; Hong, Jeong S; Falk Libby, Emily; Liang, Feng; Shang, Haibo; Mense, Martin; Suto, Mark J; Bedwell, David M; Rowe, Steven M

2016-11-01

Premature termination codons (PTCs) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF). Several agents are known to suppress PTCs but are poorly efficacious or toxic. To determine whether there are clinically available agents that elicit translational readthrough and improve CFTR function sufficient to confer therapeutic benefit to patients with CF with PTCs. Two independent screens, firefly luciferase and CFTR-mediated transepithelial chloride conductance assay, were performed on a library of 1,600 clinically approved compounds using fisher rat thyroid cells stably transfected with stop codons. Select agents were further evaluated using secondary screening assays including short circuit current analysis on primary cells from patients with CF. In addition, the effect of CFTR modulators (ivacaftor) was tested in combination with the most efficacious agents. From the primary screen, 48 agents were selected as potentially active. Following confirmatory tests in the transepithelial chloride conductance assay and prioritizing agents based on favorable pharmacologic properties, eight agents were advanced for secondary screening. Ivacaftor significantly increased short circuit current following forskolin stimulation in cells treated with pyranoradine tetraphosphate, potassium p-aminobenzoate, and escin as compared with vehicle control. Escin, an herbal agent, consistently induced readthrough activity as demonstrated by enhanced CFTR expression and function in vitro. Clinically approved drugs identified as potential readthrough agents, in combination with ivacaftor, may induce nonsense suppression to restore therapeutic levels of CFTR function. One or more agents may be suitable to advance to human testing.

To what extent have functional studies of ischaemia in animals been useful in the assessment of potential neuroprotective agents?

PubMed

Hunter, A J; Mackay, K B; Rogers, D C

1998-02-01

A general consensus is being reached on the use of a combination of mortality and functional end-points in clinical trials of neuroprotective agents. However, to date, few preclinical studies have examined the effects of putative neuroprotective agents on functional outcome after ischaemia. The data described in this review show the importance of combining both histopathological and neurobehavioural studies when evaluating the neuroprotective efficacy of anti-ischaemic agents in animal models of cerebral ischaemia. Here, Jackie Hunter, Ken Mackay and Derek Rogers argue that measures of functional improvement in models of ischaemia should be incorporated to characterize further the neuroprotection afforded by a compound that could aid the selection of doses and end-point measures in early clinical trials.

Chlorophyll-a analogues conjugated with aminobenzyl-DTPA as potential bifunctional agents for magnetic resonance imaging and photodynamic therapy.

PubMed

Li, Guolin; Slansky, Adam; Dobhal, Mahabeer P; Goswami, Lalit N; Graham, Andrew; Chen, Yihui; Kanter, Peter; Alberico, Ronald A; Spernyak, Joseph; Morgan, Janet; Mazurchuk, Richard; Oseroff, Allan; Grossman, Zachary; Pandey, Ravindra K

2005-01-01

A clinically relevant photosensitizer, 3-devinyl-3-(1-hexyloxyethyl)pyropheophorbide-a (HPPH, a chlorophyll-a derivative), was conjugated with Gd(III)-aminobenzyl-diethylenetriaminepentaacetic acid (DTPA), an experimental magnetic resonance (MR) imaging agent. In vivo reflectance spectroscopy confirmed tumor uptake of HPPH-aminobenzyl-Gd(III)-DTPA conjugate was higher than free HPPH administered intraveneously (iv) to C3H mice with subcutaneously (sc) implanted radiation-induced fibrosarcoma (RIF) tumor cells. In other experiments, Sprague-Dawley (SD) rats with sc implanted Ward Colon Carcinoma cells yielded markedly increased MR signal intensities from tumor regions-of-interest (ROIs) 24 h post-iv injection of HPPH-aminobenzyl-Gd(III)-DTPA conjugate as compared to unconjugated HPPH. In both in vitro (RIF tumor cells) and in vivo (mice bearing RIF tumors and rats bearing Ward Colon tumors) the conjugate produced significant increases in tumor conspicuity at 1.5 T and retained therapeutic efficacy following PDT. Also synthesized were a series of novel bifunctional agents containing two Gd(III) atoms per HPPH molecule that remained tumor-avid and PDT-active and yielded improved MR tumor conspicuity compared to their corresponding mono-Gd(III) analogues. Administered iv at a MR imaging dose of 10 micromol/kg, these conjugates produced severe skin phototoxicity. However, by replacing the hexyl group of the pyropheophorbide-a with a tri(ethylene glycol) monomethyl ether (PEG-methyl ether), these conjugates produced remarkable MR tumor enhancement at 8 h post-iv injection, significant tumoricidal activity (80% of mice were tumor-free on day 90), and reduced skin phototoxicity compared to their corresponding hexyl ether analogues. The poor water-solubility characteristic of these conjugates was resolved by incorporation into a liposomal formulation. This paper presents the synthesis of tumor-avid contrast enhancing agents for MR imaging and thus represents an important

