Sample records for emergency drugs agents
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Designing multi-targeted agents: An emerging anticancer drug discovery paradigm.
Fu, Rong-Geng; Sun, Yuan; Sheng, Wen-Bing; Liao, Duan-Fang
2017-08-18
The dominant paradigm in drug discovery is to design ligands with maximum selectivity to act on individual drug targets. With the target-based approach, many new chemical entities have been discovered, developed, and further approved as drugs. However, there are a large number of complex diseases such as cancer that cannot be effectively treated or cured only with one medicine to modulate the biological function of a single target. As simultaneous intervention of two (or multiple) cancer progression relevant targets has shown improved therapeutic efficacy, the innovation of multi-targeted drugs has become a promising and prevailing research topic and numerous multi-targeted anticancer agents are currently at various developmental stages. However, most multi-pharmacophore scaffolds are usually discovered by serendipity or screening, while rational design by combining existing pharmacophore scaffolds remains an enormous challenge. In this review, four types of multi-pharmacophore modes are discussed, and the examples from literature will be used to introduce attractive lead compounds with the capability of simultaneously interfering with different enzyme or signaling pathway of cancer progression, which will reveal the trends and insights to help the design of the next generation multi-targeted anticancer agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
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Emerging Frontiers in Drug Delivery.
Tibbitt, Mark W; Dahlman, James E; Langer, Robert
2016-01-27
Medicine relies on the use of pharmacologically active agents (drugs) to manage and treat disease. However, drugs are not inherently effective; the benefit of a drug is directly related to the manner by which it is administered or delivered. Drug delivery can affect drug pharmacokinetics, absorption, distribution, metabolism, duration of therapeutic effect, excretion, and toxicity. As new therapeutics (e.g., biologics) are being developed, there is an accompanying need for improved chemistries and materials to deliver them to the target site in the body, at a therapeutic concentration, and for the required period of time. In this Perspective, we provide an historical overview of drug delivery and controlled release followed by highlights of four emerging areas in the field of drug delivery: systemic RNA delivery, drug delivery for localized therapy, oral drug delivery systems, and biologic drug delivery systems. In each case, we present the barriers to effective drug delivery as well as chemical and materials advances that are enabling the field to overcome these hurdles for clinical impact.
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Heterocyclic N-Oxides – An Emerging Class of Therapeutic Agents
Mfuh, Adelphe M.; Larionov, Oleg V.
2016-01-01
Heterocyclic N-oxides have emerged as potent compounds with anticancer, antibacterial, antihypertensive, antiparasitic, anti-HIV, anti-inflammatory, herbicidal, neuroprotective, and procognitive activities. The N-oxide motif has been successfully employed in a number of recent drug development projects. This review surveys the emergence of this scaffold in the mainstream medicinal chemistry with a focus on the discovery of the heterocyclic N-oxide drugs, N-oxide-specific mechanisms of action, drug-receptor interactions and synthetic avenues to these compounds. As the first review on this subject that covers the developments since 1950s to date, it is expected that it will inspire wider implementation of the heterocyclic N-oxide motif in the rational design of new medicinal agents. PMID:26087764
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Emerging drugs for sickle cell anemia.
Singh, Priya C; Ballas, Samir K
2015-03-01
The search for effective therapeutic interventions for sickle cell disease (SCD) has been an ongoing endeavor for over 50 years. During this period, only hydroxyurea (HU), which received US FDA approval in February 1998, was identified as an effective therapeutic agent in preventing or ameliorating the frequency of vaso-occlusive crises, acute chest syndrome and the need for blood transfusion. Approximately 25% of patients with sickle cell anemia (SCA), however, do not respond to HU and some patients experiencing serious side effects of this chemotherapeutic agent. Nevertheless, the success of HU opened the sluice gates to identify other effective drug therapies. The objective of this review is to describe the emerging drug therapies for SCA. In this review, we describe the pathophysiology of SCD and provide an in-depth analysis of the current and new pharmacologic therapies in the field. Literature searches involved multiple databases including Medline In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Scopus. SCA is a heterogeneous disease that has caused tremendous global morbidity and early mortality. More effective, individualized and inexpensive therapies are needed. New therapies targeting multiple pathways in its complex pathophysiology are under investigation.
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"Not for human consumption": a review of emerging designer drugs.
Musselman, Megan E; Hampton, Jeremy P
2014-07-01
Synthetic, or "designer" drugs, are created by manipulating the chemical structures of other psychoactive drugs so that the resulting product is structurally similar but not identical to illegal psychoactive drugs. Originally developed in the 1960s as a way to evade existing drug laws, the use of designer drugs has increased dramatically over the past few years. These drugs are deceptively packaged as "research chemicals," "incense," "bath salts," or "plant food," among other names, with labels that may contain warnings such as "not for human consumption" or "not for sale to minors." The clinical effects of most new designer drugs can be described as either hallucinogenic, stimulant, or opioid-like. They may also have a combination of these effects due to designer side-chain substitutions. The easy accessibility and rapid emergence of new designer drugs have created challenges for health care providers when treating patients presenting with acute toxicity from these substances, many of which can produce significant and/or life-threatening adverse effects. Moreover, the health care provider has no way to verify the contents and/or potency of the agent ingested because it can vary between packages and distributors. Therefore, a thorough knowledge of the available designer drugs, common signs and symptoms of toxicity associated with these agents, and potential effective treatment modalities are essential to appropriately manage these patients. © 2014 Pharmacotherapy Publications, Inc.
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Neuropathic Pain and Lung Delivery of Nanoparticulate Drugs: An Emerging Novel Therapeutic Strategy.
Islam, Nazrul; Abbas, Muzaffar; Rahman, Shafiqur
2017-01-01
Neuropathic pain is a chronic neurological disorder affecting millions of people around the world. The currently available pharmacologic agents for the treatment of neuropathic pain have limited efficacy and are associated with dose related unwanted adverse effects. Due to the limited access of drug molecules across blood-brain barrier, a small percentage of drug that is administered systematically, reaches the central nervous system in active form. These therapeutic agents also require daily treatment regimen that is inconvenient and potentially impact patient compliance. Application of nanoparticulate drugs for enhanced delivery system has been explored extensively in the last decades. Pulmonary delivery of nanomedicines for the management of various diseases has become an emerging treatment strategy that ensures the targeted delivery of drugs both for systemic and local effects with low dose and limited adverse effects. To the best of our knowledge, there are no inhaled drug products available on market for the treatment of neuropathic pain. The advantages of delivering therapeutics into deep lungs include non-invasive drug delivery, higher bioavailability with low dose, lower systemic toxicity, and potentially greater blood-brain barrier penetration. This review discusses and highlights the important issues on the application of emerging nanoparticulate lung delivery of drugs for the effective treatment of neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Drug-drug interactions of antifungal agents and implications for patient care.
Gubbins, Paul O; Amsden, Jarrett R
2005-10-01
Drug interactions in the gastrointestinal tract, liver and kidneys result from alterations in pH, ionic complexation, and interference with membrane transport proteins and enzymatic processes involved in intestinal absorption, enteric and hepatic metabolism, renal filtration and excretion. Azole antifungals can be involved in drug interactions at all the sites, by one or more of the above mechanisms. Consequently, azoles interact with a vast array of compounds. Drug-drug interactions associated with amphotericin B formulations are predictable and result from the renal toxicity and electrolyte disturbances associated with these compounds. The echinocandins are unknown cytochrome P450 substrates and to date are relatively devoid of significant drug-drug interactions. This article reviews drug interactions involving antifungal agents that affect other agents and implications for patient care are highlighted.
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Ulipristal acetate as an emergency contraceptive agent.
Martinez, Alan M; Thomas, Michael A
2012-09-01
Emergency contraceptive agents play a crucial role in preventing unplanned pregnancy. These agents and devices have been studied since the 1960s and have had varied results in terms of side effects and efficacy. A new oral tablet for emergency contraception (EC), ulipristal acetate (UPA) , is a selective progesterone receptor modulator and can be used up to 120 h following unprotected intercourse, without an increase in adverse effects or a decrease in efficacy. This article reviews studies that evaluate the pharmacodynamics, pharmacokinetics, clinical efficacy, and safety profile of UPA as an emergency contraceptive agent. UPA, a selective progesterone receptor modulator, is administered as a single 30 mg dose for EC. This agent provides a comparable, if not better, efficacy and side effect profile than seen with levonorgestrel or mifepristone. Because it has both agonistic and antagonistic effects on the progesterone receptor, ongoing clinical trials are documenting UPA's use for patients with endometriosis and as an extended use contraceptive.
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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
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Nelson, Michael E; Bryant, Sean M; Aks, Steven E
2014-02-01
Many new emerging drugs of abuse are marketed as legal highs despite being labeled "not for human consumption" to avoid regulation. The availability of these substances over the Internet and in "head shops" has lead to a multitude of emergency department visits with severe complications including deaths worldwide. Despite recent media attention, many of the newer drugs of abuse are still largely unknown by health care providers. Slight alterations of the basic chemical structure of substances create an entirely new drug no longer regulated by current laws and an ever-changing landscape of clinical effects. The purity of each substance with exact pharmacokinetic and toxicity profiles is largely unknown. Many of these substances can be grouped by the class of drug and includes synthetic cannabinoids, synthetic cathinones, phenethylamines, as well as piperazine derivatives. Resultant effects generally include psychoactive and sympathomimetic-like symptoms. Additionally, prescription medications, performance enhancing medications, and herbal supplements are also becoming more commonly abused. Most new drugs of abuse have no specific antidote and management largely involves symptom based goal directed supportive care with benzodiazepines as a useful adjunct. This paper will focus on the history, epidemiology, clinical effects, laboratory analysis, and management strategy for many of these emerging drugs of abuse. Copyright © 2014 Elsevier Inc. All rights reserved.
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Drug abuse: newly-emerging drugs and trends.
Davis, Gregory G
2012-09-01
Drug abusers have access to new, more potent compounds that evade existing laws by virtue of their novel chemical structures. These drugs are available for purchase at stores and over the internet. The drugs are not illegal because they are so new that laws have not yet been passed to ban them. These drugs are leading to emergency department visits for cardiovascular, neurologic, and psychiatric complications. Standard drug screens are not designed to detect these new substances. The internet provides access to drugs for substance abusers but also provides physicians speed of access to the habits of substance abusers.
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A Multi Agent Based Approach for Prehospital Emergency Management.
Safdari, Reza; Shoshtarian Malak, Jaleh; Mohammadzadeh, Niloofar; Danesh Shahraki, Azimeh
2017-07-01
To demonstrate an architecture to automate the prehospital emergency process to categorize the specialized care according to the situation at the right time for reducing the patient mortality and morbidity. Prehospital emergency process were analyzed using existing prehospital management systems, frameworks and the extracted process were modeled using sequence diagram in Rational Rose software. System main agents were identified and modeled via component diagram, considering the main system actors and by logically dividing business functionalities, finally the conceptual architecture for prehospital emergency management was proposed. The proposed architecture was simulated using Anylogic simulation software. Anylogic Agent Model, State Chart and Process Model were used to model the system. Multi agent systems (MAS) had a great success in distributed, complex and dynamic problem solving environments, and utilizing autonomous agents provides intelligent decision making capabilities. The proposed architecture presents prehospital management operations. The main identified agents are: EMS Center, Ambulance, Traffic Station, Healthcare Provider, Patient, Consultation Center, National Medical Record System and quality of service monitoring agent. In a critical condition like prehospital emergency we are coping with sophisticated processes like ambulance navigation health care provider and service assignment, consultation, recalling patients past medical history through a centralized EHR system and monitoring healthcare quality in a real-time manner. The main advantage of our work has been the multi agent system utilization. Our Future work will include proposed architecture implementation and evaluation of its impact on patient quality care improvement.
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Devarbhavi, Harshad; Andrade, Raúl J
2014-05-01
Antimicrobial agents including antituberculosis (anti-TB) agents are the most common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced liver failure across the world. Better molecular and genetic biomarkers are acutely needed to help identify those at risk of liver injury particularly for those needing antituberculosis therapy. Some antibiotics such as amoxicillin-clavulanate and isoniazid consistently top the lists of agents in retrospective and prospective DILI databases. Central nervous system agents, particularly antiepileptics, account for the second most common class of agents implicated in DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine, phenytoin, and phenobarbital are often associated with hypersensitivity features, whereas newer antiepileptic drugs have a more favorable safety profile. Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of significant liver injury, but their prolific use make them important causes of DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays of minimizing hepatotoxicity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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Development of novel alkylating drugs as anticancer agents.
Izbicka, Elzbieta; Tolcher, Anthony W
2004-06-01
Although conventional alkylating drugs have proven efficacy in the treatment of malignancies, the agents themselves are not selective. Therefore, non-specific alkylation of cellular nucleophilic targets may contribute to many of the observed toxic effects. Novel approaches to drug discovery have resulted in candidate agents that are focused on 'soft alkylation'--alkylators with greater target selectivity. This review highlights the discovery of small molecule drugs that bind to DNA with higher selectivity, act in a unique hypoxic tumor environment, or covalently bind specific protein targets overexpressed in cancer, such as topoisomerase II, glutathione transferase pi1, beta-tubulin and histone deacetylase.
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Emergence of heterogeneity in an agent-based model
Abdullah, Wan Ahmad Tajuddin Wan
2002-01-01
We study an interacting agent model of a game-theoretical economy. The agents play a minority-subsequently-majority game and they learn, using backpropagation networks, to obtain higher payoffs. We study the relevance of heterogeneity to performance, and how heterogeneity emerges.
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Agent-Based Crowd Simulation Considering Emotion Contagion for Emergency Evacuation Problem
Faroqi, H.; Mesgari, M.-S.
2015-12-01
During emergencies, emotions greatly affect human behaviour. For more realistic multi-agent systems in simulations of emergency evacuations, it is important to incorporate emotions and their effects on the agents. In few words, emotional contagion is a process in which a person or group influences the emotions or behavior of another person or group through the conscious or unconscious induction of emotion states and behavioral attitudes. In this study, we simulate an emergency situation in an open square area with three exits considering Adults and Children agents with different behavior. Also, Security agents are considered in order to guide Adults and Children for finding the exits and be calm. Six levels of emotion levels are considered for each agent in different scenarios and situations. The agent-based simulated model initialize with the random scattering of agent populations and then when an alarm occurs, each agent react to the situation based on its and neighbors current circumstances. The main goal of each agent is firstly to find the exit, and then help other agents to find their ways. Numbers of exited agents along with their emotion levels and damaged agents are compared in different scenarios with different initialization in order to evaluate the achieved results of the simulated model. NetLogo 5.2 is used as the multi-agent simulation framework with R language as the developing language.
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AGENT-BASED CROWD SIMULATION CONSIDERING EMOTION CONTAGION FOR EMERGENCY EVACUATION PROBLEM
Directory of Open Access Journals (Sweden)
H. Faroqi
2015-12-01
Full Text Available During emergencies, emotions greatly affect human behaviour. For more realistic multi-agent systems in simulations of emergency evacuations, it is important to incorporate emotions and their effects on the agents. In few words, emotional contagion is a process in which a person or group influences the emotions or behavior of another person or group through the conscious or unconscious induction of emotion states and behavioral attitudes. In this study, we simulate an emergency situation in an open square area with three exits considering Adults and Children agents with different behavior. Also, Security agents are considered in order to guide Adults and Children for finding the exits and be calm. Six levels of emotion levels are considered for each agent in different scenarios and situations. The agent-based simulated model initialize with the random scattering of agent populations and then when an alarm occurs, each agent react to the situation based on its and neighbors current circumstances. The main goal of each agent is firstly to find the exit, and then help other agents to find their ways. Numbers of exited agents along with their emotion levels and damaged agents are compared in different scenarios with different initialization in order to evaluate the achieved results of the simulated model. NetLogo 5.2 is used as the multi-agent simulation framework with R language as the developing language.
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A systematic screen of FDA-approved drugs for inhibitors of biological threat agents.
Directory of Open Access Journals (Sweden)
Peter B Madrid
Full Text Available 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.
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A Systematic Screen of FDA-Approved Drugs for Inhibitors of Biological Threat Agents
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
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Emergence of Extensively Drug Resistant Tuberculosis
Centers for Disease Control (CDC) Podcasts
2007-03-01
Extensively drug-resistant tuberculosis (XDR TB) outbreaks have been reported in South Africa, and strains have been identified on 6 continents. Dr. Peter Cegielski, team leader for drug-resistant TB with the Division of Tuberculosis Elimination at CDC, comments on a multinational team's report on this emerging global public health threat. Created: 3/1/2007 by Emerging Infectious Diseases. Date Released: 3/26/2007.
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[Substance-abuse related emergencies--illegal drugs, part I].
Kinn, Michael; Holzbach, Rüdiger; Pajonk, Frank-Gerald Bernhard
2008-11-01
For the first time since the year 2000 the number of death due to substance abuse of illegal drugs has increased in Germany in 2007 (+8 % compared to 2006). Emergency situations due to drug abuse are frequent, particular in big cities. They may be, however, difficult to diagnose and/or treat for an emergency physician on scene because of a lack of diagnostic tools, the local and personal surroundings, and the unknown number and nature of drugs. Many drug intoxications must be considered suicidal. On the other hand, drug intoxications may mask (other) life-threatening conditions. Emergency situations due to withdrawal offer the possibility to motivate patients to take advantage of specialist-guided abstinence programs.
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A screen to identify drug resistant variants to target-directed anti-cancer agents
Directory of Open Access Journals (Sweden)
Azam Mohammad
2003-01-01
Full Text Available The discovery of oncogenes and signal transduction pathways important for mitogenesis has triggered the development of target-specific small molecule anti-cancer compounds. As exemplified by imatinib (Gleevec, a specific inhibitor of the Chronic Myeloid Leukemia (CML-associated Bcr-Abl kinase, these agents promise impressive activity in clinical trials, with low levels of clinical toxicity. However, such therapy is susceptible to the emergence of drug resistance due to amino acid substitutions in the target protein. Defining the spectrum of such mutations is important for patient monitoring and the design of next-generation inhibitors. Using imatinib and BCR/ABL as a paradigm for a drug-target pair, we recently reported a retroviral vector-based screening strategy to identify the spectrum of resistance-conferring mutations. Here we provide a detailed methodology for the screen, which can be generally applied to any drug-target pair.
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Trends in GPCR drug discovery: new agents, targets and indications
DEFF Research Database (Denmark)
Hauser, Alexander Sebastian; Gloriam, David E.; Attwood, Misty M.
2017-01-01
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...... 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......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...
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Emerging RNA-based drugs: siRNAs, microRNAs and derivates.
Pereira, Tiago Campos; Lopes-Cendes, Iscia
2012-09-01
An emerging new category of therapeutic agents based on ribonucleic acid has emerged and shown very promising in vitro, animal and pre-clinical results, known as small interfering RNAs (siRNAs), microRNAs mimics (miRNA mimics) and their derivates. siRNAs are small RNA molecules that promote potent and specific silencing of mutant, exogenous or aberrant genes through a mechanism known as RNA interference. These agents have called special attention to medicine since they have been used to experimentally treat a series of neurological conditions with distinct etiologies such as prion, viral, bacterial, fungal, genetic disorders and others. siRNAs have also been tested in other scenarios such as: control of anxiety, alcohol consumption, drug-receptor blockage and inhibition of pain signaling. Although in a much earlier stage, miRNAs mimics, anti-miRs and small activating RNAs (saRNAs) also promise novel therapeutic approaches to control gene expression. In this review we intend to introduce clinicians and medical researchers to the most recent advances in the world of siRNA- and miRNA-mediated gene control, its history, applications in cells, animals and humans, delivery methods (an yet unsolved hurdle), current status and possible applications in future clinical practice.
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Khan, Haroon; Saeedi, Mina; Nabavi, Seyed Mohammad; Mubarak, Mohammad S; Bishayee, Anupam
2018-04-03
Cancer continues to be a global burden, despite the advancement of various technological and pharmaceutical improvements over the past two decades. Methods for treating cancer include surgery, radiotherapy and chemotherapy in addition to other specialized techniques. On the other hand, medicinal plants have been traditionally employed either as the complementary medicine or dietary agents in the treatment and management of cancer. Medicinal plants are a rich source of secondary metabolites with interesting biological and pharmacological activities. Among these metabolites, glycosides are naturally occurring substances and have outstanding therapeutic potential and clinical utility. Different medical research engines such GoogleScholar, PubMed, SpringerLink, ScienceDirect were used to collect related literature on the subject matter. In this regard, only peer reviewed journals were considered. Emerging results showed that numerous glycosides isolated from various plants possessed marked anticancer activity against a variety of cancer cell lines. Accordingly, the aim of the present review is to shed light on the anticancer effects of glycosides, analyze possible mechanisms of action, and highlight the role of these natural agents as complementary and alternative medicine in combating and managing cancer. The glycosides isolated from different plants demonstrated potent cytotoxic effects against various cancer cell lines in initial preclinical studies. The anticancer effect was mediated through multiple mechanisms; however further detail studies are needed to understand the full potential of glycosides for clinical utility. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Liposomal Drug Delivery of Anticancer Agents
DEFF Research Database (Denmark)
Pedersen, Palle Jacob
and retention (EPR) effect. The liposomes consists of sPLA2 IIA sensitive phospholipids having anticancer drugs covalently attached to the sn-2 position of the glycerol backbone in the phospholipids, hence drug leakage is avoided from the carrier system. Various known anticancer agents, like chlorambucil, all......) based strategy using a limited number of reaction types. Upon coupling of unsaturated building blocks ring closing metathesis cascades were used to “reprogram” the molecular scaffold and highly diverse structures were obtained. In total 20 novel compounds with a broad structural diversity were prepared...
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Cadagan, David; Merry, Stephen
2013-10-01
Modulating agents are used to circumvent drug resistance in the clinical setting. However achievable serum concentrations are often lower than those which are optimal in vitro. Combination of modulating agents with non-overlapping toxicities may overcome this obstacle. We have investigated combinations of three modulating agents (quinine, verapamil, and cinnarizine) to circumvent inherent or acquired resistance to the cytotoxic drugs doxorubicin, vincristine and paclitaxel. Dose-response curves to cytotoxic drugs in the presence/absence of modulating agents were determined using colony formation and cell proliferation assays. Doxorubicin accumulation into cell monolayers was measured by fluorescence spectrophotometry. Greater (1.9-fold) sensitisation to particular cytotoxic drugs was observed for certain combinations of modulating agents compared to individual effects. The most effective combination was quinine-plus-verapamil with the cytotoxic drug doxorubicin. This increase in sensitivity was associated with increased doxorubicin accumulation. Such enhanced activity was, however, not observed for all combinations of modulating agents or for all studied cytotoxic drugs. The findings of the present study suggest certain combinations of modulating agents to have a clinical role in circumventing drug resistance. Particular combinations of modulating agents must be carefully chosen to suit particular cytotoxic drug treatments.
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Trends in GPCR drug discovery: new agents, targets and indications.
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.
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Emerging protein targets for metal-based pharmaceutical agents : An update
de Almeida, Andreia; Oliveira, Bruno L.; Correia, Joao D. G.; Soveral, Graca; Casini, Angela
2013-01-01
The peculiar chemical properties of metal-based drugs impart innovative pharmacological profiles to this class of therapeutic and diagnostic agents, most likely in relation to novel molecular mechanisms still poorly understood. However, inorganic drugs have been scarcely considered for medicinal
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Sherry, Norelle; Howden, Benjamin
2018-04-01
Multidrug-resistant (MDR) and extensively-drug-resistant (XDR) Gram-negative bacteria have emerged as a major threat to human health globally. This has resulted in the 're-discovery' of some older antimicrobials and development of new agents, however resistance has also rapidly emerged to these agents. Areas covered: Here we describe recent developments in resistance to three of the most important last-line antimicrobials for treatment of MDR and XDR Gram negatives: fosfomycin, colistin and ceftazidime-avibactam. Expert commentary: A key challenge for microbiologists and clinicians using these agents for treating patients with MDR and XDR Gram negative infections is the need to ensure appropriate reference methods are being used to test susceptibility to these agents, especially colistin and fosfomycin. These methods are not available in all laboratories meaning accurate results are either delayed, or potentially inaccurate as non-reference methods are employed. Combination therapy for MDR and XDR Gram negatives is likely to become more common, and future studies should focus on the clinical effects of monotherapy vs combination therapy, as well as validation of synergy testing methods. Effective national and international surveillance systems to detect and respond to resistance to these last line agents are also critical.
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Mechanisms of resistance to alkylating agents
Damia, G.; D‘Incalci, M.
1998-01-01
Alkylating agents are the most widely used anticancer drugs whose main target is the DNA, although how exactly the DNA lesions cause cell death is still not clear. The emergence of resistance to this class of drugs as well as to other antitumor agents is one of the major causes of failure of cancer treatment. This paper reviews some of the best characterized mechanisms of resistance to alkylating agents. Pre- and post-target mechanisms are recognized, the former able to limit the formation of...
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Garbayo, E; Ansorena, E; Blanco-Prieto, M J
2013-11-01
Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood-brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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[The drug abuse patient as emergency].
Kessler, R; Ryser, D H
1991-01-15
Acute drug intoxication is a medical emergency considering its potential interference with vital functions. All 157 cases with drug overdose admitted to the emergency department of the "Inselspital" in Berne over 183 days between July 1989 and June 1990 were analyzed retrospectively. In the vast majority of cases heroin overdose was involved. In mixed poisonings with heroin mostly flunitrazepam and alcohol contributed to the clinical picture, less commonly cocaine. There were very few intoxications with cocaine alone. A practical approach to the management of patients with certain or suspected drug intoxication presenting with coma and depressed respiration is proposed. In the therapy of acute intoxications with opiates and benzodiazepines there are specific antagonists available. In contrast, therapy of cocaine overdose remains symptomatic. The medical complications of acute heroin and cocaine intoxications are discussed separately.
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Emerging and Underrecognized Complications of Illicit Drug Use
Wurcel, Alysse G.; Merchant, Elisabeth A.; Clark, Roger P.; Stone, David R.
2015-01-01
This comprehensive review of infectious and noninfectious syndromes associated with illicit drug use focuses on underrecognized complications of common illicit drugs and constellations of syndromes associated with emerging illicit drugs.
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Emergence of Extensively Drug Resistant Tuberculosis
Centers for Disease Control (CDC) Podcasts
Extensively drug-resistant tuberculosis (XDR TB) outbreaks have been reported in South Africa, and strains have been identified on 6 continents. Dr. Peter Cegielski, team leader for drug-resistant TB with the Division of Tuberculosis Elimination at CDC, comments on a multinational team's report on this emerging global public health threat.
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Statistical Agent Based Modelization of the Phenomenon of Drug Abuse
di Clemente, Riccardo; Pietronero, Luciano
2012-07-01
We introduce a statistical agent based model to describe the phenomenon of drug abuse and its dynamical evolution at the individual and global level. The agents are heterogeneous with respect to their intrinsic inclination to drugs, to their budget attitude and social environment. The various levels of drug use were inspired by the professional description of the phenomenon and this permits a direct comparison with all available data. We show that certain elements have a great importance to start the use of drugs, for example the rare events in the personal experiences which permit to overcame the barrier of drug use occasionally. The analysis of how the system reacts to perturbations is very important to understand its key elements and it provides strategies for effective policy making. The present model represents the first step of a realistic description of this phenomenon and can be easily generalized in various directions.
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Residue analysis of veterinary drugs and growth-promoting agents
Stolker, A.A.M.; Zuidema, T.; Nielen, M.W.F.
2007-01-01
Two major trends are observed in the analysis of veterinary drugs and growth-promoting agents. First is the selection of sample material for monitoring the use of registered veterinary drugs. Traditionally meat, kidney and liver were analyzed but, due to the food scandals in which meat was very
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Multi-agent simulations for emergency situations in an airport scenario
Directory of Open Access Journals (Sweden)
Ana Cristina BICHARRA
2012-12-01
Full Text Available Normal 0 21 false false false EN-US JA X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabla normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:Cambria; mso-ascii-font-family:Cambria; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Cambria; mso-hansi-theme-font:minor-latin; mso-ansi-language:EN-US;} This paper presents a multi-agent framework using Net- Logo to simulate human and collective behaviors during emergency evacuations. Emergency situation appears when an unexpected event occurs. In indoor emergency situation, evacuation plans defined by facility manager explain procedure and safety ways to follow in an emergency situation. A critical and public scenario is an airportwhere there is an everyday transit of thousands of people. In this scenario the importance is related with incidents statistics regarding overcrowding and crushing in public buildings. Simulation has the objective of evaluating building layouts considering several possible configurations. Agents could be based on reactive behavior like avoid danger or follow other agent, or in deliberative behavior based on BDI model. This tool provides decision support in a real emergency scenario like an airport, analyzing alternative solutions to the evacuation process.
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Multi-agent simulations for emergency situations in an airport scenario
Directory of Open Access Journals (Sweden)
José Manuel MOLINA
2013-06-01
Full Text Available Normal 0 21 false false false EN-US JA X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabla normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:Cambria; mso-ascii-font-family:Cambria; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Cambria; mso-hansi-theme-font:minor-latin; mso-ansi-language:EN-US;} This paper presents a multi-agent framework using Net- Logo to simulate human and collective behaviors during emergency evacuations. Emergency situation appears when an unexpected event occurs. In indoor emergency situation, evacuation plans defined by facility manager explain procedure and safety ways to follow in an emergency situation. A critical and public scenario is an airport where there is an everyday transit of thousands of people. In this scenario the importance is related with incidents statistics regarding overcrowding and crushing in public buildings. Simulation has the objective of evaluating building layouts considering several possible configurations. Agents could be based on reactive behavior like avoid danger or follow other agent, or in deliberative behavior based on BDI model. This tool provides decision support in a real emergency scenario like an airport, analyzing alternative solutions to the evacuation process.
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New oral anticoagulant and antiplatelet agents for neurosurgeons.
Kimpton, George; Dabbous, Bassam; Leach, Paul
2015-01-01
Until recently, warfarin, clopidogrel and aspirin have provided the mainstay for prevention of thrombotic disease in cardiac patients. However, new classes of drugs have recently emerged that promise better clinical outcomes and lower risks. Use of such agents has increased, but increased risk and severity of intra-cranial haemorrhage (ICH) still remain. These cases of intra-cranial bleeds present as emergencies to neurosurgical units. It is of paramount importance that neurosurgical practitioners are aware of those new drugs, useful monitoring tests and available emergency reversal options in case the patient needs emergency intervention. In this review we survey newly available agents in the U.K. at the time of publication. We look at the data provided by the manufacturers, related publications and international guidelines for their use and reversal. New anticoagulants offer a lower incidence of ICH compared with warfarin. Advanced and accurate monitoring tests are emerging, as are prospective data on reversal of anticoagulation in bleeding. Some standard coagulation tests may be of use, whilst reversal agents are available and being evaluated. The trial data shows that new antiplatelet agents have similar or increased incidence and severity of intra-cranial ICH compared with clopidogrel. There is currently limited data on monitoring or reversal. We suggest they may be managed similarly to clopidogrel by using platelet reactivity assays, optimising platelet count and using platelet transfusion with adjunctive agents.
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Emergent Macroeconomics An Agent-Based Approach to Business Fluctuations
Delli Gatti, Domenico; Gallegati, Mauro; Giulioni, Gianfranco; Palestrini, Antonio
2008-01-01
This book contributes substantively to the current state-of-the-art of macroeconomics by providing a method for building models in which business cycles and economic growth emerge from the interactions of a large number of heterogeneous agents. Drawing from recent advances in agent-based computational modeling, the authors show how insights from dispersed fields like the microeconomics of capital market imperfections, industrial dynamics and the theory of stochastic processes can be fruitfully combined to improve our understanding of macroeconomic dynamics. This book should be a valuable resource for all researchers interested in analyzing macroeconomic issues without recurring to a fictitious representative agent.
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[Adverse drug reaction reporting in emergency medicine].
Milojevic, Kolia; Chassagnol, Isabelle; Brion, Nathalie; Cléro, Joël; Degrèze, Nathalie; Lambert, Yves
2004-01-01
A regional survey was performed between June and September 2002, to evaluate knowledge and attitudes of emergency physicians regarding adverse drug reaction (ADR) reporting in a French district. 100 questionnaires completed by physicians working in emergency departments and/or mobile intensive care units were analysed. The frequency of ADRs encountered by emergency practitioners was estimated at > or = 0.73 per year and per physician. The ADR notification rate in emergency medicine was estimated at advertising ADR reporting procedures could help to improve the notification rate in emergency medicine.
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[Use of Emerging Drugs in Medellín, Colombia].
Castaño Pérez, Guillermo A; Calderón Vallejo, Gustavo A; Berbesi Fernández, Dedsy Yajaira
2013-09-01
The ongoing emergence of new synthetic substances that are used as drugs is a constant challenge to public health. Emerging drugs is the concept used in this research project to define the emergence of new psychoactive substances at a given time, a specific context and group, the reemergence of others that some epidemiologists considered had lost their prevalence, and the sudden prevalence of drugs that had low levels of consumption. This research project was carried out using an empirical-analytical approach using a mixed methods study. The convenience sample was made up of 510 drug dependents institutionalized in treatment centers in Medellin in the year 2011. The examination was carried out related to the consumption of emerging drugs. An ad hoc tool was applied to all the drug users in order to identify which of the drugs of this study they considered to be emergent. Once the consumers were identified and selected based on the frequency of consumption, and the prevalence in the last year and last month, a semi-structured interview was carried out to find out details on the substances and their consumption characteristics. Based on the new drug consumers in Medellin, 82.2% were male and 17.8% female. As regards education levels, 58.2% were in high school, 26.8% hold higher technical or college degrees, and 1.4% had no schooling. Only 27.8% held a steady job, occasional employment, or were independent business owners, 40.7% were students and 8.9% were housewives. More than three-quarters (76.3%) were single, and 17.8% had a steady partner. The sample represented all social classes. Of all the emerging drugs found in this study, the prevalence of benzodiazepines stands out (flunitrazepam and clonazepam), life prevalence (LP), 97.5%; last year prevalence (LYP), 67.9%, and last month prevalence (LMP), 46.7%. These were followed by the synthetic drugs (LSD, Ecstasies, amphetamines, GHB, Vegetable Ecstasies, Phencyclidine; Methamphetamine, Ketamine, 2CB), with LP, 96
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Weiner, Scott G; Griggs, Christopher A; Mitchell, Patricia M; Langlois, Breanne K; Friedman, Franklin D; Moore, Rebecca L; Lin, Shuo Cheng; Nelson, Kerrie P; Feldman, James A
2013-10-01
We compare emergency provider impression of drug-seeking behavior with objective criteria from a state prescription drug monitoring program, assess change in opioid pain reliever prescribing after prescription drug monitoring program review, and examine clinical factors associated with suspected drug-seeking behavior. This was a prospective observational study of emergency providers assessing a convenience sample of patients aged 18 to 64 years who presented to either of 2 academic medical centers with chief complaint of back pain, dental pain, or headache. Drug-seeking behavior was objectively defined as present when a patient had greater than or equal to 4 opioid prescriptions by greater than or equal to 4 providers in the 12 months before emergency department evaluation. Emergency providers completed data forms recording their impression of the likelihood of drug-seeking behavior, patient characteristics, and plan for prescribing pre- and post-prescription drug monitoring program review. Descriptive statistics were generated. We calculated agreement between emergency provider impression of drug-seeking behavior and prescription drug monitoring program definition, and sensitivity, specificity, and positive predictive value of emergency provider impression, using prescription drug monitoring program criteria as the criterion standard. A multivariate logistic regression analysis was conducted to determine clinical factors associated with drug-seeking behavior. Thirty-eight emergency providers with prescription drug monitoring program access participated. There were 544 patient visits entered into the study from June 2011 to January 2013. There was fair agreement between emergency provider impression of drug-seeking behavior and prescription drug monitoring program (κ=0.30). Emergency providers had sensitivity 63.2% (95% confidence interval [CI] 54.8% to 71.7%), specificity 72.7% (95% CI 68.4% to 77.0%), and positive predictive value 41.2% (95% CI 34.4% to 48
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Rituximab: An emerging therapeutic agent for kidney transplantation
Directory of Open Access Journals (Sweden)
Joseph Kahwaji
2009-10-01
Full Text Available Joseph Kahwaji, Chris Tong, Stanley C Jordan, Ashley A VoComprehensive Transplant Center, Transplant immunology Laboratory, HLA Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USAAbstract: Rituximab (anti-CD20, anti-B-cell is now emerging as an important drug for modification of B-cell and antibody responses in solid-organ transplant recipients. Its uses are varied and range from facilitating desensitization and ABO blood group-incompatible transplantation to the treatment of antibody-mediated rejection (AMR, post-transplant lymphoproliferative disorder (PTLD, and recurrent glomerular diseases in the renal allograft. Despite these uses, prospective randomized trials are lacking. Only case reports exist in regards to its use in de novo and recurrent diseases in the renal allograft. Recent reports suggests that the addition of rituximab to intravenous immunoglobulin (IVIG may have significant benefits for desensitization and treatment of AMR and chronic rejection. Current dosing recommendations are based on data from United States Food and Drug Administration-approved indications for treatment of B-cell lymphomas and rheumatoid arthritis. From the initial reported experience in solid organ transplant recipients, the drug is well tolerated and not associated with increased infectious risks. However, close monitoring for viral infections is recommended with rituximab use. The occurrence of progressive multifocal leukoencephalopathy (PML has been reported with rituximab use. However, this is rare and not reported in the renal transplant population. Here we will review current information regarding the effectiveness of rituximab as an agent for desensitization of highly human leukocyte antigen-sensitized and ABO-incompatible transplant recipients and its use in treatment of AMR. In addition, the post-transplant use of rituximab for treatment of PTLD and for recurrent and de novo glomerulonephritis in the allograft will be discussed. In
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49 CFR 40.341 - Must service agents comply with DOT drug and alcohol testing requirements?
2010-10-01
... Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Roles and Responsibilities of Service Agents § 40.341 Must service agents comply with DOT drug and alcohol testing... requirements of this part and the DOT agency drug and alcohol testing regulations. (b) If you do not comply...
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Wang, Kejian; Wan, Mei; Wang, Rui-Sheng; Weng, Zuquan
2016-04-01
Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning. We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents. We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs. Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning. We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning.
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DEFF Research Database (Denmark)
Olsen, Louise Cathrine Braun; Færgeman, Nils J.
2012-01-01
and validate therapeutic targets and to discover drug candidates for rapidly and effectively generating new interventions for human diseases. The recent emergence of genomic technologies and their application on genetically tractable model organisms like Drosophila melanogaster,Caenorhabditis elegans...... critical roles in the genomic age of biological research and drug discovery. In the present review we discuss how simple biological model organisms can be used as screening platforms in combination with emerging genomic technologies to advance the identification of potential drugs and their molecular...
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The role of compensatory mutations in the emergence of drug resistance.
Directory of Open Access Journals (Sweden)
Andreas Handel
2006-10-01
Full Text Available Pathogens that evolve resistance to drugs usually have reduced fitness. However, mutations that largely compensate for this reduction in fitness often arise. We investigate how these compensatory mutations affect population-wide resistance emergence as a function of drug treatment. Using a model of gonorrhea transmission dynamics, we obtain generally applicable, qualitative results that show how compensatory mutations lead to more likely and faster resistance emergence. We further show that resistance emergence depends on the level of drug use in a strongly nonlinear fashion. We also discuss what data need to be obtained to allow future quantitative predictions of resistance emergence.
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Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery
Directory of Open Access Journals (Sweden)
Vera ePaefgen
2015-09-01
Full Text Available Ultrasound is one of the most frequently used diagnostic methods. It is a non-invasive, comparably inexpensive imaging method with a broad spectrum of applications, which can be increased even more by using bubbles as contrast agents. There are various different types of bubbles: filled with different gases, composed of soft- or hard-shell materials, and ranging in size from nano- to micrometers. These intravascular contrast agents enable functional analyses, e.g. to acquire organ perfusion in real-time. Molecular analyses are achieved by coupling specific ligands to the bubbles’ shell, which bind to marker molecules in the area of interest. Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by ultrasound pulses to locally release the entrapped agent. Recent studies show that ultrasound contrast agents are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability. This review summarizes important steps in the development of ultrasound contrast agents and introduces the current clinical applications of contrast-enhanced ultrasound. Additionally, an overview of the recent developments in ultrasound probe design for functional and molecular diagnosis as well as for drug delivery is given.
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Corny, Jennifer; Pelletier, Elaine; Lebel, Denis; Bussières, Jean-François
2017-03-10
Only few medicines are licensed for children. The use of emerging drugs (unmarketed drug, off-label drug with poorly documented use, and/or costly drugs) might represent an essential alternative for pediatric patients. The objective of the study was to assess emerging drug uses rate and profile in our women's and children's centre to support the implementation of an appropriate policy. We identified retrospectively emerging drugs used between 2013-01-01 and 2014-02-28, using computerized pharmacist software extraction of drugs used. Conventional oncologic drugs were excluded. Retrospective analysis of medical charts for patients who received an emerging drug and literature review for each drug were performed to determine efficacy and safety endpoints. Median delays between first intention and final decision to use the drug and between final decision and first administration were calculated. Proportion of patients who experienced a positive evolution under treatment or a side effect possibly related to the drug was calculated. A total of 26 emerging drugs were identified (89 patients, 99 uses). Median treatment duration was 66 days [1-1435]. Median delay between first evocation and final decision to use the drug was 2 days [0-333] and 0 day [0-404] between final decision and first administration. 52/99 (53%) of patients experienced a positive evolution under treatment and 26/99 (26%) experienced a side effect possibly related to emerging drug use. This study allowed us to describe emerging drug uses in a women and children tertiary hospital. It led to the implementation of a local emerging drug use policy ensuring optimal and safe use of these drugs. There is a significant number of emerging drugs used in pediatric which shows positive improvement in 56% of patients. © 2017 Journal of Population Therapeutics and Clinical Pharmacology. All rights reserved.
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Parenting styles and emerging adult drug use in Cebu, the Philippines.
Hock, Rebecca S; Hindin, Michelle J; Bass, Judith K; Surkan, Pamela J; Bradshaw, Catherine P; Mendelson, Tamar
Parenting style is a potent and malleable influence on emerging adult substance use. Most of the parenting-substance use literature has been conducted in Western populations and it is unknown whether findings are generalizable to other cultures and contexts. We extended the parenting-substance use literature to a cohort of emerging adults in the Philippines using the Cebu Longitudinal Health and Nutrition Survey. We assessed associations between mothers' and fathers' parenting styles (authoritative, permissive, authoritarian, and neglectful) reported by offspring at age 18 and odds of offspring-reported drug use three years later, adjusted for a range of offspring- and parent/household-level characteristics. Females were dropped from analyses due to low prevalence of drug users. We found that many emerging adults in Cebu reported having used drugs, particularly methamphetamine-a dangerous drug with high abuse potential. Authoritative (warm, firm) mothering was significantly associated with sons' reduced odds of drug use and neglectful fathering was related at a trend level with sons' increased odds of having tried drugs. Findings underscore the relation of parenting styles to emerging adults' drug use and add to the literature on cross-cultural variability in parenting styles.
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Evolution of natural agents: preservation, advance, and emergence of functional information.
Sharov, Alexei A
2016-04-01
Biological evolution is often viewed narrowly as a change of morphology or allele frequency in a sequence of generations. Here I pursue an alternative informational concept of evolution, as preservation, advance, and emergence of functional information in natural agents. Functional information is a network of signs (e.g., memory, transient messengers, and external signs) that are used by agents to preserve and regulate their functions. Functional information is preserved in evolution via complex interplay of copying and construction processes: the digital components are copied, whereas interpreting subagents together with scaffolds, tools, and resources, are constructed. Some of these processes are simple and invariant, whereas others are complex and contextual. Advance of functional information includes improvement and modification of already existing functions. Although the genome information may change passively and randomly, the interpretation is active and guided by the logic of agent behavior and embryonic development. Emergence of new functions is based on the reinterpretation of already existing information, when old tools, resources, and control algorithms are adopted for novel functions. Evolution of functional information progressed from protosemiosis, where signs correspond directly to actions, to eusemiosis, where agents associate signs with objects. Language is the most advanced form of eusemiosis, where the knowledge of objects and models is communicated between agents.
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Alexander, Walter
2016-03-01
What started as a trickle of new agents that help the body's immune system fight cancer has now become a flood, despite some daunting adverse effects. This report discusses the new drugs, indications, and combinations that continue to emerge.
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Sivasubramanian, Kathyayini; Mathiyazhakan, Malathi; Wiraja, Christian; Upputuri, Paul Kumar; Xu, Chenjie; Pramanik, Manojit
2017-04-01
Photoacoustic imaging has become an emerging tool for theranostic applications. Not only does it help in release and therapeutic applications. We explore near-infrared light-sensitive liposomes coated with gold nanostars (AuNSs) for both imaging and drug release applications using a photoacoustic imaging system. Being amphiphilic, the liposomes lipid bilayer and the aqueous core enable encapsulation of both hydrophobic and hydrophilic drugs. The AuNSs on the surface of the liposomes act as photon absorbers due to their intrinsic surface plasmon resonance. Upon excitation by laser light at specific wavelength, AuNSs facilitate rapid release of the contents encapsulated in the liposomes due to local heating and pressure wave formation (photoacoustic wave). Herein, we describe the design and optimization of the AuNSs-coated liposomes and demonstrate the release of both hydrophobic and hydrophilic model drugs (paclitaxel and calcein, respectively) through laser excitation at near-infrared wavelength. The use of AuNSs-coated liposomes as contrast agents for photoacoustic imaging is also explored with tissue phantom experiments. In comparison to blood, the AuNSs-coated liposomes have better contrast (approximately two times) at 2-cm imaging depth.
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Directory of Open Access Journals (Sweden)
Lisa Corina Barros de Andrade e Sousa1
2016-01-01
Full Text Available The fungus Candida albicans is the most common causative agent of human fungal infections and better drugs or drug combination strategies are urgently needed. Here, we present an agent-based model of the interplay of C. albicans with the host immune system and with the microflora of the host. We took into account the morphological change of C. albicans from the yeast to hyphae form and its dynamics during infection. The model allowed us to follow the dynamics of fungal growth and morphology, of the immune cells and of microflora in different perturbing situations. We specifically focused on the consequences of microflora reduction following antibiotic treatment. Using the agent-based model, different drug types have been tested for their effectiveness, namely drugs that inhibit cell division and drugs that constrain the yeast-to-hyphae transition. Applied individually, the division drug turned out to successfully decrease hyphae while the transition drug leads to a burst in hyphae after the end of the treatment. To evaluate the effect of different drug combinations, doses, and schedules, we introduced a measure for the return to a healthy state, the infection score. Using this measure, we found that the addition of a transition drug to a division drug treatment can improve the treatment reliability while minimizing treatment duration and drug dosage. In this work we present a theoretical study. Although our model has not been calibrated to quantitative experimental data, the technique of computationally identifying synergistic treatment combinations in an agent based model exemplifies the importance of computational techniques in translational research.
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Mehdizadeh, Mohammad; Nosrati, Kamran; Hamzeh, Mahtab
2014-11-01
Medical emergencies can frequently happen in dental settings and it is critical to outfit the clinic by emergency drugs and equipment. The aim of this study was to evaluate the emergency drugs and equipment in general and specialist dental settings in Babol, Iran. A questionnaire containing closed ended questions about the available emergency drugs and equipment was used in this descriptive-analytical study. Data were subjected to descriptive analysis using SPSS 18.0 to identify the most frequent drugs and equipment. Chi-square and t-test were used to evaluate the correlation between the variables. p < 0.05 was considered statistically significant. One hundred and twelve dentists answered the questionnaire. The most available drug and equipment were epinephrine (67%) and single use syringe (81.3%) respectively. Significant correlation was found between degree of education and availability of first group of emergency drugs and between sex and possession of second group of emergency equipment (p < 0.05). Degree of availability of emergency drugs and equipment was moderate to low and training about emergencies should be included in the didactic topics of universities and workshops. Information about emergency drug and equipment would help to manage the unwanted emergency situations.
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Analytical toxicology of emerging drugs of abuse--an update.
Meyer, Markus R; Peters, Frank T
2012-12-01
The steady increase of new drugs of abuse on the illicit drug market is a great challenge for analytical toxicologists. Because most of these new drugs or drug classes are not included in established analytical methods targeting classic drugs of abuse, analytical procedures must be adapted or new procedures must be developed to cover such new compounds. This review summarizes procedures for analysis of these drugs of abuse published from January 2009 to January 2012 covering the following classes of emerging drugs of abuse as follows: β-keto-amphetamines, pyrrolidinophenones, tryptamines, and synthetic cannabinoids.
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Stabilizing Agents for Drug Nanocrystals: Effect on Bioavailability
Directory of Open Access Journals (Sweden)
Annika Tuomela
2016-05-01
Full Text Available Drug nanocrystals are a versatile option for drug delivery purposes, and while the number of poorly soluble drug materials is all the time increasing, more research in this area is performed. Drug nanocrystals have a simple structure—a solid drug core is surrounded by a layer of stabilizing agent. However, despite the considerably simple structure, the selection of an appropriate stabilizer for a certain drug can be challenging. Mostly, the stabilizer selection is based purely on the requirement of physical stability, e.g., maintaining the nanosized particle size as long as possible after the formation of drug nanocrystals. However, it is also worth taking into account that stabilizer can affect the bioavailability in the final formulation via interactions with cells and cell layers. In addition, formation of nanocrystals is only one process step, and for the final formulation, more excipients are often added to the composition. The role of the stabilizers in the final formulation can be more than only stabilizing the nanocrystal particle size. A good example is the stabilizer’s role as cryoprotectant during freeze drying. In this review, the stabilizing effect, role of stabilizers in final nanocrystalline formulations, challenges in reaching in vitro–in vivo correlation with nanocrystalline products, and stabilizers’ effect on higher bioavailability are discussed.
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Emerging drugs for the treatment of erectile dysfunction.
Peak, Taylor C; Yafi, Faysal A; Sangkum, Premsant; Hellstrom, Wayne J G
2015-06-01
Erectile dysfunction adversely affects the lives of millions of men, and is the most commonly treated sexual disorder today. The erectile process has been extensively investigated, with major advances made in elucidating many of the complex molecular pathways involved. These advances have allowed researchers to design and study drug formulations that target various aspects of this complex process. The initial culmination of this research was the introduction of phosphodiesterase 5-inhibitors. While effective in many patients, they are not satisfactory for all afflicted men. As a result, researchers are developing novel drugs that target different molecular pathways. The paper will review these pathways, and the potential agents that target them. More specifically, first dopaminergic and melanocortin receptor agonists that act centrally will be covered. Then, the paper will examine the "second-generation" phosphodiesterase 5-inhibitors, soluble guanylate cyclases, rho-kinase inhibitors, and maxi-k channel activators that act peripherally. Most of these novel drugs have yet to reach Phase III studies. However, it is likely that in years to come, patients will be selectively treated with these novel agents as a monotherapy or in combination with others acting in a synergistic manner.
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Drug Interactions in Childhood Cancer
Haidar, Cyrine; Jeha, Sima
2016-01-01
Children with cancer are increasingly benefiting from novel therapeutic strategies and advances in supportive care, as reflected in improvements in both their survival and quality of life. However, the continuous emergence of new oncology drugs and supportive care agents has also increased the possibility of deleterious drug interactions and healthcare providers need to practice extreme caution when combining medications. In this review, we discuss the most common interactions of chemotherapeutic agents with supportive care drugs such as anticonvulsants, antiemetics, uric acid–lowering agents, acid suppressants, antimicrobials, and pain management medications in pediatric oncology patients. As chemotherapy agents interact not only with medications but also with foods and herbal supplements that patients receive during the course of their treatment, we also briefly review such interactions and provide recommendations to avoid unwanted and potentially fatal interactions in children with cancer. PMID:20869315
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Evolution of natural agents: preservation, advance, and emergence of functional information
Sharov, Alexei A.
2016-01-01
Biological evolution is often viewed narrowly as a change of morphology or allele frequency in a sequence of generations. Here I pursue an alternative informational concept of evolution, as preservation, advance, and emergence of functional information in natural agents. Functional information is a network of signs (e.g., memory, transient messengers, and external signs) that are used by agents to preserve and regulate their functions. Functional information is preserved in evolution via comp...
