Effects of biological control agents and exotic plant invasion on deer mouse populations

Treesearch

Yvette K. Ortega; Dean E. Pearson; Kevin S. McKelvey

2004-01-01

Exotic insects are commonly introduced as biological control agents to reduce densities of invasive exotic plants. Although current biocontrol programs for weeds take precautions to minimize ecological risks, little attention is paid to the potential nontarget effects of introduced food subsidies on native consumers. Previous research demonstrated that two gall flies (...

Enhancing biological control of basal stem rot disease (Ganoderma boninense) in oil palm plantations.

PubMed

Susanto, A; Sudharto, P S; Purba, R Y

2005-01-01

Basal Stem Rot (BSR) disease caused by Ganoderma boninense is the most destructive disease in oil palm, especially in Indonesia and Malaysia. The available control measures for BSR disease such as cultural practices and mechanical and chemical treatment have not proved satisfactory due to the fact that Ganoderma has various resting stages such as melanised mycelium, basidiospores and pseudosclerotia. Alternative control measures to overcome the Ganoderma problem are focused on the use of biological control agents and planting resistant material. Present studies conducted at Indonesian Oil Palm Research Institute (IOPRI) are focused on enhancing the use of biological control agents for Ganoderma. These activities include screening biological agents from the oil palm rhizosphere in order to evaluate their effectiveness as biological agents in glasshouse and field trials, testing their antagonistic activities in large scale experiments and eradicating potential disease inoculum with biological agents. Several promising biological agents have been isolated, mainly Trichoderma harzianum, T. viride, Gliocladium viride, Pseudomonas fluorescens, and Bacillus sp. A glasshouse and field trial for Ganoderma control indicated that treatment with T. harzianum and G. viride was superior to Bacillus sp. A large scale trial showed that the disease incidence was lower in a field treated with biological agents than in untreated fields. In a short term programme, research activities at IOPRI are currently focusing on selecting fungi that can completely degrade plant material in order to eradicate inoculum. Digging holes around the palm bole and adding empty fruit bunches have been investigated as ways to stimulate biological agents.

Biological agents and respiratory infections: Causative mechanisms and practice management.

PubMed

Takayanagi, Noboru

2015-09-01

Biological agents are increasingly being used to treat patients with immune-mediated inflammatory disease. In Japan, currently approved biological agents for patients with rheumatoid arthritis (RA) include tumor necrosis factor inhibitors, interleukin-6 receptor-blocking monoclonal antibody, and T-cell costimulation inhibitor. Rheumatologists have recognized that safety issues are critical aspects of treatment decisions in RA. Therefore, a wealth of safety data has been gathered from a number of sources, including randomized clinical trials and postmarketing data from large national registries. These data revealed that the most serious adverse events from these drugs are respiratory infections, especially pneumonia, tuberculosis, nontuberculous mycobacteriosis, and Pneumocystis jirovecii pneumonia, and that the most common risk factors associated with these respiratory infections are older age, concomitant corticosteroid use, and underlying respiratory comorbidities. Because of this background, in 2014, the Japanese Respiratory Society published their consensus statement of biological agents and respiratory disorders. This review summarizes this statement and adds recent evidence, especially concerning respiratory infections in RA patients, biological agents and respiratory infections, and practice management of respiratory infections in patients treated with biological agents. To decrease the incidence of infections and reduce mortality, we should know the epidemiology, risk factors, management, and methods of prevention of respiratory infections in patients receiving biological agents. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Risks of herpes zoster in patients with rheumatoid arthritis according to biologic disease-modifying therapy.

PubMed

Yun, Huifeng; Xie, Fenglong; Delzell, Elizabeth; Chen, Lang; Levitan, Emily B; Lewis, James D; Saag, Kenneth G; Beukelman, Timothy; Winthrop, Kevin; Baddley, John W; Curtis, Jeffrey R

2015-05-01

To evaluate whether the risks of herpes zoster (HZ) differed by biologic agents with different mechanisms of action (MOAs) in older rheumatoid arthritis (RA) patients. Using Medicare data from 2006-2011, among RA patients with prior biologic agent use and no history of cancer or other autoimmune diseases, this retrospective cohort study identified new treatment episodes of abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab. Followup started on initiation of the new biologic agent and ended at any of the following: first incidence of HZ, a 30-day gap in current exposure, death, a diagnosis of other autoimmune disease or cancer, loss of insurance coverage, or December 31, 2011. We calculated the proportion of RA patients vaccinated for HZ in each calendar year prior to biologic agent initiation and HZ incidence rate for each biologic agent. We compared HZ risks among therapies using Cox regression adjusted for potential confounders. Of 29,129 new biologic treatment episodes, 28.7% used abatacept, 15.9% adalimumab, 14.8% rituximab, 12.4% infliximab, 12.2% etanercept, 6.1% tocilizumab, 5.8% certolizumab, and 4.4% golimumab. The proportion of RA patients vaccinated for HZ prior to biologic agent initiation ranged from 0.4% in 2007 to 4.1% in 2011. We identified 423 HZ diagnoses with the highest HZ incidence rate for certolizumab (2.45 per 100 person-years) and the lowest for golimumab (1.61 per 100 person-years). Neither the crude incidence rate nor the adjusted hazard ratio differed significantly among biologic agents. Glucocorticoid use had a significant association with HZ. Among older patients with RA, the HZ risk was similar across biologic agents, including those with different MOAs. © 2015, American College of Rheumatology.

Systematic review of interleukin-12, interleukin-17, and interleukin-23 pathway inhibitors for the treatment of moderate-to-severe chronic plaque psoriasis: ustekinumab, briakinumab, tildrakizumab, guselkumab, secukinumab, ixekizumab, and brodalumab.

PubMed

Tausend, William; Downing, Christopher; Tyring, Stephen

2014-01-01

Monoclonal antibodies known as biologic agents specifically targeted against interleukin-12 (IL-12), interleukin-17A (IL-17), and interleukin-23 (IL-23) have been the focus of research for moderate-to-severe chronic plaque psoriasis in recent years. To discuss the immune-mediated model of psoriasis and to summarize current knowledge of the clinical efficacy and safety of new biologic agents for moderate-to-severe chronic plaque psoriasis. The PubMed database was searched for relevant articles on ustekinumab, briakinumab, tildrakizumab (MK-322), guselkumab, secukinumab, ixekizumab, and brodalumab published between January 2005 and July 2013. Fifty-five articles were identified. These studies suggest that the biologic agents specifically targeting IL-12, IL-17, and IL-23 are efficacious and safe in the treatment of moderate-to-severe psoriasis in adults. Current data from clinical trials suggest that biologic agents targeting IL-12, IL-17, and IL-23 are safe and efficacious drugs for use in moderate-to-severe chronic plaque psoriasis. Long-term data still need to be established.

A review and update on orphan drugs for the treatment of noninfectious uveitis

PubMed Central

You, Caiyun; Sahawneh, Haitham F; Ma, Lina; Kubaisi, Buraa; Schmidt, Alexander; Foster, C Stephen

2017-01-01

Introduction Uveitis, a leading cause of preventable blindness around the world, is a critically underserved disease in regard to the medications approved for use. Multiple immunomodulatory therapy (IMT) drugs are appropriate for uveitis therapy but are still off-label. These IMT agents, including antimetabolites, calcineurin inhibitors, alkylating agents, and biologic agents, have been designated as “orphan drugs” and are widely used for systemic autoimmune diseases or organ transplantation. Area covered The purpose of this paper is to comprehensively review and summarize the approved orphan drugs and biologics that are being used to treat systemic diseases and to discuss drugs that have not yet received approval as an “orphan drug for treating uveitis” by the US Food and Drug Administration (FDA). Our perspective IMT, as a steroid-sparing agent for uveitis patients, has shown promising clinical results. Refractory and recurrent uveitis requires combination IMT agents. IMT is continued for a period of 2 years while the patient is in remission before considering tapering medication. Our current goals include developing further assessments regarding the efficacy, optimal dose, and safety in efforts to achieve FDA approval for “on-label” use of current IMT agents and biologics more quickly and to facilitate insurance coverage and expand access to the products for this orphan disease. PMID:28203051

Recommendations for incorporating biologicals into management of moderate to severe plaque psoriasis: individualized patient approaches.

PubMed

Langley, Richard G; Ho, Vincent; Lynde, Charles; Papp, Kim A; Poulin, Yves; Shear, Neil; Toole, Jack; Zip, Catherine

2006-01-01

Psoriasis is a T-cell mediated skin disease that affects approximately 2% of the population worldwide. Despite the prevalence of the disease and long-standing efforts to develop strategies to treat it, there is a need for safe and effective therapies to treat psoriasis, particularly the more severe forms. Biological agents such as alefacept, efalizumab, etanercept, and infliximab have been recognized as a class of treatment distinct from other forms of therapy in the treatment algorithm of psoriasis. Recent national and international consensus meetings have developed statements that position biological agents as an important addition to the treatment armamentarium for moderate to severe psoriasis, along with phototherapy and traditional systemic agents. There has been consensus that treatment should be individualized to each patient's needs and circumstances. Biological agents offer the hope of safe, effective, long-term management of moderate to severe psoriasis. As new agents receive approval from Health Canada, the available range of therapeutic options for treating this chronic disease will broaden. A Canadian Psoriasis Expert Panel recently convened in February 2005 to analyze, based on a series of clinical case scenarios, the indications, contraindications, and considerations for and against each of the four biological agents, derived from product labelling, where available, and from the efficacy and safety data from phase 3 and earlier clinical trials, as well as post-marketing reports. The Panel has formulated a set of recommendations for incorporating these biological agents into the current treatment paradigm of moderate to severe plaque psoriasis and has identified the preferred biological agents for each patient based on individual needs and circumstances.

Update on the management of ulcerative colitis.

PubMed

Taba Taba Vakili, Sahar; Taher, Mohammad; Ebrahimi Daryani, Nasser

2012-01-01

The present treatment goals for inflammatory bowel diseases (IBD) especially ulcerative colitis (UC) include rapid induction of clinical remission, steroid-free maintenance of clinical remission, mucosal healing and improvement of quality of life in UC patients. Immunomodulators have been reserved for steroid- dependent or steroid- refractory UC patients. Among these agents, azathioprine/6-mercaptopurine should be used for maintenance of remission in quiescent UC. Calcineurin inhibitors can be prescribed as a short-term rescue therapy in steroid- refractory UC patients, but the long term efficacy of these agents remains unclear. According to retrospective studies, methotraxate is not recommended for inducing and maintaining remission in UC. Novel biological therapies targeting different specific immunological pathways continue to be developed and introduced for a variety of clinical scenarios in IBD. Infliximab is currently used for induction and maintenance therapy in patients who have moderately to severely active UC with an inadequate response to conventional agents such as aminosalicylates, corticosteroids, or immunomodulators. Other anti-TNF agents and biologic therapies are undergoing evaluation in clinical trials for their efficacy in IBD. Most patients who start biologics should continue treatment for the foreseeable future and potential consequences of discontinuation should be discussed with individual patients. Currently, data do not exist to administer biologics as first-line therapy in UC. Emerging data suggest that biologics may have the potential to prevent complications and limit disease progression. If such benefits are proven, biologics may be used in the future to modulate subclinical inflammation and to prevent the development of clinical disease.

A Review of Biological Agent Sampling Methods and ...

EPA Pesticide Factsheets

Report This study was conducted to evaluate current sampling and analytical capabilities, from a time and resource perspective, for a large-scale biological contamination incident. The analysis will be useful for strategically directing future research investment.

Enhancement of biological control agents for use against forest insect pests and diseases through biotechnology

NASA Technical Reports Server (NTRS)

Slavicek, James M.

1991-01-01

Research and development efforts in our research group are focused on the generation of more efficacious biological control agents through the techniques of biotechnology for use against forest insect pests and diseases. Effective biological controls for the gypsy moth and for tree fungal wilt pathogens are under development. The successful use of Gypchek, a formulation of the Lymantria dispar nuclear polyhedrosis virus (LdNPV), in gypsy moth control programs has generated considerable interest in that agent. As a consequence of its specificity, LdPNV has negligible adverse ecological impacts compared to most gypsy moth control agents. However, LdNPV is not competitive with other control agents in terms of cost and efficacy. We are investigating several parameters of LdNPV replication and polyhedra production in order to enhance viral potency and efficacy thus mitigating the current disadvantages of LdNPV for gypsy moth control, and have identified LdNPV variants that will facilitate these efforts. Tree endophytic bacteria that synthesize antifungal compounds were identified and an antibiotic compound from one of these bacteria was characterized. The feasibility of developing tree endophytes as biological control agents for tree vascular fungal pathogens is being investigated.

Recent biological trends in management of fracture non-union

PubMed Central

Emara, Khaled M; Diab, Ramy Ahmed; Emara, Ahmed Khaled

2015-01-01

Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. Currently, there is a plethora of different strategies to augment the impaired or “insufficient” bone-regeneration process, including the “gold standard” autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved “local” strategies in terms of tissue engineering and gene therapy, or even “systemic” enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications. PMID:26396938

Current and Developing Technologies for Monitoring Agents of Bioterrorism and Biowarfare

PubMed Central

Lim, Daniel V.; Simpson, Joyce M.; Kearns, Elizabeth A.; Kramer, Marianne F.

2005-01-01

Recent events have made public health officials acutely aware of the importance of rapidly and accurately detecting acts of bioterrorism. Because bioterrorism is difficult to predict or prevent, reliable platforms to rapidly detect and identify biothreat agents are important to minimize the spread of these agents and to protect the public health. These platforms must not only be sensitive and specific, but must also be able to accurately detect a variety of pathogens, including modified or previously uncharacterized agents, directly from complex sample matrices. Various commercial tests utilizing biochemical, immunological, nucleic acid, and bioluminescence procedures are currently available to identify biological threat agents. Newer tests have also been developed to identify such agents using aptamers, biochips, evanescent wave biosensors, cantilevers, living cells, and other innovative technologies. This review describes these current and developing technologies and considers challenges to rapid, accurate detection of biothreat agents. Although there is no ideal platform, many of these technologies have proved invaluable for the detection and identification of biothreat agents. PMID:16223949

Aggressive treatment of early rheumatoid arthritis: recognizing the window of opportunity and treating to target goals.

PubMed

Resman-Targoff, Beth H; Cicero, Marco P

2010-11-01

Evidence supports the use of aggressive therapy for patients with early rheumatoid arthritis (RA). Clinical outcomes in patients with early RA can improve with a treat-to-target approach that sets the goal at disease remission. The current selection of antirheumatic therapies, including conventional and biologic disease-modifying antirheumatic drugs (DMARDs), has made disease remission a realistic target for patients with early RA. The challenge is selecting the optimal antirheumatic drug or combination of drugs for initial and subsequent therapy to balance the clinical benefits, risks, and economic considerations. In some cases, the use of biologic agents as part of the treatment regimen has shown superior results compared with conventional DMARDs alone in halting the progression of disease, especially in reducing radiographic damage. However, the use of biologic agents as initial therapy is challenged by cost-effectiveness analyses, which favor the use of conventional DMARDs. The use of biologic agents may be justified in certain patients with poor prognostic factors or those who experience an inadequate response to conventional DMARDs as a means to slow or halt disease progression and its associated disability. In these cases, the higher cost of treatment with biologic agents may be offset by decreased societal costs, such as lost work productivity, and increased health-related quality of life. Further research is needed to understand optimal strategies for balancing costs, benefits, and risks of antirheumatic drugs. Some key questions are (1) when biologic agents are appropriate for initial therapy, and (2) when to conclude that response to conventional DMARDs is inadequate and biologic agents should be initiated.

Mass spectrometry for the detection of bioterrorism agents: from environmental to clinical applications.

PubMed

Duriez, Elodie; Armengaud, Jean; Fenaille, François; Ezan, Eric

2016-03-01

In the current context of international conflicts and localized terrorist actions, there is unfortunately a permanent threat of attacks with unconventional warfare agents. Among these, biological agents such as toxins, microorganisms, and viruses deserve particular attention owing to their ease of production and dissemination. Mass spectrometry (MS)-based techniques for the detection and quantification of biological agents have a decisive role to play for countermeasures in a scenario of biological attacks. The application of MS to every field of both organic and macromolecular species has in recent years been revolutionized by the development of soft ionization techniques (MALDI and ESI), and by the continuous development of MS technologies (high resolution, accurate mass HR/AM instruments, novel analyzers, hybrid configurations). New possibilities have emerged for exquisite specific and sensitive detection of biological warfare agents. MS-based strategies for clinical application can now address a wide range of analytical questions mainly including issues related to the complexity of biological samples and their available volume. Multiplexed toxin detection, discovery of new markers through omics approaches, and identification of untargeted microbiological or of novel molecular targets are examples of applications. In this paper, we will present these technological advances along with the novel perspectives offered by omics approaches to clinical detection and follow-up. Copyright © 2016 John Wiley & Sons, Ltd.

Pharmacotherapy of Acute Lung Injury and Acute Respiratory Distress Syndrome

PubMed Central

Raghavendran, Krishnan; Pryhuber, Gloria S.; Chess, Patricia R.; Davidson, Bruce A.; Knight, Paul R.; Notter, Robert H.

2009-01-01

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are characterized by rapid-onset respiratory failure following a variety of direct and indirect insults to the parenchyma or vasculature of the lungs. Mortality from ALI/ARDS is substantial, and current therapy primarily emphasizes mechanical ventilation and judicial fluid management plus standard treatment of the initiating insult and any known underlying disease. Current pharmacotherapy for ALI/ARDS is not optimal, and there is a significant need for more effective medicinal chemical agents for use in these severe and lethal lung injury syndromes. To facilitate future chemical-based drug discovery research on new agent development, this paper reviews present pharmacotherapy for ALI/ARDS in the context of biological and biochemical drug activities. The complex lung injury pathophysiology of ALI/ARDS offers an array of possible targets for drug therapy, including inflammation, cell and tissue injury, vascular dysfunction, surfactant dysfunction, and oxidant injury. Added targets for pharmacotherapy outside the lungs may also be present, since multiorgan or systemic pathology is common in ALI/ARDS. The biological and physiological complexity of ALI/ARDS requires the consideration of combined-agent treatments in addition to single-agent therapies. A number of pharmacologic agents have been studied individually in ALI/ARDS, with limited or minimal success in improving survival. However, many of these agents have complementary biological/biochemical activities with the potential for synergy or additivity in combination therapy as discussed in this article. PMID:18691048

Hepatocellular Carcinoma: Molecular Biology and Therapy

PubMed Central

Abou-Alfa, Ghassan

2007-01-01

Advanced and metastatic hepatocellular carcinomas (HCC) are challenging to treat, and no cytotoxic agents have impacted survival. The underlying liver cirrhosis that commonly accompanies HCC provides an additional challenge; indeed, functional scoring of cirrhosis and HCC is a critical component of patient evaluation. Currently, the molecular biology and pathogenesis of HCC are being increasingly investigated, which may lead to better understanding of the evolution of the disease, especially differing etiologies and identification of survival genes that may affect outcome. Early studies of targeted therapies in HCC have shown disease stabilization, and an increased understanding of the mechanism(s) of these novel agents combined with correlative studies may lead to the identification of an active agent or combination of agents that impacts the natural history of HCC. PMID:17178294

Hemostatic strategies for traumatic and surgical bleeding

PubMed Central

Behrens, Adam M.; Sikorski, Michael J.; Kofinas, Peter

2017-01-01

Wide interest in new hemostatic approaches has stemmed from unmet needs in the hospital and on the battlefield. Many current commercial hemostatic agents fail to fulfill the design requirements of safety, efficacy, cost, and storage. Academic focus has led to the improvement of existing strategies as well as new developments. This review will identify and discuss the three major classes of hemostatic approaches: biologically derived materials, synthetically derived materials, and intravenously administered hemostatic agents. The general class is first discussed, then specific approaches discussed in detail, including the hemostatic mechanisms and the advancement of the method. As hemostatic strategies evolve and synthetic-biologic interactions are more fully understood, current clinical methodologies will be replaced. PMID:24307256

Biologically Targeted Therapeutics in Pediatric Brain Tumors

PubMed Central

Nageswara Rao, Amulya A.; Scafidi, Joseph; Wells, Elizabeth M.; Packer, Roger J.

2013-01-01

Pediatric brain tumors are often difficult to cure and involve significant morbidity when treated with traditional treatment modalities, including neurosurgery, conventional chemotherapy, and radiotherapy. During the past two decades, a clearer understanding of tumorigenesis, molecular growth pathways, and immune mechanisms in the pathogenesis of cancer has opened up promising avenues for therapy. Pediatric clinical trials with novel biologic agents are underway to treat various pediatric brain tumors, including high and low grade gliomas and embryonal tumors. As the therapeutic potential of these agents undergoes evaluation, their toxicity profiles are also becoming better understood. These agents have potentially better central nervous system penetration and lower toxicity profiles compared with conventional chemotherapy. In infants and younger children, biologic agents may prove to be of equal or greater efficacy compared with traditional chemotherapy and radiation therapy, and may reduce the deleterious side effects of traditional therapeutics on the developing brain. Molecular pathways implicated in pediatric brain tumors, agents that target these pathways, and current clinical trials are reviewed. Associated neurologic toxicities will be discussed subsequently. Considerable work is needed to establish the efficacy of these agents alone and in combination, but pediatric neurologists should be aware of these agents and their rationale. PMID:22490764

Biologically targeted therapeutics in pediatric brain tumors.

PubMed

Nageswara Rao, Amulya A; Scafidi, Joseph; Wells, Elizabeth M; Packer, Roger J

2012-04-01

Pediatric brain tumors are often difficult to cure and involve significant morbidity when treated with traditional treatment modalities, including neurosurgery, conventional chemotherapy, and radiotherapy. During the past two decades, a clearer understanding of tumorigenesis, molecular growth pathways, and immune mechanisms in the pathogenesis of cancer has opened up promising avenues for therapy. Pediatric clinical trials with novel biologic agents are underway to treat various pediatric brain tumors, including high and low grade gliomas and embryonal tumors. As the therapeutic potential of these agents undergoes evaluation, their toxicity profiles are also becoming better understood. These agents have potentially better central nervous system penetration and lower toxicity profiles compared with conventional chemotherapy. In infants and younger children, biologic agents may prove to be of equal or greater efficacy compared with traditional chemotherapy and radiation therapy, and may reduce the deleterious side effects of traditional therapeutics on the developing brain. Molecular pathways implicated in pediatric brain tumors, agents that target these pathways, and current clinical trials are reviewed. Associated neurologic toxicities will be discussed subsequently. Considerable work is needed to establish the efficacy of these agents alone and in combination, but pediatric neurologists should be aware of these agents and their rationale. Copyright © 2012 Elsevier Inc. All rights reserved.

Assessing Probabilistic Risk Assessment Approaches for Insect Biological Control Introductions.

PubMed

Kaufman, Leyla V; Wright, Mark G

2017-07-07

The introduction of biological control agents to new environments requires host specificity tests to estimate potential non-target impacts of a prospective agent. Currently, the approach is conservative, and is based on physiological host ranges determined under captive rearing conditions, without consideration for ecological factors that may influence realized host range. We use historical data and current field data from introduced parasitoids that attack an endemic Lepidoptera species in Hawaii to validate a probabilistic risk assessment (PRA) procedure for non-target impacts. We use data on known host range and habitat use in the place of origin of the parasitoids to determine whether contemporary levels of non-target parasitism could have been predicted using PRA. Our results show that reasonable predictions of potential non-target impacts may be made if comprehensive data are available from places of origin of biological control agents, but scant data produce poor predictions. Using apparent mortality data rather than marginal attack rate estimates in PRA resulted in over-estimates of predicted non-target impact. Incorporating ecological data into PRA models improved the predictive power of the risk assessments.

Assessing Probabilistic Risk Assessment Approaches for Insect Biological Control Introductions

PubMed Central

Kaufman, Leyla V.; Wright, Mark G.

2017-01-01

The introduction of biological control agents to new environments requires host specificity tests to estimate potential non-target impacts of a prospective agent. Currently, the approach is conservative, and is based on physiological host ranges determined under captive rearing conditions, without consideration for ecological factors that may influence realized host range. We use historical data and current field data from introduced parasitoids that attack an endemic Lepidoptera species in Hawaii to validate a probabilistic risk assessment (PRA) procedure for non-target impacts. We use data on known host range and habitat use in the place of origin of the parasitoids to determine whether contemporary levels of non-target parasitism could have been predicted using PRA. Our results show that reasonable predictions of potential non-target impacts may be made if comprehensive data are available from places of origin of biological control agents, but scant data produce poor predictions. Using apparent mortality data rather than marginal attack rate estimates in PRA resulted in over-estimates of predicted non-target impact. Incorporating ecological data into PRA models improved the predictive power of the risk assessments. PMID:28686180

Insect pathogens as biological control agents: back to the future

USDA-ARS?s Scientific Manuscript database

In the past 15 years a number of successes and setbacks have taken place regarding development and use of microbial control agents. In this Forum paper we present current information on development, use and future directions of entomopathogenic virus, bacteria, fungi and nematodes as components of i...

Fungal pollution of indoor environments and its management.

PubMed

Haleem Khan, A A; Mohan Karuppayil, S

2012-10-01

Indoor environments play important roles in human health. The health hazards posed by polluted indoor environments include allergy, infections and toxicity. Life style changes have resulted in a shift from open air environments to air tight, energy efficient, environments, in which people spend a substantial portion of their time. Most indoor air pollution comes from the hazardous non biological agents and biological agents. Fungi are ubiquitous in distribution and are a serious threat to public health in indoor environments. In this communication, we have reviewed the current status on biotic indoor air pollution, role of fungi as biological contaminants and their impact on human health.

Fungal pollution of indoor environments and its management

PubMed Central

Haleem Khan, A.A.; Mohan Karuppayil, S.

2012-01-01

Indoor environments play important roles in human health. The health hazards posed by polluted indoor environments include allergy, infections and toxicity. Life style changes have resulted in a shift from open air environments to air tight, energy efficient, environments, in which people spend a substantial portion of their time. Most indoor air pollution comes from the hazardous non biological agents and biological agents. Fungi are ubiquitous in distribution and are a serious threat to public health in indoor environments. In this communication, we have reviewed the current status on biotic indoor air pollution, role of fungi as biological contaminants and their impact on human health. PMID:23961203

Need for new technologies for detection of adventitious agents in vaccines and other biological products.

PubMed

Mallet, Laurent; Gisonni-Lex, Lucy

2014-01-01

From an industrial perspective, the conventional in vitro and in vivo assays used for detection of viral contaminants have shown their limitations, as illustrated by the unfortunate detection of porcine circovirus contamination in a licensed rotavirus vaccine. This contamination event illustrates the gaps within the existing adventitious agent strategy and the potential use of new broader molecular detection methods. This paper serves to summarize current testing approaches and challenges, along with opportunities for the use of these new technologies. Testing of biological products is required to ensure the safety of patients. Recently, a licensed vaccine was found to be contaminated with a virus. This contamination did not cause a safety concern to the patients; however, it highlights the need for using new testing methods to control our biological products. This paper introduces the benefits of these new tests and outlines the challenges with the current tests. © PDA, Inc. 2014.

The medicinal chemistry of botulinum, ricin and anthrax toxins.

PubMed

Hicks, Rickey P; Hartell, Mark G; Nichols, Daniel A; Bhattacharjee, Apurba K; van Hamont, John E; Skillman, Donald R

2005-01-01

The potential use of weapons of mass destruction (nuclear, biological or chemical) by terrorist organizations represents a major threat to world peace and safety. Only a limited number of vaccines are available to protect the general population from the medical consequences of these weapons. In addition there are major health concerns associated with a pre-exposure mass vaccination of the general population. To reduce or eliminate the impact of these terrible threats, new drugs must be developed to safely treat individuals exposed to these agents. A review of all therapeutic agents under development for the treatment of the illnesses and injuries that result from exposure to nuclear, biological or chemical warfare agents is beyond the scope of any single article. The intent here is to provide a focused review for medicinal and organic chemists of three widely discussed and easily deployed biological warfare agents, botulinum neurotoxin and ricin toxins and the bacteria Bacillus anthracis. Anthrax will be addressed because of its similarity in both structure and mechanism of catalytic activity with botulinum toxin. The common feature of these three agents is that they exhibit their biological activity via toxin enzymatic hydrolysis of a specific bond in their respective substrate molecules. A brief introduction to the history of each of the biological warfare agents is presented followed by a discussion on the mechanisms of action of each at the molecular level, and a review of current potential inhibitors under investigation.

Status of biological control projects on terrestrial invasive alien weeds in California

USDA-ARS?s Scientific Manuscript database

In cooperation with foreign scientists, we are currently developing new classical biological control agents for five species of invasive alien terrestrial weeds. Cape-Ivy. A gall-forming fly, Parafreutreta regalis, and a stem-boring moth, Digitivalva delaireae, have been favorably reviewed by TAG...

Biologic agents in rheumatology: unmet issues after 200 trials and $200 billion sales.

PubMed

Ioannidis, John P A; Karassa, Fotini B; Druyts, Eric; Thorlund, Kristian; Mills, Edward J

2013-11-01

Anti-TNF agents and other biologic therapies are widely prescribed for a variety of indications, with total sales that exceed $200 billion to date. In rheumatic diseases, biologic agents have now been studied in more than 200 randomized clinical trials and over 100 subsequent meta-analyses; however, the information obtained does not always meet the needs of patients and clinicians. In this Review, we discuss the current issues concerning the evidence derived from such studies: potential biases favouring positive results; a paucity of head-to-head comparisons between biologically active agents; overwhelming involvement of manufacturer sponsors in trials and in the synthesis of the evidence; the preference for trials with limited follow-up; and the potential for spurious findings on adverse events, leading to endless debates about malignancy risk. We debate the responsibilities of regulatory authorities, the pharmaceutical industry and academia in attempting to solve these shortcomings and challenges. We propose that improvements in the evidence regarding biologic treatments that are continually being added to the therapeutic armamentarium for rheumatic diseases might require revisiting the design and conduct of studies. For example, trials with long-term follow-up that are independent of the pharmaceutical industry, head-to-head comparisons of therapeutic agents and the use of rigorous clinical outcomes should be considered, and public availability of raw data endorsed.

9 CFR 113.113 - Autogenous biologics.

Code of Federal Regulations, 2014 CFR

2014-01-01

... herd of origin and which there is reason to believe are the causative agent(s) of the current disease... for use in herds adjacent to the herd of origin, when adjacent herds are considered to be at risk. To request authorization to prepare a product for use in herds adjacent to the herd of origin, the...

9 CFR 113.113 - Autogenous biologics.

Code of Federal Regulations, 2012 CFR

2012-01-01

... herd of origin and which there is reason to believe are the causative agent(s) of the current disease... for use in herds adjacent to the herd of origin, when adjacent herds are considered to be at risk. To request authorization to prepare a product for use in herds adjacent to the herd of origin, the...

9 CFR 113.113 - Autogenous biologics.

Code of Federal Regulations, 2013 CFR

2013-01-01

... herd of origin and which there is reason to believe are the causative agent(s) of the current disease... for use in herds adjacent to the herd of origin, when adjacent herds are considered to be at risk. To request authorization to prepare a product for use in herds adjacent to the herd of origin, the...

Emergence of Laricobius nigrinus (Fender) (Coleoptera: Derodontidae) in the North Georgia mountains.

Treesearch

C.E. Jones; James Hanula; S.K. Braman

2014-01-01

Hemlock woolly adelgid, Adelges tsugae Annand, is currently found throughout most of the range of eastern hemlock, Tsuga Canadensis (L.) Carriere. Biological control agents have been released in attempts to control this pest, but how different climates influence the efficacy and survival of these agents has not been studied.

Status of biological control projects on yellow starthistle, Russian thistle, Scotch thistle, Cape-ivy and French broom

USDA-ARS?s Scientific Manuscript database

The USDA-ARS quarantine laboratory in Albany, CA, in cooperation with foreign scientists, is currently developing classical biological control agents for five species of invasive alien terrestrial weeds. Host specificity testing of the yellow starthistle rosette weevil, Ceratapion basicorne, indica...

Insect-gene-activity detection system for chemical and biological warfare agents and toxic industrial chemicals

NASA Astrophysics Data System (ADS)

Mackie, Ryan S.; Schilling, Amanda S.; Lopez, Arturo M.; Rayms-Keller, Alfredo

2002-02-01

Detection of multiple chemical and biological weapons (CBW) agents and/or complex mixtures of toxic industrial chemicals (TIC) is imperative for both the commercial and military sectors. In a military scenario, a multi-CBW attack would create confusion, thereby delaying decontamination and therapeutic efforts. In the commercial sector, polluted sites invariably contain a mixture of TIC. Novel detection systems capable of detecting CBW and TIC are sorely needed. While it may be impossible to build a detector capable of discriminating all the possible combinations of CBW, a detection system capable of statistically predicting the most likely composition of a given mixture is within the reach of current emerging technologies. Aquatic insect-gene activity may prove to be a sensitive, discriminating, and elegant paradigm for the detection of CBW and TIC. We propose to systematically establish the expression patterns of selected protein markers in insects exposed to specific mixtures of chemical and biological warfare agents to generate a library of biosignatures of exposure. The predicting capabilities of an operational library of biosignatures of exposures will allow the detection of emerging novel or genetically engineered agents, as well as complex mixtures of chemical and biological weapons agents. CBW and TIC are discussed in the context of war, terrorism, and pollution.

Current trends in pharmacy benefit designs: a threat to disease management in chronic complex diseases.

PubMed

Owens, Gary; Emons, Matthew F; Christian-Herman, Jennifer; Lawless, Grant

2007-04-01

With a focus on those patients who are candidates for treatment with biologic agents, we review the impact that current pharmacy benefit trends have on patients with chronic complex diseases and how they affect opportunities for disease management in this unique patient population. Dramatic increases in health care costs have led to a variety of strategies to manage cost. Many of these strategies either limit access to care or increase the patient's responsibility for choosing and paying for care, especially for medications. These strategies have a disproportionate impact on patients with chronic complex diseases, particularly those who require the use of biologic medications. A fundamental prerequisite of disease management has been coverage of disease-modifying therapies. If current pharmacy benefit trends continue, unintended consequences will likely occur including lost opportunities for disease management. Current pharmacy benefit trends could adversely impact disease management, particularly for patients requiring the use of biologic agents. Health plans should consider innovative benefit designs that reflect an appropriate level of cost sharing across all key stake-holders, ensuring appropriate access to needed therapies. Additional research is needed to clarify the value of newer approaches to therapies or benefit design changes.

Update on the use of systemic biologic agents in the treatment of noninfectious uveitis

PubMed Central

Pasadhika, Sirichai; Rosenbaum, James T

2014-01-01

Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet’s disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine) may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet’s disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present work aims to provide a broad and updated review of the current and in-development systemic biologic agents for the treatment of noninfectious uveitis. PMID:24600203

Biological Agents

EPA Pesticide Factsheets

These chemicals or organisms increase the rate at which microorganisms break down complex compounds into simpler products (biodegredation). Two bioremediation technologies currently being used for oil spill cleanups are fertilization and seeding.

Management of Behçet's syndrome.

PubMed

Ozguler, Yesim; Hatemi, Gulen

2016-01-01

Current trends in the management of Behçet's syndrome will be reviewed in this article. Biologic agents have gained increasing importance over the years in the management of Behçet's syndrome. Long-term results of observational studies have shown that anti-tumor necrosis factor agents may be effective in Behçet's syndrome patients with refractory eye involvement. Case series reporting about use of anti-tumor necrosis factor agents in vascular and gastrointestinal involvement have also shown good results. Caution is required for infectious complications with these agents. Apremilast is an immunomodulatory agent that works through phosphodiesterase 4 inhibition. A randomized controlled trial has shown that it is effective for the management of oral and genital ulcers and is generally well tolerated. The outcome of Behçet's syndrome with major organ involvement has improved with more effective management strategies, especially with the use of biologic agents in severe cases. Controlled trials are needed to guide physicians in making treatment decisions.

The weapon potential of a microbe.

PubMed

Casadevall, Arturo; Pirofski, Liise-anne

2004-06-01

The designation of a microbe as a potential biological weapon poses the vexing question of how such a decision is made given the many pathogenic microbes that cause disease. Analysis of the properties of microbes that are currently considered biological weapons against humans revealed no obvious relationship to virulence, except that all are pathogenic for humans. Notably, the weapon potential of a microbe rather than its pathogenic properties or virulence appeared to be the major consideration when categorizing certain agents as biological weapons. In an effort to standardize the assessment of the risk that is posed by microbes as biological warfare agents using the basic principles of microbial communicability (defined here as a parameter of transmission) and virulence, a simple formula is proposed for estimating the weapon potential of a microbe.

Influence of temperature on the reproductive and developmental biology of Ontsira mellipes (Hymenoptera: Braconidae): Implications for biological control of the Asian Longhorned Beetle (Coleoptera: Cerambycidae)

USDA-ARS?s Scientific Manuscript database

Ontsira mellipes Ashmead (Hymenoptera: Braconidae) is a North American parasitoid that develops on the invasive pest, Anoplophora glabripennis (Moltschulsky) (Coleoptera: Cerambycidae) under laboratory conditions, and is currently being considered as a potential new-association biocontrol agent. In ...

Retroperitoneal Liposarcoma: Current Insights in Diagnosis and Treatment

PubMed Central

Matthyssens, Lucas E.; Creytens, David; Ceelen, Wim P.

2015-01-01

Retroperitoneal liposarcoma (RLS) is a rare, biologically heterogeneous tumor that present considerable challenges due to its size and deep location. As a consequence, the majority of patients with high-grade RLS will develop locally recurrent disease following surgery, and this constitutes the cause of death in most patients. Here, we review current insights and controversies regarding histology, molecular biology, extent of surgery, (neo)adjuvant treatment, and systemic treatment including novel targeted agents in RLS. PMID:25713799

Interim Consequence Management Guidance for a Wide-Area Biological Attack

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

Raber, Ellen; Kirvel, Robert; MacQueen, Don

2011-05-17

The Interagency Biological Restoration Demonstration (IBRD) program is a collaborative, interagency effort co-chaired by the Department of Homeland Security and Department of Defense aimed at improving the nation‘s ability to respond to and recover from a large-scale, wide-area, domestic attack involving the release of an environmentally persistent biological warfare agent. The program is focused on understanding interactions between the civilian and military sectors, and in building mutual support to carry out such remediations. This Interim Consequence Management Guidance document provides guidance for decisionmakers in executing activities required to respond to and recover from a biological incident affecting a wide urbanmore » area insofar as information is currently available. The spore-forming bacterium Bacillus anthracis is discussed as the biological agent of primary concern because it is the most difficult of known bioterrorism agents to inactivate and is considered to be one of the key threat agents. Most other biological threat agents are much easier to remediate, and in many cases, inactivation would occur naturally within days as a result of environmental exposure; however, the framework and operational questions that need to be addressed are expected to remain the same. The guidance in this document is applicable to (1) enclosed facilities, such as commercial, residential, and continental U.S. military facilities; (2) semi-enclosed facilities, such as subways and public transit facilities; (3) outdoor areas (both localized and wide area), such as building exteriors, streets, parks, and other open spaces; (4) drinking water facilities; and (5) drinking water sources. This document follows an interagency framework [Planning Guidance for Recovery Following Biological Incidents (DHS and EPA 2009)]—which considered Raber et al. (2002) in its development—but takes the framework to a more operational level and provides guidance at key action and decision points.« less

Synthesis and biological activity of imidazopyridine anticoccidial agents: part I.

PubMed

Scribner, Andrew; Dennis, Richard; Hong, Jean; Lee, Shuliang; McIntyre, Donald; Perrey, David; Feng, Dennis; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

2007-01-01

Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we present the synthesis and biological activity of imidazo[1,2-a]pyridine anticoccidial agents. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

Improved Dye Stability in Single-Molecule Fluorescence Experiments

NASA Astrophysics Data System (ADS)

EcheverrÍa Aitken, Colin; Marshall, R. Andrew; Pugi, Joseph D.

Complex biological systems challenge existing single-molecule methods. In particular, dye stability limits observation time in singlemolecule fluorescence applications. Current approaches to improving dye performance involve the addition of enzymatic oxygen scavenging systems and small molecule additives. We present an enzymatic oxygen scavenging system that improves dye stability in single-molecule experiments. Compared to the currently-employed glucose-oxidase/catalase system, the protocatechuate-3,4-dioxygenase system achieves lower dissolved oxygen concentration and stabilizes single Cy3, Cy5, and Alexa488 fluorophores. Moreover, this system possesses none of the limitations associated with the glucose oxidase/catalase system. We also tested the effects of small molecule additives in this system. Biological reducing agents significantly destabilize the Cy5 fluorophore as a function of reducing potential. In contrast, anti-oxidants stabilize the Cy3 and Alexa488 fluorophores. We recommend use of the protocatechuate-3,4,-dioxygenase system with antioxidant additives, and in the absence of biological reducing agents. This system should have wide application to single-molecule fluorescence experiments.

Review of Pasteuria penetrans: Biology, Ecology, and Biological Control Potential.

PubMed

Chen, Z X; Dickson, D W

1998-09-01

Pasteuria penetrans is a mycelial, endospore-forming, bacterial parasite that has shown great potential as a biological control agent of root-knot nematodes. Considerable progress has been made during the last 10 years in understanding its biology and importance as an agent capable of effectively suppressing root-knot nematodes in field soil. The objective of this review is to summarize the current knowledge of the biology, ecology, and biological control potential of P. penetrans and other Pasteuria members. Pasteuria spp. are distributed worldwide and have been reported from 323 nematode species belonging to 116 genera of free-living, predatory, plant-parasitic, and entomopathogenic nematodes. Artificial cultivation of P. penetrans has met with limited success; large-scale production of endospores depends on in vivo cultivation. Temperature affects endospore attachment, germination, pathogenesis, and completion of the life cycle in the nematode pseudocoelom. The biological control potential of Pasteuria spp. have been demonstrated on 20 crops; host nematodes include Belonolaimus longicaudatus, Heterodera spp., Meloidogyne spp., and Xiphinema diversicaudatum. Pasteuria penetrans plays an important role in some suppressive soils. The efficacy of the bacterium as a biological control agent has been examined. Approximately 100,000 endospores/g of soil provided immediate control of the peanut root-knot nematode, whereas 1,000 and 5,000 endospores/g of soil each amplified in the host nematode and became suppressive after 3 years.

Classical to current approach for treatment of psoriasis: a review.

PubMed

Rahman, Mahfoozur; Alam, Kainat; Ahmad, Mohammad Zaki; Gupta, Gaurav; Afzal, Muhammad; Akhter, Sohail; Kazmi, Imran; Jyoti; Ahmad, Farhan Jalees; Anwar, Firoz

2012-09-01

Psoriasis is a genetic predisposition with T-cell mediated autoimmune inflammatory skin disorder, characterized by cutaneous inflammation, increased epidermal proliferation, hyperkeratosis, angiogenesis, and abnormal keratinization that affects up to 2 - 3% of the population worldwide. Common therapies that are used for the treatment of psoriasis include topical, systemic, phototherapy, combination, herbal therapy and novel molecules. Topically used agents include Vit D, calcipotriol, corticosteroids, dithranol and retinoids etc. Systemically used agents include methotrexate and cyclosporine etc. Phototherapy includes UV-B, Psoralen plus ultraviolet therapy and excimer laser etc. These therapies have a number of potential problems, such as limited in efficacy, inconvenience, organ toxicity, carcinogenic and broadband immunosuppression. In natural treatment a variety of natural agents such as methanolic extracts of duzhong (Eucommia ulmoides Oliv.), yerba mate (Ilex paraguariensis,) linseed oil, fish oil, and Indigo naturalis etc., that modulates T cell and cytokine action at various steps along with the pathogenic sequence have been developed. But till now there is no more in vivo, dose and its efficacy data has been established. Current therapy includes biologicals, small molecules inhibitor and enzyme inhibitors etc, which serve as novel therapeutic options for psoriasis treatment. All these avoid the side effects of the prebiologically developed systemic agents including hepatotoxicity, nephrotoxicity, and bone marrow suppression. Currently, Denilukin diftitox, Efalizumab, Alefacept, Ustekinumab and Etanercept are approved by the FDA, and others molecules are at clinical stage. Patents issued by the US office are also included in current psoriasis treatment scenario. In the United States, biologicals are widely used for moderate-to-severe psoriasis. But because of the high cost of medication and their availability in injection form, it remains to be seen how widely these agents will be utilized worldwide. Still, developing countries prefer conventional drugs.

A proposed CT contrast agent using carboxybetaine zwitterionic tantalum oxide nanoparticles: Imaging, biological, and physicochemical performance

PubMed Central

FitzGerald, Paul F.; Butts, Matthew D.; Roberts, Jeannette C.; Colborn, Robert E.; Torres, Andrew S.; Lee, Brian D.; Yeh, Benjamin M.; Bonitatibus, Peter J.

2016-01-01

Objectives To produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ) coated soluble tantalum oxide nanoparticles (CZ-TaO NPs). We chose tantalum to provide superior imaging performance compared to current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. The aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared to clinically-used iodinated agents. Materials and Methods We evaluated CT imaging performance of our CZ-TaO NPs compared to an iodinated agent in live rats, imaged centrally-located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats’ great vessels at high temporal resolution during and following contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. CZ-TaO NPs were synthesized and analyzed in detail. We used multi-dimensional nuclear magnetic resonance (NMR) to determine surface functionality of the nanoparticles. We measured nanoparticle size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations, including the high concentrations required for standard clinical CT imaging. Results CT imaging studies demonstrated image contrast improvement of approximately 40–50% using CZ-TaO NPs compared with an iodinated agent injected at the same mass concentration. Blood and organ analyses showed no adverse effects following injection in healthy naïve rats at 3 times the ACD. Retention of tantalum at 48 hours after injection was less than 2% of the injected dose in the whole carcass, which very closely matched the reported retention of existing commercial iodine-based contrast agents. Urine analysis of sensitive markers for acute kidney injury showed no responses at 1 week following injection at 3 times the ACD; however, a moderate response in the neutrophil gelatinase-associated lipocalin (NGAL) biomarker was measured at 24 and 48 hours. Compared to other tantalum oxide nanoparticles reported in the literature, CZ-TaO NPs had relatively low osmolality and viscosity at concentrations >200 mg Ta/mL, and were similar in these physical properties to dimeric iodine-based contrast agents. Conclusions We found that a CZ-TaO NP-based contrast agent is potentially viable for general-purpose clinical CT imaging. Our results suggest that such an agent can be formulated with clinically-viable physicochemical properties, can be biologically safe and cleared rapidly in urine, and can provide substantially improved image contrast at CT compared to current iodinated agents. PMID:27115702

A Proposed Computed Tomography Contrast Agent Using Carboxybetaine Zwitterionic Tantalum Oxide Nanoparticles: Imaging, Biological, and Physicochemical Performance.

PubMed

FitzGerald, Paul F; Butts, Matthew D; Roberts, Jeannette C; Colborn, Robert E; Torres, Andrew S; Lee, Brian D; Yeh, Benjamin M; Bonitatibus, Peter J

2016-12-01

The aim of this study was to produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ)-coated soluble tantalum oxide (TaO) nanoparticles (NPs). We chose tantalum to provide superior imaging performance compared with current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. In addition, the aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared with clinically used iodinated agents. We evaluated CT imaging performance of our CZ-TaO NPs compared with that of an iodinated agent in live rats, imaged centrally located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats' great vessels at high temporal resolution during and after contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. Carboxybetaine zwitterionic TaO NPs were synthesized and analyzed in detail. We used multidimensional nuclear magnetic resonance to determine surface functionality of the NPs. We measured NP size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations, including the high concentrations required for standard clinical CT imaging. Computed tomography imaging studies demonstrated image contrast improvement of approximately 40% to 50% using CZ-TaO NPs compared with an iodinated agent injected at the same mass concentration. Blood and organ analyses showed no adverse effects after injection in healthy naive rats at 3 times the ACD. Retention of tantalum at 48 hours after injection was less than 2% of the injected dose in the whole carcass, which very closely matched the reported retention of existing commercial iodine-based contrast agents. Urine analysis of sensitive markers for acute kidney injury showed no responses at 1 week after injection at 3 times the ACD; however, a moderate response in the neutrophil gelatinase-associated lipocalin biomarker was measured at 24 and 48 hours. Compared with other TaO NPs reported in the literature, CZ-TaO NPs had relatively low osmolality and viscosity at concentrations greater than 200 mg Ta/mL and were similar in these physical properties to dimeric iodine-based contrast agents. We found that a CZ-TaO NP-based contrast agent is potentially viable for general-purpose clinical CT imaging. Our results suggest that such an agent can be formulated with clinically viable physicochemical properties, can be biologically safe and cleared rapidly in urine, and can provide substantially improved image contrast at CT compared with current iodinated agents.

Microbiological control of soil-borne phytopathogenic fungi with special emphasis on wilt-inducing Fusarium oxysporum.

PubMed

Alabouvette, Claude; Olivain, Chantal; Migheli, Quirico; Steinberg, Christian

2009-11-01

Plant diseases induced by soil-borne plant pathogens are among the most difficult to control. In the absence of effective chemical control methods, there is renewed interest in biological control based on application of populations of antagonistic micro-organisms. In addition to Pseudomonas spp. and Trichoderma spp., which are the two most widely studied groups of biological control agents, the protective strains of Fusarium oxysporum represent an original model. These protective strains of F. oxysporum can be used to control wilt induced by pathogenic strains of the same species. Exploring the mechanisms involved in the protective capability of these strains is not only necessary for their development as commercial biocontrol agents but raises many basic questions related to the determinism of pathogenicity versus biocontrol capacity in the F. oxysporum species complex. In this paper, current knowledge regarding the interaction between the plant and the protective strains is reviewed in comparison with interactions between the plant and pathogenic strains. The success of biological control depends not only on plant-microbial interactions but also on the ecological fitness of the biological control agents.

Thin membrane sensor with biochemical switch

NASA Technical Reports Server (NTRS)

Worley, III, Jennings F. (Inventor); Case, George D. (Inventor)

1994-01-01

A modular biosensor system for chemical or biological agent detection utilizes electrochemical measurement of an ion current across a gate membrane triggered by the reaction of the target agent with a recognition protein conjugated to a channel blocker. The sensor system includes a bioresponse simulator or biochemical switch module which contains the recognition protein-channel blocker conjugate, and in which the detection reactions occur, and a transducer module which contains a gate membrane and a measuring electrode, and in which the presence of agent is sensed electrically. In the poised state, ion channels in the gate membrane are blocked by the recognition protein-channel blocker conjugate. Detection reactions remove the recognition protein-channel blocker conjugate from the ion channels, thus eliciting an ion current surge in the gate membrane which subsequently triggers an output alarm. Sufficiently large currents are generated that simple direct current electronics are adequate for the measurements. The biosensor has applications for environmental, medical, and industrial use.

[Laboratory diagnosis of toxoplasmosis].

PubMed

Strhársky, J; Mad'arová, L; Klement, C

2009-04-01

Under Central European climatic conditions, toxoplasmosis is one of the most common human parasitic diseases. A wide range of methods for both direct and indirect detection of the causative agent are currently available for the laboratory diagnosis of toxoplasmosis. The purpose of the article is to review the history of the discovery of the causative agent of toxoplasmosis and how laboratory diagnostic methods were developed and improved. The main emphasis is placed on current options in the diagnosis of Toxoplasma gondii, more precisely on the serodiagnosis and new trends in molecular biology-based techniques.

Insights on methotrexate in psoriatic disease.

PubMed

Greb, Jacqueline E; Goldminz, Ari M; Gottlieb, Alice B

2016-11-01

The folic acid analogue methotrexate is used as an anti-neoplastic agent and treatment for inflammatory disorders including psoriasis, dermatomyositis, lupus erythematous, sarcoidosis, and systemic sclerosis. Despite the introduction of newer biologic agents, methotrexate remains a first-line systemic therapy for many patients with disorders of chronic inflammation. Here we briefly describe the current clinical evidence for methotrexate use in psoriatic disease, our current understanding of methotrexate's anti-inflammatory properties, and the future role of methotrexate in the treatment of immune mediated disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

The Innate and Adaptive Immune System as Targets for Biologic Therapies in Inflammatory Bowel Disease.

PubMed

Holleran, Grainne; Lopetuso, Loris; Petito, Valentina; Graziani, Cristina; Ianiro, Gianluca; McNamara, Deirdre; Gasbarrini, Antonio; Scaldaferri, Franco

2017-09-21

Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition causing inflammation of gastrointestinal and systemic cells, with an increasing prevalence worldwide. Many factors are known to trigger and maintain inflammation in IBD including the innate and adaptive immune systems, genetics, the gastrointestinal microbiome and several environmental factors. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. The initial focus of these agents was directed against the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) leading to dramatic changes in the disease course for a proportion of patients with IBD. However, more recently, it has been shown that a significant proportion of patients do not respond to anti-TNF-α directed therapies, leading a shift to other inflammatory pathways and targets, including those of both the innate and adaptive immune systems, and targets linking both systems including anti-leukocyte trafficking agents-integrins and adhesion molecules. This review briefly describes the molecular basis of immune based gastrointestinal inflammation in IBD, and then describes how several current and future biologic agents work to manipulate these pathways, and their clinical success to date.

Pharmacological therapy of spondyloarthritis.

PubMed

Palazzi, Carlo; D'Angelo, Salvatore; Gilio, Michele; Leccese, Pietro; Padula, Angela; Olivieri, Ignazio

2015-01-01

The current pharmacological therapy of spondyloarthritis (SpA) includes several drugs: Non-steroidal anti-inflammatory drugs, corticosteroids, traditional disease-modifying antirheumatic drugs and biologic drugs. A systematic literature search was completed using the largest electronic databases (Medline, Embase and Cochrane), starting from 1995, with the aim to review data on traditional and biologic agents commercialised for SpA treatment. Randomised controlled trials and large observational studies were considered. In addition, studies performed in SpA patients treated with other, still unapproved, drugs (rituximab, anti-IL6 agents, apremilast, IL17 inhibitors and anakinra) were also taken into account. Biologic agents, especially anti-TNF drugs, have resulted in significant progress in improving clinical symptoms and signs, reducing inflammatory features in laboratory tests and imaging findings, and recovering all functional indexes. Anti-TNF drugs have radically changed the evolution of radiographic progression in peripheral joints; the first disappointing data concerning their efficacy on new bone formation of axial SpA has been recently challenged by studies enrolling patients who have been earlier diagnosed and treated. The opportunity to extend the interval of administration or to reduce the doses of anti-TNF agents can favourably influence the costs. Ustekinumab, the first non-anti-TNF biologic drug commercialised for psoriatic arthritis, offers new chances to patients that are unresponsive to anti-TNF.

The Innate and Adaptive Immune System as Targets for Biologic Therapies in Inflammatory Bowel Disease

PubMed Central

Holleran, Grainne; Lopetuso, Loris; Petito, Valentina; Graziani, Cristina; Ianiro, Gianluca; McNamara, Deirdre; Gasbarrini, Antonio; Scaldaferri, Franco

2017-01-01

Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition causing inflammation of gastrointestinal and systemic cells, with an increasing prevalence worldwide. Many factors are known to trigger and maintain inflammation in IBD including the innate and adaptive immune systems, genetics, the gastrointestinal microbiome and several environmental factors. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. The initial focus of these agents was directed against the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) leading to dramatic changes in the disease course for a proportion of patients with IBD. However, more recently, it has been shown that a significant proportion of patients do not respond to anti-TNF-α directed therapies, leading a shift to other inflammatory pathways and targets, including those of both the innate and adaptive immune systems, and targets linking both systems including anti-leukocyte trafficking agents-integrins and adhesion molecules. This review briefly describes the molecular basis of immune based gastrointestinal inflammation in IBD, and then describes how several current and future biologic agents work to manipulate these pathways, and their clinical success to date. PMID:28934123

Possible application of a nematophagous fungus as a biological control agent of parasitic nematodes on commercial sheep farms in South Africa.

PubMed

Faedo, M; Krecek, R C

2002-03-01

Biological control of parasitic nematodes of livestock is currently under development and represents another tool that may be integrated into helminth parasite control strategies. This paper presents a brief introduction to commercial sheep farming in South Africa and currently available nematode parasite control methods. These include the FAMACHA clinical assay, strategies of pasture management, dilution of resistant worm species by introduction of susceptible worms, breed resistant sheep and nutritional supplementation. The purpose of this paper is to outline the principles of biological control using nematophagous fungi and how it may be applied on sheep farms in South Africa.