Coating agents affected toward magnetite nanoparticles properties

NASA Astrophysics Data System (ADS)

Petcharoen, Karat; Sirivat, Anuvat

2012-02-01

Magnetite nanoparticles --MNPs-- are innovative materials used in biological and medical applications. They respond to magnetic field through the superparamagnetic behavior at room temperature. In this study, the MNPs were synthesized via the chemical co-precipitation method using various coating agents. Fatty acids, found naturally in the animal fats, can be used as a coating agent. Oleic acid and hexanoic acid were chosen as the surface modification agents to study the improvement in the suspension of MNPs in water and the magnetite properties. Suspension stability, particle size, and electrical conductivity of MNPs are critically affected by the modification process. The well-dispersed MNPs in water can be improved by the surface modification and the oleic acid coated MNPs possess excellent suspension stability over 1 week. The particle size of MNPs increases up to 40 nm using oleic acid coated MNPs. The electrical conductivity of the smallest particle size is 1.3x10-3 S/cm, which is 5 times higher than that of the largest particle, suggesting potential applications as a biomedical material under both of the electrical and magnetic fields.

In vitro metabolism and drug-drug interaction potential of UTL-5g, a novel chemo- and radioprotective agent.

PubMed

Wu, Jianmei; Shaw, Jiajiu; Dubaisi, Sarah; Valeriote, Frederick; Li, Jing

2014-12-01

N-(2,4-dichlorophenyl)-5-methyl-1,2-oxazole-3-carboxamide (UTL-5g), a potential chemo- and radioprotective agent, acts as a prodrug requiring bioactivation to the active metabolite 5-methylisoxazole-3-carboxylic acid (ISOX). UTL-5g hydrolysis to ISOX and 2,4-dichloroaniline (DCA) has been identified in porcine and rabbit liver esterases. The purpose of this study was to provide insights on the metabolism and drug interaction potential of UTL-5g in humans. The kinetics of UTL-5g hydrolysis was determined in human liver microsomes (HLM) and recombinant human carboxylesterases (hCE1b and hCE2). The potential of UTL-5g and its metabolites for competitive inhibition and time-dependent inhibition of microsomal cytochrome P450 (P450) was examined in HLM. UTL-5g hydrolysis to ISOX and DCA in HLM were NADPH-independent, with a maximum rate of reaction (Vmax) of 11.1 nmol/min per mg and substrate affinity (Km) of 41.6 µM. Both hCE1b and hCE2 effectively catalyzed UTL-5g hydrolysis, but hCE2 exhibited ∼30-fold higher catalytic efficiency (Vmax/Km) than hCE1b. UTL-5g and DCA competitively inhibited microsomal CYP1A2, CYP2B6, and CYP2C19 (IC50 values <50 µM), and exhibited time-dependent inhibition of microsomal CYP1A2 with the inactivation efficiency (kinact/KI) of 0.68 and 0.51 minute(-1)·mM(-1), respectively. ISOX did not inhibit or inactivate any tested microsomal P450. In conclusion, hCE1b and hCE2 play a key role in the bioactivation of UTL-5g. Factors influencing carboxylesterase activities may have a significant impact on the pharmacological and therapeutic effects of UTL-5g. UTL-5g has the potential to inhibit P450-mediated metabolism through competitive inhibition or time-dependent inhibition. Caution is particularly needed for potential drug interactions involving competitive inhibition or time-dependent inhibition of CYP1A2 in the future clinical development of UTL-5g. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