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Rong, Carola; Carmona, Nicole E; Lee, Yena L; Ragguett, Renee-Marie; Pan, Zihang; Rosenblat, Joshua D; Subramaniapillai, Mehala; Shekotikhina, Margarita; Almatham, Fahad; Alageel, Asem; Mansur, Rodrigo; Ho, Roger C; McIntyre, Roger S
2018-01-01
To determine, via narrative, non-systematic review of pre-clinical and clinical studies, whether the effect of cannabis on hepatic biotransformation pathways would be predicted to result in clinically significant drug-drug interactions (DDIs) with commonly prescribed psychotropic agents. Areas covered: A non-systematic literature search was conducted using the following databases: PubMed, PsycInfo, and Scopus from inception to January 2017. The search term cannabis was cross-referenced with the terms drug interactions, cytochrome, cannabinoids, cannabidiol, and medical marijuana. Pharmacological, molecular, and physiologic studies evaluating the pharmacokinetics of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD), both in vitro and in vivo, were included. Bibliographies were also manually searched for additional citations that were relevant to the overarching aim of this paper. Expert opinion: Δ 9 -Tetrahydrocannabinol and CBD are substrates and inhibitors of cytochrome P450 enzymatic pathways relevant to the biotransformation of commonly prescribed psychotropic agents. The high frequency and increasing use of cannabis invites the need for healthcare providers to familiarize themselves with potential DDIs in persons receiving select psychotropic agents, and additionally consuming medical marijuana and/or recreational marijuana.
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[The actual Russian legislation in sphere of turn-over of drug agents and psychotropic substances].
Abramov, A Yu; Kosolapova, N V; Mikhaiylova, Yu V
2014-01-01
The drug abuse is a social occurrence. Hence, the social economic methods are the first of all means of combating this evil. At the same time, measures of especially juridical character possess significant value since they develop corresponding legal base for applying another measures. In the Russian Federation, during fifteen years the new policy of public regulation and normative legal base in the area of legal turn-over of drug agents, psychotropic substances and their precursors were developed factually from zero ground. However, the current national legislation is not deprived of some flaws and contradictions. Frequently a uniform practice of interpretation and application of legal rules regulating the controlled turn-over is lacking. On the one hand, this circumstance decreases effectiveness of action of such rules and on the other hand favors development of situations for outflow of pharmaceuticals from legal turn-over to illegal traffic. The becoming of the Russian legislation in the area of turn-over of drug agents, precursors and psychotropic substances relates to the period of late 1990s when the Federal Law No 3 FZ "On drug agents and psychotropic substances" of January 8 1998 was developed and passed by the State Duma of the Russian Federation. The given law completely conforms to principles of legal regulation of turn-over of drug agents and psychotropic substances determined by the Constitution of the Russian Federation (provisions 76, 90, 104, 105) and federal laws ("On the government of the Russian Federation" of December 17 1997, "On the ombudsman in the Russian Federation" of February 26 1997). The main characteristic of legal rules included into given group of sources of law is that they contain regulations of general disposition as basic ones for inferior sources of law. The analysis of basic Federal law No 3 FZ "On drug agents and psychotropic substances" of January 8 1998 makes it possible to conclude that in in Russia the international legal
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Medical emergencies facing general practitioners: Drugs for the doctor's bag
Janković Slobodan
2014-01-01
General practitioners are frequently facing medical emergencies. In order to react properly and administer therapy on time, a general practitioner needs to prepare and keep with himself the appropriate set of drugs which could be effectively used for treatment of the emergencies. The following drugs should find their place in the doctor's bag: acetaminophen (for mild and moderate pain, and for fever), morphine (for severe pain), naloxone (for heroin poisoning), ceftriaxone (for meningococcal ...
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Anti-Obesity Agents and the US Food and Drug Administration.
Casey, Martin F; Mechanick, Jeffrey I
2014-09-01
Despite the growing market for obesity care, the US Food and Drug Administration (FDA) has approved only two new pharmaceutical agents-lorcaserin and combination phentermine/topiramate-for weight reduction since 2000, while removing three agents from the market in the same time period. This article explores the FDA's history and role in the approval of anti-obesity medications within the context of a public health model of obesity. Through the review of obesity literature and FDA approval documents, we identified two major barriers preventing fair evaluation of anti-obesity agents including: (1) methodological pitfalls in clinical trials and (2) misaligned values in the assessment of anti-obesity agents. Specific recommendations include the use of adaptive (Bayesian) design protocols, value-based analyses of risks and benefits, and regulatory guidance based on a comprehensive, multi-platform obesity disease model. Positively addressing barriers in the FDA approval process of anti-obesity agents may have many beneficial effects within an obesity disease model.
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Papastavros, Efthimia; Remmers, Rachael A; Snow, Daniel D; Cassada, David A; Hage, David S
2018-03-01
Affinity sorbents using bovine serum albumin as a binding agent were developed and tested for the extraction of environmental contaminants from water. Computer simulations based on a countercurrent distribution model were also used to study the behavior of these sorbents. Several model drugs, pesticides, and hormones of interest as emerging contaminants were considered in this work, with carbamazepine being used as a representative analyte when coupling the albumin column on-line with liquid chromatography and tandem mass spectrometry. The albumin column was found to be capable of extracting carbamazepine from aqueous solutions that contained trace levels of this analyte. Further studies of the bovine serum albumin sorbent indicated that it had higher retention under aqueous conditions than a traditional C 18 support for most of the tested emerging contaminants. Potential advantages of using these protein-based sorbents included the low cost of bovine serum albumin and its ability to bind to a relatively wide range of drugs and related compounds. It was also shown how simulations could be used to describe the elution behavior of the model compounds on the bovine serum albumin sorbents as an aid in optimizing the retention and selectivity of these supports for use with liquid chromatography or methods such as liquid chromatography with tandem mass spectrometry. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Medical emergencies facing general practitioners: Drugs for the doctor's bag
Directory of Open Access Journals (Sweden)
Janković Slobodan
2014-01-01
Full Text Available General practitioners are frequently facing medical emergencies. In order to react properly and administer therapy on time, a general practitioner needs to prepare and keep with himself the appropriate set of drugs which could be effectively used for treatment of the emergencies. The following drugs should find their place in the doctor's bag: acetaminophen (for mild and moderate pain, and for fever, morphine (for severe pain, naloxone (for heroin poisoning, ceftriaxone (for meningococcal meningitis, albuterol (for bronchial asthma attack, hydrocortisone (for bronchial asthma attack, glucagon (for severe hypoglycemia, dextrose (for mild to moderate hypoglycemia, diazepam (for febrile convulsions or epileptic status, epinephrine (for anaphylaxis and cardiac arrest, atropine (for symptomatic bradicardia, chloropyramine (for acute allergy, aspirin (for acute myocardial infarction, nitroglycerine (for acute coronary syndrome, metoclopramide (for nausea and vomiting, haloperidol (for delirium, methylergometrine (for control of bleeding after delivery or abortion, furosemide (for acute pulmonary edema and flumazenil (for benzodiazepine poisoning. For each of the listed drugs a physician should well know the recommended doses, indications, contraindications and warnings. All of the listed drugs are either registered in Serbia or available through special import, so general practitioners may fill their bags with all necessary drugs and effectively and safely treat medical emergencies.
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Emergency Physicians' Knowledge of Cannabinoid Designer Drugs
Directory of Open Access Journals (Sweden)
Patrick M Lank
2013-09-01
Full Text Available Introduction: The use of synthetic drugs of abuse in the United States has grown in the last few years, with little information available on how much physicians know about these drugs and how they are treating patients using them. The objective of this study was to assess emergency physician (EP knowledge of synthetic cannabinoids (SC.Methods: A self-administered internet-based survey of resident and attending EPs at a large urban emergency department (ED was administered to assess familiarity with the terms Spice or K2 and basic knowledge of SC, and to describe some practice patterns when managing SC intoxication in the ED.Results: Of the 83 physicians invited to participate, 73 (88% completed surveys. The terms “Spice” and “K2” for SC were known to 25/73 (34% and 36/73 (49% of respondents. Knowledge of SC came most commonly (72% from non-medical sources, with lay publications and the internet providing most respondents with information. Among those with previous knowledge of synthetic cannabinoids, 25% were not aware that SC are synthetic drugs, and 17% did not know they are chemically most similar to marijuana. Among all participants, 80% felt unprepared caring for a patient in the ED who had used synthetic cannabinoids.Conclusion: Clinically active EPs are unfamiliar with synthetic cannabinoids. Even those who stated they had heard of synthetic cannabinoids answered poorly on basic knowledge questions. More education is needed among EPs of all ages and levels of training on synthetic cannabinoids. [West J Emerg Med. 2013;14(5:467–470.
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Emerging drug targets for Aβ and tau in Alzheimer’s disease: a systematic review
West, Sophie; Bhugra, Praveen
2015-01-01
Aims Currently, treatment for Alzheimer’s disease (AD) focuses on the cholinergic hypothesis and provides limited symptomatic effects. Research currently focuses on other factors that are thought to contribute to AD development such as tau proteins and Aβ deposits, and how modification of the associated pathology affects outcomes in patients. This systematic review summarizes and appraises the evidence for the emerging drugs affecting Aβ and tau pathology in AD. Methods A comprehensive, systematic online database search was conducted using the databases ScienceDirect and PubMed to include original research articles. A systematic review was conducted following a minimum set of standards, as outlined by The PRISMA Group 1. Specific inclusion and exclusion criteria were followed and studies fitting the criteria were selected. No human trials were included in this review. In vitro and in vivo AD models were used to assess efficacy to ensure studied agents were emerging targets without large bodies of evidence. Results The majority of studies showed statistically significant improvement (P < 0.05) of Aβ and/or tau pathology, or cognitive effects. Many studies conducted in AD animal models have shown a reduction in Aβ peptide burden and a reduction in tau phosphorylation post-intervention. This has the potential to reduce plaque formation and neuronal degeneration. Conclusions There are many emerging targets showing promising results in the effort to modify the pathological effects associated with AD. Many of the trials also provided evidence of the clinical effects of such drugs reducing pathological outcomes, which was often demonstrated as an improvement of cognition. PMID:25753046
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Emergency management of drug abuse in South Africa
African Journals Online (AJOL)
Drug abuse remains both a global scourge and a significant social and medical problem ... medicine at the Wits Emergency Medicine Department, ATLS Director, occasional media spokesman, .... Respiratory depression caused by morphine.
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Biodegradable Drug-Loaded Hydroxyapatite Nanotherapeutic Agent for Targeted Drug Release in Tumors.
Sun, Wen; Fan, Jiangli; Wang, Suzhen; Kang, Yao; Du, Jianjun; Peng, Xiaojun
2018-03-07
Tumor-targeted drug delivery systems have been increasingly used to improve the therapeutic efficiency of anticancer drugs and reduce their toxic side effects in vivo. Focused on this point, doxorubicin (DOX)-loaded hydroxyapatite (HAP) nanorods consisting of folic acid (FA) modification (DOX@HAP-FA) were developed for efficient antitumor treatment. The DOX-loaded nanorods were synthesized through in situ coprecipitation and hydrothermal method with a DOX template, demonstrating a new procedure for drug loading in HAP materials. DOX could be efficiently released from DOX@HAP-FA within 24 h in weakly acidic buffer solution (pH = 6.0) because of the degradation of HAP nanorods. With endocytosis under the mediation of folate receptors, the nanorods exhibited enhanced cellular uptake and further degraded, and consequently, the proliferation of targeted cells was inhibited. More importantly, in a tumor-bearing mouse model, DOX@HAP-FA treatment demonstrated excellent tumor growth inhibition. In addition, no apparent side effects were observed during the treatment. These results suggested that DOX@HAP-FA may be a promising nanotherapeutic agent for effective cancer treatment in vivo.
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Erythrocytes as Carriers for Drugs and Contrast Agents
Directory of Open Access Journals (Sweden)
Mauro Magnani
2014-01-01
Full Text Available Erythrocytes, also known as Red Blood Cells (RBC, are typically used in transfusion medicine to replace lost blood in patients who underwent different kinds of medical treatments as well as those involved in accidents resulting in blood loss. In addition to these common uses, RBC are being used for a variety of new applications either as therapeutics or as diagnostics. Most of these novel approaches are made possible due to the peculiar properties of these cells. We have invented a technology that allows cells to be opened and resealed without affecting their main physiological characteristics with a minimal amount of patient blood. Uses of processed RBCs in biomedical engineering include work with drugs, biomedical compounds and/or nanomaterials. These constructs are a new armamentarium available to the physicians for the release of drugs in circulation, for targeting drugs to selected sites in the body, or for in vivo diagnostic procedures based on magnetic and/or optical methods. Autologous human RBC loaded with dexamethasone (EryDex, a common corticosteroid, have been used in the treatment of Cystic Fibrosis, Crohn’s Disease, and other severe inflammatory conditions. Benefits and safety of this technology have been documented in over 2,500 treatments. EryDel SpA is a company focused on developing and commercializing innovative therapies and diagnostics based on the use of autologous RBCs as agent carriers. More recently, EryDel SpA completed a Phase II Proof of Concept study in patients with Ataxia Telangiectasia (AT, a rare progressive neurological autosomal recessive disorder that leads to mortality in most patients at an early age, with significant benefit seen on primary and secondary end-points. EryDex treatment has received Orphan Drug Designation by EMA for the treatment of Cystic Fibrosis and both by EMA and FDA for the treatment of AT. The encapsulation of superparamagnetic nanoparticles within RBC has lead to the generation
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Kooiman, K.; Böhmer, M.R.; Emmer, M.; Vos, Hendrik J.; Chlon, C.; Foppen-Harteveld, M.; Versluis, Michel; de Jong, N.; van Wamel, A.; Hennink, W.E.; Feijen, J.; Sam, A.P.
2008-01-01
The advantage of ultrasound contrast agents (UCAs) as drug delivery systems is the ability to non-invasively control the local and triggered release of a drug or gene. In this study we designed and characterized a novel UCA-based drug delivery system, based on polymer-shelled microcapsules filled
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Emerging sulfated flavonoids and other polyphenols as drugs: nature as an inspiration.
Correia-da-Silva, Marta; Sousa, Emília; Pinto, Madalena M M
2014-03-01
Nature uses sulfation of endogenous and exogenous molecules mainly to avoid potential toxicity. The growing importance of natural sulfated molecules, as modulators of a number of physiological and pathological processes, has inspired the synthesis of non-natural sulfated scaffolds. Until the 1990s, the synthesis of sulfated small molecules was almost restricted to derivatives of flavonoids and aimed mainly at structure elucidation and plant biosynthesis studies. Currently, the synthesis of this type of compounds concerns structurally diverse scaffolds and is aimed at the development of potential drugs and/or exploitation of the biological effects of sulfated metabolites. Some important hit compounds are emerging from sulfated flavonoids and other polyphenols mainly as anticoagulant and antiviral agents. When compared with polymeric macromolecules such as heparins, sulfated small molecules could be of value in therapeutics due to their hydrophobic nature that can contribute to improve the bioavailability. This review highlights the synthetic approaches that were applied to obtain monosulfated or polysulfated phenolic small molecules and compiles the diverse biological activities already reported for this type of derivatives. Toxicity and pharmacokinetic parameters of this emerging class of derivatives will also be considered, emphasizing their value for therapeutic applications. © 2013 Wiley Periodicals, Inc.
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Sexual Orientation Disparities in the Use of Emerging Drugs.
Goldbach, Jeremy T; Mereish, Ethan H; Burgess, Claire
2017-01-28
Prescription drug, e-cigarette, smokeless tobacco, and synthetic marijuana use has risen dramatically in the United States over the past decade. This paper investigates the use of risky substances among adolescents, and examines disparities between sexual minority (i.e., mostly heterosexual and lesbian, gay, bisexual; LGB) and heterosexual adolescents in use of novel and emerging substances. Given the public health risk and the imminence of these substances in the media, emerging drug use was examined in a county wide sample of adolescents in a Southern state. A probability sample of middle and high school students (N = 3012; ages 11-18) using random cluster methods was obtained in a mid-sized school district in the Southeastern United States. LGB adolescents reported higher past-30 day and lifetime use of cigarettes (AORs =2.77, 2.90, respectively), smokeless tobacco (lifetime only: AOR = 1.88), e-cigarettes (lifetime only; AOR = 1.92), alcohol (AORs = 1.7, 2.20), marijuana (AORs = 3.02, 3.06), synesthetic marijuana (AORs = 3.77, 2.48), and prescription drugs (AORs = 3.82, 2.55). Adolescents who self-identified as "mostly heterosexual" reported higher lifetime cigarette use, and past 30-day use of e-cigarettes and prescription drugs as compared with heterosexual adolescents. Our results are notable given the dearth of data documenting use of increasingly emerging or "trendy" substances such as prescription drugs. More research is needed to understand the underlying cause of these disparities, and efforts should be targeted toward this population to reduce negative outcomes from misuse.
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Surveillance of emerging drugs of abuse in Hong Kong: validation of an analytical tool.
Tang, Magdalene H Y; Ching, C K; Tse, M L; Ng, Carol; Lee, Caroline; Chong, Y K; Wong, Watson; Mak, Tony W L
2015-04-01
To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. Cross-sectional study. Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.
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Interactions between recreational drugs and antiretroviral agents.
Antoniou, Tony; Tseng, Alice Lin-In
2002-10-01
concomitant PIs, and patients should be monitored for signs of toxicity and/or loss of analgesia. PIs should not be coadministered with midazolam and triazolam, since prolonged sedation may occur. Interactions between agents commonly prescribed for patients with HIV and recreational drugs can occur, and may be associated with serious clinical consequences. Clinicians should encourage open dialog with their patients on this topic, to avoid compromising antiretroviral efficacy and increasing the risk of drug toxicity.
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Emerging therapies in multiple myeloma.
El-Amm, Joelle; Tabbara, Imad A
2015-06-01
The treatment of multiple myeloma has evolved significantly over the past 2 decades due to the use of high-dose chemotherapy and autologous stem cell transplantation, and the subsequent introduction of the immunomodulatory agents (thalidomide and lenalidomide) and the proteasome inhibitor (bortezomib). The median overall survival of multiple myeloma patients has increased significantly with patients younger than age 50 years experiencing a 10-year survival rate of around 40%. However, despite the increased effectiveness of the first-line agents, the majority of patients will eventually relapse and become drug resistant. Promising novel therapies have recently emerged and are being used to treat relapsed and refractory patients. This review will cover the clinical data regarding these emergent therapies that include new generation of proteasome inhibitors (carfilzomib, ixazomib, oprozomib, and marizomib), immunomodulatory drugs (pomalidomide), monoclonal antibodies (elotuzumab and daratumumab), signal transduction modulator (perifosine), and histone deacetylase inhibitors (vorinostat and panobinostat).
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Emergency First Response to a Crisis Event: A Multi-Agent Simulation Approach
National Research Council Canada - National Science Library
Roginski, Jonathan W
2006-01-01
.... This process led to the development of a multi-agent simulation methodology for emergency first response specifically applied to analyze a notional vehicle bomb attack during a festival in the Baltimore Inner Harbor...
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Drug Abuse on College Campuses: Emerging Issues. Issues in Prevention
Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2012
2012-01-01
This "Issues in Prevention" focuses on emerging issues concerning drug abuse on college campuses. This issue contains the following articles: (1) Drug Abuse Trends; (2) Q&A With Jim Lange; (3) Bath Salts; (4) Refuse to Abuse; (5) Related Federal Resource; and (6) Higher Education Center Resources.
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Emerging trends in the stabilization of amorphous drugs
DEFF Research Database (Denmark)
Laitinen, Riikka; Löbmann, Korbinian; Strachan, Clare J.
2013-01-01
The number of active pharmaceutical substances having high therapeutic potential but low water solubility is constantly increasing, making it difficult to formulate these compounds as oral dosage forms. The solubility and dissolution rate, and thus potentially the bioavailability, of these poorly...... water-soluble drugs can be increased by the formation of stabilized amorphous forms. Currently, formulation as solid polymer dispersions is the preferred method to enhance drug dissolution and to stabilize the amorphous form of a drug. The purpose of this review is to highlight emerging alternative...... of mesoporous silicon and silica-based carriers are presented as potential means to increase the stability of amorphous pharmaceuticals....
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New paradigm for drug developments--from emerging market statistical perspective.
Quan, Hui; Chen, Xun; Zhang, Ji; Zhao, Peng-Liang
2013-11-01
Paradigm for new drug development has changed dramatically over the last decade. Even though new technology increases efficiency in many aspects, partially due to much more stringent regulatory requirements, it actually now takes longer and costs more to develop a new drug. To deal with challenge, some initiatives are taken by the pharmaceutical industry. These initiatives include exploring emerging markets, conducting global trials and building research and development centers in emerging markets to curb spending. It is particularly the current trend that major pharmaceutical companies offshore a part of their biostatistical support to China. In this paper, we first discuss the skill set for trial statisticians in the new era. We then elaborate on some of the approaches for acquiring statistical talent and capacity in general, particularly in emerging markets. We also make some recommendations on the use of the PDUFA strategy and collaborations among industry, health authority and academia from emerging market statistical perspective. © 2013.
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International Nuclear Information System (INIS)
Matsumoto, Hideki
2012-01-01
Described is a flow of authors' studies on the drug development in the title, aiming to save the life after the emergent exposure to peri-lethal dose. Medicals with radioprotective properties have been essentially those to be given before the exposure. Authors have studied the mechanism of bystander effect of non-exposed cells where they, localizing around the directly radiation-exposed cells, acquire the radioresistance; have found that nitrogen oxide (NO) is one of mediators for the effect; and have thought to apply the NO generating agents for the drug already clinically available, such as sodium nitroprusside (SNP), isosorbide nitrate (ISDN), nicolandil (NC), nitroglycerin (NG), and nipradilol (NP). ISDN, NC, NG and NP exhibited no in vitro-toxicity in colony formation of human fibroblast AG1522 cells up to 30 micro-M whereas SNP was toxic at the level >3 micro-M due to the formation of cyanide which could be detoxicated in vivo. Actually, the 5 agents were not toxic in vivo. When male jcl/ICR mice were irradiated with lethal dose of 7.5 Gy X-ray and the 5 agents were given to make their level 30 micro-M immediately, 1, 2 and 7 days after the exposure, 3/5 animals given SNP survived. With the half lethal dose of 6.5 Gy X-ray and 50 animals, SNP was further examined in details: survival was found to be 75-85% in mice given SNP in contrast to 30-40% in the control and the life-saving effect was suggested to be due to suppression of intestinal and marrow death with the improved feature of peripheral platelet and leukocyte. Thus SNP, a drug for angina pectoris, is found radioprotective even post exposure. (T.T.)
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Crucial factors and emerging concepts in ultrasound-triggered drug delivery.
Geers, Bart; Dewitte, Heleen; De Smedt, Stefaan C; Lentacker, Ine
2012-12-28
Time and space controlled drug delivery still remains a huge challenge in medicine. A novel approach that could offer a solution is ultrasound guided drug delivery. “Ultrasonic drug delivery” is often based on the use of small gas bubbles (so-called microbubbles) that oscillate and cavitate upon exposure to ultrasound waves. Some microbubbles are FDA approved contrast agents for ultrasound imaging and are nowadays widely investigated as promising drug carriers. Indeed, it has been observed that upon exposure to ultrasound waves, microbubbles may (a) release the encapsulated drugs and (b) simultaneously change the structure of the cell membranes in contact with the microbubbles which may facilitate drug entrance into cells. This review aims to highlight (a) major factors known so far which affect ultrasonic drug delivery (like the structure of the microbubbles, acoustic settings, etc.) and (b) summarizes the recent preclinical progress in this field together with a number of promising new concepts and applications.
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Williamson, Deborah A; Carter, Glen P; Howden, Benjamin P
2017-07-01
Bacterial skin infections represent some of the most common infectious diseases globally. Prevention and treatment of skin infections can involve application of a topical antimicrobial, which may be an antibiotic (such as mupirocin or fusidic acid) or an antiseptic (such as chlorhexidine or alcohol). However, there is limited evidence to support the widespread prophylactic or therapeutic use of topical agents. Challenges involved in the use of topical antimicrobials include increasing rates of bacterial resistance, local hypersensitivity reactions (particularly to older agents, such as bacitracin), and concerns about the indiscriminate use of antiseptics potentially coselecting for antibiotic resistance. We review the evidence for the major clinical uses of topical antibiotics and antiseptics. In addition, we review the mechanisms of action of common topical agents and define the clinical and molecular epidemiology of antimicrobial resistance in these agents. Moreover, we review the potential use of newer and emerging agents, such as retapamulin and ebselen, and discuss the role of antiseptic agents in preventing bacterial skin infections. A comprehensive understanding of the clinical efficacy and drivers of resistance to topical agents will inform the optimal use of these agents to preserve their activity in the future. Copyright © 2017 American Society for Microbiology.
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Using data-driven agent-based models for forecasting emerging infectious diseases
Directory of Open Access Journals (Sweden)
Srinivasan Venkatramanan
2018-03-01
Full Text Available Producing timely, well-informed and reliable forecasts for an ongoing epidemic of an emerging infectious disease is a huge challenge. Epidemiologists and policy makers have to deal with poor data quality, limited understanding of the disease dynamics, rapidly changing social environment and the uncertainty on effects of various interventions in place. Under this setting, detailed computational models provide a comprehensive framework for integrating diverse data sources into a well-defined model of disease dynamics and social behavior, potentially leading to better understanding and actions. In this paper, we describe one such agent-based model framework developed for forecasting the 2014–2015 Ebola epidemic in Liberia, and subsequently used during the Ebola forecasting challenge. We describe the various components of the model, the calibration process and summarize the forecast performance across scenarios of the challenge. We conclude by highlighting how such a data-driven approach can be refined and adapted for future epidemics, and share the lessons learned over the course of the challenge. Keywords: Emerging infectious diseases, Agent-based models, Simulation optimization, Bayesian calibration, Ebola
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Drug-resistant tuberculosis: emerging treatment options
Directory of Open Access Journals (Sweden)
Adhvaryu MR
2011-12-01
Full Text Available Meghna Adhvaryu1, Bhasker Vakharia21Department of Biotechnology, SRK Institute of Computer Education and Applied Sciences, 2R&D, Bhuma Research in Ayurvedic and Herbal Medicine, Surat, Gujarat, IndiaAbstract: Multidrug-resistant tuberculosis has emerged worldwide, with an increasing incidence due to failure of implementation of apparently effective first-line antituberculous therapy as well as primary infection with drug-resistant strains. Failure of current therapy is attributed to a long duration of treatment leading to nonadherence and irregular therapy, lack of patient education about the disease, poverty, irregular supply by care providers, drug–drug interactions in patients coinfected with human immunodeficiency virus (HIV, inadequate regulations causing market overlap and irresponsible drug usage in the private sector, and lack of research, with no addition of new drugs in the last four decades. Present standards of care for the treatment of drug-susceptible tuberculosis, multidrug-resistant tuberculosis, tuberculosis-HIV coinfection, and latent tuberculosis infection are all unsatisfactory. Since 2000, the World Health Organization (WHO has focused on drug development for tuberculosis, as well as research in all relevant aspects to discover new regimens by 2015 and to eliminate tuberculosis as a public health concern by 2050. As a result, some 20 promising compounds from 14 groups of drugs have been discovered. Twelve candidates from eight classes are currently being evaluated in clinical trials. Ongoing research should prioritize identification of novel targets and newer application of existing drugs, discovery of multitargeted drugs from natural compounds, strengthening host factors by immunopotentiation with herbal immunomodulators, as well as protective vaccines before and after exposure, consideration of surgical measures when indicated, development of tools for rapid diagnosis, early identification of resistant strains, and
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Enhanced risk management by an emerging multi-agent architecture
Lin, Sin-Jin; Hsu, Ming-Fu
2014-07-01
Classification in imbalanced datasets has attracted much attention from researchers in the field of machine learning. Most existing techniques tend not to perform well on minority class instances when the dataset is highly skewed because they focus on minimising the forecasting error without considering the relative distribution of each class. This investigation proposes an emerging multi-agent architecture, grounded on cooperative learning, to solve the class-imbalanced classification problem. Additionally, this study deals further with the obscure nature of the multi-agent architecture and expresses comprehensive rules for auditors. The results from this study indicate that the presented model performs satisfactorily in risk management and is able to tackle a highly class-imbalanced dataset comparatively well. Furthermore, the knowledge visualised process, supported by real examples, can assist both internal and external auditors who must allocate limited detecting resources; they can take the rules as roadmaps to modify the auditing programme.
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Gahlawat, Geeta; Shikha, Sristy; Chaddha, Baldev Singh; Chaudhuri, Saumya Ray; Mayilraj, Shanmugam; Choudhury, Anirban Roy
2016-02-01
With the increased number of cholera outbreaks and emergence of multidrug resistance in Vibrio cholerae strains it has become necessary for the scientific community to devise and develop novel therapeutic approaches against cholera. Recent studies have indicated plausibility of therapeutic application of metal nano-materials. Among these, silver nanoparticles (AgNPs) have emerged as a potential antimicrobial agent to combat infectious diseases. At present nanoparticles are mostly produced using physical or chemical techniques which are toxic and hazardous. Thus exploitation of microbial systems could be a green eco-friendly approach for the synthesis of nanoparticles having similar or even better antimicrobial activity and biocompatibility. Hence, it would be worth to explore the possibility of utilization of microbial silver nanoparticles and their conjugates as potential novel therapeutic agent against infectious diseases like cholera. The present study attempted utilization of Ochrobactrum rhizosphaerae for the production of AgNPs and focused on investigating their role as antimicrobial agents against cholera. Later the exopolymer, purified from the culture supernatant, was used for the synthesis of spherical shaped AgNPs of around 10 nm size. Further the exopolymer was characterized as glycolipoprotein (GLP). Antibacterial activity of the novel GLP-AgNPs conjugate was evaluated by minimum inhibitory concentration, XTT reduction assay, scanning electron microscopy (SEM) and growth curve analysis. SEM studies revealed that AgNPs treatment resulted in intracellular contents leakage and cell lysis. The potential of microbially synthesized nanoparticles, as novel therapeutic agents, is still relatively less explored. In fact, the present study first time demonstrated that a glycolipoprotein secreted by the O. rhizosphaerae strain can be exploited for production of AgNPs which can further be employed to treat infectious diseases. Although this type of polymer has
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Targeting Antibacterial Agents by Using Drug-Carrying Filamentous Bacteriophages
Yacoby, Iftach; Shamis, Marina; Bar, Hagit; Shabat, Doron; Benhar, Itai
2006-01-01
Bacteriophages have been used for more than a century for (unconventional) therapy of bacterial infections, for half a century as tools in genetic research, for 2 decades as tools for discovery of specific target-binding proteins, and for nearly a decade as tools for vaccination or as gene delivery vehicles. Here we present a novel application of filamentous bacteriophages (phages) as targeted drug carriers for the eradication of (pathogenic) bacteria. The phages are genetically modified to display a targeting moiety on their surface and are used to deliver a large payload of a cytotoxic drug to the target bacteria. The drug is linked to the phages by means of chemical conjugation through a labile linker subject to controlled release. In the conjugated state, the drug is in fact a prodrug devoid of cytotoxic activity and is activated following its dissociation from the phage at the target site in a temporally and spatially controlled manner. Our model target was Staphylococcus aureus, and the model drug was the antibiotic chloramphenicol. We demonstrated the potential of using filamentous phages as universal drug carriers for targetable cells involved in disease. Our approach replaces the selectivity of the drug itself with target selectivity borne by the targeting moiety, which may allow the reintroduction of nonspecific drugs that have thus far been excluded from antibacterial use (because of toxicity or low selectivity). Reintroduction of such drugs into the arsenal of useful tools may help to combat emerging bacterial antibiotic resistance. PMID:16723570
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Nivolumab, a new immunomodulatory drug, a new adverse effect; adrenal crisis
Directory of Open Access Journals (Sweden)
Funda Karbek Akarca
2017-12-01
Full Text Available Owing to the advancements in medicine, new information is obtained regarding cancer, new antineoplastic agents are developed. Frequent use of these new pharmacological agents emergency physicians to be vigilant about their side effects. We present a case of adrenal crisis in a patient with non-small cell lung cancer (NSCLC, caused by an immunomodulatory drug; nivolumab. While adverse events are related to other immunomodulatory drugs have been reported in literature, our case is the first nivolumab-related adrenal failure to be reported. A patient with lung cancer presented to the emergency room(ER with nausea and vomiting. Hyponatremia, hyperkalemia, persistent hypoglycemia led to the diagnosis of adrenal crisis. Having direct effect on the immune system, these drugs were claimed to be highly reliable. However, there is no reliable data on the side effect profile of these agents. It should be kept in mind that life-threatening auto-immune reactions may occur. Keywords: Nivolumab, Immunomodulation, CTLA 4 antigen, Adrenal crisis
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Emerging therapies for the treatment of osteoporosis
Directory of Open Access Journals (Sweden)
Garima Bhutani
2013-01-01
Full Text Available Osteoporosis is a chronic disease of the osseous system characterized by decreased bone strength and increased fracture risk. It is due to an imbalance in the dynamic ongoing processes of bone formation and bone resorption. Currently available osteoporosis therapies like bisphosphonates, selective estrogen receptor modulators (SERMs, and denosumab are anti-resorptive agents. Parathyroid hormone analogs like teriparatide are the only anabolic agents currently approved for osteoporosis treatment. The side-effects and limited efficacy of the presently available therapies has encouraged extensive research into the pathophysiology of the disease and newer drug targets for its treatment. The novel anti-resorptive agents being developed are newer SERMs, osteoprotegerin, c-src (cellular-sarcoma kinase inhibitors, αVβ3 integrin antagonists, cathepsin K inhibitors, chloride channel inhibitors, and nitrates. Upcoming anabolic agents include calcilytics, antibodies against sclerostin and Dickkopf-1, statins, matrix extracellular phosphoglycoprotein fragments activin inhibitiors, and endo-cannabinoid agonists. Many of these new drugs are still in development. This article provides an insight into the emerging drugs for the treatment of osteoporosis.
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Dewantara, Fauzi; Budianto, Emil
2018-04-01
Chitosan-methyl cellulose semi-IPN hydrogel is used as floating drug delivery system, and calcium carbonate also added as pore forming agent. The hydrogel network arranged by not only using biopolymer chitosan and methyl cellulose, but also the crosslink agent that is glutaraldehyde. Amoxicillin trihydrate entrapped into the polymer network with two different method, in situ loading and post loading. Furthermore both method has been tested for drug entrapment efficiency along with drug dissolution test, and the result for drug entrapment efficiency is in situ loading method has highest value of 100%, compared to post loading method which has value only 71%. Moreover, at the final time of drug dissolution test shows in situ loading method has value of 96% for total accumulative of drug dissolution, meanwhile post loading method has 72%. The value of drug dissolution test from both method is used for analyzing drug dissolution mechanism of amoxicillin trihydrate from hydrogel network with four mathematical drug mechanism models as parameter. The polymer network encounter destructive degradation causes by acid solution which used as dissolution medium, and the level of degradation is observed with optical microscope. However the result shows that degradation of the polymer network doesn't affect drug dissolution mechanism directly. Although the pore forming agent causes the pore inside the hydrogel network create interconnection and it was quite influential to drug dissolution mechanism. Interconnected pore is observed with Scanning Electron Microscope (SEM) and shows that the amount and area of interconnected pore inside the hydrogel network is increasing as drug dissolution goes on.
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Trends and emerging drugs in Kenya: A case study in Mombasa and ...
African Journals Online (AJOL)
Most of the highly abused drugs were 'kuber, shisha, shashaman, mau, tambuu, jet fuel, kukumanga, mkorogo, mshomoro, rohypnol, Artaine and kamusi. 'Shisha' and 'kuber' were most commonly abused drugs in both counties. Over 25% of the shisha and kuber abusers aged between 26 to 35 years. The emerging drugs ...
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Social influence, agent heterogeneity and the emergence of the urban informal sector
García-Díaz, César; Moreno-Monroy, Ana I.
2012-02-01
We develop an agent-based computational model in which the urban informal sector acts as a buffer where rural migrants can earn some income while queuing for higher paying modern-sector jobs. In the model, the informal sector emerges as a result of rural-urban migration decisions of heterogeneous agents subject to social influence in the form of neighboring effects of varying strengths. Besides using a multinomial logit choice model that allows for agent idiosyncrasy, explicit agent heterogeneity is introduced in the form of socio-demographic characteristics preferred by modern-sector employers. We find that different combinations of the strength of social influence and the socio-economic composition of the workforce lead to very different urbanization and urban informal sector shares. In particular, moderate levels of social influence and a large proportion of rural inhabitants with preferred socio-demographic characteristics are conducive to a higher urbanization rate and a larger informal sector.
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Smelick, Gillian S; Heffron, Timothy P; Chu, Laura; Dean, Brian; West, David A; Duvall, Scott L; Lum, Bert L; Budha, Nageshwar; Holden, Scott N; Benet, Leslie Z; Frymoyer, Adam; Dresser, Mark J; Ware, Joseph A
2013-11-04
Acid-reducing agents (ARAs) are the most commonly prescribed medications in North America and Western Europe. There are currently no data describing the prevalence of their use among cancer patients. However, this is a paramount question due to the potential for significant drug-drug interactions (DDIs) between ARAs, most commonly proton pump inhibitors (PPIs), and orally administered cancer therapeutics that display pH-dependent solubility, which may lead to decreased drug absorption and decreased therapeutic benefit. Of recently approved orally administered cancer therapeutics, >50% are characterized as having pH-dependent solubility, but there are currently no data describing the potential for this ARA-DDI liability among targeted agents currently in clinical development. The objectives of this study were to (1) determine the prevalence of ARA use among different cancer populations and (2) investigate the prevalence of orally administered cancer therapeutics currently in development that may be liable for an ARA-DDI. To address the question of ARA use among cancer patients, a retrospective cross-sectional analysis was performed using two large healthcare databases: Thomson Reuters MarketScan (N = 1,776,443) and the U.S. Department of Veterans Affairs (VA, N = 1,171,833). Among all cancer patients, the total prevalence proportion of ARA use (no. of cancer patients receiving an ARA/total no. of cancer patients) was 20% and 33% for the MarketScan and VA databases, respectively. PPIs were the most commonly prescribed agent, comprising 79% and 65% of all cancer patients receiving a prescription for an ARA (no. of cancer patients receiving a PPI /no. of cancer patients receiving an ARA) for the MarketScan and VA databases, respectively. To estimate the ARA-DDI liability of orally administered molecular targeted cancer therapeutics currently in development, two publicly available databases, (1) Kinase SARfari and (2) canSAR, were examined. For those orally administered
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A study of the web as DTC drug marketing agent.
Lorence, Daniel; Churchill, Rick
2007-12-01
The growth of direct-to-consumer (DTC) marketing of pharmaceuticals in the USA has spawned the generation of web sites for consumer information and discussion, related to specific medical conditions and the efficacy of specific drugs. In such an environment consumers often find and act upon health information of variable quality, with little input from health professionals. Some health policy analysts argue that the emergence of such consumer "drug networks" will lead to unnecessary expenditure of money on prescription drugs, as consumers see ads and then demand that their providers prescribe that drug. Others say that an intelligent consumer will be able to research the information and narrow down a drug that will likely work for them personally, rather than having the provider "experiment" with different medications. There exist few cross-disciplinary evaluative frameworks for assessing such health information, especially within commercial search engines. This study serves as an exploratory technology assessment that examines the prevalence of web-based DTC for a popular prescription drug and the impact on healthcare consumers.
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Emerging trends in the stabilization of amorphous drugs.
Laitinen, Riikka; Löbmann, Korbinian; Strachan, Clare J; Grohganz, Holger; Rades, Thomas
2013-08-30
The number of active pharmaceutical substances having high therapeutic potential but low water solubility is constantly increasing, making it difficult to formulate these compounds as oral dosage forms. The solubility and dissolution rate, and thus potentially the bioavailability, of these poorly water-soluble drugs can be increased by the formation of stabilized amorphous forms. Currently, formulation as solid polymer dispersions is the preferred method to enhance drug dissolution and to stabilize the amorphous form of a drug. The purpose of this review is to highlight emerging alternative methods to amorphous polymer dispersions for stabilizing the amorphous form of drugs. First, an overview of the properties and stabilization mechanisms of amorphous forms is provided. Subsequently, formulation approaches such as the preparation of co-amorphous small-molecule mixtures and the use of mesoporous silicon and silica-based carriers are presented as potential means to increase the stability of amorphous pharmaceuticals. Copyright © 2012 Elsevier B.V. All rights reserved.
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Brazil: An emerging partner in drug R&D.
Rodrigues, Debora G
2009-08-01
With the need for innovation in drug discovery and development and changes to patent laws that are enabling greater IP protection, many pharmaceutical companies are pursuing international cooperation agreements with foreign companies as part of a global development strategy to enhance product pipelines. Brazil, the largest pharmaceutical market in Latin America, has improved its infrastructure, scientific and technological capabilities and has created a sustainable strategy to promote drug discovery research activities. Positive economic growth, a stable political structure, expanding patient populations an increasing governmental, private and foreign investments are creating a new landscape for drug R&D in the country. As Brazilian-based pharmaceutical companies become further established, new opportunities for partnerships and collaborative alliances are becoming available for the drug discovery process, as well as for co-manufacturing and co-marketing efforts. This feature review provides an overview of the Brazilian pharmaceutical market and discusses current opportunities, emerging trends and challenges for this expanding market.
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Liu, Zhihong; Wang, Yutao; Zhang, Na
2012-07-01
During the past decades, polymer-drug conjugates are one of the hottest topics in novel drug development fields. Amphiphilic polymer-drug conjugates in aqueous solution could form micelles or micelle-like nanoassemblies. Compared with polymer-drug conjugates and the micelles into which drugs are physically entrapped, micelles or micelle-like nanoassemblies based on polymer-drug conjugates bring several additional advantages, including increased drug-loading capacity, enhanced intracellular uptake, reduced systemic toxicity, and improved therapeutic efficacy. This review focuses on recent progress achieved in the research field of micelles or micelle-like nanoassemblies based on polymer-drug conjugates. Firstly, properties of polymers, drugs, and linkers which could be used to build polymer-drug conjugate micelles or micelle-like nanoassemblies are summarized. Then, the characterization methods are described. Finally, the drug-targeting mechanisms are discussed. Micelles or micelle-like nanoassemblies based on polymer-drug conjugates as an emerging platform have the potential to achieve medical treatments with enhanced therapeutic effect. The application of micelles or micelle-like nanoassemblies based on polymer-drug conjugates may give new life to old active compounds abandoned due to their low solubility problems. For clinical application, there is a need to further optimize the properties of the polymer, drug, and linker.
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Directory of Open Access Journals (Sweden)
Jasleen K. Sodhi
2017-07-01
Full Text Available In some cases, the formation of reactive species from the metabolism of xenobiotics has been linked to toxicity and therefore it is imperative to detect potential bioactivation for candidate drugs during drug discovery. Reactive species can covalently bind to trapping agents in in vitro incubations of compound with human liver microsomes (HLM fortified with β-nicotinamide adenine dinucleotide phosphate (NADPH, resulting in a stable conjugate of trapping agent and reactive species, thereby facilitating analytical detection and providing evidence of short-lived reactive metabolites. Since reactive metabolites are typically generated by cytochrome P450 (CYP oxidation, it is important to ensure high concentrations of trapping agents are not inhibiting the activities of CYP isoforms. Here we assessed the inhibitory properties of fourteen trapping agents against the major human CYP isoforms (CYP1A2, 2C9, 2C19, 2D6 and 3A. Based on our findings, eleven trapping agents displayed inhibition, three of which had IC50 values less than 1 mM (2-mercaptoethanol, N-methylmaleimide and N-ethylmaleimide (NEM. Three trapping agents (dimedone, N-acetyl-lysine and arsenite did not inhibit CYP isoforms at concentrations tested. To illustrate effects of CYP inhibition by trapping agents on reactive intermediate trapping, an example drug (ticlopidine and trapping agent (NEM were chosen for further studies. For the same amount of ticlopidine (1 μM, increasing concentrations of the trapping agent NEM (0.007–40 mM resulted in a bell-shaped response curve of NEM-trapped ticlopidine S-oxide (TSO-NEM, due to CYP inhibition by NEM. Thus, trapping studies should be designed to include several concentrations of trapping agent to ensure optimal trapping of reactive metabolites.
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Cyber-pharmacies and emerging concerns on marketing drugs online
Directory of Open Access Journals (Sweden)
Vinod Scaria
2003-08-01
Full Text Available The booming e-commerce and a regulation-less environment online have led to the rise of a new generation of websites that market drugs and other products over the Internet. Some of these drugs are often herbal products or of dubious quality, often marketed with a mix of professional design and unverified/fraudulent claims. Several concerns have arisen from different corners and evidence of malpractice has emerged. But there is a lack of sufficient evidence confirming the concerns.
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Manual Engineering and Evolution of Emergent Algorithms for Agents on Two-dimensional Grids
Komann, Marcus
2011-01-01
In this thesis, the problem of detecting the attributes of multiple objects in binary images in realtime is solved. It is a common problem in industrial machine vision. For the solution, the usage of emergent algorithms on a smart camera with a fine-grained massively-parallel processor is proposed. Combining both is promising since such processors can exploit the abilities of emergent algorithms. Therefore, so-called Marching Pixels are introduced. These are local agents that traverse the pix...
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Carbon Nanotubes: An Emerging Drug Carrier for Targeting Cancer Cells
Bhattacharya, Shiv Sankar; Mishra, Arun Kumar; Verma, Navneet; Verma, Anurag; Pandit, Jayanta Kumar
2014-01-01
During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review. PMID:24872894
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Pang, Hui; Li, Guilian; Zhao, Xiuqin; Liu, Haican; Wan, Kanglin; Yu, Ping
2015-01-01
Several species of rapidly growing mycobacteria (RGM) are now recognized as human pathogens. However, limited data on effective drug treatments against these organisms exists. Here, we describe the species distribution and drug susceptibility profiles of RGM clinical isolates collected from four southern Chinese provinces from January 2005 to December 2012. Clinical isolates (73) were subjected to in vitro testing with 31 antimicrobial agents using the cation-adjusted Mueller-Hinton broth microdilution method. The isolates included 55 M. abscessus, 11 M. fortuitum, 3 M. chelonae, 2 M. neoaurum, and 2 M. septicum isolates. M. abscessus (75.34%) and M. fortuitum (15.07%), the most common species, exhibited greater antibiotic resistance than the other three species. The isolates had low resistance to amikacin, linezolid, and tigecycline, and high resistance to first-line antituberculous agents, amoxicillin-clavulanic acid, rifapentine, dapsone, thioacetazone, and pasiniazid. M. abscessus and M. fortuitum were highly resistant to ofloxacin and rifabutin, respectively. The isolates showed moderate resistance to the other antimicrobial agents. Our results suggest that tigecycline, linezolid, clofazimine, and cefmetazole are appropriate choices for M. abscessus infections. Capreomycin, sulfamethoxazole, tigecycline, clofazimine, and cefmetazole are potentially good choices for M. fortuitum infections. Our drug susceptibility data should be useful to clinicians.
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Directory of Open Access Journals (Sweden)
Hui Pang
2015-01-01
Full Text Available Objectives. Several species of rapidly growing mycobacteria (RGM are now recognized as human pathogens. However, limited data on effective drug treatments against these organisms exists. Here, we describe the species distribution and drug susceptibility profiles of RGM clinical isolates collected from four southern Chinese provinces from January 2005 to December 2012. Methods. Clinical isolates (73 were subjected to in vitro testing with 31 antimicrobial agents using the cation-adjusted Mueller-Hinton broth microdilution method. The isolates included 55 M. abscessus, 11 M. fortuitum, 3 M. chelonae, 2 M. neoaurum, and 2 M. septicum isolates. Results. M. abscessus (75.34% and M. fortuitum (15.07%, the most common species, exhibited greater antibiotic resistance than the other three species. The isolates had low resistance to amikacin, linezolid, and tigecycline, and high resistance to first-line antituberculous agents, amoxicillin-clavulanic acid, rifapentine, dapsone, thioacetazone, and pasiniazid. M. abscessus and M. fortuitum were highly resistant to ofloxacin and rifabutin, respectively. The isolates showed moderate resistance to the other antimicrobial agents. Conclusions. Our results suggest that tigecycline, linezolid, clofazimine, and cefmetazole are appropriate choices for M. abscessus infections. Capreomycin, sulfamethoxazole, tigecycline, clofazimine, and cefmetazole are potentially good choices for M. fortuitum infections. Our drug susceptibility data should be useful to clinicians.
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Emergence of Drug-Resistant Tuberculosis at a South African Mine
Centers for Disease Control (CDC) Podcasts
2010-03-03
This podcast describes the emergence of increasingly drug resistant tuberculosis at a mine in South Africa. CDCâs Dr. Dixie Snider discusses the outbreak and some of the reasons it may have occurred, despite the existence of a well-functioning TB control program at the mine. Created: 3/3/2010 by Emerging Infectious Diseases. Date Released: 3/3/2010.
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Directory of Open Access Journals (Sweden)
I. A. Vasilyeva
2017-01-01
Full Text Available Objective of the study: to study the effect of specific TB drugs and antimicrobial agents constituting chemotherapy regimens on the efficiency of treatment of tuberculosis patients with various patterns of multiple drug resistance.Subjects and Methods. 412 pulmonary tuberculosis patients with bacillary excretion and various patterns of multiple drug resistance were enrolled into the study (117 patients with MDR TB (non pre-XDR and non-XDR; 120 patients with pre-XDR TB and 175 with XDR TB. Patients in the subgroups were compatible regarding sex and age. The patients were prescribed regimens including 5-6 drugs in accordance with their drug resistance pattern. The time of sputum conversion (by culture versus the year of treatment was selected as a surrogate endpoint. The effect of specific TB drugs and antimicrobial agents on treatment efficiency was assessed through calculation of odds ratio (OR of achieving a surrogate endpoint in the patients receiving and not receiving a certain drug.Results. In the subgroup of pre-XDR TB, the following drugs demonstrated the valid increase of odds of sputum conversion: ethambutol (OR 11.8, pyrazinamide (OR 10.2, moxifloxacin (OR 7.8, capreomicin (OR 4.41. Sputum conversion was achieved in all 11 patients treated with bedaquiline.In the subgroup of XDR TB, the following drugs provided a positive effect on the achievement of sputum conversion: bedaquiline (OR 9.62, linezolid (OR 8.15, cycloserine (OR 7.88, pyrazinamide (OR 7.29, moxifloxacin (OR 7.08, and ethambutol (OR 6.69. Ofloxacin demonstrated a confident negative effect on achieving sputum conversion (95% CI 0.06-0.32.
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Calibrating emergent phenomena in stock markets with agent based models.
Fievet, Lucas; Sornette, Didier
2018-01-01
Since the 2008 financial crisis, agent-based models (ABMs), which account for out-of-equilibrium dynamics, heterogeneous preferences, time horizons and strategies, have often been envisioned as the new frontier that could revolutionise and displace the more standard models and tools in economics. However, their adoption and generalisation is drastically hindered by the absence of general reliable operational calibration methods. Here, we start with a different calibration angle that qualifies an ABM for its ability to achieve abnormal trading performance with respect to the buy-and-hold strategy when fed with real financial data. Starting from the common definition of standard minority and majority agents with binary strategies, we prove their equivalence to optimal decision trees. This efficient representation allows us to exhaustively test all meaningful single agent models for their potential anomalous investment performance, which we apply to the NASDAQ Composite index over the last 20 years. We uncover large significant predictive power, with anomalous Sharpe ratio and directional accuracy, in particular during the dotcom bubble and crash and the 2008 financial crisis. A principal component analysis reveals transient convergence between the anomalous minority and majority models. A novel combination of the optimal single-agent models of both classes into a two-agents model leads to remarkable superior investment performance, especially during the periods of bubbles and crashes. Our design opens the field of ABMs to construct novel types of advanced warning systems of market crises, based on the emergent collective intelligence of ABMs built on carefully designed optimal decision trees that can be reversed engineered from real financial data.