Review of the treatment of psoriatic arthritis with biological agents: choice of drug for initial therapy and switch therapy for non-responders.

PubMed

D'Angelo, Salvatore; Tramontano, Giuseppina; Gilio, Michele; Leccese, Pietro; Olivieri, Ignazio

2017-01-01

Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease with a broad clinical spectrum and variable course. It can involve musculoskeletal structures as well as skin, nails, eyes, and gut. The management of PsA has changed tremendously in the last decade, thanks to an earlier diagnosis, an advancement in pharmacological therapies, and a wider application of a multidisciplinary approach. The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) as well as interleukin (IL)-12/23 (ustekinumab) and IL-17 (secukinumab) inhibitors is representative of a revolution in the treatment of PsA. No evidence-based strategies are currently available for guiding the rheumatologist to prescribe biological drugs. Several international and national recommendation sets are currently available with the aim to help rheumatologists in everyday clinical practice management of PsA patients treated with biological therapy. Since no specific biological agent has been demonstrated to be more effective than others, the drug choice should be made according to the available safety data, the presence of extra-articular manifestations, the patient's preferences (e.g., administration route), and the drug price. However, future studies directly comparing different biological drugs and assessing the efficacy of treatment strategies specific for PsA are urgently needed.

[Pharmacotherapy of solid tumors. New hopes and frustrations].

PubMed

Grünwald, V; Rickmann, M

2014-10-01

Recent years have seen dramatic changes in the biological understanding and treatment of solid tumors. Based on the tumor biology, targeting agents have been developed which directly affect the underlying genetic or immunological changes found in specific tumor entities. Significant increases in survival have delivered the functional proof of the concept of targeted and immunological tumor therapy. The management and adherence of the patient as well as optimized cooperation with clinicians are decisive for the results of therapy and disease control.Several solid tumors are currently under investigation in clinical studies evaluating the (sequential) therapy with targeting and immunologically active agents, e.g. tyrosine kinase and mTOR inhibitors, targeting antibodies, such as bevacizumab, specific antagonists, such as enzalutamide and immunological checkpoint inhibitors via PD(L)1 and/or CTLA 4 antibodies.Currently approved agents have dramatically changed the landscape of treatment options especially for prostate cancer. Such agents include hormone therapy with enzalutamide and abiraterone, radiotherapy with cabazitaxel and xofigo (radium 223), metastatic breast cancer (eribulin and everolimus), renal cell carcinoma (sunitinib, sorafenib, axitinib, everolimus and temsirolimus), non-small cell lung cancer (crizotinib and afatinib), colorectal cancer and gastrointestinal stromal tumor (regorafenib) and melanoma (ipilimumab and vemurafenib). The treatment of rarer tumors, such as pancreatic and hepatocellular cancer and soft tissue sarcoma has entered the stage of targeted therapy with the approval of nanoparticle albumin-bound (nab)-paclitaxel, sorafenib, and eribulin/pazopanib. Current clinical trials are focusing on the best time point and sequence of therapy and also improvement in the management of these promising agents.

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. ...

The rise of biosimilars: potential benefits and drawbacks in rheumatoid arthritis.

PubMed

Yoo, Dae Hyun

2014-08-01

Although biologic agents are effective in the treatment of rheumatoid arthritis, the high price of drugs and restricted health care budgets have restricted easy access to biologics. Eventually, the use of biologic disease-modifying antirheumatic drugs might be inversely associated with disease activity in countries with low gross domestic product. The EMA approved an infliximab biosimilar for the first time in September 2013. The first approval of a biosimilar monoclonal antibody by a major regulatory authority provided a global standard for subsequent biosimilars and for biopharmaceutical companies developing biosimilars. Biosimilars with a highly similar quality and efficacy profile at an acceptable lower cost would significantly increase affordability of biologic disease-modifying antirheumatic drugs in the treatment of rheumatoid arthritis. Here, we will review the current status of first biosimilar antibody agent and the potential discussion points raised against biosimilars. In addition, the importance of awareness on biosimilars for stakeholders is discussed.

Molecular Aspects of Head and Neck Cancer Therapy

PubMed Central

Puram, Sidharth V.; Rocco, James W.

2015-01-01

Synopsis In spite of a rapidly expanding understanding of head and neck tumor biology as well as optimization of radiation, chemotherapy, and surgical treatment modalities, head and neck squamous cell carcinoma (HNSCC) remains a major cause of cancer related morbidity and mortality. Although our biologic understanding of these tumors had largely been limited to pathways driving proliferation, survival, and differentiation, the identification of HPV as a major driver of HNSCC, specifically oropharyngeal SCC, as well as recent genomic sequencing analyses of HNSCC has dramatically influenced our understanding of the underlying biology behind carcinogenesis, and in part, our approach to therapy. In particular, we are at a major molecular and clinical crossroads with an explosion of promising diagnostic and therapeutic agents that hold great promise. Here, we summarize our current understanding of HNSCC biology, including a review of recent sequencing analyses, and identify promising areas for potential diagnostic and therapeutic agents. PMID:26568543

[Exposure to biological agents used in Polish enterprises: analysis of data derived from the National Register of Biological Agent].

PubMed

Kozajda, Anna; Szadkowska-Stańczyk, Irena

2011-01-01

The National Register of Biological Agents at Work and the National Information Centre for Biological Agents Present at Workplaces were established in the Nofer Institute of Occupational Medicine in 2005. The National Information Centre carries out consultation and education activities concerning occupational exposure and risk assessment, development and implementation of preventive programs and accurate registration of reliable information about the use of biological agents. Educational materials on biological exposure are published on the website. The National Register of Biological Agents (database) collects and periodically analyzes the information obtained from employers about the use of biological agents for research, diagnostic or industrial purposes. As of 10 December 2010 there were 240 notifications from companies, which use biological agents for the following purposes: research--69, industrial--30 and diagnostic--321. Near 75% of all notifications were obtained from different diagnostic laboratories (public and private). In total, 3226 workers, including 2967 (92%) women and 256 (8%) men were exposed to biological agents. In general, occupational exposure to 209 biological agents (186 of risk group 2 and 23 of risk group 3, of which 16 are additionally marked by 3**) were registered in the data base.

Evolution of a multi-agent system in a cyclical environment.

PubMed

Baptista, Tiago; Costa, Ernesto

2008-06-01

The synchronisation phenomena in biological systems is a current and recurring subject of scientific study. This topic, namely that of circadian clocks, served as inspiration to develop an agent-based simulation that serves the main purpose of being a proof-of-concept of the model used in the BitBang framework, that implements a modern autonomous agent model. Despite having been extensively studied, circadian clocks still have much to be investigated. Rather than wanting to learn more about the internals of this biological process, we look to study the emergence of this kind of adaptation to a daily cycle. To that end we implemented a world with a day/night cycle, and analyse the ways the agents adapt to that cycle. The results show the evolution of the agents' ability to gather food. If we look at the total number of agents over the course of an experiment, we can pinpoint the time when reproductive technology emerges. We also show that the agents adapt to the daily cycle. This circadian rhythm can be shown by analysing the variation on the agents metabolic rate, which is affected by the variation of their movement patterns. In the experiments conducted we can observe that the metabolic rate of the agents varies according to the daily cycle.

Emerging Drugs for Uveitis

PubMed Central

Larson, Theresa; Nussenblatt, Robert B.; Sen, H. Nida

2010-01-01

Importance of the Field Uveitis is a challenging disease covering both infectious and noninfectious conditions. The current treatment strategies are hampered by the paucity of randomized controlled trials (RCTs) and few trials comparing efficacy of different agents. Areas Covered in this Review This review describes the current and future treatments of uveitis. A literature search was performed in PUBMED from 1965 to 2010 on drugs treating ocular inflammation with emphasis placed on more recent, larger studies. What the Reader Will Gain Readers should gain a basic understanding of current treatment strategies beginning with corticosteroids and transitioning to steroid sparing agents. Steroid sparing agents include the antimetabolites which include methotrexate, azathioprine, and mycophenolate mofetil; the calcineurin inhibitors which include cyclosporine, tacrolimus; alkylating agents which include cyclophosphamide and chlorambucil; and biologics which include the TNF-α inhibitors infliximab, adalimumab, and etanercept; daclizumab, interferon α2a, and rituximab. Take Home Message Newer agents are typically formulated from existing drugs or developed based on new advances in immunology. Future treatment will require a better understanding of the mechanisms involved in autoimmune diseases and better delivery systems in order to provide targeted treatment with minimal side effects. PMID:21210752

Waldenstrom Macroglobulinemia☆

PubMed Central

Leleu, Xavier; Roccaro, Aldo M.; Moreau, Anne-Sophie; Dupire, Sophie; Robu, Daniela; Gay, Julie; Hatjiharissi, Evdoxia; Burwik, Nicholas; Ghobrial, Irene M.

2011-01-01

In the past years, new developments have occurred both in the understanding of the biology of Waldenstrom Macroglobulinemia (WM) and in therapeutic options for WM. WM is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells, along with demonstration of an IgM monoclonal gammopathy. Despite advances in therapy, WM remains incurable, with 5–6 years median overall survival of patients in symptomatic WM. Therapy is postponed for asymptomatic patients, and progressive anemia is the most common indication for initiation of treatment. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab. Studies involving combination chemotherapy are ongoing, and preliminary results are encouraging. No specific agent or regimen has been shown to be superior to another for treatment of WM. As such, novel therapeutic agents are needed for the treatment of WM. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of WM so as to better target therapeutics for this malignancy. These efforts have led to the development of several novel agents including the proteasome inhibitor bortezomib, and several Akt/mTor inhibitors, perifosine and Rad001, and immunomodulatory agents such as thalidomide and lenalidomide. Studies with monoclonal antibodies are ongoing and promising including the use of alemtuzumab, SGN-70, and the APRIL/BLYS blocking protein TACI-Ig atacicept. Other agents currently being tested in clinical trials include the PKC inhibitor enzastaurin, the natural product resveratrol, as well as the statin simvastatin. This report provides an update of the current preclinical studies and clinical efforts for the development of novel agents in the treatment of WM. PMID:18555588

Method for photo-altering a biological system to improve biological effect

DOEpatents

Hill, Richard A.; Doiron, Daniel R.; Crean, David H.

2000-08-01

Photodynamic therapy is a new adjunctive therapy for filtration surgery that does not use chemotherapy agents or radiation, but uses pharmacologically-active sensitizing compounds to produce a titratable, localized, transient, post operative avascular conjunctiva. A photosensitizing agent in a biological system is selectively activated by delivering the photosensitive agent to the biological system and laser activating only a spatially selected portion of the delivered photosensitive agent. The activated portion of the photosensitive agent reacts with the biological system to obtain a predetermined biological effect. As a result, an improved spatial disposition and effectuation of the biological effect by the photosensitive agent in the biological system is achieved.

Preapproval and postapproval availability of published comparative efficacy research on biological agents.

PubMed

Thomas, Rachel Hutchins; Freeman, Maisha Kelly; Hughes, Peter J

2013-07-15

Preapproval and postapproval availability of published comparative efficacy studies on biological agents approved between 2000 and 2010 was investigated. Approval packages published on the Food and Drug Administration (FDA) website were examined for all biological agents approved between 2000 and 2010 to determine if comparative efficacy studies were available at the time of FDA approval. The availability of comparative efficacy studies published subsequent to approval was determined by searching PubMed for randomized, active-controlled experimental or observational study designs that measured efficacy as the primary endpoint and were relevant to the original FDA-approved indication. From 2000 to 2010, 107 biological agents were approved by FDA. Of the biological agents with alternative treatments, 54.6% had comparative efficacy data available at the time of approval. Although standard-reviewed biological agents were more likely to have comparative efficacy trials included in the FDA approval packages than priority-reviewed biological agents, statistically significant differences are unlikely. Subsequent to approval, 58.1% of biological agents had at least one published comparative efficacy trial, representing a 3.5% absolute increase in the availability of comparative efficacy studies since the time of approval. Vaccines and biological agents in the hematologic diseases, oncology, and miscellaneous diseases classes had fewer published postapproval comparative efficacy studies per agent compared with the overall group of biological agents. Nearly half of all biological agents approved for marketing between 2000 and 2010 lacked publicly accessible, active-controlled efficacy studies at the time of drug approval; a slightly greater proportion of biological agents had comparative efficacy data published subsequent to their approval.

Histone deacetylase inhibitors: current status and overview of recent clinical trials.

PubMed

Ma, Xujun; Ezzeldin, Hany H; Diasio, Robert B

2009-10-01

Histone deacetylase (HDAC) inhibitors are a new group of anticancer agents that have a potential role in the regulation of gene expression, induction of cell death, apoptosis and cell cycle arrest of cancer cells by altering the acetylation status of chromatin and other non-histone proteins. In clinical trials, HDAC inhibitors have demonstrated promising antitumour activity as monotherapy in cutaneous T-cell lymphoma and other haematological malignancies. In solid tumours, several HDAC inhibitors have been shown to be efficacious as single agents; however, results of most clinical trials were in favour of using HDAC inhibitors either prior to the initiation of chemotherapy or in combination with other treatments. Currently, the molecular basis of response to HDAC inhibitors in patients is not fully understood. In this review, we summarize the current status of HDAC inhibitors, as single agents or in combination with other agents in different phases of clinical trials. In most of the clinical trials, HDAC inhibitors were tolerable and exerted biological or antitumor activity. HDAC inhibitors have been studied in phase I, II and III clinical trials with variable efficacy. The combination of HDAC inhibitors with other anticancer agents including epigenetic or chemotherapeutic agents demonstrated favourable clinical outcome.

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.

Molecular mechanisms in therapy of acid-related diseases

PubMed Central

Shin, J. M.; Vagin, O.; Munson, K.; Kidd, M.; Modlin, I. M.; Sachs, G.

2011-01-01

Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration; therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities. Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of a novel class of agents, the acid pump antagonists. PMID:17928953

2006 Joint Chemical Biological, Radiological and Nuclear (CBRN) Conference and Exhibition

DTIC Science & Technology

2006-06-28

methods that might counter or cancel our current military advantages • Defeat terrorist networks • Defend homeland in depth • Prevent acquisition or...Systems approach to the detection of chemical and biological agents with a focus on genetically engineered organisms ( GMOs )/genetically engineered...and possessing breakthrough technological capabilities intended to supplant U.S. advantages in particular operational domains. (capsize our power

Comparative Proteomics of Tandem Mass Spectrometry Analyses for Bacterial Strains Identification and Differentiation

DTIC Science & Technology

2012-02-01

risk, bio -terrorism utility, Homeland Security, agricultural monitoring, quality of foodstuffs, environmental monitoring, and biological warfare agents...CAL19717 Putative surface antigen CAL21872 Putative sigma 54 modulation protein NP_395233 Plasminogen activator protease precursor CAL19882 OMP...S. (2005). Chemical and biological weapons : current concepts for future defenses. Johns Hopkins APL Tech. Digest, 26, 321-333. Dworzanski, J.P

Aspects of Tactical Biological Defense

DTIC Science & Technology

1994-06-03

physical proof of Soviet emplcyment of mycotoxins in those countries had been obtained. 30 Biochemical casualties in Laos, Kampuchea and Afghanistan...detection capability. The current system planned for use is the XM-21 Remote Sensing Chemical Agent Alarm (RSCAAL). It uses infrared sensors to detect...Micrometer(s). min. Minute(s). MS. Mans spectroscopy /mass spectrometer. NBC, Nuclear, biological and chemical. pfu. Plaque forming units--the number of

A new threat to bees? Entomopathogenic nematodes used in biological pest control cause rapid mortality in Bombus terrestris.

PubMed

Dutka, Alexandrea; McNulty, Alison; Williamson, Sally M

2015-01-01

There is currently a great deal of concern about population declines in pollinating insects. Many potential threats have been identified which may adversely affect the behaviour and health of both honey bees and bumble bees: these include pesticide exposure, and parasites and pathogens. Whether biological pest control agents adversely affect bees has been much less well studied: it is generally assumed that biological agents are safer for wildlife than chemical pesticides. The aim of this study was to test whether entomopathogenic nematodes sold as biological pest control products could potentially have adverse effects on the bumble bee Bombus terrestris. One product was a broad spectrum pest control agent containing both Heterorhabditis sp. and Steinernema sp., the other product was specifically for weevil control and contained only Steinernema kraussei. Both nematode products caused ≥80% mortality within the 96 h test period when bees were exposed to soil containing entomopathogenic nematodes at the recommended field concentration of 50 nematodes per cm(2) soil. Of particular concern is the fact that nematodes from the broad spectrum product could proliferate in the carcasses of dead bees, and therefore potentially infect a whole bee colony or spread to the wider environment.

Mu Opioids and Their Receptors: Evolution of a Concept

PubMed Central

Pan, Ying-Xian

2013-01-01

Opiates are among the oldest medications available to manage a number of medical problems. Although pain is the current focus, early use initially focused upon the treatment of dysentery. Opium contains high concentrations of both morphine and codeine, along with thebaine, which is used in the synthesis of a number of semisynthetic opioid analgesics. Thus, it is not surprising that new agents were initially based upon the morphine scaffold. The concept of multiple opioid receptors was first suggested almost 50 years ago (Martin, 1967), opening the possibility of new classes of drugs, but the morphine-like agents have remained the mainstay in the medical management of pain. Termed mu, our understanding of these morphine-like agents and their receptors has undergone an evolution in thinking over the past 35 years. Early pharmacological studies identified three major classes of receptors, helped by the discovery of endogenous opioid peptides and receptor subtypes—primarily through the synthesis of novel agents. These chemical biologic approaches were then eclipsed by the molecular biology revolution, which now reveals a complexity of the morphine-like agents and their receptors that had not been previously appreciated. PMID:24076545

A Biologically Inspired Cooperative Multi-Robot Control Architecture

NASA Technical Reports Server (NTRS)

Howsman, Tom; Craft, Mike; ONeil, Daniel; Howell, Joe T. (Technical Monitor)

2002-01-01

A prototype cooperative multi-robot control architecture suitable for the eventual construction of large space structures has been developed. In nature, there are numerous examples of complex architectures constructed by relatively simple insects, such as termites and wasps, which cooperatively assemble their nests. The prototype control architecture emulates this biological model. Actions of each of the autonomous robotic construction agents are only indirectly coordinated, thus mimicking the distributed construction processes of various social insects. The robotic construction agents perform their primary duties stigmergically i.e., without direct inter-agent communication and without a preprogrammed global blueprint of the final design. Communication and coordination between individual agents occurs indirectly through the sensed modifications that each agent makes to the structure. The global stigmergic building algorithm prototyped during the initial research assumes that the robotic builders only perceive the current state of the structure under construction. Simulation studies have established that an idealized form of the proposed architecture was indeed capable of producing representative large space structures with autonomous robots. This paper will explore the construction simulations in order to illustrate the multi-robot control architecture.

Clinical Trials in Noninfectious Uveitis

PubMed Central

Kim, Jane S.; Knickelbein, Jared E.; Nussenblatt, Robert B.; Sen, H. Nida

2015-01-01

The treatment of noninfectious uveitis continues to remain a challenge for many ophthalmologists. Historically, clinical trials in uveitis have been sparse, and thus, most treatment decisions have largely been based on clinical experience and consensus guidelines. The current treatment paradigm favors initiation then tapering of corticosteroids with addition of steroid-sparing immunosuppressive agents for persistence or recurrence of disease. Unfortunately, in spite of a multitude of highly unfavorable systemic effects, corticosteroids are still regarded as the mainstay of treatment for many patients with chronic and refractory noninfectious uveitis. However, with the success of other conventional and biologic immunomodulatory agents in treating systemic inflammatory and autoimmune conditions, interest in targeted treatment strategies for uveitis has been renewed. Multiple clinical trials on steroid-sparing immunosuppressive agents, biologic agents, intraocular corticosteroid implants, and topical ophthalmic solutions have already been completed, and many more are ongoing. This review discusses the results and implications of these clinical trials investigating both alternative and novel treatment options for noninfectious uveitis. PMID:26035763

Biological Control of Tephritid Fruit Flies in Argentina: Historical Review, Current Status, and Future Trends for Developing a Parasitoid Mass-Release Program

PubMed Central

Ovruski, Sergio M.; Schliserman, Pablo

2012-01-01

In Argentina there are two tephritid fruit fly species of major economic and quarantine importance: the exotic Ceratitis capitata that originated from Southeast Africa and the native Anastrepha fraterculus. In recent years, the use of fruit fly parasitoids as biocontrol agents has received renewed attention. This increasing interest has recently led to the establishment of a program for the mass rearing of five million Diachasmimorpha longicaudata parasitoids per week in the BioPlanta San Juan facility, San Juan, Argentina. The first augmentative releases of D. longicaudata in Argentina are currently occurring on commercial fig crops in rural areas of San Juan as part of an integrated fruit fly management program on an area-wide basis. In this context, research is ongoing to assess the suitability of indigenous parasitoid species for successful mass rearing on larvae of either C. capitata or A. fraterculus. The purpose of this article is to provide a historical overview of the biological control of the fruit fly in Argentina, report on the strategies currently used in Argentina, present information on native parasitoids as potential biocontrol agents, and discuss the establishment of a long-term fruit fly biological control program, including augmentative and conservation modalities, in Argentina’s various fruit growing regions. PMID:26466633

The Role of Interleukins 4 and/or 13 in the Pathophysiology and Treatment of Atopic Dermatitis.

PubMed

Silverberg, Jonathan I; Kantor, Robert

2017-07-01

Moderate to severe atopic dermatitis (AD) can be debilitating and often requires use of systemic immunosuppressant therapy to achieve adequate disease control. There are currently no US Food and Drug Administration-approved systemic agents for the long-term treatment of AD. Recent insight has identified the T helper 2 cytokines, interleukins 4 and 13, as playing a major role in the pathogenesis of AD. There are multiple novel biologic agents in development that target interleukins 4 and/or 13 for the treatment of moderate to severe AD. The age of targeted biologics for AD has arrived. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Human-Robot Teams Collaborating Socially Organizationally, and Culturally

DTIC Science & Technology

2011-09-01

C., Myerscough, Graham, S., & Oldroyd, B. P. (2004). Honey Bee Nest Thermoregulation: Diversity Promotes Stability. Science, 305, 5682, 402-404...from biology tend to be very robust, stable, and adaptable. These systems tend to be massively parallel, with a many to one mapping of agents to...Kaminski, G., Chaline, N., & Jaisson, P. (2007). Individual experience alone can generate lasting division of labor in ants. Current Biology 17, 1308

New era of biologic therapeutics in atopic dermatitis.

PubMed

Guttman-Yassky, Emma; Dhingra, Nikhil; Leung, Donald Y M

2013-04-01

Atopic dermatitis (AD) is a common inflammatory skin disease regulated by genetic and environmental factors. Both skin barrier defects and aberrant immune responses are believed to drive cutaneous inflammation in AD. Existing therapies rely largely on allergen avoidance, emollients and topical and systemic immune-suppressants, some with significant toxicity and transient efficacy; no specific targeted therapies are in clinical use today. As our specific understanding of the immune and molecular pathways that cause different subsets of AD increases, a variety of experimental agents, particularly biologic agents that target pathogenic molecules bring the promise of safe and effective therapeutics for long-term use. This paper discusses the molecular pathways characterizing AD, the contributions of barrier and immune abnormalities to its pathogenesis, and development of new treatments that target key molecules in these pathways. In this review, we will discuss a variety of biologic therapies that are in development or in clinical trials for AD, perhaps revolutionizing treatment of this disease. Biologic agents in moderate to severe AD offer promise for controlling a disease that currently lacks good and safe therapeutics posing a large unmet need. Unfortunately, existing treatments for AD aim to decrease cutaneous inflammation, but are not specific for the pathways driving this disease. An increasing understanding of the immune mechanisms underlying AD brings the promise of narrow targeted therapies as has occurred for psoriasis, another inflammatory skin disease, for which specific biologic agents have been demonstrated to both control the disease and prevent occurrence of new skin lesions. Although no biologic is yet approved for AD, these are exciting times for active therapeutic development in AD that might lead to revolutionary therapeutics for this disease.

Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs

PubMed Central

Padhye, Subhash; Ahmad, Aamir; Oswal, Nikhil; Sarkar, Fazlul H

2009-01-01

Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent. PMID:19725977

Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs.

PubMed

Padhye, Subhash; Ahmad, Aamir; Oswal, Nikhil; Sarkar, Fazlul H

2009-09-02

Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent.

Synthesis and biological activity of imidazopyridine anticoccidial agents: Part II.

PubMed

Scribner, Andrew; Dennis, Richard; Lee, Shuliang; Ouvry, Gilles; Perrey, David; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

2008-06-01

Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Recently, we reported the synthesis and biological activity of potent imidazo[1,2-a]pyridine anticoccidial agents. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we report the synthesis and anticoccidial activity of a second set of such compounds, focusing on derivatization of the amine side chain at the imidazopyridine 7-position. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

Clinical biomarkers of angiogenesis inhibition

PubMed Central

Brown, Aaron P.; Citrin, Deborah E.; Camphausen, Kevin A.

2009-01-01

Introduction An expanding understanding of the importance of angiogenesis in oncology and the development of numerous angiogenesis inhibitors are driving the search for biomarkers of angiogenesis. We review currently available candidate biomarkers and surrogate markers of anti-angiogenic agent effect. Discussion A number of invasive, minimally invasive, and non-invasive tools are described with their potential benefits and limitations. Diverse markers can evaluate tumor tissue or biological fluids, or specialized imaging modalities. Conclusions The inclusion of these markers into clinical trials may provide insight into appropriate dosing for desired biological effects, appropriate timing of additional therapy, prediction of individual response to an agent, insight into the interaction of chemotherapy and radiation following exposure to these agents, and perhaps most importantly, a better understanding of the complex nature of angiogenesis in human tumors. While many markers have potential for clinical use, it is not yet clear which marker or combination of markers will prove most useful. PMID:18414993

Endothelial progenitor cells (EPCs) in ageing and age-related diseases: How currently available treatment modalities affect EPC biology, atherosclerosis, and cardiovascular outcomes.

PubMed

Altabas, Velimir; Altabas, Karmela; Kirigin, Lora

2016-10-01

Endothelial progenitor cells (EPCs) are mononuclear cells that circulate in the blood and are derived from different tissues, expressing cell surface markers that are similar to mature endothelial cells. The discovery of EPCs has lead to new insights in vascular repair and atherosclerosis and also a new theory for ageing. EPCs from the bone marrow and some other organs aid in vascular repair by migrating to distant vessels where they differentiate into mature endothelial cells and replace old and injured endothelial cells. The ability of EPCs to repair vascular damage depends on their number and functionality. Currently marketed drugs used in a variety of diseases can modulate these characteristics. In this review, the effect of currently available treatment options for cardiovascular and metabolic disorders on EPC biology will be discussed. The various EPC-based therapies that will be discussed include lipid-lowering agents, antihypertensive agents, antidiabetic drugs, phosphodiesteraze inhibitors, hormones, as well as EPC capturing stents. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Molecular imaging; current status and future prospects in USA].

PubMed

Kobayashi, Hisataka

2007-02-01

The goal of this review is to introduce the definition, current status, and future prospects of the molecular imaging, which has recently been a hot topic in medicine and the biological science in USA. In vivo imaging methods to visualize the molecular events and functions in organs or animals/humans are overviewed and discussed especially in combinations of imaging modalities (machines) and contrast agents(chemicals) used in the molecular imaging. Next, the close relationship between the molecular imaging and the nanotechnology, an important part of nanomedicine, is stressed from the aspect of united multidisciplinary sciences such as physics, chemistry, biology, and medicine.

Electrostatic thin film chemical and biological sensor

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

Prelas, Mark A.; Ghosh, Tushar K.; Tompson, Jr., Robert V.

A chemical and biological agent sensor includes an electrostatic thin film supported by a substrate. The film includes an electrostatic charged surface to attract predetermined biological and chemical agents of interest. A charge collector associated with said electrostatic thin film collects charge associated with surface defects in the electrostatic film induced by the predetermined biological and chemical agents of interest. A preferred sensing system includes a charge based deep level transient spectroscopy system to read out charges from the film and match responses to data sets regarding the agents of interest. A method for sensing biological and chemical agents includesmore » providing a thin sensing film having a predetermined electrostatic charge. The film is exposed to an environment suspected of containing the biological and chemical agents. Quantum surface effects on the film are measured. Biological and/or chemical agents can be detected, identified and quantified based on the measured quantum surface effects.« less

40 CFR 152.20 - Exemptions for pesticides adequately regulated by another Federal agency.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Federal agency. (a) Certain biological control agents. (1) Except as provided by paragraphs (a)(3) and (a)(4) of this section, all biological control agents are exempt from FIFRA requirements. (2) If the Agency determines that an individual biological control agent or class of biological control agents is no...

40 CFR 152.20 - Exemptions for pesticides adequately regulated by another Federal agency.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Federal agency. (a) Certain biological control agents. (1) Except as provided by paragraphs (a)(3) and (a)(4) of this section, all biological control agents are exempt from FIFRA requirements. (2) If the Agency determines that an individual biological control agent or class of biological control agents is no...

Polymeric drugs: Advances in the development of pharmacologically active polymers

PubMed Central

Li, Jing; Yu, Fei; Chen, Yi; Oupický, David

2015-01-01

Synthetic polymers play a critical role in pharmaceutical discovery and development. Current research and applications of pharmaceutical polymers are mainly focused on their functions as excipients and inert carriers of other pharmacologically active agents. This review article surveys recent advances in alternative pharmaceutical use of polymers as pharmacologically active agents known as polymeric drugs. Emphasis is placed on the benefits of polymeric drugs that are associated with their macromolecular character and their ability to explore biologically relevant multivalency processes. We discuss the main therapeutic uses of polymeric drugs as sequestrants, antimicrobials, antivirals, and anticancer and anti-inflammatory agents. PMID:26410809

Army medical laboratory telemedicine: role of mass spectrometry in telediagnosis for chemical and biological defense.

PubMed

Smith, J R; Shih, M L; Price, E O; Platoff, G E; Schlager, J J

2001-12-01

An army medical field laboratory presently has the capability of performing standard protocols developed at the US Army Medical Research Institute of Chemical Defense for verification of nerve agent or sulfur mustard exposure. The protocols analyze hydrolysis products of chemical warfare agents using gas chromatography/mass spectrometry. Additionally, chemical warfare agents can produce alkylated or phosphorylated proteins following human exposure that have long biological half-lives and can be used as diagnostic biomarkers of chemical agent exposure. An analytical technique known as matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) currently is being examined for its potential to analyze these biomarkers. The technique is capable of detecting large biomolecules and modifications made to them. Its fast analysis time makes MALDI-TOF/MS technology suitable for screening casualties from chemical or biological attacks. Basic operation requires minimal training and the instrument has the potential to become field-portable. The limitation of the technique is that the generated data may require considerable expertise from knowledgeable personnel for consultation to ensure correct interpretation. The interaction between research scientists and field personnel in the acquisition of data and its interpretation via advanced digital telecommunication technologies can enhance rapid diagnosis and subsequently improve patient care in remote areas. Copyright 2001 John Wiley & Sons, Ltd.

Emerging biological therapies for the treatment of myelodysplastic syndromes.

PubMed

Zeidan, Amer M; Stahl, Maximilian; Komrokji, Rami

2016-09-01

No drug has resulted in a survival advantage in patients with lower-risk myelodysplastic syndromes (MDS). While hypomethylating agents (HMA) have revolutionized treatment options for patients with higher-risk MDS, the prognosis remains dismal after HMA treatment failure. Novel effective therapies are urgently needed especially after HMA failure. This review covers the current approach to disease prognostication and risk-adaptive therapy, as well as novel therapeutic approaches. We discuss the recent advancements in the understanding of MDS disease biology as a basis of targeted drug development. Several classes of novel agents are reviewed including drugs targeting dysregulated epigenetic control mechanisms, signaling pathways, abnormal splicing, as well as agents that target the immune system and the MDS bone marrow niche. Significant advancements in the understanding of the underlying biology of MDS are only starting to be translated into novel treatment options for MDS. Epigenetic therapy has shown significant clinical activity with HMA but the results of clinical trials combining HMAs with histone deacetylase inhibitors (HDACi) have been disappointing to date. Similarly, targeting several aberrant pathways in MDS has not resulted in significant improvements in therapy. Future therapies will focus both on synergic combination of existing drugs as well as novel agents targeting dysregulated immune responses and abnormal RNA splicing in MDS.

New-onset vitiligo and progression of pre-existing vitiligo during treatment with biological agents in chronic inflammatory diseases.

PubMed

Méry-Bossard, L; Bagny, K; Chaby, G; Khemis, A; Maccari, F; Marotte, H; Perrot, J L; Reguiai, Z; Sigal, M L; Avenel-Audran, M; Boyé, T; Grasland, A; Gillard, J; Jullien, D; Toussirot, E

2017-01-01

The development of vitiligo during treatment with biological agents is an unusual event and only a few isolated cases have been reported. To describe the clinical characteristics and evolution of patients developing new-onset vitiligo following initiation of a biological agent for chronic inflammatory disease; and also to report the clinical course of pre-existing vitiligo under biological therapy. This nationwide multicentre, retrospective study, carried out between July 2013 and January 2015, describes the characteristics of a large series of 18 patients (psoriasis N = 8, inflammatory rheumatic diseases N = 8, ulcerative colitis N = 1, uveitis N = 1) who developed new-onset vitiligo while receiving a biological agent. TNFα inhibitors were the most common biological agent involved (13/18) while anti-IL-12/23 and anti-IL-17 agents or abatacept were less common (4/18 and 1/18 respectively). Mean duration of biological agent exposure before vitiligo onset was 13.9 ± 16.5 months. Outcome was favourable for most patients (15/17) while maintaining the biological agent. Data were also collected for 18 patients (psoriasis N = 5, inflammatory rheumatic diseases N = 10, inflammatory bowel diseases N = 2, SAPHO N = 1) who had pre-existing vitiligo when treatment with a biological agent started (TNFα inhibitors N = 15, ustekinumab N = 1, rituximab N = 1, tocilizumab N = 1). Vitiligo progressed in seven patients and was stable or improved in eight cases. Vitiligo may thus emerge and/or progress during treatment with various biological agents, mainly TNFα inhibitors and could be a new paradoxical skin reaction. De novo vitiligo displays a favourable outcome when maintaining the biological agent, whereas the prognosis seems worse in cases of pre-existing vitiligo. © 2016 European Academy of Dermatology and Venereology.

CATALYTIC ENZYME-BASED METHODS FOR WATER TREATMENT AND WATER DISTRIBUTION SYSTEM DECONTAMINATION

EPA Science Inventory

Current chemistry-based decontaminants for chemical or biological warfare agents and related toxic materials are caustic and have the potential for causing material and environmental damage. In addition, most are bulk liquids that require significant logistics and storage capabil...

[The variola virus as a biological weapon].

PubMed

Mlinarić-Galinović, Gordana; Turković, Branko; Brudnjak, Zvonimir; Gjenero-Margan, Ira

2003-01-01

In view of the threat of use of the variola virus as a biological weapon, the interest of medical and other public in this causative agent that was eradicated in the wild at the end of the 1970s has increased. The paper gives an outline of the current knowledge on biological properties of the variola virus, and on the epidemiology, pathogenesis, clinical picture and prophylaxis of the disease caused by this virus. Descriptions of two sudden smallpox epidemics (Germany in 1970 and former Yugoslavia in 1972) could illustrate the potential of the smallpox virus as a biological weapon in bioterrorism and biological warfare. In fact, this virus can spread very readily through aerosol, which may lead to explosive epidemics. Not having been immunised, our population aged less than 25 years totally lacks the immunity. Older individuals are likely to have a low residual specific immunity to the agent. The only way to prevent a smallpox epidemic is by vaccination and patient isolation. A rapid smallpox diagnostics and prompt vaccination of all contacts is of utmost importance in stopping the outbreak.

Specialty Tier-Level Cost Sharing and Biologic Agent Use in the Medicare Part D Initial Coverage Period Among Beneficiaries With Rheumatoid Arthritis.

PubMed

Doshi, Jalpa A; Hu, Tianyan; Li, Pengxiang; Pettit, Amy R; Yu, Xinyan; Blum, Marissa

2016-11-01

To examine associations between specialty tier-level cost sharing and use of biologic agents for rheumatoid arthritis (RA) during Medicare Part D's initial coverage period (ICP). This was a retrospective study using 2007-2010 5% sample Medicare files to examine RA patients with use of a Part D RA biologic agent in the prior year. Patients without low-income subsidies (non-LIS group), who faced specialty tier-level cost sharing, were compared to a control group of low-income subsidy patients (LIS group), who faced nominal out-of-pocket costs in the ICP. Outcomes included use of a Part D or Part B RA biologic agent during the ICP and presence of a ≥30-day continuous gap in treatment among Part D biologic agent users in the ICP. Risk-adjusted outcomes were estimated using logistic regressions, controlling for patient demographic, clinical, and Part D plan characteristics. On average, a 30-day Part D biologic agent supply cost the non-LIS group $484 out of pocket (29.9% cost sharing) versus $5 (0.3% cost sharing) for the LIS group. The non-LIS group was less likely to fill Part D biologic agents (61.2% versus 72.7%, odds ratio [OR] 0.58 [95% confidence interval (95% CI) 0.46-0.72]; P < 0.001), more than twice as likely to receive Part B biologic agents (9.9% versus 4.4%, OR 2.41 [95% CI 1.61-3.60]; P < 0.001), and less likely to use any biologic agent (70.1% versus 76.9%, OR 0.69 [95% CI 0.55-0.88]; P = 0.002). The non-LIS subgroup filling Part D biologic agents had approximately twice the odds of a gap in both Part D biologic agent and any biologic agent availability. Specialty tier-level cost sharing was associated with interruptions in RA biologic agent treatment among Medicare patients. © 2016, American College of Rheumatology.

Botulinum neurotoxin: where are we with detection technologies?

PubMed

Singh, Ajay K; Stanker, Larry H; Sharma, Shashi K

2013-02-01

Because of its high toxicity, botulinum neurotoxin (BoNT) poses a significant risk to humans and it represents a possible biological warfare agent. Nevertheless, BoNT serotypes A and B are considered an effective treatment for a variety of neurological disorders. The growing applicability of BoNT as a drug, and its potential use as a biological threat agent, highlight the urgent need to develop sensitive detection assays and therapeutic counter measures. In the last decade, significant progress has been made in BoNT detection technologies but none have fully replaced the mouse lethality assay, the current "gold standard". Recently, new advances in robotics and the availability of new reagents have allowed development of methods for rapid toxin analysis. These technologies while promising need further refinement.

Voltammetric detection of biological molecules using chopped carbon fiber.

PubMed

Sugawara, Kazuharu; Yugami, Asako; Kojima, Akira

2010-01-01

Voltammetric detection of biological molecules was carried out using chopped carbon fibers produced from carbon fiber reinforced plastics that are biocompatible and inexpensive. Because chopped carbon fibers normally are covered with a sizing agent, they are difficult to use as an electrode. However, when the surface of a chopped carbon fiber was treated with ethanol and hydrochloric acid, it became conductive. To evaluate the functioning of chopped carbon fibers, voltammetric measurements of [Fe(CN)(6)](3-) were carried out. Redoxes of FAD, ascorbic acid and NADH as biomolecules were recorded using cyclic voltammetry. The sizing agents used to bundle the fibers were epoxy, polyamide and polyurethane resins. The peak currents were the greatest when using the chopped carbon fibers that were created with epoxy resins. When the electrode response of the chopped carbon fibers was compared with that of a glassy carbon electrode, the peak currents and the reversibility of the electrode reaction were sufficient. Therefore, the chopped carbon fibers will be useful as disposable electrodes for the sensing of biomolecules.

Irreversible pan-ErbB tyrosine kinase inhibitors and breast cancer: current status and future directions.

PubMed

Ocaña, Alberto; Amir, Eitan

2009-12-01

Aberrant activation of HER2 through overexpression has been shown to play an important role in some breast cancers. Therapies against this receptor including the monoclonal antibody, trastuzumab, or the small tyrosine kinase inhibitor, lapatinib have shown to improve the prognosis of such patients. Despite overexpressing HER2, some patients do not respond to these targeted treatments or progress after a short period of time. Irreversible tyrosine kinase inhibitors have been developed to bypass several pathways that could be involved in this resistance. In vitro, these agents have been shown to be more potent and to prolong target inhibition. Clinical development of these agents is ongoing and early results are promising. This review will describe the biologic rationale that justifies the development of these agents in breast cancer focusing on the current status and future directions.

Peptide-based protein capture agents with high affinity, selectivity, and stability as antibody replacements in biodetection assays

NASA Astrophysics Data System (ADS)

Coppock, Matthew B.; Farrow, Blake; Warner, Candice; Finch, Amethist S.; Lai, Bert; Sarkes, Deborah A.; Heath, James R.; Stratis-Cullum, Dimitra

2014-05-01

Current biodetection assays that employ monoclonal antibodies as primary capture agents exhibit limited fieldability, shelf life, and performance due to batch-to-batch production variability and restricted thermal stability. In order to improve upon the detection of biological threats in fieldable assays and systems for the Army, we are investigating protein catalyzed capture (PCC) agents as drop-in replacements for the existing antibody technology through iterative in situ click chemistry. The PCC agent oligopeptides are developed against known protein epitopes and can be mass produced using robotic methods. In this work, a PCC agent under development will be discussed. The performance, including affinity, selectivity, and stability of the capture agent technology, is analyzed by immunoprecipitation, western blotting, and ELISA experiments. The oligopeptide demonstrates superb selectivity coupled with high affinity through multi-ligand design, and improved thermal, chemical, and biochemical stability due to non-natural amino acid PCC agent design.

Non-target effects of an introduced biological control agent on deer mouse ecology

Treesearch

Dean E. Pearson; Kevin S. McKelvey; Leonard F. Ruggiero

2000-01-01

Release of exotic insects as biological control agents is a common approach to controlling exotic plants. Though controversy has ensued regarding the deleterious direct effects of biological control agents to non-target species, few have examined the indirect effects of a "well-behaved" biological control agent on native fauna. We studied a grassland in west-...

Biological agents database in the armed forces.

PubMed

Niemcewicz, Marcin; Kocik, Janusz; Bielecka, Anna; Wierciński, Michał

2014-10-01

Rapid detection and identification of the biological agent during both, natural or deliberate outbreak is crucial for implementation of appropriate control measures and procedures in order to mitigate the spread of disease. Determination of pathogen etiology may not only support epidemiological investigation and safety of human beings, but also enhance forensic efforts in pathogen tracing, collection of evidences and correct inference. The article presents objectives of the Biological Agents Database, which was developed for the purpose of the Ministry of National Defense of the Republic of Poland under the European Defence Agency frame. The Biological Agents Database is an electronic catalogue of genetic markers of highly dangerous pathogens and biological agents of weapon of mass destruction concern, which provides full identification of biological threats emerging in Poland and in locations of activity of Polish troops. The Biological Agents Database is a supportive tool used for tracing biological agents' origin as well as rapid identification of agent causing the disease of unknown etiology. It also provides support in diagnosis, analysis, response and exchange of information between institutions that use information contained in it. Therefore, it can be used not only for military purposes, but also in a civilian environment.

Development of Novel Pharmacotherapeutics for Tobacco Dependence: Progress and Future Directions

PubMed Central

Kenny, Paul J.

2012-01-01

Introduction: The vast majority of tobacco smokers seeking to quit will relapse within the first month of abstinence. Currently available smoking cessation agents have limited utility in increasing rates of smoking cessation and in some cases there are notable safety concerns related to their use. Hence, there is a pressing need to develop safer and more efficacious smoking cessation medications. Methods: Here, we provide an overview of current efforts to develop new pharmacotherapeutic agents to facilitate smoking cessation, identified from ongoing clinical trials and published reports. Results: Nicotine is considered the major addictive agent in tobacco smoke, and the vast majority of currently available smoking cessation agents act by modulating nicotinic acetylcholine receptor (nAChR) signaling. Accordingly, there is much effort directed toward developing novel small molecule therapeutics and biological agents such as nicotine vaccines for smoking cessation that act by modulating nAChR activity. Our increasing knowledge of the neurobiology of nicotine addiction has revealed new targets for novel smoking cessation therapeutics. Indeed, we highlight many examples of novel small molecule drug development around non-nAChR targets. Finally, there is a growing appreciation that medications already approved for other disease indications could show promise as smoking cessation agents, and we consider examples of such repurposing efforts. Conclusion: Ongoing clinical assessment of potential smoking cessation agents offers the promise of new effective medications. Nevertheless, much of our current knowledge of molecular mechanisms of nicotine addiction derived from preclinical studies has not yet been leveraged for medications development. PMID:23024249

Biological conversion system

DOEpatents

Scott, C.D.

A system for bioconversion of organic material comprises a primary bioreactor column wherein a biological active agent (zymomonas mobilis) converts the organic material (sugar) to a product (alcohol), a rejuvenator column wherein the biological activity of said biological active agent is enhanced, and means for circulating said biological active agent between said primary bioreactor column and said rejuvenator column.

Lipopeptides as the Antifungal and Antibacterial Agents: Applications in Food Safety and Therapeutics

PubMed Central

Meena, Khem Raj; Kanwar, Shamsher S.

2015-01-01

A lot of crops are destroyed by the phytopathogens such as fungi, bacteria, and yeast leading to economic losses to the farmers. Members of the Bacillus genus are considered as the factories for the production of biologically active molecules that are potential inhibitors of growth of phytopathogens. Plant diseases constitute an emerging threat to global food security. Many of the currently available antimicrobial agents for agriculture are highly toxic and nonbiodegradable and thus cause extended environmental pollution. Moreover, an increasing number of phytopathogens have developed resistance to antimicrobial agents. The lipopeptides have been tried as potent versatile weapons to deal with a variety of phytopathogens. All the three families of Bacillus lipopeptides, namely, Surfactins, Iturins and Fengycins, have been explored for their antagonistic activities towards a wide range of phytopathogens including bacteria, fungi, and oomycetes. Iturin and Fengycin have antifungal activities, while Surfactin has broad range of potent antibacterial activities and this has also been used as larvicidal agent. Interestingly, lipopeptides being the molecules of biological origin are environmentally acceptable. PMID:25632392

The various aspects of genetic and epigenetic toxicology: testing methods and clinical applications.

PubMed

Ren, Ning; Atyah, Manar; Chen, Wan-Yong; Zhou, Chen-Hao

2017-05-22

Genotoxicity refers to the ability of harmful substances to damage genetic information in cells. Being exposed to chemical and biological agents can result in genomic instabilities and/or epigenetic alterations, which translate into a variety of diseases, cancer included. This concise review discusses, from both a genetic and epigenetic point of view, the current detection methods of different agents' genotoxicity, along with their basic and clinical relation to human cancer, chemotherapy, germ cells and stem cells.

Chemical warfare agents

PubMed Central

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

2010-01-01

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

More About Thin-Membrane Biosensor

NASA Technical Reports Server (NTRS)

Case, George D.; Worley, Jennings F., III

1994-01-01

Report presents additional information about device described in "Thin-Membrane Sensor With Biochemical Switch" (MFS-26121). Device is modular sensor that puts out electrical signal indicative of chemical or biological agent. Signal produced as membrane-crossing ion current triggered by chemical reaction between agent and recognition protein conjugated to channel blocker. Prototype of biosensor useful in numerous laboratory, industrial, or field applications; such as to detect bacterial toxins in food, to screen for disease-producing micro-organisms, or to warn of toxins or pollutants in air.

Testing the efficacy of eGFP-transformed Aspergillus flavus as biocontrol strains

USDA-ARS?s Scientific Manuscript database

Current biological control methods to prevent pre-harvest aflatoxin contamination of corn, cottonseed, and ground and tree nuts involve field inoculation of non-aflatoxigenic Aspergillus flavus. To date, the efficacy of this approach requires annual reapplication of the biocontrol agent. The reason ...

Real-time point-of-care measurement of impaired renal function in a rat acute injury model employing exogenous fluorescent tracer agents

NASA Astrophysics Data System (ADS)

Dorshow, Richard B.; Fitch, Richard M.; Galen, Karen P.; Wojdyla, Jolette K.; Poreddy, Amruta R.; Freskos, John N.; Rajagopalan, Raghavan; Shieh, Jeng-Jong; Demirjian, Sevag G.

2013-02-01

Renal function assessment is needed for the detection of acute kidney injury and chronic kidney disease. Glomerular filtration rate (GFR) is now widely accepted as the best indicator of renal function, and current clinical guidelines advocate its use in the staging of kidney disease. The optimum measure of GFR is by the use of exogenous tracer agents. However current clinically employed agents lack sensitivity or are cumbersome to use. An exogenous GFR fluorescent tracer agent, whose elimination rate could be monitored noninvasively through skin would provide a substantial improvement over currently available methods. We developed a series of novel aminopyrazine analogs for use as exogenous fluorescent GFR tracer agents that emit light in the visible region for monitoring GFR noninvasively over skin. In rats, these compounds are eliminated by the kidney with urine recovery greater than 90% of injected dose, are not broken down or metabolized in vivo, are not secreted by the renal tubules, and have clearance values similar to a GFR reference compound, iothalamate. In addition, biological half-life of these compounds measured in rats by noninvasive optical methods correlated with plasma derived methods. In this study, we show that this noninvasive methodology with our novel fluorescent tracer agents can detect impaired renal function. A 5/6th nephrectomy rat model is employed.

Prostate cancer chemoprevention agent development: the National Cancer Institute, Division of Cancer Prevention portfolio.

PubMed

Parnes, Howard L; House, Margaret G; Kagan, Jacob; Kausal, David J; Lieberman, Ronald

2004-02-01

We describe the current National Cancer Institute chemoprevention agent development program and provide a summary of the intermediate end points used. The National Cancer Institute is currently sponsoring a wide range of studies of promising chemoprevention agents in a variety of informative cohorts, eg high grade prostatic intraepithelial neoplasia, positive family history of cancer, increased prostate specific antigen with negative biopsies, prostate cancer followed expectantly, prostate cancer awaiting definitive therapy and the general population. The rationale for each agent under investigation is derived from epidemiological observations, prostate cancer treatment trials, secondary analyses of large cancer prevention studies, an understanding of cancer biology and prostate carcinogenesis, and/or experimental animal models. Carcinogenesis is a multistep process occurring over decades which is characterized by disruption of the normal regulatory pathways controlling cellular proliferation, programmed cell death and differentiation. Administration of agents to reverse, inhibit or slow this process of malignant transformation is known as chemoprevention. Chemoprevention represents a promising approach to reducing the morbidity and mortality of prostate cancer. A variety of agents are currently being studied in phase 2 clinical trials, some of which may warrant subsequent evaluation in phase 3 trials with definitive cancer end points. Two large phase 3 trials, the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, which are ongoing, are also sponsored by the National Cancer Institute.

Molecular Contrast Optical Coherence Tomography: A Review¶

PubMed Central

Yang, Changhuei

2005-01-01

This article reviews the current state of research on the use of molecular contrast agents in optical coherence tomography (OCT) imaging techniques. After a brief discussion of the basic principle of OCT and the importance of incorporating molecular contrast agent usage into this imaging modality, we shall present an overview of the different molecular contrast OCT (MCOCT) methods that have been developed thus far. We will then discuss several important practical issues that define the possible range of contrast agent choice, the design criteria for engineered molecular contrast agent and the implementability of a given MCOCT method for clinical or biological applications. We will conclude by outlining a few areas of pursuit that deserve a greater degree of research and development. PMID:15588122

Targeted therapies: a nursing perspective.

PubMed

Kay, Polly

2006-02-01

To review the development of targeted therapies and the biology of relevant therapeutic targets. To analyze the relevance of targeted agents as part of current clinical practice. Research articles. Several targeted agents are now available for clinical use. Their mechanisms of action are more specific against tumor cells than traditional cytotoxics. Monotherapy regimens based on targeted agents tend to be better tolerated than chemotherapy, and most combination regimens with targeted agents have proven feasible. Their availability has greatly expanded cancer treatment options, especially for chemorefractory patients. Nurses involved in the care of patients with cancer can benefit from an increased understanding of targeted therapies, including their mechanisms of action, their efficacy profile, as well as prophylaxis and management of adverse events and administration procedures.

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.

Population dynamics and impacts of the red-headed leafy spurge stem borer on leafy spurge (Euphorbia esula)

Treesearch

Robert A. Progar; George Markin; Joseph Milan; Tom Barbouletos; Matthew J. Rinella

2011-01-01

We evaluated the efficacy of the biological control agent, red-headed leafy spurge stem borer, against the nonnative invasive plant leafy spurge. Our three treatments were release of the biological control agent into uncaged plots, release of the biological control agent into plots caged to prevent agent escape, and control plots caged to prevent agent entry. These...

Emerging Technologies: Biosecurity and Consequence Management Implications

NASA Astrophysics Data System (ADS)

Perkins, Dana; Nordmann, Brian

The natural outbreaks of disease and pandemics are transnational threats that create international challenges when detection and containment are not timely due to scarce human and material resources. Whether the cause of those outbreaks is natural or intentional in origin, the main goal of consequence management operations is to save lives. The consequence management process is a continuum of inter-connected phases such as planning, preparation, response, and recovery. The rapid advances of life sciences and the emergence of dual-use technologies such as synthetic biology and nanotechnology pose additional challenges in terms of planning for the unknown potential threats whether they may be synthetic microorganisms with unpredictable dissemination patterns or nanoscale-manipulated biological agents evading current detection capabilities. The US National Strategy for Countering Biological Threats is emphasizing prevention while continuing to support the national preparedness goals and response/recovery capabilities. The recent policies, guidelines, and recommendations on overhauling the biological risk management in the United States are a proactive stance to a rapidly changing global environment. They include optimization of the current oversight frameworks and active engagement of the industry and academia in order to reduce the risk that individuals with ill intent may exploit the commercial application of nucleic acid synthesis technology to access genetic material derived from or by encoding Biological Select Agents or Toxins. We are also actively seeking to increase our knowledge of health effects of various types of nanomaterials, and how to assess, control, and prevent harmful exposure, taking into consideration the numerous gaps that currently exist with regard to the distinct behavior of nanoparticles compared to the same chemical or material at "macro-scale". Fundamentally, a biological incident, whether it is of natural, accidental, or deliberate origin, constitutes a public health problem and the United States is engaged with the international community to enhance our collective capability to address emerging health security threats.

Indirect effects of host-specific biological control agents

Treesearch

Dean E. Pearson; Ragan M. Callaway

2003-01-01

Biological control is a crucial tool in the battle against biological invasions, but biocontrol agents can have a deleterious impact on native species. Recognition of risks associated with host shifting has increased the emphasis on host specificity of biocontrol agents for invasive weeds. However, recent studies indicate host-specific biocontrol agents can...

Weed biocontrol in the EU: from serendipity to strategy

USDA-ARS?s Scientific Manuscript database

Biological control of weeds is a globally-recognized approach to the management of the worst invasive plants in the world. Unfortunately, accidental introduction of agents account for most weed biocontrol in the EU, but do include a number of current or emerging successes. From the redistribution of...

Bacterial elicitation of transcriptional response of female squash bug, Anasa tristis (De Geer)

USDA-ARS?s Scientific Manuscript database

The Squash bug, Anasa tristis (De Geer), is a major pest of squash, pumpkin, and other cucurbits throughout North America. A. tristis is a piercing/sucking feeder which causes extensive foliar wilting, fruit scarring, and in addition transmits plant pathogens. Current biological control agents ava...

Immunologic responses to therapeutic biologic agents.

PubMed

Purcell, R T; Lockey, R F

2008-01-01

Recombinant protein technology and the subsequent development of biologic agents for pharmacotherapy have greatly improved the treatment of a wide variety of diseases in humans. These products are subject to reactions not previously seen in other drug classes. Additionally, subtle alteration in the manufacture or administration of a biologic agent may cause reactions in subjects who previously tolerated it. This review highlights the unique immunologic reactions that are associated with the more commonly used biologic agents.

The prevention of oral mucositis in patients with blood cancers: current concepts and emerging landscapes.