In Vitro Metabolism and Drug-Drug Interaction Potential of UTL-5g, a Novel Chemo- and Radioprotective Agent

PubMed Central

Wu, Jianmei; Shaw, Jiajiu; Dubaisi, Sarah; Valeriote, Frederick

2014-01-01

N-(2,4-dichlorophenyl)-5-methyl-1,2-oxazole-3-carboxamide (UTL-5g), a potential chemo- and radioprotective agent, acts as a prodrug requiring bioactivation to the active metabolite 5-methylisoxazole-3-carboxylic acid (ISOX). UTL-5g hydrolysis to ISOX and 2,4-dichloroaniline (DCA) has been identified in porcine and rabbit liver esterases. The purpose of this study was to provide insights on the metabolism and drug interaction potential of UTL-5g in humans. The kinetics of UTL-5g hydrolysis was determined in human liver microsomes (HLM) and recombinant human carboxylesterases (hCE1b and hCE2). The potential of UTL-5g and its metabolites for competitive inhibition and time-dependent inhibition of microsomal cytochrome P450 (P450) was examined in HLM. UTL-5g hydrolysis to ISOX and DCA in HLM were NADPH-independent, with a maximum rate of reaction (Vmax) of 11.1 nmol/min per mg and substrate affinity (Km) of 41.6 µM. Both hCE1b and hCE2 effectively catalyzed UTL-5g hydrolysis, but hCE2 exhibited ∼30-fold higher catalytic efficiency (Vmax/Km) than hCE1b. UTL-5g and DCA competitively inhibited microsomal CYP1A2, CYP2B6, and CYP2C19 (IC50 values <50 µM), and exhibited time-dependent inhibition of microsomal CYP1A2 with the inactivation efficiency (kinact/KI) of 0.68 and 0.51 minute−1·mM−1, respectively. ISOX did not inhibit or inactivate any tested microsomal P450. In conclusion, hCE1b and hCE2 play a key role in the bioactivation of UTL-5g. Factors influencing carboxylesterase activities may have a significant impact on the pharmacological and therapeutic effects of UTL-5g. UTL-5g has the potential to inhibit P450-mediated metabolism through competitive inhibition or time-dependent inhibition. Caution is particularly needed for potential drug interactions involving competitive inhibition or time-dependent inhibition of CYP1A2 in the future clinical development of UTL-5g. PMID:25249693

Paired-agent fluorescent imaging to detect micrometastases in breast sentinel lymph node biopsy: experiment design and protocol development

NASA Astrophysics Data System (ADS)

Li, Chengyue; Xu, Xiaochun; Basheer, Yusairah; He, Yusheng; Sattar, Husain A.; Brankov, Jovan G.; Tichauer, Kenneth M.

2018-02-01

Sentinel lymph node status is a critical prognostic factor in breast cancer treatment and is essential to guide future adjuvant treatment. The estimation that 20-60% of micrometastases are missed by conventional pathology has created a demand for the development of more accurate approaches. Here, a paired-agent imaging approach is presented that employs a control imaging agent to allow rapid, quantitative mapping of microscopic populations of tumor cells in lymph nodes to guide pathology sectioning. To test the feasibility of this approach to identify micrometastases, healthy pig lymph nodes were stained with targeted and control imaging agent solution to evaluate the potential for the agents to diffuse into and out of intact nodes. Aby-029, an anti-EGFR affibody was labeled with IRDye 800CW (LICOR) as targeted agent and IRDye 700DX was hydrolyzed as a control agent. Lymph nodes were stained and rinsed by directly injecting the agents into the lymph nodes after immobilization in agarose gel. Subsequently, lymph nodes were frozen-sectioned and imaged under an 80-um resolution fluorescence imaging system (Pearl, LICOR) to confirm equivalence of spatial distribution of both agents in the entire node. The binding potentials were acquired by a pixel-by-pixel calculation and was found to be 0.02 +/- 0.06 along the lymph node in the absence of binding. The results demonstrate this approach's potential to enhance the sensitivity of lymph node pathology by detecting fewer than 1000 cell in a whole human lymph node.