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Calibrating emergent phenomena in stock markets with agent based models
Sornette, Didier
2018-01-01
Since the 2008 financial crisis, agent-based models (ABMs), which account for out-of-equilibrium dynamics, heterogeneous preferences, time horizons and strategies, have often been envisioned as the new frontier that could revolutionise and displace the more standard models and tools in economics. However, their adoption and generalisation is drastically hindered by the absence of general reliable operational calibration methods. Here, we start with a different calibration angle that qualifies an ABM for its ability to achieve abnormal trading performance with respect to the buy-and-hold strategy when fed with real financial data. Starting from the common definition of standard minority and majority agents with binary strategies, we prove their equivalence to optimal decision trees. This efficient representation allows us to exhaustively test all meaningful single agent models for their potential anomalous investment performance, which we apply to the NASDAQ Composite index over the last 20 years. We uncover large significant predictive power, with anomalous Sharpe ratio and directional accuracy, in particular during the dotcom bubble and crash and the 2008 financial crisis. A principal component analysis reveals transient convergence between the anomalous minority and majority models. A novel combination of the optimal single-agent models of both classes into a two-agents model leads to remarkable superior investment performance, especially during the periods of bubbles and crashes. Our design opens the field of ABMs to construct novel types of advanced warning systems of market crises, based on the emergent collective intelligence of ABMs built on carefully designed optimal decision trees that can be reversed engineered from real financial data. PMID:29499049
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Emerging drugs for secondary hyperparathyroidism.
Cozzolino, Mario; Tomlinson, James; Walsh, Liron; Bellasi, Antonio
2015-06-01
Secondary hyperparathyroidism (SHPT), a common, serious, and progressive complication of chronic kidney disease (CKD), is characterized by elevated serum parathyroid hormone (PTH), parathyroid gland hyperplasia, and mineral metabolism abnormalities. These disturbances may result in CKD-mineral and bone disorder (CKD-MBD), which is associated with poor quality of life and short life expectancy. The goal of SHPT treatment is to maintain PTH, calcium, and phosphorus within accepted targeted ranges. This review highlights the pathogenesis of SHPT and current SHPT therapeutic approaches, including the use of low-phosphate diets, phosphate binders, 1,25-dihydroxyvitamin D3 (calcitriol) and its analogs, calcimimetics, and parathyroidectomy in addition to discussing emerging drugs in development for SHPT. Numerous studies indicate that mineral abnormalities occur early in the course of CKD, are prevalent by the time patients enter dialysis, and foreshadow a risk of cardiovascular and all-cause mortality. Several newly developed compounds may potentially overcome the limitations of current SHPT therapies. If emerging therapies can reduce PTH, normalize mineral metabolism, promote treatment adherence, and reduce the risk of side effects, they may provide the requisite features for improving long-term outcomes in patients with SHPT receiving dialysis and reduce the risks of CKD-MBD.
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Vera, Javier
2018-01-01
What is the influence of short-term memory enhancement on the emergence of grammatical agreement systems in multi-agent language games? Agreement systems suppose that at least two words share some features with each other, such as gender, number, or case. Previous work, within the multi-agent language-game framework, has recently proposed models stressing the hypothesis that the emergence of a grammatical agreement system arises from the minimization of semantic ambiguity. On the other hand, neurobiological evidence argues for the hypothesis that language evolution has mainly related to an increasing of short-term memory capacity, which has allowed the online manipulation of words and meanings participating particularly in grammatical agreement systems. Here, the main aim is to propose a multi-agent language game for the emergence of a grammatical agreement system, under measurable long-range relations depending on the short-term memory capacity. Computer simulations, based on a parameter that measures the amount of short-term memory capacity, suggest that agreement marker systems arise in a population of agents equipped at least with a critical short-term memory capacity.
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Ai-Ho Liao
2016-01-01
This report discusses a new development in the use of ultrasound microbubble contrast agents on transdermal drug delivery. The medium surrounding the microbubbles at the optimum concentration from liquid to gel can be modified and it can still achieve the same enhancement for transdermal drug permeation as liquid medium. It was also found that under the same ultrasound power density, microbubbles of larger particle sizes can extend the penetration depths of dye at the phantom surface.
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Nanoparticle-based drug delivery systems: promising approaches against infections
International Nuclear Information System (INIS)
Ranghar, Shweta; Sirohi, Parul; Verma, Pritam; Agarwal, Vishnu
2014-01-01
Despite the fact that many new drugs and technologies have been developed to combat the infectious diseases, these have continued to be global health challenges. The use of conventional antimicrobial agents against these infections is always associated with problems such as the development of multiple drug resistance and adverse side effects. In addition, the inefficient traditional drug delivery system results in inadequate therapeutic index, low bioavailability of drugs and many other limitations. In this regard, antimicrobial nanoparticles and nanosized drug delivery carriers have emerged as potent effective agents against the infections. Nanoparticles have unique properties owing to their ultra small and controllable size such as high surface area, enhanced reactivity, and functionalizable structure. This review focused on different classes of antimicrobial nanoparticles, including metal, metal oxide and others along with their mechanism of action and their potential use against the infections. The review also focused on the development of nanoparticle systems for antimicrobial drug delivery and use of these systems for delivery of various antimicrobial agents, giving an overview about modern nanoparticle based therapeutic strategies against the infections. (author)
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Nanoparticle-based drug delivery systems: promising approaches against infections
Energy Technology Data Exchange (ETDEWEB)
Ranghar, Shweta; Sirohi, Parul [Department of Applied Mechanics, Motilal Nehru National Institute of Technology, Allahabad (India); Verma, Pritam; Agarwal, Vishnu [Department of Biotechnology, Motilal Nehru National Institute of Technology, Allahabad (India)
2014-03-15
Despite the fact that many new drugs and technologies have been developed to combat the infectious diseases, these have continued to be global health challenges. The use of conventional antimicrobial agents against these infections is always associated with problems such as the development of multiple drug resistance and adverse side effects. In addition, the inefficient traditional drug delivery system results in inadequate therapeutic index, low bioavailability of drugs and many other limitations. In this regard, antimicrobial nanoparticles and nanosized drug delivery carriers have emerged as potent effective agents against the infections. Nanoparticles have unique properties owing to their ultra small and controllable size such as high surface area, enhanced reactivity, and functionalizable structure. This review focused on different classes of antimicrobial nanoparticles, including metal, metal oxide and others along with their mechanism of action and their potential use against the infections. The review also focused on the development of nanoparticle systems for antimicrobial drug delivery and use of these systems for delivery of various antimicrobial agents, giving an overview about modern nanoparticle based therapeutic strategies against the infections. (author)
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Drug induced hypertension--An unappreciated cause of secondary hypertension.
Grossman, Alon; Messerli, Franz H; Grossman, Ehud
2015-09-15
Most patients with hypertension have essential hypertension or well-known forms of secondary hypertension, such as renal disease, renal artery stenosis, or common endocrine diseases (hyperaldosteronism or pheochromocytoma). Physicians are less aware of drug induced hypertension. A variety of therapeutic agents or chemical substances may increase blood pressure. When a patient with well controlled hypertension is presented with acute blood pressure elevation, use of drug or chemical substance which increases blood pressure should be suspected. Drug-induced blood pressure increases are usually minor and short-lived, although rare hypertensive emergencies associated with use of certain drugs have been reported. Careful evaluation of prescription and non-prescription medications is crucial in the evaluation of the hypertensive individual and may obviate the need for expensive and unnecessary evaluations. Discontinuation of the offending agent will usually achieve adequate blood pressure control. When use of a chemical agent which increases blood pressure is mandatory, anti-hypertensive therapy may facilitate continued use of this agent. We summarize the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action. Copyright © 2015 Elsevier B.V. All rights reserved.
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Nanotechnology-based combinational drug delivery: an emerging approach for cancer therapy.
Parhi, Priyambada; Mohanty, Chandana; Sahoo, Sanjeeb Kumar
2012-09-01
Combination therapy for the treatment of cancer is becoming more popular because it generates synergistic anticancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. In recent years, nanotechnology-based combination drug delivery to tumor tissues has emerged as an effective strategy by overcoming many biological, biophysical and biomedical barriers that the body stages against successful delivery of anticancer drugs. The sustained, controlled and targeted delivery of chemotherapeutic drugs in a combination approach enhanced therapeutic anticancer effects with reduced drug-associated side effects. In this article, we have reviewed the scope of various nanotechnology-based combination drug delivery approaches and also summarized the current perspective and challenges facing the successful treatment of cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.
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Optimal Implementation of Prescription Drug Monitoring Programs in the Emergency Department
Directory of Open Access Journals (Sweden)
Garrett DePalma
2018-02-01
Full Text Available The opioid epidemic is the most significant modern-day, public health crisis. Physicians and lawmakers have developed methods and practices to curb opioid use. This article describes one method, prescription drug monitoring programs (PDMP, through the lens of how to optimize use for emergency departments (ED. EDs have rapidly become a central location to combat opioid abuse and drug diversion. PDMPs can provide emergency physicians with comprehensive prescribing information to improve clinical decisions around opioids. However, PDMPs vary tremendously in their accessibility and usability in the ED, which limits their effectiveness at the point of care. Problems are complicated by varying state-to-state requirements for data availability and accessibility. Several potential solutions to improving the utility of PDMPs in EDs include integrating PDMPs with electronic health records, implementing unsolicited reporting and prescription context, improving PDMP accessibility, data analytics, and expanding the scope of PDMPs. These improvements may help improve clinical decision-making for emergency physicians through better data, data presentation, and accessibility.
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[Evaluation of the safety of innovative drugs against viruses and infectious agents].
Kobayashi, Tetsu; Yusa, Keisuke; Kawasaki, Nana
2013-01-01
Recently, several novel cellular therapy products and biological drugs are being developed to treat various previously untreatable diseases. One of the most important issues regarding these innovations is how to ensure safety over infectious agents, including viruses and prions, in the earliest treatments with these products. The object of this study is a risk assessment of cases of human infectious with the agents and to present a sample risk management plan based on a collaboration among the National Institute of Health Sciences, universities, marketing authorization holders, and scientific societies. There are three subjects of study: (1) the viral safety of cellular therapy products, (2) the viral safety of biological drugs, and (3) the safety of prions. In this report, we describe the objects of the study, the project members, the study plan outline, and the ongoing plans. The results of the viral risk identification and the risk analysis of cellular therapy products will also be described, based on a review of the literature and case reports obtained during the first year of this project.
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Growing Up of Autonomous Agents: an Emergent Phenomenon
Morgavi, Giovanna; Marconi, Lucia
2008-10-01
A fundamental research challenge is the design of robust artifacts that are capable of operating under changing environments and noisy input, and yet exhibit the desired behavior and response time. These systems should be able to adapt and learn how to react to unforeseen scenarios as well as to display properties comparable to biological entities. The turn to nature has brought us many unforeseen great concepts. Biological systems are able to handle many of these challenges with an elegance and efficiency still far beyond current human artifacts. A living artifact grows up when its capabilities, abilities/knowledge, shift to a further level of complexity, i.e. the complexity rank of its internal capabilities performs a step forward. In the attempt to define an architecture for autonomous growing up agents [1]. We conducted an experiment on the abstraction process in children as natural parts of a cognitive system. We found that linguistic growing up involve a number of different trial processes. We identified a fixed number of distinct paths that were crossed by children. Once a given interpretation paths was discovered useless, they tried to follow another path, until the new meaning was emerging. This study generates suggestion about the evolutionary conditions conducive to the emergence of growing up in robots and provides guidelines for designing artificial evolutionary systems displaying spontaneous adaptation abilities. The importance of multi-sensor perception, motivation and emotional drives are underlined and, above all, the growing up insights shows similarities to emergent self-organized behaviors.
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Directory of Open Access Journals (Sweden)
Apurv Patel
2016-01-01
Full Text Available The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients.
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When good times go bad: managing 'legal high' complications in the emergency department.
Caffrey, Charles R; Lank, Patrick M
2018-01-01
Patients can use numerous drugs that exist outside of existing regulatory statutes in order to get "legal highs." Legal psychoactive substances represent a challenge to the emergency medicine physician due to the sheer number of available agents, their multiple toxidromes and presentations, their escaping traditional methods of analysis, and the reluctance of patients to divulge their use of these agents. This paper endeavors to cover a wide variety of "legal highs," or uncontrolled psychoactive substances that may have abuse potential and may result in serious toxicity. These agents include not only some novel psychoactive substances aka "designer drugs," but also a wide variety of over-the-counter medications, herbal supplements, and even a household culinary spice. The care of patients in the emergency department who have used "legal high" substances is challenging. Patients may misunderstand the substance they have been exposed to, there are rarely any readily available laboratory confirmatory tests for these substances, and the exact substances being abused may change on a near-daily basis. This review will attempt to group legal agents into expected toxidromes and discuss associated common clinical manifestations and management. A focus on aggressive symptom-based supportive care as well as management of end-organ dysfunction is the mainstay of treatment for these patients in the emergency department.
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Budianto, E.; Al-Shidqi, M. F.; Cahyana, A. H.
2017-07-01
Eradicating H. pylori-based infection by using conventional oral dosage form of amoxicillin trihydrate finds difficulties to overcome rapid gastric retention time. Encapsulating amoxicillin trihydrate in floating drug delivery system may solve the problem. In this research, the floating drug delivery system of amoxicillin trihydrate encapsulated in floating chitosan-graft-poly(N-vinyl pyrrolidone) hydrogels containing CaCO3 and NaHCO3 as pore forming agents has been successfully prepared. Pore forming agents used was varied with the ratio of 10 to 25% pore forming agents to total mass of the used materials. The hydrogel were characterizedusing FTIR spectrophotometer and stereo microscope. As pore forming agents compositions increased, the porosity (%) and floating properties increased but followed by decrease in drug entrapment efficiency. Most of the floating hydrogels possessed floating ability longer than 180 min and the highest porosity was found in hydrogel containing 25% NaHCO3. Hydrogel containing CaCO3 showed sustained drug release profile than hydrogel containing NaHCO3. However, the optimum formulation was achieved at composition of 10% NaHCO3 with 57% of drug entrapped within the hydrogel and 43% drug released. The results of these studies show that NaHCO3 is an effective pore forming agents for chitosan-graft-poly(N-vinyl pyrrolidone) hydrogel preparation as compare to CaCO3.
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An agent-based computational model of the spread of tuberculosis
International Nuclear Information System (INIS)
De Espíndola, Aquino L; Bauch, Chris T; Troca Cabella, Brenno C; Martinez, Alexandre Souto
2011-01-01
In this work we propose an alternative model of the spread of tuberculosis (TB) and the emergence of drug resistance due to the treatment with antibiotics. We implement the simulations by an agent-based model computational approach where the spatial structure is taken into account. The spread of tuberculosis occurs according to probabilities defined by the interactions among individuals. The model was validated by reproducing results already known from the literature in which different treatment regimes yield the emergence of drug resistance. The different patterns of TB spread can be visualized at any time of the system evolution. The implementation details as well as some results of this alternative approach are discussed
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Indolealkylamines: biotransformations and potential drug-drug interactions.
Yu, Ai-Ming
2008-06-01
Indolealkylamine (IAA) drugs are 5-hydroxytryptamine (5-HT or serotonin) analogs that mainly act on the serotonin system. Some IAAs are clinically utilized for antimigraine therapy, whereas other substances are notable as drugs of abuse. In the clinical evaluation of antimigraine triptan drugs, studies on their biotransformations and pharmacokinetics would facilitate the understanding and prevention of unwanted drug-drug interactions (DDIs). A stable, principal metabolite of an IAA drug of abuse could serve as a useful biomarker in assessing intoxication of the IAA substance. Studies on the metabolism of IAA drugs of abuse including lysergic acid amides, tryptamine derivatives and beta-carbolines are therefore emerging. An important role for polymorphic cytochrome P450 2D6 (CYP2D6) in the metabolism of IAA drugs of abuse has been revealed by recent studies, suggesting that variations in IAA metabolism, pharmaco- or toxicokinetics and dynamics can arise from distinct CYP2D6 status, and CYP2D6 polymorphism may represent an additional risk factor in the use of these IAA drugs. Furthermore, DDIs with IAA agents could occur additively at the pharmaco/toxicokinetic and dynamic levels, leading to severe or even fatal serotonin toxicity. In this review, the metabolism and potential DDIs of these therapeutic and abused IAA drugs are described.
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Susceptibility of Select Agents to Predation by Predatory Bacteria
Directory of Open Access Journals (Sweden)
Riccardo Russo
2015-12-01
Full Text Available Select Agents are microorganisms and toxins considered to be exploitable as biological weapons. Although infections by many Select Agents can be treated by conventional antibiotics, the risk of an emerging or engineered drug resistant strain is of great concern. One group of microorganisms that is showing potential to control drug resistant Gram-negative bacteria are the predatory bacteria from the genera Bdellovibrio spp. and Micavibrio spp. In this study, we have examined the ability of Bdellovibrio bacteriovorus (B. bacteriovorus strain 109J, HD100 and Micavibrio aeruginosavorus (M. aeruginosavorus ARL-13 to prey on a variety of Select Agents. Our findings demonstrate that B. bacteriovorus and M. aeruginosavorus are able to prey efficiently on Yersinia pestis and Burkholderia mallei. Modest predation was also measured in co-cultures of B. bacteriovorus and Francisella tularensis. However, neither of the predators showed predation when Burkholderia pseudomallei and Brucella melitensis were used as prey.
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Matsui, Kazuki; Tsume, Yasuhiro; Amidon, Gregory E; Amidon, Gordon L
2015-07-06
Weakly basic drugs typically exhibit pH-dependent solubility in the physiological pH range, displaying supersaturation or precipitation along the gastrointestinal tract. Additionally, their oral bioavailabilities may be affected by coadministration of acid-reducing agents that elevate gastric pH. The purpose of this study was to assess the feasibility of a multicompartmental in vitro dissolution apparatus, Gastrointestinal Simulator (GIS), in predicting in vivo dissolution of certain oral medications. In vitro dissolution studies of fluconazole, a BCS class I, and dipyridamole, a BCS class II weak bases (class IIb), were performed in the GIS as well as United States Pharmacopeia (USP) apparatus II and compared with the results of clinical drug-drug interaction (DDI) studies. In both USP apparatus II and GIS, fluconazole completely dissolved within 60 min regardless of pH, reflecting no DDI between fluconazole and acid-reducing agents in a clinical study. On the other hand, seven-fold and 15-fold higher concentrations of dipyridamole than saturation solubility were observed in the intestinal compartments in GIS with gastric pH 2.0. Precipitation of dipyridamole was also observed in the GIS, and the percentage of dipyridamole in solution was 45.2 ± 7.0%. In GIS with gastric pH 6.0, mimicking the coadministration of acid-reducing agents, the concentration of dipyridamole was equal to its saturation solubility, and the percentage of drug in solution was 9.3 ± 2.7%. These results are consistent with the clinical DDI study of dipyridamole with famotidine, which significantly reduced the Cmax and area under the curve. An In situ mouse infusion study combined with GIS revealed that high concentration of dipyridamole in the GIS enhanced oral drug absorption, which confirmed the supersaturation of dipyridamole. In conclusion, GIS was shown to be a useful apparatus to predict in vivo dissolution for BCS class IIb drugs.
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Champion, Katrina E; Teesson, Maree; Newton, Nicola C
2013-12-12
The use of ecstasy is a public health problem and is associated with a range of social costs and harms. In recent years, there has been growing concern about the availability and misuse of new and emerging drugs designed to mimic the effects of illicit drugs, including ecstasy. This, coupled with the fact that the age of use and the risk factors for using ecstasy and emerging drugs are similar, provides a compelling argument to implement prevention for these substances simultaneously. The proposed study will evaluate whether a universal Internet-based prevention program, known as the Climate Schools: Ecstasy and Emerging Drugs Module, can address and prevent the use of ecstasy and emerging drugs among adolescents. A cluster randomised controlled trial will be conducted among Year 10 students (aged 15-16 years) from 12 secondary schools in Sydney, Australia. Schools will be randomly assigned to either the Climate Schools intervention group or the control group. All students will complete a self-report questionnaire at baseline, immediately post-intervention, and 6-, 12- and 24-months post-baseline. The primary outcome measures will include ecstasy and emerging drug-related knowledge, intentions to use these substances in the future, and the patterns of use of ecstasy and emerging drugs. A range of secondary outcomes will also be assessed, including beliefs and attitudes about ecstasy and emerging drugs, peer pressure resistance, other substance use and mental health outcomes. To our knowledge, this will be the first evaluation of an Internet-based program designed to specifically target ecstasy and NED use among adolescents. If deemed effective, the Climate Schools: Ecstasy and Emerging Drugs Module will provide schools with an interactive and novel prevention program for ecstasy and emerging drugs that can be readily implemented by teachers. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000708752.
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Directory of Open Access Journals (Sweden)
Songzhe eHE
2015-05-01
Full Text Available Objective To investigate the in vitro and in vivo antibacterial activities of tigecycline and other 13 common antimicrobial agents, alone or in combination, against multi-drug resistant Acinetobacter baumannii.MethodsAn in vitro susceptibility test of 101 Acinetobacter baumannii was used to detect minimal inhibitory concentrations (MICs. A mouse lung infection model of multi-drug resistant Acinetobacter baumannii,established by the ultrasonic atomization method, was used to define in vivo antimicrobial activities.Results Multi-drug resistant Acinetobacter baumannii showed high sensitivity to tigecycline (98% inhibition, polymyxin B (78.2% inhibition, and minocycline (74.2% inhibition. However, the use of these antimicrobial agents in combination with other antimicrobial agents produced synergistic or additive effects. In vivo data showed that white blood cell (WBC counts in drug combination groups C (minocycline + amikacin and D (minocycline + rifampicin were significantly higher than in groups A (tigecycline and B (polymyxin B (P < 0.05, after administration of the drugs 24h post-infection. Lung tissue inflammation gradually increased in the model group during the first 24h after ultrasonic atomization infection; vasodilation, congestion with hemorrhage were observed 48h post infection. After three days of anti-infective therapy in groups A, B, C and D, lung tissue inflammation in each group gradually recovered with clear structures. The mortality rates in drug combination groups (groups C and D were much lower than in groups A and B.ConclusionThe combination of minocycline with either rifampicin or amikacin is more effective against multidrug-resistant Acinetobacter baumannii than single-agent tigecycline or polymyxin B. In addition, the mouse lung infection by ultrasonic atomization is a suitable model for drug screening and analysis of infection mechanism.
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Sexual side effects induced by psychotropic drugs
DEFF Research Database (Denmark)
Kristensen, Ellids
2002-01-01
The majority of psychotropic drugs entail sexual side effects. The sexual side effects may reduce quality of life and may give rise to non-compliance. For example, 30-60 per cent of patients treated with antidepressants are known to develop a sexual dysfunction. However, some psychotropic drugs...... with no or very few sexual side effects have begun to emerge. The treatment of sexual side effects induced by psychotropic drugs may consist of: modified sexual habits, reduction in dosage, switching to another medication, possibly in combination with different psychotropic agents, other varieties...
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Clingan, Sarah E; Woodruff, Susan I
2017-07-29
Medical care in the emergency department (ED) is a growing and complex area of outpatient care, with about 256 visits made to EDs every minute in 2013. Studies report that, compared to people who do not use drugs, people who use illicit drugs are more likely to use the ED for their medical care. Self-efficacy has been shown to be a predictor of abstinence or reduced use among drug-using individuals. The current study describes drug avoidance self-efficacy among exclusive cannabis-using individuals and other drug-using individuals who use the ED for any reason. Participants were 693 adult patients visiting the trauma units and EDs of two large urban "safety net" hospitals (i.e., providing care to low-income, uninsured, and vulnerable population) in Southern California who reported using illicit drugs in the past 30 days. For people who use only cannabis, higher drug-avoidance self-efficacy was associated with older age, lower drug involvement scores, lower drug severity scores, and higher readiness to change use. For people who use other drugs, higher drug avoidance self-efficacy scores was associated with lower drug severity scores, lower psychiatric severity scores, higher medical severity scores, and higher readiness to change use. This study identified several factors (some common, some unique) related to higher drug-avoidance self-efficacy for both groups. Results may be important when designing intervention protocols for use in the ED.
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2010-10-01
... drug and alcohol testing requirements? 40.15 Section 40.15 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Employer Responsibilities § 40.15 May an employer use a service agent to meet DOT drug and alcohol testing requirements? (a...
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Sedative-hypnotic drug withdrawal syndrome: recognition and treatment [digest].
Santos, Cynthia; Olmedo, Ruben E; Kim, Jeremy
2017-03-22
Sedative-hypnotic drugs include gamma-Aminobutyric acid (GABA)ergic agents such as benzodiazepines, barbiturates, gamma-Hydroxybutyric acid [GHB], gamma-Butyrolactone [GBL], baclofen, and ethanol. Chronic use of these substances can cause tolerance, and abrupt cessation or a reduction in the quantity of the drug can precipitate a life-threatening withdrawal syndrome. Benzodiazepines, phenobarbital, propofol, and other GABA agonists or analogues can effectively control symptoms of withdrawal from GABAergic agents. Managing withdrawal symptoms requires a patient-specific approach that takes into account the physiologic pathways of the particular drugs used as well as the patient's age and comorbidities. Adjunctive therapies include alpha agonists, beta blockers, anticonvulsants, and antipsychotics. Newer pharmacological therapies offer promise in managing withdrawal symptoms. [Points & Pearls is a digest of Emergency Medicine Practice].
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Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji
2010-09-01
We describe herein for the first time our medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and boron tracedrugs as newly emerging drug classes. A new area of antineoplastic drugs and treatments has recently focused on neoplastic cells of the tumor environment/microenvironment involving accessory cells. This tumor hypoxic environment is now considered as a major factor that influences not only the response to antineoplastic therapies but also the potential for malignant progression and metastasis. We review our medicinal electronomics bricolage design of hypoxia-targeting drugs, antiangiogenic hypoxic cell radiosensitizers, sugar-hybrid hypoxic cell radiosensitizers, and hypoxia-targeting 10B delivery agents, in which we design drug candidates based on their electronic structures obtained by molecular orbital calculations, not based solely on pharmacophore development. These drugs include an antiangiogenic hypoxic cell radiosensitizer TX-2036, a sugar-hybrid hypoxic cell radiosensitizer TX-2244, new hypoxia-targeting indoleamine 2,3-dioxygenase (IDO) inhibitors, and a hypoxia-targeting BNCT agent, BSH (sodium borocaptate-10B)-hypoxic cytotoxin tirapazamine (TPZ) hybrid drug TX-2100. We then discuss the concept of boron tracedrugs as a new drug class having broad potential in many areas.
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Fe-S Clusters Emerging as Targets of Therapeutic Drugs
Directory of Open Access Journals (Sweden)
Laurence Vernis
2017-01-01
Full Text Available Fe-S centers exhibit strong electronic plasticity, which is of importance for insuring fine redox tuning of protein biological properties. In accordance, Fe-S clusters are also highly sensitive to oxidation and can be very easily altered in vivo by different drugs, either directly or indirectly due to catabolic by-products, such as nitric oxide species (NOS or reactive oxygen species (ROS. In case of metal ions, Fe-S cluster alteration might be the result of metal liganding to the coordinating sulfur atoms, as suggested for copper. Several drugs presented through this review are either capable of direct interaction with Fe-S clusters or of secondary Fe-S clusters alteration following ROS or NOS production. Reactions leading to Fe-S cluster disruption are also reported. Due to the recent interest and progress in Fe-S biology, it is very likely that an increasing number of drugs already used in clinics will emerge as molecules interfering with Fe-S centers in the near future. Targeting Fe-S centers could also become a promising strategy for drug development.
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Emergence of Drug-Resistant Tuberculosis at a South African Mine
Centers for Disease Control (CDC) Podcasts
This podcast describes the emergence of increasingly drug resistant tuberculosis at a mine in South Africa. CDCâs Dr. Dixie Snider discusses the outbreak and some of the reasons it may have occurred, despite the existence of a well-functioning TB control program at the mine.
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Drug Rash with Eosinophilia and Systemic Symptoms: Two Emergency Department Cases
Tsyrulnik, Alina; Landman, Adam B.
2011-01-01
Drug rash with eosinophilia and systemic symptoms (DRESS) is a rare, severe adverse drug event that appears with a generalized rash, fevers, and dysfunction of 1 or more organ systems. We describe 2 patients (1 adult and 1 pediatric) seen in the emergency department with DRESS, and review the clinical presentations, potential complications, and management of DRESS. Although rare, it can be associated with significant morbidity, including liver failure and death, and should be considered in th...
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Oral delivery of anticancer drugs
DEFF Research Database (Denmark)
Thanki, Kaushik; Gangwal, Rahul P; Sangamwar, Abhay T
2013-01-01
The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes improvement in quality of life of patients and reduced health care costs. Subsequently, the challenges...... incurred in the oral delivery of anticancer agents have been especially emphasized. Sincere efforts have been made to compile the various physicochemical properties of anticancer drugs from either literature or predicted in silico via GastroPlus™. The later section of the paper reviews various emerging...... trends to tackle the challenges associated with oral delivery of anticancer drugs. These invariably include efflux transporter based-, functional excipient- and nanocarrier based-approaches. The role of drug nanocrystals and various others such as polymer based- and lipid based...
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Mignani, Serge; El Kazzouli, Saïd; Bousmina, Mosto; Majoral, Jean-Pierre
2013-10-01
Drugs are introduced into the body by numerous routes such as enteral (oral, sublingual and rectum administration), parenteral (intravascular, intramuscular, subcutaneous and inhalation administration), or topical (skin and mucosal membranes). Each route has specific purposes, advantages and disadvantages. Today, the oral route remains the preferred one for different reasons such as ease and compliance by patients. Several nanoformulated drugs have been already approved by the FDA, such as Abelcet®, Doxil®, Abraxane® or Vivagel®(Starpharma) which is an anionic G4-poly(L-lysine)-type dendrimer showing potent topical vaginal microbicide activity. Numerous biochemical studies, as well as biological and pharmacological applications of both dendrimer based products (dendrimers as therapeutic compounds per se, like Vivagel®) and dendrimers as drug carriers (covalent conjugation or noncovalent encapsulation of drugs) were described. It is widely known that due to their outstanding physical and chemical properties, dendrimers afforded improvement of corresponding carried-drugs as dendrimer-drug complexes or conjugates (versus plain drug) such as biodistribution and pharmacokinetic behaviors. The purpose of this manuscript is to review the recent progresses of dendrimers as nanoscale drug delivery systems for the delivery of drugs using enteral, parenteral and topical routes. In particular, we focus our attention on the emerging and promising routes such as oral, transdermal, ocular and transmucosal routes using dendrimers as delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.
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Directory of Open Access Journals (Sweden)
M. Yousefi
Full Text Available This study presents an agent-based simulation modeling in an emergency department. In a traditional approach, a supervisor (or a manager allocates the resources (receptionist, nurses, doctors, etc. to different sections based on personal experience or by using decision-support tools. In this study, each staff agent took part in the process of allocating resources based on their observation in their respective sections, which gave the system the advantage of utilizing all the available human resources during the workday by being allocated to a different section. In this simulation, unlike previous studies, all staff agents took part in the decision-making process to re-allocate the resources in the emergency department. The simulation modeled the behavior of patients, receptionists, triage nurses, emergency room nurses and doctors. Patients were able to decide whether to stay in the system or leave the department at any stage of treatment. In order to evaluate the performance of this approach, 6 different scenarios were introduced. In each scenario, various key performance indicators were investigated before and after applying the group decision-making. The outputs of each simulation were number of deaths, number of patients who leave the emergency department without being attended, length of stay, waiting time and total number of discharged patients from the emergency department. Applying the self-organizing approach in the simulation showed an average of 12.7 and 14.4% decrease in total waiting time and number of patients who left without being seen, respectively. The results showed an average increase of 11.5% in total number of discharged patients from emergency department.
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International Nuclear Information System (INIS)
Siemann, Dietmar W.; Rojiani, Amyn M.
2002-01-01
Purpose: The present report reviews the preclinical data on combined chemotherapy/vascular targeting agent treatments. Basic principles are illustrated in studies evaluating the antitumor efficacy of the vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) when combined with the anticancer drug cisplatin in experimental rodent (KHT sarcoma) and human renal (Caki-1) tumor models. Methods and Materials: C3H/HeJ and NCR/nu-nu mice bearing i.m. tumors were injected i.p. with ZD6126 (0-150 mg/kg) or cisplatin (0-20 mg/kg) either alone or in combination. Tumor response to treatment was assessed by clonogenic cell survival. Results: Treatment with ZD6126 was found to damage existing neovasculature, leading to a rapid vascular shutdown. Histologic evaluation showed dose-dependent morphologic damage of tumor cells within a few hours after drug exposure, followed by extensive central tumor necrosis and neoplastic cell death as a result of prolonged ischemia. ZD6126 doses that led to pathophysiologic effects also enhanced the tumor cell killing of cisplatin when administered either 24 h before or 1-24 h after chemotherapy. In both tumor models, the administration of a 150 mg/kg dose of ZD6126 1 h after a range of doses of cisplatin resulted in an increase in tumor cell kill 10-500-fold greater than that seen with chemotherapy alone. In contrast, the inclusion of the antivascular agent did not increase bone marrow stem cell toxicity associated with this anticancer drug. Conclusion: The results obtained in the KHT and Caki-1 tumor models indicate that ZD6126 effectively enhanced the antitumor effects of cisplatin therapy. These findings are representative of the marked enhancements generally observed when vascular targeting agents are combined with chemotherapy in solid tumor therapy
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Drugs currently under investigation for the treatment of invasive candidiasis.
McCarthy, Matthew W; Walsh, Thomas J
2017-07-01
The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed. Areas covered: In this paper, we explore investigational agents for the treatment of invasive candidiasis, with particular attention paid to compounds that have recently entered phase I or phase II clinical trials. Expert opinion: The antifungal drug development pipeline has been severely limited due to regulatory hurdles and a systemic lack of investment in novel compounds. However, several promising drug development strategies have recently emerged, including chemical screens involving Pathogen Box compounds, combination antifungal therapy, and repurposing of existing agents that were initially developed to treat other conditions, all of which have the potential to redefine the treatment of invasive candidiasis.
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Universal, class-specific and drug-specific reversal agents for the new oral anticoagulants.
Ansell, Jack E
2016-02-01
Although there is controversy about the absolute need for a reversal agent for the new direct oral anticoagulants (DOACs), the absence of such an agent is a barrier to more widespread use of these agents. For the management of major life-threatening bleeding with the DOACs, most authorities recommend the use of four factor prothrombin complex concentrates, although the evidence to support their use in terms of improving outcomes is meager. At the present time, there are three antidotes in development and poised to enter the market. Idarucizumab is a drug-specific antidote targeted to reverse the direct thrombin inhibitor, dabigatran. Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Ciraparantag is a universal antidote targeted to reverse the direct thrombin and factor Xa inhibitors as well as the indirect inhibitor, enoxaparin.
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James, Thomas; Wyke, Stacey; Marczylo, Tim; Collins, Samuel; Gaulton, Tom; Foxall, Kerry; Amlôt, Richard; Duarte-Davidson, Raquel
2018-01-01
Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may need to be undertaken to reduce injury and possible loss of life. To ensure these methods are effective, human volunteer trials (HVTs) of decontamination protocols, using simulant contaminants, have been conducted. Simulants must be used to mimic the physicochemical properties of more harmful chemicals, while remaining non-toxic at the dose applied. This review focuses on studies that employed chemical warfare agent simulants in decontamination contexts, to identify those simulants most suitable for use in HVTs of emergency decontamination. Twenty-two simulants were identified, of which 17 were determined unsuitable for use in HVTs. The remaining simulants (n = 5) were further scrutinized for potential suitability according to toxicity, physicochemical properties and similarities to their equivalent toxic counterparts. Three suitable simulants, for use in HVTs were identified; methyl salicylate (simulant for sulphur mustard), diethyl malonate (simulant for soman) and malathion (simulant for VX or toxic industrial chemicals). All have been safely used in previous HVTs, and have a range of physicochemical properties that would allow useful inference to more toxic chemicals when employed in future studies of emergency decontamination systems. © 2017 Crown Copyright. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.
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Hyperthermia and chemotherapy agent
International Nuclear Information System (INIS)
Roizin-Towle, L.; Hall, E.J.
1981-01-01
The use of chemotherapeutic agents for the treatment of cancer dates back to the late 19th century, but the modern era of chemotherapy drugs was ushered in during the 1940's with the development of the polyfunctional alkylating agent. Since then, numerous classes of drugs have evolved and the combined use of antineoplastic agents with other treatment modalities such as radiation or heat, remains a large relatively unexplored area. This approach, combining local hyperthermia with chemotherapy agents affords a measure of targeting and selective toxicity not previously available for drugs. In this paper, the effects of adriamycin, bleomycin and cis-platinum are examined. The adjuvant use of heat may also reverse the resistance of hypoxic cells noted for some chemotherapy agents
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Pendhari, Shabbir Rafiq; Chaudhari, Devendra Ramesh; Burute, Shreyas Ramchandra; Bite, Bapurao Motiram
2013-04-01
To observe the cardiovascular emergencies which were most frequently treated and to quantify the drug utilization trends in the cardiovascular emergencies, in terms of the Defined Daily Doses [DDD] and the prescribing prevalence in the cardiovascular emergencies. This prescription based study was undertaken in the Medicine ICU of the government medical hospital. The age, sex, diagnosis (only cardiovascular) and the drugs which were prescribed, were recorded for each patient. Also, the brand names and the generic names of the prescribed drugs were noted. The collected data was analyzed to study the drug utilization trends. It was observed that the most commonly treated cardiovascular disease was IHD. The IHD was more in males than in females who were below 50 years of age and it was nearly equal in the age groups which were above 50 years. The use of Angiotensin Converting Enzyme (ACE) inhibitors was higher than that of the beta blockers and the calcium channel blockers. The patients with cardiovascular emergencies also had preceding associated diseases like diabetes mellitus and hypertension. The protocol of the management which was followed by the college in the treatment of cardiovascular emergencies was competent enough, as the clinical outcomes of the patients were favourable. But there was a guideline incongruent prescribing behaviour which was statistically significant, for which there is a need to undertake large scale studies.
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Directory of Open Access Journals (Sweden)
Ryan J Mailloux
2010-10-01
Full Text Available Uncoupling protein-2 (UCP2 is known to suppress mitochondrial reactive oxygen species (ROS production and is employed by drug-resistant cancer cells to mitigate oxidative stress. Using the drug-sensitive HL-60 cells and the drug-resistant MX2 subline as model systems, we show that genipin, a UCP2 inhibitor, sensitizes drug-resistant cells to cytotoxic agents. Increased MX2 cell death was observed upon co-treatment with genipin and different doses of menadione, doxorubicin, and epirubicin. DCFH-DA fluorimetry revealed that the increase in MX2 cell death was accompanied by enhanced cellular ROS levels. The drug-induced increase in ROS was linked to genipin-mediated inhibition of mitochondrial proton leak. State 4 and resting cellular respiratory rates were higher in the MX2 cells in comparison to the HL-60 cells, and the increased respiration was readily suppressed by genipin in the MX2 cells. UCP2 accounted for a remarkable 37% of the resting cellular oxygen consumption indicating that the MX2 cells are functionally reliant on this protein. Higher amounts of UCP2 protein were detected in the MX2 versus the HL-60 mitochondria. The observed effects of genipin were absent in the HL-60 cells pointing to the selectivity of this natural product for drug-resistant cells. The specificity of genipin for UCP2 was confirmed using CHO cells stably expressing UCP2 in which genipin induced an ∼22% decrease in state 4 respiration. These effects were absent in empty vector CHO cells expressing no UCP2. Thus, the chemical inhibition of UCP2 with genipin sensitizes multidrug-resistant cancer cells to cytotoxic agents.
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Drug lag and key regulatory barriers in the emerging markets
Directory of Open Access Journals (Sweden)
Harriet Wileman
2010-01-01
This work concludes that the overall relative drug lag in the emerging markets has decreased over time and that there are seven key regulatory barriers which need to be targeted in order to make further improvements; ′Western Approval′, local clinical development (LCD, Certificate of Pharmaceutical Product (CPP, Good Manufacturing Practice (GMP, pricing approval, document authentication and harmonisation.
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Directory of Open Access Journals (Sweden)
Li X
2015-12-01
Full Text Available Xiaoyu Li, Meiying Wu, Limin Pan, Jianlin Shi State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: To overcome the drawback of drug non-selectivity in traditional chemotherapy, the construction of multifunctional targeting drug delivery systems is one of the most effective and prevailing approaches. The intratumoral anti-angiogenesis and the tumor cell-killing are two basic approaches in fighting tumors. Herein we report a novel tumor vascular-targeting multidrug delivery system using mesoporous silica nanoparticles as carrier to co-load an antiangiogenic agent (combretastatin A4 and a chemotherapeutic drug (doxorubicin and conjugate with targeting molecules (iRGD peptide for combined anti-angiogenesis and chemotherapy. Such a dual-loaded drug delivery system is capable of delivering the two agents at tumor vasculature and then within tumors through a differentiated drug release strategy, which consequently results in greatly improved antitumor efficacy at a very low doxorubicin dose of 1.5 mg/kg. The fast release of the antiangiogenic agent at tumor vasculatures led to the disruption of vascular structure and had a synergetic effect with the chemotherapeutic drug slowly released in the following delivery of chemotherapeutic drug into tumors. Keywords: mesoporous silica nanoparticles, drug delivery, tumor vasculatures targeting, antiangiogenic agent
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Trends and emerging drugs in Kenya: A case study in Mombasa and ...
African Journals Online (AJOL)
SARAH
2013-07-30
Jul 30, 2013 ... Emerging psychoactive substances e.g. morphine, carnabinoids, cathinones ... Results: The drug initiation age ranged from 5 to 28 years though most started ...... and psychological health problems and their drain on health.
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Abe, Hiromi; Hayes, C Nelson; Hiraga, Nobuhiko; Imamura, Michio; Tsuge, Masataka; Miki, Daiki; Takahashi, Shoichi; Ochi, Hidenori; Chayama, Kazuaki
2013-09-01
Direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) have recently been developed and are ultimately hoped to replace interferon-based therapy. However, DAA monotherapy results in rapid emergence of resistant strains and DAAs must be used in combinations that present a high genetic barrier to resistance, although viral kinetics of multidrug-resistant strains remain poorly characterized. The aim of this study is to track the emergence and fitness of resistance using combinations of telaprevir and NS5A or NS5B inhibitors with genotype 1b clones. HCV-infected chimeric mice were treated with DAAs, and resistance was monitored using direct and ultra-deep sequencing. Combination therapy with telaprevir and BMS-788329 (NS5A inhibitor) reduced serum HCV RNA to undetectable levels. The presence of an NS3-V36A telaprevir resistance mutation resulted in poor response to telaprevir monotherapy but showed significant HCV reduction when telaprevir was combined with BMS-788329. However, a BMS-788329-resistant strain emerged at low frequency. Infection with a BMS-788329-resistant NS5A-L31V mutation rapidly resulted in gain of an additional NS5A-Y93A mutation that conferred telaprevir resistance during combination therapy. Infection with dual NS5AL31V/NS5AY93H mutations resulted in poor response to combination therapy and development of telaprevir resistance. Although HCV RNA became undetectable soon after the beginning of combination therapy with BMS-788329 and BMS-821095 (NS5B inhibitor), rebound with emergence of resistance against all three drugs occurred. Triple resistance also occurred following infection with the NS3V36A/NS5AL31V/NS5AY93H triple mutation. Resistant strains easily develop from cloned virus strains. Sequential use of DAAs should be avoided to prevent emergence of multidrug-resistant strains.
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Xiao, Da; Chen, Yi-Tzai; Yang, Dongfang; Yan, Bingfang
2014-01-01
Carboxylesterases (CES) constitute a class of hydrolytic enzymes that play critical roles in drug metabolism and lipid mobilization. Previous studies with a large number of human liver samples have suggested that the inducibility of carboxylesterases is inversely related with age. To directly test this possibility, neonatal (10 days of age) and adult mice were treated with the antiepileptic agent phenobarbital. The expression and hydrolytic activity were determined on six major carboxylesterases including ces1d, the ortholog of human CES1. Without exception, all carboxylesterases tested were induced to a greater extent in neonatal than adult mice. The induction was detected at mRNA, protein and catalytic levels. Ces1d was greatly induced and found to rapidly hydrolyze the antiplatelet agent clopidogrel and support the accumulation of neutral lipids. Phenobarbital represents a large number of therapeutic agents that induce drug metabolizing enzymes and transporters in a species-conserved manner. The higher inducibility of carboxylesterases in the developmental age likely represents a general phenomenon cross species including human. Consequently, individuals in the developmental age may experience greater drug-drug interactions. The greater induction of ces1d also provides a molecular explanation to the clinical observation that children on antiepileptic drugs increase plasma lipids. PMID:22513142
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21 CFR 181.28 - Release agents.
2010-04-01
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Release agents. 181.28 Section 181.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Release agents. Substances classified as release agents, when migrating from food-packaging material shall...
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Management of novel oral anticoagulants in emergency and trauma surgery.
Pinho-Gomes, Ana-Catarina; Hague, Adam; Ghosh, Jonathan
2016-08-01
The compelling safety, efficacy and predictable effect of novel oral anticoagulants (NOACs) is driving a rapid expansion in their therapeutic indications. Management of the increasing number of patients on those new agents in the setting of emergency or trauma surgery can be challenging and the absence of specific reversal agents has been a matter of concern. This review summarises the key principles that underpin the management of those patients with a particular emphasis on the recent development of specific antidotes. As of 2015, a new line of antidotes, specific for these drugs, are at different stages of their development with their release imminent. However, as NOACs are innately reversible due to their short half-life, the use of reversal agents will probably be restricted to a few exceptional cases. Post-marketing surveillance will be paramount to better clarify the role of these promising drugs. Management of patients on NOACs in the context of emergency or trauma surgery relies on best supportive care in combination with the blood products and/or specific antidotes as required. Familiarity with the new reversal agents is essential but further evidence on their indications, safety and efficacy as well as consensus guidelines are warranted prior to widespread adoption. Copyright © 2016 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.
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Emerging Technologies and Generic Assays for the Detection of Anti-Drug Antibodies
Directory of Open Access Journals (Sweden)
Michael A. Partridge
2016-01-01
Full Text Available Anti-drug antibodies induced by biologic therapeutics often impact drug pharmacokinetics, pharmacodynamics response, clinical efficacy, and patient safety. It is critical to assess the immunogenicity risk of potential biotherapeutics in producing neutralizing and nonneutralizing anti-drug antibodies, especially in clinical phases of drug development. Different assay methodologies have been used to detect all anti-drug antibodies, including ELISA, radioimmunoassay, surface plasmon resonance, and electrochemiluminescence-based technologies. The most commonly used method is a bridging assay, performed in an ELISA or on the Meso Scale Discovery platform. In this report, we aim to review the emerging new assay technologies that can complement or address challenges associated with the bridging assay format in screening and confirmation of ADAs. We also summarize generic anti-drug antibody assays that do not require drug-specific reagents for nonclinical studies. These generic assays significantly reduce assay development efforts and, therefore, shorten the assay readiness timeline.
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On the emergence of an ‘intention field’ for socially cohesive agents
International Nuclear Information System (INIS)
Bouchaud, Jean-Philippe; Borghesi, Christian; Jensen, Pablo
2014-01-01
We argue that when a social convergence mechanism exists and is strong enough, one should expect the emergence of a well-defined ‘field’, i.e. a slowly evolving, local quantity around which individual attributes fluctuate in a finite range. This condensation phenomenon is well illustrated by the Deffuant–Weisbuch opinion model for which we provide a natural extension to allow for spatial heterogeneities. We show analytically and numerically that the resulting dynamics of the emergent field is a noisy diffusion equation that has a slow dynamics. This random diffusion equation reproduces the long-ranged, logarithmic decrease of the correlation of spatial voting patterns empirically found in Borghesi and Bouchaud (2010 Eur. Phys. J. B 75 395) and Borghesi et al (2012 PLoS One 7 e36289). Interestingly enough, we find that when the social cohesion mechanism becomes too weak, cultural cohesion breaks down completely, in the sense that the distribution of intentions/opinions becomes infinitely broad. No emerging field exists in this case. All these analytical findings are confirmed by numerical simulations of an agent-based model. (paper)
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Evolution of and perspectives on therapeutic approaches to nerve agent poisoning.
Masson, Patrick
2011-09-25
After more than 70 years of considerable efforts, research on medical defense against nerve agents has come to a standstill. Major progress in medical countermeasures was achieved between the 50s and 70s with the development of anticholinergic drugs and carbamate-based pretreatment, the introduction of pyridinium oximes as antidotes, and benzodiazepines in emergency treatments. These drugs ensure good protection of the peripheral nervous system and mitigate the acute effects of exposure to lethal doses of nerve agents. However, pyridostigmine and cholinesterase reactivators currently used in the armed forces do not protect/reactivate central acetylcholinesterases. Moreover, other drugs used are not sufficiently effective in protecting the central nervous system against seizures, irreversible brain damages and long-term sequelae of nerve agent poisoning.New developments of medical counter-measures focus on: (a) detoxification of organophosphorus molecules before they react with acetylcholinesterase and other physiological targets by administration of stoichiometric or catalytic scavengers; (b) protection and reactivation of central acetylcholinesterases, and (c) improvement of neuroprotection following delayed therapy.Future developments will aim at treatment of acute and long-term effects of low level exposure to nerve agents, research on alternative routes for optimizing drug delivery, and therapies. Though gene therapy for in situ generation of bioscavengers, and cell therapy based on neural progenitor engraftment for neuronal regeneration have been successfully explored, more studies are needed before practical medical applications can be made of these new approaches. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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International Nuclear Information System (INIS)
Deng Qiwei; Liu Xiaojun; Shi Jianfen; Jiang Guohua; Ye Jinqing; Shen Jun; Song Ting
2009-01-01
Objective: To analyze the value of nonionic contrast agent combined with low tensive drug in the hysterosalpingography in diagnosis of infertility. Methods: 203 patients with infertility were randomly classified into two groups. Group 1 contained 108 patients administrated intramuscularly anisodamine (654-2) 30 minutes before hysterosalpingography. 95 patients in group 2 did not use 654-2. Non-ionic contrast agent was used in all patients. The image quality and post-contrast displaying status of uterus and uterine tube between the two groups were analyzed. Results: No allergic response occurred in all patients. The image quality and post-contrast displaying status of uterus and uterine tube of group 1 were obviously superior to that of group 2 (P<0.01). Conclusion: Hysterosalpingography clearly showed lesions of uterus and uterine tube when using non-ionic contrast agent combined with low-tensive drug. It is more safety with less side effects. The contraction of uterine tube can be relieved by the low-tensive drug effectively, so as to decrease the false positive rate, raise the diagnostic accuracy, and lessen patients sufferings. It is deserved to be applied generally. (authors)
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Aini, Nurul; Rahayu, Dyah Utami Cahyaning; Budianto, Emil
2018-04-01
The limitation of amoxicillin trihydrate in the treatment of H. pylori bacteria is relatively short retention time in the stomach. The FDDS (Floating Drug Delivery System) amoxicillin trihydrate into a chitosan-poly(N-vinylcaprolactam) full-Ipn hydrogel matrix using a pore-forming agent KHCO3 is expected to overcome these limitations. The pore-forming agent to be used is 15% KHCO3 compound. Chemical kinetics approach is performed to determine the dissolution mechanism of amoxicillin trihydrate from K-PNVCL hydrogel in vitro on gastric pH and characterization using SEM performed to confirm the dissolution mechanism. Hydrogels with the addition of pore-forming agents will be loading in situ loading and post loading. Fourier Transform Infra Red (FTIR) spectroscopy was used to characterize K-PNVCL and UV-Vis hydrogels used to calculate the efficiency of encapsulation and drug dissolution rate in K-PNVCL hydrogel. Hydrogel K-PNVCL / KHCO3 that encapsulated by in situ loading method resulted in an encapsulation efficiency of 93.5% and dissolution of 93.4%. While the Hydrogel K-PNVCL / KHCO3 which is drug encapsulation resulted in an encapsulation efficiency of 87.2% with dissolution of 81.5%. Chemical kinetics approach to in situ encapsulation of loading and post loading shows the dissolution mechanism occurring in the K-PNVCL / KHCO3 hydrogel matrix occurs by diffusion. Observation using optical microscope and SEM showed the mechanism of drug dissolution in Hydrogel K-PNVCL occurred by diffusion.