PubMed

Niscola, Pasquale; Tendas, Andrea; Cupelli, Luca; Catalano, Gianfranco; Scaramucci, Laura; Giovannini, Marco; Trinchieri, Vito; Sharma, Atul; Efficace, Fabio; Cartoni, Claudio; Piccioni, Daniela; Perrotti, Alessio; Dentamaro, Teresa; de Fabritiis, Paolo; Keefe, Dorothy M K

2012-12-01

The prevention of oral mucositis (OM) in the management of hematological malignancies continues to represent an unmet clinical need. Addressing this issue has major clinical implications as OM can also greatly impair patient's quality of life. To review currently available measures and investigational agents to prevent OM in hematological patients. we searched for OM and related issues using Medline; the abstract books of the most important hematological and oncological meetings were also reviewed. Many agents targeting different mechanisms of mucosal damage have been applied in order to prevent OM; most of them have failed or its efficacy has not been fully demonstrated. Palifermin is the first pharmaceutical/biological agent approved for the prevention of OM; its use is currently restricted to patients who have received radiotherapy-containing conditioning regimens prior to autologous hematopoietic stem cell transplantation. No clear benefit by this agent has been demonstrated outside of this specific setting and its application should be limited to clinical trials. Other interventions, such as other growth factors and non mitogenic measures are under investigation or in development and their application in the hematological setting is expected in the short term.

Catheter-related thrombosis: biological and clinical evidence for risk with currently available anticoagulants.

PubMed

Montalescot, Gilles; Walenga, Jeanine M

2009-01-01

Anticoagulants used during percutaneous coronary intervention (PCI) should not only prevent coronary events, but also minimize the risk of periprocedural complications. Current anticoagulation therapies for PCI include unfractionated heparin (UFH), enoxaparin, fondaparinux, and bivalirudin. UFH and enoxaparin have good efficacy and safety profiles in PCI; furthermore, associated periprocedural complications such as catheter thrombosis are rare. Although newer anticoagulants seem safe and effective in patients with acute coronary syndrome, clinical trial data suggest that some pure factor Xa (FXa) inhibitors are associated with increased rates of catheter thrombosis, compared with heparin-based agents. Experimental systems show that polytherapeutic agents, including UFH and enoxaparin, are more effective anticoagulants than certain single-target agents. More studies are needed to assess whether catheter thrombosis is a class-, drug-, or dose-related effect, and how best to prevent it. Future trials should report the rates of periprocedural complications when assessing the safety of novel anticoagulation therapies in PCI.

Discovery of new anticancer agents from higher plants

PubMed Central

Pan, Li; Chai, Hee-Byung; Kinghorn, A. Douglas

2012-01-01

1. ABSTRACT Small organic molecules derived from higher plants have been one of the mainstays of cancer chemotherapy for approximately the past half a century. In the present review, selected single chemical entity natural products of plant origin and their semi-synthetic derivatives currently in clinical trials are featured as examples of new cancer chemotherapeutic drug candidates. Several more recently isolated compounds obtained from plants showing promising in vivo biological activity are also discussed in terms of their potential as anticancer agents, with many of these obtained from species that grow in tropical regions. Since extracts of only a relatively small proportion of the ca. 300,000 higher plants on earth have been screened biologically to date, bioactive compounds from plants should play an important role in future anticancer drug discovery efforts. PMID:22202049

A Clinical Picture of the Visual Outcome in Adamantiades-Behçet's Disease

PubMed Central

Figus, Michele; Albert, Timothy G.; Talarico, Rosaria; Nardi, Marco

2015-01-01

Adamantiades-Behçet's disease is a multisystemic vasculitis with multiorgan involvement. Ocular disorders occur often in this syndrome typically in the form of a relapsing-remitting panuveitis and vasculitis and can lead to blindness as one of its most disabling complications if left untreated. There are known risk factors related with the worst visual prognosis, which require early and intensive treatment in order to obtain a rapid suppression of inflammation and to prevent future relapses. The management strategy to avoid vision loss and blindness currently involves the use of local and systemic drugs including steroids and immunosuppressive and biologic agents. This review aims to demonstrate how the introduction and the use of biologic agents improves the visual outcome of patients with Adamantiades-Behçet's disease. PMID:26558256

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...

Biologic interventions for fatigue in rheumatoid arthritis.

PubMed

Almeida, Celia; Choy, Ernest H S; Hewlett, Sarah; Kirwan, John R; Cramp, Fiona; Chalder, Trudie; Pollock, Jon; Christensen, Robin

2016-06-06

Fatigue is a common and potentially distressing symptom for patients with rheumatoid arthritis (RA), with no accepted evidence-based management guidelines. Evidence suggests that biologic interventions improve symptoms and signs in RA as well as reducing joint damage. To evaluate the effect of biologic interventions on fatigue in rheumatoid arthritis. We searched the following electronic databases up to 1 April 2014: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Controlled Trials Register, the National Research Register Archive, The UKCRN Portfolio Database, AMED, CINAHL, PsycINFO, Social Science Citation Index, Web of Science, and Dissertation Abstracts International. In addition, we checked the reference lists of articles identified for inclusion for additional studies and contacted key authors. We included randomised controlled trials if they evaluated a biologic intervention in people with rheumatoid arthritis and had self reported fatigue as an outcome measure. Two reviewers selected relevant trials, assessed methodological quality and extracted data. Where appropriate, we pooled data in meta-analyses using a random-effects model. We identified 32 studies for inclusion in this current review. Twenty studies evaluated five anti-tumour necrosis factor (anti-TNF) biologic agents (adalimumab, certolizumab, etanercept, golimumab and infliximab), and 12 studies focused on five non-anti-TNF biologic agents (abatacept, canakinumab, rituximab, tocilizumab and an anti-interferon gamma monoclonal antibody). All but two of the studies were double-blind randomised placebo-controlled trials. In some trials, patients could receive concomitant disease-modifying anti-rheumatic drugs (DMARDs). These studies added either biologics or placebo to DMARDs. Investigators did not change the dose of the latter from baseline. In total, these studies included 9946 participants in the intervention groups and 4682 participants in the control groups. Overall, quality of randomised controlled trials was moderate with a low to unclear risk of bias in the reporting of the outcome of fatigue. We downgraded the quality of the studies from high to moderate because of potential reporting bias (studies included post hoc analyses favouring reporting of positive result and did not always include all randomised individuals). Some studies recruited only participants with early disease. The studies used five different instruments to assess fatigue in these studies: the Functional Assessment of Chronic Illness Therapy Fatigue Domain (FACIT-F), Short Form-36 Vitality Domain (SF-36 VT), Visual Analogue Scale (VAS) (0 to 100 or 0 to 10) and the Numerical Rating Scale (NRS). We calculated standard mean differences for pooled data in meta-analyses. Overall treatment by biologic agents led to statistically significant reduction in fatigue with a standardised mean difference of -0.43 (95% confidence interval (CI) -0.38 to -0.49). This equates to a difference of 6.45 units (95% CI 5.7 to 7.35) of FACIT-F score (range 0 to 52). Both types of biologic agents achieved a similar level of improvement: for anti-TNF agents, this stood at -0.42 (95% CI -0.35 to -0.49), equivalent to 6.3 units (95% CI 5.3 to 7.4) on the FACIT-F score; and for non-anti-TNF agents, it was -0.46 (95% CI -0.39 to -0.53), equivalent to 6.9 units (95% CI 5.85 to 7.95) on the FACIT-F score. In most studies, the double-blind period was 24 weeks or less. No study assessed long-term changes in fatigue. Treatment with biologic interventions in patients with active RA can lead to a small to moderate improvement in fatigue. The magnitude of improvement is similar for anti-TNF and non-anti-TNF biologics. However, it is unclear whether the improvement results from a direct action of the biologics on fatigue or indirectly through reduction in inflammation, disease activity or some other mechanism.

The benefits of paired-agent imaging in molecular-guided surgery: an update on methods and applications (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tichauer, Kenneth M.

2016-03-01

One of the major complications with conventional imaging-agent-based molecular imaging, particularly for cancer imaging, is variability in agent delivery and nonspecific retention in biological tissue. Such factors can account to "swamp" the signal arising from specifically bound imaging agent, which is presumably indicative of the concentration of targeted biomolecule. In the 1950s, Pressman et al. proposed a method of accounting for these delivery and retention effects by normalizing targeted antibody retention to the retention of a co-administered "untargeted"/control imaging agent [1]. Our group resurrected the approach within the last 5 years, finding ways to utilize this so-called "paired-agent" imaging approach to directly quantify biomolecule concentration in tissue (in vitro, ex vivo, and in vivo) [2]. These novel paired-agent imaging approaches capable of quantifying biomolecule concentration provide enormous potential for being adapted to and optimizing molecular-guided surgery, which has a principle goal of identifying distinct biological tissues (tumor, nerves, etc…) based on their distinct molecular environment. This presentation will cover the principles and nuances of paired-agent imaging, as well as the current status of the field and future applications. [1] D. Pressman, E. D. Day, and M. Blau, "The use of paired labeling in the determination of tumor-localizing antibodies," Cancer Res, 17(9), 845-50 (1957). [2] K. M. Tichauer, Y. Wang, B. W. Pogue et al., "Quantitative in vivo cell-surface receptor imaging in oncology: kinetic modeling and paired-agent principles from nuclear medicine and optical imaging," Phys Med Biol, 60(14), R239-69 (2015).

Microcantilever technology for law enforcement and anti-terrorism applications: chemical, biological, and explosive material detection

NASA Astrophysics Data System (ADS)

Adams, J. D.; Rogers, B.; Whitten, R.

2005-05-01

The remarkable sensitivity, compactness, low cost, low power-consumption, scalability, and versatility of microcantilever sensors make this technology among the most promising solutions for detection of chemical and biological agents, as well as explosives. The University of Nevada, Reno, and Nevada Nanotech Systems, Inc (NNTS) are currently developing a microcantilever-based detection system that will measure trace concentrations of explosives, toxic chemicals, and biological agents in air. A baseline sensor unit design that includes the sensor array, electronics, power supply and air handling has been created and preliminary demonstrations of the microcantilever platform have been conducted. The envisioned device would measure about two cubic inches, run on a small watch battery and cost a few hundred dollars. The device could be operated by untrained law enforcement personnel. Microcantilever-based devices could be used to "sniff out" illegal and/or hazardous chemical and biological agents in high traffic public areas, or be packaged as a compact, low-power system used to monitor cargo in shipping containers. Among the best detectors for such applications at present is the dog, an animal which is expensive, requires significant training and can only be made to work for limited time periods. The public is already accustomed to explosives and metal detection systems in airports and other public venues, making the integration of the proposed device into such security protocols straightforward.

Decontamination of biological agents from drinking water infrastructure: a literature review and summary.

PubMed

Szabo, Jeff; Minamyer, Scott

2014-11-01

This report summarizes the current state of knowledge on the persistence of biological agents on drinking water infrastructure (such as pipes) along with information on decontamination should persistence occur. Decontamination options for drinking water infrastructure have been explored for some biological agents, but data gaps remain. Data on bacterial spore persistence on common water infrastructure materials such as iron and cement-mortar lined iron show that spores can be persistent for weeks after contamination. Decontamination data show that common disinfectants such as free chlorine have limited effectiveness. Decontamination results with germinant and alternate disinfectants such as chlorine dioxide are more promising. Persistence and decontamination data were collected on vegetative bacteria, such as coliforms, Legionella and Salmonella. Vegetative bacteria are less persistent than spores and more susceptible to disinfection, but the surfaces and water quality conditions in many studies were only marginally related to drinking water systems. However, results of real-world case studies on accidental contamination of water systems with E. coli and Salmonella contamination show that flushing and chlorination can help return a water system to service. Some viral persistence data were found, but decontamination data were lacking. Future research suggestions focus on expanding the available biological persistence data to other common infrastructure materials. Further exploration of non-traditional drinking water disinfectants is recommended for future studies. Published by Elsevier Ltd.

The contribution of molecular epidemiology to the identification of human carcinogens: current status and future perspectives.

PubMed

Boffetta, P; Islami, F

2013-04-01

The use of biological-based markers of exposure, intermediate effect, outcome, and susceptibility has become standard practice in cancer epidemiology, which has contributed to identification of several carcinogenic agents. Nevertheless, with the exception of biological agents, this contribution, in terms of providing sufficiently strong evidence as required by the International Agency for Research on Cancer (IARC) monographs, has been modest. We discuss the overall contribution of molecular epidemiology to identification of carcinogens, with focus on IARC monographs. For many carcinogens, valid biological markers of exposure and mechanisms of actions are not available. Molecular markers are usually assessed in single biological samples, which may not represent the actual exposure or biological events related to carcinogens. The contribution of molecular epidemiology to identification of carcinogens has mainly been limited to the carcinogens acting through a genotoxic mechanism, i.e. when carcinogens induce DNA damage. A number of factors, including certain hormones and overweight/obesity, may show carcinogenic effects through nongenotoxic pathways, for which mechanisms of carcinogenicity are not well identified and their biomarkers are sparse. Longitudinal assessment of biomarkers may provide more informative data in molecular epidemiology studies. For many carcinogens and mechanistic pathways, in particular nongenotoxic carcinogenicity, valid biological markers still need to be identified.

Agents of Bioterrorism: Curriculum and Pedagogy in an Online Masters Course

PubMed Central

Page, Eric J.; Gray, Joshua P.

2014-01-01

The Agents of Bioterrorism course (BSBD 640, University of Maryland University College) is a graduate level course created in response to an elevated need for scientists working in the field of medical countermeasures to biological and chemical weapons in the years following 9/11. Students read and evaluate assigned current primary literature articles investigating medical countermeasures at each stage of development. In addition, students learn concepts of risk assessment, comparing and ranking several agents of terror. Student learning is assessed through a variety of assignments. A term paper focuses on a lesser known weapon of terror, with students recommending the best countermeasure in development and delivering a risk assessment comparing their agent to other major weapons of terror discussed throughout the semester. Similarly, a group project on an assigned major weapon of terror (anthrax, plague, smallpox, vesicants, or nerve agent) focuses more heavily on evaluating primary literature and concluding which countermeasure(s) in development are the best. Students complete the course with a fundamental understanding of the mechanism of action of many biological agents, information literacy for the medical literature available at PubMed and the primary scientific literature, and a basic understanding of the role of the government in biodefense research. This paper describes the pedagogical approaches used to teach this course and how they might be adopted for other courses. PMID:25089297

Agents of Bioterrorism: Curriculum and Pedagogy in an Online Masters Course.

PubMed

Page, Eric J; Gray, Joshua P

2014-01-10

The Agents of Bioterrorism course (BSBD 640, University of Maryland University College) is a graduate level course created in response to an elevated need for scientists working in the field of medical countermeasures to biological and chemical weapons in the years following 9/11. Students read and evaluate assigned current primary literature articles investigating medical countermeasures at each stage of development. In addition, students learn concepts of risk assessment, comparing and ranking several agents of terror. Student learning is assessed through a variety of assignments. A term paper focuses on a lesser known weapon of terror, with students recommending the best countermeasure in development and delivering a risk assessment comparing their agent to other major weapons of terror discussed throughout the semester. Similarly, a group project on an assigned major weapon of terror (anthrax, plague, smallpox, vesicants, or nerve agent) focuses more heavily on evaluating primary literature and concluding which countermeasure(s) in development are the best. Students complete the course with a fundamental understanding of the mechanism of action of many biological agents, information literacy for the medical literature available at PubMed and the primary scientific literature, and a basic understanding of the role of the government in biodefense research. This paper describes the pedagogical approaches used to teach this course and how they might be adopted for other courses.

Simulated experiment for elimination of chemical and biological warfare agents by making use of microwave plasma torch

NASA Astrophysics Data System (ADS)

Hong, Yong C.; Kim, Jeong H.; Uhm, Han S.

2004-02-01

The threat of chemical and biological warfare agents in a domestic terrorist attack and in military conflict is increasing worldwide. Elimination and decontamination of chemical and biological warfare (CBW) agents are immediately required after such an attack. Simulated experiment for elimination of CBW agents by making use of atmospheric-pressure microwave plasma torches is carried out. Elimination of biological warfare agents indicated by the vitrification or burnout of sewage sludge powders and decomposition of toluene gas as a chemical agent stimulant are presented. A detailed characterization for the elimination of the simulant chemicals using Fourier transform infrared and gas chromatography is also presented.

Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids.

PubMed

Hamilton, Gregory S

2015-09-01

Antibody-drug conjugates (ADCs) are a new class of therapeutic agents that combine the targeting ability of monoclonal antibodies (mAbs) with small molecule drugs. The combination of a mAb targeting a cancer-specific antigen with a cytotoxin has tremendous promise as a new type of targeted cancer therapy. Two ADCs have been approved and many more are in clinical development, suggesting that this new class of drugs is coming to the forefront. Because of their unique nature as biologic-small drug hybrids, ADCs are challenging to develop, from both the scientific and regulatory perspectives. This review discusses both these aspects in current practice, and surveys the current state of the art of ADC drug development. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Objects of consciousness

PubMed Central

Hoffman, Donald D.; Prakash, Chetan

2014-01-01

Current models of visual perception typically assume that human vision estimates true properties of physical objects, properties that exist even if unperceived. However, recent studies of perceptual evolution, using evolutionary games and genetic algorithms, reveal that natural selection often drives true perceptions to extinction when they compete with perceptions tuned to fitness rather than truth: Perception guides adaptive behavior; it does not estimate a preexisting physical truth. Moreover, shifting from evolutionary biology to quantum physics, there is reason to disbelieve in preexisting physical truths: Certain interpretations of quantum theory deny that dynamical properties of physical objects have definite values when unobserved. In some of these interpretations the observer is fundamental, and wave functions are compendia of subjective probabilities, not preexisting elements of physical reality. These two considerations, from evolutionary biology and quantum physics, suggest that current models of object perception require fundamental reformulation. Here we begin such a reformulation, starting with a formal model of consciousness that we call a “conscious agent.” We develop the dynamics of interacting conscious agents, and study how the perception of objects and space-time can emerge from such dynamics. We show that one particular object, the quantum free particle, has a wave function that is identical in form to the harmonic functions that characterize the asymptotic dynamics of conscious agents; particles are vibrations not of strings but of interacting conscious agents. This allows us to reinterpret physical properties such as position, momentum, and energy as properties of interacting conscious agents, rather than as preexisting physical truths. We sketch how this approach might extend to the perception of relativistic quantum objects, and to classical objects of macroscopic scale. PMID:24987382

Population dynamics and impacts of the red-headed leafy spurge stem borer on leafy spurge

Treesearch

R. A. Progar; G. P. Markin; J. Milan; T. Barbouletos; M. J. Rinella

2013-01-01

We evaluated the efficacy of the biological control agent, red-headed leafy spurge stem borer (Oberea erythrocephala Schrank.) against the nonnative invasive plant leafy spurge (Euphorbia esula L.). Our three treatments were release of the biological control agent into uncaged plots, release of the biological control agent into plots caged to prevent agent escape and...

Solid-water detoxifying reagents for chemical and biological agents

DOEpatents

Hoffman, Dennis M [Livermore, CA; Chiu, Ing Lap [Castro Valley, CA

2006-04-18

Formation of solid-water detoxifying reagents for chemical and biological agents. Solutions of detoxifying reagent for chemical and biological agents are coated using small quantities of hydrophobic nanoparticles by vigorous agitation or by aerosolization of the solution in the presence of the hydrophobic nanoparticles to form a solid powder. For example, when hydrophobic fumed silica particles are shaken in the presence of IN oxone solution in approximately a 95:5-weight ratio, a dry powder results. The hydrophobic silica forms a porous coating of insoluble fine particles around the solution. Since the chemical or biological agent tends to be hydrophobic on contact with the weakly encapsulated detoxifying solution, the porous coating breaks down and the detoxifying reagent is delivered directly to the chemical or biological agent for maximum concentration at the point of need. The solid-water (coated) detoxifying solutions can be blown into contaminated ventilation ducting or other difficult to reach sites for detoxification of pools of chemical or biological agent. Once the agent has been detoxified, it can be removed by flushing the area with air or other techniques.

History of chemical and biological warfare agents.

PubMed

Szinicz, L

2005-10-30

Chemical and biological warfare agents constitute a low-probability, but high-impact risk both to the military and to the civilian population. The use of hazardous materials of chemical or biological origin as weapons and for homicide has been documented since ancient times. The first use of chemicals in terms of weapons of mass destruction goes back to World War I, when on April 22, 1915 large amounts of chlorine were released by German military forces at Ypres, Belgium. Until around the 1970s of the 20th century, the awareness of the threat by chemical and biological agents had been mainly confined to the military sector. In the following time, the development of increasing range delivery systems by chemical and biological agents possessors sensitised public attention to the threat emanating from these agents. Their proliferation to the terrorists field during the 1990s with the expanding scale and globalisation of terrorist attacks suggested that these agents are becoming an increasing threat to the whole world community. The following article gives a condensed overview on the history of use and development of the more prominent chemical and biological warfare agents.

Biological agents for moderately to severely active ulcerative colitis: a systematic review and network meta-analysis.

PubMed

Danese, Silvio; Fiorino, Gionata; Peyrin-Biroulet, Laurent; Lucenteforte, Ersilia; Virgili, Gianni; Moja, Lorenzo; Bonovas, Stefanos

2014-05-20

Biological agents are emerging treatment options for the management of ulcerative colitis (UC). To assess the comparative efficacy and harm of biological agents in adult patients with moderately to severely active UC who are naive to biological agents. MEDLINE, EMBASE, and Cochrane Library from inception through December 2013, without language restrictions, and ClinicalTrials.gov, European Medicines Agency, and U.S. Food and Drug Administration Web sites. Randomized, placebo-controlled or head-to-head trials assessing biological agents as induction or maintenance therapy for moderately to severely active UC. Two reviewers independently abstracted study data and outcomes and rated each trial's risk of bias. There were no head-to-head trials. There were 7 double-blind, placebo-controlled trials that were rated as low risk of bias and showed that all biological agents (adalimumab, golimumab, infliximab, and vedolizumab) resulted in more clinical responses, clinical remissions, and mucosal healings than placebo for induction therapy. The results of network meta-analysis suggested that infliximab is more effective to induce clinical response (odds ratio, 2.36 [95% credible interval, 1.22 to 4.63]) and mucosal healing (odds ratio, 2.02 [95% credible interval, 1.13 to 3.59]) than adalimumab. No other indirect comparison reached statistical significance. For maintenance, 6 double-blind, placebo-controlled trials that were rated high risk of bias showed that all biological agents have greater clinical efficacy than placebo. The occurrence of adverse events was not different between biological agents and placebo. Few trials, no head-to-head comparisons, and inadequate follow-up in maintenance trials. Biological agents are effective treatments for UC, but head-to-head trials are warranted to establish the best therapeutic option.

Implementing a bioterrorism response plan in your pharmacy.

PubMed

Teeter, David; Terriff, Colleen

2002-01-01

Pharmacies and other types of health care facilities need emergency response plans. Pharmacists need to stay current on biologic and other agents that can be used as agents of mass destruction and their clinical management. Local plans should incorporate federal resources that can be used in emergencies, but the time required for these resources to be organized, delivered, and distributed needs to be considered. Pharmacists are urged to assist with inventories of available health care facilities, supplies, and medications. Planning needs to be coordinated with local emergency preparedness officials.

Review of the contemporary cytotoxic and biologic combinations available for the treatment of metastatic breast cancer.

PubMed

Tkaczuk, Katherine H Rak

2009-01-01

Treatment of metastatic breast cancer (MBC) with > or =2 chemotherapeutic agents concurrently has been shown to increase response rates, often at the cost of a substantial increase in toxicity, and with minimal impact on the overall survival. However, some combinations of the newer cytotoxic agents, as well as combinations of chemotherapeutic agents and targeted biologic anticancer agents, can produce synergistic efficacy with a manageable toxicity profile. The aims of this work were to provide an overview of the currently approved combination regimens available for the treatment of MBC and to consider the clinical data supporting other drug combinations that may supplement the current therapeutic choices in the near future. Literature searches were performed using MEDLINE/PubMed, with a focus on combination therapies for the treatment of MBC that are approved by the US Food and Drug Administration (FDA) or in Phase III clinical trials. The National Institutes of Health's Clinical Trial Registry was searched for relevant ongoing clinical trials in specific areas. Bibliographies were also searched for additional relevant material. Preference was given to recently published, larger, well-designed clinical trials that influence current prescribing practices. Phase I and II studies, and/or studies older than 10 years (ie, published earlier than 1999), were afforded less emphasis or were disregarded. Combinations of taxanes with capecitabine or gemcitabine, and ixabepilone plus capecitabine, are approved by the FDA as combination regimens for the treatment of MBC. The use of targeted therapies such as trastuzumab, bevacizumab, or lapatinib in combination with taxanes (for the former two) or capecitabine (for lapatinib) is also approved. Several investigational drug combinations are also currently undergoing evaluation in clinical trials, including combinations of bevacizumab and gemcitabine with capecitabine or alternative taxanes. Although results from Phase I and II studies are largely encouraging so far, the data from ongoing Phase III studies will ultimately dictate changes in clinical practice. It seems unlikely that any single agent or combination regimen will emerge as superior in all patients with MBC, given the heterogeneous nature of the disease and patient population. New combination regimens for MBC may broaden the range of treatment options currently available to delay disease progression for as long as possible. Copyright 2009 Excerpta Medica Inc. All rights reserved.

Rational Combinations of Targeted Agents in AML

PubMed Central

Bose, Prithviraj; Grant, Steven

2015-01-01

Despite modest improvements in survival over the last several decades, the treatment of AML continues to present a formidable challenge. Most patients are elderly, and these individuals, as well as those with secondary, therapy-related, or relapsed/refractory AML, are particularly difficult to treat, owing to both aggressive disease biology and the high toxicity of current chemotherapeutic regimens. It has become increasingly apparent in recent years that coordinated interruption of cooperative survival signaling pathways in malignant cells is necessary for optimal therapeutic results. The modest efficacy of monotherapy with both cytotoxic and targeted agents in AML testifies to this. As the complex biology of AML continues to be elucidated, many “synthetic lethal” strategies involving rational combinations of targeted agents have been developed. Unfortunately, relatively few of these have been tested clinically, although there is growing interest in this area. In this article, the preclinical and, where available, clinical data on some of the most promising rational combinations of targeted agents in AML are summarized. While new molecules should continue to be combined with conventional genotoxic drugs of proven efficacy, there is perhaps a need to rethink traditional philosophies of clinical trial development and regulatory approval with a focus on mechanism-based, synergistic strategies. PMID:26113989

Detecting Biological Warfare Agents

PubMed Central

Song, Linan; Ahn, Soohyoun

2005-01-01

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

Desensitization: Overcoming the Immunologic Barriers to Transplantation

PubMed Central

Choi, Jua; Vo, Ashley; Peng, Alice; Jordan, Stanley C.

2017-01-01

HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection. PMID:28127571

Passive Antibody Administration (Immediate Immunity) as a Specific Defense Against Biological Weapons

PubMed Central

2002-01-01

The potential threat of biological warfare with a specific agent is proportional to the susceptibility of the population to that agent. Preventing disease after exposure to a biological agent is partially a function of the immunity of the exposed individual. The only available countermeasure that can provide immediate immunity against a biological agent is passive antibody. Unlike vaccines, which require time to induce protective immunity and depend on the host’s ability to mount an immune response, passive antibody can theoretically confer protection regardless of the immune status of the host. Passive antibody therapy has substantial advantages over antimicrobial agents and other measures for postexposure prophylaxis, including low toxicity and high specific activity. Specific antibodies are active against the major agents of bioterrorism, including anthrax, smallpox, botulinum toxin, tularemia, and plague. This article proposes a biological defense initiative based on developing, producing, and stockpiling specific antibody reagents that can be used to protect the population against biological warfare threats. PMID:12141970

Targeting Ovarian Cancer with Porphysome Nanotechnology

DTIC Science & Technology

2015-10-01

human administration; these specifications include requirements/restrictions on the volume, pH , appearance, sterility, bacterial endotoxins ...the translational success of nanomedicines is the ability to produce agents in accordance with quality control systems such as current Good...sufficiently robust and reliable for producing the same product time after time with the intended physicochemical characteristics, biological behaviors, and

The Cost-Effectiveness of Vedolizumab for Inflammatory Bowel Disease: A Review of the Current Literature

PubMed Central

Saumoy, Monica; Cohen-Mekelburg, Shirley; Steinlauf, Adam F.; Scherl, Ellen J.

2016-01-01

The United States spends a greater share per gross domestic product on health care than any other developed country in the world. Cost-conscious, high-value care has an important role in the practice of medicine. Inflammatory bowel disease (IBD) affects 1.6 million people in the United States and is responsible for significant health care costs, with estimates as high as $31.6 billion annually, a large portion of which is attributable to the use of biologic therapies. As the number of therapeutic targets for IBD expands, gastroenterologists can anticipate the arrival of novel therapeutic agents on the market, and these may carry significant costs. Vedolizumab, a monoclonal antibody directed against the gut-selective integrin α4β7, is a novel biologic agent approved for the treatment of Crohn’s disease and ulcerative colitis. Cost-effectiveness is an area of research that aims to assess the added value (in terms of both cost and utility) of diagnostic or therapeutic interventions. This article reviews the current literature evaluating the cost-effectiveness of vedolizumab for the treatment of IBD. PMID:27917076

Immunopharmacotherapy of non-infectious uveitis: where do we stand?

PubMed

Agrawal, Rupesh; Lee, Cecilia; Phatak, Sumita; Pavesio, Carlos

2014-12-01

With ever-evolving concept of personalised medicine backed up with specific biomarkers for ocular inflammatory disease, there is a sudden surge of using biologics in non-infectious recalcitrant posterior uveitis. Have we understood these biologic agents enough to embark on this long enduring journey with the patient to optimise control of intraocular inflammation? On the other hand, there is still a strong inhibition of using these novel agents in management of uveitis even at tertiary referral centres. Immunopharmacotherapy of non-infectious uveitis poses a significant conundrum for both physicians and patients as it is like a two-edged sword effective to control inflammation but at the same time potentially toxic, suspected of causing long-term adverse effects. Systemic immunosuppressive therapy is used in a substantial number of most vision-threatening ocular inflammatory diseases. There is lack of randomised control trials establishing the safety of this therapy and our current practice pattern is based on retrospective studies and personal experience in using this treatment modality. This overview will highlight on the current dilemma faced by the clinicians in opting for steroid-sparing immunosuppressive therapy.

[Occupational exposure to biological agents intentionally used in Polish enterprises].

PubMed

Kozajda, Anna; Szadkowska-Stańczyk, Irena

2015-01-01

The paper presents the intentional use of biological agents for industrial, diagnostic and research purposes in Polish enterprises. The National Register of Biological Agents (Krajowy Rejestr Czynników Biologicznych - KRCB) is an online database that collects the data on the intentional use of biological agents at work in Poland. As of December 2013 there were 533 notifications in KRCB, mainly for diagnostic (73%), research (20%) and industrial purposes (7%). Mostly there were hospital diagnostic laboratories (37%), and other laboratories (35%), as well as higher education and research institutions (11%). In total, 4015 workers (91.7% of women, 8.3% of men) were exposed tobiological agents. Agents classified in risk group 2 were used in 518 enterprises, and in risk group 3 in 107 enterprises. Of those agents the following bacteria were the most frequently used: Escherichia coli except for non-pathogenic strains (455 enterprises and 3314 exposed workers); Staphylococcus aureus (445 and 3270); and Pseudomonas aeruginosa (406 and 2969, respectively). In 66 enterprises there were used biological agents recognized by the International Agency for Research on Cancer (IARC) as carcinogens. They are viruses: Epstein-Barr (7 enterprises, 181 exposed workers); hepatitis B (16 and 257); hepatitis C virus (15 and 243); human immunodefi- ciency virus (8 and 107); human papillomaviruses (2 and 4); parasites: Clonorchis viverrini (1 and 2 ); Clonorchos sinensis (1 and 2); Schistosoma haematobium (1 and 2) and bacteria Helicobacter pylori; (15 and 230, respectively). The National Register of Biological Agents at Work permits to evaluate the situation of occupational exposure to biological agents used intentionally in enterprises in Poland.

Evaluation of time required for water-only decontamination of an oil-based agent.

PubMed

Moffett, Peter M; Baker, Benjamin L; Kang, Christopher S; Johnson, Melinda S

2010-03-01

The objective was to evaluate the time to decontaminate an area of skin exposed to an oil-based agent using a water-only decontamination protocol. A fluorescent mock chemical/biological agent was created. Each of 20 subjects had his/her forearm sprayed with the agent. Each subject placed his/her arm under a decontamination shower, which provided water at a pressure of 60-70 psi and 35 degrees C. After 30 sec a black light was used by three evaluators to determine whether the agent was removed. The process of 30 sec decontamination and re-evaluation was repeated for a total of 5 min. The primary endpoint was proportion decontaminated over time. After 90 sec, 100% of subjects were decontaminated. Whereas the data suggest the possibility of rapid water-only decontamination, the applicability of this data in current form is doubtful, but provides a model as a basis for future study.

Potent antitumor bifunctional DNA alkylating agents, synthesis and biological activities of 3a-aza-cyclopenta[a]indenes.

PubMed

Kakadiya, Rajesh; Dong, Huajin; Lee, Pei-Chih; Kapuriya, Naval; Zhang, Xiuguo; Chou, Ting-Chao; Lee, Te-Chang; Kapuriya, Kalpana; Shah, Anamik; Su, Tsann-Long

2009-08-01

A series of bifunctional DNA interstrand cross-linking agents, bis(hydroxymethyl)- and bis(carbamates)-8H-3a-azacyclopenta[a]indene-1-yl derivatives were synthesized for antitumor evaluation. The preliminary antitumor studies revealed that these agents exhibited potent cytotoxicity in vitro and antitumor therapeutic efficacy against human tumor xenografts in vivo. Furthermore, these derivatives have little or no cross-resistance to either Taxol or Vinblastine. Remarkably, complete tumor remission in nude mice bearing human breast carcinoma MX-1 xenograft by 13a,b and 14g,h and significant suppression against prostate adenocarcinoma PC3 xenograft by 13b were achieved at the maximum tolerable dose with relatively low toxicity. In addition, these agents induce DNA interstrand cross-linking and substantial G2/M phase arrest in human non-small lung carcinoma H1299 cells. The current studies suggested that these agents are promising candidates for preclinical studies.

Biologic agents therapy for Saudi children with rheumatic diseases: indications and safety.

PubMed

Al-Mayouf, Sulaiman M; Alenazi, Abdullatif; AlJasser, Hind

2016-06-01

To report the indications and safety of biologic agents in childhood rheumatic diseases at a tertiary hospital. Children with rheumatic diseases treated with biologic agents at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, from January 2001 to December 2011 were included. All patients were reviewed for: demographic characteristics, diagnosis, concomitant treatment and indications of using biologic agents, age at start of therapy and side effects during the treatment period. In all, 134 children (89 female) with various rheumatic diseases were treated with biologic agents. Mean age at starting biologic treatment was 9.3 (4.25-14) years and mean therapy duration was 14.7 (3-88) months. Juvenile idiopathic arthritis (JIA) was the most frequent diagnosis (70.1%) followed by systemic lupus erythematosus (12.7%) and vasculitis (4.5%). All patients received concomitant therapy (corticosteroids and disease-modifying antirheumatic drugs). In total, 273 treatments with biologic agents were used, (95 etanercept, 52 rituximab, 47 adalimumab, 37 infliximab, 23 anakinra, 10 tocilizumab and nine abatacept). Therapy was switched to another agent in 57 (42.5%) patients, mainly because of inefficacy (89.4%) or adverse event (10.6%). A total of 95 (34.8%) adverse events were notified; of these, the most frequent were infusion-related reactions (33.7%) followed by infections (24.2%) and autoantibody positivity (10.6%). One patient developed macrophage activation syndrome. Biologic agents were used in children with a range of rheumatic diseases. Of these, the most frequent was JIA. Off-label use of biologic agents in our cohort is common. These agents seem safe. However, they may associated with various adverse events. Sequential therapy seems well tolerated. However, this should be carefully balanced and considered on an individual basis. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Pythium species and isolate diversity influence inhibition by the biological control agent Streptomyces lydicus

USDA-ARS?s Scientific Manuscript database

Disease control of soilborne pathogens by biological control agents has often been inconsistent under field conditions. One factor that may contribute to this inconsistency is the variability in response among pathogen populations and/or communities to the selected biological control agent. One hund...

Biologic agents for anterior cruciate ligament healing: A systematic review

PubMed Central

Di Matteo, Berardo; Loibl, Markus; Andriolo, Luca; Filardo, Giuseppe; Zellner, Johannes; Koch, Matthias; Angele, Peter

2016-01-01

AIM To systematically review the currently available literature concerning the application of biologic agents such as platelet-rich plasma (PRP) and stem cells to promote anterior cruciate ligament (ACL) healing. METHODS A systematic review of the literature was performed on the use of biologic agents (i.e., PRP or stem cells) to favor ACL healing during reconstruction or repair. The following inclusion criteria for relevant articles were used: Clinical reports of any level of evidence, written in English language, on the use of PRP or stem cells during ACL reconstruction/repair. Exclusion criteria were articles written in other languages, reviews, or studies analyzing other applications of PRP/stem cells in knee surgery not related to promoting ACL healing. RESULTS The database search identified 394 records that were screened. A total of 23 studies were included in the final analysis: In one paper stem cells were applied for ACL healing, in one paper there was a concomitant application of PRP and stem cells, whereas in the remaining 21 papers PRP was used. Based on the ACL injury pattern, two papers investigated biologic agents in ACL partial tears whereas 21 papers in ACL reconstruction. Looking at the quality of the available literature, 17 out of 21 studies dealing with ACL reconstruction were randomized controlled trials. Both studies on ACL repair were case series. CONCLUSION There is a paucity of clinical trials investigating the role of stem cells in promoting ACL healing both in case of partial and complete tears. The role of PRP is still controversial and the only advantage emerging from the literature is related to a better graft maturation over time, without documenting beneficial effects in terms of clinical outcome, bone-graft integration and prevention of bony tunnel enlargement. PMID:27672573

Immunosuppressive Treatment of Non-infectious Uveitis: History and Current Choices.

PubMed

Zhao, Chan; Zhang, Meifen

2017-04-10

Non-infectious uveitis is one of the leading causes of preventable blindness worldwide. Long-term immunosuppressive treatment is generally required to achieve durable control of inflammation in posterior and panuveitis. Although systemic corticosteroids have been the gold standard of immunosup- pressive treatment for uveitis since first introduced in 1950s, its side effects of long-term use often warrant an adjuvant treatment to reduce the dosage/duration of corticosteroids needed to maintain disease control. Conventional immunosuppressive drugs, classified into alkylating agent, antimetabolites and T cell inhibitors, have been widely used as corticosteroid-sparing agents, each with characteristic safety/tolerance profiles on different uveitis entities. Recently, biologic agents, which target specific molecules in immunopathogenesis of uveitis, have gained great interest as alternative treatments for refractory uveitis based on their favorable safety and effectiveness in a variety of uveitis entities. However, lack of large randomized controlled clinical trials, concerns about efficacy and safety of long-term usage, and economic burden are limiting the use of biologics in non-infectious uveitis. Local administration of immunosuppressive drugs (from corticosteroids to biologics) through intraocular drug delivery systems represent another direction for drug development and is now under intense investigation, but more evidences are needed to support their use as regular alternative treatments for uveitis. With the numerous choices belonging to different treatment modalities (conventional immunosuppressive agents, biologics and local drug delivery systems) on hand, the practice patterns have been reported to vary greatly from center to center. Factors influence uveitis specialists' choices of immunosuppressive agents may be complex and may include personal familiarity, treatment availability, safety/tolerability, effectiveness, patient compliance, cost concerns and suggestions from related specialists such as rheumatologists and pediatricians. The focus of this review is to provide an overview of each treatment modality on safety/tolerability and effectiveness, which are believed to be the two most important factors affecting treatment decision making.

Utilization and viability of biologically-inspired algorithms in a dynamic multiagent camera surveillance system

NASA Astrophysics Data System (ADS)

Mundhenk, Terrell N.; Dhavale, Nitin; Marmol, Salvador; Calleja, Elizabeth; Navalpakkam, Vidhya; Bellman, Kirstie; Landauer, Chris; Arbib, Michael A.; Itti, Laurent

2003-10-01

In view of the growing complexity of computational tasks and their design, we propose that certain interactive systems may be better designed by utilizing computational strategies based on the study of the human brain. Compared with current engineering paradigms, brain theory offers the promise of improved self-organization and adaptation to the current environment, freeing the programmer from having to address those issues in a procedural manner when designing and implementing large-scale complex systems. To advance this hypothesis, we discus a multi-agent surveillance system where 12 agent CPUs each with its own camera, compete and cooperate to monitor a large room. To cope with the overload of image data streaming from 12 cameras, we take inspiration from the primate"s visual system, which allows the animal to operate a real-time selection of the few most conspicuous locations in visual input. This is accomplished by having each camera agent utilize the bottom-up, saliency-based visual attention algorithm of Itti and Koch (Vision Research 2000;40(10-12):1489-1506) to scan the scene for objects of interest. Real time operation is achieved using a distributed version that runs on a 16-CPU Beowulf cluster composed of the agent computers. The algorithm guides cameras to track and monitor salient objects based on maps of color, orientation, intensity, and motion. To spread camera view points or create cooperation in monitoring highly salient targets, camera agents bias each other by increasing or decreasing the weight of different feature vectors in other cameras, using mechanisms similar to excitation and suppression that have been documented in electrophysiology, psychophysics and imaging studies of low-level visual processing. In addition, if cameras need to compete for computing resources, allocation of computational time is weighed based upon the history of each camera. A camera agent that has a history of seeing more salient targets is more likely to obtain computational resources. The system demonstrates the viability of biologically inspired systems in a real time tracking. In future work we plan on implementing additional biological mechanisms for cooperative management of both the sensor and processing resources in this system that include top down biasing for target specificity as well as novelty and the activity of the tracked object in relation to sensitive features of the environment.

Developmental Biology and Regenerative Medicine: Addressing the Vexing Problem of Persistent Muscle Atrophy in the Chronically Torn Human Rotator Cuff.

PubMed

Meyer, Gretchen A; Ward, Samuel R

2016-05-01

Persistent muscle atrophy in the chronically torn rotator cuff is a significant obstacle for treatment and recovery. Large atrophic changes are predictive of poor surgical and nonsurgical outcomes and frequently fail to resolve even following functional restoration of loading and rehabilitation. New insights into the processes of muscle atrophy and recovery gained through studies in developmental biology combined with the novel tools and strategies emerging in regenerative medicine provide new avenues to combat the vexing problem of muscle atrophy in the rotator cuff. Moving these treatment strategies forward likely will involve the combination of surgery, biologic/cellular agents, and physical interventions, as increasing experimental evidence points to the beneficial interaction between biologic therapies and physiologic stresses. Thus, the physical therapy profession is poised to play a significant role in defining the success of these combinatorial therapies. This perspective article will provide an overview of the developmental biology and regenerative medicine strategies currently under investigation to combat muscle atrophy and how they may integrate into the current and future practice of physical therapy. © 2016 American Physical Therapy Association.

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.

76 FR 10602 - Medicare Program; Public Meetings in Calendar Year 2011 for All New Public Requests for Revisions...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-25

.../Biologicals/Radiopharmaceuticals/Radiologic Imaging Agents). 2. Wednesday, May 18, 2011, 9 a.m. to 5 p.m. e.d.t. (Drugs/ Biologicals/Radiopharmaceuticals/Radiologic Imaging Agents). 3. Tuesday, May 24, 2011, 9... not need the second day of Drugs/Biologicals/ Radiopharmaceuticals/Radiologic Imaging Agents Public...

75 FR 8971 - Medicare Program; Public Meetings in Calendar Year 2010 for All New Public Requests for Revisions...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-26

.../Biologicals/Radiopharmaceuticals/Radiologic Imaging Agents). 2. Wednesday, May 5, 2010, 9 a.m. to 5 p.m., e.d.t. (Drugs/ Biologicals/Radiopharmaceuticals/Radiologic Imaging Agents). 3. Tuesday, May 25, 2010, 9... not need the second day of Drugs/Biologicals/ Radiopharmaceuticals/Radiologic Imaging Agents Public...

Issues in chemical and biological terrorism.

PubMed

Salem, Harry

2003-01-01

This manuscript describes the overview presented at the 23rd Annual Meeting of the American College of Toxicology in 2002. Although it is recognized that weapons of mass destruction that can be used against our military and civilian populations include chemical, biological, radiological, and nuclear (CBRN) agents, this overview is limited primarily to chemical and biological (CB) agents. The issues of CB terrorism are discussed in terms of When, What, How, and Who. The US Army has been providing chemical and biological solutions since 1917, and has since 1996 applied these solutions to homeland defense and domestic preparedness. The use of chemical and biological agents as terrorist weapons both in the United States and elsewhere in the world is reviewed. The CB threat spectrum is presented, as is the further categorization of biological threat agents by the Centers for Disease Control and Prevention (CDC). In addition, the CB agents considered to be a potential threat to our water supply are also presented. These are agents that are water soluble, stable, and resistant to water treatment and/or disinfection. The overview concludes with the chronological accomplishments of ECBC since 1917.

[Interpretation of the updates of NCCN 2017 version 1.0 guideline for colorectal cancer].

PubMed

Chen, Gong

2017-01-25

The NCCN has recently released its 2017 version 1.0 guideline for colorectal cancer. There are several updates from this new version guideline which are believed to change the current clinical practice. Update one, low-dose aspirin is recommended for patients with colorectal cancer after colectomy for secondary chemoprevention. Update two, biological agents are removed from the neoadjuvant treatment regimen for resectable metastatic colorectal cancer (mCRC). This update is based on lack of evidence to support benefits of biological agents including bevacizumab and cetuximab in the neoadjuvant setting. Both technical criteria and prognostic information should be considered for decision-making. Currently biological agents may not be excluded from the neoadjuvant setting for patients with resectable but poor prognostic disease. Update three, panitumumab and cetuximab combination therapy is only recommended for left-sided tumors in the first line therapy. The location of the primary tumor can be both prognostic and predictive in response to EGFR inhibitors in metastatic colorectal cancer. Cetuximab and panitumumab confer little benefit to patients with metastatic colorectal cancer in the primary tumor originated on the right side. On the other hand, EGFR inhibitors provide significant benefit compared with bevacizumab-containing therapy or chemotherapy alone for patients with left primary tumor. Update four, PD-1 immune checkpoint inhibitors including pembrolizumab or nivolumab are recommended as treatment options in patients with metastatic deficient mismatch repair (dMMR) colorectal cancer in second- or third-line therapy. dMMR tumors contain thousands of mutations, which can encode mutant proteins with the potential to be recognized and targeted by the immune system. It has therefore been hypothesized that dMMR tumors may be sensitive to PD-1 inhibitors.

The Concept of Biosimilars: From Characterization to Evolution-A Narrative Review.

PubMed

Farhat, Fadi; Torres, Alfredo; Park, Wungki; de Lima Lopes, Gilberto; Mudad, Raja; Ikpeazu, Chukwuemeka; Abi Aad, Simon

2018-03-01

Biologic agents are currently the fastest emerging segment of drug expenditure. Unlike chemically synthesized small-molecule drugs, biologics are more complex, medicinal products produced by a living organism. They have become part of the standard of care in the treatment of a large variety of diseases, such as growth disorders, autoimmune diseases, cancer, cardiovascular illnesses, hemophilia, and rare genetic conditions, to name a few. Biosimilars, which are copies of biologics that are highly similar, were introduced in the market with an aim to offer efficacy that is not clinically different from the originator or reference product, at lower prices. We aim to clarify the concept of biosimilar, from definitions, history, market entry, challenges faced, and future evolution. For that purpose, we performed a literature search on the sites of the medicines regulatory agencies and PubMed from 1990 to 2014 with the keywords "biosimilars," "market," and "regulatory." In 2006, the first biosimilar, somatropin [rDNA origin], was marketed and led the way for biosimilar drug manufacturing. As a result, manufacturers have entered a diversified competition, facing challenges in manufacturing these complex agents, such as immunogenicity and efficiency. Biosimilars are set to evolve differently in various markets, namely the U.S., Japan, the European Union, and the "pharmerging" economies. This article highlights the importance of biosimilars, as a cost-cutting strategy, in the delivery of state-of-the-art health care in developing countries, at a fraction of what a reference biological agent would cost. © AlphaMed Press 2017.

Management Options in Triple-Negative Breast Cancer

PubMed Central

Minami, Christina A.; Chung, Debra U.; Chang, Helena R.

2011-01-01

Notorious for its poor prognosis and aggressive nature, triple-negative breast cancer (TNBC) is a heterogeneous disease entity. The nature of its biological specificity, which is similar to basal-like cancers, tumors arising in BRCA1 mutation carriers, and claudin-low cancers, is currently being explored in hopes of finding the targets for novel biologics and chemotherapeutic agents. In this review, we aim to give a broad overview of the disease’s nomenclature and epidemiology, as well as the basic mechanisms of emerging targeted therapies and their performance in clinical trials to date. PMID:21863131

Bioterrorism--are you ready for the silent killer?

PubMed

Stillsmoking, Kristina

2002-09-01

Current biological threats to the United States have generated fear and panic among many, but nursing professionals who are educated about bioterrorism and its effects can answer questions confidently and calm fears when peers, family members, and friends ask about this issue. Perioperative nurses can become ambassadors of confidence via their ability to project calm and thus stem the tide of panic and fear. This article explains the definition of bioterrorism, its history, biological agents and their transmission, treatment options, and what nurses can do to facilitate preventive measures and help avert panic.

Accomplishments in 2007 in the treatment of advanced colorectal cancer.

PubMed

Goldberg, Richard M; Carrato, Alfredo

2008-05-01

Overview of the Disease IncidencePrognosis Prognostic or Predictive FactorsCurrent General Therapy Standards and Regional Variations STANDARDS IN THE US AND EUROPE: Combination Therapy Plus a Biologic FOCUS and CAIRO 1: Serial Single Agents vs. Combination TherapyStop-and-Go StrategyLimited Availability of Biologics in Some RegionsAccomplishments During the Year TherapyWhat Needs To Be Done Controversies and Disagreements BOND-2 and PACCE: Chemotherapy + Bevacizumab + Cetuximab or PanitumumabSpecial Populations (Elderly and Poor Performance Status)Future Directions Comments on ResearchObstacles to Progress.

Accomplishments in 2007 in the Treatment of Advanced Colorectal Cancer

PubMed Central

Carrato, Alfredo

2008-01-01

Overview of the Disease IncidencePrognosis Prognostic or Predictive FactorsCurrent General Therapy Standards and Regional Variations Standards in the US and Europe: Combination Therapy Plus a Biologic FOCUS and CAIRO 1: Serial Single Agents vs. Combination TherapyStop-and-Go StrategyLimited Availability of Biologics in Some RegionsAccomplishments During the Year TherapyWhat Needs To Be Done Controversies and Disagreements BOND-2 and PACCE: Chemotherapy + Bevacizumab + Cetuximab or PanitumumabSpecial Populations (Elderly and Poor Performance Status)Future Directions Comments on ResearchObstacles to Progress PMID:19352463

Monitoring of interaction of low-frequency electric field with biological tissues upon optical clearing with optical coherence tomography.

PubMed

Peña, Adrián F; Doronin, Alexander; Tuchin, Valery V; Meglinski, Igor

2014-08-01

The influence of a low-frequency electric field applied to soft biological tissues ex vivo at normal conditions and upon the topical application of optical clearing agents has been studied by optical coherence tomography (OCT). The electro-kinetic response of tissues has been observed and quantitatively evaluated by the double correlation OCT approach, utilizing consistent application of an adaptive Wiener filtering and Fourier domain correlation algorithm. The results show that fluctuations, induced by the electric field within the biological tissues are exponentially increased in time. We demonstrate that in comparison to impedance measurements and the mapping of the temperature profile at the surface of the tissue samples, the double correlation OCT approach is much more sensitive to the changes associated with the tissues' electro-kinetic response. We also found that topical application of the optical clearing agent reduces the tissues' electro-kinetic response and is cooling the tissue, thus reducing the temperature induced by the electric current by a few degrees. We anticipate that dcOCT approach can find a new application in bioelectrical impedance analysis and monitoring of the electric properties of biological tissues, including the resistivity of high water content tissues and its variations.

Biologics as countermeasures for acute radiation syndrome: where are we now?

PubMed

Singh, Vijay K; Romaine, Patricia L P; Newman, Victoria L

2015-04-01

Despite significant scientific advances toward the development of a safe, nontoxic and effective radiation countermeasure for acute radiation syndrome (ARS) over the past six decades, no drug has been approved by the US FDA. Several biologics are currently under development as radiation countermeasures for ARS, of which three have received FDA Investigational New Drug (IND) status for clinical investigation. Presently, two of these agents, entolimod (CBLB502) and HemaMax (recombinant human IL-12) are progressing with large animal studies and clinical trials. Neupogen (G-CSF, filgrastim) has recently been recommended for approval by an FDA Advisory Committee. Filgrastim, GM-CSF (Leukine, sargramostim), and PEGylated G-CSF (Neulasta) have high potential and well-documented therapeutic effects in countering myelosuppression and may receive full licensing approval by the FDA in the future. The former two biologics are available in the US Strategic National Stockpile (SNS) for use in the event of nuclear or radiological emergency. The Emergency Use Authorization (EAU) application for entolimod may be filed soon with the FDA. Biologics are attractive agents that are progressing along the path for FDA approval, to fill the unmet need for ARS countermeasures.

Effects of light intensity on Tropical Soda Apple and the consequences for performance of its biological control agent, Gratiana boliviana (Chrysomelidae).

USDA-ARS?s Scientific Manuscript database

The current research was directed at determining the impact of light intensity on the architecture, amino acid content and trichome density and characteristics of Tropical Soda Apple (TSA), Solanum viarum (Solanaceae). TSA plants were grown in a greenhouse either covered with a shade cloth (75% bloc...

Forty-Five Years of Marburg Virus Research

PubMed Central

Brauburger, Kristina; Hume, Adam J.; Mühlberger, Elke; Olejnik, Judith

2012-01-01

In 1967, the first reported filovirus hemorrhagic fever outbreak took place in Germany and the former Yugoslavia. The causative agent that was identified during this outbreak, Marburg virus, is one of the most deadly human pathogens. This article provides a comprehensive overview of our current knowledge about Marburg virus disease ranging from ecology to pathogenesis and molecular biology. PMID:23202446

Forty-five years of Marburg virus research.

PubMed

Brauburger, Kristina; Hume, Adam J; Mühlberger, Elke; Olejnik, Judith

2012-10-01

In 1967, the first reported filovirus hemorrhagic fever outbreak took place in Germany and the former Yugoslavia. The causative agent that was identified during this outbreak, Marburg virus, is one of the most deadly human pathogens. This article provides a comprehensive overview of our current knowledge about Marburg virus disease ranging from ecology to pathogenesis and molecular biology.

Nanoparticle-labeled DNA capture elements for detection and identification of biological agents

NASA Astrophysics Data System (ADS)

Kiel, Johnathan L.; Holwitt, Eric A.; Parker, Jill E.; Vivekananda, Jeevalatha; Franz, Veronica

2004-12-01

Aptamers, synthetic DNA capture elements (DCEs), can be made chemically or in genetically engineered bacteria. DNA capture elements are artificial DNA sequences, from a random pool of sequences, selected for their specific binding to potential biological warfare or terrorism agents. These sequences were selected by an affinity method using filters to which the target agent was attached and the DNA isolated and amplified by polymerase chain reaction (PCR) in an iterative, increasingly stringent, process. The probes can then be conjugated to Quantum Dots and super paramagnetic nanoparticles. The former provide intense, bleach-resistant fluorescent detection of bioagent and the latter provide a means to collect the bioagents with a magnet. The fluorescence can be detected in a flow cytometer, in a fluorescence plate reader, or with a fluorescence microscope. To date, we have made DCEs to Bacillus anthracis spores, Shiga toxin, Venezuelan Equine Encephalitis (VEE) virus, and Francisella tularensis. DCEs can easily distinguish Bacillus anthracis from its nearest relatives, Bacillus cereus and Bacillus thuringiensis. Development of a high through-put process is currently being investigated.

The Key Events Dose-Response Framework: a cross-disciplinary mode-of-action based approach to examining dose-response and thresholds.