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

PubMed

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.

Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue.

PubMed

Jost, Gregor; Frenzel, Thomas; Lohrke, Jessica; Lenhard, Diana Constanze; Naganawa, Shinji; Pietsch, Hubertus

2017-07-01

Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study. GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry. Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h. In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs. • Gadolinium-based contrast agents can cross the blood-CSF barrier. • Fluid-attenuated MRI shows GBCA distribution with CSF flow. • GBCA structure and physicochemical properties do not impact CSF penetration and distribution. • GBCA clearance from CSF was almost complete within 24 h in rats. • CSF is a potential pathway of GBCA entry into the brain.

Comparison of the Lonidamine Potentiated Effect of Nitrogen Mustard Alkylating Agents on the Systemic Treatment of DB-1 Human Melanoma Xenografts in Mice

PubMed Central

Nath, Kavindra; Nelson, David S.; Putt, Mary E.; Leeper, Dennis B.; Garman, Bradley; Nathanson, Katherine L.; Glickson, Jerry D.

2016-01-01

Previous NMR studies demonstrated that lonidamine (LND) selectively diminishes the intracellular pH (pHi) of DB-1 melanoma and mouse xenografts of a variety of other prevalent human cancers while decreasing their bioenergetic status (tumor βNTP/Pi ratio) and enhancing the activities of melphalan and doxorubicin in these cancer models. Since melphalan and doxorubicin are highly toxic agents, we have examined three other nitrogen (N)-mustards, chlorambucil, cyclophosphamide and bendamustine, to determine if they exhibit similar potentiation by LND. As single agents LND, melphalan and these N-mustards exhibited the following activities in DB-1 melanoma xenografts; LND: 100% tumor surviving fraction (SF); chlorambucil: 100% SF; cyclophosphamide: 100% SF; bendamustine: 79% SF; melphalan: 41% SF. When combined with LND administered 40 min prior to administration of the N-mustard (to maximize intracellular acidification) the following responses were obtained; chlorambucil: 62% SF; cyclophosphamide: 42% SF; bendamustine: 36% SF; melphalan: 10% SF. The effect of LND on the activities of these N-mustards is generally attributed to acid stabilization of the aziridinium active intermediate, acid inhibition of glutathione-S-transferase, which acts as a scavenger of aziridinium, and acid inhibition of DNA repair by O6-alkyltransferase. Depletion of ATP by LND may also decrease multidrug resistance and increase tumor response. At similar maximum tolerated doses, our data indicate that melphalan is the most effective N-mustard in combination with LND when treating DB-1 melanoma in mice, but the choice of N-mustard for coadministration with LND will also depend on the relative toxicities of these agents, and remains to be determined. PMID:27285585

DNA Damage Induced by Alkylating Agents and Repair Pathways

PubMed Central

Kondo, Natsuko; Takahashi, Akihisa; Ono, Koji; Ohnishi, Takeo

2010-01-01

The cytotoxic effects of alkylating agents are strongly attenuated by cellular DNA repair processes, necessitating a clear understanding of the repair mechanisms. Simple methylating agents form adducts at N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O6-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O6-methylguanine-DNA methyltransferase, and O6MeG:T mispairs are recognized by the mismatch repair system (MMR). MMR cannot repair the O6MeG/T mispairs, which eventually lead to double-strand breaks. Bifunctional alkylating agents form interstrand cross-links (ICLs) which are more complex and highly cytotoxic. ICLs are repaired by complex of NER factors (e.g., endnuclease xeroderma pigmentosum complementation group F-excision repair cross-complementing rodent repair deficiency complementation group 1), Fanconi anemia repair, and homologous recombination. A detailed understanding of how cells cope with DNA damage caused by alkylating agents is therefore potentially useful in clinical medicine. PMID:21113301