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Urby, Heriberto; McEntire, David A
2015-01-01
This article discusses the influence of management theory, some principles of leadership, four strategic management considerations, that are applied to emergency management, allow emergency managers to transform their followers, organizations, and communities at large. The authors argue that in the past there has been little recognition of the value, or application, of these three areas of emphasis in the disaster profession. Using more of these principles, emergency managers may transform into transformational change agents who make a difference in their followers' lives, who themselves transform other people and improve emergency management.
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Energy Technology Data Exchange (ETDEWEB)
Hassan, S H.M. [Durng Research Dept., National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, (Egypt)
1995-10-01
The present study represents two main subjects. The first encounters the effect of radiosterilization of certain pharmaceretical preparations such as antihistaminics (cimetidine), anticonvulsants (diazepam), beta and calcium channel blacker (propranolol and verapamil) on their pharmacological activity. Results of this study revealed that the previously mentioned drugs can be effectively and safely sterilized by gamma irradiation without deleterious effect on their pharmacological activity. The other subject presented in this study is essentially a pharmacological subject encountering toxicological problems. Data of this study demonstrated that chemical radiation protection has been successfully reported using single drug administration has been successfully reported using single drug administration such as imidazole, and Sh-bearing compounds. In the present work, the radioprotective effect of imidazole was demonstrated on the cardiovascular and respiratory systems. Furthermore, combined drug administration was found to exert more protective action with less toxicity and therefore minimize the side effects of the radioprotective drugs. Thus, combination of imidazole and serotonin showed potential protective effect on blood gases was also reported. In addition, combination of cysteine and vitamin E afforded a better protection on adrenocortical function in rats than either agent alone. 4 figs., 1 tab.
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International Nuclear Information System (INIS)
Hassan, S.H.M.
1995-01-01
The present study represents two main subjects. The first encounters the effect of radiosterilization of certain pharmaceretical preparations such as antihistaminics (cimetidine), anticonvulsants (diazepam), beta and calcium channel blacker (propranolol and verapamil) on their pharmacological activity. Results of this study revealed that the previously mentioned drugs can be effectively and safely sterilized by gamma irradiation without deleterious effect on their pharmacological activity. The other subject presented in this study is essentially a pharmacological subject encountering toxicological problems. Data of this study demonstrated that chemical radiation protection has been successfully reported using single drug administration has been successfully reported using single drug administration such as imidazole, and Sh-bearing compounds. In the present work, the radioprotective effect of imidazole was demonstrated on the cardiovascular and respiratory systems. Furthermore, combined drug administration was found to exert more protective action with less toxicity and therefore minimize the side effects of the radioprotective drugs. Thus, combination of imidazole and serotonin showed potential protective effect on blood gases was also reported. In addition, combination of cysteine and vitamin E afforded a better protection on adrenocortical function in rats than either agent alone. 4 figs., 1 tab
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"Hits" emerge through self-organized coordination in collective response of free agents
Chakrabarti, Anindya S.; Sinha, Sitabhra
2016-10-01
Individuals in free societies frequently exhibit striking coordination when making independent decisions en masse. Examples include the regular appearance of hit products or memes with substantially higher popularity compared to their otherwise equivalent competitors or extreme polarization in public opinion. Such segregation of events manifests as bimodality in the distribution of collective choices. Here we quantify how apparently independent choices made by individuals result in a significantly polarized but stable distribution of success in the context of the box-office performance of movies and show that it is an emergent feature of a system of noninteracting agents who respond to sequentially arriving signals. The aggregate response exhibits extreme variability amplifying much smaller differences in individual cost of adoption. Due to self-organization of the competitive landscape, most events elicit only a muted response but a few stimulate widespread adoption, emerging as "hits".
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Rech, Megan A; Donahey, Elisabeth; Cappiello Dziedzic, Jacqueline M; Oh, Laura; Greenhalgh, Elizabeth
2015-02-01
Drug abuse is a common problem and growing concern in the United States, and over the past decade, novel or atypical drugs have emerged and have become increasingly popular. Recognition and treatment of new drugs of abuse pose many challenges for health care providers due to lack of quantitative reporting and routine surveillance, and the difficulty of detection in routine blood and urine analyses. Furthermore, street manufacturers are able to rapidly adapt and develop new synthetic isolates of older drugs as soon as law enforcement agencies render them illegal. In this article, we describe the clinical and adverse effects and purported pharmacology of several new classes of drugs of abuse including synthetic cannabinoids, synthetic cathinones, salvia, desomorphine, and kratom. Because many of these substances can have severe or life-threatening adverse effects, knowledge of general toxicology is key in recognizing acute intoxication and overdose; however, typical toxidromes (e.g., cholinergic, sympathomimetic, opioid, etc.) are not precipitated by many of these agents. Medical management of patients who abuse or overdose on these drugs largely consists of supportive care, although naloxone may be used as an antidote for desomorphine overdose. Symptoms of aggression and psychosis may be treated with sedation (benzodiazepines, propofol) and antipsychotics (haloperidol or atypical agents such as quetiapine or ziprasidone). Other facets of management to consider include treatment for withdrawal or addiction, nutrition support, and potential for transmission of infectious diseases. © 2014 Pharmacotherapy Publications, Inc.
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When good times go bad: managing ‘legal high’ complications in the emergency department
Directory of Open Access Journals (Sweden)
Caffrey CR
2017-12-01
Full Text Available Charles R Caffrey, Patrick M Lank Department of Emergency Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Abstract: Patients can use numerous drugs that exist outside of existing regulatory statutes in order to get “legal highs.” Legal psychoactive substances represent a challenge to the emergency medicine physician due to the sheer number of available agents, their multiple toxidromes and presentations, their escaping traditional methods of analysis, and the reluctance of patients to divulge their use of these agents. This paper endeavors to cover a wide variety of “legal highs,” or uncontrolled psychoactive substances that may have abuse potential and may result in serious toxicity. These agents include not only some novel psychoactive substances aka “designer drugs,” but also a wide variety of over-the-counter medications, herbal supplements, and even a household culinary spice. The care of patients in the emergency department who have used “legal high” substances is challenging. Patients may misunderstand the substance they have been exposed to, there are rarely any readily available laboratory confirmatory tests for these substances, and the exact substances being abused may change on a near-daily basis. This review will attempt to group legal agents into expected toxidromes and discuss associated common clinical manifestations and management. A focus on aggressive symptom-based supportive care as well as management of end-organ dysfunction is the mainstay of treatment for these patients in the emergency department. Keywords: legal highs, novel psychoactive substances, toxicology, opioid toxidrome, anticholinergic toxidrome, sympathomimetic toxidrome, hallucinogens, inhalants
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Mello, Juliana da Fonseca Rezende E; Gomes, Renan Augusto; Vital-Fujii, Drielli Gomes; Ferreira, Glaucio Monteiro; Trossini, Gustavo Henrique Goulart
2017-12-01
Neglected diseases (NDs) affect large populations and almost whole continents, representing 12% of the global health burden. In contrast, the treatment available today is limited and sometimes ineffective. Under this scenery, the Fragment-Based Drug Discovery emerged as one of the most promising alternatives to the traditional methods of drug development. This method allows achieving new lead compounds with smaller size of fragment libraries. Even with the wide Fragment-Based Drug Discovery success resulting in new effective therapeutic agents against different diseases, until this moment few studies have been applied this approach for NDs area. In this article, we discuss the basic Fragment-Based Drug Discovery process, brief successful ideas of general applications and show a landscape of its use in NDs, encouraging the implementation of this strategy as an interesting way to optimize the development of new drugs to NDs. © 2017 John Wiley & Sons A/S.
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Directory of Open Access Journals (Sweden)
Thiago Gatti Pianca
Full Text Available Abstract Objective: To review the screening, diagnosis, evaluation, and treatment of intoxication by alcohol and other drugs in children and adolescents in the emergency scenario. Data source: This was a narrative literature review. Data summary: The detection of this problem in the emergency room can be a challenge, especially when its assessment is not standardized. The intentional and episodic use of large amounts of psychoactive substances by adolescents is a usual occurrence, and unintentional intoxication is more common in children younger than 12 years. The clinical picture in adolescents and children differs from that in adults and some particularities are important in the emergency scenario. After management of the acute condition, interventions targeting the adolescent at risk may be effective. Conclusion: The diagnosis and treatment of intoxication by alcohol and other drugs in adolescents and children in the emergency scenario requires a systematic evaluation of the use of these drugs. There are few specific treatments for intoxication, and the management comprehends support measures and management of related clinical complications.
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Pianca, Thiago Gatti; Sordi, Anne Orgle; Hartmann, Thiago Casarin; von Diemen, Lisia
To review the screening, diagnosis, evaluation, and treatment of intoxication by alcohol and other drugs in children and adolescents in the emergency scenario. This was a narrative literature review. The detection of this problem in the emergency room can be a challenge, especially when its assessment is not standardized. The intentional and episodic use of large amounts of psychoactive substances by adolescents is a usual occurrence, and unintentional intoxication is more common in children younger than 12 years. The clinical picture in adolescents and children differs from that in adults and some particularities are important in the emergency scenario. After management of the acute condition, interventions targeting the adolescent at risk may be effective. The diagnosis and treatment of intoxication by alcohol and other drugs in adolescents and children in the emergency scenario requires a systematic evaluation of the use of these drugs. There are few specific treatments for intoxication, and the management comprehends support measures and management of related clinical complications. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.
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Lu, Wenjie; Xu, Youzhi; Zhao, Yinglan; Cen, Xiaobo
2014-01-01
Drug metabolite identification and metabolic characteristics analysis play a crucial role in new drug research and development, because they can lead to varied efficacy, severe adverse reactions, and even toxicity. Classical methodologies for metabolite identification have mainly been based on mass spectrometry (MS) coupled with gas chromatography (GC) or liquid chromatography (LC), and some other techniques are used as complementary approaches, such as nuclear magnetic resonance (NMR). Over the past decade, more and more newly emerging techniques or technologies have been applied to metabolite identification, and are making the procedure easier and more robust, such as LC-NMR-MS, ion mobility MS, ambient ionization techniques, and imaging MS. A novel application of drug metabolite identification based on "omics" known as pharmacometabonomics is discussed, which is an interdisciplinary field that combines pre-dose metabolite profiling and chemometrics methods for data analysis and modeling, aiming to predict the responses of individuals to drugs.
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Drug interactions between common illicit drugs and prescription therapies.
Lindsey, Wesley T; Stewart, David; Childress, Darrell
2012-07-01
The aim was to summarize the clinical literature on interactions between common illicit drugs and prescription therapies. Medline, Iowa Drug Information Service, International Pharmaceutical Abstracts, EBSCO Academic Search Premier, and Google Scholar were searched from date of origin of database to March 2011. Search terms were cocaine, marijuana, cannabis, methamphetamine, amphetamine, ecstasy, N-methyl-3,4-methylenedioxymethamphetamine, methylenedioxymethamphetamine, heroin, gamma-hydroxybutyrate, sodium oxybate, and combined with interactions, drug interactions, and drug-drug interactions. This review focuses on established clinical evidence. All applicable full-text English language articles and abstracts found were evaluated and included in the review as appropriate. The interactions of illicit drugs with prescription therapies have the ability to potentiate or attenuate the effects of both the illicit agent and/or the prescription therapeutic agent, which can lead to toxic effects or a reduction in the prescription agent's therapeutic activity. Most texts and databases focus on theoretical or probable interactions due to the kinetic properties of the drugs and do not fully explore the pharmacodynamic and clinical implications of these interactions. Clinical trials with coadministration of illicit drugs and prescription drugs are discussed along with case reports that demonstrate a potential interaction between agents. The illicit drugs discussed are cocaine, marijuana, amphetamines, methylenedioxymethamphetamine, heroin, and sodium oxybate. Although the use of illicit drugs is widespread, there are little experimental or clinical data regarding the effects of these agents on common prescription therapies. Potential drug interactions between illicit drugs and prescription drugs are described and evaluated on the Drug Interaction Probability Scale by Horn and Hansten.
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Advances in the Applications of Polyhydroxyalkanoate Nanoparticles for Novel Drug Delivery System
Directory of Open Access Journals (Sweden)
Anupama Shrivastav
2013-01-01
Full Text Available Drug delivery technology is emerging as an interdisciplinary science aimed at improving human health. The controlled delivery of pharmacologically active agents to the specific site of action at the therapeutically optimal rate and dose regimen has been a major goal in designing drug delivery systems. Over the past few decades, there has been considerable interest in developing biodegradable drug carriers as effective drug delivery systems. Polymeric materials from natural sources play an important role in controlled release of drug at a particular site. Polyhydroxyalkanoates, due to their origin from natural sources, are given attention as candidates for drug delivery materials. Biodegradable and biocompatible polyhydroxyalkanoates are linear polyesters produced by microorganisms under unbalanced growth conditions, which have emerged as potential polymers for use as biomedical materials for drug delivery due to their unique physiochemical and mechanical properties. This review summarizes many of the key findings in the applications of polyhydroxyalkanoates and polyhydroxyalkanoate nanoparticles for drug delivery system.
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Scheen, André J
2014-04-01
Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions (DDIs) regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure [assessed by peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC)] to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose-lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin. Some modest changes were not considered as clinically relevant. However, drugs that could specifically interfere with the metabolic pathways of SGLT2 inhibitors [rifampicin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase (UGT)] may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin. Potential DDIs in patients with type 2 diabetes receiving chronic treatment with an SGLT2 inhibitor deserve further attention, especially in individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment.
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Current challenges and emerging drug delivery strategies for the treatment of psoriasis.
Hoffman, Melissa B; Hill, Dane; Feldman, Steven R
2016-10-01
Psoriasis is a common skin disorder associated with physical, social, psychological and financial burden. Over the past two decades, advances in our understanding of pathogenesis and increased appreciation for the multifaceted burden of psoriasis has led to new treatment development and better patient outcomes. Yet, surveys demonstrate that many psoriasis patients are either undertreated or are dissatisfied with treatment. There are many barriers that need be overcome to optimize patient outcomes and satisfaction. This review covers the current challenges associated with each major psoriasis treatment strategy (topical, phototherapy, oral medications and biologics). It also reviews the challenges associated with the psychosocial aspects of the disease and how they affect treatment outcomes. Patient adherence, inconvenience, high costs, and drug toxicities are all discussed. Then, we review the emerging drug delivery strategies in topical, oral, and biologic therapy. By outlining current treatment challenges and emerging drug delivery strategies, we hope to highlight the deficits in psoriasis treatment and strategies for how to overcome them. Regardless of disease severity, clinicians should use a patient-centered approach. In all cases, we need to balance patients' psychosocial needs, treatment costs, convenience, and effectiveness with patients' preferences in order to optimize treatment outcomes.
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The Hofmeister effect on nanodiamonds: How addition of ions provides superior drug loading platforms
Guo, Yong; Li, Song; Li, Wengang; Moosa, Basem; Khashab, Niveen M.
2014-01-01
Colloidal nanodiamonds (NDs) have emerged as highly versatile platforms for the controlled delivery of therapeutics, proteins, DNA, and other assorted biological agents. The most common mechanism of drug loading onto the ND surface depends mainly
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Modified Gadonanotubes as a Promising Novel MRI Contrasting Agent
Rouzbeh Jahanbakhsh; Fatemeh Atyabi; Saeed Shanehsazzadeh; Zahra Sobhani; Mohsen Adeli; Rassoul Dinarvand
2013-01-01
Background and purpose of the study Carbon nanotubes (CNTs) are emerging drug and imaging carrier systems which show significant versatility. One of the extraordinary characteristics of CNTs as Magnetic Resonance Imaging (MRI) contrasting agent is the extremely large proton relaxivities when loaded with gadolinium ion (Gdn 3+) clusters. Methods In this study equated Gdn 3+ clusters were loaded in the sidewall defects of oxidized multiwalled (MW) CNTs. The amount of loaded gadolinium ion into ...
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Li, Z; Chen, Z W; Ren, H; Hu, P
2017-03-20
Direct-acting antiviral agents (DAAs) achieve a high sustained virologic response rate in the treatment of chronic hepatitis C virus infection. However, drug resistance-associated mutations play an important role in treatment failure and have attracted more and more attention. This article elaborates on the clinical significance of drug resistance-associated mutations from the aspects of their definition, association with genotype, known drug resistance-associated mutations and their prevalence rates, the impact of drug resistance-associated mutations on treatment naive and treatment-experienced patients, and the role of clinical detection, in order to provide a reference for clinical regimens with DAAs and help to achieve higher sustained virologic response rates.
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Directory of Open Access Journals (Sweden)
Pei-Chih Lee
2010-05-01
Full Text Available Drug resistance is a crucial factor in the failure of cancer chemotherapy. In this study, we explored the effect of combining alkylating agents and arsenic trioxide (ATO on the suppression of tumor cells with inherited or acquired resistance to therapeutic agents. Our results showed that combining ATO and a synthetic derivative of 3a-aza-cyclopenta[a]indenes (BO-1012, a bifunctional alkylating agent causing DNA interstrand cross-links, was more effective in killing human cancer cell lines (H460, H1299, and PC3 than combining ATO and melphalan or thiotepa. We further demonstrated that the combination treatment of H460 cells with BO-1012 and ATO resulted in severe G2/M arrest and apoptosis. In a xenograft mouse model, the combination treatment with BO-1012 and ATO synergistically reduced tumor volumes in nude mice inoculated with H460 cells. Similarly, the combination of BO-1012 and ATO effectively reduced the growth of cisplatin-resistant NTUB1/P human bladder carcinoma cells. Furthermore, the repair of BO-1012-induced DNA interstrand cross-links was significantly inhibited by ATO, and consequently, γH2AX was remarkably increased and formed nuclear foci in H460 cells treated with this drug combination. In addition, Rad51 was activated by translocating and forming foci in nuclei on treatment with BO-1012, whereas its activation was significantly suppressed by ATO. We further revealed that ATO might mediate through the suppression of AKT activity to inactivate Rad51. Taken together, the present study reveals that a combination of bifunctional alkylating agents and ATO may be a rational strategy for treating cancers with inherited or acquired drug resistance.
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Directory of Open Access Journals (Sweden)
Yong-Yeol Ahn
Full Text Available The 2001 anthrax mail attacks in the United States demonstrated the potential threat of bioterrorism, hence driving the need to develop sophisticated treatment and diagnostic protocols to counter biological warfare. Here, by performing flux balance analyses on the fully-annotated metabolic networks of multiple, whole genome-sequenced bacterial strains, we have identified a large number of metabolic enzymes as potential drug targets for each of the three Category A-designated bioterrorism agents including Bacillus anthracis, Francisella tularensis and Yersinia pestis. Nine metabolic enzymes- belonging to the coenzyme A, folate, phosphatidyl-ethanolamine and nucleic acid pathways common to all strains across the three distinct genera were identified as targets. Antimicrobial agents against some of these enzymes are available. Thus, a combination of cross species-specific antibiotics and common antimicrobials against shared targets may represent a useful combinatorial therapeutic approach against all Category A bioterrorism agents.
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International Nuclear Information System (INIS)
Xiao Yueyong; Zhang Jinshan; Cui Fuzhai; Meng Bo
2004-01-01
Objective: To define the effect of drug eluting BIS with antiproliferation agent-paclitaxel in preventing vascular restenosis. Methods: Bare BIS and drug BIS with 60 μg paclitaxel were prepared. Both types of the BIS were implanted into the infrarenal restenosis aortas in canine models, and the animals were euthanized 6 weeks after implantation for histopathological, morphometric and immunohistochemical assessment. Results: The mean lumen area of bare BIS group was (77 586.5 ± 66.0) μm 2 , and lumen of paclitaxel eluting BIS group was (113 435.9 ±71.0) μm 2 . The mean neointima area of bare BIS group was (24 803 ± 56) μm 2 , and paclitaxel eluting BIS group was (12 931 ± 63) μm 2 . The PCNA-positive ratio was (38 ± 15)% in bare BIS group and (11 ± 0.31)% in paclitaxel eluting BIS group. The statistically significant difference between the two groups were noted (P<0.01). Conclusion: BIS as a vehicle of loading and releasing drugs could significantly inhibit the VSMC and neointimal hyperplasia with antiproliferation agent-paclitaxel. BIS is a promising and new strategy in preventing the restenosis
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Finding a new drug and vaccine for emerging swine flu: What is the concept?
Directory of Open Access Journals (Sweden)
Viroj Wiwanitkit
2009-08-01
Full Text Available Viroj WiwanitkitWiwanitkit House, Bangkhae, Bangkok 10160Abstract: Influenza is a well known infection of the respiratory system. The main clinical manifestations of influenza include fever, sore throat, headache, cough, coryza, and malaise. Apart from the well known classical influenza, there are also groups of influenza virus infections that are called “atypical infection”. These infections are usually due to a novel influenza virus infection. In early 2009, an emerging novel influenza originating from Mexico called swine flu was reported. The World Health Organization noted a level VI precaution, the highest level precaution possible, for this newest influenza virus infection. As of June 2009, it is not known if this disease will be successfully controlled. Finding new drugs and vaccine for the emerging swine flu is still required to cope with this emerging worldwide problem.Keywords: swine flu, drug, vaccine, concept
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A collaborative virtual environment for training of security agents in nuclear emergencies
Energy Technology Data Exchange (ETDEWEB)
Fernandes, Sara I.; Passos, Cláudio A.; Silva, Marcio H.; Carvalho, Paulo Victor R.; Legey, Ana Paula; Mol, Antonio Carlos; Machado, Daniel M.; Cotelli, André; Rocha, Tiago L., E-mail: mol@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Departamento de Realidade Virtual
2017-07-01
In face the recently observed security menaces related to terrorist actions and natural disasters, there is a need for a major qualification and training of the agents responsible for avoid any problems regarding to abnormal conditions. In the conventional training procedures, however, field simulations are associated to logistical and operational constraints regarded to the execution of the tests which can expose the user to risk. On the other hand, the use of virtual simulations provides an alternative to such limitations besides of promote the qualifying of professionals with a great reliability. For this reason, this paper proposes the development of a collaborative virtual environment that will be used to prepare the security agents on identifying individuals suspected of carrying radioactive materials. The development of the virtual environment consisted on modeling using Autodesk 3ds Max, where the scene itself and the scene objects were modeled besides the terrain creation and basic features programming using the Game Engine Unity 3D. In the Engine Game were included radiation detectors and avatars. The security agents were able to communicate to each other by means of auxiliary external tools like a headset software that makes possible the communication, coordination and cooperation required for an effective collaboration. Experimental tests of the virtual simulations were performed with the participation of CNEN radiological protection agents and collaborators. The tests have shown that the proposed method can contribute to improve the training results of the basic collaborative skills required for a CNEN agent in an emergency situation without the need to expose him to any kind of risk. In face of that, we hope that it can contribute to minimize the demand for qualified security professionals. (author)
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A collaborative virtual environment for training of security agents in nuclear emergencies
International Nuclear Information System (INIS)
Fernandes, Sara I.; Passos, Cláudio A.; Silva, Marcio H.; Carvalho, Paulo Victor R.; Legey, Ana Paula; Mol, Antonio Carlos; Machado, Daniel M.; Cotelli, André; Rocha, Tiago L.
2017-01-01
In face the recently observed security menaces related to terrorist actions and natural disasters, there is a need for a major qualification and training of the agents responsible for avoid any problems regarding to abnormal conditions. In the conventional training procedures, however, field simulations are associated to logistical and operational constraints regarded to the execution of the tests which can expose the user to risk. On the other hand, the use of virtual simulations provides an alternative to such limitations besides of promote the qualifying of professionals with a great reliability. For this reason, this paper proposes the development of a collaborative virtual environment that will be used to prepare the security agents on identifying individuals suspected of carrying radioactive materials. The development of the virtual environment consisted on modeling using Autodesk 3ds Max, where the scene itself and the scene objects were modeled besides the terrain creation and basic features programming using the Game Engine Unity 3D. In the Engine Game were included radiation detectors and avatars. The security agents were able to communicate to each other by means of auxiliary external tools like a headset software that makes possible the communication, coordination and cooperation required for an effective collaboration. Experimental tests of the virtual simulations were performed with the participation of CNEN radiological protection agents and collaborators. The tests have shown that the proposed method can contribute to improve the training results of the basic collaborative skills required for a CNEN agent in an emergency situation without the need to expose him to any kind of risk. In face of that, we hope that it can contribute to minimize the demand for qualified security professionals. (author)
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Ivanov, Sergey; Semin, Maxim; Lagunin, Alexey; Filimonov, Dmitry; Poroikov, Vladimir
2017-07-01
Drug-induced liver injury (DILI) is the leading cause of acute liver failure as well as one of the major reasons for drug withdrawal from clinical trials and the market. Elucidation of molecular interactions associated with DILI may help to detect potentially hazardous pharmacological agents at the early stages of drug development. The purpose of our study is to investigate which interactions with specific human protein targets may cause DILI. Prediction of interactions with 1534 human proteins was performed for the dataset with information about 699 drugs, which were divided into three categories of DILI: severe (178 drugs), moderate (310 drugs) and without DILI (211 drugs). Based on the comparison of drug-target interactions predicted for different drugs' categories and interpretation of those results using clustering, Gene Ontology, pathway and gene expression analysis, we identified 61 protein targets associated with DILI. Most of the revealed proteins were linked with hepatocytes' death caused by disruption of vital cellular processes, as well as the emergence of inflammation in the liver. It was found that interaction of a drug with the identified targets is the essential molecular mechanism of the severe DILI for the most of the considered pharmaceuticals. Thus, pharmaceutical agents interacting with many of the identified targets may be considered as candidates for filtering out at the early stages of drug research. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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James, Thomas; Wyke, Stacey; Marczylo, Tim; Collins, Samuel; Gaulton, Tom; Foxall, Kerry; Amlôt, Richard; Duarte‐Davidson, Raquel
2017-01-01
Abstract Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may need to be undertaken to reduce injury and possible loss of life. To ensure these methods are effective, human volunteer trials (HVTs) of decontamination protocols, using simulant contaminants, have been conducted. Simulants must be used to mimic the physicochemical properties of more harmful chemicals, while remaining ...
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Soekmadji, Carolina; Nelson, Colleen C
2015-01-01
Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.
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Meyer, A.P.
2004-01-01
In distributed problem solving with multi-agent systems it is assumed that collective behaviour emerges from interaction among rational agents. The dissemination of mobile agents will lead to open systems. Emergent behaviour in open systems must fulfil common goals based on goals of individual
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[From the discovery of antibiotics to emerging highly drug-resistant bacteria].
Meunier, Olivier
2015-01-01
The discovery of antibiotics has enabled serious infections to be treated. However, bacteria resistant to several families of antibiotics and the emergence of new highly drug-resistant bacteria constitute a public health issue in France and across the world. Actions to prevent their transmission are being put in place. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
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Jablonowski, Lauren J; Alfego, David; Andorko, James I; Eisenbrey, John R; Teraphongphom, Nutte; Wheatley, Margaret A
2016-10-01
Contrast agents are currently being modified to combine diagnostic and therapeutic capabilities. For ultrasound (US) imaging with polymeric contrast agents, it is necessary to modify the shell to create "stealth" microbubbles but without these modifications sacrificing the agent's ability to interact with the focused US beam. We hypothesize that addition of the classic immune shielding molecule polyethylene glycol (PEG) to a polylactide (PLA) microbubble shell will affect the acoustic and physical properties of the resulting agents. In an effort to determine the best formulation to achieve a balance between stealth and acoustic activity, we compared two PEGylation techniques; addition of increasing amounts of PEG-PLA copolymer and employing incorporation of a PEG lipid (LipidPEG) into the shell. Loss of acoustic enhancement occurred in a dose-dependent manner for both types of PEGylated agents (loss of signal occurred at >5 wt% PEG-PLA and >1 wt% LipidPEG), while immune activation was also reduced in a dose-dependent manner for the PEG-PLA agents. This study shows that the balance between acoustic behavior and improved immune avoidance was scalable and successful to different degrees with both PEGylation methods, and was best achieved using for PEG-PLA at 5 wt% and for LipidPEG at 1 wt%. Studies are ongoing to evaluate the best method for the targeting and drug delivery capabilities of these agents for applications in cancer treatment. This study represents the basis for understanding the consequences of making modifications to the native polymeric shell. Copyright © 2016 Elsevier Ltd. All rights reserved.
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SENSITIVITY TO ANTIBACTERIAL DRUGS IN AGENTS OF COMMUNITY-ACQUIRED INFECTIONS
Directory of Open Access Journals (Sweden)
Osolodchenko T.,
2015-04-01
Full Text Available Introduction The widespread and uncontrolled use of antibiotics leads to selection of resistant strains and rise to atypical forms of most infectious agents. Constantly progressive resistance of microorganisms is currently the most important negative phenomenon of antibiotic therapy. The aim of the work was to optimize antibiotic therapy in community-acquired infections. The objective of study was to determine the range and degree of resistance in clinical isolates of microorganisms of different taxonomic groups, obtained from patients in outpatient care. Material and methods 213 clinical isolates of microorganisms obtained from patients in outpatient care were studied: 34,7 % strains were obtained from patients with inflammatory processes in upper respiratory tract, 11,7 % – with ear inflammation, 36,6 % – with inflammatory diseases of urinary and genital tracts, 11,3 % – with of skin and soft tissues inflammation, 4,2 % – eye inflammation and 1,4 % – with postoperative infectious complications. The collection of clinical material was performed accordingly before the start of antibacterial therapy. Microorganisms’ isolation and identification were carried out with the help of microbiological methods according to the regulatory documents. The study of resistance of bacterial strains to the antibacterial drugs was performed with the help of disc diffusion method on the Muller-Hinton nutritional medium and of fungal strains – on Saburo medium with the use of standard commercial discs. Results and discussion The array and level of resistance to antibacterial drugs in clinical isolates of microorganisms of different taxonomic groups obtained from patients in outpatient care was established. The research has established that 43,3 % Staphylococcus spp. isolates possessed polyantibiotic resistance and 3,8 % – extensive resistance, only sensitivity to aminoglycosides and glycopeptides was preserved. The majority of beta
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Maravall, Darío; de Lope, Javier; Domínguez, Raúl
In Multi-agent systems, the study of language and communication is an active field of research. In this paper we present the application of evolutionary strategies to the self-emergence of a common lexicon in a population of agents. By modeling the vocabulary or lexicon of each agent as an association matrix or look-up table that maps the meanings (i.e. the objects encountered by the agents or the states of the environment itself) into symbols or signals we check whether it is possible for the population to converge in an autonomous, decentralized way to a common lexicon, so that the communication efficiency of the entire population is optimal. We have conducted several experiments, from the simplest case of a 2×2 association matrix (i.e. two meanings and two symbols) to a 3×3 lexicon case and in both cases we have attained convergence to the optimal communication system by means of evolutionary strategies. To analyze the convergence of the population of agents we have defined the population's consensus when all the agents (i.e. the 100% of the population) share the same association matrix or lexicon. As a general conclusion we have shown that evolutionary strategies are powerful enough optimizers to guarantee the convergence to lexicon consensus in a population of autonomous agents.
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Shepherd, Marvin D
2013-09-01
independent pharmacy respondents (14.3%). A total of 77.7% of the respondents estimated that they make the decision of providing or not providing a 72-hour emergency supply of medication 6 or fewer times a month. A total of 14.6% indicated that they make the decision 6 to 11 times a month, and 7.7% make the decision more than 11 times a month. When asked how often respondents had seen a 72-hour emergency prescription not being dispensed for Texas Medicaid recipients when PA was not available, 49.1% answered "never"; however, 30.0% indicated once or twice a month, 16.5% indicated from 1 to 5 times a week, and another 4.5% indicated more than 5 times a week. The top 2 reasons for not dispensing a 72 hour-emergency drug supply were: "Reluctant to open a new 'unit-of-use' container (especially 30-day supply bottles)" and "The Rx will most likely be changed with the PA call, so why dispense a 72-hour supply of the originally prescribed drug?" The top categories of 72-hour emergency prescription drug products that respondents would "likely" dispense were antibiotics; inhaler canisters; products for nausea/vomiting, cough, and cold; antiseizure agents; and diabetic treatment products. The results show that there are many factors why pharmacists do not provide 72-hour emergency medications when PA is unavailable. The lack of awareness of the federal and state requirements was significantly related to the frequency of 72-hour medications not being dispensed. In addition, other factors inhibiting the process were the pharmacists' inability to reach physicians or the lack of cooperation with physicians, prescriptions for controlled substances, drug-packing limitations, and the financial risk involved with dispensing a 72-hour supply.
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Yonucu, Sirin; Yιlmaz, Defne; Phipps, Colin; Unlu, Mehmet Burcin; Kohandel, Mohammad
2017-09-01
Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise. In order to explore the effect of microenvironmental conditions and drug scheduling on normalization benefit, we build a mathematical model that incorporates tumor growth, angiogenesis and IFP. We administer various theoretical combinations of antiangiogenic agents and cytotoxic nanoparticles through heterogeneous vasculature that displays a similar morphology to tumor vasculature. We observe differences in drug extravasation that depend on the scheduling of combined therapy; for concurrent therapy, total drug extravasation is increased but in adjuvant therapy, drugs can penetrate into deeper regions of tumor.
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Nuralitha, Suci; Siregar, Josephine E.; Syafruddin, Din; Roelands, Jessica; Verhoef, Jan; Hoepelman, Andy I M; Marzuki, Sangkot
2016-01-01
The evolutionary selection of malaria parasites within individual hosts is an important factor in the emergence of drug resistance but is still not well understood. We have examined the selection process for drug resistance in the mouse malaria agent Plasmodium berghei and compared the dynamics of
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Agent-based models of strategies for the emergence and evolution of grammatical agreement.
Directory of Open Access Journals (Sweden)
Katrien Beuls
Full Text Available Grammatical agreement means that features associated with one linguistic unit (for example number or gender become associated with another unit and then possibly overtly expressed, typically with morphological markers. It is one of the key mechanisms used in many languages to show that certain linguistic units within an utterance grammatically depend on each other. Agreement systems are puzzling because they can be highly complex in terms of what features they use and how they are expressed. Moreover, agreement systems have undergone considerable change in the historical evolution of languages. This article presents language game models with populations of agents in order to find out for what reasons and by what cultural processes and cognitive strategies agreement systems arise. It demonstrates that agreement systems are motivated by the need to minimize combinatorial search and semantic ambiguity, and it shows, for the first time, that once a population of agents adopts a strategy to invent, acquire and coordinate meaningful markers through social learning, linguistic self-organization leads to the spontaneous emergence and cultural transmission of an agreement system. The article also demonstrates how attested grammaticalization phenomena, such as phonetic reduction and conventionalized use of agreement markers, happens as a side effect of additional economizing principles, in particular minimization of articulatory effort and reduction of the marker inventory. More generally, the article illustrates a novel approach for studying how key features of human languages might emerge.
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[Decorporation agents for internal radioactive contamination].
Ohmachi, Yasushi
2015-01-01
When radionuclides are accidentally ingested or inhaled, blood circulation or tissue/organ deposition of the radionuclides causes systemic or local radiation effects. In such cases, decorporation therapy is used to reduce the health risks due to their intake. Decorporation therapy includes reduction and/or inhibition of absorption from the gastrointestinal tract, isotopic dilution, and the use of diuretics, adsorbents, and chelating agents. For example, penicillamine is recommended as a chelating agent for copper contamination, and diethylene triamine pentaacetic acid is approved for the treatment of internal contamination with plutonium. During chelation therapy, the removal effect of the drugs should be monitored using a whole-body counter and/or bioassay. Some authorities, such as the National Council on Radiation Protection and Measurements and International Atomic Energy Agency, have reported recommended decorporation agents for each radionuclide. However, few drugs are approved by the US Food and Drug Administration, and many are off-label-use agents. Because many decontamination agents are drugs that have been available for a long time and have limited efficacy, the development of new, higher-efficacy drugs has been carried out mainly in the USA and France. In this article, in addition to an outline of decorporation agents for internal radioactive contamination, an outline of our research on decorporation agents for actinide (uranium and plutonium) contamination and for radio-cesium contamination is also presented.
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Koper, Rob; Sloep, Peter
2003-01-01
Koper, E.J.R., Sloep, P.B. (2002) Learning Networks connecting people, organizations, autonomous agents and learning resources to establish the emergence of effective lifelong learning. RTD Programma into Learning Technologies 2003-2008. More is different… Heerlen, Nederland: Open Universiteit
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Drug-Induced Anaphylaxis in Latin American Countries.
Jares, Edgardo José; Baena-Cagnani, Carlos E; Sánchez-Borges, Mario; Ensina, Luis Felipe C; Arias-Cruz, Alfredo; Gómez, Maximiliano; Cuello, Mabel Noemi; Morfin-Maciel, Blanca María; De Falco, Alicia; Barayazarra, Susana; Bernstein, Jonathan A; Serrano, Carlos; Monsell, Silvana; Schuhl, Juan; Cardona-Villa, Ricardo
2015-01-01
Information regarding the clinical features and management of drug-induced anaphylaxis (DIA) in Latin America is lacking. The objective of this study was to assess implicated medications, demographics, and treatments received for DIA in Latin American patients referred to national specialty centers for evaluation. A database previously used to compile information on drug-induced allergic reactions in 11 Latin American countries was used to identify and characterize patients presenting specifically with a clinical diagnosis of DIA. Information regarding clinical presentation, causative agent(s), diagnostic studies performed, treatment, and contributing factors associated with increased reaction severity was analyzed. There were 1005 patients evaluated for possible drug hypersensitivity reactions during the study interval, and 264 (26.3%) met criteria for DIA. DIA was more frequent in adults and in elderly females (N = 129 [76.6%] and N = 30 [75%], respectively) compared with children and/or adolescents (N = 21 [42.9%], P asthma (N = 22 vs 35 [38.6% vs 61.4%], P Latin American patients referred for evaluation of DIA, NSAIDs and antibiotics were implicated in approximately 80% of cases. Most of these reactions were treated in the emergency department. Epinephrine was administered in only 27.6% of all cases, although more frequently for anaphylactic shock. Dissemination of anaphylaxis guidelines among emergency department physicians should be encouraged to improve management of DIA. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
Thiago Gatti Pianca
2017-11-01
Conclusion: The diagnosis and treatment of intoxication by alcohol and other drugs in adolescents and children in the emergency scenario requires a systematic evaluation of the use of these drugs. There are few specific treatments for intoxication, and the management comprehends support measures and management of related clinical complications.
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Abulateefeh, Samer R; Taha, Mutasem O
2015-01-01
Calcium alginate nanoparticles (NPs) suffer from sub-optimal stability in bio-relevant media leading to low drug encapsulation efficiency and uncontrolled release profiles. To sort out these drawbacks, a novel approach is proposed herein based on introducing tannic acid into these NPs to act as a bridging cross-linking aid agent. Calcium-alginate NPs were prepared by the ionotropic gelation method and loaded with diltiazem hydrochloride as a model drug. These NPs were characterized in terms of particle size, zeta potential, and morphology, and results were explained in accordance with Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The incorporation of tannic acid led to more than four folds increase in drug encapsulation efficiency (i.e. from 15.3% to 69.5%) and reduced burst drug release from 44% to around 10% within the first 30 min. These findings suggest the possibility of improving the properties of Ca-alginate NPs by incorporating cross-linking aid agents under mild conditions.
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Sutter, M E; Chenoweth, J; Albertson, T E
2014-02-01
The incidence of drug abuse with alternative agents is increasing. The term "alternative drugs of abuse" is a catch-all term for abused chemicals that do not fit into one of the classic categories of drugs of abuse. The most common age group abusing these agents range from 17 to 25 years old and are often associated with group settings. Due to their diverse pharmacological nature, legislative efforts to classify these chemicals as a schedule I drug have lagged behind the development of new alternative agents. The potential reason for abuse of these agents is their hallucinogenic, dissociative, stimulant, anti-muscarinic, or sedative properties. Some of these drugs are easily obtainable such as Datura stramonium (Jimson Weed) or Lophophora williamsii (Peyote) because they are natural plants indigenous to certain regions. The diverse pharmacology and clinical effects of these agents are so broad that they do not produce a universal constellation of signs and symptoms. Detailed physical exams are essential for identifying clues leading one to suspect an alternative drug of abuse. Testing for the presence of these agents is often limited, and even when available, the results do not return in a timely fashion. Intoxications from these agents pose unique challenges for health care providers. Physician knowledge of the physiological effects of these alternative agents and the local patterns of drug of abuse are important for the accurate diagnosis and optimal care of poisoned patients. This review summarizes the current knowledge of alternative drugs of abuse and highlights their clinical presentations.
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Reversal agents in anaesthesia and critical care
Directory of Open Access Journals (Sweden)
Nibedita Pani
2015-01-01
Full Text Available Despite the advent of short and ultra-short acting drugs, an in-depth knowledge of the reversal agents used is a necessity for any anaesthesiologist. Reversal agents are defined as any drug used to reverse the effects of anaesthetics, narcotics or potentially toxic agents. The controversy on the routine reversal of neuromuscular blockade still exists. The advent of newer reversal agents like sugammadex have made the use of steroidal neuromuscular blockers like rocuronium feasible in rapid sequence induction situations. We made a review of the older reversal agents and those still under investigation for drugs that are regularly used in our anaesthesia practice.
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Common drug-drug interactions in antifungal treatments for superficial fungal infections.
Gupta, Aditya K; Versteeg, Sarah G; Shear, Neil H
2018-04-01
Antifungal agents can be co-administered alongside several other medications for a variety of reasons such as the presence of comorbidities. Pharmacodynamic interactions such as synergistic and antagonistic interactions could be the result of co-administered medications. Pharmacokinetic interactions could also transpire through the inhibition of metabolizing enzymes and drug transport systems, altering the absorption, metabolism and excretion of co-administered medications. Both pharmacodynamic and pharmacokinetic interactions can result in hospitalization due to serious adverse effects associated with antifungal agents, lower therapeutic doses required to achieve desired antifungal activity, and prevent antifungal resistance. Areas covered: The objective of this review is to summarize pharmacodynamic and pharmacokinetic interactions associated with common antifungal agents used to treat superficial fungal infections. Pharmacodynamic and pharmacokinetic interactions that impact the therapeutic effects of antifungal agents and drugs that are influenced by the presence of antifungal agents was the context to which these antifungal agents were addressed. Expert opinion: The potential for drug-drug interactions is minimal for topical antifungals as opposed to oral antifungals as they have minimal exposure to other co-administered medications. Developing non-lipophilic antifungals that have unique metabolizing pathways and are topical applied are suggested properties that could help limit drug-drug interactions associated with future treatments.
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Millan, Mark J
2009-01-01
The past decade of efforts to find improved treatment for major depression has been dominated by genome-driven programs of rational drug discovery directed toward highly selective ligands for nonmonoaminergic agents. Selective drugs may prove beneficial for specific symptoms, for certain patient subpopulations, or both. However, network analyses of the brain and its dysfunction suggest that agents with multiple and complementary modes of action are more likely to show broad-based efficacy against core and comorbid symptoms of depression. Strategies for improved multitarget exploitation of monoaminergic mechanisms include triple inhibitors of dopamine, serotonin (5-HT) and noradrenaline reuptake, and drugs interfering with feedback actions of monoamines at inhibitory 5-HT(1A), 5-HT(1B) and possibly 5-HT(5A) and 5-HT(7) receptors. Specific subsets of postsynaptic 5-HT receptors mediating antidepressant actions are under study (e.g., 5-HT(4) and 5-HT(6)). Association of a clinically characterized antidepressant mechanism with a nonmonoaminergic component of activity is an attractive strategy. For example, agomelatine (a melatonin agonist/5-HT(2C) antagonist) has clinically proven activity in major depression. Dual neurokinin(1) antagonists/5-HT reuptake inhibitors (SRIs) and melanocortin(4) antagonists/SRIs should display advantages over their selective counterparts, and histamine H(3) antagonists/SRIs, GABA(B) antagonists/SRIs, glutamatergic/SRIs, and cholinergic agents/SRIs may counter the compromised cognitive function of depression. Finally, drugs that suppress 5-HT reuptake and blunt hypothalamo-pituitary-adrenocorticotrophic axis overdrive, or that act at intracellular proteins such as GSK-3beta, may abrogate the negative effects of chronic stress on mood and neuronal integrity. This review discusses the discovery and development of dual- and triple-acting antidepressants, focusing on novel concepts and new drugs disclosed over the last 2 to 3 years.
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SODAS: Surveillance of Drugs of Abuse Study.
Lowe, David J; Torrance, Hazel J; Ireland, Alastair J; Bloeck, Felix; Stevenson, Richard
2017-04-01
Novel psychoactive substance (NPS) as a form of recreational drug use has become increasingly popular. There is a paucity of information with regard to the prevalence and clinical sequelae of these drugs. The aim of this study was to detect NPS in patients presenting to the emergency department with suspected toxicological ingestion. The prospective study was performed in a large emergency department in the UK. During a 3-month period 80 patients were identified by clinicians as having potentially ingested a toxicological agent. Urine samples were analysed using liquid chromatography high-resolution mass spectrometry, and basic clinical data was gathered. Eighty patients with a history of illicit or recreational drug consumption had urine screenings performed. Forty-nine per cent (39) of the patients undergoing a screen had more than one illicit substance detected. Twenty per cent (16) of the patients tested positive for at least one NPS. Almost half of the presented patients revealed ingestion of multiple substances, which correlated poorly with self-reporting of patients. Developing enhanced strategies to monitor evolving drug trends is crucial to the ability of clinicians to deliver care to this challenging group of patients.
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Topical antifungal agents: an update.
Diehl, K B
1996-10-01
So many topical antifungal agents have been introduced that it has become very difficult to select the proper agent for a given infection. Nonspecific agents have been available for many years, and they are still effective in many situations. These agents include Whitfield's ointment, Castellani paint, gentian violet, potassium permanganate, undecylenic acid and selenium sulfide. Specific antifungal agents include, among others, the polyenes (nystatin, amphotericin B), the imidazoles (metronidazole, clotrimazole) and the allylamines (terbinafine, naftifine). Although the choice of an antifungal agent should be based on an accurate diagnosis, many clinicians believe that topical miconazole is a relatively effective agent for the treatment of most mycotic infections. Terbinafine and other newer drugs have primary fungicidal effects. Compared with older antifungal agents, these newer drugs can be used in lower concentrations and shorter therapeutic courses. Studies are needed to evaluate the clinical efficacies and cost advantages of both newer and traditional agents.
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Guo, Gepu; Lu, Lu; Yin, Leilei; Tu, Juan; Guo, Xiasheng; Wu, Junru; Xu, Di; Zhang, Dong
2014-11-01
Development of magnetic encapsulated microbubble agents that can integrate multiple diagnostic and therapeutic functions is a key focus in both biomedical engineering and nanotechnology and one which will have far-reaching impact on medical diagnosis and therapies. However, properly designing multifunctional agents that can satisfy particular diagnostic/therapeutic requirements has been recognized as rather challenging, because there is a lack of comprehensive understanding of how the integration of magnetic nanoparticles to microbubble encapsulating shells affects their mechanical properties and dynamic performance in ultrasound imaging and drug delivery. Here, a multifunctional imaging contrast and in-situ gene/drug delivery agent was synthesized by coupling super paramagnetic iron oxide nanoparticles (SPIOs) into albumin-shelled microbubbles. Systematical studies were performed to investigate the SPIO-concentration-dependence of microbubble mechanical properties, acoustic scattering response, inertial cavitation activity and ultrasound-facilitated gene transfection effect. These demonstrated that, with the increasing SPIO concentration, the microbubble mean diameter and shell stiffness increased and ultrasound scattering response and inertial cavitation activity could be significantly enhanced. However, an optimized ultrasound-facilitated vascular endothelial growth factor transfection outcome would be achieved by adopting magnetic albumin-shelled microbubbles with an appropriate SPIO concentration of 114.7 µg ml-1. The current results would provide helpful guidance for future development of multifunctional agents and further optimization of their diagnostic/therapeutic performance in clinic.
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International Nuclear Information System (INIS)
Guo, Gepu; Lu, Lu; Tu, Juan; Guo, Xiasheng; Zhang, Dong; Yin, Leilei; Wu, Junru; Xu, Di
2014-01-01
Development of magnetic encapsulated microbubble agents that can integrate multiple diagnostic and therapeutic functions is a key focus in both biomedical engineering and nanotechnology and one which will have far-reaching impact on medical diagnosis and therapies. However, properly designing multifunctional agents that can satisfy particular diagnostic/therapeutic requirements has been recognized as rather challenging, because there is a lack of comprehensive understanding of how the integration of magnetic nanoparticles to microbubble encapsulating shells affects their mechanical properties and dynamic performance in ultrasound imaging and drug delivery. Here, a multifunctional imaging contrast and in-situ gene/drug delivery agent was synthesized by coupling super paramagnetic iron oxide nanoparticles (SPIOs) into albumin-shelled microbubbles. Systematical studies were performed to investigate the SPIO-concentration-dependence of microbubble mechanical properties, acoustic scattering response, inertial cavitation activity and ultrasound-facilitated gene transfection effect. These demonstrated that, with the increasing SPIO concentration, the microbubble mean diameter and shell stiffness increased and ultrasound scattering response and inertial cavitation activity could be significantly enhanced. However, an optimized ultrasound-facilitated vascular endothelial growth factor transfection outcome would be achieved by adopting magnetic albumin-shelled microbubbles with an appropriate SPIO concentration of 114.7 µg ml −1 . The current results would provide helpful guidance for future development of multifunctional agents and further optimization of their diagnostic/therapeutic performance in clinic. (paper)
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Energy Technology Data Exchange (ETDEWEB)
Kay, J.S.; Litin, B.S.; Woolfenden, J.M.; Chvapil, M.; Herschler, J.
1986-10-01
Antitumor and antifibroblast agents show promise as adjuncts after glaucoma filtration surgery in reducing postoperative scarring and failure. We used nuclear imaging in rabbits to investigate periocular clearance of one such agent (/sup 57/Co-bleomycin). Sub-Tenon injection was compared to other delivery techniques. Our results showed that a collagen sponge and a silastic disc implant with a microhole prolonged drug delivery when compared to sub-Tenon injection alone or injection with a viscosity enhancing agent (0.5% sodium hyaluronate). We theorize that if an antifibroblast agent can be delivered in small and sustained amounts after filtration surgery, this may prolong bleb longevity and avoid unnecessary drug toxicity.
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International Nuclear Information System (INIS)
Kay, J.S.; Litin, B.S.; Woolfenden, J.M.; Chvapil, M.; Herschler, J.
1986-01-01
Antitumor and antifibroblast agents show promise as adjuncts after glaucoma filtration surgery in reducing postoperative scarring and failure. We used nuclear imaging in rabbits to investigate periocular clearance of one such agent ( 57 Co-bleomycin). Sub-Tenon injection was compared to other delivery techniques. Our results showed that a collagen sponge and a silastic disc implant with a microhole prolonged drug delivery when compared to sub-Tenon injection alone or injection with a viscosity enhancing agent (0.5% sodium hyaluronate). We theorize that if an antifibroblast agent can be delivered in small and sustained amounts after filtration surgery, this may prolong bleb longevity and avoid unnecessary drug toxicity
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International Nuclear Information System (INIS)
Tofilon, P.J.; Arundel, C.; Vines, C.M.
1987-01-01
Repeated administration of antineoplastic chemotherapeutic agents is generally considered to induce and/or select for drug resistant cells. The authors recently begun to investigate whether chemotherapy interdigitated with radiation can minimize or eliminate the emergence of drug resiistent cells in 9L rat brain tumor spheroids grown from defined mixtures of cells sensitive (9L) and resistant (R/sub 3/) to BCNU. In this experimental system, the sister chromatid exchange (SCE) assay is used to quantitate the proportions of sensitive and resistant cells within the spheroids. While 9L and R/sub 3/ cell have different sensitivities to BCNU, they are equally sensitive to radiation. Mixed-cell spheroids consisting of 1% R/sub 3/ cells were treated with three doses of BCNU (10 μM) every 72 hr resulting in a shift in the 9L to R/sub 3/ ratio to greater than 50% R/sub 3/ cells. The combined protocols to be investigated will involve γ rays administered either 36 hr before or after each BCNU treatment. By initiating these combined protocols on spheroids of different sizes, the effectiveness of each protocol is evaluated with respect to the number of resistant cells present
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Ochala, Julien
2010-02-01
Ca(2+) ions are key regulators of skeletal muscle contraction. By binding to contractile proteins, they initiate a cascade of molecular events leading to cross-bridge formation and ultimately, muscle shortening and force production. The ability of contractile proteins to respond to Ca(2+) attachment, also known as Ca(2+) sensitivity, is often compromised in acquired and congenital skeletal muscle disorders. It constitutes, undoubtedly, a major physiological cause of weakness for patients. In this review, we discuss recent studies giving strong molecular and cellular evidence that pharmacological modulators of some of the contractile proteins, also termed Ca(2+) sensitizers, are efficient agents to improve Ca(2+) sensitivity and function in diseased skeletal muscle cells. In fact, they compensate for the impaired contractile proteins response to Ca(2+) binding. Currently, such Ca(2+) sensitizing compounds are successfully used for reducing problems in cardiac disorders. Therefore, in the future, under certain conditions, these agents may represent an emerging class of agents to enhance the quality of life of patients suffering from skeletal muscle weakness. Copyright 2009 Elsevier B.V. All rights reserved.