PubMed

Julien, Elizabeth; Boobis, Alan R; Olin, Stephen S

2009-09-01

The ILSI Research Foundation convened a cross-disciplinary working group to examine current approaches for assessing dose-response and identifying safe levels of intake or exposure for four categories of bioactive agents-food allergens, nutrients, pathogenic microorganisms, and environmental chemicals. This effort generated a common analytical framework-the Key Events Dose-Response Framework (KEDRF)-for systematically examining key events that occur between the initial dose of a bioactive agent and the effect of concern. Individual key events are considered with regard to factors that influence the dose-response relationship and factors that underlie variability in that relationship. This approach illuminates the connection between the processes occurring at the level of fundamental biology and the outcomes observed at the individual and population levels. Thus, it promotes an evidence-based approach for using mechanistic data to reduce reliance on default assumptions, to quantify variability, and to better characterize biological thresholds. This paper provides an overview of the KEDRF and introduces a series of four companion papers that illustrate initial application of the approach to a range of bioactive agents.

Biological Control beneath the Feet: A Review of Crop Protection against Insect Root Herbivores.

PubMed

Kergunteuil, Alan; Bakhtiari, Moe; Formenti, Ludovico; Xiao, Zhenggao; Defossez, Emmanuel; Rasmann, Sergio

2016-11-29

Sustainable agriculture is certainly one of the most important challenges at present, considering both human population demography and evidence showing that crop productivity based on chemical control is plateauing. While the environmental and health threats of conventional agriculture are increasing, ecological research is offering promising solutions for crop protection against herbivore pests. While most research has focused on aboveground systems, several major crop pests are uniquely feeding on roots. We here aim at documenting the current and potential use of several biological control agents, including micro-organisms (viruses, bacteria, fungi, and nematodes) and invertebrates included among the macrofauna of soils (arthropods and annelids) that are used against root herbivores. In addition, we discuss the synergistic action of different bio-control agents when co-inoculated in soil and how the induction and priming of plant chemical defense could be synergized with the use of the bio-control agents described above to optimize root pest control. Finally, we highlight the gaps in the research for optimizing a more sustainable management of root pests.

Biological Control beneath the Feet: A Review of Crop Protection against Insect Root Herbivores

PubMed Central

Kergunteuil, Alan; Bakhtiari, Moe; Formenti, Ludovico; Xiao, Zhenggao; Defossez, Emmanuel; Rasmann, Sergio

2016-01-01

Sustainable agriculture is certainly one of the most important challenges at present, considering both human population demography and evidence showing that crop productivity based on chemical control is plateauing. While the environmental and health threats of conventional agriculture are increasing, ecological research is offering promising solutions for crop protection against herbivore pests. While most research has focused on aboveground systems, several major crop pests are uniquely feeding on roots. We here aim at documenting the current and potential use of several biological control agents, including micro-organisms (viruses, bacteria, fungi, and nematodes) and invertebrates included among the macrofauna of soils (arthropods and annelids) that are used against root herbivores. In addition, we discuss the synergistic action of different bio-control agents when co-inoculated in soil and how the induction and priming of plant chemical defense could be synergized with the use of the bio-control agents described above to optimize root pest control. Finally, we highlight the gaps in the research for optimizing a more sustainable management of root pests. PMID:27916820

Biologics in the management of ulcerative colitis – comparative safety and efficacy of TNF-α antagonists

PubMed Central

Fausel, Rebecca; Afzali, Anita

2015-01-01

Ulcerative colitis can cause debilitating symptoms and complications such as colonic strictures, colonic dysplasia, colorectal cancer, and toxic megacolon or perforation. Goals of treatment in ulcerative colitis include resolution of gastrointestinal symptoms, healing of colonic mucosa, and prevention of disease complications. Our treatment armamentarium has expanded dramatically over the past 10 years, and we now have multiple biologic agents approved for the treatment of moderate-severe disease, in addition to conventional therapies such as 5-aminosalicylates, thiopurines, and corticosteroids. In this review, we will provide a detailed discussion of the three tumor necrosis factor-alpha (TNF-α) inhibitors currently approved for treatment of ulcerative colitis: infliximab, adalimumab, and golimumab. All three agents are effective for inducing and maintaining clinical response and remission in patients with ulcerative colitis, and they have comparable safety profiles. There are no head-to-head trials comparing their efficacy, and the choice of agent is most often based on insurance coverage, route of administration, and patient preference. Combination therapy with an immunomodulator is proven to be more effective than anti-TNF monotherapy, and patients who lose response to an anti-TNF agent should undergo dose intensification in order to regain clinical response. Despite therapeutic optimization, a significant percentage of patients will not achieve clinical remission with anti-TNF agents, and so newer therapies are on the horizon. PMID:25609972

Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

PubMed Central

Riaz, Muhammad Kashif; Riaz, Muhammad Adil; Zhang, Xue; Lin, Congcong; Wong, Ka Hong; Chen, Xiaoyu; Lu, Aiping

2018-01-01

Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed. PMID:29315231

Radium-223 in metastatic castration resistant prostate cancer

PubMed Central

Vuong, Winston; Sartor, Oliver; Pal, Sumanta K

2014-01-01

In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival benefit in phase III studies. These agents include sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and (most recently) radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer (e.g. samarium-153 and strontium-89), radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors influencing clinical implementation. PMID:24713838

Molecular targeted therapies for solid tumors: management of side effects.

PubMed

Grünwald, Viktor; Soltau, Jens; Ivanyi, Philipp; Rentschler, Jochen; Reuter, Christoph; Drevs, Joachim

2009-03-01

This review will provide physicians and oncologists with an overview of side effects related to targeted agents that inhibit vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and mammalian target of rapamycin (mTOR) signaling in the treatment of solid tumors. Such targeted agents can be divided into monoclonal antibodies, tyrosine kinase inhibitors, multitargeted tyrosine kinase inhibitors and serine/threonine kinase inhibitors. Molecular targeted therapies are generally well tolerated, but inhibitory effects on the biological function of the targets in healthy tissue can result in specific treatment-related side effects, particularly with multitargeted agents. We offer some guidance on how to manage adverse events in cancer patients based on the range of options currently available. Copyright 2009 S. Karger AG, Basel.

Tackling scabies: novel agents for a neglected disease.

PubMed

Gopinath, Hima; Aishwarya, Manju; Karthikeyan, Kaliaperumal

2018-04-16

The scabies mite, Sarcoptes scabiei var hominis, is an obligate ectoparasite of humans. It has been a source of distress for humanity since antiquity. The troublesome mite is emerging triumphant over current acaricidal agents with reports of emerging resistance and treatment failures. Scabies in endemic areas and crusted scabies offer additional management challenges. Exploration of indigenous plants and better understanding of mite biology and pathogenesis provide opportunities for the development of novel agents for this common pest. We review the recent diverse approaches to scabies, including the use of novel plant products with a better safety profile, translating the use of moxidectin from veterinary practice to human scabies, vaccination, immunotherapy, and development of drugs that directly target mite molecules. © 2018 The International Society of Dermatology.

Current concepts regarding pharmacologic treatment of rheumatoid and osteoarthritis.

PubMed

Wildy, K S; Wasko, M C

2001-05-01

Treating patients with osteoarthritis (OA) and rheumatoid arthritis (RA) remains challenging; however, new agents offer the chance for an improved quality of life. As an alternative to traditional nonsteroidal anti-inflammatories, cyclooxygenase-2 inhibitors provide pain relief for OA and RA patients with possible fewer side effects. Otherwise, OA patients may opt for topical agents, injections, or supplements. Rheumatoid arthritis research has led to an improved understanding of the inflammatory cascade and an appreciation of the early tissue destruction. A new treatment philosophy has thus emerged along with the development of new biologic agents; the latter, along with combination therapy and a new disease modifying antirheumatic drug, leflunomide, have greatly expanded the chances for disease control in RA patients.

Microscopic dual-energy CT (microDECT): a flexible tool for multichannel ex vivo 3D imaging of biological specimens.

PubMed

Handschuh, S; Beisser, C J; Ruthensteiner, B; Metscher, B D

2017-07-01

Dual-energy computed tomography (DECT) uses two different x-ray energy spectra in order to differentiate between tissues, materials or elements in a single sample or patient. DECT is becoming increasingly popular in clinical imaging and preclinical in vivo imaging of small animal models, but there have been only very few reports on ex vivo DECT of biological samples at microscopic resolutions. The present study has three main aims. First, we explore the potential of microscopic DECT (microDECT) for delivering isotropic multichannel 3D images of fixed biological samples with standard commercial laboratory-based microCT setups at spatial resolutions reaching below 10 μm. Second, we aim for retaining the maximum image resolution and quality during the material decomposition. Third, we want to test the suitability for microDECT imaging of different contrast agents currently used for ex vivo staining of biological samples. To address these aims, we used microCT scans of four different samples stained with x-ray dense contrast agents. MicroDECT scans were acquired with five different commercial microCT scanners from four companies. We present a detailed description of the microDECT workflow, including sample preparation, image acquisition, image processing and postreconstruction material decomposition, which may serve as practical guide for applying microDECT. The MATLAB script (The Mathworks Inc., Natick, MA, USA) used for material decomposition (including a graphical user interface) is provided as a supplement to this paper (https://github.com/microDECT/DECTDec). In general, the presented microDECT workflow yielded satisfactory results for all tested specimens. Original scan resolutions have been mostly retained in the separate material fractions after basis material decomposition. In addition to decomposition of mineralized tissues (inherent sample contrast) and stained soft tissues, we present a case of double labelling of different soft tissues with subsequent material decomposition. We conclude that, in contrast to in vivo DECT examinations, small ex vivo specimens offer some clear advantages regarding technical parameters of the microCT setup and the use of contrast agents. These include a higher flexibility in source peak voltages and x-ray filters, a lower degree of beam hardening due to small sample size, the lack of restriction to nontoxic contrast agents and the lack of a limit in exposure time and radiation dose. We argue that microDECT, because of its flexibility combined with already established contrast agents and the vast number of currently unexploited stains, will in future represent an important technique for various applications in biological research. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

Reliable discrimination of high explosive and chemical/biological artillery using acoustic UGS

NASA Astrophysics Data System (ADS)

Hohil, Myron E.; Desai, Sachi

2005-10-01

The Army is currently developing acoustic overwatch sensor systems that will provide extended range surveillance, detection, and identification for force protection and tactical security on the battlefield. A network of such sensors remotely deployed in conjunction with a central processing node (or gateway) will provide early warning and assessment of enemy threats, near real-time situational awareness to commanders, and may reduce potential hazards to the soldier. In contrast, the current detection of chemical/biological (CB) agents expelled into a battlefield environment is limited to the response of chemical sensors that must be located within close proximity to the CB agent. Since chemical sensors detect hazardous agents through contact, the sensor range to an airburst is the key-limiting factor in identifying a potential CB weapon attack. The associated sensor reporting latencies must be minimized to give sufficient preparation time to field commanders, who must assess if an attack is about to occur, has occurred, or if occurred, the type of agent that soldiers might be exposed to. The long-range propagation of acoustic blast waves from heavy artillery blasts, which are typical in a battlefield environment, introduces a feature for using acoustics and other disparate sensor technologies for the early detection and identification of CB threats. Employing disparate sensor technologies implies that warning of a potential CB attack can be provided to the solider more rapidly and from a safer distance when compared to that which conventional methods allow. This capability facilitates the necessity of classifying the types of rounds that have burst in a specified region in order to give both warning and provide identification of CB agents found in the area. In this paper, feature extraction methods based on the discrete wavelet transform (DWT) and multiresolution analysis facilitate the development of a robust classification algorithm that affords reliable discrimination between conventional and simulated chemical/biological artillery rounds using acoustic signals produced during detonation. Distinct characteristics arise within the different airburst signatures because high explosive warheads emphasize concussive and shrapnel effects, while chemical/biological warheads are designed to disperse their contents over large areas, therefore employing a slower burning, less intense explosive to mix and spread their contents. The ensuing blast waves are readily characterized by variations in the corresponding peak pressure and rise time of the blast, differences in the ratio of positive pressure amplitude to the negative amplitude, and variations in the overall duration of the resulting waveform. We show that, highly reliable discrimination (> 98%) between conventional and potentially chemical/biological artillery is achieved at ranges exceeding 3km. A feedforward neural network classifier, trained on a feature space derived from the distribution of wavelet coefficients found within different levels of the multiresolution decomposition yields.

76 FR 3076 - Availability of an Environmental Assessment for a Biological Control Agent for Air Potato

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-19

...] Availability of an Environmental Assessment for a Biological Control Agent for Air Potato AGENCY: Animal and... environmental assessment (EA) relative to the control of air potato (Dioscorea bulbifera). The EA considers the... States for use as a biological control agent to reduce the severity of air potato infestations. We are...

Predicting spillover risk to non-target plants pre-release: Bikasha collaris a potential biological control agent of Chinese tallowtree (Triadica sebifera)

USDA-ARS?s Scientific Manuscript database

Quarantine host range tests accurately predict direct risk of biological control agents to non-target species. However, a well-known indirect effect of biological control of weeds releases is spillover damage to non-target species. Spillover damage may occur when the population of agents achieves ou...

[Tularaemia - an overview of the current knowledge].

PubMed

Lukásová, Eva; Cermák, Pavel; Smelá, Gabriela; Jedlicková, Anna

2010-02-01

Francisella tularensis belongs to the family Francisellaceae. It is the aetiological agent of a zoonosis called tularaemia, spread throughout the northern hemisphere. Currently, several subspecies of F. tularensis may be distinguished with various pathogenicity and geographical distribution. In human medicine, only sporadic infections or local epidemics are reported. Given the fact that F. tularensis is highly pathogenic for humans and is easily spread by aerosol, water or food, it may be exploited as a biological weapon. It belongs to fastidious strains requiring specially prepared culture media.

Biologic and oral disease-modifying antirheumatic drug monotherapy in rheumatoid arthritis

PubMed Central

Emery, Paul; Sebba, Anthony; Huizinga, Tom W J

2013-01-01

Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX. PMID:23918035

Portable Sensor for Chemical Nerve Agents and Organophosphorus Compounds

DTIC Science & Technology

2015-08-18

as pesticides in crop, livestock, and poultry products and as chemical and biological warfare agents. As a result of the high toxicity and the...agents have been exploited for use as pesticides in crop, livestock, and poultry products and as chemical and biological warfare agents. As a result of

Primary plasma cell leukemia 2.0: advances in biology and clinical management.

PubMed

Neri, Antonino; Todoerti, Katia; Lionetti, Marta; Simeon, Vittorio; Barbieri, Marzia; Nozza, Filomena; Vona, Gabriella; Pompa, Alessandra; Baldini, Luca; Musto, Pellegrino

2016-11-01

Primary plasma cell leukemia (PPCL) is a rare and aggressive variant of multiple myeloma. The introduction of novel agents and modern technologies has recently partially changed the clinical and biological scenario of this malignancy, allowing limited, but not negligible, progresses. Areas covered: We will discuss: the complex landscape of genetic alterations in PPCL, derived from conventional and high-throughput technologies; the best available treatments for PPCL; the possible future therapeutic perspectives. Expert commentary: PPCL requires an immediate and intensive multi-phase treatment with short therapy-free intervals, which should include novel agents and autologous stem cell transplantation in eligible patients. Allogeneic transplantation should be considered in selected cases. In older and/or frailer individuals, personalized approaches should be applied. Integrated treatments with next generation proteasome inhibitors/IMIDs and monoclonal antibodies are currently planned or under investigation. The identification of novel genomic biomarkers may be potentially helpful for risk stratification and future personalized therapies.

Drugs That Target Dynamic Microtubules: A New Molecular Perspective

PubMed Central

Stanton, Richard A.; Gernert, Kim M.; Nettles, James H.; Aneja, Ritu

2011-01-01

Microtubules have long been considered an ideal target for anticancer drugs because of the essential role they play in mitosis, forming the dynamic spindle apparatus. As such, there is a wide variety of compounds currently in clinical use and in development that act as antimitotic agents by altering microtubule dynamics. Although these diverse molecules are known to affect microtubule dynamics upon binding to one of the three established drug domains (taxane, vinca alkaloid, or colchicine site), the exact mechanism by which each drug works is still an area of intense speculation and research. In this study, we review the effects of microtubule-binding chemotherapeutic agents from a new perspective, considering how their mode of binding induces conformational changes and alters biological function relative to the molecular vectors of microtubule assembly or disassembly. These “biological vectors” can thus be used as a spatiotemporal context to describe molecular mechanisms by which microtubule-targeting drugs work. PMID:21381049

A reference protocol for comparing the biocidal properties of gas plasma generating devices

NASA Astrophysics Data System (ADS)

Shaw, A.; Seri, P.; Borghi, C. A.; Shama, G.; Iza, F.

2015-12-01

Growing interest in the use of non-thermal, atmospheric pressure gas plasmas for decontamination purposes has resulted in a multiplicity of plasma-generating devices. There is currently no universally approved method of comparing the biocidal performance of such devices and in the work described here spores of the Gram positive bacterium Bacillus subtilis (ATCC 6633) are proposed as a suitable reference biological agent. In order to achieve consistency in the form in which the biological agent in question is presented to the plasma, a polycarbonate membrane loaded with a monolayer of spores is proposed. The advantages of the proposed protocol are evaluated by comparing inactivation tests in which an alternative microorganism (methicillin resistant Staphylococcus aureus—MRSA) and the widely-used sample preparation technique of directly pipetting cell suspensions onto membranes are employed. In all cases, inactivation tests with either UV irradiation or plasma exposure were more reproducible when the proposed protocol was followed.

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

Forty Years of Ebolavirus Molecular Biology: Understanding a Novel Disease Agent Through the Development and Application of New Technologies.

PubMed

Groseth, Allison; Hoenen, Thomas

2017-01-01

Molecular biology is a broad discipline that seeks to understand biological phenomena at a molecular level, and achieves this through the study of DNA, RNA, proteins, and/or other macromolecules (e.g., those involved in the modification of these substrates). Consequently, it relies on the availability of a wide variety of methods that deal with the collection, preservation, inactivation, separation, manipulation, imaging, and analysis of these molecules. As such the state of the art in the field of ebolavirus molecular biology research (and that of all other viruses) is largely intertwined with, if not driven by, advancements in the technical methodologies available for these kinds of studies. Here we review of the current state of our knowledge regarding ebolavirus biology and emphasize the associated methods that made these discoveries possible.

Prevention and treatment of tuberculosis infection in candidates for biologic therapy: A multidisciplinary consensus statement adapted to the dermatology patient.

PubMed

Rodríguez-Jiménez, P; Mir-Viladrich, I; Chicharro, P; Solano-López, G; López-Longo, F J; Taxonera, C; Sánchez-Martínez, P; Martínez-Lacasa, X; García-Gasalla, M; Dorca, J; Arias-Guillén, M; García-García, J M; Dauden, E

2018-06-02

Patients with chronic inflammatory diseases being treated with immunosuppressive drugs, and with tumor necrosis factor inhibitors in particular, have an increased risk of infection by Mycobacterium tuberculosis. Screening for latent tuberculosis infection and preventive therapy to reduce the risk of progression to active tuberculosis are mandatory in this group of patients. This updated multidisciplinary consensus document presents the latest expert opinions on the treatment and prevention of tuberculosis in candidates for biologic therapy and establishes recommendations based on current knowledge relating to the use of biologic agents. Copyright © 2018 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

PubMed Central

Andréoletti, Olivier; Orge, Leonor; Benestad, Sylvie L.; Beringue, Vincent; Litaise, Claire; Simon, Stéphanie; Le Dur, Annick; Laude, Hubert; Simmons, Hugh; Lugan, Séverine; Corbière, Fabien; Costes, Pierrette; Morel, Nathalie; Schelcher, François; Lacroux, Caroline

2011-01-01

Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrPSc negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed. PMID:21347349

Is the whole the sum of its parts? Agent-based modelling of wastewater treatment systems.

PubMed

Schuler, A J; Majed, N; Bucci, V; Hellweger, F L; Tu, Y; Gu, A Z

2011-01-01

Agent-based models (ABMS) simulate individual units within a system, such as the bacteria in a biological wastewater treatment system. This paper outlines past, current and potential future applications of ABMs to wastewater treatment. ABMs track heterogeneities within microbial populations, and this has been demonstrated to yield different predictions of bulk behaviors than the conventional, "lumped" approaches for enhanced biological phosphorus removal (EBPR) completely mixed reactors systems. Current work included the application of the ABM approach to bacterial adaptation/evolution, using the model system of individual EBPR bacteria that are allowed to evolve a kinetic parameter (maximum glycogen storage) in a competitive environment. The ABM approach was successfully implemented to a simple anaerobic-aerobic system and it was found the differing initial states converged to the same optimal solution under uncertain hydraulic residence times associated with completely mixed hydraulics. In another study, an ABM was developed and applied to simulate the heterogeneity in intracellular polymer storage compounds, including polyphosphate (PP), in functional microbial populations in enhanced biological phosphorus removal (EBPR) process. The simulation results were compared to the experimental measurements of single-cell abundance of PP in polyphosphate accumulating organisms (PAOs), performed using Raman microscopy. The model-predicted heterogeneity was generally consistent with observations, and it was used to investigate the relative contribution of external (different life histories) and internal (biological) mechanisms leading to heterogeneity. In the future, ABMs could be combined with computational fluid dynamics (CFD) models to understand incomplete mixing, more intracellular states and mechanisms can be incorporated, and additional experimental verification is needed.

Predicting the host range of Nystalea ebalea: secondary plant chemistry and host selection by a surrogate biological control agent of Schinus terebinthifolia

USDA-ARS?s Scientific Manuscript database

The safety of weed biological control depends upon the selection and utilization of the target weed by the agent while causing minimal harm to non-target species. Selection of weed species by biological control agents is determined by the presence of behavioral cues, generally host secondary plant c...

Intelligent Design of Nano-Scale Molecular Imaging Agents

PubMed Central

Kim, Sung Bae; Hattori, Mitsuru; Ozawa, Takeaki

2012-01-01

Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs), biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on–off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents. PMID:23235326

Intelligent design of nano-scale molecular imaging agents.

PubMed

Kim, Sung Bae; Hattori, Mitsuru; Ozawa, Takeaki

2012-12-12

Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs), biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on-off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents.

Computerized bioterrorism education and training for nurses on bioterrorism attack agents.

PubMed

Nyamathi, Adeline M; Casillas, Adrian; King, Major L; Gresham, Louise; Pierce, Elaine; Farb, Daniel; Wiechmann, Carrie; Weichmann, Carrie

2010-08-01

Biological agents have the ability to cause large-scale mass casualties. For this reason, their likely use in future terrorist attacks is a concern for national security. Recent studies show that nurses are ill prepared to deal with agents used in biological warfare. Achieving a goal for bioterrorism preparedness is directly linked to comprehensive education and training that enables first-line responders such as nurses to diagnose infectious agents rapidly. The study evaluated participants' responses to biological agents using a computerized bioterrorism education and training program versus a standard bioterrorism education and training program. Both programs improved participants' ability to complete and solve case studies involving the identification of specific biological agents. Participants in the computerized bioterrorism education and training program were more likely to solve the cases critically without reliance on expert consultants. However, participants in the standard bioterrorism education and training program reduced the use of unnecessary diagnostic tests.

A decontamination study of simulated chemical and biological agents

NASA Astrophysics Data System (ADS)

Uhm, Han S.; Lee, Han Y.; Hong, Yong C.; Shin, Dong H.; Park, Yun H.; Hong, Yi F.; Lee, Chong K.

2007-07-01

A comprehensive decontamination scheme of the chemical and biological agents, including airborne agents and surface contaminating agents, is presented. When a chemical and biological attack occurs, it is critical to decontaminate facilities or equipments to an acceptable level in a very short time. The plasma flame presented here may provide a rapid and effective elimination of toxic substances in the interior air in isolated spaces. As an example, a reaction chamber, with the dimensions of a 22cm diameter and 30cm length, purifies air with an airflow rate of 5000l/min contaminated with toluene, the simulated chemical agent, and soot from a diesel engine, the simulated aerosol for biological agents. Although the airborne agents in an isolated space are eliminated to an acceptable level by the plasma flame, the decontamination of the chemical and biological agents cannot be completed without cleaning surfaces of the facilities. A simulated sterilization study of micro-organisms was carried out using the electrolyzed ozone water. The electrolyzed ozone water very effectively kills endospores of Bacillus atrophaeus (ATCC 9372) within 3min. The electrolyzed ozone water also kills the vegetative micro-organisms, fungi, and virus. The electrolyzed ozone water, after the decontamination process, disintegrates into ordinary water and oxygen without any trace of harmful materials to the environment.

75 FR 13674 - Wassenaar Arrangement 2008 Plenary Agreements Implementation: Categories 1, 2, 3, 4, 5 Parts I...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-23

...'', biological agents ``adapted for use in war'', chemical warfare agents, 'simulants' or ``riot control agents... AGENCY: Bureau of Industry and Security, Commerce. ACTION: Final rule; correcting amendment. SUMMARY: The.... 'Simulant': A substance or material that is used in place of toxic agent (chemical or biological) in...

A Bayesian Dose-finding Design for Oncology Clinical Trials of Combinational Biological Agents

PubMed Central

Cai, Chunyan; Yuan, Ying; Ji, Yuan

2013-01-01

Treating patients with novel biological agents is becoming a leading trend in oncology. Unlike cytotoxic agents, for which efficacy and toxicity monotonically increase with dose, biological agents may exhibit non-monotonic patterns in their dose-response relationships. Using a trial with two biological agents as an example, we propose a dose-finding design to identify the biologically optimal dose combination (BODC), which is defined as the dose combination of the two agents with the highest efficacy and tolerable toxicity. A change-point model is used to reflect the fact that the dose-toxicity surface of the combinational agents may plateau at higher dose levels, and a flexible logistic model is proposed to accommodate the possible non-monotonic pattern for the dose-efficacy relationship. During the trial, we continuously update the posterior estimates of toxicity and efficacy and assign patients to the most appropriate dose combination. We propose a novel dose-finding algorithm to encourage sufficient exploration of untried dose combinations in the two-dimensional space. Extensive simulation studies show that the proposed design has desirable operating characteristics in identifying the BODC under various patterns of dose-toxicity and dose-efficacy relationships. PMID:24511160

Oxidative decontamination of chemical and biological warfare agents using L-Gel.

PubMed

Raber, Ellen; McGuire, Raymond

2002-08-05

A decontamination method has been developed using a single reagent that is effective both against chemical warfare (CW) and biological warfare (BW) agents. The new reagent, "L-Gel", consists of an aqueous solution of a mild commercial oxidizer, Oxone, together with a commercial fumed silica gelling agent, Cab-O-Sil EH-5. L-Gel is non-toxic, environmentally friendly, relatively non-corrosive, maximizes contact time because of its thixotropic nature, clings to walls and ceilings, and does not harm carpets or painted surfaces. The new reagent also addresses the most demanding requirements for decontamination in the civilian sector, including availability, low maintenance, ease of application and deployment by a variety of dispersal mechanisms, minimal training and acceptable expense. Experiments to test the effectiveness of L-Gel were conducted at Lawrence Livermore National Laboratory and independently at four other locations. L-Gel was tested against all classes of chemical warfare agents and against various biological warfare agent surrogates, including spore-forming bacteria and non-virulent strains of real biological agents. Testing showed that L-Gel is as effective against chemical agents and biological materials, including spores, as the best military decontaminants.

Testing Carea varipes and Neostauropus alternus as biological control agents for the Florida invasive plant species Rhodomyrtus tomentosa.

USDA-ARS?s Scientific Manuscript database

Rhodomyrtus tomentosa (RT) a native plant to Southeastern Asia, commonly known as downy rose myrtle, is invasive to the regions of Central and South Florida. Introduced in the early 1920’s, this weed is currently considered a Category I invasive species by the Florida Exotic Pest Plant Council. RT...

Fighting Cancer with Mathematics and Viruses.

PubMed

Santiago, Daniel N; Heidbuechel, Johannes P W; Kandell, Wendy M; Walker, Rachel; Djeu, Julie; Engeland, Christine E; Abate-Daga, Daniel; Enderling, Heiko

2017-08-23

After decades of research, oncolytic virotherapy has recently advanced to clinical application, and currently a multitude of novel agents and combination treatments are being evaluated for cancer therapy. Oncolytic agents preferentially replicate in tumor cells, inducing tumor cell lysis and complex antitumor effects, such as innate and adaptive immune responses and the destruction of tumor vasculature. With the availability of different vector platforms and the potential of both genetic engineering and combination regimens to enhance particular aspects of safety and efficacy, the identification of optimal treatments for patient subpopulations or even individual patients becomes a top priority. Mathematical modeling can provide support in this arena by making use of experimental and clinical data to generate hypotheses about the mechanisms underlying complex biology and, ultimately, predict optimal treatment protocols. Increasingly complex models can be applied to account for therapeutically relevant parameters such as components of the immune system. In this review, we describe current developments in oncolytic virotherapy and mathematical modeling to discuss the benefit of integrating different modeling approaches into biological and clinical experimentation. Conclusively, we propose a mutual combination of these research fields to increase the value of the preclinical development and the therapeutic efficacy of the resulting treatments.

Fighting Cancer with Mathematics and Viruses

PubMed Central

Santiago, Daniel N.; Heidbuechel, Johannes P. W.; Kandell, Wendy M.; Walker, Rachel; Djeu, Julie; Abate-Daga, Daniel; Enderling, Heiko

2017-01-01

After decades of research, oncolytic virotherapy has recently advanced to clinical application, and currently a multitude of novel agents and combination treatments are being evaluated for cancer therapy. Oncolytic agents preferentially replicate in tumor cells, inducing tumor cell lysis and complex antitumor effects, such as innate and adaptive immune responses and the destruction of tumor vasculature. With the availability of different vector platforms and the potential of both genetic engineering and combination regimens to enhance particular aspects of safety and efficacy, the identification of optimal treatments for patient subpopulations or even individual patients becomes a top priority. Mathematical modeling can provide support in this arena by making use of experimental and clinical data to generate hypotheses about the mechanisms underlying complex biology and, ultimately, predict optimal treatment protocols. Increasingly complex models can be applied to account for therapeutically relevant parameters such as components of the immune system. In this review, we describe current developments in oncolytic virotherapy and mathematical modeling to discuss the benefit of integrating different modeling approaches into biological and clinical experimentation. Conclusively, we propose a mutual combination of these research fields to increase the value of the preclinical development and the therapeutic efficacy of the resulting treatments. PMID:28832539

Severe and acute complications of biologics in psoriasis.

PubMed

Oussedik, Elias; Patel, Nupur U; Cash, Devin R; Gupta, Angela S; Feldman, Steven R

2017-12-01

Biologic therapies have revolutionized the approach to immune-mediated diseases such as psoriasis. Due to their favorable safety profiles and excellent efficacy, biologic agents are considered the gold standard for moderate-to-severe psoriasis. The aim of this paper is to saliently review the severe and acute complications of the Food and Drug Administration (FDA) approved biologic agents for psoriasis. Reviewed agents include tumor necrosis factor alpha inhibitors (etanercept, infliximab, and adalimumab), interleukin 12/23 inhibitors (ustekinumab), and interleukin 17 (IL-17) inhibitors (secukinumab and ixekizumab). While malignancies, serious infections, and major adverse cardiovascular events have been reported, their association with biologic therapy are not hypothesized as causal. However, IL-17 inhibitors appear to cause exacerbations and new cases of inflammatory bowel disease. While more long-term studies are warranted in understanding the biologic's long-term side effect profile, short-term studies have confirmed that the biologics are some of the safest treatment options for psoriasis. Nevertheless, certain populations yield higher risk to acute complications with the biologics than others - physicians must use their judgement and vigilance when monitoring and treating patients undergoing therapy with biological agents.

Development of vaccines for bio-warfare agents.

PubMed

Rosenthal, S R; Clifford, J C M

2002-01-01

There is a recognized need for the development of new vaccines (as well as other biologicals and drugs) to counteract the effects of a potential bio-terrorist or bio-warfare event in the U.S. domestic population and military forces. Regulation of products to protect against potential bio-warfare agents poses unique challenges since the usual measures of efficacy that require exposure to natural disease may not currently be possible, for epidemiological and ethical reasons. To help to address this issue, the FDA has published and requested comments on a proposed animal rule intended to address certain efficacy issues for new agents for use against lethal or permanently disabling toxic substances. Recent product development activity has focused on Bacillus anthracis (anthrax) and variola major (smallpox), agents that are regarded as highest priority in posing a risk to national security. FDA resources exist to assist vaccine developers with regard to the novel challenges posed in the dinical development of these products.

Synthesis and Biological Evaluation of Water-soluble Progesterone-Conjugated Probes for Magnetic Resonance Imaging of Hormone Related Cancers

PubMed Central

Sukerkar, Preeti A.; MacRenaris, Keith W.; Townsend, Taryn R.; Ahmed, Roshan A.; Burdette, Joanna E.; Meade, Thomas J.

2011-01-01

Progesterone receptor (PR) is strongly associated with disease prognosis and therapeutic efficacy in hormone related diseases such as endometriosis and breast, ovarian, and uterine cancers. Receptor status is currently determined by immunohistochemistry assays. However, noninvasive PR imaging agents could improve disease detection and help elucidate pathological molecular pathways, leading to new therapies and animal disease models. A series of water-soluble PR-targeted magnetic resonance imaging (MRI) probes were synthesized using Cu(I)-catalyzed click chemistry and evaluated in vitro and in vivo. These agents demonstrated activation of PR in vitro and preferential accumulation in PR(+) compared to PR(−) human breast cancer cells with low toxicity. In xenograft tumor models, the agents demonstrated enhanced signal intensity in PR(+) tumors compared to PR(−) tumors. The results suggest that these agents may be promising MRI probes for PR(+) diseases. PMID:21972997

IPA (v1): a framework for agent-based modelling of soil water movement

NASA Astrophysics Data System (ADS)

Mewes, Benjamin; Schumann, Andreas H.

2018-06-01

In the last decade, agent-based modelling (ABM) became a popular modelling technique in social sciences, medicine, biology, and ecology. ABM was designed to simulate systems that are highly dynamic and sensitive to small variations in their composition and their state. As hydrological systems, and natural systems in general, often show dynamic and non-linear behaviour, ABM can be an appropriate way to model these systems. Nevertheless, only a few studies have utilized the ABM method for process-based modelling in hydrology. The percolation of water through the unsaturated soil is highly responsive to the current state of the soil system; small variations in composition lead to major changes in the transport system. Hence, we present a new approach for modelling the movement of water through a soil column: autonomous water agents that transport water through the soil while interacting with their environment as well as with other agents under physical laws.

Environmental genotoxicity: Probing the underlying mechanisms

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

Shugart, L.; Theodorakis, C.

1993-12-31

Environmental pollution is a complex issue because of the diversity of anthropogenic agents, both chemical and physical, that have been detected and catalogued. The consequences to biota from exposure to genotoxic agents present an additional problem because of the potential for these agents to produce adverse change at the cellular and organismal levels. Past studies in genetic toxicology at the Oak Ridge National Laboratory have focused on structural damage to the DNA of environmental species that may occur after exposure to genotoxic agents and the use of this information to document exposure and to monitor remediation. In an effort tomore » predict effects at the population, community and ecosystem levels, current studies in genetic ecotoxicology are attempting to characterize the biological mechanisms at the gene level that regulate and limit the response of an individual organism to genotoxic factors in their environment.« less

The use of immunosuppression in autoimmune hepatitis: A current literature review.

PubMed

Cropley, Angela; Weltman, Martin

2017-03-01

Autoimmune hepatitis (AIH) is an organ specific autoimmune condition which can manifest at any age of life. The heterogeneous nature of this condition means that great variation can be seen in severity, progression of disease and response to treatment within this patient group. Since the 1980s prednisolone and azathioprine have been used for induction and remission of the disease and remain the mainstay of treatment. Other immunosuppressive agents have been employed in difficult to treat cases. While there is less published data regarding these agents compared with the conventional treatments of steroid and azathioprine, there is mounting evidence to support the use of mycophenolate mofetil as a second-line agent. The calcineurin inhibitors, though less studied, additionally show promise. More data is needed on the use of biological agents in refractory disease. This review focuses on our centre's approach to treatment of AIH in the context of a contemporary review of the literature.

Variations in Health Insurance Policies Regarding Biologic Therapy Use in Inflammatory Bowel Disease.

PubMed

Yadav, Abhijeet; Foromera, Joshua; Feuerstein, Ilana; Falchuk, Kenneth R; Feuerstein, Joseph D

2017-06-01

The American Gastroenterological Association (AGA) has developed guidelines for the management of ulcerative colitis and Crohn's disease (CD) recommending anti-TNF therapy in moderate-severe disease. However, which drug is used is often dictated by insurance company policies. We sought to determine the insurance policy requirements prior to approval of biologic therapies. Using the National Association of Insurance Commissioners report of the top 125 insurance companies by market share in 2014, we reviewed the first 50 that had online policies regarding anti-TNF and vedolizumab available. Policies were reviewed for criteria needed for approval of anti-TNF or vedolizumab therapy, and for compliance with the current AGA clinical pathway recommendations. Ninety-eight percent of policies are inconsistent with the AGA ulcerative colitis pathway and require step-wise drug failure before approval of an anti-TNF. Only 11% of the policies allowed starting vedolizumab without initial failures of an anti-TNF agent, and 21% required the failure of two or more anti-TNF agents. Ninety percent of the policies are inconsistent with AGA CD pathway and require step-wise drug failure before approval of an anti-TNF. Seventy-four percent allowed for initiating infliximab specifically for fistulizing CD. Twenty-eight percent required failing of at least two or more drugs before starting anti-TNF. Only 8% policies allowed starting vedolizumab without initial failures of an anti-TNF agent, and 28% required the failure of two anti-TNF agents. The majority of the policies reviewed fail to adhere to the current AGA pathway recommendations for ulcerative colitis and CD. Further interventions are needed to better align policies with optimal evidence-based drug therapy.

Glucocorticoids in the management of systemic juvenile idiopathic arthritis.

PubMed

Vannucci, Gaia; Cantarini, Luca; Giani, Teresa; Marrani, Edoardo; Moretti, Davide; Pagnini, Ilaria; Simonini, Gabriele; Cimaz, Rolando

2013-10-01

Glucocorticoids have been the mainstay of treatment for many years in systemic-onset juvenile idiopathic arthritis (sJIA), causing important side effects and some difficulties in the management of this disease. Until the introduction of biologic agents, oral glucocorticoids were used to control fever and other systemic features for several months or even years if systemic manifestations persisted. Nowadays, clinicians have valid alternatives that have revolutionized the natural history of sJIA. Biologic agents, such as the interleukin-1 inhibitors anakinra and the more recent canakinumab, or the interleukin-6 inhibitor tocilizumab, have improved the prognosis of this debilitating disease. Glucocorticoids still have to be considered at the onset of disease when a non-steroidal anti-inflammatory drug therapy fails or when there are life-threatening complications such as severe anemia or pericarditis, or macrophage activation syndrome. Local (intra-articular) triamcinolone hexacetonide is the treatment of choice for arthritis limited to one joint or a few joints in patients without systemic activity. To date, there is still great heterogeneity in the management of sJIA patients, but in recent years there have been attempts to design algorithms and treatment protocols for glucocorticoids, disease-modifying anti-rheumatic drugs, and biologic agents. This review provides an overview of the current knowledge of glucocorticoid therapy in sJIA, comments on recently published recommendations, and gives practical support to the clinician for management of this disease.

Interleukin-21: updated review of Phase I and II clinical trials in metastatic renal cell carcinoma, metastatic melanoma and relapsed/refractory indolent non-Hodgkin's lymphoma.

PubMed

Hashmi, Mehmood H; Van Veldhuizen, Peter J

2010-05-01

In advanced renal cell cancer and malignant melanoma, the current FDA approved immune modulators, such as IL-2, are the only agents which provide a durable complete remission. These responses, however, occur in < 10% of treated patients and their applicability is limited to selected patients because of their toxicity. The identification of new immunotherapeutic agents with an improved response rate and toxicity profile would represent a significant advancement in the treatment of these malignancies. This is a comprehensive review of IL-21 including its pharmacology and current developmental status. A literature review was performed using all PubMed listed publications involving IL-21, including original research articles, reviews and abstracts. It also includes a review of current ongoing trials and information from the official product website. Recombinant IL-21 (rIL-21) is a new immune modulator currently undergoing Phase I and II testing. It is a cytokine with a four helix structure that has structural and sequence homology to IL-2 and -15, but also possesses many unique biological properties. In this review, we evaluate the development, pharmacologic properties, safety profile and current clinical efficacy of rIL-21. rIL-21 has an acceptable safety profile and encouraging single agent activity in early phase renal cell carcinoma and melanoma clinical trials.

Pharmacogenetics and pharmacogenomics in psoriasis treatment: current challenges and future prospects.

PubMed

Sutherland, Alison; Power, Rebecca J; Rahman, Proton; O'Rielly, Darren D

2016-08-01

Topical, systemic, oral disease modifying, and biologic agents are part of the armamentarium to manage psoriatic disease. The choice of therapy depends upon disease severity, relevant co-morbidities and patient preference. There is great variability in patient response with these agents, and there is still no clear method of selecting the preferred therapeutic agent for efficacy or lack of adverse events. This article will review the pharmacogenetic and pharmacogenomic targets that are currently known with respect to psoriasis vulgaris, and the most frequent co-morbidity of psoriasis, psoriatic arthritis. Presently, no clinically actionable biomarker exists for any therapeutic agent used to treat psoriasis or psoriatic arthritis. The lack of validated outcome measures and conflicting results of open-label studies conducted may be attributed to a multitude of issues that confound discovery. Consequently, studies have been underpowered to identify genes or genetic variants worth translating to clinical practice. In order to achieve a pharmacogenetic/pharmacogenomic signature, improvements in study design of future investigations are required, including carefully designed prospective studies. It is imperative to combine known clinical, serological, and molecular markers with consistent outcomes and an adequate health economic evaluation before they can be adopted widely in clinical practice.

The pharmacology and toxicology of three new biologic agents used in pulmonary medicine.

PubMed

Albertson, T E; Walby, W F; Allen, R P; Tharratt, R S

1995-01-01

Biological agents have played an important role in the evolution of modern medical therapeutics. Recent advances in biologicals have in part been stimulated by the biotechnology revolution seen over the last several years. Toxicologists need to be aware of the proposed mechanisms and approved and experimental uses of these new biologic agents. Further, controversies about their use, efficacy, cost issues and potential toxicities should be known. Often these drugs are designed for small patient populations thus limiting the availability of human toxicological data bases. This paper reviews the pharmacology and toxicology of three new biologics (recombinant human DNase I, alpha 1-protease inhibitor, and nitric oxide). These agents appear to have important roles in treating specific diseases or disease states seen in pulmonary medicine.

Biological control agents elevate hantavirus by subsidizing deer mouse populations.

PubMed

Pearson, Dean E; Callaway, Ragan M

2006-04-01

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 knapweed (Centaurea maculosa) control, to indirectly elevate Sin Nombre hantavirus by providing food subsidies to populations of deer mice (Peromyscus maniculatus), the primary reservoir for the virus. We show that seropositive deer mice (mice testing positive for hantavirus) were over three times more abundant in the presence of the biocontrol food subsidy. Elevating densities of seropositive mice may increase risk of hantavirus infection in humans and significantly alter hantavirus ecology. Host specificity alone does not ensure safe biological control. To minimize indirect risks to non-target species, biological control agents must suppress pest populations enough to reduce their own numbers.

Biologic Therapy for HLA-B27-associated Ocular Disorders.

PubMed

Gueudry, Julie; Thorne, Jennifer E; Bansie, Rakesh; Braun, Juergen; van Hagen, P Martin; Bodaghi, Bahram

2017-04-01

The treatment of articular and extra-articular manifestations associated with HLA-B27 has undergone dramatic changes over the past two decades, mainly as a consequence of the introduction of biologic agents and in particular anti-tumor necrosis factor α (anti-TNFα) agents. Uveitis is known to be the most frequent extra-articular feature in HLA-B27-associated spondyloarthritides. Topical corticosteroids and cycloplegic agents remain the cornerstones of treatment. However, biologic therapy may be effective in the management of refractory or recurrent forms of uveitis. This review gives an update on the management of HLA-B27-associated ocular disorders with biologics, including anti-TNFα agents and non-anti-TNFα biologic modifier drugs. There is an emerging role for newer biologics targeting interleukin-12/23 and interleukin-17 for the treatment of spondyloarthritides but data on their efficacy on anterior uveitis are sparse.

How watching Pinocchio movies changes our subjective experience of extrapersonal space.

PubMed

Fini, Chiara; Committeri, Giorgia; Müller, Barbara C N; Deschrijver, Eliane; Brass, Marcel

2015-01-01

The way we experience the space around us is highly subjective. It has been shown that motion potentialities that are intrinsic to our body influence our space categorization. Furthermore, we have recently demonstrated that in the extrapersonal space, our categorization also depends on the movement potential of other agents. When we have to categorize the space as "Near" or "Far" between a reference and a target, the space categorized as "Near" is wider if the reference corresponds to a biological agent that has the potential to walk, instead of a biological and non-biological agent that cannot walk. But what exactly drives this "Near space extension"? In the present paper, we tested whether abstract beliefs about the biological nature of an agent determine how we categorize the space between the agent and an object. Participants were asked to first read a Pinocchio story and watch a correspondent video in which Pinocchio acts like a real human, in order to become more transported into the initial story. Then they had to categorize the location ("Near" or "Far") of a target object located at progressively increasing or decreasing distances from a non-biological agent (i.e., a wooden dummy) and from a biological agent (i.e., a human-like avatar). The results indicate that being transported into the Pinocchio story, induces an equal "Near" space threshold with both the avatar and the wooden dummy as reference frames.

Simulating Cancer Growth with Multiscale Agent-Based Modeling

PubMed Central

Wang, Zhihui; Butner, Joseph D.; Kerketta, Romica; Cristini, Vittorio; Deisboeck, Thomas S.

2014-01-01

There have been many techniques developed in recent years to in silico model a variety of cancer behaviors. Agent-based modeling is a specific discrete-based hybrid modeling approach that allows simulating the role of diversity in cell populations as well as within each individual cell; it has therefore become a powerful modeling method widely used by computational cancer researchers. Many aspects of tumor morphology including phenotype-changing mutations, the adaptation to microenvironment, the process of angiogenesis, the influence of extracellular matrix, reactions to chemotherapy or surgical intervention, the effects of oxygen and nutrient availability, and metastasis and invasion of healthy tissues have been incorporated and investigated in agent-based models. In this review, we introduce some of the most recent agent-based models that have provided insight into the understanding of cancer growth and invasion, spanning multiple biological scales in time and space, and we further describe several experimentally testable hypotheses generated by those models. We also discuss some of the current challenges of multiscale agent-based cancer models. PMID:24793698

Vedolizumab as a Treatment for Crohn's Disease and Ulcerative Colitis.

PubMed

Ha, Christina; Kornbluth, Asher

2014-12-01

The management of Crohn's disease and ulcerative colitis has become increasingly complex. With the current utilization of immunosuppressive therapies earlier in the disease course for patients presenting with moderate to severe disease, there is a great need for additional biologic agents targeting inflammatory mediators other than anti-tumor necrosis factor-α (anti-TNF) agents. Although anti-TNF agents have positively impacted the treatment of inflammatory bowel disease, many patients can lose their response or develop intolerance to these agents over time through the formation of antidrug antibodies. Furthermore, a sizeable percentage of patients are primary nonresponders to anti-TNF drugs. Vedolizumab (Entyvio, Takeda Pharmaceuticals), a monoclonal antibody to the α4β7 integrin, inhibits gut lymphocyte trafficking and has been demonstrated to be an effective and safe agent for the treatment of both Crohn's disease and ulcerative colitis. This article reviews the clinical trial evidence and rationale for the use of vedolizumab in moderate to severe Crohn's disease and ulcerative colitis.

Vedolizumab as a Treatment for Crohn’s Disease and Ulcerative Colitis

PubMed Central

Ha, Christina

2014-01-01

The management of Crohn’s disease and ulcerative colitis has become increasingly complex. With the current utilization of immunosuppressive therapies earlier in the disease course for patients presenting with moderate to severe disease, there is a great need for additional biologic agents targeting inflammatory mediators other than anti-tumor necrosis factor-α (anti-TNF) agents. Although anti-TNF agents have positively impacted the treatment of inflammatory bowel disease, many patients can lose their response or develop intolerance to these agents over time through the formation of antidrug antibodies. Furthermore, a sizeable percentage of patients are primary nonresponders to anti-TNF drugs. Vedolizumab (Entyvio, Takeda Pharmaceuticals), a monoclonal antibody to the α4β7 integrin, inhibits gut lymphocyte trafficking and has been demonstrated to be an effective and safe agent for the treatment of both Crohn’s disease and ulcerative colitis. This article reviews the clinical trial evidence and rationale for the use of vedolizumab in moderate to severe Crohn’s disease and ulcerative colitis. PMID:27524947

Genomic Characterization of Paediatric Acute Lymphoblastic Leukaemia: an Opportunity for Precision Medicine Therapeutics

PubMed Central

Tasian, Sarah K; Hunger, Stephen P

2016-01-01

Major advances in genetic and epigenetic profiling of acute lymphoblastic leukaemia (ALL) have enhanced the understanding of key biological subsets of de novo and relapsed ALL, which has led to improved risk stratification of patients. These achievements have further defined critical leukaemia-associated pathways and somatic alterations that may be preferentially sensitive to treatment with kinase inhibitors, epigenetic therapy or other novel agents. Therapeutic success in childhood ALL currently relies upon refined risk stratification of patients based on (1) underlying biological and clinical characteristics and (2) depth of initial treatment response with appropriate modulation of chemotherapy intensity. This review describes the current mutational landscape of childhood ALL and discusses opportunities for substantial improvements in survival with implementation of molecularly targeted therapies. PMID:27984637

Genomic characterization of paediatric acute lymphoblastic leukaemia: an opportunity for precision medicine therapeutics.

PubMed

Tasian, Sarah K; Hunger, Stephen P

2017-03-01

Major advances in genetic and epigenetic profiling of acute lymphoblastic leukaemia (ALL) have enhanced the understanding of key biological subsets of de novo and relapsed ALL, which has led to improved risk stratification of patients. These achievements have further defined critical leukaemia-associated pathways and somatic alterations that may be preferentially sensitive to treatment with kinase inhibitors, epigenetic therapy or other novel agents. Therapeutic success in childhood ALL currently relies upon refined risk stratification of patients based on (i) underlying biological and clinical characteristics, and (ii) depth of initial treatment response with appropriate modulation of chemotherapy intensity. This review describes the current mutational landscape of childhood ALL and discusses opportunities for substantial improvements in survival with implementation of molecularly targeted therapies. © 2016 John Wiley & Sons Ltd.

Insights into the use of gadolinium and gadolinium/boron-based agents in imaging-guided neutron capture therapy applications.

PubMed

Deagostino, Annamaria; Protti, Nicoletta; Alberti, Diego; Boggio, Paolo; Bortolussi, Silva; Altieri, Saverio; Crich, Simonetta Geninatti

2016-05-01

Gadolinium neutron capture therapy (Gd-NCT) is currently under development as an alternative approach for cancer therapy. All of the clinical experience to date with NCT is done with (10)B, known as boron neutron capture therapy (BNCT), a binary treatment combining neutron irradiation with the delivery of boron-containing compounds to tumors. Currently, the use of Gd for NCT has been getting more attention because of its highest neutron cross-section. Although Gd-NCT was first proposed many years ago, its development has suffered due to lack of appropriate tumor-selective Gd agents. This review aims to highlight the recent advances for the design, synthesis and biological testing of new Gd- and B-Gd-containing compounds with the task of finding the best systems able to improve the NCT clinical outcome.

IFN-λ cancer immunotherapy: new kid on the block.

PubMed

Lasfar, Ahmed; Gogas, Helen; Zloza, Andrew; Kaufman, Howard L; Kirkwood, John M

2016-07-01

Interferon-lambda (IFN-λ) is a new IFN type, related to IFN-α, that is commonly used in the clinic. However, significant side effects accompanying IFN-α treatment limit enthusiasm for IFN-α. In this review, we discuss the current landscape of IFN-α use in oncology and describe the biologic characteristics of IFN-λ. IFN-λ offers unique advantages, including a more tumor cell selective targeting, lower off-target binding and an ability to generate both innate and adaptive immune responses. IFN-λ has also demonstrated therapeutic benefit in murine cancer models. IFN-λ may be used in clinic as a single agent or in combination with other immunotherapy agents, such as immune checkpoint inhibitors. Further clinical trials will be needed to fully elucidate the potential of this novel agent in oncology.

Basic analytical methods for identification of erythropoiesis-stimulating agents in doping control

NASA Astrophysics Data System (ADS)

Postnikov, P. V.; Krotov, G. I.; Efimova, Yu A.; Rodchenkov, G. M.

2016-02-01

The design of new erythropoiesis-stimulating agents for clinical use necessitates constant development of methods for detecting the abuse of these substances, which are prohibited under the World Anti-Doping Code and are included in the World Anti-Doping Agency (WADA) prohibited list. This review integrates and describes systematically the published data on the key methods currently used by WADA-accredited anti-doping laboratories around the world to detect the abuse of erythropoiesis-stimulating agents, including direct methods (various polyacrylamide gel electrophoresis techniques, enzyme-linked immunosorbent assay, membrane enzyme immunoassay and mass spectrometry) and indirect methods (athlete biological passport). Particular attention is given to promising approaches and investigations that can be used to control prohibited erythropoietins in the near future. The bibliography includes 122 references.

[Biological and toxin terrorism weapons].

PubMed

Bokan, Slavko

2003-03-01

The use of biological agents and toxins in warfare and terrorism has a long history. Human, animal and plant pathogens and toxins can cause disease and can be used as a threat to humans, animals and staple crops. The same is true for biological agents. Although the use of biological agents and toxins in military conflicts has been a concern of military communities for many years, several recent events have increased the awareness of terrorist use of these weapons against civilian population. A Mass Casualty Biological (Toxin) Weapon (MCBTW) is any biological and toxin weapon capable of causing death or disease on a large scale, such that the military or civilian infrastructure of the state or organization being attacked is overwhelmed. A militarily significant (or terrorist) weapon is any weapon capable of affecting, directly or indirectly, that is physically or psychologically, the outcome of a military operation. Although many biological agents such as toxins and bioregulators can be used to cause diseases, there are only a few that can truly threaten civilian populations on a large scale. Bioregulators or modulators are biochemical compounds, such as peptides, that occur naturally in organisms. They are new class of weapons that can damage nervous system, alter moods, trigger psychological changes and kill. The potential military or terrorist use of bioregulators is similar to that of toxins. Some of these compounds are several hundred times more potent than traditional chemical warfare agents. Important features and military advantages of new bioregulators are novel sites of toxic action; rapid and specific effects; penetration of protective filters and equipment, and militarily effective physical incapacitation. This overview of biological agents and toxins is largely intended to help healthcare providers on all levels to make decisions in protecting general population from these agents.

Pharmacological management of osteogenesis

PubMed Central

Nardone, Valeria; D'Asta, Federica; Brandi, Maria Luisa

2014-01-01

Osteogenesis and bone remodeling are complex biological processes that are essential for the formation of new bone tissue and its correct functioning. When the balance between bone resorption and formation is disrupted, bone diseases and disorders such as Paget's disease, fibrous dysplasia, osteoporosis and fragility fractures may result. Recent advances in bone cell biology have revealed new specific targets for the treatment of bone loss that are based on the inhibition of bone resorption by osteoclasts or the stimulation of bone formation by osteoblasts. Bisphosphonates, antiresorptive agents that reduce bone resorption, are usually recommended as first-line therapy in women with postmenopausal osteoporosis. Numerous studies have shown that bisphosphonates are able to significantly reduce the risk of femoral and vertebral fractures. Other antiresorptive agents indicated for the treatment of osteoporosis include selective estrogen receptor modulators, such as raloxifene. Denosumab, a human monoclonal antibody, is another antiresorptive agent that has been approved in Europe and the USA. This agent blocks the RANK/RANKL/OPG system, which is responsible for osteoclastic activation, thus reducing bone resorption. Other approved agents include bone anabolic agents, such as teriparatide, a recombinant parathyroid hormone that improves bone microarchitecture and strength, and strontium ranelate, considered to be a dual-action drug that acts by both osteoclastic inhibition and osteoblastic stimulation. Currently, anti-catabolic drugs that act through the Wnt-β catenin signaling pathway, serving as Dickkopf-related protein 1 inhibitors and sclerostin antagonists, are also in development. This concise review provides an overview of the drugs most commonly used for the control of osteogenesis in bone diseases. PMID:24964310

Interactions of dendrimers with biological drug targets: reality or mystery - a gap in drug delivery and development research.