Simulations of population dynamics of hemlock woolly adelgid and potential impact of biological control agents

Treesearch

Joseph S. Elkinton; Robert T. Trotter; Ann F. Paradis

2011-01-01

The hemlock woolly adelgid (Adelges tsugae) is a small invasive Hemipteran herbivore that threatens the continued presence and abundance of hemlock in eastern North America. Efforts to control the adelgid have focused on the introduction of classical biological control agents. These biological controls include six different species of predatory...

Mobile Agents Applications.

ERIC Educational Resources Information Center

Martins, Rosane Maria; Chaves, Magali Ribeiro; Pirmez, Luci; Rust da Costa Carmo, Luiz Fernando

2001-01-01

Discussion of the need to filter and retrieval relevant information from the Internet focuses on the use of mobile agents, specific software components which are based on distributed artificial intelligence and integrated systems. Surveys agent technology and discusses the agent building package used to develop two applications using IBM's Aglet…

Intelligent Software Agents: Sensor Integration and Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kulesz, James J; Lee, Ronald W

2013-01-01

Abstract In a post Macondo world the buzzwords are Integrity Management and Incident Response Management. The twin processes are not new but the opportunity to link the two is novel. Intelligent software agents can be used with sensor networks in distributed and centralized computing systems to enhance real-time monitoring of system integrity as well as manage the follow-on incident response to changing, and potentially hazardous, environmental conditions. The software components are embedded at the sensor network nodes in surveillance systems used for monitoring unusual events. When an event occurs, the software agents establish a new concept of operation at themore » sensing node, post the event status to a blackboard for software agents at other nodes to see , and then react quickly and efficiently to monitor the scale of the event. The technology addresses a current challenge in sensor networks that prevents a rapid and efficient response when a sensor measurement indicates that an event has occurred. By using intelligent software agents - which can be stationary or mobile, interact socially, and adapt to changing situations - the technology offers features that are particularly important when systems need to adapt to active circumstances. For example, when a release is detected, the local software agent collaborates with other agents at the node to exercise the appropriate operation, such as: targeted detection, increased detection frequency, decreased detection frequency for other non-alarming sensors, and determination of environmental conditions so that adjacent nodes can be informed that an event is occurring and when it will arrive. The software agents at the nodes can also post the data in a targeted manner, so that agents at other nodes and the command center can exercise appropriate operations to recalibrate the overall sensor network and associated intelligence systems. The paper describes the concepts and provides examples of real

Isoindoline-1,3-dione derivatives targeting cholinesterases: design, synthesis and biological evaluation of potential anti-Alzheimer's agents.

PubMed

Guzior, Natalia; Bajda, Marek; Rakoczy, Jurand; Brus, Boris; Gobec, Stanislav; Malawska, Barbara

2015-04-01

Alzheimer's disease is a fatal neurodegenerative disorder with a complex etiology. Because the available therapy brings limited benefits, the effective treatment for Alzheimer's disease remains the unmet challenge. Our aim was to develop a new series of donepezil-based compounds endowed with inhibitory properties against cholinesterases and β-amyloid aggregation. We designed the target compounds as dual binding site acetylcholinesterase inhibitors with N-benzylamine moiety interacting with the catalytic site of the enzyme and an isoindoline-1,3-dione fragment interacting with the peripheral anionic site of the enzyme. The results of pharmacological evaluation lead us to identify a compound 3b as the most potent and selective human acetylcholinesterase inhibitor (hAChE IC50=0.361μM). Kinetic studies revealed that 3b inhibited acetylcholinesterase in non-competitive mode. The result of the parallel artificial membrane permeability assay for the blood-brain barrier indicated that the compound 3b would be able to cross the blood-brain barrier and reach its biological targets in the central nervous system. The selected compound 3b represents a potential lead structure for further development of anti-Alzheimer's agents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Can immunostimulatory agents enhance the abscopal effect of radiotherapy?