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Osteoarthritis: Key elements in its pathogenesis and current agents for pathogenetic therapy
Directory of Open Access Journals (Sweden)
Yu. A. Olyunin
2017-01-01
Full Text Available Three main areas can be arbitrarily identified in the modern concept of treatment for osteoarthritis (OA; these are: 1 an impact on the progression of joint destruction; 2 suppression of peripheral pain mechanisms; and 3 inhibition of the central processes involved in the formation of pain sensation. Glucosamine and chondroitin sulfate (CS have become the first agents that are able to retard the development of cartilage degeneration. They have been used in medical practice for more than 40 years. A number of clinical trials of these drugs have yielded favorable results during their use in patients with OA. Another agent containing amino sugars and CS – sea fish cartilage hydrolysate has more recently emerged. Clinical trials have demonstrated that it is able to significantly relieve OA-induced pain. To date, the main agent for the analgesic therapy of OA is considered to be nonsteroidal anti-inflammatory drugs (NSAIDs that act on the peripheral mechanisms of pain and are widely used to treat diseases that are accompanied by chronic pain. However, a large-scale meta-analysis dealing with the experience with NSAIDs used to treat OA has shown that pain relief due to this therapy averaged only about 10 mm on a 100-mm visual analogue scale. To enhance the efficiency of therapy for OA, drug and non-drug treatments that affect the central mechanisms of pain in this disease are also used.
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Imbalanced decision hierarchy in addicts emerging from drug-hijacked dopamine spiraling circuit.
Directory of Open Access Journals (Sweden)
Mehdi Keramati
Full Text Available Despite explicitly wanting to quit, long-term addicts find themselves powerless to resist drugs, despite knowing that drug-taking may be a harmful course of action. Such inconsistency between the explicit knowledge of negative consequences and the compulsive behavioral patterns represents a cognitive/behavioral conflict that is a central characteristic of addiction. Neurobiologically, differential cue-induced activity in distinct striatal subregions, as well as the dopamine connectivity spiraling from ventral striatal regions to the dorsal regions, play critical roles in compulsive drug seeking. However, the functional mechanism that integrates these neuropharmacological observations with the above-mentioned cognitive/behavioral conflict is unknown. Here we provide a formal computational explanation for the drug-induced cognitive inconsistency that is apparent in the addicts' "self-described mistake". We show that addictive drugs gradually produce a motivational bias toward drug-seeking at low-level habitual decision processes, despite the low abstract cognitive valuation of this behavior. This pathology emerges within the hierarchical reinforcement learning framework when chronic exposure to the drug pharmacologically produces pathologicaly persistent phasic dopamine signals. Thereby the drug hijacks the dopaminergic spirals that cascade the reinforcement signals down the ventro-dorsal cortico-striatal hierarchy. Neurobiologically, our theory accounts for rapid development of drug cue-elicited dopamine efflux in the ventral striatum and a delayed response in the dorsal striatum. Our theory also shows how this response pattern depends critically on the dopamine spiraling circuitry. Behaviorally, our framework explains gradual insensitivity of drug-seeking to drug-associated punishments, the blocking phenomenon for drug outcomes, and the persistent preference for drugs over natural rewards by addicts. The model suggests testable predictions and
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Ultrasound-Mediated Drug/Gene Delivery in Solid Tumor Treatment
Directory of Open Access Journals (Sweden)
Yufeng Zhou
2013-01-01
Full Text Available Ultrasound is an emerging modality for drug delivery in chemotherapy. This paper reviews this novel technology by first introducing the designs and characteristics of three classes of drug/gene vehicles, microbubble (including nanoemulsion, liposomes, and micelles. In comparison to conventional free drug, the targeted drug-release and delivery through vessel wall and interstitial space to cancerous cells can be activated and enhanced under certain sonication conditions. In the acoustic field, there are several reactions of these drug vehicles, including hyperthermia, bubble cavitation, sonoporation, and sonodynamics, whose physical properties are illustrated for better understanding of this approach. In vitro and in vivo results are summarized, and future directions are discussed. Altogether, ultrasound-mediated drug/gene delivery under imaging guidance provides a promising option in cancer treatment with enhanced agent release and site specificity and reduced toxicity.
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Possible inclinations for psychostimulant, toxic agent and drug abuse among youths and students
Directory of Open Access Journals (Sweden)
V. G. Ginzburg
2012-03-01
Full Text Available Taking into account modern achievements in medicine, psychology and sociology, the attempt at complex research of possible inclinations for psychostimulant, toxic agent and drug abuse among youths and students was made with the subsequent determination of the possible alternates of primary prevention. It is analysed the basic and additional risk factors promoting smoking, drinking, psychostimulant abuse, toxicomania and narcomania among young people. The dynamics of possible influences of medical, psychological and social factors is studied. The attempt of short-term prognostication and ranking was made.
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Pharmacogenetics in diverse ethnic populations--implications for drug discovery and development.
McCarthy, Linda C; Davies, Kirstie J; Campbell, David A
2002-07-01
It is widely acknowledged that the vast quantities of data now publicly available as a result of the human genome initiative have the potential to revolutionize the pharmaceutical industry. More tangibly to the drug development business, the dawn of the pharmacogenetics era has the potential to impact not only the discovery of new medicines but also the safety and efficacy of pharmaceutical agents. Coincident with these scientific advances is the emergence of new markets for pharmaceutical agents. Japan, which represents the world's second biggest market, is a good example. With the ICH E5 agreement in 1998 and a rapid change in the drug registration process in Japan, there are increasing opportunities to improve access to more medicines in all parts of the world. However, it is increasingly clear that significant genetic variation still exists between populations, with a host of data on interethnic variation in drug metabolizing enzyme and drug transporter activity. Evidence suggesting that this genetic variation may play an important role in defining some of the interethnic variation in drug response to currently marketed compounds is reviewed here, and future possibilities of using such information to better streamline the drug development process are discussed.
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[Interactions of cytostatic agents with other drugs].
Sauter, C
1991-08-31
With the degree of polypharmacy currently practiced in the field of oncology, there are undoubtedly many drug interactions. In the present study the influence of "non-cytotoxic" drugs on anticancer drugs is discussed, but not the reverse. Not only is the augmentation (reversal of multidrug resistance) or the reduction of antitumor properties of cytotoxic drugs observed, but also cytostatic activities of "non-cytotoxic" drugs themselves. Examples are calmodulin inhibitors such as phenothiazines and tricyclic antidepressants. Interactions may also increase side effects of cytostatic drugs or even neutralize the antitumoral activity. To ensure that interactions are not overlooked, all medicaments being administered should be listed. It is, however, not feasible yet to determine serum concentrations of all the drugs given to the patient. The antitumor activity of supportive care could be evaluated in randomized studies (e.g. cytostatic drugs +/- antidepressants).
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Emerging role of Amiodarone and Dronedarone, as antiarrhythmic drugs, in treatment of leishmaniasis.
Oryan, A; Bemani, E; Bahrami, S
2018-04-21
Leishmaniasis is a group of human and animal diseases causing 20,000 to 40,000 annual deaths and its etiological agents belong to the Leishmania genus. The most current treatment against leishmaniasis is chemotherapy. Pentavalent antimonials such as glucantime and pentostam have been administrated as the first-line drugs in treatment of various forms of leishmaniasis. The second-line drugs such as amphotericin B, liposomal amphotericin B, miltefosine, pentamidine, azole drugs and paromomycin are used in resistant cases to pentavalent antimonials. Because of drawbacks of the first-line and second-line drugs including adverse side effects on different organs, increasing resistance, high cost, need to hospitalization and long-term treatment, it is necessary to find an alternative drug for leishmaniasis treatment. Several investigations have reported the effectiveness of amiodarone, the most commonly used antiarrhythmic drug, against fungi, Trypanosomes and Leishmania spp. in vitro, in vivo and clinical conditions. Moreover, the beneficial effects of dronedarone, amiodarone analogues, against Trypanosoma cruzi and Leishmania mexicana have recently been demonstrated and such treatment regimens resulted in lower side effects. The anti- leishmanial and anti- trypanosomal effectiveness of amiodarone and dronedarone has been attributed to destabilization of intracellular Ca 2+ homeostasis, inhibition of sterol biosynthesis and collapse of mitochondrial membrane potential. Because of relative low cost, excellent pharmacokinetic properties, easy accessibility and beneficial effects of amiodarone and dronedarone on leishmaniasis, they are proper candidates to replace the current drugs used in leishmaniasis treatment. Copyright © 2018 Elsevier B.V. All rights reserved.
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Emerging integrated nanoclay-facilitated drug delivery system for papillary thyroid cancer therapy
Zhang, Yi; Long, Mei; Huang, Peng; Yang, Huaming; Chang, Shi; Hu, Yuehua; Tang, Aidong; Mao, Linfeng
2016-09-01
Nanoclay can be incorporated into emerging dual functional drug delivery systems (DDSs) to promote efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX) used for thyroid cancer treatment. This paper reports the expansion of the basal spacing of kaolinite nanoclay was expanded from 0.72 nm to 0.85 nm, which could provide sufficiently spacious site for hosting doxorubicin molecules and controlling the diffusion rate. A targeted design for papillary thyroid cancer cells was achieved by introducing KI, which is consumed by the sodium-iodide symporter (NIS). As indicated by MTT assays, confocal laser scanning microscopy and bio-TEM observations, methoxy-intercalated kaolinite (KaolinMeOH) exhibited negligible cytotoxicity against papillary thyroid cancer cells. By contrast, DOX-KaolinMeOH showed dose-dependent therapeutic effects in vitro, and KI@DOX-KaolinMeOH was found to act as a powerful targeted therapeutic drug. Furthermore, active and passive targeting strategies played a role in the accumulation of the drug molecules, as verified by an in vivo bio-distribution analysis.
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Cailhol, Lionel; Allen, Michael; Moncany, Anne-Hélène; Cicotti, Andrei; Virgillito, Salvatore; Barbe, Rémy P; Lazignac, Coralie; Damsa, Cristian
2007-01-01
In spite of much effort to create guidelines on the management of violent behavior (VB) in emergency departments, little is known about the impact of such guidelines on a real-life emergency environment. The aim of this study is to investigate the impact of a staff educational crisis intervention (SECI) on the reduction of VB in patients admitted to emergency departments following drug suicidal attempt. The impact of a SECI on VB of patient consulting the ER following a drug suicide attempt was assessed by comparing the occurrence of VB before (5 months) and after (5 months) the introduction of a SECI. A significant reduction in VB (from 17.32% to 7.14%) was found with the comparison of two 5-month periods: before (254 patients) and after (224 patients) the introduction of a SECI program (chi(2)=11.238; P=.0008). These preliminary data suggest the need for further prospective randomized studies aiming to prevent VB in emergency departments by developing specific SECI programs.
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Methotrexate: the emerging drug of choice for serious rheumatoid arthritis.
Salach, R H; Cash, J M
1994-01-01
The recently recognized high morbidity and unexpected mortality associated with rheumatoid arthritis (RA) has spurred new interest in more aggressive, early treatment of this disease. Methotrexate (MTX) has rapidly become the rheumatologist's drug of choice for serious RA because of its favorable efficacy to toxicity ratio and rapid onset of action compared with other second-line agents. The initial concerns about hepatic fibrosis and cirrhosis in psoriatic patients has subsided somewhat as long-term liver toxicity data are accumulating in patients with RA. Routine liver biopsy with incremental doses of MTX is no longer recommended. Potential for severe lung, hematologic, and infectious complications exists, mandating careful monitoring of RA patients taking MTX.
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Stolker, A.A.M.; Brinkman, U.A.T.
2005-01-01
After a brief introduction into the field of veterinary drugs and growth-promoting agents, the most important EU regulations and directives for the inspection of food-producing animals and animal products regarding the residue control of these substances are presented and discussed. Main attention
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REBAMIPIDE: EFFECTIVE DRUG PREVENTION OF NSAID ENTEROPATHY IS POSSIBLE
Directory of Open Access Journals (Sweden)
E. V. Moroz
2016-01-01
Full Text Available Prevention of gastrointestinal tract (GIT complications is the most important element for the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs and low-dose aspirin (LDA. Proton pump inhibitors (PPIs have long been the only medication to prevent these complications. However, PPIs are only effective in preventing and treating upper GIT diseases (NSAID gastropathy rather than small intestinal injury (NSAID enteropathy. Rebamipide has emerged as a novel agent to protect the gastrointestinal mucosa today. The effect of the drug differs from that of PPIs: it is a typical gastroand enteroprotector that enhances the synthesis of endogenous prostaglandins and possesses a significant anti-inflammatory potential. Rebamipide has long been widely used by doctors inJapan,South Korea, andChinaas an effective and safe agent for the treatment of many diseases of the digestive system. There is a strong evidence base for the efficacy of rebamipide in preventing and treating NSAID gastropathy and NSAID enteropathy (including LDA-induced injuries. Controlled studies have found that the drug is not inferior to the classic gastroprotective agent misoprostol, significantly outperforming the latter in its tolerability. This review describes the mechanism of action of rebamipide and main clinical trials of its therapeutic effect in NSAID gastropathy and NSAID enteropathy.
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The Emerging Role of Biotechnological Drugs in the Treatment of Gout
Directory of Open Access Journals (Sweden)
L. Cavagna
2014-01-01
Full Text Available One of the most important therapeutic advances obtained in the field of rheumatology is the availability of the so-called bio(technological drugs, which have deeply changed treatment perspectives in diseases such as rheumatoid arthritis and ankylosing spondylitis. According to the steadily increasing attention on gout, due to well-established prognostic and epidemiology implications, in the last 5 years, the same change of perspective has been observed also for this disease. In fact, several bio(technological agents have been investigated both for the management of the articular gout symptoms, targeting mainly interleukin-1β, as well as urate-lowering therapies such as recombinant uricases. Among the IL-1β inhibitors, the majority of studies involve drugs such as anakinra, canakinumab, and rilonacept, but other compounds are under development. Moreover, other potential targets have been suggested, as, for example, the TNF alpha and IL-6, even if data obtained are less robust than those of IL-1β inhibitors. Regarding urate-lowering therapies, the recombinant uricases pegloticase and rasburicase clearly showed their effectiveness in gout patients. Also in this case, new compounds are under development. The aim of this review is to focus on the various aspects of different bio(technological drugs in gouty patients.
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Yang, Lucie; Krefting, Ira; Gorovets, Alex; Marzella, Louis; Kaiser, James; Boucher, Robert; Rieves, Dwaine
2012-10-01
In 2007, the Food and Drug Administration requested that manufacturers of all approved gadolinium-based contrast agents (GBCAs), drugs widely used in magnetic resonance imaging, use nearly identical text in their product labeling to describe the risk of nephrogenic systemic fibrosis (NSF). Accumulating information about NSF risks led to revision of the labeling text for all of these drugs in 2010. The present report summarizes the basis and purpose of this class-labeling approach and describes some of the related challenges, given the evolutionary nature of the NSF risk evidence. The class-labeling approach for presentation of product risk is designed to decrease the occurrence of NSF and to enhance the safe use of GBCAs in radiologic practice. © RSNA, 2012.
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Ambient agents: embedded agents for remote control and monitoring using the PANGEA platform.
Villarrubia, Gabriel; De Paz, Juan F; Bajo, Javier; Corchado, Juan M
2014-07-31
Ambient intelligence has advanced significantly during the last few years. The incorporation of image processing and artificial intelligence techniques have opened the possibility for such aspects as pattern recognition, thus allowing for a better adaptation of these systems. This study presents a new model of an embedded agent especially designed to be implemented in sensing devices with resource constraints. This new model of an agent is integrated within the PANGEA (Platform for the Automatic Construction of Organiztions of Intelligent Agents) platform, an organizational-based platform, defining a new sensor role in the system and aimed at providing contextual information and interacting with the environment. A case study was developed over the PANGEA platform and designed using different agents and sensors responsible for providing user support at home in the event of incidents or emergencies. The system presented in the case study incorporates agents in Arduino hardware devices with recognition modules and illuminated bands; it also incorporates IP cameras programmed for automatic tracking, which can connect remotely in the event of emergencies. The user wears a bracelet, which contains a simple vibration sensor that can receive notifications about the emergency situation.
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Ambient Agents: Embedded Agents for Remote Control and Monitoring Using the PANGEA Platform
Directory of Open Access Journals (Sweden)
Gabriel Villarrubia
2014-07-01
Full Text Available Ambient intelligence has advanced significantly during the last few years. The incorporation of image processing and artificial intelligence techniques have opened the possibility for such aspects as pattern recognition, thus allowing for a better adaptation of these systems. This study presents a new model of an embedded agent especially designed to be implemented in sensing devices with resource constraints. This new model of an agent is integrated within the PANGEA (Platform for the Automatic Construction of Organiztions of Intelligent Agents platform, an organizational-based platform, defining a new sensor role in the system and aimed at providing contextual information and interacting with the environment. A case study was developed over the PANGEA platform and designed using different agents and sensors responsible for providing user support at home in the event of incidents or emergencies. The system presented in the case study incorporates agents in Arduino hardware devices with recognition modules and illuminated bands; it also incorporates IP cameras programmed for automatic tracking, which can connect remotely in the event of emergencies. The user wears a bracelet, which contains a simple vibration sensor that can receive notifications about the emergency situation.
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Selenium nanoparticles: potential in cancer gene and drug delivery.
Maiyo, Fiona; Singh, Moganavelli
2017-05-01
In recent decades, colloidal selenium nanoparticles have emerged as exceptional selenium species with reported chemopreventative and therapeutic properties. This has sparked widespread interest in their use as a carrier of therapeutic agents with results displaying synergistic effects of selenium with its therapeutic cargo and improved anticancer activity. Functionalization remains a critical step in selenium nanoparticles' development for application in gene or drug delivery. In this review, we highlight recent developments in the synthesis and functionalization strategies of selenium nanoparticles used in cancer drug and gene delivery systems. We also provide an update of recent preclinical studies utilizing selenium nanoparticles in cancer therapeutics.
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Wang, Yao; Ding, Xiali; Chen, Yuan; Guo, Mingquan; Zhang, Yan; Guo, Xiaokui; Gu, Hongchen
2016-09-01
Drug-resistant bacterial infections have become one of the most serious risks in public health as they make the conventional antibiotics less efficient. There is an urgent need for developing new generations of antibacterial agents in this field. In this work, a nanoplatform of LEVO-loaded and silver core-embedded mesoporous silica nanovehicles (Ag@MSNs@LEVO) is demonstrated as a synergistic antibacterial agent for the treatment of drug-resistant infections both in vitro and in vivo. The combination of the inner Ag core and the loaded antibiotic drug in mesopores endows the single-particle nanoplatform with a synergistic effect on killing the drug-resistant bacteria. The nanoplatform of Ag@MSNs@LEVO exhibits superior antibacterial activity to LEVO-loaded MSNs (MSNs@LEVO) and silver core-embedded MSNs (Ag@MSNs) in vitro. In the in vivo acute peritonitis model, the infected drug-resistant Escherichia coli GN102 in peritoneal cavity of the mice is reduced by nearly three orders of magnitude and the aberrant pathological feature of spleen and peritoneum disappears after treatment with Ag@MSNs@LEVO. Importantly, this nanopaltform renders no obvious toxic side effect to the mice during the tested time. There is no doubt that this study strongly indicates a promising potential of Ag@MSNs@LEVO as a synergistic and safety therapy tool for the clinical drug-resistant infections. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Proc. Agent 2004 Conf. on Social Dynamics : Interaction, Reflexivity and Emergence
Energy Technology Data Exchange (ETDEWEB)
C. M. Macal, D. Sallach, M. J. North, eds.
2004-01-01
I'd like to welcome you to the Agent 2004 conference. As most of you are aware, this conference is the fifth in a series of meetings that began in 1999. A conference followed the next year in 2000. The 2001 conference was skipped because of some conflicts with other conferences, and the conferences have proceeded annually since then. We have the proceedings of the previous conferences available here on CDs. One CD has the proceedings from 1999, 2000, and 2002; the other contains last year's proceedings. The purpose of these conferences is to advance the state of the computational social sciences and to integrate the social sciences with the decision sciences and something that is traditionally known as the management sciences. Those of you in the operations/research area are familiar with the traditional school of modeling simulation that emerged from that scientific area. This conference will bring together a different group of people to talk about the topic of agent-based theories and simulations. This fifth agent conference is one of a group of conferences held annually around the country. Most of you are probably aware of the CASOS Conference held at Carnegie Mellon University, usually in July. UCLA holds the Arrowhead Conference, generally around May. The University of Michigan is now holding a conference as well. Of course everyone is aware of SwarmFest, which has been held annually for about a decade. The Swarm seems to 'swarm' in different locations each year. As you're well aware, this conference is organized into a three-day program. This is the first time we've used three days for the full conference setting. Last year, we held simultaneous sessions, and that didn't work well for most of those who attended. We had complaints from people who missed sessions and papers because of scheduling, so we decided to extend this year's conference by one day. As a result, we now have a program designed to present the papers in
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Genetically engineered nanocarriers for drug delivery
Directory of Open Access Journals (Sweden)
Shi P
2014-03-01
Full Text Available Pu Shi, Joshua A Gustafson, J Andrew MacKayDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USAAbstract: Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins.Keywords: polymeric drug carrier, non-polymeric drug carrier, gene delivery, GE drug carriers
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Directory of Open Access Journals (Sweden)
Duraipandian Thavaselvam
2010-01-01
Full Text Available The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies.
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Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan
2010-01-01
The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies. PMID:21829313
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Directory of Open Access Journals (Sweden)
Sean M. Curry
2012-12-01
Full Text Available Introduction: Drug-seeking behavior (DSB in the emergency department (ED is a very commonproblem, yet there has been little quantitative study to date of such behavior.The goal of this study wasto assess the frequency with which drug seeking patients in the ED use classic drug seeking behaviorsto obtain prescription medication.Methods: We performed a retrospective chart review on patients in an ED case management programfor DSB. We reviewed all visits by patients in the program that occurred during a 1-year period, andrecorded the frequency of the following behaviors: complaining of headache, complaining of backpain, complaining of dental pain, requesting medication by name, requesting a refill of medication,reporting medications as having been lost or stolen, reporting 10/10 pain, reporting greater than 10/10pain, reporting being out of medication, and requesting medication parenterally. These behaviors werechosen because they are described as “classic” for DSB in the existing literature.Results: We studied 178 patients from the case management program, who made 2,486 visits in 1year. The frequency of each behavior was: headache 21.7%, back pain 20.8%, dental pain 1.8%,medication by name 15.2%, requesting refill 7.0%, lost or stolen medication 0.6%, pain 10/10 29.1%,pain greater than 10/10 1.8%, out of medication 9.5%, and requesting parenteral medication 4.3%.Patients averaged 1.1 behaviors per visit.Conclusion: Drug-seeking patients appear to exhibit “classically” described drug-seeking behaviorswith only low to moderate frequency. Reliance on historical features may be inadequate when trying toassess whether or not a patient is drug-seeking.
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Emerging drugs of abuse: current perspectives on synthetic cannabinoids
Directory of Open Access Journals (Sweden)
Debruyne D
2015-10-01
Full Text Available Danièle Debruyne,1,2 Reynald Le Boisselier1 1Centre for Evaluation and Information on Pharmacodependence - Addictovigilance (CEIP-A, 2Toxicology and Pharmacology Laboratory, Department of Pharmacology, University Hospital Centre Côte de Nacre, Caen, France Abstract: New psychoactive drugs that have appeared over the last decade are typically dominated by cathinones and synthetic cannabinoids (SCs. SCs have been emerging as recreational drugs because they mimic the euphoria effect of cannabis while still being legal. Sprayed on natural herb mixtures, SCs have been primarily sold as “herbal smoking blends” or “herbal incense” under brand names like “Spice” or “K2”. Currently, SCs pure compounds are available from websites for the combination with herbal materials or for the use in e-cigarettes. For the past 5 years, an ever increasing number of compounds, representative of different chemical classes, have been promoted and now represent a large assortment of new popular drugs of abuse, which are difficult to properly identify. Their legal status varies by country with many government institutions currently pushing for their control. The in vitro binding to CB1/CB2 receptors is usually well-known and considerable differences have been found in the CB1 versus CB2 selectivity and potency within the different SCs, with several structure-activity relations being evident. Desired effects by CB1 agonist users are relaxation/recreative, however, cardiovascular, gastrointestinal, or psychiatric/neurological side effects are commonly reported. At present there is no specific antidote existing if an overdose of designer drugs was to occur, and no curative treatment has been approved by health authorities. Management of acute toxic effects is mainly symptomatic and extrapolated from experience with cannabis. Keywords: synthetic cannabinoids, chemistry, analysis, pharmacology, toxicology, dependence, medical care
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Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.
Directory of Open Access Journals (Sweden)
Donghee Park
Full Text Available Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with
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Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.
Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum
2016-01-01
Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the
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Wood, Matthew R; Lalancette, Roger A; Bernal, Ivan
2015-01-01
The name `bath salts', for an emerging class of synthetic cathinones, is derived from an attempt to evade prosecution and law enforcement. These are truly illicit drugs that have psychoactive CNS (central nervous system) stimulant effects and they have seen a rise in abuse as recreational drugs in the last few years since first having been seen in Japan in 2006. The ease of synthesis and modification of specific functional groups of the parent cathinone make these drugs particularly difficult to regulate. MDPV (3,4-methylenedioxypyrovalerone) is commonly encountered as its hydrochloride salt (C16H21NO3·HCl), in either the hydrated or the anhydrous forms. This `bath salt' has various names in the US, e.g. `Super Coke', `Cloud Nine', and `Ivory Wave', to name just a few. We report here the structures of two forms of the HCl salt, one as a mixed bromide/chloride salt, C16H22NO3(+)·0.343Br(-)·0.657Cl(-) [systematic name: 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one bromide/chloride (0.343/0.657)], and the other with the H7O3(+) cation, as well as the HCl counter-ion [systematic name: hydroxonium 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one dichloride, H7O3(+)·C16H22NO3(+)·2Cl(-)]. This is one of a very few structures (11 to be exact) in which we have a new example of a precisely determined hydroxonium cation. During the course of researching the clandestine manufacture of MDPV, we were surprised by the fact that a common precursor of this illicit stimulant is known to be the fragrant species piperonal, which is present in the fragrances of orchids, most particularly in the case of the vanilla orchid. We found that MDPV can be made by a Grignard reaction of this heliotropin. This may also explain the unexpected appearance of the bromide counter-ion in some of the salts we encountered (C16H21NO3·HBr), one of which is presented here [systematic name: 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one
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An overview of aldehyde oxidase: an enzyme of emerging importance in novel drug discovery.
Rashidi, Mohammad-Reza; Soltani, Somaieh
2017-03-01
Given the rising trend in medicinal chemistry strategy to reduce cytochrome P450-dependent metabolism, aldehyde oxidase (AOX) has recently gained increased attention in drug discovery programs and the number of drug candidates that are metabolized by AOX is steadily growing. Areas covered: Despite the emerging importance of AOX in drug discovery, there are certain major recognized problems associated with AOX-mediated metabolism of drugs. Intra- and inter-species variations in AOX activity, the lack of reliable and predictive animal models using the common experimental animals, and failure in the predictions of in vivo metabolic activity of AOX using traditional in vitro methods are among these issues that are covered in this article. A comprehensive review of computational human AOX (hAOX) related studies are also provided. Expert opinion: Following the recent progress in the stem cell field, the authors recommend the application of organoids technology as an effective tool to solve the fundamental problems associated with the evaluation of AOX in drug discovery. The recent success in resolving the hAOX crystal structure can too be another valuable data source for the study of AOX-catalyzed metabolism of new drug candidates, using computer-aided drug discovery methods.
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Qin, Lingzhen; Mei, Liling; Shan, Ziyun; Huang, Ying; Pan, Xin; Li, Ge; Gu, Yukun; Wu, Chuanbin
2016-01-01
Phytantriol has received increasing amount of attention in drug delivery system, however, the ability of the phytantriol based liquid crystal as a novel embolic agent to provide a sustained release delivery system is yet to be comprehensively demonstrated. The purpose of this study was to prepare a phytantriol-based cubic phase precursor solution loaded with anticancer drug hydroxycamptothecine (HCPT) and evaluate its embolization properties, in vitro drug release and cytotoxicity. Phase behavior of the phytantriol-solvent-water system was investigated by visual inspection and polarized light microscopy, and no phase transition was observed in the presence of HCPT within the studied dose range. Water uptake by the phytantriol matrices was determined gravimetrically, suggesting that the swelling complied with the second order kinetics. In vitro evaluation of embolic efficacy indicated that the isotropic solution displayed a satisfactory embolization effect. In vitro drug release results showed a sustained-release up to 30 days and the release behavior was affected by the initial composition and drug loading. Moreover, the in vitro cytotoxicity and anticancer activity were evaluated by MTT assay. No appreciable mortality was observed for NIH 3T3 cells after 48 h exposure to blank formulations, and the anticancer activity of HCPT-loaded formulations to HepG2 and SMMC7721 cells was strongly dependent on the drug loading and treatment time. Taken together, these results indicate that phytantriol-based cubic phase embolic gelling solution is a promising potential carrier for HCPT delivery to achieve a sustained drug release by vascular embolization, and this technology may be potential for clinical applications.
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Directory of Open Access Journals (Sweden)
Juliana Alves Parente-Rocha
2017-01-01
Full Text Available Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins. An overview of new antifungal agents, including nanostructured antifungals, as well as of repositioning approaches is discussed. Studies focusing on the development of vaccines against antifungal diseases have increased in recent years, as these strategies can be applied in combination with antifungal therapy to prevent posttreatment sequelae. Studies focused on the development of a pan-fungal vaccine and antifungal drugs can improve the treatment of immunocompromised patients and reduce treatment costs.
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Perspectives in the development of hybrid bifunctional antitumour agents.
Musso, Loana; Dallavalle, Sabrina; Zunino, Franco
2015-08-15
In spite of the development of a large number of novel target-specific antitumour agents, the single-agent therapy is in general not able to provide an effective durable control of the malignant process. The limited efficacy of the available agents (both conventional cytotoxic and novel target-specific) reflects not only the expression of defence mechanisms, but also the complexity of tumour cell alterations and the redundancy of survival pathways, thus resulting in tumour cell ability to survive under stress conditions. A well-established strategy to improve the efficacy of antitumour therapy is the rational design of drug combinations aimed at achieving synergistic effects and overcoming drug resistance. An alternative strategy could be the use of agents designed to inhibit simultaneously multiple cellular targets relevant to tumour growth/survival. Among these novel agents are hybrid bifunctional drugs, i.e. compounds resulting by conjugation of different drugs or containing the pharmocophores of different drugs. This strategy has been pursued using various conventional or target-specific agents (with DNA damaging agents and histone deacetylase inhibitors as the most exploited compounds). A critical overview of the most representative compounds is provided with emphasis on the HDAC inhibitor-based hybrid agents. In spite of some promising results, the actual pharmacological advantages of the hybrid agents remain to be defined. This commentary summarizes the recent advances in this field and highlights the pharmacological basis for a rational design of hybrid bifunctional agents. Copyright © 2015. Published by Elsevier Inc.
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Pajic, Marina; Blatter, Sohvi; Guyader, Charlotte; Gonggrijp, Maaike; Kersbergen, Ariena; Küçükosmanoğlu, Aslι; Sol, Wendy; Drost, Rinske; Jonkers, Jos; Borst, Piet; Rottenberg, Sven
2017-11-15
Purpose: We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse. Experimental Design: We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for BRCA1/p53 -mutant breast cancer. Because of the large intragenic deletion of the Brca1 gene, no restoration of BRCA1 function is possible, and therefore, no BRCA1-dependent acquired resistance occurs. To characterize the cell-cycle stage from which Brca1 -/- ;p53 -/- mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell-cycle indicator (FUCCI) construct into the tumor cells. Results: Despite repeated sensitivity to the MTD of platinum drugs, the Brca1 -mutated mammary tumors are not eradicated, not even by a frequent dosing schedule. We show that relapse comes from single-nucleated cells delaying entry into the S-phase. Such slowly cycling cells, which are present within the drug-naïve tumors, are enriched in tumor remnants. Using the FUCCI construct, we identified nonfluorescent G 0 -like cells as the population most tolerant to platinum drugs. Intriguingly, these cells are more sensitive to the DNA-crosslinking agent nimustine, resulting in an increased number of multinucleated cells that lack clonogenicity. This is consistent with our in vivo finding that the nimustine MTD, among several alkylating agents, is the most effective in eradicating Brca1 -mutated mouse mammary tumors. Conclusions: Our data show that targeting G 0 -like cells is crucial for the eradication of BRCA1/p53-deficient tumor cells. This can be achieved with selected alkylating agents such as nimustine. Clin Cancer Res; 23(22); 7020-33. ©2017 AACR . ©2017 American Association for Cancer Research.
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Biosimilar Drugs for Cancer Emerge
As the patents on widely used biological drugs to treat cancer expire, biosimilar drugs are being developed for the treatment of patients with cancer. You can learn how biosimilars may expand treatment options in this Cancer Currents blog post.
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Directory of Open Access Journals (Sweden)
Sharma V
2001-04-01
Full Text Available AIM: To study the different clinical spectrum of cutaneous adverse drug reactions (ADR and to determine the causative drugs. MATERIALS & METHODS: A prospective, hospital based study was carried out over a period of 6 years recording various cutaneous ADR. RESULTS: A total of 500 patients with cutaneous ADR were enrolled in the study. The most common types of cutaneous ADR patterns were maculopapular rash (34.6%, fixed drug eruption (FDE (30% and urticaria (14%. The drugs most often incriminated for the various cutaneous ADR were antimicrobials (42.6%, anticonvulsants (22.2% and NSAIDs (18%. Anticonvulsants were implicated in 41.6% of maculopapular rashes. Sulfonamides accounted for 43.3% and NSAIDs for 30.7% of FDE. Urticaria was caused mainly by NSAIDs(24.3% and penicillins(20%. Anticonvulsants were responsible for 43.8% of life-threatening toxic epidermal necrolysis and Stevens Johnson syndrome. CONCLUSIONS: The clinical pattern and drugs causing cutaneous ADR are similar to those observed in other countries except for minor variations. Cutaneous ADR patterns and the drugs causing various reactions are changing every year, which may be due to the emergence of newer molecules and changing trends in the use of drugs.
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Directory of Open Access Journals (Sweden)
Susan I Woodruff
2013-05-01
Full Text Available Introduction: Visits to settings such as emergency departments (EDs may present a “teachable moment” in that a patient may be more open to feedback and suggestions regarding their risky alcohol and illicit drug-use behaviors. Screening, Brief Intervention, and Referral to Treatment (SBIRT is an ’opportunistic’ public health approach that targets low-risk users, in addition to those already dependent on alcohol and/or drugs. SBIRT programs provide patients with comprehensive screening and assessments, and deliver interventions of appropriate intensity to reduce risks related to alcohol and drug use. Methods: This study used a single group pre-post test design to assess the effect of the California SBIRT service program (i.e., CASBIRT on 6 substance-use outcomes (past-month prevalence and number of days of binge drinking, illegal drug use, and marijuana use. Trained bilingual/bicultural Health Educators attempted to screen all adult patients in 12 EDs/trauma centers (regardless of the reason for the patient’s visit using a short instrument, and then delivered a brief motivational intervention matched to the patient’s risk level. A total of 2,436 randomly selected patients who screened positive for alcohol and/or drug use consented to be in a 6-month telephone follow-up interview. Because of the high loss to follow-up rate, we used an intention-to-treat approach for the data analysis. Results: Results of generalized linear mixed models showed modest reductions in all 6 drug- and alcohol-use outcomes. Men (versus women, those at relatively higher risk status (versus lower risk, and those with only one substance of misuse (versus both alcohol and illicit drug misuse tended to show more positive change. Conclusion: These results suggest that SBIRT services provided in acute care settings are associated with modest changes in self-reported recent alcohol and illicit drug use. [West J Emerg Med. 2013;14(3:263–270.
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Bioenergetics of Mycobacterium: An Emerging Landscape for Drug Discovery
Directory of Open Access Journals (Sweden)
Iram Khan Iqbal
2018-02-01
Full Text Available Mycobacterium tuberculosis (Mtb exhibits remarkable metabolic flexibility that enables it to survive a plethora of host environments during its life cycle. With the advent of bedaquiline for treatment of multidrug-resistant tuberculosis, oxidative phosphorylation has been validated as an important target and a vulnerable component of mycobacterial metabolism. Exploiting the dependence of Mtb on oxidative phosphorylation for energy production, several components of this pathway have been targeted for the development of new antimycobacterial agents. This includes targeting NADH dehydrogenase by phenothiazine derivatives, menaquinone biosynthesis by DG70 and other compounds, terminal oxidase by imidazopyridine amides and ATP synthase by diarylquinolines. Importantly, oxidative phosphorylation also plays a critical role in the survival of persisters. Thus, inhibitors of oxidative phosphorylation can synergize with frontline TB drugs to shorten the course of treatment. In this review, we discuss the oxidative phosphorylation pathway and development of its inhibitors in detail.
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Bioenergetics of Mycobacterium: An Emerging Landscape for Drug Discovery
Iqbal, Iram Khan; Bajeli, Sapna; Akela, Ajit Kumar
2018-01-01
Mycobacterium tuberculosis (Mtb) exhibits remarkable metabolic flexibility that enables it to survive a plethora of host environments during its life cycle. With the advent of bedaquiline for treatment of multidrug-resistant tuberculosis, oxidative phosphorylation has been validated as an important target and a vulnerable component of mycobacterial metabolism. Exploiting the dependence of Mtb on oxidative phosphorylation for energy production, several components of this pathway have been targeted for the development of new antimycobacterial agents. This includes targeting NADH dehydrogenase by phenothiazine derivatives, menaquinone biosynthesis by DG70 and other compounds, terminal oxidase by imidazopyridine amides and ATP synthase by diarylquinolines. Importantly, oxidative phosphorylation also plays a critical role in the survival of persisters. Thus, inhibitors of oxidative phosphorylation can synergize with frontline TB drugs to shorten the course of treatment. In this review, we discuss the oxidative phosphorylation pathway and development of its inhibitors in detail. PMID:29473841
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Reassessing the Role of Intra-Arterial Drug Delivery for Glioblastoma Multiforme Treatment
Directory of Open Access Journals (Sweden)
Jason A. Ellis
2015-01-01
Full Text Available Effective treatment for glioblastoma (GBM will likely require targeted delivery of several specific pharmacological agents simultaneously. Intra-arterial (IA delivery is one technique for targeting the tumor site with multiple agents. Although IA chemotherapy for glioblastoma (GBM has been attempted since the 1950s, the predicted benefits remain unproven in clinical practice. This review focuses on innovative approaches to IA drug delivery in treating GBM. Guided by novel in vitro and in vivo optical measurements, newer pharmacokinetic models promise to better define the complex relationship between background cerebral blood flow and drug injection parameters. Advanced optical technologies and tracers, unique nanoparticles designs, new cellular targets, and rational drug formulations are continuously modifying the therapeutic landscape for GBM. Personalized treatment approaches are emerging; however, such tailored approaches will largely depend on effective drug delivery techniques and on the ability to simultaneously deliver multidrug regimens. These new paradigms for tumor-selective drug delivery herald dramatic improvements in the effectiveness of IA chemotherapy for GBM. Therefore, within this context of so-called “precision medicine,” the role of IA delivery for GBM is thoroughly reassessed.
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REBAMIPIDE: EFFECTIVE DRUG PREVENTION OF NSAID ENTEROPATHY IS POSSIBLE
E. V. Moroz; A. E. Karateev
2016-01-01
Prevention of gastrointestinal tract (GIT) complications is the most important element for the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin (LDA). Proton pump inhibitors (PPIs) have long been the only medication to prevent these complications. However, PPIs are only effective in preventing and treating upper GIT diseases (NSAID gastropathy) rather than small intestinal injury (NSAID enteropathy). Rebamipide has emerged as a novel agent to protect the gast...
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Clinical toxicology of newer recreational drugs.
Hill, Simon L; Thomas, Simon H L
2011-10-01
Novel synthetic 'designer' drugs with stimulant, ecstasy-like (entactogenic) and/or hallucinogenic properties have become increasingly popular among recreational drug users in recent years. The substances used change frequently in response to market trends and legislative controls and it is an important challenge for poisons centres and clinical toxicologists to remain updated on the pharmacological and toxicological effects of these emerging agents. To review the available information on newer synthetic stimulant, entactogenic and hallucinogenic drugs, provide a framework for classification of these drugs based on chemical structure and describe their pharmacology and clinical toxicology. A comprehensive review of the published literature was performed using PUBMED and Medline databases, together with additional non-peer reviewed information sources, including books, media reports, government publications and internet resources, including drug user web forums. Novel synthetic stimulant, entactogenic or hallucinogenic designer drugs are increasingly available to users as demonstrated by user surveys, poisons centre calls, activity on internet drug forums, hospital attendance data and mortality data. Some population sub groups such as younger adults who attend dance music clubs are more likely to use these substances. The internet plays an important role in determining the awareness of and availability of these newer drugs of abuse. Most novel synthetic stimulant, entactogenic or hallucinogenic drugs of abuse can be classified according to chemical structure as piperazines (e.g. benzylpiperazine (BZP), trifluoromethylphenylpiperazine), phenethylamines (e.g. 2C or D-series of ring-substituted amfetamines, benzodifurans, cathinones, aminoindans), tryptamines (e.g. dimethyltryptamine, alpha-methyltryptamine, ethyltryptamine, 5-methoxy-alphamethyltryptamine) or piperidines and related substances (e.g. desoxypipradrol, diphenylprolinol). Alternatively classification may
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Admissions through the emergency department due to drug-related problems
International Nuclear Information System (INIS)
Yosef H Al-Olah; Khalifa M Al Thiab
2010-01-01
Hospital admissions due to drug-related problems (DRPs) have been studied internationally, but local data are limited. Therefore, we undertook a prospective, observational study of all admissions through the emergency department (ED) at a tertiary referral hospital in Saudi Arabia to determine the incidence of admissions through the ED due to DRPs, types of DRPs, length of stay (LOS) in the hospital after ED admissions due to DRPs, and assessment of preventability of admissions due to DRPs.All admissions through the ED over a period of 28 consecutive days were evaluated to determine if they were due to definite or possible DRPs. Data was collected on a daily basis for each admission over the previous 24 hours. Each incident was assessed by three investigators Of 557 patients admitted through the ED, 82 (14.7%) admissions were due to DRP (53 definite, 29 possible). The most common types of DRP were failure to receive medication in 25 cases (47.2%), an adverse drug reaction in 13 cases (24.5%), and drug overdose in 6 cases (11.3%). In the definite DRP group, 83.0% were definitely preventable, 3.8% were possibly preventable and 13.2% were definitely non-preventable.DRPs are a serious and costly issue facing health care professionals and health care systems. Most admissions due to DRPs are avoidable (Author).
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Causes of poisoning in patients evaluated in a hospital emergency department in Konya, Turkey
International Nuclear Information System (INIS)
Kara, H.; Bayir, A.; Degirmenci, S.; Akinci, M.; Ak, A.; Azap, M.
2014-01-01
Objectives: To evaluate demographic and clinical characteristics of patients with poisoning at a community hospital. Methods: The retrospective study comprised records of patients who were admitted to the emergency department of Konya Numune Hospital, Turkey, because of poisoning between January 1, 2009, and December 31, 2011. Data was evaluated for age, gender, educational status, occupation, arrival time, mechanism of intoxication , body temperature, pulse, respiratory rate, Glasgow Coma Scale score, treatment applied, duration of hospital stay, duration of follow-up, test results, final diagnosis, clinical disposition, and outcome. Agents causing the poisoning were also determined. Results: Records of 1036 patients were evaluated. Of them, 764(74%) were female and 272(26%) were male. The predominant age range was 15-24 years in 617(60%) patients. The median time from substance exposure to admission to the emergency department was 2 hours. The most common cause of poisoning was attempted suicide in 955 (92%) patients and drug intoxication was the agent involved in 932 (90%). In the 15-24 year age range, there were 469(76%) female patients. Of the total female population in the study, 716(94%) attempted suicide. The median hospital stay was 24 hours. There were 908(88%) patients who were advised to seek further evaluation at the psychiatry clinic, and 9 (0.9%) patients were admitted to the psychiatry inpatient units after medical treatment. In patients who were hospitalized and followed up, 1 (0.1%) died because of multiple drug poisoning. Conclusion: Most admissions to the emergency department for poisoning related to young women had used drugs during a suicide attempt. (author)
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Salvage Therapy of Multiple Myeloma: The New Generation Drugs
Directory of Open Access Journals (Sweden)
Alessandra Romano
2014-01-01
Full Text Available During the past decade, overall results of treatment of multiple myeloma (MM have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs. However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways.
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Salvage Therapy of Multiple Myeloma: The New Generation Drugs
Romano, Alessandra; Conticello, Concetta; Di Raimondo, Cosimo; Schinocca, Elena; La Fauci, Alessia; Parrinello, Nunziatina Laura; Chiarenza, Annalisa
2014-01-01
During the past decade, overall results of treatment of multiple myeloma (MM) have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs). However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways. PMID:24967371
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The Rise, Fall and Subsequent Triumph of Thalidomide: Lessons Learned in Drug Development
Rehman, Waqas; Arfons, Lisa M.; Lazarus, Hillard M.
2011-01-01
Perhaps no other drug in modern medicine rivals the dramatic revitalization of thalidomide. Originally marketed as a sedative, thalidomide gained immense popularity worldwide among pregnant women because of its effective anti-emetic properties in morning sickness. Mounting evidence of human teratogenicity marked a dramatic fall from grace and led to widespread social, legal and economic ramifications. Despite its tragic past thalidomide emerged several decades later as a novel and highly effective agent in the treatment of various inflammatory and malignant diseases. In 2006 thalidomide completed its remarkable renaissance becoming the first new agent in over a decade to gain approval for the treatment of plasma cell myeloma. The catastrophic collapse yet subsequent revival of thalidomide provides important lessons in drug development. Never entirely abandoned by the medical community, thalidomide resurfaced as an important drug once the mechanisms of action were further studied and better understood. Ongoing research and development of related drugs such as lenalidomide now represent a class of irreplaceable drugs in hematological malignancies. Further, the tragedies associated with this agent stimulated the legislation which revamped the FDA regulatory process, expanded patient informed consent procedures and mandated more transparency from drug manufacturers. Finally, we review recent clinical trials summarizing selected medical indications for thalidomide with an emphasis on hematologic malignancies. Herein, we provide a historic perspective regarding the up-and-down development of thalidomide. Using PubMed databases we conducted searches using thalidomide and associated keywords highlighting pharmacology, mechanisms of action, and clinical uses. PMID:23556097
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Directory of Open Access Journals (Sweden)
Kamila J. Pacholarz
2016-06-01
Full Text Available Antibody-drug-conjugates (ADC are a growing class of anticancer biopharmaceuticals. Conjugation of cysteine linked ADCs, requires initial reduction of mAb inter-chain disulfide bonds, as the drugs are attached via thiol chemistry. This results in the active mAb moiety being transformed from a covalently linked tetramer to non-covalently linked complexes, which hinders precise determination of drug load with LC–MS. Here, we show how the addition of the charge reducing agent triethylammonium acetate (TEAA preserves the intact mAb structure, is well suited to the study of cysteine linked conjugates and facilitates easy drug load determination by direct infusion native MS.
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Ujhelyi, Zoltán; Kalantari, Azin; Vecsernyés, Miklós; Róka, Eszter; Fenyvesi, Ferenc; Póka, Róbert; Kozma, Bence; Bácskay, Ildikó
2015-07-21
The aim of this study was to develop topical self-microemulsifying drug delivery systems (SMEDDS) containing antitumor agents (bleomycin, cisplatin and ifosfamide) and to investigate their inhibitory potential in SMEDDS on human cervical cancer HeLa cells. The physicochemical properties of cytostatic drug loaded SMEDDS were characterized. The cytotoxicity of main components of SMEDDS was also investigated. Their IC50 values were determined. HeLa cells were treated by different concentrations of cisplatin, bleomycin and ifosfamide alone and in various SMEDDS. The inhibitory effect on cell growth was analyzed by MTT cell viability assay. Inflammation is a driving force that accelerates cancer development. The inhibitory effect of these antitumor agents has also been tested on HeLa cells in the presence of inflammatory mediators (IL-1-β, TNF-α) as an in vitro model of inflamed human cervix. Significant differences in the cytotoxicity of cytostatic drugs alone and in SMEDDS have been found in a concentration-dependent manner. The self-micro emulsifying system may potentiate the effectiveness of bleomycin, cisplatin and ifosfamide topically. The effect of SMEDDS containing antitumor agents was decreased significantly in the presence of inflammatory mediators. According to our experiments, the optimal SMEDDS formulation is 1:1:2:6:2 ratios of Isopropyl myristate, Capryol 90, Kolliphor RH 40, Cremophor RH40, Transcutol HP and Labrasol. It can be concluded that SMEDDS may increase the inhibitory effect of bleomycin, ifosfamide and cisplatin on human cervical cancer HeLa cells. Inflammation on HeLa cells hinders the effectiveness of SMEDDS containing antitumor agents. Our results might ensure useful data for development of optimal antitumor formulations.
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Directory of Open Access Journals (Sweden)
Maria N. Gamaletsou
2018-02-01
Full Text Available Invasive fungal infections caused by drug-resistant organisms are an emerging threat to heavily immunosuppressed patients with hematological malignancies. Modern early antifungal treatment strategies, such as prophylaxis and empirical and preemptive therapy, result in long-term exposure to antifungal agents, which is a major driving force for the development of resistance. The extended use of central venous catheters, the nonlinear pharmacokinetics of certain antifungal agents, neutropenia, other forms of intense immunosuppression, and drug toxicities are other contributing factors. The widespread use of agricultural and industrial fungicides with similar chemical structures and mechanisms of action has resulted in the development of environmental reservoirs for some drug-resistant fungi, especially azole-resistant Aspergillus species, which have been reported from four continents. The majority of resistant strains have the mutation TR34/L98H, a finding suggesting that the source of resistance is the environment. The global emergence of new fungal pathogens with inherent resistance, such as Candida auris, is a new public health threat. The most common mechanism of antifungal drug resistance is the induction of efflux pumps, which decrease intracellular drug concentrations. Overexpression, depletion, and alteration of the drug target are other mechanisms of resistance. Mutations in the ERG11 gene alter the protein structure of C-demethylase, reducing the efficacy of antifungal triazoles. Candida species become echinocandin-resistant by mutations in FKS genes. A shift in the epidemiology of Candida towards resistant non-albicans Candida spp. has emerged among patients with hematological malignancies. There is no definite association between antifungal resistance, as defined by elevated minimum inhibitory concentrations, and clinical outcomes in this population. Detection of genes or mutations conferring resistance with the use of molecular methods
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New and emerging immune-targeted drugs for the treatment of multiple sclerosis.
Palmer, Alan M
2014-07-01
Multiple sclerosis (MS) is a neurodegenerative disease with a major inflammatory component that constitutes the most common progressive and disabling neurological condition in young adults. Injectable immunomodulatory medicines such as interferon drugs and glatiramer acetate have dominated the MS market for over the past two decades but this situation is set to change. This is because of: (i) patent expirations, (ii) the introduction of natalizumab, which targets the interaction between leukocytes and the blood-CNS barrier, (iii) the launch of three oral immunomodulatory drugs (fingolimod, dimethyl fumarate and teriflunomide), with another (laquinimod) under regulatory review and (iv) a number of immunomodulatory monoclonal antibodies (alemtuzumab, daclizumab and ocrelizumab) about to enter the market. Current and emerging medicines are reviewed and their impact on people with MS considered. © 2013 The British Pharmacological Society.