PubMed

Ahmed, Shaimaa; Vepuri, Suresh B; Kalhapure, Rahul S; Govender, Thirumala

2016-07-21

Dendrimers have emerged as novel and efficient materials that can be used as therapeutic agents/drugs or as drug delivery carriers to enhance therapeutic outcomes. Molecular dendrimer interactions are central to their applications and realising their potential. The molecular interactions of dendrimers with drugs or other materials in drug delivery systems or drug conjugates have been extensively reported in the literature. However, despite the growing application of dendrimers as biologically active materials, research focusing on the mechanistic analysis of dendrimer interactions with therapeutic biological targets is currently lacking in the literature. This comprehensive review on dendrimers over the last 15 years therefore attempts to identify the reasons behind the apparent lack of dendrimer-receptor research and proposes approaches to address this issue. The structure, hierarchy and applications of dendrimers are briefly highlighted, followed by a review of their various applications, specifically as biologically active materials, with a focus on their interactions at the target site. It concludes with a technical guide to assist researchers on how to employ various molecular modelling and computational approaches for research on dendrimer interactions with biological targets at a molecular level. This review highlights the impact of a mechanistic analysis of dendrimer interactions on a molecular level, serves to guide and optimise their discovery as medicinal agents, and hopes to stimulate multidisciplinary research between scientific, experimental and molecular modelling research teams.

High-throughput assay for optimising microbial biological control agent production and delivery

USDA-ARS?s Scientific Manuscript database

Lack of technologies to produce and deliver effective biological control agents (BCAs) is a major barrier to their commercialization. A myriad of variables associated with BCA cultivation, formulation, drying, storage, and reconstitution processes complicates agent quality maximization. An efficie...

Biology and life history of Argopistes tsekooni (Coleoptera: Chrysomelidae) in China, a promising biological control agent of Chinese privet.

Treesearch

Y-Z Zhang; J. Sun; J.L. Hanula

2009-01-01

The biology and life history of Argopistes tsekooni Chen (Coleoptera: Chrysomelidae), a potential biological control agent of Chinese privet, Ligustrum sinense Lour., was studied under laboratory and outdoor conditions in Huangshan City of Anhui Province, China, in 2006. A. tsekooni larvae are leafminers that...

Biological and chemical weapons of mass destruction: updated clinical therapeutic countermeasures since 2003.

PubMed

Pettineo, Christopher; Aitchison, Robert; Leikin, Scott M; Vogel, Stephen N; Leikin, Jerrold B

2009-01-01

The objective of this article is to provide updated treatment options for bioterrorism agents. This updated synopsis includes recent clinical cases and treatment recommendations that have arisen in the last 5 years. The decontamination, treatment, and disposition of these biologic and chemical agents are presented alphabetically by agent type: biologic, chemical, and radiologic/nuclear. The information provided outlines only new treatment options since 2003.

Personal protection during resuscitation of casualties contaminated with chemical or biological warfare agents--a survey of medical first responders.

PubMed

Brinker, Andrea; Prior, Kate; Schumacher, Jan

2009-01-01

The threat of mass casualties caused by an unconventional terrorist attack is a challenge for the public health system, with special implications for emergency medicine, anesthesia, and intensive care. Advanced life support of patients injured by chemical or biological warfare agents requires an adequate level of personal protection. The aim of this study was to evaluate the personal protection knowledge of emergency physicians and anesthetists who would be at the frontline of the initial health response to a chemical/biological warfare agent incident. After institutional review board approval, knowledge of personal protection measures among emergency medicine (n = 28) and anesthetics (n = 47) specialty registrars in the South Thames Region of the United Kingdom was surveyed using a standardized questionnaire. Participants were asked for the recommended level of personal protection if a chemical/biological warfare agent(s) casualty required advanced life support in the designated hospital resuscitation area. The best awareness within both groups was regarding severe acute respiratory syndrome, and fair knowledge was found regarding anthrax, plague, Ebola, and smallpox. In both groups, knowledge about personal protection requirements against chemical warfare agents was limited. Knowledge about personal protection measures for biological agents was acceptable, but was limited for chemical warfare agents. The results highlight the need to improve training and education regarding personal protection measures for medical first receivers.

Impact of Release Rates on the Effectiveness of Augmentative Biological Control Agents

PubMed Central

Crowder, David W.

2007-01-01

To access the effect of augmentative biological control agents, 31 articles were reviewed that investigated the impact of release rates of 35 augmentative biological control agents on the control of 42 arthropod pests. In 64% of the cases, the release rate of the biological control agent did not significantly affect the density or mortality of the pest insect. Results where similar when parasitoidsor predators were utilized as the natural enemy. Within any order of natural enemy, there were more cases where release rates did not affect augmentative biological control than cases where release rates were significant. There were more cases in which release rates did not affect augmentative biological control when pests were from the orders Hemiptera, Acari, or Diptera, but not with pests from the order Lepidoptera. In most cases, there was an optimal release rate that produced effective control of a pest species. This was especially true when predators were used as a biological control agent. Increasing the release rate above the optimal rate did not improve control of the pest and thus would be economically detrimental. Lower release rates were of ten optimal when biological control was used in conjunction with insecticides. In many cases, the timing and method of biological control applications were more significant factors impacting the effectiveness of biological control than the release rate. Additional factors that may limit the relative impact of release rates include natural enemy fecundity, establishment rates, prey availability, dispersal, and cannibalism. PMID:20307240

Astaxanthin: Sources, Extraction, Stability, Biological Activities and Its Commercial Applications—A Review

PubMed Central

Ambati, Ranga Rao; Siew Moi, Phang; Ravi, Sarada; Aswathanarayana, Ravishankar Gokare

2014-01-01

There is currently much interest in biological active compounds derived from natural resources, especially compounds that can efficiently act on molecular targets, which are involved in various diseases. Astaxanthin (3,3′-dihydroxy-β, β′-carotene-4,4′-dione) is a xanthophyll carotenoid, contained in Haematococcus pluvialis, Chlorella zofingiensis, Chlorococcum, and Phaffia rhodozyma. It accumulates up to 3.8% on the dry weight basis in H. pluvialis. Our recent published data on astaxanthin extraction, analysis, stability studies, and its biological activities results were added to this review paper. Based on our results and current literature, astaxanthin showed potential biological activity in in vitro and in vivo models. These studies emphasize the influence of astaxanthin and its beneficial effects on the metabolism in animals and humans. Bioavailability of astaxanthin in animals was enhanced after feeding Haematococcus biomass as a source of astaxanthin. Astaxanthin, used as a nutritional supplement, antioxidant and anticancer agent, prevents diabetes, cardiovascular diseases, and neurodegenerative disorders, and also stimulates immunization. Astaxanthin products are used for commercial applications in the dosage forms as tablets, capsules, syrups, oils, soft gels, creams, biomass and granulated powders. Astaxanthin patent applications are available in food, feed and nutraceutical applications. The current review provides up-to-date information on astaxanthin sources, extraction, analysis, stability, biological activities, health benefits and special attention paid to its commercial applications. PMID:24402174

Improving performance of HVAC systems to reduce exposure to aerosolized infectious agents in buildings; recommendations to reduce risks posed by biological attacks.

PubMed

Hitchcock, Penny J; Mair, Michael; Inglesby, Thomas V; Gross, Jonathan; Henderson, D A; O'Toole, Tara; Ahern-Seronde, Joa; Bahnfleth, William P; Brennan, Terry; Burroughs, H E Barney; Davidson, Cliff; Delp, William; Ensor, David S; Gomory, Ralph; Olsiewski, Paula; Samet, Jonathan M; Smith, William M; Streifel, Andrew J; White, Ronald H; Woods, James E

2006-01-01

The prospect of biological attacks is a growing strategic threat. Covert aerosol attacks inside a building are of particular concern. In the summer of 2005, the Center for Biosecurity of the University of Pittsburgh Medical Center convened a Working Group to determine what steps could be taken to reduce the risk of exposure of building occupants after an aerosol release of a biological weapon. The Working Group was composed of subject matter experts in air filtration, building ventilation and pressurization, air conditioning and air distribution, biosecurity, building design and operation, building decontamination and restoration, economics, medicine, public health, and public policy. The group focused on functions of the heating, ventilation, and air conditioning systems in commercial or public buildings that could reduce the risk of exposure to deleterious aerosols following biological attacks. The Working Group's recommendations for building owners are based on the use of currently available, off-the-shelf technologies. These recommendations are modest in expense and could be implemented immediately. It is also the Working Group's judgment that the commitment and stewardship of a lead government agency is essential to secure the necessary financial and human resources and to plan and build a comprehensive, effective program to reduce exposure to aerosolized infectious agents in buildings.

Progress with the use of monoclonal antibodies for the treatment of systemic lupus erythematosus.

PubMed

Jordan, Natasha; Lutalo, Pamela Mk; D'Cruz, David P

2015-01-01

In recent years, significant progress has been made in the use of monoclonal antibodies in the treatment of systemic lupus erythematosus (SLE). Advances in our understanding of the complexity of SLE immunopathogenesis have led to the testing of several biologic agents in clinical trials. Monoclonal therapies currently emerging or under development include B-cell depletion therapies, agents targeting B-cell survival factors, blockade of T-cell co-stimulation and anticytokine therapies. Issues remain, however, regarding clinical trial design and outcome measures in SLE which need to be addressed to optimize translation of these promising therapies into clinical practice.

The management of systemic lupus erythematosus: Facts and controversies.

PubMed

Elbirt, Daniel; Sthoeger, Dalia; Asher, Ilan; Sthoeger, Zev Moshe

2010-01-01

Systemic lupus erythematosus is a multisystem disease of unknown etiology in which dysregulation of the innate and adaptive immune systems has a major effect in the pathogenesis of the disease. The treatment should be tailored for each patient according to how the disease manifests itself. Although there is no cure for systemic lupus erythematosus, the current treatment, using anti-inflammatory, antimalarial, and immunosuppressive agents, is fairly effective, but serious adverse events are possible. New biologic agents that target various components of the immune system recently have been developed for the treatment of patients with systemic lupus erythematosus. Copyright 2010 Elsevier Inc. All rights reserved.

Integrating biodefense topics into secondary education curriculum

NASA Astrophysics Data System (ADS)

Dalfrey, Karen E.

Concerns about threats posed by microorganisms found in nature are compounded with the possibility for intentional dissemination. Our vulnerability has increased due to more frequent travel between geographical regions, newly emerging pathogens, changes in terrorist activities, and advances in biotechnology. To increase awareness and global preparedness for threats posed by biological agents, educators need to have access to training and materials to educate the next generation in these issues. To assess what approach would provide educators with the tools necessary to incorporate biodefense related content into their current curricula, secondary education science teachers were surveyed about factors limiting the content of curricula presented in their courses. Results indicate that the most influential barriers to curricula change are time limitations and state mandated exam pressures. Analysis measuring differences in survey responses between two groups of teachers who are separated based on their level of using mandated state objectives to guide their curricula planning indicates that pressures of state mandated exam scores and a general fear of unsuccessful results are determinants for separating teachers into one of these two groups. A teacher training workshop conducive to supporting curricula change was held with the goal of increasing awareness of current threats posed by biological agents and modern biodefense strategies. The workshop was also designed to assist participants in overcoming barriers challenging their ability to incorporate new content into curricula. Participant responses to a post-workshop survey were favorable for measurements of the workshop effectiveness towards diminishing barriers to teacher initiated curricula changes. Respondents reported increased understanding of modern biology, increased realization of the importance of updating curricula with modern knowledge, and increased likeliness of incorporating content from the workshop into current curriculum.

History and perspectives of bioanalytical methods for chemical warfare agent detection.

PubMed

Black, Robin M

2010-05-15

This paper provides a short historical overview of the development of bioanalytical methods for chemical warfare (CW) agents and their biological markers of exposure, with a more detailed overview of methods for organophosphorus nerve agents. Bioanalytical methods for unchanged CW agents are used primarily for toxicokinetic/toxicodynamic studies. An important aspect of nerve agent toxicokinetics is the different biological activity and detoxification pathways for enantiomers. CW agents have a relatively short lifetime in the human body, and are hydrolysed, metabolised, or adducted to nucleophilic sites on macromolecules such as proteins and DNA. These provide biological markers of exposure. In the past two decades, metabolites, protein adducts of nerve agents, vesicants and phosgene, and DNA adducts of sulfur and nitrogen mustards, have been identified and characterized. Sensitive analytical methods have been developed for their detection, based mainly on mass spectrometry combined with gas or liquid chromatography. Biological markers for sarin, VX and sulfur mustard have been validated in cases of accidental and deliberate human exposures. The concern for terrorist use of CW agents has stimulated the development of higher throughput analytical methods in support of homeland security. Copyright (c) 2010. Published by Elsevier B.V.

Entamoeba histolytica: a snapshot of current research and methods for genetic analysis

PubMed Central

Morf, Laura; Singh, Upinder

2012-01-01

Entamoeba histolytica represents one of the leading causes of parasitic death worldwide. Although identified as the causative agent of amebiasis since 1875, the molecular mechanisms by which the parasite causes disease are still not fully understood. Studying Entamoeba reveals insights into a eukaryotic cell that differs in many ways from better-studied model organisms. Thus, much can be learned from this protozoan parasite on evolution, cell biology and RNA biology. In this review we discuss selected research highlights in Entamoeba research and focus on the development of molecular biological techniques to study this pathogen. We end by highlighting some of the many questions that remain to be answered in order to fully understand this important human pathogen. PMID:22664276

Castles and cuitlacoche: the first international Ustilago conference.

PubMed

Kronstad, J W

2003-04-01

The first international Ustilago conference was held in Marburg, Germany from August 22 to 25, 2002. The meeting focused on molecular genetic and cell biology research with Ustilago maydis, the causative agent of common smut of maize. This fungus has emerged as a useful experimental organism for studying the biology of basidiomycete fungi, with a particular emphasis on the interaction of the fungus with the host plant. Thus presentations at the meeting covered the range of current research topics including DNA recombination and repair, mating and sexual development, phytopathology, cell biology, the cell cycle, signaling, and genomics. The meeting also highlighted historical aspects of U. maydis research with presentations by pioneers in the field including Robin Holiday (recombination), Yigal Koltin (killer phenomenon) and Peter Day (plant pathology).

Current and future pharmaceutical therapy for rheumatoid arthritis.

PubMed

Ruderman, Eric M

2005-01-01

Rheumatoid arthritis (RA) is a chronic, inflammatory arthritis with a population prevalence of approximately 1%. Pharmaceutical treatment includes both anti-inflammatory medications and disease modifying drugs (DMARDs) that impact the course of the damage associated with this disease. Traditional DMARD therapy includes immunomodulatory agents such as methotrexate, used both alone and in combination. Recently available biologic response modifiers are very effective at reducing both the clinical symptoms of disease and the radiographic damage that accompanies them. This manuscript describes the clinical assessments used to measure response to therapy in RA and reviews the results seen with the various treatment strategies in this disease. In addition, the clinical and structural outcomes seen in trials of newly available and pending biologic therapies are reviewed, along with the specific toxicity issues associated with these agents. Clinical trial data is reviewed for the TNF antagonists, which have become the standard of care in RA patients with an inadequate response to methotrexate. RA has been clearly shown to be a destructive and disabling disease. The widespread use of newer agents, however, along with more aggressive use of existing therapies, appears to limit disease progression very effectively, and should lead to better long-term outcomes for these patients.

Update on the Treatment of Early-Stage Triple-Negative Breast Cancer.

PubMed

Sharma, Priyanka

2018-04-14

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared to other breast cancer subtypes. Currently, chemotherapy remains the main modality of treatment for early-stage TNBC, as there is no approved targeted therapy for this subtype. The biologic heterogeneity of TNBC has hindered the development and evaluation of novel agents, but recent advancements in subclassifying TNBC have paved the way for further investigation of more effective systemic therapies, including cytotoxic and targeted agents. TNBC is enriched for germline BRCA mutation and for somatic deficiencies in homologous recombination DNA repair, the so-called "BRCAness" phenotype. Together, germline BRCA mutations and BRCAness are promising biomarkers of susceptibility to DNA-damaging therapy. Various investigational approaches are consequently being investigated in early-stage TNBC, including immune checkpoint inhibitors, platinum compounds, PI3K pathway inhibitors, and androgen receptor inhibitors. Due to the biological diversity found within TNBC, patient selection based on molecular biomarkers could aid the design of early-phase clinical trials, ultimately accelerating the clinical application of effective new agents. TNBC is an aggressive breast cancer subtype, for which multiple targeted approaches will likely be required for patient outcomes to be substantially improved.

Repair and tissue engineering techniques for articular cartilage

PubMed Central

Makris, Eleftherios A.; Gomoll, Andreas H.; Malizos, Konstantinos N.; Hu, Jerry C.; Athanasiou, Kyriacos A.

2015-01-01

Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of regenerative biological products that over the next decade could revolutionize joint care by functionally healing articular cartilage. These products include cell-based and cell-free materials such as autologous and allogeneic cell-based approaches and multipotent and pluripotent stem-cell-based techniques. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed. PMID:25247412

Traditional schemes for treatment of psoriatic arthritis.

PubMed

McHugh, Neil J

2009-08-01

Prior to the availability of biologic agents such as anti-tumor necrosis factor (TNF), traditional treatment schemes for psoriatic arthritis were not extensively evaluated. While it appears that the newer forms of treatment are more effective, conventional agents still need to be scrutinized with similar methodology and will still have a role in those patients with less progressive disease, in combination with biologic agents, and in patients where biologics are not tolerated or have failed.

Decontamination of biological warfare agents by a microwave plasma torch

NASA Astrophysics Data System (ADS)

Lai, Wilson; Lai, Henry; Kuo, Spencer P.; Tarasenko, Olga; Levon, Kalle

2005-02-01

A portable arc-seeded microwave plasma torch running stably with airflow is described and applied for the decontamination of biological warfare agents. Emission spectroscopy of the plasma torch indicated that this torch produced an abundance of reactive atomic oxygen that could effectively oxidize biological agents. Bacillus cereus was chosen as a simulant of Bacillus anthracis spores for biological agent in the decontamination experiments. Decontamination was performed with the airflow rate of 0.393l/s, corresponding to a maximum concentration of atomic oxygen produced by the torch. The experimental results showed that all spores were killed in less than 8 s at 3 cm distance, 12 s at 4 cm distance, and 16 s at 5 cm distance away from the nozzle of the torch.

New treatments for psoriasis: which biologic is best?

PubMed

Nelson, Andrew A; Pearce, Daniel J; Fleischer, Alan B; Balkrishnan, Rajesh; Feldman, Steven R

2006-01-01

Psoriasis is a chronic, debilitating disease affecting not only the skin, but also having a significant impact on a patient's quality of life. The treatment of severe psoriasis is quite challenging due to the chronic, relapsing nature of the disease and the difficulties inherent in treatment planning. Though the biologics are perhaps the most promising of available psoriasis treatments, the decision to institute a given therapy may be fraught with complexity for the clinician. Patients now hear of these promising new treatments for psoriasis via print, television and radio advertising; they frequently come to their physician asking if they are eligible for any of these agents and, if so, 'which biologic is best?'. This paper attempts to determine the ideal biologic agent based upon several parameters: FDA- and EU-approved indications, therapeutic efficacy, impact on quality of life, cost-effectiveness, and safety profile. Certainly the physician is central to medical decision-making, though ultimately patient preference may play the largest role in determining the 'best' biologic agent. There is no single ideal biologic for all patients and a physician's job is to educate patients on the relative advantages and disadvantages of each agent. Through informed discussion, the clinician can help each individual patient decide which biologic agent is ideal for them.

Biological agents with potential for misuse: a historical perspective and defensive measures.

PubMed

Bhalla, Deepak K; Warheit, David B

2004-08-15

Biological and chemical agents capable of producing serious illness or mortality have been used in biowarfare from ancient times. Use of these agents has progressed from crude forms in early and middle ages, when snakes and infected cadavers were used as weapons in battles, to sophisticated preparations for use during and after the second World War. Cults and terrorist organizations have attempted the use of biological agents with an aim to immobilize populations or cause serious harm. The reasons for interest in these agents by individuals and organizations include relative ease of acquisition, potential for causing mass casualty or panic, modest financing requirement, availability of technology, and relative ease of delivery. The Centers for Disease Control and Prevention has classified Critical Biological Agents into three major categories. This classification was based on several criteria, which include severity of impact on human health, potential for delivery in a weapon, capacity to cause panic and special needs for development, and stockpiling of medication. Agents that could cause the greatest harm following deliberate use were placed in category A. Category B included agents capable of producing serious harm and significant mortality but of lower magnitude than category A agents. Category C included emerging pathogens that could be developed for mass dispersion in future and their potential as a major health threat. A brief description of the category A bioagents is included and the pathophysiology of two particularly prominent agents, namely anthrax and smallpox, is discussed in detail. The potential danger from biological agents and their ever increasing threat to human populations have created a need for developing technologies for their early detection, for developing treatment strategies, and for refinement of procedures to ensure survival of affected individuals so as to attain the ultimate goal of eliminating the threat from intentional use of these agents. International treaties limiting development and proliferation of weapons and continuing development of defense strategies and safe guards against agents of concern are important elements of plans for eliminating this threat.

Trends in GPCR drug discovery: new agents, targets and indications.

PubMed

Hauser, Alexander S; Attwood, Misty M; Rask-Andersen, Mathias; Schiöth, Helgi B; Gloriam, David E

2017-12-01

G protein-coupled receptors (GPCRs) are the most intensively studied drug targets, mostly due to their substantial involvement in human pathophysiology and their pharmacological tractability. Here, we report an up-to-date analysis of all GPCR drugs and agents in clinical trials, which reveals current trends across molecule types, drug targets and therapeutic indications, including showing that 475 drugs (~34% of all drugs approved by the US Food and Drug Administration (FDA)) act at 108 unique GPCRs. Approximately 321 agents are currently in clinical trials, of which ~20% target 66 potentially novel GPCR targets without an approved drug, and the number of biological drugs, allosteric modulators and biased agonists has increased. The major disease indications for GPCR modulators show a shift towards diabetes, obesity and Alzheimer disease, although several central nervous system disorders are also highly represented. The 224 (56%) non-olfactory GPCRs that have not yet been explored in clinical trials have broad untapped therapeutic potential, particularly in genetic and immune system disorders. Finally, we provide an interactive online resource to analyse and infer trends in GPCR drug discovery.

Biomedical Applications of Nanomaterials as Therapeutics.

PubMed

Ng, Cheng-Teng; Baeg, Gyeong-Hun; Yu, Liya E; Ong, Choon-Nam; Bay, Boon-Huat

2018-01-01

As nanomaterials possess attractive physicochemical properties, immense research efforts have been channeled towards their development for biological and biomedical applications. In particular, zinc nanomaterials (nZnOs) have shown great potential for use in in the medical and pharmaceutical fields, and as tools for novel antimicrobial treatment, thereby capitalizing on their unique antimicrobial effects. We conducted a literature search using databases to retrieve the relevant articles related to the synthesis, properties and current applications of nZnOs in the diagnosis and treatment of diseases. A total of 86 publications were selected for inclusion in this review. Besides studies on the properties and the methodology for the synthesis of nZnOs, many studies have focused on the application of nZnOs as delivery agents, biosensors and antimicrobial agents, as well as in bioimaging. This review gives an overview of the current development of nZnOs for their potential use as theranostic agents. However, more comprehensive studies are needed to better assess the valuable contributions and the safety of nZnOs in nanomedicine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Combining Targeted Agents With Modern Radiotherapy in Soft Tissue Sarcomas

PubMed Central

Wong, Philip; Houghton, Peter; Kirsch, David G.; Finkelstein, Steven E.; Monjazeb, Arta M.; Xu-Welliver, Meng; Dicker, Adam P.; Ahmed, Mansoor; Vikram, Bhadrasain; Teicher, Beverly A.; Coleman, C. Norman; Machtay, Mitchell; Curran, Walter J.

2014-01-01

Improved understanding of soft-tissue sarcoma (STS) biology has led to better distinction and subtyping of these diseases with the hope of exploiting the molecular characteristics of each subtype to develop appropriately targeted treatment regimens. In the care of patients with extremity STS, adjunctive radiation therapy (RT) is used to facilitate limb and function, preserving surgeries while maintaining five-year local control above 85%. In contrast, for STS originating from nonextremity anatomical sites, the rate of local recurrence is much higher (five-year local control is approximately 50%) and a major cause of death and morbidity in these patients. Incorporating novel technological advancements to administer accurate RT in combination with novel radiosensitizing agents could potentially improve local control and overall survival. RT efficacy in STS can be increased by modulating biological pathways such as angiogenesis, cell cycle regulation, cell survival signaling, and cancer-host immune interactions. Previous experiences, advancements, ongoing research, and current clinical trials combining RT with agents modulating one or more of the above pathways are reviewed. The standard clinical management of patients with STS with pretreatment biopsy, neoadjuvant treatment, and primary surgery provides an opportune disease model for interrogating translational hypotheses. The purpose of this review is to outline a strategic vision for clinical translation of preclinical findings and to identify appropriate targeted agents to combine with radiotherapy in the treatment of STS from different sites and/or different histology subtypes. PMID:25326640

Privileged structures: efficient chemical "navigators" toward unexplored biologically relevant chemical spaces.

PubMed

Kim, Jonghoon; Kim, Heejun; Park, Seung Bum

2014-10-22

In the search for new therapeutic agents for currently incurable diseases, attention has turned to traditionally "undruggable" targets, and collections of drug-like small molecules with high diversity and quality have become a prerequisite for new breakthroughs. To generate such collections, the diversity-oriented synthesis (DOS) strategy was developed, which aims to populate new chemical space with drug-like compounds containing a high degree of molecular diversity. The resulting DOS-derived libraries have been of great value for the discovery of various bioactive small molecules and therapeutic agents, and thus DOS has emerged as an essential tool in chemical biology and drug discovery. However, the key challenge has become how to design and synthesize drug-like small-molecule libraries with improved biological relevancy as well as maximum molecular diversity. This Perspective presents the development of privileged substructure-based DOS (pDOS), an efficient strategy for the construction of polyheterocyclic compound libraries with high biological relevancy. We envisioned the specific interaction of drug-like small molecules with certain biopolymers via the incorporation of privileged substructures into polyheterocyclic core skeletons. The importance of privileged substructures such as benzopyran, pyrimidine, and oxopiperazine in rigid skeletons was clearly demonstrated through the discovery of bioactive small molecules and the subsequent identification of appropriate target biomolecule using a method called "fluorescence difference in two-dimensional gel electrophoresis". Focusing on examples of pDOS-derived bioactive compounds with exceptional specificity, we discuss the capability of privileged structures to serve as chemical "navigators" toward biologically relevant chemical spaces. We also provide an outlook on chemical biology research and drug discovery using biologically relevant compound libraries constructed by pDOS, biology-oriented synthesis, or natural product-inspired DOS.

Fibrous Filter to Protect Building Environments from Polluting Agents: A Review

NASA Astrophysics Data System (ADS)

Chavhan, Md. Vaseem; Mukhopadhyay, Arunangshu

2016-04-01

This paper discusses the use of fibrous filter to protect the building environments from air born polluting agents and especially of concern chemical, biological and radiological agents. Air-filtration includes removal of particulate from air and toxic gases from air. In air filtration, particulate which are mostly biological and radioactive types of agents can be removed by using mechanical and electrostatic filters. Some biological agents, which cannot be removed by air filtration alone, special techniques like antimicrobial finish, UV germicides, coated filters etc. are required. Biocide agent can be added into the fibre itself by grafting reaction to impart antimicrobial activity. Chemical agents like toxic gases can be removed by integrating adsorbents and sorbents in filters or by fibre modifications. It is also possible to impart catalytic conversion properties into the fibre to remove volatile gasous. Radioactive agents can be removed by particulate filter if present in the form of aerosol or by gas cleaning by the use of specific fibre impregnate.

Infliximab is superior to other biological agents for treatment of active ulcerative colitis: A meta-analysis.

PubMed

Mei, Wei-Qun; Hu, Hui-Zhen; Liu, Ying; Li, Zhi-Chen; Wang, Wei-Guo

2015-05-21

To compare the efficacy and safety of biological agents for the treatment of active ulcerative colitis (UC). PubMed, MEDLINE, EMBASE and the Cochrane library were searched to screen relevant articles from January 1996 to August 2014. The mixed treatment comparison meta-analysis within a Bayesian framework was performed using WinBUGS14 software. The proportions of patients reaching clinical response, clinical remission and mucosal healing in induction and maintenance phases were analyzed as efficacy indicators. Serious adverse events in maintenance phase were analyzed as safety indicators. The meta-analysis results showed that biological agents achieved better clinical response, clinical remission and mucosal healing than placebo. Indirect comparison indicated that in induction phase, infliximab was more effective than adalimumab in inducing clinical response (OR = 0.41, 95%CI: 0.29-0.57), clinical remission (OR = 0.33, 95%CI: 0.19-0.56) and mucosal healing (OR = 0.33, 95%CI: 0.19-0.56), and golimumab in inducing clinical response (OR = 0.66, 95%CI: 0.39-2.33) and mucosal healing (OR = 2.15, 95%CI: 1.18-4.22). No significant difference was found between placebo and biological agents regarding their safety. All biological agents were superior to placebo for UC treatment in both induction and maintenance phases with a similar safety profile, and infliximab had a better clinical effect than the other biological agents.

Follow-on biologics: competition in the biopharmaceutical marketplace.

PubMed

Devine, Joshua W; Cline, Richard R; Farley, Joel F

2006-01-01

To describe the implications of a follow-on biologic approval process with focus on current stakeholders, implications of the status quo, and recommendations for future policy. A search using Medline, International Pharmaceutical Abstracts, Med Ad News, F-D-C Reports/Pink Sheets, and Google index directories was conducted with terms such as biologic, biopharmaceutical, generic, and follow-on. Articles pertaining to the follow-on biologic debate. By the authors. Over the past decade, the biopharmaceutical market has experienced substantial growth in the number of product approvals and sales. In contrast with prescription medications, biologic agents currently lack an abbreviated regulatory approval process. Evidence from the Drug Price Competition and Patent Term Restoration Act of 1984 suggests that reducing barriers to generic competition in the pharmaceutical market successfully increases generic market penetration and reduces overall prices to consumers. Although scientific and regulatory dissimilarities between biopharmaceuticals and other medications exist, a follow-on biologic approval process has the potential to play an important role in containing growth in pharmaceutical spending. In addition to biopharmaceutical and generic biopharmaceutical manufacturers, stakeholders with a vested interest in this debate include individual consumers who continue to bear the burden of spending increases in the pharmaceutical market. The debate over a follow-on process likely will be difficult as parties seek a balance between incentives for biopharmaceutical innovation, consumer safety, and affordability of existing biologic products.

PERMANENCE OF BIOLOGICAL AND CHEMICAL WARFARE AGENTS IN MUNICIPAL SOLID WASTE LANDFILL LEACHATES

EPA Science Inventory

The objective of this work is to permit EPA/ORD's National Homeland Security Research Center (NHSRC) and Edgewood Chemical Biological Center to collaborate together to test the permanence of biological and chemical warfare agents in municipal solid waste landfills. Research into ...

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...

Patient care in a biological safety level-4 (BSL-4) environment.

PubMed

Marklund, LeRoy A

2003-06-01

The greatest threats to America's public health include accidental importation of deadly diseases by international travelers and the release of biologic weapons by our adversaries. The greatest failure is unpreparedness because international travel and dispersion of biologic agents by our enemies are inevitable. An effective medical defense program is the recommended deterrent against these threats. The United States has a federal response plan in place that includes patient care and patient transport by using the highest level of biologic containment: BSL-4. The DoD has the capability to provide intensive care for victims infected with highly infectious yet unknown biologic agents in an environment that protects the caregiver while allowing scientists to study the characteristics of these new agents and assess the effectiveness of treatment. Army critical care nurses are vital in the biologic medical defense against unidentified infectious diseases, accidental occupational exposures, or intentional dispersion of weaponized biologic agents. Research that carefully advances healthcare using BSL-4 technology addresses the challenges of the human element of BSL-4 containment patient care, and BSL-4 patient transport enhances our nation's ability to address the emerging biologic threats we confront in the future.

Apparent synergy among defense mechanisms in subterranean termites (Rhinotermitidae) against epizootic events: limits and potential for biological control.

PubMed

Chouvenc, Thomas; Su, Nan-Yao

2010-08-01

The use of entomopathogens for biological control of subterranean termites (Rhinotermitidae) has attracted attention in the past four decades, and several laboratory studies have shown promising results with fungal agents. This approach was based on the concept of classical biological control with the use of a virulent agent that can self-replicate in a termite nest and be transmitted among individuals, resulting in an epizootic to kill the entire colony. However, the absence of positive results in field studies challenged the potential of fungal pathogens as a realistic approach for subterranean termite control, and the relationship between fungi and subterranean termites remains poorly understood. A multimodal approach of the currently identified defense mechanisms allowed us to show that subterranean termites have the ability to prevent an epizootic from occurring. The defense mechanisms involved in such resistance are reviewed and documented. Finally, the interactions among three major defense mechanisms (grooming, cellular encapsulation, and gut antifungal activity) were analyzed, and it is suggested that these mechanisms act synergistically to produce an efficient defense against the infection of the fungus at the individual and group level so as to protect the colony from epizootics.

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative.

PubMed

Dick, Andrew D; Rosenbaum, James T; Al-Dhibi, Hassan A; Belfort, Rubens; Brézin, Antoine P; Chee, Soon Phaik; Davis, Janet L; Ramanan, Athimalaipet V; Sonoda, Koh-Hei; Carreño, Ester; Nascimento, Heloisa; Salah, Sawsen; Salek, Sherveen; Siak, Jay; Steeples, Laura

2018-05-01

An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

IFN-λ cancer immunotherapy: new kid on the block

PubMed Central

Lasfar, Ahmed; Gogas, Helen; Zloza, Andrew; Kaufman, Howard L; Kirkwood, John M

2016-01-01

Interferon-lambda (IFN-λ) is a new IFN type, related to IFN-α, that is commonly used in the clinic. However, significant side effects accompanying IFN-α treatment limit enthusiasm for IFN-α. In this review, we discuss the current landscape of IFN-α use in oncology and describe the biologic characteristics of IFN-λ. IFN-λ offers unique advantages, including a more tumor cell selective targeting, lower off-target binding and an ability to generate both innate and adaptive immune responses. IFN-λ has also demonstrated therapeutic benefit in murine cancer models. IFN-λ may be used in clinic as a single agent or in combination with other immunotherapy agents, such as immune checkpoint inhibitors. Further clinical trials will be needed to fully elucidate the potential of this novel agent in oncology. PMID:27381684

Tuning the properties of conjugated polyelectrolytes and application in a biosensor platform

DOEpatents

Chen, Liaohai

2004-05-18

The present invention provides a method of detecting a biological agent including contacting a sample with a sensor including a polymer system capable of having an alterable measurable property from the group of luminescence, anisotropy, redox potential and uv/vis absorption, the polymer system including an ionic conjugated polymer and an electronically inert polyelectrolyte having a biological agent recognition element bound thereto, the electronically inert polyelectrolyte adapted for undergoing a conformational structural change upon exposure to a biological agent having affinity for binding to the recognition element bound to the electronically inert polyelectrolyte, and, detecting the detectable change in the alterable measurable property. A chemical moiety being the reaction product of (i) a polyelectrolyte monomer and (ii) a biological agent recognition element-substituted polyelectrolyte monomer is also provided.

Biological Select Agents and Toxins: Risk-Based Assessment Management and Oversight.

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

Burnett, LouAnn Crawford; Brodsky, Benjamin H.

Sandia National Laboratories' International Biological and Chemical Threat Reduction (SNL/IBCTR) conducted, on behalf of the Federal Select Agent Program (FSAP), a review of risk assessment in modern select agent laboratories. This review and analysis consisted of literature review, interviews of FSAP staff, entities regulated by FSAP, and deliberations of an expert panel. Additionally, SNL/IBCTR reviewed oversight mechanisms used by industries, US agencies, and other countries for high-consequence risks (e.g, nuclear, chemical, or biological materials, aviation, off-shore drilling, etc.) to determine if alternate oversight mechanisms existed that might be applicable to FSAP oversight of biological select agents and toxins. This reportmore » contains five findings, based on these reviews and analyses, with recommendations and suggested actions for FSAP to consider.« less

EEG theta and Mu oscillations during perception of human and robot actions

PubMed Central

Urgen, Burcu A.; Plank, Markus; Ishiguro, Hiroshi; Poizner, Howard; Saygin, Ayse P.

2013-01-01

The perception of others’ actions supports important skills such as communication, intention understanding, and empathy. Are mechanisms of action processing in the human brain specifically tuned to process biological agents? Humanoid robots can perform recognizable actions, but can look and move differently from humans, and as such, can be used in experiments to address such questions. Here, we recorded EEG as participants viewed actions performed by three agents. In the Human condition, the agent had biological appearance and motion. The other two conditions featured a state-of-the-art robot in two different appearances: Android, which had biological appearance but mechanical motion, and Robot, which had mechanical appearance and motion. We explored whether sensorimotor mu (8–13 Hz) and frontal theta (4–8 Hz) activity exhibited selectivity for biological entities, in particular for whether the visual appearance and/or the motion of the observed agent was biological. Sensorimotor mu suppression has been linked to the motor simulation aspect of action processing (and the human mirror neuron system, MNS), and frontal theta to semantic and memory-related aspects. For all three agents, action observation induced significant attenuation in the power of mu oscillations, with no difference between agents. Thus, mu suppression, considered an index of MNS activity, does not appear to be selective for biological agents. Observation of the Robot resulted in greater frontal theta activity compared to the Android and the Human, whereas the latter two did not differ from each other. Frontal theta thus appears to be sensitive to visual appearance, suggesting agents that are not sufficiently biological in appearance may result in greater memory processing demands for the observer. Studies combining robotics and neuroscience such as this one can allow us to explore neural basis of action processing on the one hand, and inform the design of social robots on the other. PMID:24348375

EEG theta and Mu oscillations during perception of human and robot actions.

PubMed

Urgen, Burcu A; Plank, Markus; Ishiguro, Hiroshi; Poizner, Howard; Saygin, Ayse P

2013-01-01

The perception of others' actions supports important skills such as communication, intention understanding, and empathy. Are mechanisms of action processing in the human brain specifically tuned to process biological agents? Humanoid robots can perform recognizable actions, but can look and move differently from humans, and as such, can be used in experiments to address such questions. Here, we recorded EEG as participants viewed actions performed by three agents. In the Human condition, the agent had biological appearance and motion. The other two conditions featured a state-of-the-art robot in two different appearances: Android, which had biological appearance but mechanical motion, and Robot, which had mechanical appearance and motion. We explored whether sensorimotor mu (8-13 Hz) and frontal theta (4-8 Hz) activity exhibited selectivity for biological entities, in particular for whether the visual appearance and/or the motion of the observed agent was biological. Sensorimotor mu suppression has been linked to the motor simulation aspect of action processing (and the human mirror neuron system, MNS), and frontal theta to semantic and memory-related aspects. For all three agents, action observation induced significant attenuation in the power of mu oscillations, with no difference between agents. Thus, mu suppression, considered an index of MNS activity, does not appear to be selective for biological agents. Observation of the Robot resulted in greater frontal theta activity compared to the Android and the Human, whereas the latter two did not differ from each other. Frontal theta thus appears to be sensitive to visual appearance, suggesting agents that are not sufficiently biological in appearance may result in greater memory processing demands for the observer. Studies combining robotics and neuroscience such as this one can allow us to explore neural basis of action processing on the one hand, and inform the design of social robots on the other.

Biological Warfare Agents, Toxins, Vectors and Pests as Biological Terrorism Agents

DTIC Science & Technology

2003-07-01

number of positive answers. According to criterion, no effective prophylaxis or therapy, positive answer signifies the absence of effective ...likelihood that the agent will be used. There are not effective prophylaxis and therapy against for the bulk of enlisted agents and toxins if used as...difficult to imagine how it would be looked like mass- vaccination often maybe simultaneously against more than one disease. Toxins are effective and

Post-exposure temperature influence on the toxicity of conventional and new chemistry insecticides to green lacewing Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae)

PubMed Central

Mansoor, Muhammad Mudassir; Afzal, Muhammad; Raza, Abu Bakar M.; Akram, Zeeshan; Waqar, Adil; Afzal, Muhammad Babar Shahzad

2014-01-01

Chrysoperla carnea (Stephens) is an important biological control agent currently being used in many integrated pest management (IPM) programs to control insect pests. The effect of post-treatment temperature on insecticide toxicity of a spinosyn (spinosad), pyrethroid (lambda cyhalothrin), organophosphate (chlorpyrifos) and new chemistry (acetamiprid) to C. carnea larvae was investigated under laboratory conditions. Temperature coefficients of each insecticide tested were evaluated. From 20 to 40 °C, toxicity of lambda cyhalothrin and spinosad decreased by 2.15- and 1.87-fold while toxicity of acetamiprid and chlorpyrifos increased by 2.00 and 1.79-fold, respectively. The study demonstrates that pesticide effectiveness may vary according to environmental conditions. In cropping systems where multiple insecticide products are used, attention should be given to temperature variation as a key factor in making pest management strategies safer for biological control agents. Insecticides with a negative temperature coefficient may play a constructive role to conserve C. carnea populations. PMID:25972753

Post-exposure temperature influence on the toxicity of conventional and new chemistry insecticides to green lacewing Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae).

PubMed

Mansoor, Muhammad Mudassir; Afzal, Muhammad; Raza, Abu Bakar M; Akram, Zeeshan; Waqar, Adil; Afzal, Muhammad Babar Shahzad

2015-05-01

Chrysoperla carnea (Stephens) is an important biological control agent currently being used in many integrated pest management (IPM) programs to control insect pests. The effect of post-treatment temperature on insecticide toxicity of a spinosyn (spinosad), pyrethroid (lambda cyhalothrin), organophosphate (chlorpyrifos) and new chemistry (acetamiprid) to C. carnea larvae was investigated under laboratory conditions. Temperature coefficients of each insecticide tested were evaluated. From 20 to 40 °C, toxicity of lambda cyhalothrin and spinosad decreased by 2.15- and 1.87-fold while toxicity of acetamiprid and chlorpyrifos increased by 2.00 and 1.79-fold, respectively. The study demonstrates that pesticide effectiveness may vary according to environmental conditions. In cropping systems where multiple insecticide products are used, attention should be given to temperature variation as a key factor in making pest management strategies safer for biological control agents. Insecticides with a negative temperature coefficient may play a constructive role to conserve C. carnea populations.

Toxins as biological weapons for terror-characteristics, challenges and medical countermeasures: a mini-review.

PubMed

Berger, Tamar; Eisenkraft, Arik; Bar-Haim, Erez; Kassirer, Michael; Aran, Adi Avniel; Fogel, Itay

2016-01-01

Toxins are hazardous biochemical compounds derived from bacteria, fungi, or plants. Some have mechanisms of action and physical properties that make them amenable for use as potential warfare agents. Currently, some toxins are classified as potential biological weapons, although they have several differences from classic living bio-terror pathogens and some similarities to manmade chemical warfare agents. This review focuses on category A and B bio-terror toxins recognized by the Centers for Disease Control and Prevention: Botulinum neurotoxin, staphylococcal enterotoxin B, Clostridium perfringens epsilon toxin, and ricin. Their derivation, pathogenesis, mechanism of action, associated clinical signs and symptoms, diagnosis, and treatment are discussed in detail. Given their expected covert use, the primary diagnostic challenge in toxin exposure is the early detection of morbidity clusters, apart from background morbidity, after a relatively short incubation period. For this reason, it is important that clinicians be familiar with the clinical manifestations of toxins and the appropriate methods of management and countermeasures.

Specific Pathogen Free Macaque Colonies: A Review of Principles and Recent Advances for Viral Testing and Colony Management

PubMed Central

Yee, JoAnn L.; Vandeford, Thomas H.; Didier, Elizabeth S.; Gray, Stanton; Lewis, Anne; Roberts, Jeffrey; Taylor, Kerry; Bohm, Rudolf P.

2016-01-01

Specific Pathogen Free (SPF) macaques provide valuable animal models for biomedical research. In 1989 the National Center for Research Resources (now Office of Research Infrastructure Programs ORIP) of the National Institutes of Health initiated experimental research contracts to establish and maintain SPF colonies. The derivation and maintenance of SPF macaque colonies is a complex undertaking requiring knowledge of the biology of the agents for exclusion and normal physiology and behavior of macaques, application of the latest diagnostic technology, facilities management, and animal husbandry. This review provides information on the biology of the four viral agents targeted for exclusion in ORIP SPF macaque colonies, describes current state-of-the-art viral diagnostic algorithms, presents data from proficiency testing of diagnostic assays between laboratories at institutions participating in the ORIP SPF program, and outlines management strategies for maintaining the integrity of SPF colonies using results of diagnostic testing as a guide to decision making. PMID:26932456

The current state of bioterrorist attack surveillance and preparedness in the US

PubMed Central

Grundmann, Oliver

2014-01-01

The use of biological agents as weapons to disrupt established structures, such as governments and especially larger urban populations, has been prevalent throughout history. Following the anthrax letters sent to various government officials in the fall of 2001, the US has been investing in prevention, surveillance, and preparation for a potential bioterrorism attack. Additional funding authorized since 2002 has assisted the Centers for Disease Control and Prevention, the Department of Health and Human Services, and the Environmental Protection Agency to invest in preventative research measures as well as preparedness programs, such as the Laboratory Response Network, Hospital Preparedness Program, and BioWatch. With both sentinel monitoring systems and epidemiological surveillance programs in place for metropolitan areas, the immediate threat of a large-scale bioterrorist attack may be limited. However, early detection is a crucial factor to initiate immediate response measures to prevent further spread following dissemination of a biological agent. Especially in rural areas, an interagency approach to train health care workers and raise awareness for the general public remain primary tasks, which is an ongoing challenge. Risk-management approaches in responding to dissemination of biological agents, as well as appropriate decontamination measures that reduce the probability of further contamination, have been provided, and suggest further investments in preparedness and surveillance. Ongoing efforts to improve preparedness and response to a bioterrorist attack are crucial to further reduce morbidity, mortality, and economic impact on public health. PMID:25328421

Recent Advances in Tumor Ablation for Hepatocellular Carcinoma

PubMed Central

Kang, Tae Wook; Rhim, Hyunchul

2015-01-01

Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

Is the efficacy of biological control against plant diseases likely to be more durable than that of chemical pesticides?

PubMed Central

Bardin, Marc; Ajouz, Sakhr; Comby, Morgane; Lopez-Ferber, Miguel; Graillot, Benoît; Siegwart, Myriam; Nicot, Philippe C.

2015-01-01

The durability of a control method for plant protection is defined as the persistence of its efficacy in space and time. It depends on (i) the selection pressure exerted by it on populations of plant pathogens and (ii) on the capacity of these pathogens to adapt to the control method. Erosion of effectiveness of conventional plant protection methods has been widely studied in the past. For example, apparition of resistance to chemical pesticides in plant pathogens or pests has been extensively documented. The durability of biological control has often been assumed to be higher than that of chemical control. Results concerning pest management in agricultural systems have shown that this assumption may not always be justified. Resistance of various pests to one or several toxins of Bacillus thuringiensis and apparition of resistance of the codling moth Cydia pomonella to the C. pomonella granulovirus have, for example, been described. In contrast with the situation for pests, the durability of biological control of plant diseases has hardly been studied and no scientific reports proving the loss of efficiency of biological control agents against plant pathogens in practice has been published so far. Knowledge concerning the possible erosion of effectiveness of biological control is essential to ensure a durable efficacy of biological control agents on target plant pathogens. This knowledge will result in identifying risk factors that can foster the selection of strains of plant pathogens resistant to biological control agents. It will also result in identifying types of biological control agents with lower risk of efficacy loss, i.e., modes of action of biological control agents that does not favor the selection of resistant isolates in natural populations of plant pathogens. An analysis of the scientific literature was then conducted to assess the potential for plant pathogens to become resistant to biological control agents. PMID:26284088

Biodefense and Bioterrorism

MedlinePlus

... to cause disease, spread, or resist medical treatment. Biological agents spread through the air, water, or in ... viruses, plague, or smallpox could be used as biological agents. Biodefense uses medical measures to protect people ...

Pre-release biological control agent recommendations for swallow-wort (Vincetoxicum spp.) informed by demographic matrix models

USDA-ARS?s Scientific Manuscript database

Weed biological control workers have advocated for the advance assessment of agent efficacy in order to minimize the release of host-specific but ineffective agents. One method involves demographic matrix modeling of target weed populations in order to identify plant life stage transitions that cont...

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

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.

Addenda to Allied Medical Publication 8, NATO Planning Guide for the Estimation of Chemical, Biological, Radiological, and Nuclear (CBRN) Casualties (AMedP-8(C)) to Consider the Impact of Medical Treatment on Casualty Estimation

DTIC Science & Technology

2013-05-01

122 I. Q Fever Model Parameters (Section C131) ....................................................128 1...needed to incorporate human response models for five biological agents not originally considered in AMedP-8(C): brucellosis, glanders, Q fever ...0103.1b should be modified to read: b. Biological agents include the causative agents of anthrax, brucellosis, glanders, Q fever , tularemia

Enteric Disease Surveillance Under the AFHSC-GEIS: Current Efforts, Landscape Analysis and Vision Forward

DTIC Science & Technology

2011-01-01

Severe diarrhea study at Cairo University • Case-control study of modifiable risk behaviors • Molecular biology and cholera/ rotavirus microbiology...capacity as WHO Rotavirus Reference Laboratory • Norovirus outbreak response support, Incirlik Air Base, Turkey NMRCD-Peru • Cohort study among basic...identified rotavirus as the leading causative agent • Advanced characterization of Campylobacter spp. and Shigella spp. USAMRU-K • Movement of Enteric

Chemical, Biological, and Radiological (CBR) Contamination Survivability, Small Items of Equipment

DTIC Science & Technology

2012-06-22

thickness (number of coats), paint condition, and surface cleanliness (mud, grease, and other). j. Pretest (baseline) and posttest (30 days after...survivability testing of small items of mission-essential (ME) Army materiel. Small items, for example , include personal gear, small arms, radios...their effects. An example would be the age of the paint on the surface (aged, new, etc.). f. The only current mechanism for converting agent mass

Electrophysiological and Electrochemical Methods Development for the Detection of Biologically Active Chemical Agents

DTIC Science & Technology

1988-11-01

Bilayer ........................................... 14 5. Current-Voltage Curve for Gramacidin in a Lecithin -Sphingomyelin Patch Bilayer... lecithin (Avanti). 9 2. MATERIALS 2.1 Patch Microprobe Instrumentation. The basis of the microprobe system is an AxoPatch Patch- Clamping Amplifier System...histogram of 1024 events cut above 2 pA. Events sampled are thought to be from the same single gramacidin channel in a lecithin : sphingomyelin (5:1) patch

A comparison of organophosphate degradation genes and bioremediation applications.

PubMed

Iyer, Rupa; Iken, Brian; Damania, Ashish

2013-12-01

Organophosphates (OPs) form the bulk of pesticides that are currently in use around the world accounting for more than 30% of the world market. They also form the core for many nerve-based warfare agents including sarin and soman. The widespread use and the resultant build-up of OP pesticides and chemical nerve agents has led to the development of major health problems due to their extremely toxic interaction with any biological system that encounters them. Growing concern over the accumulation of OP compounds in our food products, in the soils from which they are harvested and in wastewater run-off has fuelled a growing interest in microbial biotechnology that provides cheap, efficient OP detoxification to supplement expensive chemical methods. In this article, we review the current state of knowledge of OP pesticide and chemical agent degradation and attempt to clarify confusion over identification and nomenclature of two major families of OP-degrading enzymes through a comparison of their structure and function. The isolation, characterization, utilization and manipulation of the major detoxifying enzymes and the molecular basis of degradation of OP pesticides and chemical nerve agents are discussed as well as the achievements and technological advancements made towards the bioremediation of such compounds. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

Advancements in the management of medically less-fit and older adults with newly diagnosed acute myeloid leukemia.

PubMed

Michaelis, Laura C; Klepin, Heidi D; Walter, Roland B

2018-06-01

Treating acute myeloid leukemia (AML) in older adults remains daunting. The unique biology often renders conventional chemotherapies less effective. Accurately predicting the toxicities of treatment is another unresolved challenge. Treatment planning thus requires a good knowledge of the current trial data and familiarity with clinical tools, including formal fitness and geriatric assessments. Both obstacles - disease biology and patient fitness - might be easier overcome with specific, AML cell-targeted agents rather than traditional cytotoxic chemotherapy. This may be the future of AML therapy, but it is not our current state. Areas covered: Herein, the authors appraise the data supporting a standard induction approach, including an outline of how to predict treatment-related mortality and a review of the most up-to-date methods of geriatric assessment. They also discuss treatment expectations with less-intense therapies and highlight novel agents in development. Finally, they provide a basic approach to choosing treatment intensity. Expert opinion: In an older and/or medically less-fit patient, treatment choice should begin with a thorough disease assessment, a formal evaluation of patient fitness and frailty. There should also be a clear communication with the patient and patient's family about the risks and anticipated benefits of either an intense or nonintense treatment approach.

Dysthyroid Optic Neuropathy.

PubMed

Saeed, Peerooz; Tavakoli Rad, Shahzad; Bisschop, Peter H L T

2018-06-19

Dysthyroid optic neuropathy (DON) is a serious complication of Graves orbitopathy that can result in irreversible and profound visual loss. Controversy exists regarding the pathogenesis and management of the disease. The authors provide an overview of the current understanding of DON and present a therapeutic guideline. A review of the literature. The mechanism of DON appears to be multifactorial: direct compression of the optic nerve by enlarged extraocular muscles, stretching of the optic nerve by proptosis, orbital pressure, vascular insufficiency, and inflammation. Some or all of these factors may be involved in an individual patient. There has only been one controlled trial comparing high-dose intravenous methylprednisolone to bony orbital decompression for DON. Both 2-wall and 3-wall decompression techniques successfully improve visual functions of patients with DON. There are few case reports/case series that suggest biologic agents may improve visual function in DON. DON is a serious complication of Graves orbitopathy, the diagnosis and management of which is complex and requires a multidisciplinary approach. There is little evidence regarding the optimum management strategy. Based on the current literature, the first line of treatment is intravenous methylprednisolone, with the exact timing and indication of bony orbital decompression still to be determined. In addition, there may be a role for the use of biologic agents that will require a systematic program to determine efficacy.

Bioengineering approaches to controlled protein delivery.

PubMed

Kobsa, Serge; Saltzman, W Mark

2008-05-01

Proteins are of crucial importance in all biologic organisms, in terms of both structure and function. Their deficits play central roles in many pathologic states, and their potential as powerful therapeutic agents has been widely recognized. Many issues, however, exist in delivery of biologically active proteins to target tissues and organs. Recent advances in biomedical engineering have lead to development of advanced techniques for controlled delivery of peptides and proteins, paving the way for their efficient use in treating human injury and disease. With a particular emphasis on most recent advances, this review discusses currently available techniques for controlled delivery of proteins and considers future research directions.

Rethinking gender, heterosexual men, and women's vulnerability to HIV/AIDS.

PubMed

Higgins, Jenny A; Hoffman, Susie; Dworkin, Shari L

2010-03-01

Most HIV prevention literature portrays women as especially vulnerable to HIV infection because of biological susceptibility and men's sexual power and privilege. Conversely, heterosexual men are perceived as active transmitters of HIV but not active agents in prevention. Although the women's vulnerability paradigm was a radical revision of earlier views of women in the epidemic, mounting challenges undermine its current usefulness. We review the etiology and successes of the paradigm as well as its accruing limitations. We also call for an expanded model that acknowledges biology, gender inequality, and gendered power relations but also directly examines social structure, gender, and HIV risk for heterosexual women and men.

A Horizon Scan of Global Conservation Issues for 2016.