PubMed

Levy, Antonin; Chargari, Cyrus; Marabelle, Aurelien; Perfettini, Jean-Luc; Magné, Nicolas; Deutsch, Eric

2016-07-01

Ionising radiation (IR) may harm cancer cells through a rare indirect out-of-field phenomenon described as the abscopal effect. Increasing evidence demonstrates that radiotherapy could be capable of generating tumour-specific immune responses. On the other hand, effects of IR also include inhibitory immune signals on the tumour microenvironment. Following these observations, and in the context of newly available immunostimulatory agents in metastatic cancers (anti-cytotoxic T lymphocyte-associated antigen 4 and programmed cell death protein-1 or -ligand 1 [PD1 or PDL-1]), there is a remarkable potential for synergistic combinations of IR with such agents that act through the reactivation of immune surveillance. Here, we present and discuss the pre-clinical and clinical rationale supporting the enhancement of the abscopal effect of IR on the blockade of immune checkpoints and discuss the evolving potential of immunoradiotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Civilian exposure to toxic agents: emergency medical response.

PubMed

Baker, David

2004-01-01

Civilian populations are at risk from exposure to toxic materials as a result of accidental or deliberate exposure. In addition to industrial hazards, toxic agents designed for use in warfare now are a potential hazard in everyday life through terrorist action. Civil emergency medical responders should be able to adapt their plans for dealing with casualties from hazardous materials (HazMat) to deal with the new threat. Chemical and biological warfare (CBW) and HazMat agents can be viewed as a continuous spectrum. Each of these hazards is characterized by qualities of toxicity, latency of action, persistency, and transmissibility. The incident and medical responses to release of any agent is determined by these characteristics. Chemical and biological wardare agents usually are classified as weapons of mass destruction, but strictly, they are agents of mass injury. The relationship between mass injury and major loss of life depends very much on the protection, organization, and emergency care provided. Detection of a civil toxic agent release where signs and symptoms in casualties may be the first indicator of exposure is different from the military situation where intelligence information and tuned detection systems generally will be available. It is important that emergency medical care should be given in the context of a specific action plan. Within an organized and protected perimeter, triage and decontamination (if the agent is persistent) can proceed while emergency medical care is provided at the same time. The provision of advanced life support (TOXALS) in this zone by protected and trained medical responders now is technically feasible using specially designed ventilation equipment. Leaving life support until after decontamination may have fatal consequences. Casualties from terrorist attacks also may suffer physical as well as toxic trauma and the medical response also should be capable of dealing with mixed injuries.

Biological warfare agents

PubMed Central

Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

2010-01-01

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

Spacecraft sanitation agent development

NASA Technical Reports Server (NTRS)

1972-01-01

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

Section 6—Mechanical Bioeffects in the Presence of Gas-Carrier Ultrasound Contrast Agents

PubMed Central

2007-01-01

This review addresses the issue of mechanical ultrasound-induced bioeffects in the presence of gas carrier contrast agents (GCAs). Here, the term “contrast agent” refers to those agents that provide ultrasound contrast by being composed of microbubbles, encapsulated or not, containing one or more gases. Provided in this section are summaries on how contrast agents work, some of their current uses, and the potential for bio-effects associated with their presence in an ultrasonic field. PMID:10680618

Gene transfer agents: phage-like elements of genetic exchange

PubMed Central

Lang, Andrew S.; Zhaxybayeva, Olga; Beatty, J. Thomas

2013-01-01

Horizontal gene transfer is important in the evolution of bacterial and archaeal genomes. An interesting genetic exchange process is carried out by diverse phage-like gene transfer agents (GTAs) that are found in a wide range of prokaryotes. Although GTAs resemble phages, they lack the hallmark capabilities that define typical phages, and they package random pieces of the producing cell’s genome. In this Review, we discuss the defining characteristics of the GTAs that have been identified to date, along with potential functions for these agents and the possible evolutionary forces that act on the genes involved in their production. PMID:22683880