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Lai, Foon Yin; Thai, Phong K; O'Brien, Jake; Gartner, Coral; Bruno, Raimondo; Kele, Benjamin; Ort, Christoph; Prichard, Jeremy; Kirkbride, Paul; Hall, Wayne; Carter, Steve; Mueller, Jochen F
2013-11-01
Wastewater analysis provides a non-intrusive way of measuring drug use within a population. We used this approach to determine daily use of conventional illicit drugs [cannabis, cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA)] and emerging illicit psychostimulants (benzylpiperazine, mephedrone and methylone) in two consecutive years (2010 and 2011) at an annual music festival. Daily composite wastewater samples, representative of the festival, were collected from the on-site wastewater treatment plant and analysed for drug metabolites. Data over 2 years were compared using Wilcoxon matched-pair test. Data from 2010 festival were compared with data collected at the same time from a nearby urban community using equivalent methods. Conventional illicit drugs were detected in all samples whereas emerging illicit psychostimulants were found only on specific days. The estimated per capita consumption of MDMA, cocaine and cannabis was similar between the two festival years. Statistically significant (P popularity in music settings. Our study demonstrated that wastewater analysis can objectively capture changes in substance use at a music setting without raising major ethical issues. It would potentially allow effective assessments of drug prevention strategies in such settings in the future. © 2013 Australasian Professional Society on Alcohol and other Drugs.
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International Nuclear Information System (INIS)
Chamberland, David L; Agarwal, Ashish; Kotov, Nicholas; Fowlkes, J Brian; Carson, Paul L; Wang Xueding
2008-01-01
Monitoring of anti-rheumatic drug delivery in experimental models and in human diseases would undoubtedly be very helpful for both basic research and clinical management of inflammatory diseases. In this study, we have investigated the potential of an emerging hybrid imaging technology-photoacoustic tomography-in noninvasive monitoring of anti-TNF drug delivery. After the contrast agent composed of gold nanorods conjugated with Etanercept molecules was produced, ELISA experiments were performed to prove the conjugation and to show that the conjugated anti-TNF-α drug was biologically active. PAT of ex vivo rat tail joints with the joint connective tissue enhanced by intra-articularly injected contrast agent was conducted to examine the performance of PAT in visualizing the distribution of the gold-nanorod-conjugated drug in articular tissues. By using the described system, gold nanorods with a concentration down to 1 pM in phantoms or 10 pM in biological tissues can be imaged with good signal-to-noise ratio and high spatial resolution. This study demonstrates the feasibility of conjugating TNF antagonist pharmaceutical preparations with gold nanorods, preservation of the mechanism of action of TNF antagonist along with preliminary evaluation of novel PAT technology in imaging optical contrast agents conjugated with anti-rheumatic drugs. Further in vivo studies on animals are warranted to test the specific binding between such conjugates and targeted antigen in joint tissues affected by inflammation
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Emerging Drugs for the Treatment of Anxiety
Murrough, James W.; Yaqubi, Sahab; Sayed, Sehrish; Charney, Dennis S.
2016-01-01
Introduction Anxiety disorders are among the most prevalent and disabling psychiatric disorders in the United States and worldwide. Basic research has provided critical insights into the mechanism regulating fear behavior in animals and a host of animal models have been developed in order to screen compounds for anxiolytic properties. Despite this progress, no mechanistically novel agents for the treatment of anxiety have come to market in more than two decades. Areas covered The current review will provide a critical summary of current pharmacological approaches to the treatment of anxiety and will examine the pharmacotherapeutic pipeline for treatments in development. Anxiety and related disorders considered herein include panic disorder, social anxiety disorder, generalized anxiety disorder and posttraumatic stress disorder. The glutamate, neuropeptide and endocannabinoid systems show particular promise as future targets for novel drug development. Expert opinion In the face of an ever-growing understanding of fear related behavior, the field awaits the translation of this research into mechanistically novel treatments. Obstacles will be overcome through close collaboration between basic and clinical researchers with the goal of aligning valid endophenotypes of human anxiety disorders with improved animal models. Novel approaches are needed to move basic discoveries into new, more effective treatments for our patients. PMID:26012843
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21 CFR 316.22 - Permanent-resident agent for foreign sponsor.
2010-04-01
... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.22 Permanent-resident agent for foreign sponsor. Every foreign sponsor that seeks orphan-drug designation shall name a permanent resident of the United States as the sponsor's agent upon whom service of all processes, notices...
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Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery
Kesharwani, Prashant; Iyer, Arun K.
2015-01-01
Advances in the application of nanotechnology in medicine have given rise to multifunctional smart nanocarriers that can be engineered with tunable physicochemical characteristics to deliver one or more therapeutic agent(s) safely and selectively to cancer cells, including intracellular organelle-specific targeting. Dendrimers having properties resembling biomolecules, with well-defined 3D nanopolymeric architectures, are emerging as a highly attractive class of drug and gene delivery vector. The presence of numerous peripheral functional groups on hyperbranched dendrimers affords efficient conjugation of targeting ligands and biomarkers that can recognize and bind to receptors overexpressed on cancer cells for tumor-cell-specific delivery. The present review compiles the recent advances in dendrimer-mediated drug and gene delivery to tumors by passive and active targeting principles with illustrative examples. PMID:25555748
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Swarm controlled emergence for ant clustering
DEFF Research Database (Denmark)
Scheidler, Alexander; Merkle, Daniel; Middendorf, Martin
2013-01-01
.g. moving robots, and clustering algorithms. Design/methodology/approach: Different types of control agents for that ant clustering model are designed by introducing slight changes to the behavioural rules of the normal agents. The clustering behaviour of the resulting swarms is investigated by extensive...... for future research to investigate the application of the method in other swarm systems. Swarm controlled emergence might be applied to control emergent effects in computing systems that consist of many autonomous components which make decentralized decisions based on local information. Practical...... simulation studies. Findings: It is shown that complex behavior can emerge in systems with two types of agents (normal agents and control agents). For a particular behavior of the control agents, an interesting swarm size dependent effect was found. The behaviour prevents clustering when the number...
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Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee
2008-01-01
Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery de...
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Reyes, J C; Negrón, J L; Colón, H M; Padilla, A M; Millán, M Y; Matos, T D; Robles, R R
2012-06-01
During the last decade, the veterinary anesthetics have gained popularity as recreational drugs. The aim of this study was to document the use of "anestecia de caballo" (xylazine) and its consequences among drug users in Puerto Rico. The study combined a cross-sectional survey with 89 drug users and two focus groups conducted in Mayagüez with frontline drug treatment providers. Drug users were recruited from communities of the San Juan metropolitan area using a variety of ethnographic and outreach strategies. A short questionnaire developed for the study collected information on sociodemographics, xylazine use, and its consequences. The two focus groups were conducted to discuss the details related to xylazine use, its consequences, and utilization awareness. The sample comprised 63 males (70.8%) and 26 females with a mean age of 37.2 years. The mean number of years of drug use was 14.3, with a mean frequency of drug use of 5.9 times daily. More than 65% reported speedball as the principal drug of use. The prevalence of xylazine use was 80.7%. More than 42% of the sample used xylazine in a mixture with speedball. The main route of administration of xylazine was injection but 14% reported the use of xylazine by inhalation. More than 35% of the sample reported skin lesions and 21.1% reported at least one overdose episode. Multiple logistic regression analysis revealed that males (OR = 3.47, CI = 1.10-12.00) and those who reported speedball as their main drug of use (OR = 9.34, CI = 2.51-34.70) were significantly more likely to be xylazine users. Focus groups revealed that drug users claimed to recognize the presence of xylaxine in a mixture of speedball based on its effects, taste, the color of the drug (dark brown), and its odor. In conclusion, the use of xylazine among drug users in Puerto Rico seems to be an emerging trend with potentially serious health consequences.
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Ijaz, S.; Nadeem, S.
2017-11-01
A theoretical examination is presented in this analysis to study the flow of a bio-nanofluid through a curved stenotic channel. The curved channel is considered with an overlapping stenotic region. The effect of convective conditions is incorporated to discuss the heat transfer characteristic. The mathematical problem of a curved stenotic channel is formulated and then solved by using the exact technique. To discuss the hemodynamics of a curved stenotic channel the expression of resistance to blood is evaluated by dividing the channel into pre-stenotic, stenotic and post stenotic region. In this investigation gold, silver and copper nanoparticles are used as drug carriers. The outcomes of the graphical illustration reveal that with an increase in nanoparticle concentration hemodynamics effects of stenosed curved channel are reduced and they also conclude that the drug Au nanoparticles are more effective to minimize hemodynamics when compared to the drug Ag and Cu nanoparticles. This analysis finds valuable theoretical information for nanoparticles used as drug agents in the field of bio-inspired applications.
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Public health emergencies in urban India
Directory of Open Access Journals (Sweden)
Bhabani Prasad Acharya
2018-03-01
Full Text Available Public health emergencies in urban India can be caused by natural or man-made disasters. Occurrence of a public health emergency adds to the already stretched health system. This paper looks into the public health emergency conditions in urban India, and our preparedness to tackle them. To address this composite threat to nation’s health and development, a concerted public health response is needed, that can ensure efficient delivery in emergency situations Public health emergency is an occurrence or eminent threat of an illness or health condition caused by bio-terrorism, epidemic or pandemic disease, or novel and highly fatal infectious agent or biological toxin, that possess a substantial risk of a significant number of human facilities or incidents or permanent or long–term disability (1. It is a condition that requires the government to declare a state of public health emergency. The declaration of a state of public health emergency permits the government to suspend state regulations,and change the functions of state agencies (2. Term “Urban” refers to perplexing variety of environments. Health circumstances of small cities and town differ in many ways from larger cities and metros. Within cities, change in lifestyle of residents is observed. The urban system is often present with full array of health providers ranging from traditional healer, street drug seller to highly –trained surgeons (3.
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DEFF Research Database (Denmark)
Liu, Zhou
relay operations due to low voltage or overload state in the post stage of N-1 (or N-k) contingency. If such state could be sensed and adjusted appropriately before those relay actions, the system stability might be sustained. So it is of great significance to develop a suitable protection scheme...... the proposed protection strategy in this thesis, a real time simulation platform based on Real Time Digital Simulator (RTDS) and LabVIEW is built. In this platform, the cases of cascaded blackouts are simulated on the test system simplified from the East Denmark power system. For the MAS based control system......, the distributed power system agents are set up in RTDS, while the agents in higher level are designed by LabVIEW toolkits. The case studies and simulation results demonstrate the effectiveness of real time application of the proposed MAS based special protection and emergency control scheme against the cascaded...
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Directory of Open Access Journals (Sweden)
Kirsi Ketola
Full Text Available Current treatment options for castration- and treatment-resistant prostate cancer are limited and novel approaches are desperately needed. Our recent results from a systematic chemical biology sensitivity screen covering most known drugs and drug-like molecules indicated that aldehyde dehydrogenase inhibitor disulfiram is one of the most potent cancer-specific inhibitors of prostate cancer cell growth, including TMPRSS2-ERG fusion positive cancers. However, the results revealed that disulfiram alone does not block tumor growth in vivo nor induce apoptosis in vitro, indicating that combinatorial approaches may be required to enhance the anti-neoplastic effects.In this study, we utilized a chemical biology drug sensitivity screen to explore disulfiram mechanistic details and to identify compounds potentiating the effect of disulfiram in TMPRSS2-ERG fusion positive prostate cancer cells. In total, 3357 compounds including current chemotherapeutic agents as well as drug-like small molecular compounds were screened alone and in combination with disulfiram. Interestingly, the results indicated that androgenic and antioxidative compounds antagonized disulfiram effect whereas inhibitors of receptor tyrosine kinase, proteasome, topoisomerase II, glucosylceramide synthase or cell cycle were among compounds sensitizing prostate cancer cells to disulfiram. The combination of disulfiram and an antiangiogenic agent sunitinib was studied in more detail, since both are already in clinical use in humans. Disulfiram-sunitinib combination induced apoptosis and reduced androgen receptor protein expression more than either of the compounds alone. Moreover, combinatorial exposure reduced metastatic characteristics such as cell migration and 3D cell invasion as well as induced epithelial differentiation shown as elevated E-cadherin expression.Taken together, our results propose novel combinatorial approaches to inhibit prostate cancer cell growth. Disulfiram
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The management of hypertensive emergencies in children after stem cell transplantation.
Horn, D G; Trame, M N; Hempel, G
2011-04-01
This work presents a short overview on the available data about drugs that are currently used to treat hypertensive emergencies in children with a focus on incidents after stem cell transplantation. It shows that the pediatric use of all hypotensive agents appears to be mainly based on personal experience of the attending physicians rather than on convincing clinical trials. A literature search was performed in MEDLINE, through PubMed, using the medical subject headings (MeSH) hypertensive emergencies, nifedipine, nicardipine, and children. Further articles were identified by checking cross-references of articles and books. Hypertensive emergencies in children after stem cell transplantation usually have a renal etiology, because of the treatment with the calcineurin inhibitors cyclosporine and tacrolimus. In these severe cases an immediate action is necessary to avoid possible appearance or exacerbation of endorgan damage. Because of their mechanism of action and a potential nephroprotective effect calcium channel blockers may be particularly suitable in cases of hypertensive emergencies. An intravenous application of nifedipine may compensate the difficulties of accurate dosing, but keeping in mind possible severe side effects and the lack of published experience its use in children is at least questionable. Nicardipine appears to be the hypotensive agent of first choice. In adults, the treatment of hypertensive emergencies with intravenous nicardipine is well-documented, but for an evaluation of safety in pediatric use, the published studies and case reports appear to be barely adequate. The actual treatment approaches vary widely, demonstrating the lack of hard science on which current treatment of hypertensive emergencies in children is based. The hypotensive agent for the individual situation should be chosen considering the properties, side effects, the limited experiences with its use and the patient's anamnesis.
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DEFF Research Database (Denmark)
Søgaard, Thomas F.; Houborg, Esben; Pedersen, Michael M.
2017-01-01
in local ‘drug policing assemblages’ characterized by inter-agency relation-building, the creative combination of public and private (legal) resources and internal power struggles. It also provides evidence of how drug policing assemblages give rise to many different, and often surprising, forms...... how zonal banning is also used to target drug-using clubbers in Denmark. Methods: Based on ethnographic observations and interviews with nightlife control agents in two Danish cities, the article aims to provide new insights into how the enforcement of national drug policies on drug-using clubbers......, is shaped by plural nightlife policing complexes. Results: The paper demonstrates how the policing of drug-using clubbers is a growing priority for both police and private security agents. The article also demonstrates how the enforcement of zonal bans on drug-using clubbers involves complex collaborative...
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Future immunosuppressive agents in solid-organ transplantation.
Gabardi, Steven; Cerio, Jeffrey
2004-06-01
To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium, everolimus, and FTY720. Clinical trials and abstracts evaluating mycophenolate sodium, everolimus, and FTY720 in solid-organ transplantation were considered for evaluation. English-language studies and published abstracts were selected for inclusion. Mycophenolate sodium has recently been approved by the Food and Drug Adminstration for marketing in the United States; everolimus and FTY720 are immunosuppressive agents that may soon be available in the United States. These agents have proven efficacy in reducing the incidence of acute rejection in solid-organ transplantation. Clinical trials have shown that these newer agents are relatively well tolerated. The most common adverse events associated with these agents were gastrointestinal and hematologic effects (mycophenolate sodium); hyperlipidemia, increased serum creatinine, and hematologic effects (everolimus): and gastrointestinal effects, headache, and bradycardia (FTY720). Mycophenolate sodium has been approved in some European countries and the United States. Everolimus has been approved in some European countries and a new drug application has been submitted to the Food and Drug Administration. FTY720 is currently in phase III clinical trials and submission to the Food and Drug Administration for approval is a few years away. The approval of these agents will furnish the transplant practitioner with even more options for immunosuppression.
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A drug's life: the pathway to drug approval.
Keng, Michael K; Wenzell, Candice M; Sekeres, Mikkael A
2013-10-01
In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process-specifically the orphan drug designation and accelerated approval process-and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs-axitinib (Inlyta, Pfizer) and tivozanib-that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.
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Oral agents for ovulation induction:Old drugs revisited and new drugs re-evaluated
Badawy, A.M.M.
2008-01-01
The aim of this thesis was to address a number of questions regarding oral agents used for ovulation induction. We were motivated to run the presented trials because of many reasons. Firstly, although oral agents, namely CC, have been in the market for decades, many basic aspects regarding the
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A review of mechanisms of circumvention and modulation of chemotherapeutic drug resistance.
O'Connor, R
2009-05-01
Drug resistance is a serious limitation to the effective treatment of a number of common malignancies. Thirty years of laboratory and clinical research have greatly defined the molecular alterations underlying many drug resistance processes in cancer. Based on this knowledge, strategies to overcome the impact of resistance and increase the efficacy of cancer treatment have been translated from laboratory models to clinical trials. This article reviews laboratory and, in particular, clinical attempts at drug resistance circumvention from early forays in the inhibition of cellular efflux pump-mediated drug resistance through to more selective circumvention agent strategies and into inhibition of the other important mechanisms which can allow cancer cells to survive therapy, such as apoptosis resistance. Despite some promising results to date, resistance inhibition strategies have largely failed due to poor understanding of the pharmacology, dynamics and complexity of the resistance phenotype. With the realisation that new molecularly-targeted agents can also be rendered ineffectual by the actions of resistance mechanisms, a major focus is once again emerging on identifying new strategies/pharmaceuticals which can augment the activity of the arsenal of more conventional cytotoxics and newer targeted anti-cancer drugs. Future tactical directions where old and new resistance strategies may merge to overcome this challenge are discussed.
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Radujkovic, Aleksandar; Luft, Thomas; Dreger, Peter; Ho, Anthony D; Jens Zeller, W; Fruehauf, Stefan; Topaly, Julian
2014-08-01
The prognosis of patients with advanced-phase chronic myeloid leukemia (CML) remains dismal despite the availability of targeted therapies and allogeneic stem cell transplantation (allo-SCT). Increasing the antileukemic efficacy of the pretransplant conditioning regimen may be a strategy to increase remission rates and duration. We therefore investigated the antiproliferative effects of nilotinib in combination with drugs that are usually used for conditioning: the alkylating agents mafosfamide, treosulfan, and busulfan. Drug combinations were tested in vitro in different imatinib-sensitive and imatinib-resistant BCR-ABL-positive cell lines. A tetrazolium-based MTT assay was used for the assessment and quantification of growth inhibition after exposure to alkylating agents alone or to combinations with nilotinib. Drug interaction was analyzed using the median-effect method of Chou and Talalay, and combination index (CI) values were calculated according to the classic isobologram equation. Treatment of imatinib-sensitive, BCR-ABL-positive K562 and LAMA84 cells with nilotinib in combination with mafosfamide, treosulfan, or busulfan resulted in synergistic (CI 1) effects, respectively. In imatinib-resistant K562-R and LAMA84-R cells, all applied drug combinations were synergistic (CI conditioning regimens for allo-SCT in advanced-phase CML.
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Gillingham, Dennis; Sauter, Basilius
2018-05-06
Drugs that covalently modify DNA are components of most chemotherapy regimens, often serving as first-line treatments. Classically the chemical reactivity of DNA alkylators has been determined in vitro with short oligonucleotides. Here we use next generation RNA sequencing to report on the chemoselectivity of alkylating agents. We develop the method with the well-known clinically used DNA modifiying drugs streptozotocin and temozolomide, and then apply the technique to profile RNA modification with uncharacterized alkylation reactions such as with powerful electrophiles like trimethylsilyldiazomethane. The multiplexed and massively parallel format of NGS offers analyses of chemical reactivity in nucleic acids to be accomplished in less time with greater statistical power. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Understanding release kinetics of biopolymer drug delivery microcapsules for biomedical applications
International Nuclear Information System (INIS)
Desai, Salil; Perkins, Jessica; Harrison, Benjamin S.; Sankar, Jag
2010-01-01
Drug delivery and dosage concentrations are considered as major focal points in conventional as well as battlefield emergency medicine. The concept of localizing drug delivery via microcapsules is an evolving field to confine the adverse side effects of high concentration drug doses. This paper focuses on understanding release kinetics through biopolymer microcapsules for time-dependent drug release. Calcium alginate microcapsules were manufactured using a direct-write inkjet technique. Rhodamine 6G was used as the release agent to observe the release kinetics from calcium alginate beads in distilled water. A design of experiments was constructed to compare the effect of the microcapsule diameter and different concentrations of calcium chloride (M) and sodium alginate (%, w/v) solutions on the release kinetics profiles of the microcapsules. This research gives insight to identify favorable sizes of microcapsules and concentrations of sodium alginate and calcium chloride solutions for controlled release behavior of drug delivery microcapsules.
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Recent advances in (therapeutic protein drug development [version 1; referees: 2 approved
Directory of Open Access Journals (Sweden)
H.A. Daniel Lagassé
2017-02-01
Full Text Available Therapeutic protein drugs are an important class of medicines serving patients most in need of novel therapies. Recently approved recombinant protein therapeutics have been developed to treat a wide variety of clinical indications, including cancers, autoimmunity/inflammation, exposure to infectious agents, and genetic disorders. The latest advances in protein-engineering technologies have allowed drug developers and manufacturers to fine-tune and exploit desirable functional characteristics of proteins of interest while maintaining (and in some cases enhancing product safety or efficacy or both. In this review, we highlight the emerging trends and approaches in protein drug development by using examples of therapeutic proteins approved by the U.S. Food and Drug Administration over the previous five years (2011–2016, namely January 1, 2011, through August 31, 2016.
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YouTube, "Drug Videos" and Drugs Education
Manning, Paul
2013-01-01
Aims: This article reports on findings to emerge from a project examining YouTube "drug videos" in the light of an emerging literature on the relationship between YouTube and health education. The aim of this article is to describe the variety of discourses circulated by the "drug videos" available on YouTube and to consider…
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Drugs of abuse: the highs and lows of altered mental states in the emergency department.
Meehan, Timothy J; Bryant, Sean M; Aks, Steven E
2010-08-01
The diagnosis and management of poisoned patients presenting with alterations in mental status can be challenging, as patients are often unable (or unwilling) to provide an adequate history. Several toxidromes exist. Recognition hinges upon vital signs and the physical examination. Understanding these "toxic syndromes" may guide early therapy and management, providing insight into the patient's underlying medical problem. Despite toxidrome recognition guiding antidotal therapy, the fundamental aspect of managing these patients involves meticulous supportive care. The authors begin with a discussion of various toxidromes and then delve into the drugs responsible for each syndrome. They conclude with a discussion on drug-facilitated sexual assault ("date rape"), which is both an underrecognized problem in the emergency department (ED) and representative of the drug-related problems faced in a modern ED. Copyright 2010. Published by Elsevier Inc.
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Liakoni, Evangelia; Dolder, Patrick C.; Rentsch, Katharina; Liechti, Matthias E.
2015-01-01
QUESTIONS UNDER STUDY: To describe acute toxicity of recreational drugs including novel psychoactive substances. METHODS: We included all cases presenting at the emergency department (ED) of the University Hospital of Basel, Switzerland, between October 2013 and September 2014 with acute toxicity due to self-reported recreational drug use or with symptoms/signs consistent with acute toxicity. Isolated ethanol intoxications were excluded. Intoxications were confirmed with immunoassa...
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Bao, Yuping; Wen, Tianlong; Samia, Anna Cristina S.; Khandhar, Amit; Krishnan, Kannan M.
2015-01-01
We present an interdisciplinary overview of material engineering and emerging applications of iron oxide nanoparticles. We discuss material engineering of nanoparticles in the broadest sense, emphasizing size and shape control, large-area self-assembly, composite/hybrid structures, and surface engineering. This is followed by a discussion of several non-traditional, emerging applications of iron oxide nanoparticles, including nanoparticle lithography, magnetic particle imaging, magnetic guided drug delivery, and positive contrast agents for magnetic resonance imaging. We conclude with a succinct discussion of the pharmacokinetics pathways of iron oxide nanoparticles in the human body –– an important and required practical consideration for any in vivo biomedical application, followed by a brief outlook of the field. PMID:26586919
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Sawyer, Andrew J; Kyriakides, Themis R
2016-02-01
Extracellular matrix is composed of a complex array of molecules that together provide structural and functional support to cells. These properties are mainly mediated by the activity of collagenous and elastic fibers, proteoglycans, and proteins such as fibronectin and laminin. ECM composition is tissue-specific and could include matricellular proteins whose primary role is to modulate cell-matrix interactions. In adults, matricellular proteins are primarily expressed during injury, inflammation and disease. Particularly, they are closely associated with the progression and prognosis of cardiovascular and fibrotic diseases, and cancer. This review aims to provide an overview of the potential use of matricellular proteins in drug delivery including the generation of therapeutic agents based on the properties and structures of these proteins as well as their utility as biomarkers for specific diseases. Copyright © 2016 Elsevier B.V. All rights reserved.
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Extensively Drug-Resistant Tuberculosis: Principles of Resistance, Diagnosis, and Management.
Wilson, John W; Tsukayama, Dean T
2016-04-01
Extensively drug-resistant (XDR) tuberculosis (TB) is an unfortunate by-product of mankind's medical and pharmaceutical ingenuity during the past 60 years. Although new drug developments have enabled TB to be more readily curable, inappropriate TB management has led to the emergence of drug-resistant disease. Extensively drug-resistant TB describes Mycobacterium tuberculosis that is collectively resistant to isoniazid, rifampin, a fluoroquinolone, and an injectable agent. It proliferates when established case management and infection control procedures are not followed. Optimized treatment outcomes necessitate time-sensitive diagnoses, along with expanded combinations and prolonged durations of antimicrobial drug therapy. The challenges to public health institutions are immense and most noteworthy in underresourced communities and in patients coinfected with human immunodeficiency virus. A comprehensive and multidisciplinary case management approach is required to optimize outcomes. We review the principles of TB drug resistance and the risk factors, diagnosis, and managerial approaches for extensively drug-resistant TB. Treatment outcomes, cost, and unresolved medical issues are also discussed. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
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Grimling, Bozena; Pluta, Janusz
2005-01-01
Adsorbance of certain prokinetic drugs, regulating the motility of the digestive tract, on a cytoprotective drug--sucralfate was investigated. The evaluation of adsorbance capability was carried out by means of a statistical method in in vitro conditions, taking into account environmental pH, concentration of the investigated drugs as well as the form of sucralfate. Obtained results prove that the analyzed active agents are adsorbed on sucralfate at all the investigated pH ranges and the capability of sucralfate binding depends on its form and environmental pH. The highest binding capability was revealed by samples with pH = 3.6 in the presence of sucralfate in the form of suspension, while the lowest binding capability was observed at pH = 1.5 in the presence of sucralfate in the form of paste. The adsorbance capacity of sucralfate (k) at pH = 3.6 is the highest for cisaprid (k = 8.5) and it is significantly lower for metoclopramide (k = 1.5)
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Terbinafine-induced lichenoid drug eruption.
Zheng, Yue; Zhang, Jie; Chen, Haiyan; Lai, Wei; Maibach, Howard I
2017-03-01
Drug-induced lichen planus has been induced by antibiotics, anticonvulsants, antidiabetics, antimalarials, antitubercular drugs, antihypertensives, psychiatric drugs, chemotherapeutic agents, diuretic, heavy metals, NSAIDs, etc. Terbinafine, an antifungal agent, is widely used for dermatophyte infections and onychomycosis. Cutaneous adverse effects of terbinafine are rarely reported. Here, we report a case of terbinafine-induced lichenoid drug eruption in a 22-year-old who presented with generalized lichenoid eruption 2 weeks after terbinafine initiation of. The body and lip cleared completely after 8 weeks of drug withdrawal; nail change cleared after 12 weeks.
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Newer antidiabetic drugs and calorie restriction mimicry
Directory of Open Access Journals (Sweden)
Sanjay Kalra
2016-01-01
Full Text Available De-acceleration of aging and delayed development of age-related morbidity accompanies the restriction of calories (without malnutrition in laboratory mice, nematodes, yeast, fish, and dogs. Recent results from long-term longitudinal studies conducted on primates have suggested longevity benefits of a 30% restriction of calories in rhesus monkeys as well. Among calorie restricted rhesus monkeys one of the mechanisms for the improvement in lifespan was the reduction in the development of glucose intolerance and cardiovascular disease. Although there are no comparable human studies, it is likely that metabolic and longevity benefits will accompany a reduction in calories in humans as well. However, considering the difficulties in getting healthy adults to limit food intake science has focused on understanding the biochemical processes that accompany calorie restriction (CR to formulate drugs that would mimic the effects of CR without the need to actually restrict calories. Drugs in this emerging therapeutic field are called CR mimetics. Some of the currently used anti-diabetic agents may have some CR mimetic like effects. This review focuses on the CR mimetic properties of the currently available anti-diabetic agents.
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Munro, N B; Watson, A P; Ambrose, K R; Griffin, G D
1990-01-01
Current treatment protocols for exposure to nerve and vesicant agents found in the U.S. stockpile of unitary chemical weapons are summarized, and the toxicities of available antidotes are evaluated. The status of the most promising of the new nerve agent antidotes is reviewed. In the U.S. atropine and pralidoxime compose the only approved antidote regimen for organophosphate nerve agent poisoning. Diazepam may also be used if necessary to control convulsions. To avoid death, administration must occur within minutes of substantial exposure together with immediate decontamination. Continuous observation and repeated administration of antidotes are necessary as symptoms warrant. Available antidotes do not necessarily prevent respiratory failure or incapacitation. The toxicity of the antidotes themselves and the individualized nature of medical care preclude recommending that autoinjectors be distributed to the general public. In addition, precautionary administration of protective drugs to the general population would not be feasible or desirable. No antidote exists for poisoning by the vesicant sulfur mustard (H, HD, HT); effective intervention can only be accomplished by rapid decontamination followed by palliative treatment of symptoms. British anti-Lewisite (BAL) (2,3-dimercapto-1-propanolol) is the antidote of choice for treatment of exposure to Lewisite, another potent vesicant. Experimental water-soluble BAL analogues have been developed that are less toxic than BAL. Treatment protocols for each antidote are summarized in tabular form for use by health care providers. PMID:2088748
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Drug abuse-related accidents leading to emergency department visits at two medical centers.
Chen, Isaac Chun-Jen; Hung, Dong-Zong; Hsu, Chi-Ho; Wu, Ming-Ling; Deng, Jou-Fang; Chang, Chin-Yu; Shih, Hsin-Chin; Liu, Chen-Chi; Wang, Chien-Ying; Wen, Yi-Szu; Wu, Jackson Jer-Kan; Huang, Mu-Shun; Yang, Chen-Chang
2012-05-01
Drug abuse is becoming more prevalent in Taiwan, as evidenced by increasing reports of drug trafficking and drug abuse-related criminal activity, and the wide use of more contemporary illicit drugs. Consequently, drug abuse-related accidents are also expected to occur with greater frequency. However, no study has yet specifically evaluated the prevalence, pattern, and outcomes of drug abuse-related accidents among patients visiting emergency departments (EDs) in Taiwan. We conducted an ambidirectional study with patients who visited the EDs of Taipei Veterans General Hospital (TVGH) and China Medical University Hospital (CMUH) due to drug abuse-related accidents from January 2007 through September 2009. Information on the patients' baseline characteristics and clinical outcomes was collected and analyzed. During the study period, a total of 166 patients visited the EDs of one of the two study hospitals due to drug abuse-related accidents. This yielded a prevalence of drug abuse of 0.1% among all patients visiting the ED due to accident and/or trauma. Fifty-six out of the 166 patients visited the ED at TVGH, most patients being between 21 and 40 years old. Opioids (41.1%) were the drugs most commonly abused by the patients, followed by benzodiazepines (32.1%). More than two-thirds of the patients (n=38, 67.9%) required hospitalization, and three patients died (5.4%). In contrast, 110 patients with drug abuse-related accidents visited the ED at CMUH during the study period. Most of these subjects had abused benzodiazepines (69.1%), were between 21 and 40 years old, and were female. Fewer than one-fifth of the patients (n=19, 17.3%) required hospitalization, with no deaths reported. There were significant between-hospital differences in terms of patient gender, drugs of choice, injury mechanisms, method and time of the ED visit, triage levels, and need for hospitalization. Although the prevalence of drug abuse-related accidents was low, and only three patient deaths
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Directory of Open Access Journals (Sweden)
Sonja Kolen
2018-01-01
Full Text Available In future electrical distribution systems, component heterogeneity and their cyber-physical interactions through electrical lines and communication lead to emergent system behavior. As the distribution systems represent the largest part of an energy system with respect to the number of nodes and components, large-scale studies of their emergent behavior are vital for the development of decentralized control strategies. This paper presents and evaluates DistAIX, a novel agent-based modeling and simulation tool to conduct such studies. The major novelty is a parallelization of the entire model—including the power system, communication system, control, and all interactions—using processes instead of threads. Thereby, a distribution of the simulation to multiple computing nodes with a distributed memory architecture becomes possible. This makes DistAIX scalable and allows the inclusion of as many processing units in the simulation as desired. The scalability of DistAIX is demonstrated by simulations of large-scale scenarios. Additionally, the capability of observing emergent behavior is demonstrated for an exemplary distribution grid with a large number of interacting components.
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Which drugs are risk factors for the development of gastroesophageal reflux disease?
Mungan, Zeynel; Pınarbaşı Şimşek, Binnur
2017-12-01
Gastroesophageal reflux disease (GERD), which is common in many communities, is associated with structural factors, eating habits, and the use of certain drugs. The use of such drugs can lead to the emergence of GERD and can also exacerbate existing reflux symptoms. These drugs can contribute to GERD by directly causing mucosal damage, by reducing lower esophageal sphincter pressure (LESP), or by affecting esophagogastric motility. In this article, we report our investigation of the relationships between GERD and medications within the scope of the "Turkish GERD Consensus Group." For the medication groups for which sufficient data were obtained (Figure 1), a systematic literature review in English was conducted using the keywords "gastroesophageal reflux" [MeSH Terms] and "anti-inflammatory agents, non-steroidal" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "acetylsalicylic acid" [MeSH Terms], "gastroesophageal reflux" [All Fields] and "estrogenic agents" [All Fields], "gastroesophageal reflux" [All Fields] and "progesterones" [All Fields], "gastroesophageal reflux" [All Fields] and "hormone replacement therapy" [All Fields], "gastroesophageal reflux" [MeSH Terms] and "diphosphonates" [MeSH Terms] OR "diphosphonates" [All Fields], "calcium channel blockers" [MeSH Terms] and "gastroesophageal reflux" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "nitrates" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "antidepressive agents" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "benzodiazepines" [MeSH Terms] and "hypnotic drugs" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "cholinergic antagonists" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "theophylline" [MeSH Terms], and "gastroesophageal reflux [MeSH Terms] AND "anti-asthmatic agents" [MeSH Terms]. The studies were analyzed and the results are presented here.
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Kangaspeska, Sara; Hultsch, Susanne; Jaiswal, Alok; Edgren, Henrik; Mpindi, John-Patrick; Eldfors, Samuli; Brück, Oscar; Aittokallio, Tero; Kallioniemi, Olli
2016-07-04
The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains. Using high throughput drug sensitivity and resistance testing (DSRT) with 279 approved and investigational oncology drugs, exome-sequencing and network analysis, we for the first time, systematically determine the drug response profiles specific to tamoxifen resistance. We discovered emerging vulnerabilities towards specific drugs, such as ERK1/2-, proteasome- and BCL-family inhibitors as the cells became tamoxifen-resistant. Co-resistance to other drugs such as the survivin inhibitor YM155 and the chemotherapeutic agent paclitaxel also occurred. This study indicates that multiple molecular mechanisms dictate endocrine resistance, resulting in unexpected vulnerabilities to initially ineffective drugs, as well as in emerging co-resistances. Thus, combatting drug-resistant tumors will require patient-tailored strategies in order to identify new drug vulnerabilities, and to understand the associated co-resistance patterns.
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“On-Target” Cardiac Effects of Anticancer Drugs
Simons, Michael; Eichmann, Anne
2014-01-01
The development of new biological therapeutics such as neutralizing antibodies and small molecule inhibitors of receptors signaling is revolutionizing many fields of medicine—and creating new insights into normal biology. In particular, inhibition of blood vessel growth has been vigorously pursued in a number of fields, including oncology and ophthalmology. To date, most experience with this class of drugs centers on anti-vascular endothelial growth factor (VEGF) agents such as a neutralizing antibody bevacizumab and small molecule inhibitors of VEGF receptor-2 (VEGFR2). Anti-VEGF therapies have been spectacularly successful for treatment of macular degeneration, and somewhat less so in the treatment of cancer. Hand in hand with these advances is the emergence of new cardiac illnesses directly related to the activity of these agents. PMID:22703925
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Hon, Chun-Yip; Chua, Prescillia Ps; Danyluk, Quinn; Astrakianakis, George
2014-06-01
Occupational exposure to antineoplastic drugs has been documented to result in various adverse health effects. Despite the implementation of control measures to minimize exposure, detectable levels of drug residual are still found on hospital work surfaces. Cleaning these surfaces is considered as one means to minimize the exposure potential. However, there are no consistent guiding principles related to cleaning of contaminated surfaces resulting in hospitals to adopt varying practices. As such, this pilot study sought to evaluate current cleaning protocols and identify those factors that were most effective in reducing contamination on drug preparation surfaces. Three cleaning variables were examined: (1) type of cleaning agent (CaviCide®, Phenokil II™, bleach and chlorhexidine), (2) application method of cleaning agent (directly onto surface or indirectly onto a wipe) and (3) use of isopropyl alcohol after cleaning agent application. Known concentrations of antineoplastic drugs (either methotrexate or cyclophosphamide) were placed on a stainless steel swatch and then, systematically, each of the three cleaning variables was tested. Surface wipes were collected and quantified using high-performance liquid chromatography-tandem mass spectrometry to determine the percent residual of drug remaining (with 100% being complete elimination of the drug). No one single cleaning agent proved to be effective in completely eliminating all drug contamination. The method of application had minimal effect on the amount of drug residual. In general, application of isopropyl alcohol after the use of cleaning agent further reduced the level of drug contamination although measureable levels of drug were still found in some cases.
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Abbasi Pour, Sajjad; Shaterian, Hamid Reza; Afradi, Mojgan; Yazdani-Elah-Abadi, Afshin
2017-09-01
We synthesized Co0.25Cu0.25Mn0.5Fe2O4@CMC (CCMFe2O4@CMC) nanorods as a new dual-modal simultaneous for magnetic resonance imaging contrast agent and nanocarrier for drug delivery system. Impact of CCMFe2O4@CMC nanorods were investigated on the longitudinal (T1), transverse (T2) and transverse (T2∗) relaxation times for in vitro MRI contrast agent in water and also for drug delivery system, L-dopa was coated on CCMFe2O4@CMC nanorods and then in vitro drug release test was carried out at three PHs values and different temperatures. In vitro MR imaging demonstrated that r2 value of CCMFe2O4@CMC nanorods is 138.33 mM-1 s-1, CCMFe2O4@CMC is useful as T2 contrast agent relative to other T2 contrast agants. In vitro drug release test shows the amount of released L-dopa from CCMFe2O4@CMC nanorods at medium with pH = 1.2 is more than pH = 5.3 and 7.4.
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Nano particles: An emerging tool in biomedicine
Directory of Open Access Journals (Sweden)
Muhammad Shoaib Amjad
2015-10-01
Full Text Available Nanotechnology is an emerging scientific discipline with numerous applications in the field of biomedicine and manufacturing new materials. They hold potential to be applied in different biological fields and most strictly focused in medical applications, e.g., tools for noninvasive imaging, diagnostic test assays for early disease detection, drug development and targeted drug delivery systems to reduce secondary systemic negative effects. Nanoparticles have contributed a lot to the advancement of the medical arena. To extract gold nanoparticles with different techniques, green biosynthesis is under exploration due to its cost-effective, ecofriendly preparations with controllable shape, size and disparity, great physical and chemical inertness, optical properties related with surface plasmon resonance, surface modification, surface bio-conjugation with molecular probes, excellent biocompatibility and less toxicity. A significant potential of nanoparticles in biomedical applications including imaging of tissues and cells, sensing of target molecules, drug delivery is among recent efforts in their synthesis and functionalization e.g., Feridex (iron oxide nanoparticles have been clinically administered as a contrast agent in MRI.
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Sadée, Wolfgang; El Sayed, Yousry Mahmoud
The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).
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Tuberculosis drug issues: prices, fixed-dose combination products and second-line drugs.
Laing, R O; McGoldrick, K M
2000-12-01
Access to tuberculosis drugs depends on multiple factors. Selection of a standard list of TB drugs to procure is the first step. This paper reviews the advantages and disadvantages of procuring and using fixed-dose combination (FDC) products for both the intensive and continuation phases of treatment. The major advantages are to prevent the emergence of resistance, to simplify logistic management and to reduce costs. The major disadvantage is the need for the manufacturers to assure the quality of these FDCs by bioavailability testing. The paper reports on the inclusion of second-line TB drugs in the 1999 WHO Essential Drug List (EDL). The need to ensure that these drugs are used within established DOTS-Plus programs is stressed. The price of TB drugs is determined by many factors, including producer prices, local taxes and duties as well as mark-ups and fees. TB drug prices for both the public and private sectors from industrialized and developing countries are reported. Price trends over time are also reported. The key findings of this study are that TB drug prices have generally declined in developing countries while they have increased in developed countries, both for the public and private sectors. Prices vary between countries, with the US paying as much as 95 times the price paid in a specific developing country. The prices of public sector first-line TB drugs vary little between countries, although differences do exist due to the procurement methods used. The price of tuberculin, a diagnostic agent, has increased dramatically in the US, with substantial inter-country variations in price. The paper suggests that further research is necessary to identify the reasons for the price disparities and changes over time, and suggests methods which can be used by National Tuberculosis Programme managers to ensure availability of quality assured TB drugs at low prices.
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The social determinants of emergency department and hospital use by injection drug users in Canada.
Palepu, A; Strathdee, S A; Hogg, R S; Anis, A H; Rae, S; Cornelisse, P G; Patrick, D M; O'Shaughnessy, M V; Schechter, M T
1999-12-01
The aim of this study was to describe the relationship between sociodemographic characteristics and human immunodeficiency (HIV) status of a cohort of injection drug users (IDUs) on their self-reported health service utilization. Interviewer-administered questionnaire. IDUs who had injected illicit drugs within the previous month were recruited through street outreach. They underwent serology for HIV-1 and questionnaires on demographics, drug using behaviors, housing status, and health service utilization (hospitalization overnight and emergency department visits) in the previous 6 months. Logistic regression analysis was used to identify independent associations with the use of health services. Of 1,103 cohort participants, 65% were male, 63% were white, and 23% were HIV positive. Cocaine was the most frequently injected drug used. Almost half (47%) had used health services in the previous 6 months. The following variables were associated independently with health service utilization (adjusted odds ratio; 95% confidence interval): unstable housing, defined as living primarily in a hotel, boarding room, or transition house or on the street in the past 6 months (1.44; 1.11-1.86); female gender (1.45; 1.11-1.89); HIV-positive status (1.43; 1.06-1.92); injection of cocaine (1.50; 1.12-2.02); and primary care I physician visit in past 6 months (1.91; 1.39-2.64). IDUs with unstable housing were more likely to report emergency department and hospital use, which may be a reflection of their disorganized lifestyle or poorer health status. Further studies are required to assess the effect on the health status and health care use of IDUs of interventions that increase the availability of safe, affordable housing.
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Klaus, Christine R; Iwanowicz, Dorothy; Johnston, Danielle; Campbell, Carly A; Smith, Jesse J; Moyer, Mikel P; Copeland, Robert A; Olhava, Edward J; Scott, Margaret Porter; Pollock, Roy M; Daigle, Scott R; Raimondi, Alejandra
2014-09-01
EPZ-5676 [(2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol], a small-molecule inhibitor of the protein methyltransferase DOT1L, is currently under clinical investigation for acute leukemias bearing MLL-rearrangements (MLL-r). In this study, we evaluated EPZ-5676 in combination with standard of care (SOC) agents for acute leukemias as well as other chromatin-modifying drugs in cellular assays with three human acute leukemia cell lines: MOLM-13 (MLL-AF9), MV4-11 (MLL-AF4), and SKM-1 (non-MLL-r). Studies were performed to evaluate the antiproliferative effects of EPZ-5676 combinations in a cotreatment model in which the second agent was added simultaneously with EPZ-5676 at the beginning of the assay, or in a pretreatment model in which cells were incubated for several days in the presence of EPZ-5676 prior to the addition of the second agent. EPZ-5676 was found to act synergistically with the acute myeloid leukemia (AML) SOC agents cytarabine or daunorubicin in MOLM-13 and MV4-11 MLL-r cell lines. EPZ-5676 is selective for MLL-r cell lines as demonstrated by its lack of effect either alone or in combination in the nonrearranged SKM-1 cell line. In MLL-r cells, the combination benefit was observed even when EPZ-5676 was washed out prior to the addition of the chemotherapeutic agents, suggesting that EPZ-5676 sets up a durable, altered chromatin state that enhances the chemotherapeutic effects. Our evaluation of EPZ-5676 in conjunction with other chromatin-modifying drugs also revealed a consistent combination benefit, including synergy with DNA hypomethylating agents. These results indicate that EPZ-5676 is highly efficacious as a single agent and synergistically acts with other chemotherapeutics, including AML SOC drugs and DNA hypomethylating agents in MLL-r cells. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.
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Moynihan, Patrick Joseph; Besra, Gurdyal S
2017-10-01
Mycobacterium tuberculosis is the aetiological agent of tuberculosis (TB) and is the leading bacterial cause of mortality and morbidity in the world. One third of the world's population is infected with TB, and in conjunction with HIV represents a serious problem that urgently needs addressing. TB is a disease of poverty and mostly affects young adults in their productive years, primarily in the developing world. The most recent report from the World Health Organisation states that 8 million new cases of TB were reported and that ~1.5 million people died from TB. The efficacy of treatment is threatened by the emergence of multi-drug and extensively drug-resistant strains of M. tuberculosis. It can be argued that, globally, M. tuberculosis is the single most important infectious agent affecting mankind. Our research aims to establish an academic-industrial partnership with the goal of discovering new drug targets and hit-to-lead new chemical entities for TB drug discovery.
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Daryaei, Iman; Pagel, Mark D
2015-01-01
Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a "double-agent" approach to molecular imaging. Exogenous T 2 -exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T 1 and T 2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as "secret agents" in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging.
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21 CFR 178.3860 - Release agents.
2010-04-01
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Release agents. 178.3860 Section 178.3860 Food and... and Production Aids § 178.3860 Release agents. Substances listed in paragraph (b) of this section may be safely used as release agents in petroleum wax complying with § 178.3710 and in polymeric resins...
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Venerito, M; Schneider, C; Costanzo, R; Breja, R; Röhl, F-W; Malfertheiner, P
2018-06-01
Nonsteroidal anti-inflammatory drugs, low-dose aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors and corticosteroids increase the risk of gastroduodenal bleeding. To determine in a retrospective cohort study the contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients taking these drugs. Among patients with peptic ulcer disease diagnosed by endoscopy from 01/2004 to 12/2014 (N = 1719, 60% males, age 65.8 ± 14.5), 56.9% had peptic ulcer bleeding (cases) and 43.1% uncomplicated peptic ulcer disease (controls). Demographics, intake of nonsteroidal anti-inflammatory drugs, aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors, proton pump inhibitors and corticosteroids were documented. H. pylori status was determined by histology, rapid urease test or serology. Adjusted odds ratios (OR) were estimated by logistic regression analysis. Helicobacter pylori infection increased the risk of peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users (OR = 2.91, 95% CI = 1.71-4.98 and OR = 2.23, 95% CI = 1.52-3.28, respectively), but not in patients on anticoagulants, selective serotonin reuptake inhibitor or corticosteroid therapy. H. pylori-positive status substantially increased the risk of peptic ulcer bleeding in patients on non-aspirin antiplatelet agents (OR = 4.37, 95% CI = 1.28-14.99), concomitant aspirin/nonsteroidal anti-inflammatory drug intake (OR = 5.85, 95% CI = 1.68-20.36) and combined antiplatelet therapy (OR = 8.43, 95% CI = 1.09-65.17). After further adjustment for proton pump inhibitor intake, H. pylori infection was still a risk factor for peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users. Helicobacter pylori infection increases the risk of peptic ulcer bleeding in peptic ulcer disease patients on nonsteroidal anti-inflammatory drugs, aspirin and non
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Lopes-Bezerra, Leila M; Mora-Montes, Hector M; Zhang, Yu; Nino-Vega, Gustavo; Rodrigues, Anderson Messias; de Camargo, Zoilo Pires; de Hoog, Sybren
2018-04-01
The description of cryptic species with different pathogenic potentials has changed the perspectives on sporotrichosis. Sporothrix schenckii causes a benign chronic subcutaneous mycosis, Sporothrix brasiliensis is highly virulent, and Sporothrix globosa mainly causes fixed cutaneous lesions. Furthermore, S. brasiliensis is the prevalent species related to cat-transmitted sporotrichosis. Sources of infection, transmission, and distribution patterns also differ between species, and variability differs between species because of different degrees of clonality. The present review article will cover several aspects of the biology of clinically relevant agents of sporotrichosis, including epidemiological aspects of emerging species. Genomic information of Sporothrix spp. is also discussed. The cell wall is an essential structure for cell viability, interaction with the environment, and the host immune cells and contains several macromolecules involved in virulence. Due to its importance, aspects of glycosylation and cell wall polysaccharides are reviewed. Recent genome data and bioinformatics analyses helped to identify specific enzymes of the biosynthetic glycosylation routes, with no homologs in mammalian cells, which can be putative targets for development of antifungal drugs. A diversity of molecular techniques is available for the recognition of the clinically relevant species of Sporothrix. Furthermore, antigens identified as diagnostic markers and putative vaccine candidates are described. Cell-mediated immunity plays a key role in controlling infection, but Sporothrix species differ in their interaction with the host. The adaptive branch of the immune response is essential for appropriate control of infection.
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An In Vivo Platform for Rapid High-Throughput Antitubercular Drug Discovery
Directory of Open Access Journals (Sweden)
Kevin Takaki
2012-07-01
Full Text Available Treatment of tuberculosis, like other infectious diseases, is increasingly hindered by the emergence of drug resistance. Drug discovery efforts would be facilitated by facile screening tools that incorporate the complexities of human disease. Mycobacterium marinum-infected zebrafish larvae recapitulate key aspects of tuberculosis pathogenesis and drug treatment. Here, we develop a model for rapid in vivo drug screening using fluorescence-based methods for serial quantitative assessment of drug efficacy and toxicity. We provide proof-of-concept that both traditional bacterial-targeting antitubercular drugs and newly identified host-targeting drugs would be discovered through the use of this model. We demonstrate the model’s utility for the identification of synergistic combinations of antibacterial drugs and demonstrate synergy between bacterial- and host-targeting compounds. Thus, the platform can be used to identify new antibacterial agents and entirely new classes of drugs that thwart infection by targeting host pathways. The methods developed here should be widely applicable to small-molecule screens for other infectious and noninfectious diseases.
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Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 1.
Drusano, G L; Louie, Arnold; MacGowan, Alasdair; Hope, William
2015-12-28
We are in a crisis of bacterial resistance. For economic reasons, most pharmaceutical companies are abandoning antimicrobial discovery efforts, while, in health care itself, infection control and antibiotic stewardship programs have generally failed to prevent the spread of drug-resistant bacteria. At this point, what can be done? The first step has been taken. Governments and international bodies have declared there is a worldwide crisis in antibiotic drug resistance. As discovery efforts begin anew, what more can be done to protect newly developing agents and improve the use of new drugs to suppress resistance emergence? A neglected path has been the use of recent knowledge regarding antibiotic dosing as single agents and in combination to minimize resistance emergence, while also providing sufficient early bacterial kill. In this review, we look at the data for resistance suppression. Approaches include increasing the intensity of therapy to suppress resistant subpopulations; developing concepts of clinical breakpoints to include issues surrounding suppression of resistance; and paying attention to the duration of therapy, which is another important issue for resistance suppression. New understanding of optimizing combination therapy is of interest for difficult-to-treat pathogens like Pseudomonas aeruginosa, Acinetobacter spp., and multidrug-resistant (MDR) Enterobacteriaceae. These lessons need to be applied to our old drugs to preserve them as well and need to be put into national and international antibiotic resistance strategies. As importantly, from a regulatory perspective, new chemical entities should have a corresponding resistance suppression plan at the time of regulatory review. In this way, we can make the best of our current situation and improve future prospects. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 2.