PubMed

Sutherland, William J; Broad, Steven; Caine, Jacqueline; Clout, Mick; Dicks, Lynn V; Doran, Helen; Entwistle, Abigail C; Fleishman, Erica; Gibbons, David W; Keim, Brandon; LeAnstey, Becky; Lickorish, Fiona A; Markillie, Paul; Monk, Kathryn A; Mortimer, Diana; Ockendon, Nancy; Pearce-Higgins, James W; Peck, Lloyd S; Pretty, Jules; Rockström, Johan; Spalding, Mark D; Tonneijck, Femke H; Wintle, Bonnie C; Wright, Katherine E

2016-01-01

This paper presents the results of our seventh annual horizon scan, in which we aimed to identify issues that could have substantial effects on global biological diversity in the future, but are not currently widely well known or understood within the conservation community. Fifteen issues were identified by a team that included researchers, practitioners, professional horizon scanners, and journalists. The topics include use of managed bees as transporters of biological control agents, artificial superintelligence, electric pulse trawling, testosterone in the aquatic environment, building artificial oceanic islands, and the incorporation of ecological civilization principles into government policies in China. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

Rethinking Gender, Heterosexual Men, and Women's Vulnerability to HIV/AIDS

PubMed Central

Hoffman, Susie; Dworkin, Shari L.

2010-01-01

Most HIV prevention literature portrays women as especially vulnerable to HIV infection because of biological susceptibility and men's sexual power and privilege. Conversely, heterosexual men are perceived as active transmitters of HIV but not active agents in prevention. Although the women's vulnerability paradigm was a radical revision of earlier views of women in the epidemic, mounting challenges undermine its current usefulness. We review the etiology and successes of the paradigm as well as its accruing limitations. We also call for an expanded model that acknowledges biology, gender inequality, and gendered power relations but also directly examines social structure, gender, and HIV risk for heterosexual women and men. PMID:20075321

Lanthanide-doped upconverting phosphors for bioassay and therapy

NASA Astrophysics Data System (ADS)

Guo, Huichen; Sun, Shiqi

2012-10-01

Lanthanide-doped fluorescent materials have gained increasing attention in recent years due to their unique luminescence properties which have led to their use in wide-ranging fields including those of biological applications. Aside from being used as agents for in vivo imaging, lanthanide-doped fluorescent materials also present many advantages for use in bioassays and therapy. In this review, we summarize the applications of lanthanide-doped up-converting phosphors (UCPs) in protein and gene detection, as well as in photodynamic and gene therapy in recent years, and outline their future potential in biological applications. The current report could serve as a reference for researchers in relevant fields.

Micro-masters of glioblastoma biology and therapy: increasingly recognized roles for microRNAs.

PubMed

Floyd, Desiree; Purow, Benjamin

2014-05-01

MicroRNAs are small noncoding RNAs encoded in eukaryotic genomes that have been found to play critical roles in most biological processes, including cancer. This is true for glioblastoma, the most common and lethal primary brain tumor, for which microRNAs have been shown to strongly influence cell viability, stem cell characteristics, invasiveness, angiogenesis, metabolism, and immune evasion. Developing microRNAs as prognostic markers or as therapeutic agents is showing increasing promise and has potential to reach the clinic in the next several years. This succinct review summarizes current progress and future directions in this exciting and steadily expanding field.

Biological therapies in moderate and severe psoriasis: perspectives and certainties

PubMed Central

Constantin, MM; Poenaru, E; Constantin, T; Poenaru, C; Purcarea, VL; Mateescu, BR

2014-01-01

An inflammatory, proliferative condition with chronic evolution and systemic response, psoriasis, is positioned today among the most common inflammatory skin diseases affecting the Caucasian population worldwide. With a significant incidence, psoriasis has been increasingly defined as a disease with a major impact on the patient's life and the society to which he/she belongs. This paper conducts an analysis of the currently available therapies for the treatment of moderate and severe psoriasis, therapies with biological agents obtained through sophisticated genetic engineering technologies. Recent research and the increasing interest in therapeutic methods as complete and efficient as possible make us optimistic and confident in the future. PMID:25870666

Interleukin-17 inhibitors. A new era in treatment of psoriasis and other skin diseases.

PubMed

Wasilewska, Agnieszka; Winiarska, Marta; Olszewska, Małgorzata; Rudnicka, Lidia

2016-08-01

Psoriasis is a chronic skin disease caused by the excessive secretion of inflammatory cytokines. Available therapeutic options include biologic drugs such as tumor necrosis factor alpha inhibitors and interleukin 12/23 (IL-12/23) inhibitors. The recent discovery of IL-17, which contributes to development of psoriasis, opened new possibilities for further treatment modalities. Currently, one anti-IL17 biological agent is approved for the treatment - a fully human monoclonal antibody that targets IL-17A (secukinumab). Further clinical trials, including a humanized IgG4 specific for IL-17 (ixekizumab) and a fully human antibody that targets the IL-17 receptor A (brodalumab).

Industry Studies 2004: Biotechnology

DTIC Science & Technology

2004-01-01

for biological agent research, development, and production are available on the open market. Since biological weapons are relatively cheap, easy to...growing concern is that non-state actors will acquire and use a biological weapon , the “poor man’s nuclear weapon .” Such action is extremely difficult...to detect and counter. International Protocols and the Need to Control Agents and Technologies - The Biological and Toxin Weapons Convention

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...

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...

Conservation Biological Control of Pests in the Molecular Era: New Opportunities to Address Old Constraints

PubMed Central

Gurr, Geoff M.; You, Minsheng

2016-01-01

Biological control has long been considered a potential alternative to pesticidal strategies for pest management but its impact and level of use globally remain modest and inconsistent. A rapidly expanding range of molecular – particularly DNA-related – techniques is currently revolutionizing many life sciences. This review identifies a series of constraints on the development and uptake of conservation biological control and considers the contemporary and likely future influence of molecular methods on these constraints. Molecular approaches are now often used to complement morphological taxonomic methods for the identification and study of biological control agents including microbes. A succession of molecular techniques has been applied to ‘who eats whom’ questions in food-web ecology. Polymerase chain reaction (PCR) approaches have largely superseded immunological approaches such as enzyme-linked immunosorbent assay (ELISA) and now – in turn – are being overtaken by next generation sequencing (NGS)-based approaches that offer unparalleled power at a rapidly diminishing cost. There is scope also to use molecular techniques to manipulate biological control agents, which will be accelerated with the advent of gene editing tools, the CRISPR/Cas9 system in particular. Gene editing tools also offer unparalleled power to both elucidate and manipulate plant defense mechanisms including those that involve natural enemy attraction to attacked plants. Rapid advances in technology will allow the development of still more novel pest management options for which uptake is likely to be limited chiefly by regulatory hurdles. PMID:26793225

Relapsed or refractory pediatric acute lymphoblastic leukemia: current and emerging treatments.

PubMed

Martin, Alissa; Morgan, Elaine; Hijiya, Nobuko

2012-12-01

Relapsed acute lymphoblastic leukemia (ALL) represents a major cause of morbidity and mortality in pediatrics. With contemporary chemotherapy, >85% of patients with newly diagnosed ALL survive. Unfortunately, 20% of these patients will relapse and for these children, outcomes remain poor despite our best known chemotherapy protocols. Most of these children will achieve a second complete remission, but maintaining this remission remains difficult. Because relapsed ALL is such a significant cause of morbidity and mortality, it is the focus of much research interest. Efforts have been made and continue to focus on understanding the underlying biology that drives relapse. The role of hematopoietic stem cell transplantation in relapsed ALL remains unclear, but many clinicians still favor this for high-risk patients given the poor prognosis with current chemotherapy alone. It is important to use new drugs with little cross-resistance in the treatment of relapsed ALL. New classes of agents are currently being studied. We also discuss prognostic factors and the biology of relapsed ALL.

The role of chemotherapy in the treatment of malignant astrocytomas.

PubMed

Mathieu, David; Fortin, David

2006-05-01

Malignant astrocytomas are aggressive neoplasms with a dismal prognosis despite optimal treatment. Maximal resective surgery is traditionally complemented by radiation therapy. Chemotherapy is now used on patients as initial therapy when their functional status is congruent with further treatment. The classic agents used are nitrosoureas, but temozolomide has taken the front seat recently, with recent data demonstrating increased survival when this agent is used concurrently with radiation therapy in newly diagnosed glioblastoma patients. A new class of agents, refered to as biological modifiers, are increasingly used in clinical trials in an effort to affect the intrinsic biologic aberrations harboured by tumor cells. These drugs comprise differentiation agents, anti-angiogenic agents, matrix-metalloproteinase inhibitors and signal transduction inhibitors, among others. This article reviews the standard cytotoxic agents that have been used to treat malignant astrocytomas, and the different combination regimens offering promise. In addition, recent advances with biological modifiers are also discussed.

Simulating cancer growth with multiscale agent-based modeling.

PubMed

Wang, Zhihui; Butner, Joseph D; Kerketta, Romica; Cristini, Vittorio; Deisboeck, Thomas S

2015-02-01

There have been many techniques developed in recent years to in silico model a variety of cancer behaviors. Agent-based modeling is a specific discrete-based hybrid modeling approach that allows simulating the role of diversity in cell populations as well as within each individual cell; it has therefore become a powerful modeling method widely used by computational cancer researchers. Many aspects of tumor morphology including phenotype-changing mutations, the adaptation to microenvironment, the process of angiogenesis, the influence of extracellular matrix, reactions to chemotherapy or surgical intervention, the effects of oxygen and nutrient availability, and metastasis and invasion of healthy tissues have been incorporated and investigated in agent-based models. In this review, we introduce some of the most recent agent-based models that have provided insight into the understanding of cancer growth and invasion, spanning multiple biological scales in time and space, and we further describe several experimentally testable hypotheses generated by those models. We also discuss some of the current challenges of multiscale agent-based cancer models. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Stigmergic Cooperative Multi-Robot Control Architecture

NASA Technical Reports Server (NTRS)

Howsman, Thomas G.; O'Neil, Daniel; Craft, Michael A.

2004-01-01

In nature, there are numerous examples of complex architectures constructed by relatively simple insects, such as termites and wasps, which cooperatively assemble their nests. A prototype cooperative multi-robot control architecture which may be suitable for the eventual construction of large space structures has been developed which emulates this biological model. Actions of each of the autonomous robotic construction agents are only indirectly coordinated, thus mimicking the distributed construction processes of various social insects. The robotic construction agents perform their primary duties stigmergically, i.e., without direct inter-agent communication and without a preprogrammed global blueprint of the final design. Communication and coordination between individual agents occurs indirectly through the sensed modifications that each agent makes to the structure. The global stigmergic building algorithm prototyped during the initial research assumes that the robotic builders only perceive the current state of the structure under construction. Simulation studies have established that an idealized form of the proposed architecture was indeed capable of producing representative large space structures with autonomous robots. This paper will explore the construction simulations in order to illustrate the multi-robot control architecture.

Bioprocessing development: Immune/cellular applications: Anti-Ig autoantibody and complement-mediated destruction of neoplastic cells

NASA Technical Reports Server (NTRS)

Twomey, J. J.

1976-01-01

This space bioprocessing contract effort was comprised of four general objectives. These were: (1) the evaluation of current separation processes, (2) the identification of problems relevant to the separation of important biologicals, (3) the identification of ground-based assay methods needed for pre- and postflight analysis of space bioprocessing separation technology; and (4) the establishment of methods to determine the efficiency of space bioprocessing separation procedures. Immunology was deemed advantageous to study the diversity of cells and cell products involved and the extensive interest being given to their separation. Upon recognition of a cellular or molecular agent as foreign to the body, the immune system becomes activated to produce cells whose function is to destroy that agent and cell products whose function is to inactivate the agent and assist in its destruction. Long after the agent is removed from the body, some cells remain in a state of readiness to continue these destructive actions specifically against that agent should further exposure to it occur. This is the basis of acquired immunity to disease.

Will novel agents for ALL finally change the natural history?

PubMed

Douer, Dan

2014-01-01

Pediatric acute lymphoblastic leukemia (ALL) cure rates have markedly improved over the past years to approximately 85%, but remain at 40%-50% in adults. Redefining current adult chemotherapy regimens is likely to improve the natural course of the disease, but new agents are needed. Immunotherapy approaches for pre-B ALL are in the forefront of research on novel agents; in particular, advances are being made in manipulating autologous T cells either by infusion of a bifunctional antibody (eg, blinatumomab) or by ex vivo genetic modification of chimeric antigen receptors (CARs). The natural course of Philadelphia positive ALL has already improved by targeting ABL/BCR1. Other mutated genes are being discovered and novel small molecules that target their products are being studied in clinical trials. Finally, ALL is a heterogeneous disease and novel agents are likely to impact the natural course of smaller populations of biologically defined ALL subtypes. Copyright © 2014 Elsevier Ltd. All rights reserved.

The use of immunosuppression in autoimmune hepatitis: A current literature review

PubMed Central

Cropley, Angela; Weltman, Martin

2017-01-01

Autoimmune hepatitis (AIH) is an organ specific autoimmune condition which can manifest at any age of life. The heterogeneous nature of this condition means that great variation can be seen in severity, progression of disease and response to treatment within this patient group. Since the 1980s prednisolone and azathioprine have been used for induction and remission of the disease and remain the mainstay of treatment. Other immunosuppressive agents have been employed in difficult to treat cases. While there is less published data regarding these agents compared with the conventional treatments of steroid and azathioprine, there is mounting evidence to support the use of mycophenolate mofetil as a second-line agent. The calcineurin inhibitors, though less studied, additionally show promise. More data is needed on the use of biological agents in refractory disease. This review focuses on our centre’s approach to treatment of AIH in the context of a contemporary review of the literature. PMID:28288505

Marine products with anti-protozoal activity: a review.

PubMed

García, Marley; Monzote, Lianet

2014-01-01

The marine organisms are a rich source of varied natural products with unique functionality. A variety of natural products of new molecular structures with diverse biological activities have been reported from marine flora and fauna for treatment and/or prevention of human diseases. The present review briefly illustrates current status of marine products as antiprotozoal agents. The in vitro and in vivo studies of marine algae, invertebrates and micro-organism against different protozoa parasites are included. The marine products studied, according to international criterions for selection of more promisory products in the different models reported, demonstrated their potentialities as antiprozoal agents. Herein, the interest of scientific community to search new alternatives from marine environment has been demonstrated.

Viral infection and antiviral therapy in the neonatal intensive care unit.

PubMed

Barford, Galina; Rentz, Alison C; Faix, Roger G

2004-01-01

Viral diseases are leading causes of mortality and morbidity among infants requiring care in the neonatal intensive care unit (NICU), with ongoing discoveries of new viral pathology likely to add to the burdens posed. Many viral diseases in NICU infants are undiagnosed or appreciated only late in the course because of subtle or asymptomatic presentation, confusion with bacterial disease, and failure to consider viral disease. We present an overview of viral disease in NICU infants, with emphasis on pharmacologic agents currently employed for prophylaxis and treatment of such diseases. Advances in molecular biology and popular demand to develop antiviral agents for viral diseases (eg, human immunodeficiency virus) offer great promise for the future.

Biological and Clinical Aspects of Lanthanide Coordination Compounds

PubMed Central

Misra, Sudhindra N.; M., Indira Devi; Shukla, Ram S.

2004-01-01

The coordinating chemistry of lanthanides, relevant to the biological, biochemical and medical aspects, makes a significant contribution to understanding the basis of application of lanthanides, particularly in biological and medical systems. The importance of the applications of lanthanides, as an excellent diagnostic and prognostic probe in clinical diagnostics, and an anticancer material, is remarkably increasing. Lanthanide complexes based X-ray contrast imaging and lanthanide chelates based contrast enhancing agents for magnetic resonance imaging (MRI) are being excessively used in radiological analysis in our body systems. The most important property of the chelating agents, in lanthanide chelate complex, is its ability to alter the behaviour of lanthanide ion with which it binds in biological systems, and the chelation markedly modifies the biodistribution and excretion profile of the lanthanide ions. The chelating agents, especially aminopoly carboxylic acids, being hydrophilic, increase the proportion of their complex excreted from complexed lanthanide ion form biological systems. Lanthanide polyamino carboxylate-chelate complexes are used as contrast enhancing agents for Magnetic Resonance Imaging. Conjugation of antibodies and other tissue specific molecules to lanthanide chelates has led to a new type of specific MRI contrast agents and their conjugated MRI contrast agents with improved relaxivity, functioning in the body similar to drugs. Many specific features of contrast agent assisted MRI make it particularly effective for musculoskeletal and cerebrospinal imaging. Lanthanide-chelate contrast agents are effectively used in clinical diagnostic investigations involving cerebrospinal diseases and in evaluation of central nervous system. Chelated lanthanide complexes shift reagent aided 23Na NMR spectroscopic analysis is used in cellular, tissue and whole organ systems. PMID:18365075

Biology, host specificity tests, and risk assessment of the sawfly Heteroperreyia hubrichi, a potential biological control agent of Schinus terebinthifolius in Hawaii

USDA-ARS?s Scientific Manuscript database

Abstract. Heteroperreyia hubrichi Malaise (Hymenoptera: Pergidae), a foliage feeding sawfly of Schinus terebinthifolius Raddi (Sapindales: Anacardiaceae), was studied to assess its suitability as a classical biological control agent of this invasive weed in Hawaii. Nochoice host-specificity tests we...

75 FR 69396 - Availability of an Environmental Assessment for a Biological Control Agent for Arundo donax

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-12

... infestations. The proposed biological control agent, Arundo scale, is one of the most damaging insects to A... feeding on cells that carry out photosynthesis and cellular respiration, resulting over time in gradual... donacis (Hemiptera: Diaspididae), an Insect for Biological Control of Arundo donax (Poaceae) in the...

Modeling biological disturbances in LANDIS: a module description and demonstration using spruce budworm

Treesearch

Brian R. Sturtevant; Eric J. Gustafson; Wei Li; Hong S. He

2004-01-01

Insects and diseases are common disturbance agents in forested ecosystems. Severe outbreaks can cause significant changes in tree species composition, age structure, and fuel conditions over broad areas. To investigate the role of biological disturbances in shaping forest landscapes over time, we constructed a new "biological disturbance agent" (BDA) module...

Infliximab is superior to other biological agents for treatment of active ulcerative colitis: A meta-analysis

PubMed Central

Mei, Wei-Qun; Hu, Hui-Zhen; Liu, Ying; Li, Zhi-Chen; Wang, Wei-Guo

2015-01-01

AIM: To compare the efficacy and safety of biological agents for the treatment of active ulcerative colitis (UC). METHODS: PubMed, MEDLINE, EMBASE and the Cochrane library were searched to screen relevant articles from January 1996 to August 2014. The mixed treatment comparison meta-analysis within a Bayesian framework was performed using WinBUGS14 software. The proportions of patients reaching clinical response, clinical remission and mucosal healing in induction and maintenance phases were analyzed as efficacy indicators. Serious adverse events in maintenance phase were analyzed as safety indicators. RESULTS: The meta-analysis results showed that biological agents achieved better clinical response, clinical remission and mucosal healing than placebo. Indirect comparison indicated that in induction phase, infliximab was more effective than adalimumab in inducing clinical response (OR = 0.41, 95%CI: 0.29-0.57), clinical remission (OR = 0.33, 95%CI: 0.19-0.56) and mucosal healing (OR = 0.33, 95%CI: 0.19-0.56), and golimumab in inducing clinical response (OR = 0.66, 95%CI: 0.39-2.33) and mucosal healing (OR = 2.15, 95%CI: 1.18-4.22). No significant difference was found between placebo and biological agents regarding their safety. CONCLUSION: All biological agents were superior to placebo for UC treatment in both induction and maintenance phases with a similar safety profile, and infliximab had a better clinical effect than the other biological agents. PMID:26019471

Identifying Ant-Mirid Spatial Interactions to Improve Biological Control in Cacao-Based Agroforestry System.

PubMed

Bagny Beilhe, Leïla; Piou, Cyril; Tadu, Zéphirin; Babin, Régis

2018-06-06

The use of ants for biological control of insect pests was the first reported case of conservation biological control. Direct and indirect community interactions between ants and pests lead to differential spatial pattern. We investigated spatial interactions between mirids, the major cocoa pest in West Africa and numerically dominant ant species, using bivariate point pattern analysis to identify potential biological control agents. We assume that potential biological control agents should display negative spatial interactions with mirids considering their niche overlap. The mirid/ant data were collected in complex cacao-based agroforestry systems sampled in three agroecological areas over a forest-savannah gradient in Cameroon. Three species, Crematogaster striatula Emery (Hymenoptera: Formicidae), Crematogaster clariventris Mayr (Hymenoptera: Formicidae), and Oecophylla longinoda Latreille (Hymenoptera: Formicidae) with high predator and aggressive behaviors were identified as dominant and showed negative spatial relationships with mirids. The weaver ant, O. longinoda was identified as the only potential biological control agent, considering its ubiquity in the plots, the similarity in niche requirements, and the spatial segregation with mirids resulting probably from exclusion mechanisms. Combining bivariate point pattern analysis to good knowledge of insect ecology was an effective method to identify a potentially good biological control agent.

Differences in seasonal variation between two biotypes of Megamelus scutellaris (Hemiptera: Delphacidae), a biological control agent for Eichhornia crassipes in Florida.

USDA-ARS?s Scientific Manuscript database

Climate matching between the native and adventive ranges of insects used for biological control is a generally accepted strategy for both increasing the likelihood of establishing an agent, as well as improving its overall performance, thereby maximizing the potential utility of an agent across the...

Integrating the Agents of Bioterrorism into the General Biology Curriculum: II. Mode of Action of the Biological Agents.

ERIC Educational Resources Information Center

Pommerville, Jeffrey C.

2003-01-01

Integrates bioterrorism into the science curriculum and explains actions against serious agents such as anthrax, plague, smallpox, botulinum toxin, and ricin toxin. Uses the learning cycle as the instructional tool which is student-centered and has three phases that include exploring, explaining, and extending. (Contains 24 references.) (YDS)

The implications of biologic therapy for elective foot and ankle surgery in patients with rheumatoid arthritis.

PubMed

Diaper, Ross; Wong, Ernest; Metcalfe, Stuart A

2017-03-01

Rheumatoid arthritis (RA) is one of a number of inflammatory arthropathies resulting in foot pain and deformity. Patients with this disease may require surgical intervention as part of their management. Many of these patients are now taking biologic agents which pose several risks to patients in the perioperative phase. The surgical team therefore need to be aware of these associated complications and how to manage these cases. This paper aims to review the current literature about perioperative needs (foot and ankle surgery) associated with patients with rheumatoid arthritis receiving biologic therapy. The majority of the literature discusses the perioperative complications associated with patients on anti-TNFα therapy with few studies investigating the other biologics in common use. There is conflicting evidence as to the safety of continuing or stopping biologic drug therapy prior to orthopaedic procedures. The British Society for Rheumatology (BSR) have produced guidelines for the management of patients on anti-TNFα therapy or the biologic agent Tocilizumab. These recommendations suggest the risks of post-operative infection need to be balanced against the risk of a post-operative disease flare. In essence, it is suggested anti-TNFα therapy is stopped 3-5 times the half-life of the drug whilst Tocilizumab is stopped 4 weeks prior to surgery. Good communication is needed between the surgical team and the local Rheumatology department managing the patient's disease in order to optimise perioperative care. Local pathways may vary from the BSR recommendations to determine the most suitable course of action with regards to continuing or stopping biologic therapy prior to foot and ankle surgery. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biosafety and biosecurity as essential pillars of international health security and cross-cutting elements of biological nonproliferation

PubMed Central

2010-01-01

The critical aspects of biosafety, biosecurity, and biocontainment have been in the spotlight in recent years. There have also been increased international efforts to improve awareness of modern practices and concerns with regard to the safe pursuit of life sciences research, and to optimize current oversight frameworks, thereby resulting in decreased risk of terrorist/malevolent acquisition of deadly pathogens or accidental release of a biological agent, and increased safety of laboratory workers. Our purpose is to highlight how the World Health Organization’s (WHO) revised International Health Regulations (IHR[2005]), the Biological Weapons Convention (BWC), and the United Nations Security Council Resolution (UNSCR) 1540 overlap in their requirements with regard to biosafety and biosecurity in order to improve the understanding of practitioners and policymakers and maximize the use of national resources employed to comply with internationally-mandated requirements. The broad range of goals of these international instruments, which are linked by the common thread of biosafety and biosecurity, highlight their significance as essential pillars of international health security and cross-cutting elements of biological nonproliferation. The current efforts of the Republic of Georgia to enhance biosafety and biosecurity in accordance with these international instruments are summarized. PMID:21143822

Relationships between chronic obstructive pulmonary disease and lung cancer: biological insights

PubMed Central

Bustamante, Víctor; Curull, Víctor; Gea, Joaquim; López-Campos, José Luis; Muñoz, Xavier

2016-01-01

Lung cancer (LC) has become one of the leading causes of preventable death in the last few decades. Cigarette smoking (CS) stays as the main etiologic factor of LC despite that many other causes such as occupational exposures, air pollution, asbestos, or radiation have also been implicated. Patients with chronic obstructive pulmonary disease (COPD), which also represents a major cause of morbidity and mortality in developed countries, exhibit a significantly greater risk of LC. The study of the underlying biological mechanisms that may predispose patients with chronic respiratory diseases to a higher incidence of LC has also gained much attention in the last few years. The present review has been divided into three major sections in which different aspects have been addressed: (I) relevant etiologic agents of LC; (II) studies confirming the hypothesis that COPD patients are exposed to a greater risk of developing LC; and (III) evidence on the most relevant underlying biological mechanisms that support the links between COPD and LC. Several carcinogenic agents have been described in the last decades but CS remains to be the leading etiologic agent in most geographical regions in which the incidence of LC is very high. Growing evidence has put the line forward the implications of COPD and especially of emphysema in LC development. Hence, COPD represents a major risk factor of LC in patients. Different avenues of research have demonstrated the presence of relevant biological mechanisms that may predispose COPD patients to develop LC. Importantly, the so far identified biological mechanisms offer targets for the design of specific therapeutic strategies that will further the current treatment options for patients with LC. Prospective screening studies, in which patients with COPD should be followed up for several years will help identify biomarkers that may predict the risk of LC among these patients. PMID:27867578

Venous thrombotic events are not increased in patients with rheumatoid arthritis treated with anti‑TNF therapy: results from the British Society for Rheumatology Biologics Register

PubMed Central

Davies, Rebecca; Galloway, James B; Watson, Kath D; Lunt, Mark; Symmons, Deborah P M; Hyrich, Kimme L

2011-01-01

Objectives Past studies have reported conflicting rates of venous thrombotic events (VTEs) in rheumatoid arthritis (RA). The current study aimed to compare (1) the rates of VTEs in patients with RA treated with anti-tumour necrosis factor (anti-TNF) therapy versus those treated with non-biological disease-modifying antirheumatic drugs (nbDMARDs) alone and (2) the rates between each individual anti-TNF agent and nbDMARDs. Methods Using data from the British Society for Rheumatology Biologics Register, a national prospective observational cohort study of biological safety in patients with RA, the authors compared the incidence of VTEs between 11 881 anti-TNF- and 3673 nbDMARD-treated patients. Analysis was limited to the first VTE per person. HRs were calculated using Cox modelling. Adjustment was made for potential confounders including surgery performed during follow-up. Results A total of 196 first VTEs were reported (151 anti-TNF, 45 nbDMARD). Overall there was no difference in the rates of VTEs between anti-TNF- and nbDMARD-treated patients (adjusted HR 0.8 (95% CI 0.5 to 1.5)). The risk was similar across all anti-TNF agents. Rates of postoperative VTEs did not significantly differ between groups. Conclusions These data suggest that anti-TNF therapy is not associated with an increased risk of VTEs in RA patients. PMID:21784722

Treatment with biologic agents improves the prognosis of patients with rheumatoid arthritis and amyloidosis.

PubMed

Kuroda, Takeshi; Tanabe, Naohito; Kobayashi, Daisuke; Sato, Hiroe; Wada, Yoko; Murakami, Shuichi; Saeki, Takako; Nakano, Masaaki; Narita, Ichiei

2012-07-01

Reactive amyloid A (AA) amyloidosis is a serious and life-threatening systemic complication of rheumatoid arthritis (RA). We evaluated the safety of therapy with anti-tumor necrosis factor and anti-interleukin 6 biologic agents in RA patients with reactive AA amyloidosis, together with prognosis and hemodialysis (HD)-free survival, in comparison with patients with AA amyloidosis without such therapy. One hundred thirty-three patients with an established diagnosis of reactive AA amyloidosis participated in the study. Clinical data were assessed from patient records at the time of amyloid detection and administration of biologics. Survival was calculated from the date when amyloid was first demonstrated histologically or the date when biologic therapy was started until the time of death or to the end of 2010 for surviving patients. Patients who had started HD were selected for inclusion only after the presence of amyloid was demonstrated. Fifty-three patients were treated with biologic agents (biologic group) and 80 were not (nonbiologic group). Survival rate was significantly higher in the biologic group than in the nonbiologic group. Nine patients in the biologics group and 33 in the nonbiologic group started HD. Biologic therapy had a tendency for reduced risk of initiation of HD without any statistical significance. Patients with amyloidosis have a higher mortality rate, but the use of biologic agents can reduce risk of death. The use of biologics may not significantly influence the HD-free survival rate.

Bioterrorism: Preparing the Plastic Surgeon

PubMed Central

Chopra, Karan; Conde-Green, Alexandra; Folstein, Matthew K.; Knepp, Erin K.; Christy, Michael R.; Singh, Devinder P.

2011-01-01

Introduction: Many medical disciplines, such as emergency medicine, trauma surgery, dermatology, psychiatry, family practice, and dentistry have documented attempts at assessing the level of bioterrorism preparedness in their communities. Currently, there is neither such an assessment nor an existing review of potential bioterrorism agents as they relate to plastic surgery. Therefore, the purpose of this article is to present plastic surgeons with a review of potential bioterrorism agents. Methods: A review of the literature on bioterrorism agents and online resources of the Centers for Disease Control and Prevention was conducted. Category A agents were identified and specific attention was paid to the management issues that plastic surgeons might face in the event that these agents are used in an attack. Results: Disease entities reviewed were smallpox, anthrax, plague, viral hemorrhagic fever, tularemia, and botulism. For each agent, we presented the microbiology, pathophysiology, clinical presentation, potential for weaponization, medical management, and surgical issues related to the plastic surgeon. Conclusion: This article is the first attempt at addressing preparedness for bioterrorism in the plastic surgery community. Many other fields have already started a similar process. This article represents a first step in developing evidence-based consensus guidelines and recommendations for the management of biological terrorism for plastic surgeons. PMID:22132252

Early investigational tubulin inhibitors as novel cancer therapeutics.

PubMed

Nepali, Kunal; Ojha, Ritu; Lee, Hsueh-Yun; Liou, Jing-Ping

2016-08-01

Microtubules represent one of the most logical and strategic molecular targets amongst the current targets for chemotherapy, alongside DNA. In the past decade, tubulin inhibitors as cancer therapeutics have been an area of focus due to the improved understanding and biological relevance of microtubules in cellular functions. Fueled by the objective of developing novel chemotherapeutics and with the aim of establishing the benefits of tubulin inhibition, several clinical trials have been conducted with others ongoing. At present, the antitubulin development pipeline contains an armful of agents under clinical investigation. This review focuses on novel tubulin inhibitors as cancer therapeutics. The article covers the agents which have completed the phase II studies along with the agents demonstrating promising results in phase I studies. Countless clinical trials evaluating the efficacy, safety and pharmacokinetics of novel tubulin inhibitors highlights the scientific efforts being paid to establish their candidature as cancer therapeutics. Colchicine binding site inhibitors as vascular disrupting agents (VDAs) and new taxanes appear to be the most likely agents for future clinical interest. Numerous agents have demonstrated clinical benefits in terms of efficacy and survival in phase I and II studies. However conclusive benefits can only be ascertained on the basis of phase III studies.

Current data of targeted therapies for the treatment of triple-negative advanced breast cancer: empiricism or evidence-based?

PubMed

Petrelli, Fausto; Cabiddu, Mary; Ghilardi, Mara; Barni, Sandro

2009-10-01

Approximately 10 - 15% of breast carcinomas (BCs) are known to be 'triple-negative (TN) receptor' (i.e., not expressing ER or PR and not exhibiting overexpression and/or gene amplification of HER2-neu). Triple-negative BCs comprise approximately 85% of all basal-type tumours. Classically, basal-like BCs have been characterised by low expression of ER, PR, and HER2 neu and high expression of CK5, CK14, caveolin-1, CAIX, p63, and EGFR (HER1), which reflects the mammary gland basal/myoepithelial cell component. Although there is no standard first-line chemotherapy regimen for metastatic TN BCs, anthracycline- and taxane-containing regimens are acceptable treatments. A large number of agents, including DNA-damaging agents, EGFR inhibitors, antiangiogenic agents and novel taxane formulations are currently being tested in clinical trials for first-line and pretreated patients. Limited experiences with platinum salts, poly(ADP-ribose) polymerase (PARP) inhibitors, cetuximab, bevacizumab and ixabepilone have been published in recent years and will be reported. Novel immunohistochemistry analysis for identification of basal like/TN phenotype are awaited to correctly select this population. The clinical trials investigating new agents have to be designed for a specific (and possibly large) subset of patients with BC. In the future, a gene array platform with greater sensitivity for distinguishing the various BC subtypes, as well as having the power to predict the molecular biology of the disease, will be an indispensible tool for treatment selection. Currently, treatment of TN BC is more empirical than evidence-based. The cornerstone of treatment is chemotherapy, but in the near future, novel target agents will emerge as possible partners.

New targets in the search for preventive and therapeutic agents for botulism.

PubMed

Anniballi, Fabrizio; Lonati, Davide; Fiore, Alfonsina; Auricchio, Bruna; De Medici, Dario; Locatelli, Carlo Alessandro

2014-09-01

Botulism is a severe neuroparalytic disease resulting from exposure to one of the most poisonous toxins to humans. Because of this high potency and the use of toxins as biological weapons, botulism is a public health concern and each case represents an emergency. Current therapy involves respiratory supportive care and anti-toxins administration. As a preventive measure, vaccination against toxins represents an effective strategy but is undesirable due the rarity of botulism and the effectiveness of toxins in treating several neuromuscular disorders. This paper summarizes the current issues in botulism treatment and prevention, highlighting the challenge for future researches.

Surveys for Biological Control Agents of Hydrilla verticillata in the People’s Republic of China in 2013

DTIC Science & Technology

2017-03-01

Hydrilla was rare at this site and only male plants were collected at 0.5-1 m from shore and a depth of 0.5-1m. The lake/wetlands were explored by boat...ER D C/ EL T R- 17 -3 Aquatic Plant Control Research Program Surveys for Biological Control Agents of Hydrilla verticillata in the...acwc.sdp.sirsi.net/client/default. Aquatic Plant Control Research Program ERDC/EL TR-17-3 March 2017 Surveys for Biological Control Agents of

NATO Planning Guide for the Estimation of Chemical, Biological, Radiological, and Nuclear (CBRN) Casualties (AMedP-8(C)) - Parameters for Estimation of Casualties from Exposure to Specified Biological Agents. Addenda to Allied Medical Publication 8

DTIC Science & Technology

2011-01-01

glanders, Q fever, and tularemia , as well as the biotoxin staphylococcal enterotoxin B. Incorporating these five agents into the published NATO guide will...Specified Biological Agents: Brucellosis, Glanders, Q Fever, SEB, and Tularemia . This document describes the research methods used by the study authors...enterotoxin B (SEB), and tularemia . Several editorial changes, such as renumbering figures and tables, updating the corresponding references in the text, and

Indirect ecological effects in invaded landscapes: Spillover and spillback from biological control agents to native analogues

USDA-ARS?s Scientific Manuscript database

Biological control remains an effective option for managing large-scale weed problems in natural areas. The predation or parasitism of biological control agents by other species present in the introduced range (biotic resistance) is well studied and is often cited as the cause for a lack of establis...

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...

Antibiotic resistance: a primer and call to action.

PubMed

Smith, Rachel A; M'ikanatha, Nkuchia M; Read, Andrew F

2015-01-01

During the past century, discoveries of microorganisms as causes of infections and antibiotics as effective therapeutic agents have contributed to significant gains in public health in many parts of the world. Health agencies worldwide are galvanizing attention toward antibiotic resistance, which is a major threat to public health (Centers for Disease Control and Prevention, 2013; World Health Organization, 2014). Some life scientists believe that we are approaching the post-antibiotic age (Davies & Davies, 2010). The growing threat of antimicrobial resistance is fueled by complex factors with biological, behavioral, and societal aspects. This primer provides an overview of antibiotic resistance and its growing burden on public health, the biological and behavioral mechanisms that increase antibiotic resistance, and examples of where health communication scholars can contribute to efforts to make our current antibiotic drugs last as long as possible. In addition, we identify compelling challenges for current communication theories and practices.

Current technologies for biological treatment of textile wastewater--a review.

PubMed

Sarayu, K; Sandhya, S

2012-06-01

The release of colored wastewater represents a serious environmental problem and public health concern. Color removal from textile wastewater has become a big challenge over the last decades, and up to now, there is no single and economically attractive treatment method that can effectively decolorize the wastewater. Effluents from textile manufacturing, dyeing, and finishing processes contain high concentrations of biologically difficult-to-degrade or even inert auxiliaries, chemicals like acids, waxes, fats, salts, binders, thickeners, urea, surfactants, reducing agents, etc. The various chemicals such as biocides and stain repellents used for brightening, sequestering, anticreasing, sizing, softening, and wetting of the yarn or fabric are also present in wastewater. Therefore, the textile wastewater needs environmental friendly, effective treatment process. This paper provides a critical review on the current technology available for decolorization and degradation of textile wastewater and also suggests effective and economically attractive alternatives.

Antibiotic Resistance: A Primer and Call to Action

PubMed Central

Smith, Rachel A.; M’ikanatha, Nkuchia M.; Read, Andrew F.

2014-01-01

During the past century, discoveries of microorganisms as causes of infections and antibiotics as effective therapeutic agents have contributed to significant gains in public health in many parts of the world. Health agencies worldwide are galvanizing attention toward antibiotic resistance, which is a major threat to public health (Centers for Disease Control and Prevention [CDC], 2013; World Health Organization [WHO], 2014). Some life scientists believe that we are approaching the post-antibiotic age (Davies & Davies, 2010). The growing threat of antimicrobial resistance is fueled by complex factors with biological, behavioral and societal aspects. This primer provides an overview of antibiotic resistance and its growing burden on public health, the biological and behavioral mechanisms that increase antibiotic resistance, and examples of where health communication scholars can contribute to efforts to make our current antibiotic drugs last as long as possible. In addition, we identify compelling challenges for current communication theories and practices. PMID:25121990

Recent Development of Benzimidazole-Containing Antibacterial Agents.

PubMed

Song, Di; Ma, Shutao

2016-04-05

Clinically significant antibiotic resistance is one of the greatest challenges of the twenty-first century. However, new antibacterial agents are currently being developed at a much slower pace than our growing need for such drugs. Given their diverse biological activities and clinical applications, many bioactive heterocyclic compounds containing a benzimidazole nucleus have been the focus of interest for many researchers. The benzimidazole nucleus is a structural isostere of naturally occurring nucleotides. This advantage allows benzimidazoles to readily interact with the various biopolymers found in living systems. In view of this situation, much attention has been given to the exploration of benzimidazole-based antibacterial agents, leading to the discovery of many new chemical entities with intriguing profiles. In this minireview we summarize novel benzimidazole derivatives active against various bacterial strains. In particular, we outline the relationship between the structures of variously modified benzimidazoles and their antibacterial activity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Management of Uveitis in Spondyloarthropathy: Current Trends

PubMed Central

Gupta, Nikhil; Agarwal, Aditi

2018-01-01

Spondyloarthritis is a chronic inflammatory disease predominantly affecting joints of the axial skeleton. However, as many as 50% of patients with this disease may have extra-articular manifestations, which include uveitis; psoriasis; inflammatory bowel disease such as Crohn disease or ulcerative colitis; cardiovascular manifestations in the form of conduction abnormalities, atherosclerosis, or valvular heart disease; pulmonary involvement; and rarely renal involvement. Uveitis occurs in 25% to 40% of patients with spondyloarthritis. Management of uveitis is crucial to prevent morbidity caused by vision loss and secondary complications. Treatment ranges from local therapies to systemic drugs and varies depending on the severity and response to treatment. Categories of medical treatment include nonsteroidal anti-inflammatory agents, corticosteroids, and steroid-sparing agents. Biologic therapies such as antitumor necrosis factor agents act early in the disease process and have revolutionized the field of rheumatology, including management of uveitis. This review will focus on the management of ophthalmic manifestations in spondyloarthropathies. PMID:29272246

Vaccines against viral hemorrhagic fevers: non-human primate models.

PubMed

Carrion, Ricardo; Patterson, Jean L

2011-06-01

Viral hemorrhagic fevers are a group of disease syndromes caused by infection with certain RNA viruses. The disease is marked by a febrile response, malaise, coagulopathy and vascular permeability culminating in death. Case fatality rates can reach 90% depending on the etiologic agent. Currently, there is no approved antiviral treatment. Because of the high case fatality, risk of importation and the potential to use these agents as biological weapons, development of countermeasures to these agents is a high priority. The sporadic nature of disease outbreaks and the ethical issues associated with conducting a human trial for such diseases make human studies impractical; therefore, development of countermeasures must occur in relevant animal models. Non-human primates are superior models to study infectious disease because their immune system is similar to humans and they are good predictors of efficacy in vaccine development and other intervention strategies. This review article summarizes viral hemorrhagic fever non-human primate models.

Therapeutic approach to Crohn disease: possible parallels with hidradenitis suppurativa.

PubMed

González Lama, Y; Marín-Jiménez, I

2016-09-01

The current controversy in the setting of dermatology surrounding the treatment of inflammatory diseases, and specifically hidradenitis suppurativa, bears strong similarities with the debate concerning inflammatory bowel disease (IBD) that took place several years ago. That debate led to new perspectives on this disease and, in particular, its treatment after the development of biological agents. Copyright © 2016 Elsevier España, S.L.U. y AEDV. All rights reserved.

Frequency-Agile LIDAR Receiver for Chemical and Biological Agent Sensing

DTIC Science & Technology

2010-06-01

transimpedance preamplifier architecture was optimized around the selected IR detector diode – Input-referenced noise density of 0.8 nV/ Hz0.5  A portion of...objectives: • Reduce baseline (background) photon flux on detector : Tunable Fabry-Perot etalon in optical train • Reduce input-referenced amplifier noise ...custom amplifier • Reduce detector dark current: High impedance detector  Performance Metrics: – Noise equivalent power of receiver system (NEP

The Use of Megamelus scutellaris Berg in the Southern United States as a Biocontrol Agent of Waterhyacinth (Eichhornia crassipes (Mart.))

DTIC Science & Technology

2014-07-01

spread to include the southern and western United States and disjunct northern populations ( US Department of Agriculture/ Natural Resources...waterhyacinth in Louisiana currently exceeds $4 million.3 Primary control methods include the use of herbicides and release of insect biological control...C with natural daylight (Figure 4). Reverse osmosis (RO) water was used in the tanks with periodic application of nutrients. Waterhyacinth was

Ecological host-range of Lilioceris cheni (Coleoptera: Chrysomelidae), a biological control agent of Dioscorea bulbifera L.

USDA-ARS?s Scientific Manuscript database

Open-field host-specificity testing assesses the host-range of a biological control agent in a setting that permits the agent to use its full complement of host-seeking behaviors. This form of testing, particularly when it includes a no-choice phase in which the target weed is killed, may provide th...

Evaluation of establishment of Cyphocleonus achates and its potential impact on spotted knapweed

Treesearch

Nancy Sturdevant; Sandy Kegley; Yvette Ortega; Dean Pearson

2006-01-01

Environmental characteristics of a site may greatly influence the establishment and impact of biological control agents on the target weed. A biological control agent that is highly successful in one region may be virtually ineffective in another (Gurr and Wratten 2000). To maximize the use of limited availability of agents and financial resources, we should...

Implementation of Multi-Agent Object Attention System Based on Biologically Inspired Attractor Selection

NASA Astrophysics Data System (ADS)

Hashimoto, Ryoji; Matsumura, Tomoya; Nozato, Yoshihiro; Watanabe, Kenji; Onoye, Takao

A multi-agent object attention system is proposed, which is based on biologically inspired attractor selection model. Object attention is facilitated by using a video sequence and a depth map obtained through a compound-eye image sensor TOMBO. Robustness of the multi-agent system over environmental changes is enhanced by utilizing the biological model of adaptive response by attractor selection. To implement the proposed system, an efficient VLSI architecture is employed with reducing enormous computational costs and memory accesses required for depth map processing and multi-agent attractor selection process. According to the FPGA implementation result of the proposed object attention system, which is accomplished by using 7,063 slices, 640×512 pixel input images can be processed in real-time with three agents at a rate of 9fps in 48MHz operation.

Effects of outside air temperature on the preparation of antineoplastic drug solutions in biological safety cabinets.

PubMed

Umemura, Masayuki; Itoh, Akio; Ando, Yuichi; Yamada, Kiyofumi; Wakiya, Yoshifumi; Nabeshima, Toshitaka

2015-08-01

In Japan, biological safety cabinets are commonly used by medical staff to prepare antineoplastic agents. At the Division of Chemotherapy for Outpatients, Nagoya University Hospital, a class II B2 biological safety cabinet is used. The temperature inside this biological safety cabinet decreases in winter. In this study, we investigated the effect of low outside air temperature on the biological safety cabinet temperature, time required to admix antineoplastic agents, and accuracy of epirubicin weight measurement. Studies were conducted from 1 January to 31 March 2008 (winter). The outside air temperature near the biological safety cabinet intake nozzle was compared with the biological safety cabinet temperature. The correlation between the outside air temperature and the biological safety cabinet temperature, time for cyclophosphamide and gemcitabine solubilization, and accuracy of epirubicin weight measurement were investigated at low and high biological safety cabinet temperatures. The biological safety cabinet temperature correlated with the outside air temperature of 5-20℃ (p < 0.0001). Compared to cyclophosphamide and gemcitabine solubilization in the biological safety cabinet at 25℃, solubilization at 10℃ was significantly delayed (p < 0.01 and p < 0.0001, respectively). Measurement of epirubicin weight by using a syringe lacked accuracy because of epirubicin's high viscosity at low temperatures (p < 0.01). These results suggest that the biological safety cabinet temperature decreases when cool winter air is drawn into the biological safety cabinet, affecting the solubilization of antineoplastic agents. We suggest that a decrease in biological safety cabinet temperature may increase the time required to admix antineoplastic agents, thereby increasing the time for which outpatients must wait for chemotherapy. © The Author(s) 2014.

Vasculitis Terms A to Z

MedlinePlus

... interleukins, and vaccines. Also called biologic agent and biological agent. Capillaries: The smallest blood vessel in the body. Capillaries connect arterioles (small arteries) with venules (small veins). Capillaries form an intricate network throughout the body for the interchange of various ...

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

Interinstrument Variability and Validation Study for the XMX/2L-MIL Biological Air Sampler

DTIC Science & Technology

2012-07-13

fixed final nozzle orientation. Three XMXs were operated in a 12-m3 aerosol test chamber (ATC) in which a Bacillus globigii (Bg) aerosol was...impactor, aerosol, biological aerosol, collection media, biological agent, Remel M5®, PBS solution, Bacillus globigii, male-specific 2 bacteriophage, MS2...Edmonton AB, Canada. The performance of the XMX was evaluated using two biological agents, spore-forming bacteria Bacillus globigii (Bg) and viral

Modeling Co-evolution of Speech and Biology.

PubMed

de Boer, Bart

2016-04-01

Two computer simulations are investigated that model interaction of cultural evolution of language and biological evolution of adaptations to language. Both are agent-based models in which a population of agents imitates each other using realistic vowels. The agents evolve under selective pressure for good imitation. In one model, the evolution of the vocal tract is modeled; in the other, a cognitive mechanism for perceiving speech accurately is modeled. In both cases, biological adaptations to using and learning speech evolve, even though the system of speech sounds itself changes at a more rapid time scale than biological evolution. However, the fact that the available acoustic space is used maximally (a self-organized result of cultural evolution) is constant, and therefore biological evolution does have a stable target. This work shows that when cultural and biological traits are continuous, their co-evolution may lead to cognitive adaptations that are strong enough to detect empirically. Copyright © 2016 Cognitive Science Society, Inc.

Anti-TNF-α therapies for the treatment of Crohn's disease: the past, present and future.

PubMed

Berns, Marc; Hommes, Daniel W

2016-01-01

Anti-TNF-α therapy is a novel approach that has transformed the way moderate-to-severe Crohn's disease (CD) is treated and has significantly improved clinical outcomes of patients with enhanced remission induction and maintenance efficacies. As a result, anti-TNF-α agents have become the primary cost driver in the treatment of CD, as the frequency of hospitalizations and surgical interventions have been drastically reduced. In the review, the authors cover current anti-TNF-α treatments for CD including efficacy, mechanisms of action, pharmacokinetics and safety. In addition, the authors discuss future anti-TNF-α agents currently in the development pipeline including biosimilars, golimumab, oral AVX-470, TNF-α-kinoid vaccine, and non-biologic HMPL-004. While new therapeutics are in the pipeline like anti-integrin and anti-interleukin therapeutics, anti-TNF-α therapy remains at the forefront of CD treatment due to its long-term efficacy and safety profiles. The next horizon for new anti-TNF-α agents is biosimilars, which offer comparable safety and effectiveness to the originator molecules. Biosimilars promise to expand accessibility to anti-TNF-α therapy while significantly reducing the cost burden to patients and healthcare systems.

[Is the price of cancer drugs related to the cost of develo-pment and production or to the economic value of their clincal efficacy?].

PubMed

Russi, Alberto; Serena, Marta; Palozzo, Angelo C

2016-04-01

In the past years, the expenditure for cancer drugs has quickly increased, especially for biologic agents. Pharmaceutical companies and national health systems have different approaches in handling the issue of drug reimbursement. Companies support a price based on research and development (R&D) expenditures including those for unsuccessful drug projects while national health systems generally argue that pricing should be based on the incremental benefit generated by the agent under examination (value-based pricing - VBP). Nevertheless, current oncologic drugs prices are too high and not really justified by their incremental benefits or innovation, nor can they demonstrate that higher thresholds in QALYs could bring wider societal benefits. In this article we discuss these two points of view in the light of the most recent national and international literature. In Italy, drug reimbursement is currently managed through a mixed approach between the recognition of R&D expenditures and VBP. Reimbursement is also integrated with post-marketing patient-based national registries, particularly in the field of anti-cancer agents, that provide rebates based on financial risk sharing, cost-sharing, payment by results and success fee methods.

Molecular Targeted Intervention for Pancreatic Cancer

PubMed Central

Mohammed, Altaf; Janakiram, Naveena B.; Pant, Shubham; Rao, Chinthalapally V.

2015-01-01

Pancreatic cancer (PC) remains one of the worst cancers, with almost uniform lethality. PC risk is associated with westernized diet, tobacco, alcohol, obesity, chronic pancreatitis, and family history of pancreatic cancer. New targeted agents and the use of various therapeutic combinations have yet to provide adequate treatments for patients with advanced cancer. To design better preventive and/or treatment strategies against PC, knowledge of PC pathogenesis at the molecular level is vital. With the advent of genetically modified animals, significant advances have been made in understanding the molecular biology and pathogenesis of PC. Currently, several clinical trials and preclinical evaluations are underway to investigate novel agents that target signaling defects in PC. An important consideration in evaluating novel drugs is determining whether an agent can reach the target in concentrations effective to treat the disease. Recently, we have reported evidence for chemoprevention of PC. Here, we provide a comprehensive review of current updates on molecularly targeted interventions, as well as dietary, phytochemical, immunoregulatory, and microenvironment-based approaches for the development of novel therapeutic and preventive regimens. Special attention is given to prevention and treatment in preclinical genetically engineered mouse studies and human clinical studies. PMID:26266422

[The future of inflammatory bowel disease from the perspective of Digestive Disease Week 2012].

PubMed

Gomollón, Fernando

2012-09-01

The new information presented in Digestive Disease Week has allowed us to speculate on the future of inflammatory bowel disease. Manipulation of diet and the microbioma will probably play an increasingly important role in the treatment of this disease and, in the long term, in its prevention. Biological agents will probably be used earlier and more widely; new information on levels of biological agents, mucosal healing and new comparative studies will also allow these agents to be used in a more precise and personalized way. In addition to infliximab, adalimumab, natalizumab and certolizumab, other biological agents will be employed; among the first of these to be used will be ustekinumab, golimumab and vedolizumab. In the near future, biological agents will be used as frequently in ulcerative colitis as in Crohn's disease. New healthcare models will be developed that will progressively include greater participation among patients and nurses. The ability to predict new diagnostic and prognostic models will allow decisions to be more individualized. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Detecting agency from the biological motion of veridical vs animated agents

PubMed Central

Kelley, William M.; Heatherton, Todd F.; Macrae, C. Neil

2007-01-01

The ability to detect agency is fundamental for understanding the social world. Underlying this capacity are neural circuits that respond to patterns of intentional biological motion in the superior temporal sulcus and temporoparietal junction. Here we show that the brain's blood oxygenation level dependent (BOLD) response to such motion is modulated by the representation of the actor. Dynamic social interactions were portrayed by either live-action agents or computer-animated agents, enacting the exact same patterns of biological motion. Using an event-related design, we found that the BOLD response associated with the perception and interpretation of agency was greater when identical physical movements were performed by real rather than animated agents. This finding has important implications for previous work on biological motion that has relied upon computer-animated stimuli and demonstrates that the neural substrates of social perception are finely tuned toward real-world agents. In addition, the response in lateral temporal areas was observed in the absence of instructions to make mental inferences, thus demonstrating the spontaneous implementation of the intentional stance. PMID:18985141

A Systematic Screen of FDA-Approved Drugs for Inhibitors of Biological Threat Agents

PubMed Central

Madrid, Peter B.; Chopra, Sidharth; Manger, Ian D.; Gilfillan, Lynne; Keepers, Tiffany R.; Shurtleff, Amy C.; Green, Carol E.; Iyer, Lalitha V.; Dilks, Holli Hutcheson; Davey, Robert A.; Kolokoltsov, Andrey A.; Carrion, Ricardo; Patterson, Jean L.; Bavari, Sina; Panchal, Rekha G.; Warren, Travis K.; Wells, Jay B.; Moos, Walter H.; Burke, RaeLyn L.; Tanga, Mary J.

2013-01-01

Background The rapid development of effective medical countermeasures against potential biological threat agents is vital. Repurposing existing drugs that may have unanticipated activities as potential countermeasures is one way to meet this important goal, since currently approved drugs already have well-established safety and pharmacokinetic profiles in patients, as well as manufacturing and distribution networks. Therefore, approved drugs could rapidly be made available for a new indication in an emergency. Methodology/Principal Findings A large systematic effort to determine whether existing drugs can be used against high containment bacterial and viral pathogens is described. We assembled and screened 1012 FDA-approved drugs for off-label broad-spectrum efficacy against Bacillus anthracis; Francisella tularensis; Coxiella burnetii; and Ebola, Marburg, and Lassa fever viruses using in vitro cell culture assays. We found a variety of hits against two or more of these biological threat pathogens, which were validated in secondary assays. As expected, antibiotic compounds were highly active against bacterial agents, but we did not identify any non-antibiotic compounds with broad-spectrum antibacterial activity. Lomefloxacin and erythromycin were found to be the most potent compounds in vivo protecting mice against Bacillus anthracis challenge. While multiple virus-specific inhibitors were identified, the most noteworthy antiviral compound identified was chloroquine, which disrupted entry and replication of two or more viruses in vitro and protected mice against Ebola virus challenge in vivo. Conclusions/Significance The feasibility of repurposing existing drugs to face novel threats is demonstrated and this represents the first effort to apply this approach to high containment bacteria and viruses. PMID:23577127

Development of insect viruses as pesticides: The case of the gypsy moth (Lymantria dispar L.) in North America

Treesearch

J.D. Podgwaite; H.M. Mazzone

1981-01-01

Biological control, one component of integrated pest management, encompasses the use of several types of biological agents to control insect pest populations. Of these biological control agents, the insect viruses appear to offer one logical alternative to the chemical insecticides. One such virus, the nucleopolyhedrosis virus of the gypsy moth, Lymantria...

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 ...