THREE-DIMENSIONAL MODELING OF THE DYNAMICS OF THERAPEUTIC ULTRASOUND CONTRAST AGENTS

PubMed Central

Hsiao, Chao-Tsung; Lu, Xiaozhen; Chahine, Georges

2010-01-01

A 3-D thick-shell contrast agent dynamics model was developed by coupling a finite volume Navier-Stokes solver and a potential boundary element method flow solver to simulate the dynamics of thick-shelled contrast agents subjected to pressure waves. The 3-D model was validated using a spherical thick-shell model validated by experimental observations. We then used this model to study shell break-up during nonspherical deformations resulting from multiple contrast agent interaction or the presence of a nearby solid wall. Our simulations indicate that the thick viscous shell resists the contrast agent from forming a re-entrant jet, as normally observed for an air bubble oscillating near a solid wall. Instead, the shell thickness varies significantly from location to location during the dynamics, and this could lead to shell break-up caused by local shell thinning and stretching. PMID:20950929

Animals as sentinels of chemical terrorism agents: an evidence-based review.

PubMed

Rabinowitz, Peter; Wiley, James; Odofin, Lynda; Wilcox, Matthew; Dein, F Joshua

2008-02-01

The goal of this systematic review was to identify evidence that animals could serve as sentinels of an attack with a chemical terrorism agent. The biomedical literature was systematically searched for evidence that wild or domestic animals exposed to certain chemical weapons of terrorism had either greater susceptibility, shorter latency period, or increased exposure risk versus humans. Additionally, we searched for documented reports of such animals historically serving as sentinels for chemical warfare agents. For a small number of agents, there was limited evidence that domestic and/or wild animals could provide sentinel information to humans following an airborne attack with chemical agents, usually related to increased potential for environmental exposure. Some of this evidence was based on anecdotal case reports, and in many cases high quality chemical terrorism agent evidence regarding comparative susceptibility, exposure, and latency between humans and sentinel animal species was not found. Currently, there is insufficient evidence for routine use of animals as sentinels for airborne chemical warfare agents. At the same time, Poison Center surveillance systems should include animal calls, and greater communication between veterinarians and physicians could help with preparedness for a chemical terrorism attack. Further analysis of comparative chemical warfare agent toxicity between sentinel animal species and humans is needed.

Data Mining in the U.S. National Toxicology Program (NTP) Database Reveals a Potential Bias Regarding Liver Tumors in Rodents Irrespective of the Test Agent

PubMed Central

Ring, Matthias; Eskofier, Bjoern M.

2015-01-01

Long-term studies in rodents are the benchmark method to assess carcinogenicity of single substances, mixtures, and multi-compounds. In such a study, mice and rats are exposed to a test agent at different dose levels for a period of two years and the incidence of neoplastic lesions is observed. However, this two-year study is also expensive, time-consuming, and burdensome to the experimental animals. Consequently, various alternatives have been proposed in the literature to assess carcinogenicity on basis of short-term studies. In this paper, we investigated if effects on the rodents’ liver weight in short-term studies can be exploited to predict the incidence of liver tumors in long-term studies. A set of 138 paired short- and long-term studies was compiled from the database of the U.S. National Toxicology Program (NTP), more precisely, from (long-term) two-year carcinogenicity studies and their preceding (short-term) dose finding studies. In this set, data mining methods revealed patterns that can predict the incidence of liver tumors with accuracies of over 80%. However, the results simultaneously indicated a potential bias regarding liver tumors in two-year NTP studies. The incidence of liver tumors does not only depend on the test agent but also on other confounding factors in the study design, e.g., species, sex, type of substance. We recommend considering this bias if the hazard or risk of a test agent is assessed on basis of a NTP carcinogenicity study. PMID:25658102

Microbial glycolipoprotein-capped silver nanoparticles as emerging antibacterial agents against cholera.

PubMed

Gahlawat, Geeta; Shikha, Sristy; Chaddha, Baldev Singh; Chaudhuri, Saumya Ray; Mayilraj, Shanmugam; Choudhury, Anirban Roy

2016-02-01