Drusano, G L; Hope, William; MacGowan, Alasdair; Louie, Arnold
2015-12-28
We are in a crisis of bacterial resistance. For economic reasons, most pharmaceutical companies are abandoning antimicrobial discovery efforts, while, in health care itself, infection control and antibiotic stewardship programs have generally failed to prevent the spread of drug-resistant bacteria. At this point, what can be done? The first step has been taken. Governments and international bodies have declared there is a worldwide crisis in antibiotic drug resistance. As discovery efforts begin anew, what more can be done to protect newly developing agents and improve the use of new drugs to suppress resistance emergence? A neglected path has been the use of recent knowledge regarding antibiotic dosing as single agents and in combination to minimize resistance emergence, while also providing sufficient early bacterial kill. In this review, we look at the data for resistance suppression. Approaches include increasing the intensity of therapy to suppress resistant subpopulations; developing concepts of clinical breakpoints to include issues surrounding suppression of resistance; and paying attention to the duration of therapy, which is another important issue for resistance suppression. New understanding of optimizing combination therapy is of interest for difficult-to-treat pathogens like Pseudomonas aeruginosa, Acinetobacter spp., and multidrug-resistant (MDR) Enterobacteriaceae. These lessons need to be applied to our old drugs as well to preserve them and to be put into national and international antibiotic resistance strategies. As importantly, from a regulatory perspective, new chemical entities should have a resistance suppression plan at the time of regulatory review. In this way, we can make the best of our current situation and improve future prospects. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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Modeling collective emotions: a stochastic approach based on Brownian agents
International Nuclear Information System (INIS)
Schweitzer, F.
2010-01-01
We develop a agent-based framework to model the emergence of collective emotions, which is applied to online communities. Agents individual emotions are described by their valence and arousal. Using the concept of Brownian agents, these variables change according to a stochastic dynamics, which also considers the feedback from online communication. Agents generate emotional information, which is stored and distributed in a field modeling the online medium. This field affects the emotional states of agents in a non-linear manner. We derive conditions for the emergence of collective emotions, observable in a bimodal valence distribution. Dependent on a saturated or a super linear feedback between the information field and the agent's arousal, we further identify scenarios where collective emotions only appear once or in a repeated manner. The analytical results are illustrated by agent-based computer simulations. Our framework provides testable hypotheses about the emergence of collective emotions, which can be verified by data from online communities. (author)
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Emerging treatment of endometriosis
Directory of Open Access Journals (Sweden)
Aboubakr Elnashar
2015-06-01
Full Text Available Current treatment of endometriosis is mainly based on surgery and ovarian suppressive agents (oral contraceptives, progestins, GnRh agonist and androgenic agents. Hormonal treatments are often associated with unwanted effects, delayed conception and recurrence of disease and symptoms when stopped. For these reasons, new drugs that aim new targets are required to cause regression of the disease & symptoms without adverse hypo-estrogenic effects. This review aims to provide an update on the new drugs used for treatment of endometriosis. These include the levonorgestrel-releasing intrauterine device, GnRH antagonists, aromatase inhibitors, selective estrogen-receptor modulators, progesterone antagonist, selective progesterone receptor modulators, angiogenesis inhibitors, and immunomodulatory drugs.
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[Drug eruptions caused by noncorticoid anti-inflammatory agents].
Roujeau, J C; Guillaume, J C; Revuz, J; Touraine, R
1984-01-01
Non-steroidal anti-inflammatory drugs (NSAI) may elicit various kinds of cutaneous side effects. The commonest ones are non-specific erythematous eruptions, sometimes with a phototoxic distribution, and urticaria. Vasculitis and severe bullous eruptions (Stevens-Johnson's syndrome and Toxic Epidermal Necrolysis) are rare but may have severe outcomes. The overall incidence of cutaneous reactions is about the same for all NSAI, 1 to 3 p. 100, during the clinical studies performed before marketing the drug, but this increases afterwards (up to 45 p. 100 for Benoxaprofen). Drugs with long half-lives may carry a higher risk for severe cutaneous reactions. NSAI are now the main cause of drug induced TEN. Urticarial reactions seem related to pharmacological phenomena while the pathogenic events leading to other kinds of skin reactions remain unknown. An hypersensitivity reaction is postulated. The therapeutic value of corticosteroids for the severe cutaneous side effects of drugs is still controversial.
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Microbial P450 Enzymes in Bioremediation and Drug Discovery: Emerging Potentials and Challenges.
Bhattacharya, Sukanta S; Yadav, Jagjit S
2018-01-01
Cytochrome P450 enzymes are a structurally conserved but functionally diverse group of heme-containing mixed function oxidases found across both prokaryotic and eukaryotic forms of the microbial world. Microbial P450s are known to perform diverse functions ranging from the synthesis of cell wall components to xenobiotic/drug metabolism to biodegradation of environmental chemicals. Conventionally, many microbial systems have been reported to mimic mammalian P450-like activation of drugs and were proposed as the in-vitro models of mammalian drug metabolism. Recent reports suggest that native or engineered forms of specific microbial P450s from these and other microbial systems could be employed for desired specific biotransformation reactions toward natural and synthetic (drug) compounds underscoring their emerging potential in drug improvement and discovery. On the other hand, microorganisms particularly fungi and actinomycetes have been shown to possess catabolic P450s with unusual potential to degrade toxic environmental chemicals including persistent organic pollutants (POPs). Wood-rotting basidiomycete fungi in particular have revealed the presence of exceptionally large P450 repertoire (P450ome) in their genomes, majority of which are however orphan (with no known function). Our pre- and post-genomic studies have led to functional characterization of several fungal P450s inducible in response to exposure to several environmental toxicants and demonstration of their potential in bioremediation of these chemicals. This review is an attempt to summarize the postgenomic unveiling of this versatile enzyme superfamily in microbial systems and investigation of their potential to synthesize new drugs and degrade persistent pollutants, among other biotechnological applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Mercolini, Laura; Protti, Michele
2016-10-25
The term "new psychoactive substances" refers to emerging drugs of abuse whose chemical structure and psychoactive effects are similar to other already known compounds, often providing a "legal" alternative to internationally regulated drugs and mostly available via on-line retail sites. There are several categories of new psychoactive substances, such as synthetic cannabinoids, cathinone analogues, phenethylamines, tryptamines, and the need to identify and quantify an unprecedented and growing number of new compounds represents a unique challenge for toxicological and forensic analysis. The purpose of this review is to highlight biosampling, sample preparation and analysis of the most important classes of emerging drugs of abuse in biological matrices, focusing on alternatives to classical blood and urine "in tube" approach, still representing the standard routine for bioanalysis, despite inherent flaws regarding handling, stability and process feasibility. Chromatographic techniques coupled to mass spectrometry are usually exploited to identify and quantify new psychoactive substances; due to their high sensitivity and selectivity, it is possible to determine low concentrations not only in plasma and urine, but also in alternative matrices like dried blood spots, oral fluid, hair, other body fluids and tissues. Current literature on analytical methodologies applied to these samples is still limited and a more thorough validation is often required, including a comparison among the results obtained from conventional approaches and from innovative strategies, in order to determine their actual suitability. Copyright © 2016 Elsevier B.V. All rights reserved.
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Factors affecting drug-induced liver injury: antithyroid drugs as instances
Directory of Open Access Journals (Sweden)
Reza Heidari
2014-09-01
Full Text Available Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.
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Papachristos, Apostolos; Kani, Chara; Litsa, Panagiota; Valsami, Georgia; Souliotis, Kyriakos; Saridi, Maria; Markantonis, Sophia
2016-05-01
Anemia in the elderly is often related to a higher prevalence of chronic diseases such as chronic kidney failure, arthritis, and malignancy. Erythropoiesis-stimulating agents (ESAs) have been used for years to effectively treat anemia and when used appropriately can substantially improve the health status and quality of life of older adults. Following the 2008 recession in Greece, the government introduced ESA price control restrictions, but no prescribing restrictions, in an effort to reduce drug expenditure. ESA prescribing patterns and treatment costs were analyzed to determine inappropriate or appropriate use of these agents and related health care resources in Greece. A retrospective register-based drug utilization study was carried out using data from prescriptions dispensed at the public pharmacy of the largest social insurance fund (IKA-ETAM), for patients receiving ESAs over a six-month period. For each patient, demographic data, ESA dosage regimen, treatment indication and cost, prescriber specialty, and prescription origin were recorded. A total of 14,387 prescriptions from 6,074 patients (median age 74 years) were reviewed. A substantial number of patients (13.5%) were treated for off-label indications, for which the average cost per patient per indication was higher. ESA dosage/frequency of administration varied but was in accordance with recommendations. The percentage of patients who received innovator and biosimilar erythropoietin (EPO) was 88% and 12%, respectively. For the optimization of ESA utilization and the reduction of treatment costs, strict ESA prescription monitoring, development of registries, and criteria for off-label indications and biosimilar use in naive patients under the umbrella of risk-sharing agreements should be proposed.
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Multimodal concepts for integration of cytotoxic drugs
International Nuclear Information System (INIS)
Brown, J.M.; Mehta, M.P.; Nieder, C.
2006-01-01
Over recent decades, combined modality treatment has drastically improved the cure rates for various malignant tumors. Further progress is expected through the design of sound combinations involving recently developed drugs. The first part of this book summarizes the rationale and the preclinical data for combined treatment with ionizing radiation and pharmaceutical agents. Individual chapters focus on different forms of combined treatment, with due consideration being given to a range of drugs and to emerging combinations with small molecules and antibodies. The second part of the book comprises a series of disease-specific chapters in which the clinical results of combined modality treatment are presented. The text, written by acknowledged experts, is specifically designed to be accessible to professionals from the various disciplines involved in multidisciplinary cancer care and to residents in radiation oncology training programs. (orig.)
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Screening of chemical compound libraries identified new anti-Toxoplasma gondii agents.
Adeyemi, Oluyomi Stephen; Sugi, Tatsuki; Han, Yongmei; Kato, Kentaro
2018-02-01
Toxoplasma gondii is the etiological agent of toxoplasmosis, a common parasitic disease that affects nearly one-third of the human population. The primary infection can be asymptomatic in healthy individuals but may prove fatal in immunocompromised individuals. Available treatment options for toxoplasmosis patients are limited, underscoring the urgent need to identify and develop new therapies. Non-biased screening of libraries of chemical compounds including the repurposing of well-characterized compounds is emerging as viable approach to achieving this goal. In the present investigation, we screened libraries of natural product and FDA-approved compounds to identify those that inhibited T. gondii growth. We identified 32 new compounds that potently inhibit T. gondii growth. Our findings are new and promising, and further strengthen the prospects of drug repurposing as well as the screening of a wide range of chemical compounds as a viable source of alternative anti-parasitic therapeutic agents.
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Microchips and controlled-release drug reservoirs.
Staples, Mark
2010-01-01
This review summarizes and updates the development of implantable microchip-containing devices that control dosing from drug reservoirs integrated with the devices. As the expense and risk of new drug development continues to increase, technologies that make the best use of existing therapeutics may add significant value. Trends of future medical care that may require advanced drug delivery systems include individualized therapy and the capability to automate drug delivery. Implantable drug delivery devices that promise to address these anticipated needs have been constructed in a variety of ways using micro- and nanoelectromechanical systems (MEMS or NEMS)-based technology. These devices expand treatment options for addressing unmet medical needs related to dosing. Within the last few years, advances in several technologies (MEMS or NEMS fabrication, materials science, polymer chemistry, and data management) have converged to enable the construction of miniaturized implantable devices for controlled delivery of therapeutic agents from one or more reservoirs. Suboptimal performance of conventional dosing methods in terms of safety, efficacy, pain, or convenience can be improved with advanced delivery devices. Microchip-based implantable drug delivery devices allow localized delivery by direct placement of the device at the treatment site, delivery on demand (emergency administration, pulsatile, or adjustable continuous dosing), programmable dosing cycles, automated delivery of multiple drugs, and dosing in response to physiological and diagnostic feedback. In addition, innovative drug-medical device combinations may protect labile active ingredients within hermetically sealed reservoirs. Copyright (c) 2010 John Wiley & Sons, Inc.
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Ceramic drug-delivery devices.
Lasserre, A; Bajpai, P K
1998-01-01
A variety of ceramics and delivery systems have been used to deliver chemicals, biologicals, and drugs at various rates for desired periods of time from different sites of implantation. In vitro and in vivo studies have shown that ceramics can successfully be used as drug-delivery devices. Matrices, inserts, reservoirs, cements, and particles have been used to deliver a large variety of therapeutic agents such as antibiotics, anticancer drugs, anticoagulants, analgesics, growth factors, hormones, steroids, and vaccines. In this article, the advantages and disadvantages of conventional drug-delivery systems and the different approaches used to deliver chemical and biological agents by means of ceramic systems will be reviewed.
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Directory of Open Access Journals (Sweden)
Qiu Ying Lau
2015-10-01
Full Text Available The lack of new antibacterial drugs entering the market and their misuse have resulted in the emergence of drug-resistant bacteria, posing a major health crisis worldwide. In particular, meticillin-resistant Staphylococcus aureus (MRSA, a pathogen responsible for numerous human infections, has become endemic in hospitals worldwide. Drug repurposing, the finding of new therapeutic indications for approved drugs, is deemed a plausible solution to accelerate drug discovery and development in this area. Towards this end, we screened 1163 drugs approved by the Food and Drug Administration (FDA for bioactivities against MRSA in a 10 μM single-point assay. After excluding known antibiotics and antiseptics, six compounds were identified and their MICs were determined against a panel of clinical MRSA strains. A toxicity assay using human keratinocytes was also conducted to gauge their potential for repurposing as topical agents for treating MRSA skin infections.
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Zhu, Zhenzhu; Wang, Xiaoyong; Li, Tuanjie; Aime, Silvio; Sadler, Peter J; Guo, Zijian
2014-11-24
Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)-gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt-Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd-DTPA. T1-weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt-Gd complexes promising theranostic agents for cancer treatment. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Emerging migraine treatments and drug targets
DEFF Research Database (Denmark)
Olesen, Jes; Ashina, Messoud
2011-01-01
Migraine has a 1-year prevalence of 10% and high socioeconomic costs. Despite recent drug developments, there is a huge unmet need for better pharmacotherapy. In this review we discuss promising anti-migraine strategies such as calcitonin gene-related peptide (CGRP) receptor antagonists and 5....... Tonabersat, a cortical spreading depression inhibitor, has shown efficacy in the prophylaxis of migraine with aura. Several new drug targets such as nitric oxide synthase, the 5-HT(1D) receptor, the prostanoid receptors EP(2) and EP(4), and the pituitary adenylate cyclase receptor PAC1 await development....... The greatest need is for new prophylactic drugs, and it seems likely that such compounds will be developed in the coming decade....
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Adulteration Practices of Psychoactive Illicit Drugs: An Updated Review.
Solimini, Renata; Rotolo, Maria C; Pellegrini, Manuela; Minutillo, Adele; Pacifici, Roberta; Busardò, Francesco P; Zaami, Simona
2017-01-01
Powdery drugs such as cocaine and heroin are frequently adulterated or diluted predominantly to obtain more doses and to increase the drug dealer's profits, but also to enhance, to modify or to oppose drug effects. The aim of this report is to provide an overview of the recent scientific literature on medicines as well as on new psychoactive substances, used as cutting agents (i.e. pharmacologically active adulterants) and on the related adverse health effects on consumers, possibly due to the synergistic effect of the adulterants laced with substances of abuse. A literature search up to January 2017 was performed on MEDLINE, Scopus and Web of Science and reports and documents of international agencies or institutions were also searched. Pharmacologically active substances such as: paracetamol, caffeine, dextromethorphan, clenbuterol for heroin; levamisole, phenacetine, lidocaine, hydroxyzine and diltiazem for cocaine; caffeine and phentermine for amphetamine, have been identified over the years. Furthermore, since cocaine and morphine (this latter as a precursor of heroin) are both extracted from natural products, some impurities and minor alkaloids can be present in the final preparation. In this context, it is worth considering that new psychoactive substances are also used as cutting agents. The wide availability of illicit psychotropic drugs is the most serious hazard threatening consumers. Indeed emergency departments are often responsible in evaluating damages caused not only by the base substance, but also by other eventual compounds added to mimic or antagonize drug effects or simply dilute the drug amount, with a possible harmful synergic toxic action. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Chen, Zhidan; Yan, Yanqin
2017-09-01
Bacopa monnieri has effect on the nervous system, digestive system and blood circulation systems. In this paper, the authors conducted pharmacological analysis on Bacopa monniera and its innovative pharmaceutical preparation of promote motor function. The extract of the drug has some effect on relieving the fatigue and providing the movement function. By analyzing the composition and efficacy of Chinese herbal extracts, it can be seen that these drugs have obvious effect on improving immunity. Experimental results show that the agent can increase the liver glycogen energy reserves, reduce Bla and BUN levels, balance and energy metabolism of muscle cells in the environment, it plays a positive role to improve the exercise capacity and exercise fatigue.
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Kim, Wooseong; Hendricks, Gabriel Lambert; Lee, Kiho; Mylonakis, Eleftherios
2017-06-01
The emergence of antibiotic-resistant and -tolerant bacteria is a major threat to human health. Although efforts for drug discovery are ongoing, conventional bacteria-centered screening strategies have thus far failed to yield new classes of effective antibiotics. Therefore, new paradigms for discovering novel antibiotics are of critical importance. Caenorhabditis elegans, a model organism used for in vivo, offers a promising solution for identification of anti-infective compounds. Areas covered: This review examines the advantages of C. elegans-based high-throughput screening over conventional, bacteria-centered in vitro screens. It discusses major anti-infective compounds identified from large-scale C. elegans-based screens and presents the first clinically-approved drugs, then known bioactive compounds, and finally novel small molecules. Expert opinion: There are clear advantages of using a C. elegans-infection based screening method. A C. elegans-based screen produces an enriched pool of non-toxic, efficacious, potential anti-infectives, covering: conventional antimicrobial agents, immunomodulators, and anti-virulence agents. Although C. elegans-based screens do not denote the mode of action of hit compounds, this can be elucidated in secondary studies by comparing the results to target-based screens, or conducting subsequent target-based screens, including the genetic knock-down of host or bacterial genes.
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Cao, Yongzhong; Shen, Yongxiu; Cheng, Lingling; Zhang, Xiaorong; Wang, Chao; Wang, Yan; Zhou, Xiaohui; Chao, Guoxiang; Wu, Yantao
2018-03-01
Salmonellae is one of the most important foodborne pathogens and becomes resistant to multiple antibiotics, which represents a significant challenge to food industry and public health. However, a molecular signature that can be used to distinguish antimicrobial resistance profile, particularly multi-drug resistance or extensive-drug resistance (XDR). In the current study, 168 isolates from the chicken and pork production chains and ill chickens were characterized by serotyping, antimicrobial susceptibility test, multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). The results showed that these isolates belonged to 13 serotypes, 14 multilocus sequence types (STs), 94 PFGE genotypes, and 70 antimicrobial resistant profiles. S. Enteritidis, S. Indiana, and S. Derby were the predominant serotypes, corresponding to the ST11, ST17, and ST40 clones, respectively and the PFGE Cluster A, Cluster E, and Cluster D, respectively. Among the ST11-S. Enteritidis (Cluster A) and the ST40-S. Derby (Cluster D) clones, the majority of isolates were resistant to 4-8 antimicrobial agents, whereas in the ST17S. Indiana (Cluster E) clone, isolates showed extensive-drug resistance (XDR) to 9-16 antimicrobial agents. The bla TEM-1-like gene was prevalent in the ST11 and ST17 clones corresponding to high ampicillin resistance. The bla TEM-1-like , bla CTX-M , bla OXA-1-like , sul1, aaC4, aac(6')-1b, dfrA17, and floR gene complex was highly prevalent among isolates of ST17, corresponding to an XDR phenotype. These results demonstrated the association of the resistant phenotypes and genotypes with ST clone and PFGE cluster. Our results also indicated that the newly identified gene complex comprising bla TEM-1-like , bla CTX-M , bla OXA-1-like , sul1, aaC4, aac(6')-1b, dfrA17, and floR, was responsible for the emergence of the ST17S. Indiana XDR clone. ST17 could be potentially used as a molecular signature to distinguish S. Indiana XDR clone. Copyright © 2017
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Directory of Open Access Journals (Sweden)
Esther Julián
Full Text Available The emergence of multidrug-resistant bacteria has encouraged vigorous efforts to develop antimicrobial agents with new mechanisms of action. Ribonucleotide reductase (RNR is a key enzyme in DNA replication that acts by converting ribonucleotides into the corresponding deoxyribonucleotides, which are the building blocks of DNA replication and repair. RNR has been extensively studied as an ideal target for DNA inhibition, and several drugs that are already available on the market are used for anticancer and antiviral activity. However, the high toxicity of these current drugs to eukaryotic cells does not permit their use as antibacterial agents. Here, we present a radical scavenger compound that inhibited bacterial RNR, and the compound's activity as an antibacterial agent together with its toxicity in eukaryotic cells were evaluated. First, the efficacy of N-methyl-hydroxylamine (M-HA in inhibiting the growth of different Gram-positive and Gram-negative bacteria was demonstrated, and no effect on eukaryotic cells was observed. M-HA showed remarkable efficacy against Mycobacterium bovis BCG and Pseudomonas aeruginosa. Thus, given the M-HA activity against these two bacteria, our results showed that M-HA has intracellular antimycobacterial activity against BCG-infected macrophages, and it is efficacious in partially disassembling and inhibiting the further formation of P. aeruginosa biofilms. Furthermore, M-HA and ciprofloxacin showed a synergistic effect that caused a massive reduction in a P. aeruginosa biofilm. Overall, our results suggest the vast potential of M-HA as an antibacterial agent, which acts by specifically targeting a bacterial RNR enzyme.
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Julián, Esther; Baelo, Aida; Gavaldà, Joan; Torrents, Eduard
2015-01-01
The emergence of multidrug-resistant bacteria has encouraged vigorous efforts to develop antimicrobial agents with new mechanisms of action. Ribonucleotide reductase (RNR) is a key enzyme in DNA replication that acts by converting ribonucleotides into the corresponding deoxyribonucleotides, which are the building blocks of DNA replication and repair. RNR has been extensively studied as an ideal target for DNA inhibition, and several drugs that are already available on the market are used for anticancer and antiviral activity. However, the high toxicity of these current drugs to eukaryotic cells does not permit their use as antibacterial agents. Here, we present a radical scavenger compound that inhibited bacterial RNR, and the compound's activity as an antibacterial agent together with its toxicity in eukaryotic cells were evaluated. First, the efficacy of N-methyl-hydroxylamine (M-HA) in inhibiting the growth of different Gram-positive and Gram-negative bacteria was demonstrated, and no effect on eukaryotic cells was observed. M-HA showed remarkable efficacy against Mycobacterium bovis BCG and Pseudomonas aeruginosa. Thus, given the M-HA activity against these two bacteria, our results showed that M-HA has intracellular antimycobacterial activity against BCG-infected macrophages, and it is efficacious in partially disassembling and inhibiting the further formation of P. aeruginosa biofilms. Furthermore, M-HA and ciprofloxacin showed a synergistic effect that caused a massive reduction in a P. aeruginosa biofilm. Overall, our results suggest the vast potential of M-HA as an antibacterial agent, which acts by specifically targeting a bacterial RNR enzyme.
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Evolutions in fragment-based drug design: the deconstruction–reconstruction approach
Chen, Haijun; Zhou, Xiaobin; Wang, Ailan; Zheng, Yunquan; Gao, Yu; Zhou, Jia
2014-01-01
Recent advances in the understanding of molecular recognition and protein–ligand interactions have facilitated rapid development of potent and selective ligands for therapeutically relevant targets. Over the past two decades, a variety of useful approaches and emerging techniques have been developed to promote the identification and optimization of leads that have high potential for generating new therapeutic agents. Intriguingly, the innovation of a fragment-based drug design (FBDD) approach has enabled rapid and efficient progress in drug discovery. In this critical review, we focus on the construction of fragment libraries and the advantages and disadvantages of various fragment-based screening (FBS) for constructing such libraries. We also highlight the deconstruction–reconstruction strategy by utilizing privileged fragments of reported ligands. PMID:25263697
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Emergence of Leadership in Communication.
Allahverdyan, Armen E; Galstyan, Aram
2016-01-01
We study a neuro-inspired model that mimics a discussion (or information dissemination) process in a network of agents. During their interaction, agents redistribute activity and network weights, resulting in emergence of leader(s). The model is able to reproduce the basic scenarios of leadership known in nature and society: laissez-faire (irregular activity, weak leadership, sizable inter-follower interaction, autonomous sub-leaders); participative or democratic (strong leadership, but with feedback from followers); and autocratic (no feedback, one-way influence). Several pertinent aspects of these scenarios are found as well-e.g., hidden leadership (a hidden clique of agents driving the official autocratic leader), and successive leadership (two leaders influence followers by turns). We study how these scenarios emerge from inter-agent dynamics and how they depend on behavior rules of agents-in particular, on their inertia against state changes.
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Electrospun polymeric nanofibers for transdermal drug delivery
Directory of Open Access Journals (Sweden)
Mahya Rahmani
2017-04-01
Full Text Available Conventional transdermal drug delivery systems (TDDS have been designed for drug delivery through the skin. These systems use the permeability property of stratum corneum, the outermost surface layer of the skin. Applying polymeric micro and nanofibers in drug delivery has recently attracted great attention and the electrospinning technique is the preferred method for polymeric micro-nanofibers fabrication with a great potential for drug delivery. More studies in the field of nanofibers containing drug are divided two categories: first, preparation and characterization of nanofibers containing drug and second, investigation of their therapeutic applications. Drugs used in electrospun nanofibers can be categorized into three main groups, including antibiotics and antimicrobial agents, anti-inflammatory agents and vitamins with therapeutic applications. In this paper, we review the application of electrospun polymeric scaffolds in TDDS and also introduce several pharmaceutical and therapeutic agents which have been used in polymer nanofibrous patches.
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Structural insights into drug development strategy targeting EGFR T790M/C797S.
Zhu, Su-Jie; Zhao, Peng; Yang, Jiao; Ma, Rui; Yan, Xiao-E; Yang, Sheng-Yong; Yang, Jing-Wen; Yun, Cai-Hong
2018-03-02
Treatment of non-small-cell lung cancers (NSCLCs) harboring primary EGFR oncogenic mutations such as L858R and exon 19 deletion delE746_A750 (Del-19) using gefitinib/erlotinib ultimately fails due to the emergence of T790M mutation. Though WZ4002/CO-1686/AZD9291 are effective in overcoming EGFR T790M by targeting Cys797 via covalent bonding, their efficacy is again limited due to the emergence of C797S mutation. New agents effectively inhibiting EGFR T790M without covalent linkage through Cys 797 may solve this problem. We presented here crystal structures of EGFR activating/drug-resistant mutants in complex with a panel of reversible inhibitors along with mutagenesis and enzyme kinetic data. These data revealed a previously un-described hydrophobic clamp structure in the EGFR kinase which may be exploited to facilitate development of next generation drugs targeting EGFR T790M with or without concomitant C797S. Interestingly, mutations in the hydrophobic clamp that hinder drug binding often also weaken ATP binding and/or abolish kinase activity, thus do not readily result in resistance to the drugs.
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Metformin in gestational diabetes: An emerging contender
Directory of Open Access Journals (Sweden)
Awadhesh Kumar Singh
2015-01-01
Full Text Available Gestational diabetes mellitus (GDM is defined as any degree of glucose intolerance occurring first time during pregnancy. Its prevalence is simultaneously increasing with the global rise of diabesity. GDM commonly develops, when maternal glucose metabolism is unable to compensate for the progressive development of insulin resistance, arising primarily from the consistently rising diabetogenic placental hormones. It classically develops during the second or third trimester. Theoretically, insulin sensitizers should have been the ideal agent in its treatment, given the insulin resistance, the major culprit in its pathogenesis. Fortunately, majority of women can be treated satisfactorily with lifestyle modification, and approximately 20% requires more intensive treatment. For several decades, insulin has been the most reliable treatment strategy and the gold standard in GDM. Metformin is effective insulin sensitizing agent and an established first line drug in type 2 diabetes currently. As it crosses the placenta, a safety issue remains an obstacle and, therefore, metformin is currently not recommended in the treatment of GDM. Nevertheless, given the emerging clinically equivalent safety and efficacy data of metformin compared to insulin, it appears that it may perhaps open a rather new door in managing GDM. The aim of this review is to critically analyze, the safety and efficacy data of metformin regarding its use in GDM and pregnant mothers with polycystic ovarian disease, which has emerged in past decades.
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Polymeric nanomedicine for cancer MR imaging and drug delivery.
Khemtong, Chalermchai; Kessinger, Chase W; Gao, Jinming
2009-06-28
Multifunctional nanomedicine is emerging as a highly integrated platform that allows for molecular diagnosis, targeted drug delivery, and simultaneous monitoring and treatment of cancer. Advances in polymer and materials science are critical for the successful development of these multi-component nanocomposites in one particulate system with such a small size confinement (nanoscopic therapeutic and diagnostic systems have been translated into clinical practice. In this feature article, we will provide an up-to-date review on the development and biomedical applications of nanocomposite materials for cancer diagnosis and therapy. An overview of each functional component, i.e. polymer carriers, MR imaging agents, and therapeutic drugs, will be presented. Integration of different functional components will be illustrated in several highlighted examples to demonstrate the synergy of the multifunctional nanomedicine design.
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The successes and failures of HIV drug discovery.
Hashimoto, Chie; Tanaka, Tomohiro; Narumi, Tetsuo; Nomura, Wataru; Tamamura, Hirokazu
2011-10-01
To date, several anti-human immunodeficiency virus (HIV) drugs, including reverse transcriptase inhibitors and protease inhibitors, have been developed and used clinically for the treatment of patients infected with HIV. Recently, novel drugs have been discovered which have different mechanisms of action from those of the above inhibitors, including entry inhibitors and integrase (IN) inhibitors; the clinical use of three of these inhibitors has been approved. Other inhibitors are still in development. This review article summarizes the history of the development of anti-HIV drugs and also focuses on successes in the development of these entry and IN inhibitors, along with looking at exploratory approaches for the development of other inhibitors. Currently used highly active antiretroviral therapy can be subject to a loss of efficacy, due to the emergence of multi-drug resistant (MDR) strains; a change of regimens of the drug combination is required to combat this, along with careful monitoring of the virus and CD4 in the blood, by methods such as cellular tropism testing. In such a situation, entry inhibitors such as CCR5/CXCR4 antagonists, CD4 mimics, fusion inhibitors and IN inhibitors might be optional agents for an expansion of the drug repertoire available to patients at all stages of HIV infection.
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[Innovative therapeutic strategies for intravesical drug administration].
Moch, C; Salmon, D; Rome, P; Marginean, R; Pivot, C; Colombel, M; Pirot, F
2013-05-01
Perspectives for innovative pharmaceutical molecules and intravesical administration of pharmacological agents are presented in the present review carried out from a recent literature. This review of the literature was built by using the PubMed and ScienceDirect databases running 20keywords revealing 34publications between 1983 and 2012. The number of referenced articles on ScienceDirect has increased in recent years, highlighting the interest of scientists for intravesical drug administration and the relevance of innovating drug delivery systems. Different modalities of intravesical administration using physical (e.g., iontophoresis, electroporation) or chemical techniques (e.g., enzyme, solvent, nanoparticles, liposomes, hydrogels) based on novel formulation methods are reported. Finally, the development of biopharmaceuticals (e.g., bacillus Calmette-Guérin, interferon α) and gene therapies is also presented and analyzed in this review. The present review exhibits new development in the pipeline for emerging intravesical drug administration strategies. Knowledge of all these therapies allows practitioners to propose a specific and tailored treatment to each patient with limiting systemic side effects. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
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Simpson, Sean S; Adams, Nikki; Brugman, Claudia M; Conners, Thomas J
2018-01-08
With the rapid development of new psychoactive substances (NPS) and changes in the use of more traditional drugs, it is increasingly difficult for researchers and public health practitioners to keep up with emerging drugs and drug terms. Substance use surveys and diagnostic tools need to be able to ask about substances using the terms that drug users themselves are likely to be using. Analyses of social media may offer new ways for researchers to uncover and track changes in drug terms in near real time. This study describes the initial results from an innovative collaboration between substance use epidemiologists and linguistic scientists employing techniques from the field of natural language processing to examine drug-related terms in a sample of tweets from the United States. The objective of this study was to assess the feasibility of using distributed word-vector embeddings trained on social media data to uncover previously unknown (to researchers) drug terms. In this pilot study, we trained a continuous bag of words (CBOW) model of distributed word-vector embeddings on a Twitter dataset collected during July 2016 (roughly 884.2 million tokens). We queried the trained word embeddings for terms with high cosine similarity (a proxy for semantic relatedness) to well-known slang terms for marijuana to produce a list of candidate terms likely to function as slang terms for this substance. This candidate list was then compared with an expert-generated list of marijuana terms to assess the accuracy and efficacy of using word-vector embeddings to search for novel drug terminology. The method described here produced a list of 200 candidate terms for the target substance (marijuana). Of these 200 candidates, 115 were determined to in fact relate to marijuana (65 terms for the substance itself, 50 terms related to paraphernalia). This included 30 terms which were used to refer to the target substance in the corpus yet did not appear on the expert-generated list and were
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Shridharani, Sachin M; Magarakis, Michael; Manson, Paul N; Singh, Navin K; Basdag, Basak; Rosson, Gedge D
2010-03-01
The management of keloids and hypertrophic scars continues to challenge health-care providers. Though both forms of pathologic scarring are distinct entities at the macro and microscopic level, their etiologies and treatment are often similar. Potential treatment approaches are progressing, and combinations of treatment options have been proposed in the literature with promising outcomes. The treatment evolution has reached a level where molecular therapeutic modalities are being investigated. Currently, no gold standard treatment exists. Overall success rates and patient satisfaction seem to be slowly climbing, but additional investigational studies must continue to be performed. Several studies have investigated antineoplastic agents, and there seems to be a marked improvement in rates of recurrence, patient satisfaction, and overall quality of scar when these agents are used. Intralesional injection and/or wound irrigation with interferon-a2b, interferon-g, mitomycin-C, bleomycin, or 5-fluorouracil seems to have a positive effect on the reduction of pathologic scars. There is mounting evidence that these drugs used alone or in combination therapy, have the potential to be an integral part of the treatment paradigm for hypertrophic scars and keloids.
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The IHO as Actor The case of cannabis and the Single Convention on Narcotic Drugs 1961
Directory of Open Access Journals (Sweden)
James H. Mills
2016-12-01
Full Text Available After the Second World War the United Nations (UN assumed the role of the League of Nations in formulating and operating the international regulatory framework for narcotic drugs. It gathered masses of information from across countries and continents while acting as both a forum and an agent for the emergence of agreed approaches to a heterodox array of substances. This article will examine the story of the inclusion of cannabis in the 1961 Single Convention on Narcotic Drugs. It will argue that in the years after 1945, it was officials at the UN and the WHO that played crucial roles in shaping opinions of the drug and in securing its place in the Convention.
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Directory of Open Access Journals (Sweden)
S. R. Gilyarevsky
2014-07-01
Full Text Available The role of P2Y12 receptor blocker clopidogrel after the introduction into clinical practice of new, more powerful and stable operating drugs belonging to this class of antiplatelet agents is discussed. The advantages and disadvantages of each of the currently used antiplatelet drugs that block the receptor P2Y12 are reviewed. On the basis of the analysis concludes that, despite the emergence of new antiplatelet agents clopidogrel, appears to be widely used for a long time in the treatment of patients with acute coronary syndrome and / or after coronary stenting. This is primarily due to the presence of large evidence base, and confirmation of safety of long-term therapy clopidogrel.
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Pain Management in the Emergency Department: a Review Article on Options and Methods
Directory of Open Access Journals (Sweden)
Ali Abdolrazaghnejad
2018-06-01
Full Text Available Context: The aim of this review is to recognizing different methods of analgesia for emergency medicine physicians (EMPs allows them to have various pain relief methods to reduce pain and to be able to use it according to the patient’s condition and to improve the quality of their services. Evidence acquisition: In this review article, the search engines and scientific databases of Google Scholar, Science Direct, PubMed, Medline, Scopus, and Cochrane for emergency pain management methods were reviewed. Among the findings, high quality articles were eventually selected from 2000 to 2018, and after reviewing them, we have conducted a comprehensive comparison of the usual methods of pain control in the emergency department (ED. Results: For better understanding, the results are reported in to separate subheadings including “Parenteral agents” and “Regional blocks”. Non-opioids analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs and acetaminophen are commonly used in the treatment of acute pain. However, the relief of acute moderate to severe pain usually requires opioid agents. Considering the side effects of systemic drugs and the restrictions on the use of analgesics, especially opioids, regional blocks of pain as part of a multimodal analgesic strategy can be helpful. Conclusion: This study was designed to investigate and identify the disadvantages and advantages of using each drug to be able to make the right choices in different clinical situations for patients while paying attention to the limitations of the use of these analgesic drugs.
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MODELING OF TARGETED DRUG DELIVERY PART II. MULTIPLE DRUG ADMINISTRATION
Directory of Open Access Journals (Sweden)
A. V. Zaborovskiy
2017-01-01
Full Text Available In oncology practice, despite significant advances in early cancer detection, surgery, radiotherapy, laser therapy, targeted therapy, etc., chemotherapy is unlikely to lose its relevance in the near future. In this context, the development of new antitumor agents is one of the most important problems of cancer research. In spite of the importance of searching for new compounds with antitumor activity, the possibilities of the “old” agents have not been fully exhausted. Targeted delivery of antitumor agents can give them a “second life”. When developing new targeted drugs and their further introduction into clinical practice, the change in their pharmacodynamics and pharmacokinetics plays a special role. The paper describes a pharmacokinetic model of the targeted drug delivery. The conditions under which it is meaningful to search for a delivery vehicle for the active substance were described. Primary screening of antitumor agents was undertaken to modify them for the targeted delivery based on underlying assumptions of the model.
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21 CFR 290.10 - Definition of emergency situation.
2010-04-01
... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Definition of emergency situation. 290.10 Section...) DRUGS: GENERAL CONTROLLED DRUGS General Provisions § 290.10 Definition of emergency situation. For the... Controlled Substances Act, the term emergency situation means those situations in which the prescribing...
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Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications.
Kannan, R M; Nance, E; Kannan, S; Tomalia, D A
2014-12-01
Dendrimers are discrete nanostructures/nanoparticles with 'onion skin-like' branched layers. Beginning with a core, these nanostructures grow in concentric layers to produce stepwise increases in size that are similar to the dimensions of many in vivo globular proteins. These branched tree-like concentric layers are referred to as 'generations'. The outer generation of each dendrimer presents a precise number of functional groups that may act as a monodispersed platform for engineering favourable nanoparticle-drug and nanoparticle-tissue interactions. These features have attracted significant attention in medicine as nanocarriers for traditional small drugs, proteins, DNA/RNA and in some instances as intrinsically active nanoscale drugs. Dendrimer-based drugs, as well as diagnostic and imaging agents, are emerging as promising candidates for many nanomedicine applications. First, we will provide a brief survey of recent nanomedicines that are either approved or in the clinical approval process. This will be followed by an introduction to a new 'nanoperiodic' concept which proposes nanoparticle structure control and the engineering of 'critical nanoscale design parameters' (CNDPs) as a strategy for optimizing pharmocokinetics, pharmocodynamics and site-specific targeting of disease. This paradigm has led to the emergence of CNDP-directed nanoperiodic property patterns relating nanoparticle behaviour to critical in vivo clinical translation issues such as cellular uptake, transport, elimination, biodistribution, accumulation and nanotoxicology. With a focus on dendrimers, these CNDP-directed nanoperiodic patterns are used as a strategy for designing and optimizing nanoparticles for a variety of drug delivery and imaging applications, including a recent dendrimer-based theranostic nanodevice for imaging and treating cancer. Several emerging preclinical dendrimer-based nanotherapy concepts related to inflammation, neuro-inflammatory disorders, oncology and infectious
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Cenek, Martin; Dahl, Spencer K.
2016-11-01
Systems with non-linear dynamics frequently exhibit emergent system behavior, which is important to find and specify rigorously to understand the nature of the modeled phenomena. Through this analysis, it is possible to characterize phenomena such as how systems assemble or dissipate and what behaviors lead to specific final system configurations. Agent Based Modeling (ABM) is one of the modeling techniques used to study the interaction dynamics between a system's agents and its environment. Although the methodology of ABM construction is well understood and practiced, there are no computational, statistically rigorous, comprehensive tools to evaluate an ABM's execution. Often, a human has to observe an ABM's execution in order to analyze how the ABM functions, identify the emergent processes in the agent's behavior, or study a parameter's effect on the system-wide behavior. This paper introduces a new statistically based framework to automatically analyze agents' behavior, identify common system-wide patterns, and record the probability of agents changing their behavior from one pattern of behavior to another. We use network based techniques to analyze the landscape of common behaviors in an ABM's execution. Finally, we test the proposed framework with a series of experiments featuring increasingly emergent behavior. The proposed framework will allow computational comparison of ABM executions, exploration of a model's parameter configuration space, and identification of the behavioral building blocks in a model's dynamics.
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Endogenous antispermatogenic agents: prospects for male contraception.
Ewing, L L; Robaire, B
1978-01-01
A review of endogenous antispermatogenic agents as prospects for male contraception is reported. It is demonstrated that endogenous compounds exert regulatory influences at 4 major levels in the male: 1) between germ cells; 2) between Sertoli and germ cells; 3) between Leydig cells and seminiferous tubules; and 4) between the central nervous system and the testis. Efforts to interrupt spermatogenesis have failed to find application as male contraceptives for various reasons: 1) some investigators ignored the vulnerable control points by utilizing nonspecific agents; 2) others attacked a vulnerable control point but used synthetic drugs that had deleterious side effects; and 3) still others attacked a vulnerable control point with a relatively innocuous drug but used an impractical mode of drug administration. The potential for devising innovative techniques for administering relatively innocuous drugs at dosages sufficient to produce sterility without causing deleterious side effects is demonstrated. The most promising solution for the development of an antispermatogenic male contraceptive is the interference with the adenohypophyseal-gonadal axis via the subcutaneous sustained release of steroid formulations containing either androgen-danazol, androgen-progestin, or androgen-estrogen formulations. Another promising agent would be luteinizing releasing hormone agonist-androgen formulation.
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Emerging drugs for the treatment of obesity
DEFF Research Database (Denmark)
Martinussen, Christoffer; Bojsen-Møller, Kirstine Nyvold; Svane, Maria Saur
2017-01-01
INTRODUCTION: The increasing prevalence of obesity represents a huge threat to public health and the current pharmacological treatment options are limited. Bariatric surgery is by far the most effective treatment for severe obesity, highlighting the urgent need for new and improved drug therapies....... Areas covered: Based on the physiological regulation of energy homeostasis, pharmacological strategies to treat obesity are evaluated with focus on drugs in phase 2 and 3 clinical development. The potential impact of these drugs on current treatment standards and the barriers for development...... are discussed and set in a historical perspective of previous antiobesity medications. Expert opinion: The radical effects of bariatric surgery have extended our understanding of the mechanisms controlling appetite and boosted the search for new drug targets in obesity treatment. Accordingly, several compounds...
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DNA nanomaterials for preclinical imaging and drug delivery.
Jiang, Dawei; England, Christopher G; Cai, Weibo
2016-10-10
Besides being the carrier of genetic information, DNA is also an excellent biological organizer to establish well-designed nanostructures in the fields of material engineering, nanotechnology, and biomedicine. DNA-based materials represent a diverse nanoscale system primarily due to their predictable base pairing and highly regulated conformations, which greatly facilitate the construction of DNA nanostructures with distinct shapes and sizes. Integrating the emerging advancements in bioconjugation techniques, DNA nanostructures can be readily functionalized with high precision for many purposes ranging from biosensors to imaging to drug delivery. Recent progress in the field of DNA nanotechnology has exhibited collective efforts to employ DNA nanostructures as smart imaging agents or delivery platforms within living organisms. Despite significant improvements in the development of DNA nanostructures, there is limited knowledge regarding the in vivo biological fate of these intriguing nanomaterials. In this review, we summarize the current strategies for designing and purifying highly-versatile DNA nanostructures for biological applications, including molecular imaging and drug delivery. Since DNA nanostructures may elicit an immune response in vivo, we also present a short discussion of their potential toxicities in biomedical applications. Lastly, we discuss future perspectives and potential challenges that may limit the effective preclinical and clinical employment of DNA nanostructures. Due to their unique properties, we predict that DNA nanomaterials will make excellent agents for effective diagnostic imaging and drug delivery, improving patient outcome in cancer and other related diseases in the near future. Copyright © 2016 Elsevier B.V. All rights reserved.
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21 CFR 178.3295 - Clarifying agents for polymers.
2010-04-01
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Clarifying agents for polymers. 178.3295 Section... SANITIZERS Certain Adjuvants and Production Aids § 178.3295 Clarifying agents for polymers. Clarifying agents may be safely used in polymers that are articles or components of articles intended for use in contact...
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Novel 3-nitrotriazole-based amides and carbinols as bifunctional anti-Chagasic agents
Papadopoulou, Maria V.; Bloomer, William D.; Lepesheva, Galina I.; Rosenzweig, Howard S.; Kaiser, Marcel; Aguilera-Venegas, Benjamín; Wilkinson, Shane R.; Chatelain, Eric; Ioset, Jean-Robert
2015-01-01
3-Nitro-1H-1,2,4-triazole-based amides with a linear, rigid core and 3-nitrotriazole-based fluconazole analogs were synthesized as dual functioning antitrypanosomal agents. Such compounds are excellent substrates for type I nitroreductase (NTR) located in the mitochondrion of trypanosomatids and, at the same time, act as inhibitors of the sterol 14α-demethylase (T. cruzi CYP51) enzyme. Because combination treatments against parasites are often superior to monotherapy, we believe that this emerging class of bifunctional compounds may introduce a new generation of antitrypanosomal drugs. In the present work, the synthesis and in vitro and in vivo evaluation of such compounds is discussed. PMID:25580906
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Nachajski, Michal Jakub; Zgoda, Marian Mikołaj
2010-01-01
Pre-formulation research was conducted on the application of Ex. Echinaceae aq. siccum in the production of a quickly disintegrating suspension tablet, a lozenge with kariostatic sugar alcohols (mannitol, sorbitol), and, above all, a solid drug form with controlled release of therapeutic agents included in the extract. Morphological parameters of tablets obtained in the course of experiment were estimated and the profiles of the release (diffusion) ofhydrophilic therapeutic agents into model receptor fluids with varying values of osmolarity (0.1 mol HCl approximately 200 mOsm/l, hypotonic hydrating fluid approximately 143 mOsm/l, and compensatory paediatric fluid approximately 272 mOsm/l) were examined. The study focused on the technological problem of determining the effect of hydrogel Carbopol structure on the ordering of diffusion ofhydrophilic therapeutic agents from a model drug form (a tablet) into model fluids with variable osmolarity.
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Recent advances in the research of heterocyclic compounds as antitubercular agents.
Yan, Mi; Ma, Shutao
2012-12-01
Tuberculosis (TB) is a major health problem, with approximately one-third of the world's population infected with Mycobacterium tuberculosis, eight million people in the active disease state, and two million dying annually. Furthermore, the prevalence of TB/HIV co-infection, and the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) have further aggravated the spread of this disease and thus mortality by it. There is an urgent need for novel antitubercular agents with improved properties, such as lower toxicity, shortened duration of therapy, rapid bactericidal action, and enhanced activity against MDR strains. Fortunately, a number of new potential antitubercular candidate drugs with heterocyclic rings, which are most likely to be effective against resistant strains, have entered clinical trials in recent years. This review highlights recent advances in the research of novel heterocyclic compounds, with particular focus on their antimycobacterial activity, mechanisms of action, toxicity, and structure-activity relationships (SARs). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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2016 guidelines for the use of antifungal agents in patients with invasive fungal diseases in Taiwan
Directory of Open Access Journals (Sweden)
Hsiang-Chi Kung
2018-02-01
Full Text Available The Infectious Diseases Society of Taiwan, Medical Foundation in Memory of Dr. Deh-Lin Cheng, Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education, and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines have updated the guidelines for the use of antifungal agents in adult patients with invasive fungal diseases in Taiwan. This guideline replaces the 2009 version. Recommendations are provided for Candida, Cryptococcus, Aspergillus and Mucormycetes. The focus is based on up-to-date evidence on indications for treatment or prophylaxis of the most common clinical problems. To support the recommendations in this guideline, the committee considered the rationale, purpose, local epidemiology, and key clinical features of invasive fungal diseases to select the primary and alternative antifungal agents. This is the first guideline that explicitly describes the quality and strength of the evidence to support these recommendations. The strengths of the recommendations are the quality of the evidence, the balance between benefits and harms, resource and cost. The guidelines are not intended nor recommended as a substitute for bedside judgment in the management of individual patients, the advice of qualified health care professionals, and more recent evidence concerning therapeutic efficacy and emergence of resistance. Practical considerations for individualized selection of antifungal agents include patient factors, pathogen, site of infection and drug-related factors, such as drug–drug interaction, drug-food intervention, cost and convenience. The guidelines are published in the Journal of Microbiology, Immunology and Infection and are also available on the Society website.
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International Nuclear Information System (INIS)
Kangaspeska, Sara; Hultsch, Susanne; Jaiswal, Alok; Edgren, Henrik; Mpindi, John-Patrick; Eldfors, Samuli; Brück, Oscar; Aittokallio, Tero; Kallioniemi, Olli
2016-01-01
The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains. Using high throughput drug sensitivity and resistance testing (DSRT) with 279 approved and investigational oncology drugs, exome-sequencing and network analysis, we for the first time, systematically determine the drug response profiles specific to tamoxifen resistance. We discovered emerging vulnerabilities towards specific drugs, such as ERK1/2-, proteasome- and BCL-family inhibitors as the cells became tamoxifen-resistant. Co-resistance to other drugs such as the survivin inhibitor YM155 and the chemotherapeutic agent paclitaxel also occurred. This study indicates that multiple molecular mechanisms dictate endocrine resistance, resulting in unexpected vulnerabilities to initially ineffective drugs, as well as in emerging co-resistances. Thus, combatting drug-resistant tumors will require patient-tailored strategies in order to identify new drug vulnerabilities, and to understand the associated co-resistance patterns. The online version of this article (doi:10.1186/s12885-016-2452-5) contains supplementary material, which is available to authorized users
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Use of allosteric targets in the discovery of safer drugs.
Grover, Ashok Kumar
2013-01-01
The need for drugs with fewer side effects cannot be overemphasized. Today, most drugs modify the actions of enzymes, receptors, transporters and other molecules by directly binding to their active (orthosteric) sites. However, orthosteric site configuration is similar in several proteins performing related functions and this leads to a lower specificity of a drug for the desired protein. Consequently, such drugs may have adverse side effects. A new basis of drug discovery is emerging based on the binding of the drug molecules to sites away (allosteric) from the orthosteric sites. It is possible to find allosteric sites which are unique and hence more specific as targets for drug discovery. Of many available examples, two are highlighted here. The first is caloxins - a new class of highly specific inhibitors of plasma membrane Ca²⁺ pumps. The second concerns the modulation of receptors for the neurotransmitter acetylcholine, which binds to 12 types of receptors. Exploitation of allosteric sites has led to the discovery of drugs which can selectively modulate the activation of only 1 (M1 muscarinic) out of the 12 different types of acetylcholine receptors. These drugs are being tested for schizophrenia treatment. It is anticipated that the drug discovery exploiting allosteric sites will lead to more effective therapeutic agents with fewer side effects. Copyright © 2013 S. Karger AG, Basel.
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Intelligent Agents under Collaborative Control in Emerging Power ...
African Journals Online (AJOL)
In the DECENT0F 1 R&D initiative we developed a multi-level, bottom-up solution where autonomous collaborative software agents negotiate available energy quantities and needs on behalf of consumer and producer groups (the DEZENT algorithm). We operate within very short time intervals of assumedly constant ...