The effect of bark thickness on the effectiveness of Tetrastichus planipennisi (Hymen: Eulophidae) and Atanycolus spp. (Hymen: Braconidae) two parasitoids of emerald ash borer (Coleop: Buprestidae)

USDA-ARS?s Scientific Manuscript database

Factors that influence the effectiveness of an introduced biological control agent must be well understood to make management decisions in a successful biological control program. Information on agent biology is also required to determine how new exotic species will interact with native natural ene...

Nanostructured thermites based on iodine pentoxide for bio agent defeat systems.

NASA Astrophysics Data System (ADS)

Hobosyan, Mkhitar; Kazansky, Alexander; Martirosyan, Karen

2011-10-01

The risk for bioterrorist events involving the intentional airborne release of contagious agents has led to development of new approaches for bio agent defeat technologies both indoors and outdoors. Novel approaches to defeat harmful biological agents have generated a strong demand for new active materials. The preferred solutions are to neutralize the biological agents within the immediate target area by using aerosolized biocidal substances released in situ by high energetic reactions. By using nano-thermite reactions, with energy release up to 25 kJ/cc, based on I2O5/Al nanoparticles we intend to generate high quantity of vaporized iodine for spatial deposition onto harmful bacteria for their destruction. In this report, the effect of reaction product on growth and survival of Escherichia coli (E-coli) expressing GFP (Green Fluorescent Protein) was investigated. Moreover, we developed an approach to increase sensitivity of the detection. The study has shown that I2O5/Al nanosystem is extremely effective to disinfect harmful biological agents such (E-coli) bacteria in seconds.

Synthesis, Characterization, and Multimillion-Atom Simulation of Halogen-Based Energetic Materials for Agent Defeat

DTIC Science & Technology

2013-04-01

DTRA-TR-13-23 Synthesis, Characterization, and Multimillion -Atom Simulation of Halogen-Based Energetic Materials for Agent Defeat Approved for...reagents for the destruction of biologically active materials and a simulation of their reactions on a multimillion atom scale with quantum...explosives for destruction of chemical & biological agents. Multimillion -atom molecular dynamics simulations with quantum mechanical accuracy were

Biological responses to engineered nanomaterials: Needs for the next decade

DOE PAGES

Murphy, Catherine J.; Vartanian, Ariane M.; Geiger, Franz M.; ...

2015-06-09

In this study, the interaction of nanomaterials with biomolecules, cells, and organisms is an enormously vital area of current research, with applications in nanoenabled diagnostics, imaging agents, therapeutics, and contaminant removal technologies. Yet the potential for adverse biological and environmental impacts of nanomaterial exposure is considerable and needs to be addressed to ensure sustainable development of nanomaterials. In this Outlook four research needs for the next decade are outlined: (i) measurement of the chemical nature of nanomaterials in dynamic, complex aqueous environments; (ii) real-time measurements of nanomaterial-biological interactions with chemical specificity; (iii) delineation of molecular modes of action for nanomaterialmore » effects on living systems as functions of nanomaterial properties; and (iv) an integrated systems approach that includes computation and simulation across orders of magnitude in time and space.« less

Current concepts for the combined treatment modality of ionizing radiation with anticancer agents.

PubMed

Oehler, Christoph; Dickinson, Daniel J; Broggini-Tenzer, Angela; Hofstetter, Barbara; Hollenstein, Andreas; Riesterer, Oliver; Vuong, Van; Pruschy, Martin

2007-01-01

In current applied radiobiology, there exists a tremendous effort in basic and translational research to identify novel treatment modalities combining ionizing radiation with anticancer agents. This is mainly due to the highly improved molecular understanding of intrinsic radioresistance and the profiling of cellular stress responses to irradiation during recent years. Ionizing radiation not only damages DNA but also affects multiple cellular components that induce a multi-layered stress response. The treatment responses can be restricted to the individual cell level but might also be part of an intercellular stress communication network. Both DNA damage-induced signaling (which results in cell cycle arrest and induction of the DNA-repair machinery) and also ionizing radiation-induced signal transduction cascades, which are generated at cellular sites distant from and independent of DNA-damage, represent interesting targets for anticancer treatment modalities to sensitize for ionizing radiation. Due to the lack of molecular knowledge classic radiobiology assembled the cellular and tissue responses into four groups (4 R's of radiotherapy) which describe biological factors influencing the treatment response to fractionated radiotherapy. These classic 4 R's are Repair, Reassortment, Repopulation and Reoxygenation. With the tremendous progress in molecular oncology we now begin to understand theses factors on the molecular level. At the same time this classification may guide modern molecular radiobiologists to identify novel pharmaceuticals and antisignaling agents which can modulate the treatment response to irradiation. In this review we describe current approaches to sensitize tumor cells with novel anticancer agents along the lines of these 4 R's.

The prospect of applying chemical elicitors and plant strengtheners to enhance the biological control of crop pests

PubMed Central

Sobhy, Islam S.; Erb, Matthias; Lou, Yonggen; Turlings, Ted C. J.

2014-01-01

An imminent food crisis reinforces the need for novel strategies to increase crop yields worldwide. Effective control of pest insects should be part of such strategies, preferentially with reduced negative impact on the environment and optimal protection and utilization of existing biodiversity. Enhancing the presence and efficacy of native biological control agents could be one such strategy. Plant strengthener is a generic term for several commercially available compounds or mixtures of compounds that can be applied to cultivated plants in order to ‘boost their vigour, resilience and performance’. Studies into the consequences of boosting plant resistance against pests and diseases on plant volatiles have found a surprising and dramatic increase in the plants' attractiveness to parasitic wasps. Here, we summarize the results from these studies and present new results from assays that illustrate the great potential of two commercially available resistance elicitors. We argue that plant strengtheners may currently be the best option to enhance the attractiveness of cultivated plants to biological control agents. Other options, such as the genetic manipulation of the release of specific volatiles may offer future solutions, but in most systems, we still miss fundamental knowledge on which key attractants should be targeted for this approach. PMID:24535390

Current and emerging drugs for the treatment of inflammatory bowel disease

PubMed Central

Triantafillidis, John K; Merikas, Emmanuel; Georgopoulos, Filippos

2011-01-01

During the last decade a large number of biological agents against tumor necrosis factor-α (TNF-α), as well as many biochemical substances and molecules specifically for the medical treatment of patients with inflammatory bowel disease (IBD), have been developed. This enormous progress was a consequence of the significant advances in biotechnology along with the increased knowledge of the underlying pathophysiological mechanisms involved in the pathogenesis of IBD. However, conventional therapies remain the cornerstone of treatment for most patients. During recent years conventional and biologic IBD therapies have been optimized. Newer mesalazine formulations with a reduced pill size and only one dose per day demonstrate similar efficacy to older formulations. New corticosteroids retain the efficacy of older corticosteroids while exhibiting a higher safety profile. The role of antibiotics and probiotics has been further clarified. Significant progress in understanding thiopurine metabolism has improved the effective dose along with adjunctive therapies. Quite a large number of substances and therapies, including biologic agents other than TNF-α inhibitors, unfractionated or low-molecular-weight heparin, omega-3 polyunsaturated fatty acids, microbes and microbial products, leukocytapheresis, and other substances under investigation, could offer important benefits to our patients. In this paper we review the established and emerging therapeutic strategies in patients with Crohn’s disease and ulcerative colitis. PMID:21552489

Personalized Exposure Assessment: Promising Approaches for Human Environmental Health Research

PubMed Central

Weis, Brenda K.; Balshaw, David; Barr, John R.; Brown, David; Ellisman, Mark; Lioy, Paul; Omenn, Gilbert; Potter, John D.; Smith, Martyn T.; Sohn, Lydia; Suk, William A.; Sumner, Susan; Swenberg, James; Walt, David R.; Watkins, Simon; Thompson, Claudia; Wilson, Samuel H.

2005-01-01

New technologies and methods for assessing human exposure to chemicals, dietary and lifestyle factors, infectious agents, and other stressors provide an opportunity to extend the range of human health investigations and advance our understanding of the relationship between environmental exposure and disease. An ad hoc Committee on Environmental Exposure Technology Development was convened to identify new technologies and methods for deriving personalized exposure measurements for application to environmental health studies. The committee identified a “toolbox” of methods for measuring external (environmental) and internal (biologic) exposure and assessing human behaviors that influence the likelihood of exposure to environmental agents. The methods use environmental sensors, geographic information systems, biologic sensors, toxicogenomics, and body burden (biologic) measurements. We discuss each of the methods in relation to current use in human health research; specific gaps in the development, validation, and application of the methods are highlighted. We also present a conceptual framework for moving these technologies into use and acceptance by the scientific community. The framework focuses on understanding complex human diseases using an integrated approach to exposure assessment to define particular exposure–disease relationships and the interaction of genetic and environmental factors in disease occurrence. Improved methods for exposure assessment will result in better means of monitoring and targeting intervention and prevention programs. PMID:16002370

Neuroimaging of the joint Simon effect with believed biological and non-biological co-actors

PubMed Central

Wen, Tanya; Hsieh, Shulan

2015-01-01

Performing a task alone or together with another agent can produce different outcomes. The current study used event-related functional magnetic resonance imaging (fMRI) to investigate the neural underpinnings when participants performed a Go/Nogo task alone or complementarily with another co-actor (unseen), whom was believed to be another human or a computer. During both complementary tasks, reaction time data suggested that participants integrated the potential action of their co-actor in their own action planning. Compared to the single-actor task, increased parietal and precentral activity during complementary tasks as shown in the fMRI data further suggested representation of the co-actor’s response. The superior frontal gyrus of the medial prefrontal cortex was differentially activated in the human co-actor condition compared to the computer co-actor condition. The medial prefrontal cortex, involved thinking about the beliefs and intentions of other people, possibly reflects a social-cognitive aspect or self-other discrimination during the joint task when believing a biological co-actor is present. Our results suggest that action co-representation can occur even offline with any agent type given a priori information that they are co-acting; however, additional regions are recruited when participants believe they are task-sharing with another human. PMID:26388760

Neuroimaging of the joint Simon effect with believed biological and non-biological co-actors.

PubMed

Wen, Tanya; Hsieh, Shulan

2015-01-01

Performing a task alone or together with another agent can produce different outcomes. The current study used event-related functional magnetic resonance imaging (fMRI) to investigate the neural underpinnings when participants performed a Go/Nogo task alone or complementarily with another co-actor (unseen), whom was believed to be another human or a computer. During both complementary tasks, reaction time data suggested that participants integrated the potential action of their co-actor in their own action planning. Compared to the single-actor task, increased parietal and precentral activity during complementary tasks as shown in the fMRI data further suggested representation of the co-actor's response. The superior frontal gyrus of the medial prefrontal cortex was differentially activated in the human co-actor condition compared to the computer co-actor condition. The medial prefrontal cortex, involved thinking about the beliefs and intentions of other people, possibly reflects a social-cognitive aspect or self-other discrimination during the joint task when believing a biological co-actor is present. Our results suggest that action co-representation can occur even offline with any agent type given a priori information that they are co-acting; however, additional regions are recruited when participants believe they are task-sharing with another human.

Biological treatments in Behçet's disease: beyond anti-TNF therapy.

PubMed

Caso, Francesco; Costa, Luisa; Rigante, Donato; Lucherini, Orso Maria; Caso, Paolo; Bascherini, Vittoria; Frediani, Bruno; Cimaz, Rolando; Marrani, Edoardo; Nieves-Martín, Laura; Atteno, Mariangela; Raffaele, Carmela G L; Tarantino, Giusyda; Galeazzi, Mauro; Punzi, Leonardo; Cantarini, Luca

2014-01-01

Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.

Guidelines for Managing Suspected Chemical and Biological Agent Incidents in Rail Tunnel Systems

DOT National Transportation Integrated Search

2002-03-01

These emergency management guidelines are designed to help transit managers (1) prepare and implement standard operating procedures (SOPs) for handling potential and actual chemical or biological agent attacks in their rail tunnel system and (2) unde...

Sugar-Coated PPE's, Novel Nanomaterial's and Sensing Modules for Disease and Bioterrorism Related Threats

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

Bunz, Uwe

2003-11-21

The detection and sensing of biological warfare agents (ricin, anthrax toxin), of disease agents (cholera, botulinum, and tetnus toxins, influenza virus, etc.) and of biologically active species important for national security and disease control.

Synthesis and biological activity of mustard derivatives of thymine.

PubMed

Hadj-Bouazza, Amel; Teste, Karine; Colombeau, Ludovic; Chaleix, Vincent; Zerrouki, Rachida; Kraemer, Michel; Sainte Catherine, Odile

2008-05-01

The synthesis and biological activity of a novel DNA cross-linking antitumor agent is presented. The new alkylating agent significantly inhibited cell proliferation, migration and invasion as tested in vitro on the A431 vulvar epidermal carcinoma cell line.

Apoptosis and Self-Destruct: A Contribution to Autonomic Agents?

NASA Technical Reports Server (NTRS)

Sterritt, Roy; Hinchey, Mike

2004-01-01

Autonomic Computing (AC), a self-managing systems initiative based on the biological metaphor of the autonomic nervous system, is increasingly gaining momentum as the way forward in designing reliable systems. Agent technologies have been identified as a key enabler for engineering autonomicity in systems, both in terms of retrofitting autonomicity into legacy systems and designing new systems. The AC initiative provides an opportunity to consider other biological systems and principles in seeking new design strategies. This paper reports on one such investigation; utilizing the apoptosis metaphor of biological systems to provide a dynamic health indicator signal between autonomic agents.

A proposal for the classification of biological weapons sensu lato.

PubMed

Rozsa, Lajos

2014-12-01

Due to historical and legislation reasons, the category of bioweapons is rather poorly defined. Authors often disagree on involving or excluding agents like hormones, psychochemicals, certain plants and animals (such as weeds or pests) or synthetic organisms. Applying a wide definition apparently threatens by eroding the regime of international legislation, while narrow definitions abandon several important issues. Therefore, I propose a category of 'biological weapons sensu lato' (BWsl) that is defined here as any tool of human aggression whose acting principle is based on disciplines of biology including particularly microbiology, epidemiology, medical biology, physiology, psychology, pharmacology and ecology, but excluding those based on inorganic agents. Synthetically produced equivalents (not necessarily exact copies) and mock weapons are also included. This definition does not involve any claim to subject all these weapons to international legislation but serves a purely scholarly purpose. BWsl may be properly categorized on the base of the magnitude of the human population potentially targeted (4 levels: individuals, towns, countries, global) and the biological nature of the weapons' intended effects (4 levels: agricultural-ecological agents, and non-pathogenic, pathogenic, or lethal agents against humans).

Magnetic nanoparticle drug delivery systems for targeting tumor

NASA Astrophysics Data System (ADS)

Mody, Vicky V.; Cox, Arthur; Shah, Samit; Singh, Ajay; Bevins, Wesley; Parihar, Harish

2014-04-01

Tumor hypoxia, or low oxygen concentration, is a result of disordered vasculature that lead to distinctive hypoxic microenvironments not found in normal tissues. Many traditional anti-cancer agents are not able to penetrate into these hypoxic zones, whereas, conventional cancer therapies that work by blocking cell division are not effective to treat tumors within hypoxic zones. Under these circumstances the use of magnetic nanoparticles as a drug delivering agent system under the influence of external magnetic field has received much attention, based on their simplicity, ease of preparation, and ability to tailor their properties for specific biological applications. Hence in this review article we have reviewed current magnetic drug delivery systems, along with their application and clinical status in the field of magnetic drug delivery.

Pathogenesis of Lassa fever.

PubMed

Yun, Nadezhda E; Walker, David H

2012-10-09

Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host's immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents.

Nanotechnology in bladder cancer: current state of development and clinical practice

PubMed Central

Tomlinson, Ben; Lin, Tzu-yin; Dall'Era, Marc; Pan, Chong-Xian

2015-01-01

Nanotechnology is being developed for the diagnosis and treatment of both nonmyoinvasive bladder cancer (NMIBC) and invasive bladder cancer. The diagnostic applications of nanotechnology in NMIBC mainly focus on tumor identification during endoscopy to increase complete resection of bladder cancer while nanotechnology to capture malignant cells or their components continues to be developed. The therapeutic applications of nanotechnology in NMIBC are to reformulate biological and cytotoxic agents for intravesical instillation, combine both diagnostic and therapeutic application in one nanoformulation. In invasive and advanced bladder cancer, magnetic resonance imaging with supraparamagnetic iron oxide nanoparticles can improve the sensitivity and specificity in detecting small metastasis to lymph nodes. Nanoformulation of cytotoxic agents can potentially decrease the toxicity while increasing efficacy. PMID:25929573

Pharmacologic management of sexual dysfunction: benefits and limitations.

PubMed

Segraves, Robert Taylor

2003-03-01

What is the current knowledge concerning the pharmacologic treatment of human sexual dysfunction? A number of interventions, including oral phophodiesterase inhibitors and intracorporeal agents with vasodilatory effects, are available to treat male erectile disorder. Serotonergic drugs have been shown to be effective in the treatment of rapid ejaculation. Various lines of research suggest that high dosages of androgenic agents may eventually have a role in the treatment of decreased libido in females. There may be a role for phophodiesterase inhibitors in the treatment of a subgroup of women with arousal disorders. Normal sexual function involves successful integration of biological, psychological, and interpersonal influences. Clinical psychiatry with its biopsychosocial model should incorporate the treatment of human sexual dysfunction within its purview.

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib.

PubMed

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib.

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib

PubMed Central

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib. PMID:28744140

TP53 dysfunction in CLL: Implications for prognosis and treatment.

PubMed

Te Raa, Gera D; Kater, Arnon P

2016-03-01

Despite the availability of novel targeted agents, TP53 defects remain the most important adverse prognostic factor in chronic lymphocytic leukemia (CLL). Detection of deletion of TP53 locus (17p deletion) by fluorescent in situ hybridization (FISH) has become standard and performed prior to every line of treatment as the incidence dramatically increases as relapses occur. As monoallelic mutations of TP53 equally affect outcome, novel methods are being developed to improve detection of TP53 defects and include next-generation sequencing (NGS) and functional assays. TP53 defects highly affect outcome of immunochemotherapy but also alter response durations of tyrosine kinase inhibitors. Although BCR-targeting agents and Bcl-2-inhibitos have achieved durable responses in some patients with TP53 defects, long-term follow-up is currently lacking. In this review biological and clinical consequences of TP53 dysfunction as well as applicability of currently available methods to detect TP53 defects are described. In addition, proposed novel therapeutic strategies specifically for patients with TP53 dysfunction are discussed. In summary, the only curative treatment option for TP53-defective CLL is still allogeneic hematopoietic stem cell transplantation. Other treatment strategies such as rationale combinations of agents with different (TP53 independent) targets, including kinase inhibitors and inhibitors of anti-apoptotic molecules but also immunomodulatory agents need to be further explored. Copyright © 2016 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%).

Agent-based models in translational systems biology

PubMed Central

An, Gary; Mi, Qi; Dutta-Moscato, Joyeeta; Vodovotz, Yoram

2013-01-01

Effective translational methodologies for knowledge representation are needed in order to make strides against the constellation of diseases that affect the world today. These diseases are defined by their mechanistic complexity, redundancy, and nonlinearity. Translational systems biology aims to harness the power of computational simulation to streamline drug/device design, simulate clinical trials, and eventually to predict the effects of drugs on individuals. The ability of agent-based modeling to encompass multiple scales of biological process as well as spatial considerations, coupled with an intuitive modeling paradigm, suggests that this modeling framework is well suited for translational systems biology. This review describes agent-based modeling and gives examples of its translational applications in the context of acute inflammation and wound healing. PMID:20835989

Antibody-based Biologics and Their Promise to Combat Staphylococcus aureus Infections

PubMed Central

Sause, William E.; Buckley, Peter T.; Strohl, William R.; Lynch, Anthony S.; Torres, Victor J.

2015-01-01

The growing incidence of serious infections mediated by methicillin-resistant Staphylococcus aureus (MRSA) strains poses a significant risk to public health. This risk is exacerbated by a prolonged void in the discovery and development of truly novel antibiotics and the absence of a vaccine. These gaps have created renewed interest in the use of biologics in the prevention and treatment of serious staphylococcal infections. This review focuses on efforts towards the discovery and development of antibody-based biologic agents and their potential as clinical agents in the management of serious S. aureus infections. Recent promising data for monoclonal antibodies (mAbs) targeting anthrax and Ebola highlight the potential of antibody-based biologics as therapeutic agents for serious infections. PMID:26719219

Current development of podophyllotoxins.

PubMed

Canetta, R; Hilgard, P; Florentine, S; Bedogni, P; Lenaz, L

1982-01-01

The unique biological properties and therapeutic efficacy of the podophyllotoxin derivatives, Vumon (VM26, teniposide) and Vepesid (VP16-213, etoposide), are stimulating the interest of both laboratory and clinical researchers. Investigations on new pharmaceutical formulations, pharmacokinetics and metabolism are providing more appropriate information in drug administration; experimental chemotherapy indicates that, among others, cytosine arabinoside and cisplatin are highly synergistic with podophyllotoxins; single agent and combination treatment clinical trials are defining the respective role of Vumon and Vepesid in cancer chemotherapy.

Electrical and Thermal Modulation of Protein Synthesis in Cartilage: A Model for Field Effects on Biological Tissues.

DTIC Science & Technology

1988-01-15

76] under physiological conditions. Oscillatory streaming currents of 1-5 pA/cm’ were recently demonstrated in bovine knee articular cartilage...in cellular metabolism or cellular acidosis ). In general, these agents are lethal in high enough doses. The stress proteins are highly conserved...which under reducing conditions subdivides into subunits of 35 kD (on SDS-PAGE) in bovine fetal epiphyseal and articular cartilage [170]. The tissue

Acute Lethality of Inhaled Hydrogen Cyanide in the Laboratory Rat: Impact of Concentration x Time Profile and Evaluation of the Predictivity of Toxic Load Models

DTIC Science & Technology

2013-05-03

public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions...AVAILABILITY STATEMENT Approved for public release; distribution is unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Toxic load models are mathematical...equal). The Department of Defense (DOD) (2005) publication “Potential Military Chemical/Biological Agents and Compounds” currently uses the toxic load

Development of an ELISA microarray assay for the sensitive and simultaneous detection of ten biodefense toxins.

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

Jenko, Kathryn; Zhang, Yanfeng; Kostenko, Yulia

Plant and microbial toxins are considered bioterrorism threat agents because of their extreme toxicity and/or ease of availability. Additionally, some of these toxins are increasingly responsible for accidental food poisonings. The current study utilized an ELISA-based protein antibody microarray for the multiplexed detection of ten biothreat toxins, botulinum neurotoxins (BoNT) A, B, C, D, E, F, ricin, shiga toxins 1 and 2 (Stx), and staphylococcus enterotoxin B (SEB), in buffer and complex biological matrices. The multiplexed assay displayed a sensitivity of 1.3 pg/mL (BoNT/A, BoNT/B, SEB, Stx-1 and Stx-2), 3.3 pg/mL (BoNT/C, BoNT/E, BoNT/F) and 8.2 pg/mL (BoNT/D, ricin). Allmore » assays demonstrated high accuracy (75-120 percent recovery) and reproducibility (most coefficients of variation < 20%). Quantification curves for the ten toxins were also evaluated in clinical samples (serum, plasma, nasal fluid, saliva, stool, and urine) and environmental samples (apple juice, milk and baby food) with overall minimal matrix effects. The multiplex assays were highly specific, with little crossreactivity observed between the selected toxin antibodies. The results demonstrate a multiplex microarray that improves current immunoassay sensitivity for biological warfare agents in buffer, clinical, and environmental samples.« less

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...

Gap Between Official Guidelines and Clinical Practice for the Treatment of Rheumatoid Arthritis in São Paulo, Brazil.

PubMed

de Camargo, Iara Alves; Almeida Barros, Bruna Cipriano; do Nascimento Silveira, Miriam Sanches; Osorio-de-Castro, Claudia Garcia Serpa; Guyatt, Gordon; Lopes, Luciane Cruz

2016-05-01

Biological agents used for the treatment of rheumatoid arthritis (RA) are associated with serious adverse events. Guidelines provide standards for the prescribing and monitoring of these drugs. In São Paulo, health litigation for access to medicines has fueled the demand for biological therapy. The extent to which biological agents are being appropriately prescribed and patients are being appropriately monitored is uncertain. Our goal was to determine whether RA clinical guidelines are being translated into clinical practice for patients receiving treatment as a result of lawsuits against the government. We identified patients through records of the State Secretary of Health of São Paulo from 2003 to 2011. We consulted guidelines from 5 countries and chose those recommendations endorsed by all of the guidelines reviewed as standards. Pharmacy records provided data regarding biologic use. The guidelines recommended the use of biological agents only when patients had been receiving treatment with at least 1 disease-modifying antirheumatic drug (DMARD) and recommended annual monitoring of laboratory blood tests. Of the 238 patients identified in the database, 216 patients were interviewed, and 124 (57.4%) patients were still using biological agents at the time of the survey. Of the patients interviewed, 167 patients (77.3%) started biological treatment when using ≥2 DMARDs before, 22 patients (10.2%) were using 1 DMARD before, and 27 patients (12.5%) had never taken a DMARD. Of the 124 patients still taking biological drugs, 117 patients (94.3%) had visited a doctor at least once per year, but 28 patients (22.6%) did not undergo the recommended laboratory blood testing. Only 43 of the 124 patients (34.7%) still taking biological agents met the guideline criteria for both the use of previous agents and the appropriate monitoring. An important gap between clinical practice and the national guidelines exists among treatments prescribed for plaintiffs obtaining medicines for RA in São Paulo. The results suggest the need for intervention by health authorities. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Department of Defense Chemical, Biological, Radiological, and Nuclear Defense Program, Annual Report to Congress, 2004

DTIC Science & Technology

2004-05-01

foldable/ portable emergency smoke hoods with extended gas sorption capabilities and regenerable, biological pathogen-destroying and gas-sorbing...traditional agents. • Cyanide Countermeasures – Potential pretreatment compounds (e.g., methemoglobin formers and sulfide donors) and regimen are being...evaluated for safety and efficacy as pretreatments. • Nerve agent antidotes – New nerve agent antidote compounds that are water soluble, have a broader

40 CFR 300.915 - Data requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... this section. (d) Bioremediation Agents. (1) Name, brand, or trademark, if any, under which the agent...) Bioremediation Agent Effectiveness. Use bioremediation agent effectiveness test methods described in appendix C to part 300. (8) Bioremediation Agent Toxicity [Reserved]. (9) Biological additives. (i) For...

Challenges and Practices in Building and Implementing Biosafety and Biosecurity Programs to Enable Basic and Translational Research with Select Agents.

PubMed

Jonsson, Colleen B; Cole, Kelly Stefano; Roy, Chad J; Perlin, David S; Byrne, Gerald

2013-04-29

Select agent research in the United States must meet federally-mandated biological surety guidelines and rules which are comprised of two main components: biosecurity and biosafety. Biosecurity is the process employed for ensuring biological agents are properly safeguarded against theft, loss, diversion, unauthorized access or use/release. Biosafety is those processes that ensure that operations with such agents are conducted in a safe, secure and reliable manner. As such, a biological surety program is generally concerned with biological agents that present high risk for adverse medical and/or agricultural consequences upon release outside of proper containment. The U.S. Regional and National Biocontainment Laboratories (RBL, NBL) represent expertise in this type of research, and are actively engaged in the development of programs to address these critical needs and federal requirements. While this comprises an ongoing activity for the RBLs, NBLs and other facilities that handle select agents as new guidelines and regulations are implemented, the present article is written with the goal of presenting a simplified yet comprehensive review of these requirements. Herein, we discuss the requirements and the various activities that the RBL/NBL programs have implemented to achieve these metrics set forth by various agencies within the U.S. Federal government.

Challenges and Practices in Building and Implementing Biosafety and Biosecurity Programs to Enable Basic and Translational Research with Select Agents

PubMed Central

Jonsson, Colleen B.; Cole, Kelly Stefano; Roy, Chad J.; Perlin, David S.; Byrne, Gerald

2014-01-01

Select agent research in the United States must meet federally-mandated biological surety guidelines and rules which are comprised of two main components: biosecurity and biosafety. Biosecurity is the process employed for ensuring biological agents are properly safeguarded against theft, loss, diversion, unauthorized access or use/release. Biosafety is those processes that ensure that operations with such agents are conducted in a safe, secure and reliable manner. As such, a biological surety program is generally concerned with biological agents that present high risk for adverse medical and/or agricultural consequences upon release outside of proper containment. The U.S. Regional and National Biocontainment Laboratories (RBL, NBL) represent expertise in this type of research, and are actively engaged in the development of programs to address these critical needs and federal requirements. While this comprises an ongoing activity for the RBLs, NBLs and other facilities that handle select agents as new guidelines and regulations are implemented, the present article is written with the goal of presenting a simplified yet comprehensive review of these requirements. Herein, we discuss the requirements and the various activities that the RBL/NBL programs have implemented to achieve these metrics set forth by various agencies within the U.S. Federal government. PMID:24900945

[Advances in peroxide-based decontaminating technologies].

PubMed

Xi, Hai-ling; Zhao, San-ping; Zhou, Wen

2013-05-01

With the boosting demand for eco-friendly decontaminants, great achievements in peroxide-based decontaminating technologies have been made in recent years. These technologies have been applied in countering chemical/biological terrorist attacks, dealing with chemical/biological disasters and destructing environmental pollutants. Recent research advances in alpha-nucleophilic/oxidative reaction mechanisms of peroxide-based decontamination against chemical warfare agents were reviewed, and some classical peroxide-based decontaminants such as aqueous decontaminating solution, decontaminating foam, decontaminating emulsions, decontaminating gels, decontaminating vapors, and some newly developed decontaminating media (e.g., peroxide-based self-decontaminating materials and heterogeneous nano-catalytic decontamination systems) were introduced. However, currently available peroxide-based decontaminants still have some deficiencies. For example, their decontamination efficiencies are not as high as those of chlorine-containing decontaminants, and some peroxide-based decontaminants show relatively poor effect against certain agents. More study on the mechanisms of peroxide-based decontaminants and the interfacial interactions in heterogeneous decontamination media is suggested. New catalysts, multifunctional surfactants, self-decontaminating materials and corrosion preventing technologies should be developed before peroxide-based decontaminants really become true "green" decontaminants.

Cellular Aspects of Prion Replication In Vitro

PubMed Central

Grassmann, Andrea; Wolf, Hanna; Hofmann, Julia; Graham, James; Vorberg, Ina

2013-01-01

Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders in mammals that are caused by unconventional agents predominantly composed of aggregated misfolded prion protein (PrP). Prions self-propagate by recruitment of host-encoded PrP into highly ordered β-sheet rich aggregates. Prion strains differ in their clinical, pathological and biochemical characteristics and are likely to be the consequence of distinct abnormal prion protein conformers that stably replicate their alternate states in the host cell. Understanding prion cell biology is fundamental for identifying potential drug targets for disease intervention. The development of permissive cell culture models has greatly enhanced our knowledge on entry, propagation and dissemination of TSE agents. However, despite extensive research, the precise mechanism of prion infection and potential strain effects remain enigmatic. This review summarizes our current knowledge of the cell biology and propagation of prions derived from cell culture experiments. We discuss recent findings on the trafficking of cellular and pathologic PrP, the potential sites of abnormal prion protein synthesis and potential co-factors involved in prion entry and propagation. PMID:23340381

Antifungal potential of marine natural products.

PubMed

El-Hossary, Ebaa M; Cheng, Cheng; Hamed, Mostafa M; El-Sayed Hamed, Ashraf Nageeb; Ohlsen, Knut; Hentschel, Ute; Abdelmohsen, Usama Ramadan

2017-01-27

Fungal diseases represent an increasing threat to human health worldwide which in some cases might be associated with substantial morbidity and mortality. However, only few antifungal drugs are currently available for the treatment of life-threatening fungal infections. Furthermore, plant diseases caused by fungal pathogens represent a worldwide economic problem for the agriculture industry. The marine environment continues to provide structurally diverse and biologically active secondary metabolites, several of which have inspired the development of new classes of therapeutic agents. Among these secondary metabolites, several compounds with noteworthy antifungal activities have been isolated from marine microorganisms, invertebrates, and algae. During the last fifteen years, around 65% of marine natural products possessing antifungal activities have been isolated from sponges and bacteria. This review gives an overview of natural products from diverse marine organisms that have shown in vitro and/or in vivo potential as antifungal agents, with their mechanism of action whenever applicable. The natural products literature is covered from January 2000 until June 2015, and we are reporting the chemical structures together with their biological activities, as well as the isolation source. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Regulatory T Cell Therapy for Uveitis: A New Promising Challenge.

PubMed

Foussat, Arnaud; Gregoire, Sylvie; Clerget-Chossat, Nathalie; Terrada, Celine; Asnagli, Hélène; Lemoine, François M; Klatzmann, David; LeHoang, Phuc; Forte, Miguel; Bodaghi, Bahram

2017-05-01

Uveitis is a sight-threatening primary intraocular inflammation of various origins in mainly young and active patients. Due to the absence of biomarkers in most of the cases, the current treatment of noninfectious entities remains nonspecific, using corticosteroids, conventional immunosuppressors, and more recently biological agents. Identification of regulatory T cells in different models of autoimmune uveitis together with the evaluation of this important subpopulation in different entities paved the way for new therapeutic strategies, in addition to exclusive pharmaceutical approaches. Upregulation of regulatory T cells induced by biological agents has been recently highlighted. Development of cell therapy in autoimmune diseases is at its stammering needing more experimental data and robust clinical trials to demonstrate safety and efficacy before larger developments. Specific or polyclonal Tregs may be used, but it is of utmost importance to determine the method of selection, the level of activation, and the route of administration. Mastering immune cell therapy remains a challenging goal in patients with autoimmune diseases, but it may significantly enlarge our therapeutic possibilities in severe and refractory situations.

New systemic agents in dermatology with respect to fertility, pregnancy, and lactation.

PubMed

Grunewald, Sonja; Jank, Alexander

2015-04-01

With the increasing use of new, predominantly biologic drugs in dermatology, questions frequently arise in clinical practice as to their safety in women wishing to conceive as well as during pregnancy and lactation. Apart from the Summary of Product Characteristics and the Physician's Desk Reference, reliable information may be obtained from databases such as the one compiled by the Center for Pharmacovigilance and Consultation on Embryonal Toxicology at Charité University Medical Center Berlin (https://www.embryotox.de). Another source of information is researching recent publications, for example via PubMed (http://www.ncbi.nlm.nih.gov/pubmed). This article presents current knowledge from the sources mentioned above, and gives detailed information about the use of new biologic agents in women wishing to conceive as well as during pregnancy and lactation. Drugs reviewed include: infliximab, adalimumab, etanercept, metastatic for psoriasis, vemurafenib, dabrafenib, imatinib, ipilimumab for melanoma, vismodegib for basal cell carcinoma, rituximab for cutaneous lymphoma as well as omalizumab and anakinra used in the treatment of allergies. © 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

15th International Conference on Human Antibodies and Hybridomas. 14-16 April 2010, Tiara Park Atlantico Hotel, Porto, Portugal.

PubMed

Kotlan, Beatrix

2010-11-01

Antibodies and antibody conjugates are currently one of the largest classes of new drug entities under development. These versatile molecules are being investigated for the treatment of many pathological conditions, such as cancer and infectious, inflammatory and autoimmune diseases. Antibodies can exert biological effects as naked antibodies by themselves, or can be used as delivery agents conjugated with various drugs (e.g., immunoconjugates) and as tools of multistep targeting. Site-specific delivery of therapeutic agents has been the ultimate goal of the pharmaceutical industry, as it has the potential to maximize drug efficiency while minimizing side effects. Antibodies have much potential for this objective. Thus, it is useful to summarize some of the main strategies currently being employed for the development of these diverse therapeutic molecules and to highlight the recent novelties in the field. These goals were the focus of the 15th International Conference on Human Antibodies and Hybridomas, held during 14-16 April 2010 in Porto, Portugal.

Treatment of severe lupus nephritis: the new horizon.

PubMed

Chan, Tak Mao

2015-01-01

Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus, and an important cause of both acute kidney injury and end-stage renal disease. Despite its aggressive course, lupus nephritis is amenable to treatment in the majority of patients. The paradigm of immunosuppressive treatment for lupus nephritis has evolved over the past few decades from corticosteroids alone to corticosteroids combined with cyclophosphamide. Sequential treatment regimens using various agents have been formulated for induction and long-term maintenance therapy, and mycophenolate mofetil has emerged as a standard of care option for both induction and maintenance immunosuppressive treatment. The current era has witnessed the emergence of multiple novel therapeutic options, such as calcineurin inhibitors and biologic agents that target key pathogenetic mechanisms of lupus nephritis. Clinical outcomes have improved in parallel with these therapeutic advances. This Review discusses the evidence in support of current standard of care immunosuppressive treatments and emerging therapies, and describes their roles and relative merits in the management of patients with lupus nephritis.

Evolution in Medicinal Chemistry of Ursolic Acid Derivatives as Anticancer Agents

PubMed Central

Chen, Haijun; Gao, Yu; Wang, Ailan; Zhou, Xiaobin; Zheng, Yunquan; Zhou, Jia

2015-01-01

Currently, there is a renewed interest in common dietaries and plant-based traditional medicines for the prevention and treatment of cancer. In the search for potential anticancer agents from natural sources, ursolic acid (UA), a pentacyclic triterpenoid widely found in various medicinal herbs and fruits, exhibits powerful biological effects including its attractive anticancer activity against various types of cancer cells. However, the limited solubility, rapid metabolism and poor bioavailability of UA restricted its further clinical applications. In the past decade, with substantial progress toward the development of new chemical entities for the treatment of cancer, numerous UA derivatives have been designed and prepared to overcome its disadvantages. Despite extensive effort, discovery of effective UA derivatives has so far met with only limited success. This review summarizes the current status of the structural diversity and evolution in medicinal chemistry of UA analogues and provides a detailed discussion of future direction for further research in the chemical modifications of UA. PMID:25617694

Biologic Therapy in Inflammatory and Immunomediated Arthritis: Safety Profile.

PubMed

Luchetti, Michele Maria; Balloni, Andrea; Gabrielli, Armando

2016-01-01

The increasing insights into the pathogenetic mechanisms of inflammatory autoimmune arthritis and the development of innovative systems of industrial production have led to discover molecules that are able to target/block other molecules that play a critical role in the immune system functioning, and that have been introduced in clinical practice alone and/or in addiction with other "old" disease-modifying anti-rheumatic drugs. For this reason, such drugs are currently known as "biological drugs" and include molecules that induce the immunosuppression acting on several immune pathways. However, though the biological drugs have been employed from more than a decade, there still exist some drawbacks of their use, in particular about the high costs of this therapy and their overall safety, including the route of administration for the intravenous use. In this review we provide an update on the correct use and current therapeutic indications of such drugs, including some of the new biologic therapies that will be soon available for the clinical use, focusing on these biological drugs: • Tumor necrosis factor-alpha (TNF-alpha) inhibitors (adalimumab, certolizumab-pegol, etanercept, golimumab and infliximab); • The T cell co-stimulation inhibitor, abatacept; • The anti-CD20 receptor monoclonal B cell agent, rituximab; • The interlukin-6 (IL-6) receptor-blocking monoclonal antibody, tocilizumab; • The interlukin-1 (IL-1) inhibitor, anakinra; • The interlukin-IL17 (IL-17) pathway inhibitors (ustekinumab, secukinumab, brodalumab).

Therapeutic Targeting of IL-17 and IL-23 Cytokines in Immune-Mediated Diseases.

PubMed

Fragoulis, George E; Siebert, Stefan; McInnes, Iain B

2016-01-01

The discovery of the biological functions of the interleukin-23/-17 axis led to the identification of IL-23 and IL-17 as important participants in the pathogenesis of several immune-mediated diseases. Therapeutic agents targeting these cytokines and/or their receptors have now been developed as potential treatment strategies for common immune-mediated diseases. Anti-IL-17 and anti-IL-12/-23 regimens appear particularly effective in psoriasis, with promising results in spondyloarthropathies also emerging. Overall, these agents appear well tolerated, with adverse-event rates that are commensurate with those in other biologic treatment programs. The strategic utility of these new agents, however, remains uncertain, and further studies will be required to determine their place in the context of existing conventional and biologic immune-modifying agents.

Evolving landscape of human epidermal growth factor receptor 2-positive breast cancer treatment and the future of biosimilars.

PubMed

Jackisch, Christian; Lammers, Philip; Jacobs, Ira

2017-04-01

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer comprises approximately 15%-20% of all breast cancers and is associated with a poor prognosis. The introduction of anti-HER2 therapy has significantly improved clinical outcomes for patients with HER2+ breast cancer, and multiple HER2-directed agents (ie, trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine [T-DM1]) are approved for clinical use in various settings. The treatment landscape for patients with HER2+ breast cancer is continuing to evolve. While novel agents and therapeutic strategies are emerging, biologic therapies, particularly trastuzumab, are likely to remain a mainstay of treatment. However, access issues create barriers to the use of biologics, and there is evidence for underuse of trastuzumab worldwide. A biosimilar is a biologic product that is highly similar to a licensed biologic in terms of product safety and effectiveness. Biosimilars of trastuzumab are in development and may soon become available. The introduction of biosimilars may improve access to anti-HER2 therapies by providing additional treatment options and lower-cost alternatives. Because HER2-targeted drugs may be administered for extended periods of time and in combination with other systemic therapies, biosimilars have the potential to result in significant savings for healthcare systems. Herein we review current and emerging treatment options for, and discuss the possible role of biosimilars in, treating patients with HER2+ breast cancer. Copyright © 2017 Authors, Pfizer Inc. Published by Elsevier Ltd.. All rights reserved.

Vaccines against biologic agents: uses and developments.

PubMed

Ales, Noel C; Katial, Rohit K

2004-03-01

Although the Geneva protocol that prohibits the use of chemical and biologic weapons was ratified in 1925, many countries failed to accept this protocol: others stipulated retaliation, and some, like the United States, did not ratify the protocol for decades. This delay allowed the continued development of chemical and biologic agents. Members of the health care community are responsible for determining the best way to protect society from the potentially devastating effects of these biologic agents. Ideally,these diseases would be prevented from ever developing into systemic illnesses. In the past, vaccination has been a successful means of eradicating disease. Vaccines remain a hopeful therapy for the future, but time is short,and there are many obstacles.Information regarding bioterrorism agents and their treatments comes mainly from dated data or from in vitro or animal studies that may not apply to human treatment and disease. Additionally, the current threat of bioterrorism does not allow enough time for accurate, well-designed,controlled studies in humans before the release of investigational vaccines. Furthermore, some human studies would not be safe or ethical. Finally,many members of society suffer from illnesses that would put them at high risk to receive prophylactic vaccination. It is therefore naive to believe that vaccines would be the ultimate protection from these agents. In addition to vaccine development, there must be concurrent investigations into disease management and treatment. Even in instances in which vaccination is known to be an effective means of disease protection. biologic agents may be presented in a manner that renders vaccines ineffective. Virulent strains of organisms may be used, more than one organism may be used in tandem to increase virulence, and strains may be selected for antibiotic and vaccine resistance. Genetically engineered strains may use virulence factors other than those targeted in vaccines, and high concentrations of organisms may overcome vaccine protection. Finally,exposure may not be immediately noted until it is too late to vaccinate, as was the case with anthrax. Even in a case, such as smallpox, in which postexposure vaccination is possible, patients will still develop disease, and the health care system may be overwhelmed. The United States government has been defensively planning and researching the use of vaccines and chemoprophylaxis against any potential biologic agents since at least 1953, and resources are still lacking. There are inadequate stockpiles of vaccine to protect the entire population. The pharmaceutical industry also lacks a means of mass producing vaccines ina short timeframe. There is no policy in place for the use of vaccines that are yet unlicensed and experimental but may be the only therapy in the event ofa terrorist attack. Investigations into these solutions have been instituted only after the September 11, 2001, attacks heightened the awareness of terrorism. Although vaccination is an effective means of prophylaxis and a means of terminating epidemics or treating active disease, there is also resistance from the general public. In some instances there is a lack of acceptance of vaccines, or the risk of side effects is too great. In other cases, a questionable benefit does not justify the expense of mass vaccination. Because of this uncertainty, mass vaccination is deemed an impractical solution to the threat of bioterrorism. Extending vaccination with most vaccines to include all members of society who may be first responders in the event of an attack should be considered. In all instances, the benefit-to-risk must be weighed ratio when deciding how and when to offer preemptive prophylaxis to protect society from a real but unknown threat.

Viral vectors for gene modification of plants as chem/bio sensors.

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

Manginell, Monica; Harper, Jason C.; Arango, Dulce C.

2006-11-01

Chemical or biological sensors that are specific, sensitive, and robust allowing intelligence gathering for verification of nuclear non-proliferation treaty compliance and detouring production of weapons of mass destruction are sorely needed. Although much progress has been made in the area of biosensors, improvements in sensor lifetime, robustness, and device packaging are required before these devices become widely used. Current chemical and biological detection and identification techniques require less-than-covert sample collection followed by transport to a laboratory for analysis. In addition to being expensive and time consuming, results can often be inconclusive due to compromised sample integrity during collection and transport.more » We report here a demonstration of a plant based sensor technology which utilizes mature and seedling plants as chemical sensors. One can envision genetically modifying native plants at a site of interest that can report the presence of specific toxins or chemicals. In this one year project we used a developed inducible expression system to show the feasibility of plant sensors. The vector was designed as a safe, non-infectious vector which could be used to invade, replicate, and introduce foreign genes into mature host plants that then allow the plant to sense chem/bio agents. The genes introduced through the vector included a reporter gene that encodes for green fluorescent protein (GFP) and a gene that encodes for a mammalian receptor that recognizes a chemical agent. Specifically, GFP was induced by the presence of 17-{beta}-Estradiol (estrogen). Detection of fluorescence indicated the presence of the target chemical agent. Since the sensor is a plant, costly device packaging development or manufacturing of the sensor were not required. Additionally, the biological recognition and reporting elements are maintained in a living, natural environment and therefore do not suffer from lifetime disadvantages typical of most biosensing platforms. Detection of the chem/bio agent reporter (GFP) can be detected only at a specific wavelength.« less

The Use of Biologic Therapies in Uveitis.

PubMed

Schwartzman, Sergio; Schwartzman, Monica

2015-12-01

Therapy for autoimmune ophthalmic disease is currently evolving. The improved understanding of the abnormal immune response in the various forms of uveitis has resulted in targeted therapy. The aberrations of the immune system have been characterized by atypical cell populations, cytokine expression, and cell-cell interactions. Different patterns of cytokine expression have now been delineated in the abnormal uveal tract with exaggerated and/or abnormal expression of TNF, IL-1, IL-2, IL-6, and IL-17. The development of therapies for other conditions in which these cytokines play an important role has resulted in the availability of biological agents that have been adopted for use in the therapy for uveitis. Adalimumab and infliximab have been the best studied anti-TNF agents and indeed have now been recommended by an expert panel as first-line treatment of ocular manifestations of Behçet's disease and second-line treatment for other forms of uveitis (Levy-Clarke et al. (Ophthalmology, 2013). Other anti-TNF agents have been studied as well. Daclizumab, a monoclonal antibody directed against the IL-2 receptor, has also demonstrated utility in treating uveitis as have some of the anti-IL1 agents. Gevokizumab has been granted orphan drug designation for the treatment of resistant forms of uveitis. Therapies affecting IL-6, including tocilizumab are being studied, and available medications that block antigen presenting cell and T cell interaction such as abatacept have been reported to be effective in uveitis. Interferons as well as rituximab have also been evaluated in small studies. Although these biologic therapies have provided a larger armamentarium to treat uveitis, challenges remain. Uveitis is not a single illness; rather, it is a manifestation of many potential systemic diseases that may have very specific individual therapeutic targets. Identifying and characterizing these underlying diseases is not always achieved, and more importantly, the most effective therapies for each entity have not been defined.

Agent-based modelling in synthetic biology.

PubMed

Gorochowski, Thomas E

2016-11-30

Biological systems exhibit complex behaviours that emerge at many different levels of organization. These span the regulation of gene expression within single cells to the use of quorum sensing to co-ordinate the action of entire bacterial colonies. Synthetic biology aims to make the engineering of biology easier, offering an opportunity to control natural systems and develop new synthetic systems with useful prescribed behaviours. However, in many cases, it is not understood how individual cells should be programmed to ensure the emergence of a required collective behaviour. Agent-based modelling aims to tackle this problem, offering a framework in which to simulate such systems and explore cellular design rules. In this article, I review the use of agent-based models in synthetic biology, outline the available computational tools, and provide details on recently engineered biological systems that are amenable to this approach. I further highlight the challenges facing this methodology and some of the potential future directions. © 2016 The Author(s).

Factors influencing plant invasiveness

Treesearch

Yvette Ortega; Dean Pearson

2009-01-01

Invasiveness of spotted knapweed and biological control agents. Dean and Yvette are examining the influence of drought on the invasiveness of spotted knapweed (Centaurea maculosa) and its susceptibility to herbivory by biological control agents. In collaboration with the University of Montana and Forest Health Protection, researchers have constructed 150...

78 FR 11202 - Medicare Program; Public Meetings in Calendar Year 2013 for All New Public Requests for Revisions...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-15

.../Biologicals/Radiopharmaceuticals/Radiologic Imaging Agents). 2. Thursday, May 9, 2013, 9 a.m. to 5 p.m., e.d.t. (Drugs/ Biologicals/Radiopharmaceuticals/Radiologic Imaging Agents). 3. Wednesday, May 29, 2013, 9 a.m...

Microarray Analysis and Mutagenesis of the Biological Control Agent Pseudomonas fluorescens Pf-5

USDA-ARS?s Scientific Manuscript database

The biological control agent Pseudomonas fluorescens Pf-5 suppresses seedling emergence diseases caused by soilborne fungi and Oomycetes. Pf-5 produces at least ten secondary metabolites. These include hydrogen cyanide, pyrrolnitrin, pyoluteorin and 2,4-diacetylphloroglucinol, which have known funct...

Oxidizer gels for detoxification of chemical and biological agents

DOEpatents

Hoffman, Dennis M.; McGuire, Raymond R.

2002-01-01

A gel composition containing oxidizing agents and thickening or gelling agents is used to detoxify chemical and biological agents by application directly to a contaminated area. The gelling agent is a colloidal material, such as silica, alumina, or alumino-silicate clays, which forms a viscous gel that does not flow when applied to tilted or contoured surfaces. Aqueous or organic solutions of oxidizing agents can be readily gelled with less than about 30% colloidal material. Gel preparation is simple and suitable for field implementation, as the gels can be prepared at the site of decontamination and applied quickly and uniformly over an area by a sprayer. After decontamination, the residue can be washed away or vacuumed up for disposal.

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

From effective biocontrol agent to successful invader: the harlequin ladybird (Harmonia axyridis) as an example of good ideas that could go wrong

PubMed Central

Ortega-Iturriaga, Adrián; del-Val, Ek

2017-01-01

The use of biological control agents to control pests is an alternative to pesticides and a tool to manage invasive alien species. However, biocontrol agents can themselves become invasive species under certain conditions. The harlequin ladybird (Harmonia axyridis) is a native Asian biocontrol agent that has become a successful invader. We reviewed articles containing “Harmonia axyridis” to gather information on its presence and surveyed entomologists researching Coccinellidae around the world to investigate further insights about the current distribution, vectors of introduction, habitat use and threats this species pose. The harlequin ladybird has established populations in at least 59 countries outside its native range. Twenty six percent of the surveyed scientists considered it a potential threat to native Coccinellidae. Published studies and scientists suggest Adalia bipunctata, native to Europe, is under the highest risk of population declines. Strict policies should be incorporated to prevent its arrival to non-invaded areas and to prevent further expansion range. Managing invasive species is a key priority to prevent biodiversity loss and promote ecosystem services. PMID:28533958

From effective biocontrol agent to successful invader: the harlequin ladybird (Harmonia axyridis) as an example of good ideas that could go wrong.

PubMed

Camacho-Cervantes, Morelia; Ortega-Iturriaga, Adrián; Del-Val, Ek

2017-01-01

The use of biological control agents to control pests is an alternative to pesticides and a tool to manage invasive alien species. However, biocontrol agents can themselves become invasive species under certain conditions. The harlequin ladybird ( Harmonia axyridis ) is a native Asian biocontrol agent that has become a successful invader. We reviewed articles containing " Harmonia axyridis " to gather information on its presence and surveyed entomologists researching Coccinellidae around the world to investigate further insights about the current distribution, vectors of introduction, habitat use and threats this species pose. The harlequin ladybird has established populations in at least 59 countries outside its native range. Twenty six percent of the surveyed scientists considered it a potential threat to native Coccinellidae. Published studies and scientists suggest Adalia bipunctata , native to Europe, is under the highest risk of population declines. Strict policies should be incorporated to prevent its arrival to non-invaded areas and to prevent further expansion range. Managing invasive species is a key priority to prevent biodiversity loss and promote ecosystem services.

The Endemic Treponematoses

PubMed Central

Giacani, Lorenzo

2014-01-01

SUMMARY The agents of human treponematoses include four closely related members of the genus Treponema: three subspecies of Treponema pallidum plus Treponema carateum. T. pallidum subsp. pallidum causes venereal syphilis, while T. pallidum subsp. pertenue, T. pallidum subsp. endemicum, and T. carateum are the agents of the endemic treponematoses yaws, bejel (or endemic syphilis), and pinta, respectively. All human treponematoses share remarkable similarities in pathogenesis and clinical manifestations, consistent with the high genetic and antigenic relatedness of their etiological agents. Distinctive features have been identified in terms of age of acquisition, most common mode of transmission, and capacity for invasion of the central nervous system and fetus, although the accuracy of these purported differences is debated among investigators and no biological basis for these differences has been identified to date. In 2012, the World Health Organization (WHO) officially set a goal for yaws eradication by 2020. This challenging but potentially feasible endeavor is favored by the adoption of oral azithromycin for mass treatment and the currently focused distribution of yaws and endemic treponematoses and has revived global interest in these fascinating diseases and their causative agents. PMID:24396138

Biologic treatment in Sjögren's syndrome.

PubMed

Sada, Pablo Ruiz; Isenberg, David; Ciurtin, Coziana

2015-02-01

SS is a chronic systemic autoimmune disease characterized by decreased exocrine gland function. A variety of other disease manifestations may also be present, including general constitutional symptoms and extraglandular features. A multidisciplinary approach focused on both local and systemic medical therapies is needed as the disease has a wide clinical spectrum. The current treatment for SS is mainly symptomatic. However, there is evidence that systemic drugs are effective in controlling extraglandular manifestations of the disease. Overall evidence for the role of conventional immunosuppressive therapy is limited. A number of attempts to use biologic therapies have led to variable results. Biologic agents targeting B cells, such as rituximab, epratuzumab and belimumab, have shown promising results, but further studies are needed to validate the findings. Early-phase studies with abatacept and alefacept proved that T cell stimulation inhibition is another potentially effective target for SS treatment. Modulation or inhibition of other targets such as IFN, IL-6 and Toll-like receptor are also currently being investigated. We have summarized the available evidence regarding the efficacy of biologic treatments and discuss other potential therapies targeting pathways or molecules recognized as being involved in the pathogenesis of SS. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Antibacterial Free Fatty Acids and Monoglycerides: Biological Activities, Experimental Testing, and Therapeutic Applications

PubMed Central

Yoon, Bo Kyeong; Jackman, Joshua A.; Valle-González, Elba R.

2018-01-01

Antimicrobial lipids such as fatty acids and monoglycerides are promising antibacterial agents that destabilize bacterial cell membranes, causing a wide range of direct and indirect inhibitory effects. The goal of this review is to introduce the latest experimental approaches for characterizing how antimicrobial lipids destabilize phospholipid membranes within the broader scope of introducing current knowledge about the biological activities of antimicrobial lipids, testing strategies, and applications for treating bacterial infections. To this end, a general background on antimicrobial lipids, including structural classification, is provided along with a detailed description of their targeting spectrum and currently understood antibacterial mechanisms. Building on this knowledge, different experimental approaches to characterize antimicrobial lipids are presented, including cell-based biological and model membrane-based biophysical measurement techniques. Particular emphasis is placed on drawing out how biological and biophysical approaches complement one another and can yield mechanistic insights into how the physicochemical properties of antimicrobial lipids influence molecular self-assembly and concentration-dependent interactions with model phospholipid and bacterial cell membranes. Examples of possible therapeutic applications are briefly introduced to highlight the potential significance of antimicrobial lipids for human health and medicine, and to motivate the importance of employing orthogonal measurement strategies to characterize the activity profile of antimicrobial lipids. PMID:29642500

The Department of Defense Chemical and Biological Defense Program: An Enabler of the Third Offset Strategy.

PubMed

Roos, Jason; Chue, Calvin; DiEuliis, Diane; Emanuel, Peter

The US Department of Defense (DOD) established programs to defend against chemical and biological weapons 100 years ago because military leaders understood that the operational capability of the US military is diminished when service member health is compromised. These threats to operational readiness can be from an overt attack using chemical and biological threats but may also arise from natural exposures. In the current era of rapidly emerging technologies, adversaries are not only rediscovering chemical and biological weapons; they are also displaying an increased propensity to employ them to cause strategic instability among deployed forces or nations undergoing conflict. The United States's investments in its Chemical and Biological Defense Program (CBDP) can be a critical enabler of the third offset strategy, which is a DOD initiative that seeks to maximize force capability to offset emerging threats. To realize this vision, the CBDP must make fundamental changes in acquiring and employing effective technologies so that enemy use of chemical and biological agents against US assets is no longer a viable option. Maximization of US force health status will provide a strategic advantage over theater opponents more vulnerable to operational degradation from chemical and biological threats.

The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response?

PubMed

D'Haens, Geert R; Panaccione, Remo; Higgins, Peter D R; Vermeire, Severine; Gassull, Miquel; Chowers, Yehuda; Hanauer, Stephen B; Herfarth, Hans; Hommes, Daan W; Kamm, Michael; Löfberg, Robert; Quary, A; Sands, Bruce; Sood, A; Watermeyer, G; Watermayer, G; Lashner, Bret; Lémann, Marc; Plevy, Scott; Reinisch, Walter; Schreiber, Stefan; Siegel, Corey; Targan, Stephen; Watanabe, M; Feagan, Brian; Sandborn, William J; Colombel, Jean Frédéric; Travis, Simon

2011-02-01

The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.

Bioterrorism and Biocrimes: The Illicit Use of Biological Agents Since 1900

DTIC Science & Technology

2001-02-01

to white supremacist groups, including the Aryan Nation and the Christian Identity movement, he 5 involve allegations of covert state activities ...toxin to poison livestock in what is now Kenya. The full extent of these activities is not known. Polish Resistance: Multiple reports suggest that...thorough reporting of Aum’s biological warfare activities . See page 47 for additional details. Table 1: Confirmed cases of illicit biological agent activity

2012 Review on the Extension of the AMedP-8(C) Methodology to New Agents, Materials, and Conditions

DTIC Science & Technology

2013-10-01

Atlantic Treaty Organization (NATO) to estimate casualties from chemical, biological , radiological, and nuclear (CBRN) weapons . The final draft...chemical, biological , radiological, and nuclear (CBRN) weapons . The final draft documenting this methodology was published by IDA in 2009 and was...from Battlefield Exposure to Chemical, Biological and Radiological Agents and Nuclear Weapon Effects. IDA Document D- 4465. Alexandria, VA: IDA

Method and apparatus for the gas phase decontamination of chemical and biological agents

DOEpatents

O'Neill, Hugh J.; Brubaker, Kenneth L.

2003-10-07

An apparatus and method for decontaminating chemical and biological agents using the reactive properties of both the single atomic oxygen and the hydroxyl radical for the decontamination of chemical and biological agents. The apparatus is self contained and portable and allows for the application of gas reactants directly at the required decontamination point. The system provides for the use of ultraviolet light of a specific spectral range to photolytically break down ozone into molecular oxygen and hydroxyl radicals where some of the molecular oxygen is in the first excited state. The excited molecular oxygen will combine with water vapor to produce two hydroxyl radicals.

Development of practical methods for removal of radiological, biological, and chemical contaminants from water supplies. Final report

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

Woodward, R.L.; Robeck, G.G.

1958-06-01

Laboratory and engineering studies were conducted to determine the design criteria and cost estimated of providing and operating devices to protect against radiological, biological and chemical warfare agents that may contaminate shore based Naval water supplies. Small disposable columns of mixed cation-anion exchange resins will remove the soluble radionuclides enough to suffice for immediate drinking and culinary purposes. Chemical warfare agents are so numerous and varied that it is not feasible to provide a single protective device to cope with them. Chlorination with free available chlorine residuals of 1 mg liter will handle most biological warfare agents.

Airborne biological hazards and urban transport infrastructure: current challenges and future directions.

PubMed

Nasir, Zaheer Ahmad; Campos, Luiza Cintra; Christie, Nicola; Colbeck, Ian

2016-08-01

Exposure to airborne biological hazards in an ever expanding urban transport infrastructure and highly diverse mobile population is of growing concern, in terms of both public health and biosecurity. The existing policies and practices on design, construction and operation of these infrastructures may have severe implications for airborne disease transmission, particularly, in the event of a pandemic or intentional release of biological of agents. This paper reviews existing knowledge on airborne disease transmission in different modes of transport, highlights the factors enhancing the vulnerability of transport infrastructures to airborne disease transmission, discusses the potential protection measures and identifies the research gaps in order to build a bioresilient transport infrastructure. The unification of security and public health research, inclusion of public health security concepts at the design and planning phase, and a holistic system approach involving all the stakeholders over the life cycle of transport infrastructure hold the key to mitigate the challenges posed by biological hazards in the twenty-first century transport infrastructure.

Agents in bioinformatics, computational and systems biology.

PubMed

Merelli, Emanuela; Armano, Giuliano; Cannata, Nicola; Corradini, Flavio; d'Inverno, Mark; Doms, Andreas; Lord, Phillip; Martin, Andrew; Milanesi, Luciano; Möller, Steffen; Schroeder, Michael; Luck, Michael

2007-01-01

The adoption of agent technologies and multi-agent systems constitutes an emerging area in bioinformatics. In this article, we report on the activity of the Working Group on Agents in Bioinformatics (BIOAGENTS) founded during the first AgentLink III Technical Forum meeting on the 2nd of July, 2004, in Rome. The meeting provided an opportunity for seeding collaborations between the agent and bioinformatics communities to develop a different (agent-based) approach of computational frameworks both for data analysis and management in bioinformatics and for systems modelling and simulation in computational and systems biology. The collaborations gave rise to applications and integrated tools that we summarize and discuss in context of the state of the art in this area. We investigate on future challenges and argue that the field should still be explored from many perspectives ranging from bio-conceptual languages for agent-based simulation, to the definition of bio-ontology-based declarative languages to be used by information agents, and to the adoption of agents for computational grids.

Design Principles of Nanoparticles as Contrast Agents for Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Shan, Liang; Gu, Xinbin; Wang, Paul

2013-09-01

Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD, ), more than 6000 molecular imaging agents with sufficient preclinical evaluation have been reported to date in the literature and this number increases by 250-300 novel agents each year. The majority of these agents are radionuclides, which are developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Contrast agents for magnetic resonance imaging (MRI) account for only a small part. This is largely due to the fact that MRI is currently not a fully quantitative imaging technique and is less sensitive than PET and SPECT. However, because of the superior ability to simultaneously extract molecular and anatomic information, molecular MRI is attracting significant interest and various targeted nanoparticle contrast agents have been synthesized for MRI. The first and one of the most critical steps in developing a targeted nanoparticle contrast agent is target selection, which plays the central role and forms the basis for success of molecular imaging. This chapter discusses the design principles of targeted contrast agents in the emerging frontiers of molecular MRI.

Comparison of traditional and molecular analytical methods for detecting biological agents in raw and drinking water following ultrafiltration

USGS Publications Warehouse

Francy, D.S.; Bushon, R.N.; Brady, A.M.G.; Bertke, E.E.; Kephart, C.M.; Likirdopulos, C.A.; Mailot, B.E.; Schaefer, F. W.; Lindquist, H.D. Alan

2009-01-01

Aims: To compare the performance of traditional methods to quantitative polymerase chain reaction (qPCR) for detecting five biological agents in large-volume drinking-water samples concentrated by ultrafiltration (UF). Methods and Results: Drinking-water samples (100 l) were seeded with Bacillus anthracis, Cryptospordium parvum, Francisella tularensis, Salmonella Typhi, and Vibrio cholerae and concentrated by UF. Recoveries by traditional methods were variable between samples and between some replicates; recoveries were not determined by qPCR. Francisella tularensis and V. cholerae were detected in all 14 samples after UF, B. anthracis was detected in 13, and C. parvum was detected in 9 out of 14 samples. Numbers found by qPCR after UF were significantly or nearly related to those found by traditional methods for all organisms except for C. parvum. A qPCR assay for S. Typhi was not available. Conclusions: qPCR can be used to rapidly detect biological agents after UF as well as traditional methods, but additional work is needed to improve qPCR assays for several biological agents, determine recoveries by qPCR, and expand the study to other areas. Significance and Impact of the Study: To our knowledge, this is the first study to compare the use of traditional and qPCR methods to detect biological agents in large-volume drinking-water samples. ?? 2009 The Society for Applied Microbiology.

Rates of, and risk factors for, severe infections in patients with systemic autoimmune diseases receiving biological agents off-label

PubMed Central

2011-01-01

Introduction The purpose of this observational study was to analyze the rates, characteristics and associated risk factors of severe infections in patients with systemic autoimmune diseases (SAD) who were treated off-label with biological agents in daily practice. Methods The BIOGEAS registry is an ongoing Spanish prospective cohort study investigating the long-term safety and efficacy of the off-label use of biological agents in adult patients with severe, refractory SAD. Severe infections were defined according to previous studies as those that required intravenous treatment or that led to hospitalization or death. Patients contributed person-years of follow-up for the period in which they were treated with biological agents. Results A total of 344 patients with SAD treated with biological agents off-label were included in the Registry until July 2010. The first biological therapies included rituximab in 264 (77%) patients, infliximab in 37 (11%), etanercept in 21 (6%), adalimumab in 19 (5%), and 'other' agents in 3 (1%). Forty-five severe infections occurred in 37 patients after a mean follow-up of 26.76 months. These infections resulted in four deaths. The crude rate of severe infections was 90.9 events/1000 person-years (112.5 for rituximab, 76.9 for infliximab, 66.9 for adalimumab and 30.5 for etanercept respectively). In patients treated with more than two courses of rituximab, the crude rate of severe infection was 226.4 events/1000 person-years. A pathogen was identified in 24 (53%) severe infections. The most common sites of severe infection were the lower respiratory tract (39%), bacteremia/sepsis (20%) and the urinary tract (16%). There were no significant differences relating to gender, SAD, agent, other previous therapies, number of previous immunosuppressive agents received or other therapies administered concomitantly. Cox regression analysis showed that age (P = 0.015) was independently associated with an increased risk of severe infection. Survival curves showed a lower survival rate in patients with severe infections (log-rank and Breslow tests < 0.001). Conclusions The rates of severe infections in SAD patients with severe, refractory disease treated depended on the biological agent used, with the highest rates being observed for rituximab and the lowest for etanercept. The rate of infection was especially high in patients receiving three or more courses of rituximab. In patients with severe infections, survival was significantly reduced. Older age was the only significant predictive factor of severe infection. PMID:21745378

Corylin increases the sensitivity of hepatocellular carcinoma cells to chemotherapy through long noncoding RNA RAD51-AS1-mediated inhibition of DNA repair.

PubMed

Chen, Chin-Chuan; Chen, Chi-Yuan; Ueng, Shir-Hwa; Hsueh, Chuen; Yeh, Chau-Ting; Ho, Jar-Yi; Chou, Li-Fang; Wang, Tong-Hong

2018-05-10

Corylin, a biologically active agent extracted from Psoralea corylifolia L. (Fabaceae), promotes bone differentiation and inhibits inflammation. Currently, few reports have addressed the biological functions that are regulated by corylin, and to date, no studies have investigated its antitumor activity. In this study, we used cell functional assays to analyze the antitumor activity of corylin in hepatocellular carcinoma (HCC). Furthermore, whole-transcriptome assays were performed to identify the downstream genes that were regulated by corylin, and gain-of-function and loss-of-function experiments were conducted to examine the regulatory roles of the above genes. We found that corylin significantly inhibited the proliferation, migration, and invasion of HCC cells and increased the toxic effects of chemotherapeutic agents against HCC cells. These properties were due to the induction of a long noncoding RNA, RAD51-AS1, which bound to RAD51 mRNA, thereby inhibiting RAD51 protein expression, thus inhibiting the DNA damage repair ability of HCC cells. Animal experiments also showed that a combination treatment with corylin significantly increased the inhibitory effects of the chemotherapeutic agent etoposide (VP16) on tumor growth. These findings indicate that corylin has strong potential as an adjuvant drug in HCC treatment and that corylin can strengthen the therapeutic efficacy of chemotherapy and radiotherapy.

Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment.

PubMed

Rizzo, Daniela; Ruggiero, Antonio; Martini, Maurizio; Rizzo, Valentina; Maurizi, Palma; Riccardi, Riccardo

2015-01-01

High-grade gliomas are the main cause of death in children with brain tumours. Despite recent advances in cancer therapy, their prognosis remains poor and the treatment is still challenging. To date, surgery followed by radiotherapy and temozolomide is the standard therapy. However, increasing knowledge of glioma biology is starting to impact drug development towards targeted therapies. The identification of agents directed against molecular targets aims at going beyond the traditional therapeutic approach in order to develop a personalized therapy and improve the outcome of pediatric high-grade gliomas. In this paper, we critically review the literature regarding the genetic abnormalities implicated in the pathogenesis of pediatric malignant gliomas and the current development of molecularly targeted therapies. In particular, we analyse the impact of molecular biology on the prognosis and treatment of pediatric high-grade glioma, comparing it to that of adult gliomas.

Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment

PubMed Central

Rizzo, Daniela; Ruggiero, Antonio; Martini, Maurizio; Rizzo, Valentina; Maurizi, Palma; Riccardi, Riccardo

2015-01-01

High-grade gliomas are the main cause of death in children with brain tumours. Despite recent advances in cancer therapy, their prognosis remains poor and the treatment is still challenging. To date, surgery followed by radiotherapy and temozolomide is the standard therapy. However, increasing knowledge of glioma biology is starting to impact drug development towards targeted therapies. The identification of agents directed against molecular targets aims at going beyond the traditional therapeutic approach in order to develop a personalized therapy and improve the outcome of pediatric high-grade gliomas. In this paper, we critically review the literature regarding the genetic abnormalities implicated in the pathogenesis of pediatric malignant gliomas and the current development of molecularly targeted therapies. In particular, we analyse the impact of molecular biology on the prognosis and treatment of pediatric high-grade glioma, comparing it to that of adult gliomas. PMID:26448930

Non-target effects of an introduced biological control agent on deer mouse ecology.

PubMed

Pearson, D E; McKelvey, K S; Ruggiero, L F

2000-01-01

Release of exotic insects as biological control agents is a common approach to controlling exotic plants. Though controversy has ensued regarding the deleterious direct effects of biological control agents to non-target species, few have examined the indirect effects of a "well-behaved" biological control agent on native fauna. We studied a grassland in west-central Montana infested with spotted knapweed (Centaurea maculosa) to examine the effects of knapweed invasion and two gall flybiological control agents (Urophora affinis and U. quadrifasciata) on the native deer mouse (Peromyscus maniculatus). Stomach-content analysis revealed that Urophora were the primary food item in Peromyscus diets for most of the year and made up 84-86% of the winter diet. Stomach contents indicated that wild-caught mice consumed on average up to 247 Urophora larvae mouse -1 day -1 , while feeding trials revealed that deer mice could depredate nearly 5 times as many larvae under laboratory conditions. In feeding trials, deer mice selected knapweed seedheads with greater numbers of galls while avoiding uninfested seedheads. When Urophora larvae were present in knapweed seedheads, deer mice selected microhabitats with moderately high (31-45% cover) and high knapweed infestation (≥46% cover). After Urophora emerged and larvae were unavailable to Peromyscus, mice reversed habitat selection to favor sites dominated by native-prairie with low knapweed infestation (0-15%). Establishment of the biological control agent, Urophora spp., has altered deer mouse diets and habitat selection by effecting changes in foraging strategies. Deer mice and other predators may reduce Urophora populations below a threshold necessary to effectively control spotted knapweed.

New oxirane derivatives of 1,4-naphthoquinones and their evaluation against T. cruzi epimastigote forms.

PubMed

Carneiro, Paula F; do Nascimento, Samara B; Pinto, Antonio V; Pinto, Maria do Carmo F R; Lechuga, Guilherme C; Santos, Dilvani O; dos Santos Júnior, Helvécio M; Resende, Jackson A L C; Bourguignon, Saulo C; Ferreira, Vitor F

2012-08-15

New oxirane derivatives were synthesized using six naphthoquinones as the starting materials. Our biological results showed that these oxiranes acted as trypanocidal agents against Trypanosoma cruzi with minimal cytotoxicity in the VERO cell line compared to naphthoquinones. In particular, oxirane derivative 14 showed low cytotoxicity in a mammalian cell line and exhibited better activity against epimastigote forms of T.cruzi than the current drug used to treat Chagas disease, benznidazole. Copyright © 2012 Elsevier Ltd. All rights reserved.

The role of IL-12/23 in T cell-related chronic inflammation: implications of immunodeficiency and therapeutic blockade.

PubMed

Schurich, Anna; Raine, Charles; Morris, Vanessa; Ciurtin, Coziana

2018-02-01

In this review we discuss the divergent role of two closely related cytokines, IL-12 and IL-23, in shaping immune responses. In light of current therapeutic developments using biologic agents to block these two pathways, a better understanding of the immunological function of these cytokines is pivotal. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

From Here to Autonomicity: Self-Managing Agents and the Biological Metaphors that Inspire Them

NASA Technical Reports Server (NTRS)

Sterritt, Roy; Hinchey, Mike

2005-01-01

We seek inspiration for self-managing systems from (obviously, pre-existing) biological mechanisms. Autonomic Computing (AC), a self-managing systems initiative based on the biological metaphor of the autonomic nervous system, is increasingly gaining momentum as the way forward for integrating and designing reliable systems, while agent technologies have been identified as a key enabler for engineering autonomicity in systems. This paper looks at other biological metaphors such as reflex and healing, heart- beat monitors, pulse monitors and apoptosis for assisting in the realization of autonomicity.

Plasma flame for mass purification of contaminated air with chemical and biological warfare agents

NASA Astrophysics Data System (ADS)

Uhm, Han S.; Shin, Dong H.; Hong, Yong C.

2006-09-01

An elimination of airborne simulated chemical and biological warfare agents was carried out by making use of a plasma flame made of atmospheric plasma and a fuel-burning flame, which can purify the interior air of a large volume in isolated spaces such as buildings, public transportation systems, and military vehicles. The plasma flame generator consists of a microwave plasma torch connected in series to a fuel injector and a reaction chamber. For example, a reaction chamber, with the dimensions of a 22cm diameter and 30cm length, purifies an airflow rate of 5000lpm contaminated with toluene (the simulated chemical agent) and soot from a diesel engine (the simulated aerosol for biological agents). Large volumes of purification by the plasma flame will free mankind from the threat of airborne warfare agents. The plasma flame may also effectively purify air that is contaminated with volatile organic compounds, in addition to eliminating soot from diesel engines as an environmental application.

Reactive decontamination formulation

DOEpatents

Giletto, Anthony [College Station, TX; White, William [College Station, TX; Cisar, Alan J [Cypress, TX; Hitchens, G Duncan [Bryan, TX; Fyffe, James [Bryan, TX

2003-05-27

The present invention provides a universal decontamination formulation and method for detoxifying chemical warfare agents (CWA's) and biological warfare agents (BWA's) without producing any toxic by-products, as well as, decontaminating surfaces that have come into contact with these agents. The formulation includes a sorbent material or gel, a peroxide source, a peroxide activator, and a compound containing a mixture of KHSO.sub.5, KHSO.sub.4 and K.sub.2 SO.sub.4. The formulation is self-decontaminating and once dried can easily be wiped from the surface being decontaminated. A method for decontaminating a surface exposed to chemical or biological agents is also disclosed.

Performance of Traditional and Molecular Methods for Detecting Biological Agents in Drinking Water

EPA Science Inventory

USGS Report - To reduce the impact from a possible bioterrorist attack on drinking-water supplies, analytical methods are needed to rapidly detect the presence of biological agents in water. To this end, 13 drinking-water samples were collected at 9 water-treatment plants in Ohio...

Radiobiological aspects of high altitude flight : relative biological effectiveness of fast neutrons in suppressing immune capacity to an infective agent.

DOT National Transportation Integrated Search

1978-02-01

We investigated the relative biological effectiveness (RBE) of fast neutrons compared with X-rays in impeding development of immunity to an infective agent, the intestinal cestode Hymenolepis nana. Mice were irradiated with neutrons or X-rays and 2 d...

75 FR 28232 - Availability of an Environmental Assessment for a Biological Control Agent for Hemlock Woolly...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-20

... conditions. Existing HWA management options include chemical control and silvicultural control, which, in...] Availability of an Environmental Assessment for a Biological Control Agent for Hemlock Woolly Adelgid AGENCY... environmental assessment relative to the control of hemlock woolly adelgid (Adelges tsugae). The environmental...

Host plant oviposition preference of Ceratapion basicorne (Coleoptera:Apionidae), a potential biological control agent of yellow starthistle

USDA-ARS?s Scientific Manuscript database

Ceratapion basicorne (Coleoptera: Apionidae) is a weevil native to Europe and western Asia that is being evaluated as a prospective classical biological control agent of Centaurea solstitialis (yellow starthistle) in the United States. Choice oviposition experiments were conducted under laboratory ...

Leveraging culture collections for the discovery and development of microbial biological control agents

USDA-ARS?s Scientific Manuscript database

The incorporation of living microbial biological control agents into integrated pest management programs is highly desirable because it reduces the use of chemical insecticides harmful to livestock, humans and the environment. In addition, it provides an alternative means to combat resistance to che...

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...

Establishment of the armored scale, Rhizaspidiotus donacis, a biological control agent of Arundo donax

USDA-ARS?s Scientific Manuscript database

The armored scale biological control agent, Rhizaspidiotus donacis (Leonardi) (Hemiptera; Diaspididae) has established populations on the invasive weed, Arundo donax L. (Poaceae; Arundinoideae) in Del Rio (Val Verde, Co.) and in field plots at the USDA-APHIS-PPQ-Moore Airbase, Edinburg (Hidalgo Co.)...

Integrated Biological Warfare Technology Platform (IBWTP). Intelligent Software Supporting Situation Awareness, Response, and Operations

DTIC Science & Technology

2007-01-01

15 4.2.3. Users of Systems for Combating Biological Warfare ................................ 16 4.2.4...21 4.3.1. Existing Biosurveillance Systems .............................................................. 22 4.3.2. Automatic Integration...74 6.4.4. Multi-Agent System Management System (MMS).................................... 75 6.4.5. Agent Glossary

Protease Inhibitors of Parasitic Flukes: Emerging Roles in Parasite Survival and Immune Defence.

PubMed

Ranasinghe, Shiwanthi L; McManus, Donald P

2017-05-01

Protease inhibitors play crucial roles in parasite development and survival, counteracting the potentially damaging immune responses of their vertebrate hosts. However, limited information is currently available on protease inhibitors from schistosomes and food-borne trematodes. Future characterization of these molecules is important not only to expand knowledge on parasitic fluke biology but also to determine whether they represent novel vaccine and/or drug targets. Moreover, protease inhibitors from flukes may represent lead compounds for the development of a new range of therapeutic agents against inflammatory disorders and cancer. This review discusses already identified protease inhibitors of fluke origin, emphasizing their biological function and their possible future development as new intervention targets. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of a neutral embedding resin for optical imaging of fluorescently labeled biological tissue

NASA Astrophysics Data System (ADS)

Zhou, Hongfu; Gang, Yadong; Chen, Shenghua; Wang, Yu; Xiong, Yumiao; Li, Longhui; Yin, Fangfang; Liu, Yue; Liu, Xiuli; Zeng, Shaoqun

2017-10-01

Plastic embedding is widely applied in light microscopy analyses. Previous studies have shown that embedding agents and related techniques can greatly affect the quality of biological tissue embedding and fluorescent imaging. Specifically, it is difficult to preserve endogenous fluorescence using currently available acidic commercial embedding resins and related embedding techniques directly. Here, we developed a neutral embedding resin that improved the green fluorescent protein (GFP), yellow fluorescent protein (YFP), and DsRed fluorescent intensity without adjusting the pH value of monomers or reactivating fluorescence in lye. The embedding resin had a high degree of polymerization, and its fluorescence preservation ratios for GFP, YFP, and DsRed were 126.5%, 155.8%, and 218.4%, respectively.

Chemical and Biological Sensor Standards Study

DTIC Science & Technology

2005-01-01

that is utilized in lieu of Bacillus anthracis in testing biological agent sensors; both are gram positive, spore forming bacteria that have similar...for a given agent dosage is as follows: C = D r 3 f B Tη4π 3 ρ See the table for the variable designation. Using Bacillus anthracis as an example...e.g., genetic similarity, aerosol dynamics, size, shape, etc.) of the agent of interest. For example, Bacillus globigii is a widely used bacterium

Activins in reproductive biology and beyond.

PubMed

Wijayarathna, R; de Kretser, D M

2016-04-01

Activins are members of the pleiotrophic family of the transforming growth factor-beta (TGF-β) superfamily of cytokines, initially isolated for their capacity to induce the release of FSH from pituitary extracts. Subsequent research has demonstrated that activins are involved in multiple biological functions including the control of inflammation, fibrosis, developmental biology and tumourigenesis. This review summarizes the current knowledge on the roles of activin in reproductive and developmental biology. It also discusses interesting advances in the field of modulating the bioactivity of activins as a therapeutic target, which would undoubtedly be beneficial for patients with reproductive pathology. A comprehensive literature search was carried out using PUBMED and Google Scholar databases to identify studies in the English language which have contributed to the advancement of the field of activin biology, since its initial isolation in 1987 until July 2015. 'Activin', 'testis', 'ovary', 'embryonic development' and 'therapeutic targets' were used as the keywords in combination with other search phrases relevant to the topic of activin biology. Activins, which are dimers of inhibin β subunits, act via a classical TGF-β signalling pathway. The bioactivity of activin is regulated by two endogenous inhibitors, inhibin and follistatin. Activin is a major regulator of testicular and ovarian development. In the ovary, activin A promotes oocyte maturation and regulates granulosa cell steroidogenesis. It is also essential in endometrial repair following menstruation, decidualization and maintaining pregnancy. Dysregulation of the activin-follistatin-inhibin system leads to disorders of female reproduction and pregnancy, including polycystic ovary syndrome, ectopic pregnancy, miscarriage, fetal growth restriction, gestational diabetes, pre-eclampsia and pre-term birth. Moreover, a rise in serum activin A, accompanied by elevated FSH, is characteristic of female reproductive aging. In the male, activin A is an autocrine and paracrine modulator of germ cell development and Sertoli cell proliferation. Disruption of normal activin signalling is characteristic of many tumours affecting reproductive organs, including endometrial carcinoma, cervical cancer, testicular and ovarian cancer as well as prostate cancer. While activin A and B aid the progression of many tumours of the reproductive organs, activin C acts as a tumour suppressor. Activins are important in embryonic induction, morphogenesis of branched glandular organs, development of limbs and nervous system, craniofacial and dental development and morphogenesis of the Wolffian duct. The field of activin biology has advanced considerably since its initial discovery as an FSH stimulating agent. Now, activin is well known as a growth factor and cytokine that regulates many aspects of reproductive biology, developmental biology and also inflammation and immunological mechanisms. Current research provides evidence for novel roles of activins in maintaining the structure and function of reproductive and other organ systems. The fact that activin A is elevated both locally as well as systemically in major disorders of the reproductive system makes it an important biomarker. Given the established role of activin A as a pro-inflammatory and pro-fibrotic agent, studies of its involvement in disorders of reproduction resulting from these processes should be examined. Follistatin, as a key regulator of the biological actions of activin, should be evaluated as a therapeutic agent in conditions where activin A overexpression is established as a contributing factor. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Antidrug Antibody Formation in Oncology: Clinical Relevance and Challenges.

PubMed

van Brummelen, Emilie M J; Ros, Willeke; Wolbink, Gertjan; Beijnen, Jos H; Schellens, Jan H M

2016-10-01

: In oncology, an increasing number of targeted anticancer agents and immunotherapies are of biological origin. These biological drugs may trigger immune responses that lead to the formation of antidrug antibodies (ADAs). ADAs are directed against immunogenic parts of the drug and may affect efficacy and safety. In other medical fields, such as rheumatology and hematology, the relevance of ADA formation is well established. However, the relevance of ADAs in oncology is just starting to be recognized, and literature on this topic is scarce. In an attempt to fill this gap in the literature, we provide an up-to-date status of ADA formation in oncology. In this focused review, data on ADAs was extracted from 81 clinical trials with biological anticancer agents. We found that most biological anticancer drugs in these trials are immunogenic and induce ADAs (63%). However, it is difficult to establish the clinical relevance of these ADAs. In order to determine this relevance, the possible effects of ADAs on pharmacokinetics, efficacy, and safety parameters need to be investigated. Our data show that this was done in fewer than 50% of the trials. In addition, we describe the incidence and consequences of ADAs for registered agents. We highlight the challenges in ADA detection and argue for the importance of validating, standardizing, and describing well the used assays. Finally, we discuss prevention strategies such as immunosuppression and regimen adaptations. We encourage the launch of clinical trials that explore these strategies in oncology. Because of the increasing use of biologicals in oncology, many patients are at risk of developing antidrug antibodies (ADAs) during therapy. Although clinical consequences are uncertain, ADAs may affect pharmacokinetics, patient safety, and treatment efficacy. ADA detection and reporting is currently highly inconsistent, which makes it difficult to evaluate the clinical consequences. Standardized reporting of ADA investigations in the context of the aforementioned parameters is critical to understanding the relevance of ADA formation for each drug. Furthermore, the development of trials that specifically aim to investigate clinical prevention strategies in oncology is needed. ©AlphaMed Press.

Pathogenesis of Lassa Fever

PubMed Central

Yun, Nadezhda E.; Walker, David H.

2012-01-01

Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host’s immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents. PMID:23202452

Long-Term Efficacy and Toxicity of Cholinesterase Inhibitors in the Treatment of Alzheimer Disease

PubMed Central

Hogan, David B

2014-01-01

Though the symptoms of Alzheimer disease go on for years, the phase 3 trials of the cholinesterase inhibitors (ChEIs), the current mainstay of symptomatic pharmacotherapy for this condition, were typically of only 3- to 6-months’ duration. We have limited data on long-term (that is, a year or more) therapy with these agents. In this review, we explore the available information on the biological and clinical effects of long-term ChEI therapy, what happens when these agents are discontinued, and examine what others have recommended. An individualized approach to deciding on whether to carry on with a ChEI should be taken. If continued, treatment goals should be clarified and patients monitored over time, for both drug-related benefits and adverse effects. PMID:25702360

Trypanosoma cruzi, the Causal Agent of Chagas Disease: Boundaries between Wild and Domestic Cycles in Venezuela.

PubMed

Herrera, Leidi

2014-01-01

Trypanosoma cruzi the etiological agent of American Trypanosomiasis or Chagas disease (ChD) is transmitted by triatomines vectors between mammals including man. T. cruzi has existed for circa 150 Ma in the Americas and nearly 10 million people are currently infected. The overlap between wild and domestic ecotopes where T. cruzi circulates is increasing. Host-parasite interactions have been determined by infection patterns in these cycles, all under natural or laboratorial conditions. This mini-review describes specific parasite niches, such as plant communities or biological corridors between domestic and wild landscapes, in order to help identify risk factors for ChD and define the boundaries between wild and domestic transmission cycles, with an emphasis on research undertaken in Venezuela.

Chemesthesis and the Chemical Senses as Components of a “Chemofensor Complex”

PubMed Central

2012-01-01

An important function of the chemical senses is to warn against dangerous biological and chemical agents in the environment. The discovery in recent years of “taste” receptor cells outside the oral cavity that appear to have protective functions has raised new questions about the nature and scope of the chemical senses in general and of chemesthesis in particular. The present paper briefly reviews these findings within the context of what is currently known about the body's chemically sensitive protective mechanisms, including nonsensory processes that help to expel or neutralize threatening agents once they have been encountered. It is proposed that this array of defense mechanisms constitutes a “chemofensor complex” in which chemesthesis is the most ubiquitous, functionally diverse, and interactive chemosensory component. PMID:22210122

Advancing cancer drug discovery towards more agile development of targeted combination therapies.

PubMed

Carragher, Neil O; Unciti-Broceta, Asier; Cameron, David A

2012-01-01

Current drug-discovery strategies are typically 'target-centric' and are based upon high-throughput screening of large chemical libraries against nominated targets and a selection of lead compounds with optimized 'on-target' potency and selectivity profiles. However, high attrition of targeted agents in clinical development suggest that combinations of targeted agents will be most effective in treating solid tumors if the biological networks that permit cancer cells to subvert monotherapies are identified and retargeted. Conventional drug-discovery and development strategies are suboptimal for the rational design and development of novel drug combinations. In this article, we highlight a series of emerging technologies supporting a less reductionist, more agile, drug-discovery and development approach for the rational design, validation, prioritization and clinical development of novel drug combinations.

Advantages of paramagnetic CEST complexes having slow-to-intermediate water exchange properties as responsive MRI agents

PubMed Central

Soesbe, Todd C.; Wu, Yunkou; Sherry, A. Dean

2012-01-01

Paramagnetic saturation transfer chemical exchange (PARACEST) complexes are exogenous contrast agents that have great potential to further extend the functional and molecular imaging capabilities of magnetic resonance. Due to the presence of a central paramagnetic lanthanide ion (Ln3+ ≠ La3+, Gd3+, Lu3+) within the chelate, the resonance frequencies of protons and water molecules bound to the PARACEST agent are shifted far away from the bulk water frequency. This large chemical shift combined with an extreme sensitivity to the chemical exchange rate make PARACEST agents ideally suited for reporting significant biological metrics such as temperature, pH, and the presence of metabolites. Also, the ability to turn PARACEST agents “off” and “on” using a frequency selective saturation pulse gives them a distinct advantage over Gd3+-based contrast agents. A current challenge for PARACEST research is translating the promising in vitro results into in vivo systems. This short review article first describes the basic theory behind PARACEST contrast agents, their benefits over other contrast agents, and their applications to magnetic resonance imaging. It then describes some of the recent PARACEST research results. Specifically, pH measurements using water molecule exchange rate modulation, T2-exchange contrast due to water molecule exchange, the use of ultra-short echo times (TE<10 μs) to overcome T2-exchange line-broadening, and the potential application of T2-exchange as a new contrast mechanism for magnetic resonance imaging. PMID:23055299

Functional Agents to Biologically Control Deoxynivalenol Contamination in Cereal Grains

PubMed Central

Tian, Ye; Tan, Yanglan; Liu, Na; Liao, Yucai; Sun, Changpo; Wang, Shuangxia; Wu, Aibo

2016-01-01

Mycotoxins, as microbial secondary metabolites, frequently contaminate cereal grains and pose a serious threat to human and animal health around the globe. Deoxynivalenol (DON), a commonly detected Fusarium mycotoxin, has drawn utmost attention due to high exposure levels and contamination frequency in the food chain. Biological control is emerging as a promising technology for the management of DON contamination. Functional biological control agents (BCAs), which include antagonistic microbes, natural fungicides derived from plants and detoxification enzymes, can be used to control DON contamination at different stages of grain production. In this review, studies regarding different biological agents for DON control in recent years are summarized for the first time. Furthermore, this article highlights the significance of BCAs for controlling DON contamination, as well as the need for more practical and efficient BCAs concerning food safety. PMID:27064760

[Biological agents].

PubMed

Amano, Koichi

2009-03-01

There are two types of biological agents for the treatment of rheumatoid arthritis (RA); monoclonal antibodies and recombinant proteins. Among the latter, etanercept, a recombinant fusion protein of soluble TNF receptor and IgG was approved in 2005 in Japan. The post-marketing surveillance of 13,894 RA patients revealed the efficacy and safety profiles of etanercept in the Japanese population, as well as overseas studies. Abatacept, a recombinant fusion protein of CTLA4 and IgG, is another biological agent for RA. Two clinical trials disclosed the efficacy of abatacept for difficult-to-treat patients: the AIM for MTX-resistant cases and the ATTAIN for patients who are resistant to anti-TNF. The ATTEST trial suggested abatacept might have more acceptable safety profile than infliximab. These biologics are also promising for the treatment of RA for not only relieving clinical symptoms and signs but retarding structural damage.

Disinfection of biological agents in the field using a mobile ...

EPA Pesticide Factsheets

Report The Army’s Net Zero Initiative is an energy-conservation program that focuses on energy as well as water and waste usage procedures. All Net Zero projects are geared toward helping the military installation or community become more sustainable and resilient, with an emphasis on taking a systems approach. Net Zero projects must advance the state of the science and are focused on three general topic areas: water, energy, and waste, and the nexuses among them. This project examined the inactivation and/or removal of biological contaminants in dirty wash water using a portable ozone-UV AOP process. The strain of E. coli used in these experiments is not a biological warfare agent, but acts as a surrogate for certain of the vegetative biological agents such as the enterohemorrhagic strain designated E. coli 0157:H7.

Shaping the Future of Nanomedicine: Anisotropy in Polymeric Nanoparticle Design

PubMed Central

Meyer, Randall A.; Green, Jordan J.

2015-01-01

Nanofabrication and biomedical applications of polymeric nanoparticles have become important areas of research. Biocompatible polymeric nanoparticles have been investigated for their use as delivery vehicles for therapeutic and diagnostic agents. Although polymeric nanoconstructs have traditionally been fabricated as isotropic spheres, anisotropic, non-spherical nanoparticles have gained interest in the biomaterials community due to their unique interactions with biological systems. Polymeric nanoparticles with different forms of anisotropy have been manufactured utilizing a variety of novel methods in recent years. In addition, they have enhanced physical, chemical, and biological properties compared to spherical nanoparticles, including increased targeting avidity and decreased non-specific in vivo clearance. With these desirable properties, anisotropic nanoparticles have been successfully utilized in many biomedical settings and have performed superiorly to analogous spherical nanoparticles. We summarize the current state-of-the-art fabrication methods for anisotropic polymeric nanoparticles including top-down, bottom-up, and microfluidic design approaches. We also summarize the current and potential future applications of these nanoparticles, including drug delivery, biological targeting, immunoengineering, and tissue engineering. Ongoing research into the properties and utility of anisotropic polymeric nanoparticles will prove critical to realizing their potential in nanomedicine. PMID:25981390

Management of lower-risk myelodysplastic syndromes without del5q: current approach and future trends.

PubMed

Stahl, Maximilian; Zeidan, Amer M

2017-04-01

Myelodysplastic syndromes (MDS) are characterized by progressive bone marrow failure manifesting as blood cytopenia and a variable risk of progression into acute myeloid leukemia. MDS is heterogeneous in biology and clinical behavior. MDS are generally divided into lower-risk (LR) and higher-risk (HR) MDS. Goals of care in HR-MDS focus on changing the natural history of the disease, whereas in LR-MDS symptom control and quality of life are the main goals. Areas covered: We review the epidemiology, tools of risk assessment, and the available therapeutic modalities for LR-MDS. We discuss the use of erythropoiesis stimulating agents (ESAs), immunosuppressive therapy (IST), lenalidomide and the hypomethylating agents (HMAs). We also discuss the predictors of response, combination treatment modalities, and management of iron overload. Lastly, we overview the most promising investigational agents for LR-MDS. Expert commentary: It remains unclear how to best incorporate a wealth of new genetic and epigenetic prognostic markers into risk assessment tools especially for LR-MDS patients. Only a subset of patients respond to current treatment modalities and most responders eventually lose their response. Once standard therapeutic options fail, management becomes more challenging. Combination-based approaches have been largely unsuccessful. Among the most promising investigational are the TPO agonists, TGF- β pathway inhibitors, telomerase inhibitors, and the splicing modifiers.

Biotherapies in Behçet's disease.

PubMed

Comarmond, Cloé; Wechsler, Bertrand; Bodaghi, Bahram; Cacoub, Patrice; Saadoun, David

2014-07-01

Behçet's disease (BD) is a systemic large-vessel vasculitis characterized by a wide clinical spectrum including recurrent oral and genital ulcerations, uveitis, vascular, neurological, articular, renal and gastrointestinal manifestations. Therapeutic management of BD depends on the clinical presentation and organ involved. Although colchicine, nonsteroidal antiinflammatory agents and topical treatments with corticosteroids are often sufficient for mucocutaneous and joint involvements, more aggressive approach with immunosuppressive agents is warranted for severe manifestations such as posterior uveitis, retinal vasculitis, vascular, and neurological and gastrointestinal involvements. However, some patients still have refractory disease, relapse, sight threatening eye disease, or irreversible organ damage. Recent improvements in the understanding of the pathogenic mechanisms have led to the identification of potential targets and future biological therapies for BD. In contrast to current non-specific immunosuppressive agents, the emergence of biotherapies provides the possibility of interfering with specific pathogenic pathways. Novel targeted biotherapies might be used in the future for BD. Copyright © 2014 Elsevier B.V. All rights reserved.

Antifungal therapy for keratomycoses.

PubMed

Ganegoda, Nihal; Rao, Srinivas K

2004-04-01

Keratomycoses have recently emerged as an important cause of ocular morbidity, especially in third-world countries. Available antifungal agents are limited in their efficacy, due to limited penetration into the cornea, the fungistatic nature and the development of drug resistance. Effective usage of the available drugs is hampered by the inefficiency of currently available antibiotic sensitivity tests for fungal organisms. There is also limited knowledge regarding the ideal combination(s) of antifungal agents, including issues of synergism and antagonism. Despite these problems, recent publications indicate encouraging outcomes in the treatment of a large series of fungal keratitis. Advances include better drug formulations, new agents and novel methods of drug delivery into the eye. As our ability to deal with advanced fungal keratitis remains limited, the importance of early diagnosis has been stressed and molecular biological techniques may play an important role in the future. This article summarises the important new advances in these areas in the past 2 years and provides guidelines for the management of these serious corneal infections.

Drug-eluting stents. Insights from invasive imaging technologies.

PubMed

Honda, Yasuhiro

2009-08-01

Drug-eluting stents (DES) represent a revolutionary technology in their unique ability to provide both mechanical and biological solutions simultaneously to the target lesion. As a result of biological effects from the pharmacological agents and interaction of DES components with the arterial wall, considerable differences exist between DES and conventional bare metal stents (BMS), yet some of the old lessons learned in the BMS era remain clinically significant. In this context, contrast angiography provides very little information about in vivo device properties and their biomechanical effects on the arterial wall. In contrast, current catheter-based imaging tools, such as intravascular ultrasound, optical coherence tomography, and intracoronary angioscopy can offer unique insights into DES through direct assessment of the device and treated vessel in the clinical setting. This article reviews these insights from current DES with particular focus on performance and safety characteristics as well as discussing an optimal deployment technique, based upon findings obtained through the use of the invasive imaging technologies.

The functional biology of human milk oligosaccharides.

PubMed

Bode, Lars

2015-11-01

Human milk oligosaccharides (HMOs) are a group of complex sugars that are highly abundant in human milk, but currently not present in infant formula. More than a hundred different HMOs have been identified so far. The amount and composition of HMOs are highly variable between women, and each structurally defined HMO might have a distinct functionality. HMOs are not digested by the infant and serve as metabolic substrates for select microbes, contributing to shape the infant gut microbiome. HMOs act as soluble decoy receptors that block the attachment of viral, bacterial or protozoan parasite pathogens to epithelial cell surface sugars, which may help prevent infectious diseases in the gut and also the respiratory and urinary tracts. HMOs are also antimicrobials that act as bacteriostatic or bacteriocidal agents. In addition, HMOs alter host epithelial and immune cell responses with potential benefits for the neonate. The article reviews current knowledge as well as future challenges and opportunities related to the functional biology of HMOs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Repair and tissue engineering techniques for articular cartilage.

PubMed

Makris, Eleftherios A; Gomoll, Andreas H; Malizos, Konstantinos N; Hu, Jerry C; Athanasiou, Kyriacos A

2015-01-01

Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.

Biological modulation of planetary atmospheres: The early Earth scenario

NASA Technical Reports Server (NTRS)

Schidlowski, M.

1985-01-01

The establishment and subsequent evolution of life on Earth had a profound impact on the chemical regime at the planet's surface and its atmosphere. A thermodynamic gradient was imposed on near-surface environments that served as the driving force for a number on important geochemical transformations. An example is the redox imbalance between the modern atmosphere and the material of the Earth's crust. Current photochemical models predict extremely low partial pressures of oxygen in the Earth's prebiological atmosphere. There is widespread consensus that any large-scale oxygenation of the primitive atmosphere was contingent on the advent of biological (autotrophic) carbon fixation. It is suggested that photoautotrophy existed both as a biochemical process and as a geochemical agent since at least 3.8 Ga ago. Combining the stoichiometry of the photosynthesis reaction with a carbon isotope mass balance and current concepts for the evolution of the stationary sedimentary mass as a funion of time, it is possible to quantify, the accumulation of oxygen and its photosynthetic oxidation equivalents through Earth history.

Comparing Effects of Biologic Agents in Treating Patients with Rheumatoid Arthritis: A Multiple Treatment Comparison Regression Analysis.

PubMed

Tvete, Ingunn Fride; Natvig, Bent; Gåsemyr, Jørund; Meland, Nils; Røine, Marianne; Klemp, Marianne

2015-01-01

Rheumatoid arthritis patients have been treated with disease modifying anti-rheumatic drugs (DMARDs) and the newer biologic drugs. We sought to compare and rank the biologics with respect to efficacy. We performed a literature search identifying 54 publications encompassing 9 biologics. We conducted a multiple treatment comparison regression analysis letting the number experiencing a 50% improvement on the ACR score be dependent upon dose level and disease duration for assessing the comparable relative effect between biologics and placebo or DMARD. The analysis embraced all treatment and comparator arms over all publications. Hence, all measured effects of any biologic agent contributed to the comparison of all biologic agents relative to each other either given alone or combined with DMARD. We found the drug effect to be dependent on dose level, but not on disease duration, and the impact of a high versus low dose level was the same for all drugs (higher doses indicated a higher frequency of ACR50 scores). The ranking of the drugs when given without DMARD was certolizumab (ranked highest), etanercept, tocilizumab/ abatacept and adalimumab. The ranking of the drugs when given with DMARD was certolizumab (ranked highest), tocilizumab, anakinra/rituximab, golimumab/ infliximab/ abatacept, adalimumab/ etanercept [corrected]. Still, all drugs were effective. All biologic agents were effective compared to placebo, with certolizumab the most effective and adalimumab (without DMARD treatment) and adalimumab/ etanercept (combined with DMARD treatment) the least effective. The drugs were in general more effective, except for etanercept, when given together with DMARDs.

Comparing Effects of Biologic Agents in Treating Patients with Rheumatoid Arthritis: A Multiple Treatment Comparison Regression Analysis

PubMed Central

Tvete, Ingunn Fride; Natvig, Bent; Gåsemyr, Jørund; Meland, Nils; Røine, Marianne; Klemp, Marianne

2015-01-01

Rheumatoid arthritis patients have been treated with disease modifying anti-rheumatic drugs (DMARDs) and the newer biologic drugs. We sought to compare and rank the biologics with respect to efficacy. We performed a literature search identifying 54 publications encompassing 9 biologics. We conducted a multiple treatment comparison regression analysis letting the number experiencing a 50% improvement on the ACR score be dependent upon dose level and disease duration for assessing the comparable relative effect between biologics and placebo or DMARD. The analysis embraced all treatment and comparator arms over all publications. Hence, all measured effects of any biologic agent contributed to the comparison of all biologic agents relative to each other either given alone or combined with DMARD. We found the drug effect to be dependent on dose level, but not on disease duration, and the impact of a high versus low dose level was the same for all drugs (higher doses indicated a higher frequency of ACR50 scores). The ranking of the drugs when given without DMARD was certolizumab (ranked highest), etanercept, tocilizumab/ abatacept and adalimumab. The ranking of the drugs when given with DMARD was certolizumab (ranked highest), tocilizumab, anakinra, rituximab, golimumab/ infliximab/ abatacept, adalimumab/ etanercept. Still, all drugs were effective. All biologic agents were effective compared to placebo, with certolizumab the most effective and adalimumab (without DMARD treatment) and adalimumab/ etanercept (combined with DMARD treatment) the least effective. The drugs were in general more effective, except for etanercept, when given together with DMARDs. PMID:26356639

Nuclear, biological and chemical warfare. Part I: Medical aspects of nuclear warfare.

PubMed

Kasthuri, A S; Pradhan, A B; Dham, S K; Bhalla, I P; Paul, J S

1990-04-01

Casualties in earlier wars were due much more to diseases than to weapons. Mention has been made in history of the use of biological agents in warfare, to deny the enemy food and water and to cause disease. In the first world war chemical agents were used to cause mass casualties. Nuclear weapons were introduced in the second world war. Several countries are now involved in developing nuclear, biological and chemical weapon systems, for the mass annihilation of human beings, animals and plants, and to destroy the economy of their enemies. Recently, natural calamities and accidents in nuclear, chemical and biological laboratories and industries have caused mass instantaneous deaths in civilian population. The effects of future wars will not be restricted to uniformed persons. It is time that physicians become aware of the destructive potential of these weapons. Awareness, immediate protective measures and first aid will save a large number of persons. This series of articles will outline the medical aspects of nuclear, biological and chemical weapon systems in three parts. Part I will deal with the biological effects of a nuclear explosion. The short and long term effects due to blast, heat and associated radiation are highlighted. In Part II, the role of biological agents which cause commoner or new disease patterns is mentioned. Some of the accidents from biological warfare laboratories are a testimony to its potential deleterious effects. Part III deals with medical aspects of chemical warfare agents, which in view of their mass effects can overwhelm the existing medical resources, both civilian and military.(ABSTRACT TRUNCATED AT 250 WORDS)

Responding to biological incidents--what are the current issues in remediation of the contaminated environment?

PubMed

Pottage, T; Goode, E; Wyke, S; Bennett, A M

2014-11-01

Since 2000 there have been a number of biological incidents resulting in environmental contamination with Bacillus anthracis, the causative agent of anthrax. These incidents include the US anthrax attacks in 2001, the US and UK drumming incidents in 2006-2008 and more recently, anthrax contamination of heroin in 2009/2010 and 2012/2013. Remediation techniques used to return environments to normal have varied between incidents, with different decontamination technologies being employed. Many factors need to be considered before a remediation strategy or recovery option can be implemented, including; cost, time (length of application), public perception of risk, and sampling strategies (and results) to name a few. These incidents have demonstrated that consolidated guidance for remediating biologically contaminated environments in the aftermath of a biological incident was required. The UK Recovery Handbook for Biological Incidents (UKRHBI) is a project led by Public Health England (PHE), formerly the Health Protection Agency (HPA) to provide guidance and advice on how to remediate the environment following a biological incident or outbreak of infection, and is expected to be published in 2015. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Weeds of Hawaii’s lands devoted to watershed protection and biodiversity conservation: Role of biological control as the missing piece in an integrated pest management strategy

USGS Publications Warehouse

Medeiros, Arthur C.; Loope, L.L.

2011-01-01

Despite Hawaii’s reputation as an extinction icon, significant biological resources remain, especially in watersheds, natural areas, and specialized edaphic sites (e.g., lava dry forest, coastal). While direct habitat destruction by humans continues, human-facilitated biological invaders are currently the primary agents of continuing degradation. The ability of invasive plants to have prolific seed production, efficient dispersal systems, and to become established in dense vegetation, complicated by Hawaii’s rugged topography, appears to render mechanical and chemical control as mere holding actions. Costly, ‘environmentally unfriendly’, and often ineffective, strategies using chemical and mechanical control on a large scale, despite the most valiant of efforts, can be viewed simply as attempts to buy time. Without increased levels of safely tested biological control, the seemingly inevitable result is the landscape level transformation of native forests, with potentially catastrophic consequences to cultural, biological, water, and economic resources. Increased levels of effective biological control for certain intractable invasive species appear to comprise a conspicuous ‘missing piece’ in our efforts to protect Hawaiian watersheds and other conservation lands.

Management of Biologic Therapy in Moderate to Severe Psoriasis in Surgical Patients: Data From the Spanish Biobadaderm Registry.

PubMed

Galiano Mejías, S; Carretero, G; Ferrandiz, C; Vanaclocha, F; Daudén, E; Gómez-García, F J; Herrera-Ceballos, E; Belinchón-Romero, I; Sánchez-Carazo, J L; López-Estebaranz, J L; Alsina, M; Ferrán, M; Torrado, R; Carrascosa, J M; Rivera, R; Llamas-Velasco, M; Jiménez-Puya, R; Mendiola, Mª V; Ruiz-Genao, D; Descalzo, M A; de la Cueva Dobao, P

We now have considerable experience in the use of biologic agents to treat psoriasis, but doubts about management arise in certain clinical settings. Surgery is one of them. Although treatment guidelines advise that biologics be suspended before major surgery, data about actual clinical practices and associated complications are lacking. We aimed to analyze current practice in the clinical management of these cases. Retrospective study of cases in the Biobadaderm database. We analyzed the management of biologic therapy in patients with psoriasis who underwent surgical procedures. Forty-eight of the 2113 patients registered in Biobadaderm underwent surgery. The largest percentage of procedures (31%) involved skin lesions. Biologic treatment was interrupted in 42% of the cases. No postsurgical complications were significantly related to treatment interruption. Likewise we detected no associations between treatment interruption and other variables, such as sex, age, or duration or severity of psoriasis. Continuity of biologic treatment and the risk of postsurgical complications were not associated in this study, although conclusions are limited by the small sample size. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Adjustable Autonomy Testbed

NASA Technical Reports Server (NTRS)

Malin, Jane T.; Schrenkenghost, Debra K.

2001-01-01

The Adjustable Autonomy Testbed (AAT) is a simulation-based testbed located in the Intelligent Systems Laboratory in the Automation, Robotics and Simulation Division at NASA Johnson Space Center. The purpose of the testbed is to support evaluation and validation of prototypes of adjustable autonomous agent software for control and fault management for complex systems. The AA T project has developed prototype adjustable autonomous agent software and human interfaces for cooperative fault management. This software builds on current autonomous agent technology by altering the architecture, components and interfaces for effective teamwork between autonomous systems and human experts. Autonomous agents include a planner, flexible executive, low level control and deductive model-based fault isolation. Adjustable autonomy is intended to increase the flexibility and effectiveness of fault management with an autonomous system. The test domain for this work is control of advanced life support systems for habitats for planetary exploration. The CONFIG hybrid discrete event simulation environment provides flexible and dynamically reconfigurable models of the behavior of components and fluids in the life support systems. Both discrete event and continuous (discrete time) simulation are supported, and flows and pressures are computed globally. This provides fast dynamic simulations of interacting hardware systems in closed loops that can be reconfigured during operations scenarios, producing complex cascading effects of operations and failures. Current object-oriented model libraries support modeling of fluid systems, and models have been developed of physico-chemical and biological subsystems for processing advanced life support gases. In FY01, water recovery system models will be developed.

Handheld hyperspectral imager for standoff detection of chemical and biological aerosols

NASA Astrophysics Data System (ADS)

Hinnrichs, Michele; Jensen, James O.; McAnally, Gerard

2004-02-01

Pacific Advanced Technology has developed a small hand held imaging spectrometer, Sherlock, for gas leak and aerosol detection and imaging. The system is based on a patent technique that uses diffractive optics and image processing algorithms to detect spectral information about objects in the scene of the camera (IMSS Image Multi-spectral Sensing). This camera has been tested at Dugway Proving Ground and Dstl Porton Down facility looking at Chemical and Biological agent simulants. The camera has been used to investigate surfaces contaminated with chemical agent simulants. In addition to Chemical and Biological detection the camera has been used for environmental monitoring of green house gases and is currently undergoing extensive laboratory and field testing by the Gas Technology Institute, British Petroleum and Shell Oil for applications for gas leak detection and repair. The camera contains an embedded Power PC and a real time image processor for performing image processing algorithms to assist in the detection and identification of gas phase species in real time. In this paper we will present an over view of the technology and show how it has performed for different applications, such as gas leak detection, surface contamination, remote sensing and surveillance applications. In addition a sampling of the results form TRE field testing at Dugway in July of 2002 and Dstl at Porton Down in September of 2002 will be given.