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Emerging advances in nanomedicine with engineered gold nanostructures.
Webb, Joseph A; Bardhan, Rizia
2014-03-07
Gold nanostructures possess unique characteristics that enable their use as contrast agents, as therapeutic entities, and as scaffolds to adhere functional molecules, therapeutic cargo, and targeting ligands. Due to their ease of synthesis, straightforward surface functionalization, and non-toxicity, gold nanostructures have emerged as powerful nanoagents for cancer detection and treatment. This comprehensive review summarizes the progress made in nanomedicine with gold nanostructures (1) as probes for various bioimaging techniques including dark-field, one-photon and two-photon fluorescence, photothermal optical coherence tomography, photoacoustic tomography, positron emission tomography, and surface-enhanced Raman scattering based imaging, (2) as therapeutic components for photothermal therapy, gene and drug delivery, and radiofrequency ablation, and (3) as a theranostic platform to simultaneously achieve both cancer detection and treatment. Distinct from other published reviews, this article also discusses the recent advances of gold nanostructures as contrast agents and therapeutic actuators for inflammatory diseases including atherosclerotic plaque and arthritis. For each of the topics discussed above, the fundamental principles and progress made in the past five years are discussed. The review concludes with a detailed future outlook discussing the challenges in using gold nanostructures, cellular trafficking, and translational considerations that are imperative for rapid clinical viability of plasmonic nanostructures, as well as the significance of emerging technologies such as Fano resonant gold nanostructures in nanomedicine.
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Psychosis associated with acute recreational drug toxicity: a European case series.
Vallersnes, Odd Martin; Dines, Alison M; Wood, David M; Yates, Christopher; Heyerdahl, Fridtjof; Hovda, Knut Erik; Giraudon, Isabelle; Dargan, Paul I
2016-08-18
Psychosis can be associated with acute recreational drug and novel psychoactive substance (NPS) toxicity. However, there is limited data available on how common this is and which drugs are most frequently implicated. We describe a European case series of psychosis associated with acute recreational drug toxicity, and estimate the frequency of psychosis for different recreational drugs. The European Drug Emergencies Network (Euro-DEN) collects data on presentations to Emergency Departments (EDs) with acute recreational drug and NPS toxicity at 16 centres in ten countries. Euro-DEN data from October 2013 through September 2014 was retrospectively searched, and cases with psychosis were included. The proportion of cases with psychosis per drug was calculated in the searched Euro-DEN dataset. Psychosis was present in 348 (6.3 %) of 5529 cases. The median (interquartile range) age was 29 (24-38) years, 276 (79.3 %) were male and 114 (32.8 %) were admitted to psychiatric ward. The drugs most commonly reported were cannabis in 90 (25.9 %) cases, amphetamine in 87 (25.0 %) and cocaine in 56 (16.1 %). More than one drug was taken in 189 (54.3 %) cases. Psychosis was frequent in those ED presentations involving tryptamines (4/7; 57.1 %), methylenedioxypyrovalerone (MDPV) (6/22; 27.3 %), methylphenidate (6/26; 23.1 %), lysergic acid diethylamide (LSD) (18/86; 20.9 %), psilocybe mushrooms (3/16; 18.8 %), synthetic cannabinoid receptor agonists (4/26; 15.4 %) and amphetamine (87/593; 14.7 %), but less common in those involving mephedrone (14/245; 5.7 %), methylenedioxymethamphetamine (MDMA) (20/461; 4.3 %) and methedrone (3/92; 3.3 %). Amphetamine was the most frequent drug associated with psychosis when only one agent was reported, with psychosis occurring in 32.4 % of these presentations. The frequency of psychosis in acute recreational drug toxicity varies considerably between drugs, but is a major problem in amphetamine poisoning. In rapidly changing drug markets and
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Emergence of Leadership in Communication
Allahverdyan, Armen E.; Galstyan, Aram
2016-01-01
We study a neuro-inspired model that mimics a discussion (or information dissemination) process in a network of agents. During their interaction, agents redistribute activity and network weights, resulting in emergence of leader(s). The model is able to reproduce the basic scenarios of leadership known in nature and society: laissez-faire (irregular activity, weak leadership, sizable inter-follower interaction, autonomous sub-leaders); participative or democratic (strong leadership, but with feedback from followers); and autocratic (no feedback, one-way influence). Several pertinent aspects of these scenarios are found as well—e.g., hidden leadership (a hidden clique of agents driving the official autocratic leader), and successive leadership (two leaders influence followers by turns). We study how these scenarios emerge from inter-agent dynamics and how they depend on behavior rules of agents—in particular, on their inertia against state changes. PMID:27532484
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International Nuclear Information System (INIS)
Song, Cunfeng; Yu, Shirong; Liu, Cheng; Deng, Yuanming; Xu, Yiting; Chen, Xiaoling; Dai, Lizong
2016-01-01
A methodology to prepare thermo-responsive graft copolymer by using a novel macro-RAFT agent was proposed. The macro-RAFT agent with pendant dithioester (ZC(S)SR) was facilely prepared via the combination of RAFT polymerization and esterification reaction. By means of ZC(S)SR-initiated RAFT polymerization, the thermo-responsive graft copolymer consisting of poly(methyl methacrylate-co-hydroxylethyl methacrylate) (P(MMA-co-HEMA)) backbone and hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) side chains was constructed through the “grafting from” approach. The chemical compositions and molecular weight distributions of the synthesized polymers were respectively characterized by "1H nuclear magnetic resonance ("1H NMR) and gel permeation chromatography (GPC). Self-assembly behavior of the amphiphilic graft copolymers (P(MMA-co-HEMA)-g-PNIPAAm) was studied by transmission electron microscopy (TEM), dynamic light scattering (DLS) and spectrofluorimeter. The critical micelle concentration (CMC) value was 0.052 mg mL"−"1. These micelles have thermo-responsibility and a low critical solution temperature (LCST) of 33.5 °C. Further investigation indicated that the guest molecule release property of these micelles, which can be well described by a first-order kinetic model, was significantly affected by temperature. Besides, the micelles exhibited excellent biocompatibility and cellular uptake property. Hence, these micelles are considered to have potential application in controlled drug delivery. - Highlights: • A novel macro-RAFT agent with ZC(S)SR was used for preparing graft copolymer. • P(MMA-co-HEMA)-g-PNIPAAm was successful prepared via the “grafting from” approach. • Thermo-responsibility of the P(MMA-co-HEMA)-g-PNIPAAm micelles was investigated. • The drug release behavior of the P(MMA-co-HEMA)-g-PNIPAAm micelles was studied. • These micelles exhibited excellent biocompatibility and cellular uptake property.
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Energy Technology Data Exchange (ETDEWEB)
Song, Cunfeng; Yu, Shirong [Department of Materials Science and Engineering, College of Materials, Xiamen University, Xiamen 361005 (China); Liu, Cheng; Deng, Yuanming; Xu, Yiting [Department of Materials Science and Engineering, College of Materials, Xiamen University, Xiamen 361005 (China); Fujian Provincial Key Laboratory of Fire Retardant Materials, Xiamen University, Xiamen 361005 (China); Chen, Xiaoling, E-mail: tinachen0628@163.com [Department of Endodontics, Xiamen Stomatology Hospital, Teaching Hospital of Fujian Medical University, Xiamen 361003 (China); Dai, Lizong, E-mail: lzdai@xmu.edu.cn [Department of Materials Science and Engineering, College of Materials, Xiamen University, Xiamen 361005 (China); Fujian Provincial Key Laboratory of Fire Retardant Materials, Xiamen University, Xiamen 361005 (China)
2016-05-01
A methodology to prepare thermo-responsive graft copolymer by using a novel macro-RAFT agent was proposed. The macro-RAFT agent with pendant dithioester (ZC(S)SR) was facilely prepared via the combination of RAFT polymerization and esterification reaction. By means of ZC(S)SR-initiated RAFT polymerization, the thermo-responsive graft copolymer consisting of poly(methyl methacrylate-co-hydroxylethyl methacrylate) (P(MMA-co-HEMA)) backbone and hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) side chains was constructed through the “grafting from” approach. The chemical compositions and molecular weight distributions of the synthesized polymers were respectively characterized by {sup 1}H nuclear magnetic resonance ({sup 1}H NMR) and gel permeation chromatography (GPC). Self-assembly behavior of the amphiphilic graft copolymers (P(MMA-co-HEMA)-g-PNIPAAm) was studied by transmission electron microscopy (TEM), dynamic light scattering (DLS) and spectrofluorimeter. The critical micelle concentration (CMC) value was 0.052 mg mL{sup −1}. These micelles have thermo-responsibility and a low critical solution temperature (LCST) of 33.5 °C. Further investigation indicated that the guest molecule release property of these micelles, which can be well described by a first-order kinetic model, was significantly affected by temperature. Besides, the micelles exhibited excellent biocompatibility and cellular uptake property. Hence, these micelles are considered to have potential application in controlled drug delivery. - Highlights: • A novel macro-RAFT agent with ZC(S)SR was used for preparing graft copolymer. • P(MMA-co-HEMA)-g-PNIPAAm was successful prepared via the “grafting from” approach. • Thermo-responsibility of the P(MMA-co-HEMA)-g-PNIPAAm micelles was investigated. • The drug release behavior of the P(MMA-co-HEMA)-g-PNIPAAm micelles was studied. • These micelles exhibited excellent biocompatibility and cellular uptake property.
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Vibrio cholerae infection, novel drug targets and phage therapy.
Fazil, Mobashar Hussain Urf Turabe; Singh, Durg V
2011-10-01
Vibrio cholerae is the causative agent of the diarrheal disease cholera. Although antibiotic therapy shortens the duration of diarrhea, excessive use has contributed to the emergence of antibiotic resistance in V. cholerae. Mobile genetic elements have been shown to be largely responsible for the shift of drug resistance genes in bacteria, including some V. cholerae strains. Quorum sensing communication systems are used for interaction among bacteria and for sensing environmental signals. Sequence analysis of the ctxB gene of toxigenic V. cholerae strains demonstrated its presence in multiple cholera toxin genotypes. Moreover, bacteriophage that lyse the bacterium have been reported to modulate epidemics by decreasing the required infectious dose of the bacterium. In this article, we will briefly discuss the disease, its clinical manifestation, antimicrobial resistance and the novel approaches to locate drug targets to treat cholera.
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Blow, Frederic C; Walton, Maureen A; Bohnert, Amy S B; Ignacio, Rosalinda V; Chermack, Stephen; Cunningham, Rebecca M; Booth, Brenda M; Ilgen, Mark; Barry, Kristen L
2017-08-01
To examine efficacy of drug brief interventions (BIs) among adults presenting to a low-income urban emergency department (ED). Randomized controlled trial on drug use outcomes at 3, 6 and 12 months. Participants were assigned to (1) computer-delivered BI (Computer BI), (2) therapist-delivered, computer-guided BI (Therapist BI) or (3) enhanced usual care (EUC-ED) for drug-using adults. Participants were re-randomized after the 3-month assessment to either adapted motivational enhancement therapy (AMET) booster or enhanced usual care booster (EUC-B). Patients recruited from low-income urban emergency departments (ED) in Flint, Michigan, USA. A total of 780 ED patients reporting recent drug use, 44% males, mean age = 31 years. Computer BI consisted of an interactive program guided by a virtual health counselor. Therapist BI included computer guidance. The EUC-ED conditions included review of community health and HIV prevention resources. The BIs and boosters were based on motivational interviewing, focusing on reduction of drug use and HIV risk behaviors. Primary outcome was past 90 days using drugs at 6 and 12 months and secondary outcomes were weighted drug-days and days of marijuana use. Percentage changes in mean days used any drug from baseline to 12 months were: Computer BI + EUC-B: -10.9%, P = 0.0844; Therapist BI + EUC-B: -26.7%, P = 0.0041, for EUC-ED + EUC-B: -20.9, P = 0.0011. In adjusted analyses, there was no significant interaction between ED intervention and booster AMET for primary and secondary outcomes. Compared with EUC-ED, Therapist BI reduced number of days using any drug [95% confidence interval (CI) = -0.41, -0.07, P = 0.0422] and weighted drug-days (95% CI = -0.41, -0.08, P = 0.0283). Both Therapist and Computer BI had significantly fewer number of days using marijuana compared to EUC-ED (Therapist BI: 95% CI = -0.42, -0.06, P = 0.0104, Computer BI: 95% CI = -0.34, -0.01, P = 0.0406). Booster effects were not
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Raschi, Emanuel; De Ponti, Fabrizio
2015-07-08
Drug-induced liver injury (DILI) and herb-induced liver injury is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications in the past 15 years. This review will first provide clues for clinicians to suspect idiosyncratic (unpredictable) DILI and succeed in diagnosis. Causality assessment remains challenging and requires careful medical history as well as awareness of multifaceted aspects, especially for herbs. Drug discontinuation and therapy reconciliation remain the mainstay in patent's management to minimize occurrence of acute liver failure. The second section will address novel agents associated with liver injury in 2014 (referred to as "signals"), especially in terms of clinical, research and drug development implications. Insights will be provided into recent trends by highlighting the contribution of different post-marketing data, especially registries and spontaneous reporting systems. This literature scrutiny suggests: (1) the importance of post-marketing databases as tools of clinical evidence to detect signals of DILI risk; and (2) the need for joining efforts in improving predictivity of pre-clinical assays, continuing post-marketing surveillance and design ad hoc post-authorization safety studies. In this context, ongoing European/United States research consortia and novel pharmaco-epidemiological tools (e.g., specialist prescription event monitoring) will support innovation in this field. Direct oral anticoagulants and herbal/dietary supplements appear as key research priorities.
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Preventing drug resistance in severe influenza
Dobrovolny, Hana; Deecke, Lucas
2015-03-01
Severe, long-lasting influenza infections are often caused by new strains of influenza. The long duration of these infections leads to an increased opportunity for the emergence of drug resistant mutants. This is particularly problematic for new strains of influenza since there is often no vaccine, so drug treatment is the first line of defense. One strategy for trying to minimize drug resistance is to apply periodic treatment. During treatment the wild-type virus decreases, but resistant virus might increase; when there is no treatment, wild-type virus will hopefully out-compete the resistant virus, driving down the number of resistant virus. We combine a mathematical model of severe influenza with a model of drug resistance to study emergence of drug resistance during a long-lasting infection. We apply periodic treatment with two types of antivirals: neuraminidase inhibitors, which block release of virions; and adamantanes, which block replication of virions. We compare the efficacy of the two drugs in reducing emergence of drug resistant mutants and examine the effect of treatment frequency on the emergence of drug resistant mutants.
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Novel versus conventional antipsychotic drugs.
Love, R C
1996-01-01
Novel antipsychotic agents differ from conventional ones in several key characteristics, including effectiveness, adverse reactions, and receptor-binding profile. Most of the newer agents have an affinity for the serotonin 5HT2 receptor that is at least 10 times greater than that for the dopamine D2 receptor. This increased affinity for the serotonin receptor may be responsible for another distinguishing characteristic of novel antipsychotic agents--decreased frequency of extrapyramidal side effects. These side effects, which include pseudoparkinsonism, acute dystonias, and akathisia, frequently are the reason for noncompliance with conventional drug therapy. The newer drugs are often effective in patients resistant to treatment with conventional agents. They also appear to reduce the negative symptoms of schizophrenia in many patients.
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Jiang, Yanjiao; Chen, Jing; Deng, Chao; Suuronen, Erik J; Zhong, Zhiyuan
2014-06-01
Hydrogels, microgels and nanogels have emerged as versatile and viable platforms for sustained protein release, targeted drug delivery, and tissue engineering due to excellent biocompatibility, a microporous structure with tunable porosity and pore size, and dimensions spanning from human organs, cells to viruses. In the past decade, remarkable advances in hydrogels, microgels and nanogels have been achieved with click chemistry. It is a most promising strategy to prepare gels with varying dimensions owing to its high reactivity, superb selectivity, and mild reaction conditions. In particular, the recent development of copper-free click chemistry such as strain-promoted azide-alkyne cycloaddition, radical mediated thiol-ene chemistry, Diels-Alder reaction, tetrazole-alkene photo-click chemistry, and oxime reaction renders it possible to form hydrogels, microgels and nanogels without the use of potentially toxic catalysts or immunogenic enzymes that are commonly required. Notably, unlike other chemical approaches, click chemistry owing to its unique bioorthogonal feature does not interfere with encapsulated bioactives such as living cells, proteins and drugs and furthermore allows versatile preparation of micropatterned biomimetic hydrogels, functional microgels and nanogels. In this review, recent exciting developments in click hydrogels, microgels and nanogels, as well as their biomedical applications such as controlled protein and drug release, tissue engineering, and regenerative medicine are presented and discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Directory of Open Access Journals (Sweden)
Maria P. Crespo-Ortiz
2012-01-01
Full Text Available Improvement of quality of life and survival of cancer patients will be greatly enhanced by the development of highly effective drugs to selectively kill malignant cells. Artemisinin and its analogs are naturally occurring antimalarials which have shown potent anticancer activity. In primary cancer cultures and cell lines, their antitumor actions were by inhibiting cancer proliferation, metastasis, and angiogenesis. In xenograft models, exposure to artemisinins substantially reduces tumor volume and progression. However, the rationale for the use of artemisinins in anticancer therapy must be addressed by a greater understanding of the underlying mechanisms involved in their cytotoxic effects. The primary targets for artemisinin and the chemical base for its preferential effects on heterologous tumor cells need yet to be elucidated. The aim of this paper is to provide an overview of the recent advances and new development of this class of drugs as potential anticancer agents.
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Fragment-based approaches to anti-HIV drug discovery: state of the art and future opportunities.
Huang, Boshi; Kang, Dongwei; Zhan, Peng; Liu, Xinyong
2015-12-01
The search for additional drugs to treat HIV infection is a continuing effort due to the emergence and spread of HIV strains resistant to nearly all current drugs. The recent literature reveals that fragment-based drug design/discovery (FBDD) has become an effective alternative to conventional high-throughput screening strategies for drug discovery. In this critical review, the authors describe the state of the art in FBDD strategies for the discovery of anti-HIV drug-like compounds. The article focuses on fragment screening techniques, direct fragment-based design and early hit-to-lead progress. Rapid progress in biophysical detection and in silico techniques has greatly aided the application of FBDD to discover candidate agents directed at a variety of anti-HIV targets. Growing evidence suggests that structural insights on key proteins in the HIV life cycle can be applied in the early phase of drug discovery campaigns, providing valuable information on the binding modes and efficiently prompting fragment hit-to-lead progression. The combination of structural insights with improved methodologies for FBDD, including the privileged fragment-based reconstruction approach, fragment hybridization based on crystallographic overlays, fragment growth exploiting dynamic combinatorial chemistry, and high-speed fragment assembly via diversity-oriented synthesis followed by in situ screening, offers the possibility of more efficient and rapid discovery of novel drugs for HIV-1 prevention or treatment. Though the use of FBDD in anti-HIV drug discovery is still in its infancy, it is anticipated that anti-HIV agents developed via fragment-based strategies will be introduced into the clinic in the future.
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Si, Ting; Zhang, Leilei; Li, Guangbin; Roberts, Cynthia J; Yin, Xiezhen; Xu, Ronald
2013-07-01
Recent developments in multimodal imaging and image-guided therapy requires multilayered microparticles that encapsulate several imaging and therapeutic agents in the same carrier. However, commonly used microencapsulation processes have multiple limitations such as low encapsulation efficiency and loss of bioactivity for the encapsulated biological cargos. To overcome these limitations, we have carried out both experimental and theoretical studies on coaxial electrospray of multilayered microparticles. On the experimental side, an improved coaxial electrospray setup has been developed. A customized coaxial needle assembly combined with two ring electrodes has been used to enhance the stability of the cone and widen the process parameter range of the stable cone-jet mode. With this assembly, we have obtained poly(lactide-co-glycolide) microparticles with fine morphology and uniform size distribution. On the theoretical side, an instability analysis of the coaxial electrified jet has been performed based on the experimental parameters. The effects of process parameters on the formation of different unstable modes have been studied. The reported experimental and theoretical research represents a significant step toward quantitative control and optimization of the coaxial electrospray process for microencapsulation of multiple drugs and imaging agents in multimodal imaging and image-guided therapy.
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Cost-effectiveness and pricing of antibacterial drugs.
Verhoef, Talitha I; Morris, Stephen
2015-01-01
Growing resistance to antibacterial agents has increased the need for the development of new drugs to treat bacterial infections. Given increasing pressure on limited health budgets, it is important to study the cost-effectiveness of these drugs, as well as their safety and efficacy, to find out whether or not they provide value for money and should be reimbursed. In this article, we systematically reviewed 38 cost-effectiveness analyses of new antibacterial agents. Most studies showed the new antibacterial drugs were cost-effective compared to older generation drugs. Drug pricing is a complicated process, involving different stakeholders, and has a large influence on cost-effectiveness. Value-based pricing is a method to determine the price of a drug at which it can be cost-effective. It is currently unclear what the influence of value-based pricing will be on the prices of new antibacterial agents, but an important factor will be the definition of 'value', which as well as the impact of the drug on patient health might also include other factors such as wider social impact and the health impact of disease. © 2015 The Authors. Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.
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The state-of-the-art of emergency contraception with the cutting edge drug
Directory of Open Access Journals (Sweden)
Sarkar, Narendra Nath
2011-01-01
Full Text Available The objective of this study is to evaluate and elucidated the potential of selective progesterone receptor modulators (SPRMs to be an effective emergency contraception (EC. The data are extracted from the literature through the MEDLINE database service from 2000–2010. The SPRMs are in fact progesterone receptor ligands that could bind to progesterone receptor (PR and exert antagonistic, agonistic or mixed agonist-antagonistic effects. These SPRMs are mifepristone, onapristone, asoprisnil, ulipristal, proellex among other compounds. Currently developed SPRMs may exert contraceptive effects by inhibiting ovulation and retarding endometrial synchronization. Low-doses of progesterone antagonists retard endometrial maturation without affecting ovulation. Mifepristone being a SPRM is effective for prevention of pregnancy but with prostaglandin acts as an excellent abortifacient; yet could not compete with levonorgestrel as EC. However, a single dose of 30 mg ulipristal acetate, another SPRM with similar effectiveness and side effect profiles as 1.5 mg levonorgestrel EC, has shown wider ‘window of effect’ by inhibition of the LH peak even if administered at the advanced pre-ovulatory phase, a time when use of levonorgestrel EC is no longer effective. Thus, ulipristal acetate goes one-step ahead of levonorgestrel in the field of emergency contraception treatment. Further studies are needed to explore the potential of other SPRMs to be cutting edge emergency contraceptive drugs.
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Directory of Open Access Journals (Sweden)
Lucianna Helene Santos
2015-11-01
Full Text Available Reverse transcriptase (RT is a multifunctional enzyme in the human immunodeficiency virus (HIV-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.
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Satpathy, Sushrut Varun; Datta, Supratim; Upreti, Binu
2016-01-01
Diabetes has gradually emerged as one of the most serious public health problems in our country. This underlines the need for timely disease detection and decisive therapeutic intervention. This prospective cross-sectional observational study aims at analyzing the utilization pattern of antidiabetic agents in a remote North-East Indian tertiary care teaching hospital in the perspective of current standard treatment guidelines. Diabetic patients receiving antidiabetic medication, both as outpatients and inpatients in our hospital over a period of 12 months (May 2013-May 2014), were included in this study. The data obtained were sorted and analyzed on the basis of gender, type of therapy, and hospital setting. A total of 310 patients were included in the study. Metformin was the single most frequently prescribed antidiabetic agent (66.8%) followed by the sulfonylureas group (37.4%). Insulin was prescribed in 23.2% of the patients. Combination antidiabetic drug therapy (65.1%) was used more frequently than monotherapy (34.8%). The use of biguanides (P standard treatment guidelines. Increased use of generic drugs is an area with scope for improvement.
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Identification of black market products and potential doping agents in Germany 2010-2013.
Krug, Oliver; Thomas, Andreas; Walpurgis, Katja; Piper, Thomas; Sigmund, Gerd; Schänzer, Wilhelm; Laussmann, Tim; Thevis, Mario
2014-11-01
The desire to increase the athletic performance, to 'optimize' an individual's appearance, and to complement but also to arguably substitute exercise by means of drugs and drug candidates has generated a considerable (illicit) market for compounds such as anabolic-androgenic steroids, stimulants, growth promoting peptide hormones, and so on. Genuinely developed for therapeutic use, their abuse/misuse generates enormous health risks, which has necessitated comprehensive controls of compound trafficking by customs and anti-doping authorities. From 2012 to 2013, the Bureau of Customs Investigation confiscated products containing anabolic-androgenic steroids (AAS; 259 kg), stimulants (13 kg), selective estrogen receptor modulators (SERMs; 24 kg), and human growth hormone (hGH; 3500 ampules). In cooperation with the Bureau and under the umbrella of the European Monitoring Center for Emerging Doping Agents (EuMoCEDA), the Cologne Anti-Doping Laboratory analyzed an additional 337 (black market) products between 2010 and 2013, allowing to monitor developments in drug use and, hence, the anticipation of new challenges in sports drug testing. Main tools utilized in characterizing confiscated materials were liquid chromatography-high resolution mass spectrometry (LC-HRMS), gas chromatography-high resolution mass spectrometry (GC-HRMS), and polyacrylamide gel electrophoresis (PAGE) with subsequent bottom-up identification of peptidic compounds using nano liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS). Among the 337 substances analyzed in the doping control laboratory in Cologne, 67 active ingredients were found, 49 of which being categorized as doping agents by the World Anti-Doping Agency (WADA). A total of 83.7 % accounted for steroidal substances (predominantly testosterone, trenbolone, and nandrolone and corresponding esters), 12.8 % accounted for peptide hormones and growth factors (predominantly hGH and growth hormone releasing peptides (GHRPs)), 3.2 % of
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Deoxypodophyllotoxin: a promising therapeutic agent from herbal medicine.
Khaled, Meyada; Jiang, Zhen-Zhou; Zhang, Lu-Yong
2013-08-26
Recently, biologically active compounds isolated from plants used in herbal medicine have been the center of interest. Deoxypodophyllotoxin (DPT), structurally closely related to the lignan podophyllotoxin, is a potent antitumor and anti-inflammatory agent. However, DPT has not been used clinically yet. Also, DPT from natural sources seems to be unavailable. Hence, it is important to establish alternative resources for the production of such lignan; especially that it is used as a precursor for the semi-synthesis of the cytostatic drugs etoposide phosphate and teniposide. The update paper provides an overview of DPT as an effective anticancer natural compound and a leader for cytotoxic drugs synthesis and development in order to highlight the gaps in our knowledge and explore future research needs. The present review covers the literature available from 1877 to 2012. The information was collected via electronic search using Chinese papers and the major scientific databases including PubMed, Sciencedirect, Web of Science and Google Scholar using the keywords. All abstracts and full-text articles reporting database on the history and current status of DPT were gathered and analyzed. Plants containing DPT have played an important role in traditional medicine. In light of the in vitro pharmacological investigations, DPT is a high valuable medicinal agent that has anti-tumor, anti-proliferative, anti-inflammatory and anti-allergic properties. Further, DPT is an important precursor for the cytotoxic aryltetralin lignan, podophyllotoxin, which is used to obtain semisynthetic derivatives like etoposide and teniposide used in cancer therapy. However, most studies have focused on the in vitro data. Therefore, DPT has not been used clinically yet. DPT has emerged as a potent chemical agent from herbal medicine. Therefore, in vivo studies are needed to carry out clinical trials in humans and enable the development of new anti-cancer agents. In addition, DPT from commercial
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21 CFR 872.6030 - Oral cavity abrasive polishing agent.
2010-04-01
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Oral cavity abrasive polishing agent. 872.6030... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6030 Oral cavity abrasive polishing agent. (a) Identification. An oral cavity abrasive polishing agent is a device in paste or powder form...
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Drugs in development for Parkinson's disease: an update.
Johnston, Tom H; Brotchie, Jonathan M
2006-01-01
The current development of emerging pharmacological treatments for Parkinson's disease (PD), front preclinical to launch, is summarized. Advances over the past year are highlighted, including the significant progress of several drugs through various stages of development. Several agents have been discontinued from development, either because of adverse effects or lack of clinical efficacy. The methyl-esterified form of L-DOPA (melevodopa) and the monoamine oxidase type B inhibitor rasagiline have both been launched. With regard to the monoamine re-uptake inhibitors, many changes have been witnessed, with new agents reaching preclinical development and pre-existing ones being discontinued or having no development reported. Of the dopamine agonists, many continue to progress successfully through clinical trials. Others have struggled to demonstrate a significant advantage over currently available treatments and have been discontinued. The field of non-dopaminergic treatments remains dynamic. The alpha2 adrenergic receptor antagonists and the adenosine A2A receptor antagonists remain in clinical trials. Trials of the neuronal' synchronization modulator levetiracetam are at an advanced stage, and there has also been a new addition to the class (ie, seletracetam). There has been a change in the landscape of neuroprotective agents that modulate disease progression. Candidates from the classes of growth factors and glyceraldehyde-3-phosphate dehydrogenase inhibitors have been discontinued, or no development has been reported, and the mixed lineage kinase inhibitor CEP-1347 has been discontinued for PD treatment. Other drugs in this field, such as neuroimmunophilins, estrogens and alpha-synuclein oligomerization inhibitors, remain in development.
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Nanotechnology based approaches for anti-diabetic drugs delivery.
Kesharwani, Prashant; Gorain, Bapi; Low, Siew Yeng; Tan, Siew Ann; Ling, Emily Chai Siaw; Lim, Yin Khai; Chin, Chuan Ming; Lee, Pei Yee; Lee, Chun Mey; Ooi, Chun Haw; Choudhury, Hira; Pandey, Manisha
2018-02-01
Nanotechnology science has been diverged its application in several fields with the advantages to operate with nanometric range of objects. Emerging field of nanotechnology has been also being approached and applied in medical biology for improved efficacy and safety. Increased success in therapeutic field has focused several approaches in the treatment of the common metabolic disorder, diabetes. The development of nanocarriers for improved delivery of different oral hypoglycemic agents compared to conventional therapies includes nanoparticles (NPs), liposomes, dendrimer, niosomes and micelles, which produces great control over the increased blood glucose level and thus becoming an eye catching and most promising technology now-a-days. Besides, embellishment of nanocarriers with several ligands makes it more targeted delivery with the protection of entrapped hypoglycaemic agents against degradation, thereby optimizing prolonged blood glucose lowering effect. Thus, nanocarriers of hypoglycemic agents provide the aim towards improved diabetes management with minimized risk of acute and chronic complications. In this review, we provide an overview on distinctive features of each nano-based drug delivery system for diabetic treatment and current NPs applications in diabetes management. Copyright © 2017 Elsevier B.V. All rights reserved.
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Human drug metabolism: an introduction
National Research Council Canada - National Science Library
Coleman, Michael D
2010-01-01
..., both under drug pressure and during inhibition. Factors affecting drug metabolism, such as genetic polymorphisms, age and diet are discussed and how metabolism can lead to toxicity is explained. The book concludes with the role of drug metabolism in the commercial development of therapeutic agents as well as the pharmacology of some illicit drugs.
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Teens and Prescription Drugs: An Analysis of Recent Trends on the Emerging Drug Threat
Office of National Drug Control Policy, 2007
2007-01-01
This report synthesizes a number of national studies that show the intentional abuse of prescription drugs to get high is a growing concern, particularly among teens. The analysis shows that teens are turning away from street drugs and using prescription drugs to get high. New users of prescription drugs have caught up with new users of marijuana.…
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Nirmalanandhan, Victor Sanjit; Sittampalam, G Sitta
2009-08-01
Stem cells, irrespective of their origin, have emerged as valuable reagents or tools in human health in the past 2 decades. Initially, a research tool to study fundamental aspects of developmental biology is now the central focus of generating transgenic animals, drug discovery, and regenerative medicine to address degenerative diseases of multiple organ systems. This is because stem cells are pluripotent or multipotent cells that can recapitulate developmental paths to repair damaged tissues. However, it is becoming clear that stem cell therapy alone may not be adequate to reverse tissue and organ damage in degenerative diseases. Existing small-molecule drugs and biologicals may be needed as "molecular adjuvants" or enhancers of stem cells administered in therapy or adult stem cells in the diseased tissues. Hence, a combination of stem cell-based, high-throughput screening and 3D tissue engineering approaches is necessary to advance the next wave of tools in preclinical drug discovery. In this review, the authors have attempted to provide a basic account of various stem cells types, as well as their biology and signaling, in the context of research in regenerative medicine. An attempt is made to link stem cells as reagents, pharmacology, and tissue engineering as converging fields of research for the next decade.
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Polypharmacology of Approved Anticancer Drugs.
Amelio, Ivano; Lisitsa, Andrey; Knight, Richard A; Melino, Gerry; Antonov, Alexey V
2017-01-01
The major drug discovery efforts in oncology have been concentrated on the development of selective molecules that are supposed to act specifically on one anticancer mechanism by modulating a single or several closely related drug targets. However, a bird's eye view on data from multiple available bioassays implies that most approved anticancer agents do, in fact, target many more proteins with different functions. Here we will review and systematize currently available information on the targets of several anticancer drugs along with revision of their potential mechanisms of action. Polypharmacology of the current antineoplastic agents suggests that drug clinical efficacy in oncology can be achieved only via modulation of multiple cellular mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Contact lenses as drug controlled release systems: a narrative review
Directory of Open Access Journals (Sweden)
Helena Prior Filipe
2016-06-01
Full Text Available ABSTRACT Topically applied therapy is the most common way to treat ocular diseases, however given the anatomical and physiological constraints of the eye, frequent dosing is required with possible repercussions in terms of patient compliance. Beyond refractive error correction, contact lenses (CLs have, in the last few decades emerged as a potential ophthalmic drug controlled release system (DCRS. Extensive research is underway to understand how to best modify CLs to increase residence time and bioavailability of drugs within therapeutic levels on the ocular surface.These devices may simultaneously correct ametropia and have a role in managing ophthalmic disorders that can hinder CL wear such as dry eye, glaucoma, ocular allergy and cornea infection and injury. In this narrative review the authors explain how the ocular surface structures determine drug diffusion in the eye and summarize the strategies to enhance drug residence time and bioavailability. They synthesize findings and clinical applications of drug soaked CLs as DCRS combined with delivery diffusion barriers, incorporation of functional monomers, ion related controlled release, molecular imprinting, nanoparticles and layering. The authors draw conclusions about the impact of these novel ophthalmic agents delivery systems in improving drug transport in the target tissue and patient compliance, in reducing systemic absorption and undesired side effects, and discuss future perspectives.
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Seferji, Kholoud; Susapto, Hepi Hari; Arab, Wafaa Talat Abdullah; Sharip, Ainur; Sundaramurthi, Dhakshinamoorthy; Rauf, Sakandar; Hauser, Charlotte
2017-01-01
Nanogels made from self-assembling ultrashort peptides (3-6 amino acids in size) are promising biomaterials for various biomedical applications such as tissue engineering, drug delivery, regenerative medicine, microbiology and biosensing.We have developed silver-releasing peptide nanogels with promising wound care applications. The peptide nanogels allow a precise control of in situ syntesized silver nanoparticles (AgNPs), using soley short UV radiation and no other chemical reducing agent. We propose these silver-releasing nanogels as excellent biomaterial to combat emerging antimicrobial resistant strains.
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Seferji, Kholoud
2017-01-08
Nanogels made from self-assembling ultrashort peptides (3-6 amino acids in size) are promising biomaterials for various biomedical applications such as tissue engineering, drug delivery, regenerative medicine, microbiology and biosensing.We have developed silver-releasing peptide nanogels with promising wound care applications. The peptide nanogels allow a precise control of in situ syntesized silver nanoparticles (AgNPs), using soley short UV radiation and no other chemical reducing agent. We propose these silver-releasing nanogels as excellent biomaterial to combat emerging antimicrobial resistant strains.
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Bosanquet, A G
1985-01-01
In vitro drug sensitivity of tumour biopsies is currently being determined using a variety of methods. For these chemosensitivity assays many drugs are required at short notice, and this in turn means that the drugs must generally be stored in solution. There are, however, a number of potential problems associated with dissolving and storing drugs for in vitro use, which include (a) drug adsorption; (b) effects of freezing; (c) drug stability under the normal conditions of dilution and setting up of an in vitro assay; and (d) insolubility of drugs in normal saline (NS) or phosphate-buffered saline (PBS). These problems are considered in general, and some recommendations for use of solutions of drugs in in vitro assays are suggested. The nitrosoureas and alkylating agents are also investigated in greater detail in this respect. The nitrosoureas are found to be very labile in PBS at pH 7, with 5% degradation (t0.95) occurring in 10-50 min at room temperature. These values are increased about 10-fold on refrigeration and about 5- to 10-fold on reduction of the pH of the medium to pH 4-5. At pH 7 and room temperature, t0.95 is observed in under 1 h with the alkylating agents nitrogen mustard, chlorambucil, melphalan, 2,5-diaziridinyl-3,6-bis(2-hydroxyethylamino)-1,4-benzoquinone (BZQ), dibromodulcitol, dibromomannitol, treosulphan, and procarbazine. Of the other alkylating agents, 4-hydroperoxycylophosphamide (sometimes used in vitro in place of cyclophosphamide), busulphan, dianhydrogalactitol, aziridinylbenzoquinone (AZQ), and dacarbazine have a t0.95 of between 2 and 24 h, while ifosfamide and pentamethylmelamine are both stable in aqueous solution for greater than 7 days. About half the drugs studied in detail have been stored frozen in solution for in vitro use, although very little is known about their stability under these conditions.
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Directory of Open Access Journals (Sweden)
Michael P. Wilson
2012-04-01
Full Text Available Agitation is common in the medical and psychiatric emergency department, and appropriate management of agitation is a core competency for emergency clinicians. In this article, the authors review the use of a variety of first-generation antipsychotic drugs, second-generation antipsychotic agents, and benzodiazepines for treatment of acute agitation, and propose specific guidelines for treatment of agitation associated with a variety of conditions, including acute intoxication, psychiatric illness, delirium, and multifocal or idiopathic causes. Pharmacologic treatment of agitation should be based on an assessment of the most likely cause for the agitation. If agitation results from a medical condition or delirium, clinicians should first attempt to treat this underlying cause instead of simply medicating with antipsychotics or benzodiazepines. [West J Emerg Med. 2012;13(1:26–34.
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The discovery and development of antiretroviral agents
Lange, Joep M. A.; Ananworanich, Jintanat
2014-01-01
Since the discovery of HIV as the causative agent of AIDS in 1983/1984, remarkable progress has been made in finding antiretroviral drugs (ARVs) that are effective against it. A major breakthrough occurred in 1996 when it was found that triple drug therapy (HAART) could durably suppress viral
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Agent-based models for higher-order theory of mind
de Weerd, Harmen; Verbrugge, Rineke; Verheij, Bart; Kamiński, Bogumił; Koloch, Grzegorz
2014-01-01
Agent-based models are a powerful tool for explaining the emergence of social phenomena in a society. In such models, individual agents typically have little cognitive ability. In this paper, we model agents with the cognitive ability to make use of theory of mind. People use this ability to reason
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Detox agents do not affect the pharmacokinetics of methamphetamine in the rat.
Lee, Sang Kyu; Kim, Yoon; Suh, Sungill; Suh, Yong Jun; In, Moon Kyo; Kim, Dong-Hyun; Jin, Changbae; Yoo, Hye Hyun
2009-04-15
Recently, 'detox' agents have been popularly used as forms of diets or nutritional supplements. Especially, several cases have been reported that these detox agents have been used to mask drug tests among drug abusers. In the present study, capsule and drink types of detox agents were evaluated for their ability to alter the elimination of methamphetamine (MA) in rats. For this study, MA and its major metabolite, amphetamine (AP) in urine samples were determined using LC-tandem mass spectrometry after administration of the detox agents to MA-treated rats. As a result, significant differences were not shown between control and detox-dosed groups in the amounts of MA and AP excreted into urine as well as the volume of excreted urine. This result suggests that the detox agents tested may not affect the metabolism or elimination of MA and further might have minimal effect on narcotics detection in the urine samples of drug abusers.
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[Self-reported substance abuse related emergencies: frequency and nature].
Schäfer, G; Smoltczyk, H; Dengler, W; Buchkremer, G
2000-04-01
The aim of this study was to estimate the frequency and nature of self-reported and drug-related emergencies. 47 patients of a ward for opiate detoxification were interviewed about their experiences with drug-related emergencies. Typical categories had to be found like overdoses, seizures, accidents and suicide attempts respectively. 68% had own experience with drug-related emergency. A majority suffered opiate overdose with different extensions as unconsciousness or breath-depression. Alcohol and polydrug use was associated with overdose. Drug-related accidents were only reported by men. Half the number of drug-related emergencies were treated in hospital. Most emergencies occurred alone either in a home environment or outside. Harm reduction interventions like observed user rooms should be established. Furthermore other strategies to reduce the number of emergencies as sharing naloxon or resuscitation programs in wards for detoxification could also be an effective method to prevent near fatal or fatal overdoses in dependent subjects.
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Small Scaffolds, Big Potential: Developing Miniature Proteins as Therapeutic Agents.
Holub, Justin M
2017-09-01
Preclinical Research Miniature proteins are a class of oligopeptide characterized by their short sequence lengths and ability to adopt well-folded, three-dimensional structures. Because of their biomimetic nature and synthetic tractability, miniature proteins have been used to study a range of biochemical processes including fast protein folding, signal transduction, catalysis and molecular transport. Recently, miniature proteins have been gaining traction as potential therapeutic agents because their small size and ability to fold into defined tertiary structures facilitates their development as protein-based drugs. This research overview discusses emerging developments involving the use of miniature proteins as scaffolds to design novel therapeutics for the treatment and study of human disease. Specifically, this review will explore strategies to: (i) stabilize miniature protein tertiary structure; (ii) optimize biomolecular recognition by grafting functional epitopes onto miniature protein scaffolds; and (iii) enhance cytosolic delivery of miniature proteins through the use of cationic motifs that facilitate endosomal escape. These objectives are discussed not only to address challenges in developing effective miniature protein-based drugs, but also to highlight the tremendous potential miniature proteins hold for combating and understanding human disease. Drug Dev Res 78 : 268-282, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
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Current obesity drug treatment
Directory of Open Access Journals (Sweden)
Marcio C. Mancini
2006-03-01
Full Text Available Pharmacological treatment of obesity is an area of sudden changes,development of new drugs and treatment propositions. This articlepresents information on physiological agents that are currentlybeing used as well as drugs that were widely used but are nomore available.
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Dry Eye Treatment Based on Contact Lens Drug Delivery: A Review.
Guzman-Aranguez, Ana; Fonseca, Begoña; Carracedo, Gonzalo; Martin-Gil, Alba; Martinez-Aguila, Alejandro; Pintor, Jesús
2016-09-01
Dry eye disease affects a substantial segment of the word population with increasing frequency. It is a multifactorial disease of the ocular surface and tear film, which causes ocular discomfort, visual disturbances, and tear instability with potential damage to the cornea and conjunctiva. Because of its multifactorial etiology, the use of different pharmacological treatment for dry eye treatment has been proposed, which include anti-inflammatory molecules, lubricants or comfort agents, and secretagogues. However, in some cases these pharmacological approaches only relieve symptoms temporarily, and consequently, eye care professionals continue to have difficulties managing dry eye. To improve pharmacological therapy that allows a more efficient and long-term action, effective ocular drug delivery of the currently available drugs for dry eye treatment is required. Contact lenses are emerging as alternative ophthalmic drugs delivery systems that provide an increased residence time of the drug at the eye, thus leading to enhanced bioavailability and more convenient and efficacious therapy. In this article, we reviewed the different techniques used to prepare contact lens-based drug delivery systems and focused on articles that describe the delivery of compounds for dry eye treatment through contact lenses.
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Bahari, Leila Azharshekoufeh; Javadzadeh, Yousef; Jalali, Mohammad Barzegar; Johari, Peyvand; Nokhodchi, Ali; Shokri, Javad
2017-05-01
In controlled porosity osmotic pumps (CPOP), usually finding a single solvent with a capability to dissolve both film former (hydrophobic) and pore former (hydrophilic) is extremely challenging. Therefore, the aim of the present investigation was to tackle the issue associated with controlled porosity osmotic pump (CPOP) system using nano-suspension coating method. In the present study 4-Amino pyridine was used as a highly water soluble drug. In this method, a hydrophilic pore former (sucrose or mannitol) in nano range was suspended in polymeric coating solution using ball-mill. The performance of the prepared formulations was assessed in terms of D 12h (cumulative release percent after 12h), Dev zero (mean percent deviation of drug release from zero order kinetic), t L (lag time of the drug release) and RSQ zero . The results revealed that gelling agent amount (HPMC E 15LV ) in core and pore former concentration in SPM had crucial effect on SPM integrity. All the optimised formulations showed a burst drug release due to fast dissolving nature of the pore formers. Results obtained from scanning electron microscopy demonstrated the formation of nanopores in the membrane where the drug release takes place via these nanopores. Nano suspension coating method can be introduced as novel method in formulation of CPOPs. Copyright © 2017 Elsevier B.V. All rights reserved.
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Thevis, Mario; Schänzer, Wilhelm
2014-12-01
The number and diversity of potentially performance-enhancing substances is continuously growing, fueled by new pharmaceutical developments but also by the inventiveness and, at the same time, unscrupulousness of black-market (designer) drug producers and providers. In terms of sports drug testing, this situation necessitates reactive as well as proactive research and expansion of the analytical armamentarium to ensure timely, adequate, and comprehensive doping controls. This review summarizes literature published over the past 5 years on new drug entities, discontinued therapeutics, and 'tailored' compounds classified as doping agents according to the regulations of the World Anti-Doping Agency, with particular attention to analytical strategies enabling their detection in human blood or urine. Among these compounds, low- and high-molecular mass substances of peptidic (e.g. modified insulin-like growth factor-1, TB-500, hematide/peginesatide, growth hormone releasing peptides, AOD-9604, etc.) and non-peptidic (selective androgen receptor modulators, hypoxia-inducible factor stabilizers, siRNA, S-107 and ARM036/aladorian, etc.) as well as inorganic (cobalt) nature are considered and discussed in terms of specific requirements originating from physicochemical properties, concentration levels, metabolism, and their amenability for chromatographic-mass spectrometric or alternative detection methods. Copyright © 2014 Elsevier B.V. All rights reserved.
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Maternal drug use: evaluation of risks to breast-fed infants.
Kirksey, A; Groziak, S M
1984-01-01
This paper, based on a review of the literature, evaluates the risks to infants of maternal drug use during lactation. The potential harm of a particular drug to the breastfed infant is related both to the complex mechanism of milk synthesis and secretion and the mode of passage of the drug from plasma into milk. The 1st part of the paper discusses mammary cell and milk synthesis, milk secretion and composition, the mode of passage of drugs into milk, and factors influencing drug concentrations in milk. Drug concentrations in milk are dependent on 6 major factors: drug dosage, proportion bound in plasma, molecular weight, lipid solubility, degree of ionization, and pH difference between plasma and milk. Drugs that are weak acids are ionized to a greater extent and are more protein-bound than weak alkaline drugs. The 2nd part of the paper evaluates the risks to breastfed infants of selected pharmacons. Some categories of drugs that contain pharmacons that should be limited or avoided by nursing mothers are alkylating agents, analgesics and anti-inflammatory agents, anticoagulants, anticonvulsants, anti-infective agents, central nervous system stimulants, hormones, laxatives, minerals, provitamins, psychotherapeutic agents, thyroid affecting agents, and vitamins. The following precautions are suggested to minimize the risks of potentially harmful pharmacons: 1) all unnecessary medications should be avoided by nrusing mothers; 2) if medication is necessary during lactation, drug dosage should be controlled and the infant should be monitored for adverse symptoms; 3) drugs should be administered shortly after breastfeeding and the interval prolonged before the next feeding; and 4) if the infant must be fed soon after a potentially harmful drug has been taken by the mother, bottle feeding is recommended.
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Directory of Open Access Journals (Sweden)
Mastour S Alghamdy
2015-01-01
Full Text Available Background and Aim: Medication Errors can result in drug-related problems (DRPs. Insight into the frequency, type, and severity of DRPs could help reduce their incidence. The aim of the present study was to estimate the prevalence of admissions as a result of DRPs at the Emergency Department (ED of a university hospital in the Kingdom of Saudi Arabia. Materials and Methods: Files of suspected cases of DRPs reporting to ED in the year 2012 were scrutinized. Suspicion arose from the hospital record system based on Diagnosis Code Numbers (ICD-9-CM, Professional 2010 and from triggers, such as some drugs, laboratory tests, and signs and symptoms pointing to DRPs. Results: Of 5574 admissions, 253 (4.5% were DRPs and were categorized as: Overdose toxicity and side effects of drugs 50 (19.8%, drug-interactions 29 (11.5%, accidental and suicidal drug ingestions 26 (10.3%, drug abuse 18 (7.1%, drug allergy 10 (4%, super-infections 8 (3.2%, and noncompliance to treatment 112 (44.3%. About 70% of DRPs were preventable; 67 (26.5% required hospital admission for 7-102 days and 10 (4% died. Conclusions: Noncompliance to treatment, overdose toxicity, drug interactions, and drug abuse are important causes of hospital admissions as a result of DRPs. Awareness of prescribers to the problem and their education would help to prevent them and improve patient care.
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Repurposing and Revival of the Drugs: A New Approach to Combat the Drug Resistant Tuberculosis
Directory of Open Access Journals (Sweden)
Divakar Sharma
2017-12-01
Full Text Available Emergence of drug resistant tuberculosis like multi drug resistant tuberculosis (MDR-TB, extensively drug-resistant tuberculosis (XDR-TB and totally drug resistant tuberculosis (TDR-TB has created a new challenge to fight against these bad bugs of Mycobacterium tuberculosis. Repurposing and revival of the drugs are the new trends/options to combat these worsen situations of tuberculosis in the antibiotics resistance era or in the situation of global emergency. Bactericidal and synergistic effect of repurposed/revived drugs along with the latest drugs bedaquiline and delamanid used in the treatment of MDR-TB, XDR-TB, and TDR-TB might be the choice for future promising combinatorial chemotherapy against these bad bugs.
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Atehmengo, Ngongeh L; Nnagbo, Chiejina S
2014-01-01
Emerging animal parasitic diseases are reviewed and appropriate strategies for efficient monitoring and surveillance in Nigeria are outlined. Animal and human parasitic infections are distinguished. Emerging diseases have been described as those diseases that are being recognised for the first time or diseases that are already recorded but their frequency and/or geographic range is being increased tremendously. Emergence of new diseases may be due to a number of factors such as the spread of a new infectious agent, recognition of an infection that has been in existence but undiagnosed, or when it is realised that an established disease has an infectious origin. The terms could also be used to describe the resurgence of a known infection after its incidence had been known to have declined. Emerging infections are compounding the control of infectious diseases and huge resources are being channeled to alleviate the rising challenge. The diseases are numerous and include helminth, protozoal / rickettsial and entomological. A list of parasitic emerging diseases in Nigeria is included. Globally occurring emerging parasitic diseases are also outlined. Emerging and re-emerging infections can be brought about by many factors including climate change and global warming, changes in biodiversity, population mobility, movement of animals, globalisation of commerce/trade and food supply, social and cultural factors such as food eating habits, religious beliefs, farming practices, trade of infected healthy animals, reduction in the available land for animals, immune-suppressed host and host density and misuse or over use of some drugs leading to drug resistance.
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Atehmengo, Ngongeh L; Nnagbo, Chiejina S
2014-01-01
Emerging animal parasitic diseases are reviewed and appropriate strategies for efficient monitoring and surveillance in Nigeria are outlined. Animal and human parasitic infections are distinguished. Emerging diseases have been described as those diseases that are being recognised for the first time or diseases that are already recorded but their frequency and/or geographic range is being increased tremendously. Emergence of new diseases may be due to a number of factors such as the spread of a new infectious agent, recognition of an infection that has been in existence but undiagnosed, or when it is realised that an established disease has an infectious origin. The terms could also be used to describe the resurgence of a known infection after its incidence had been known to have declined. Emerging infections are compounding the control of infectious diseases and huge resources are being channeled to alleviate the rising challenge. The diseases are numerous and include helminth, protozoal / rickettsial and entomological. A list of parasitic emerging diseases in Nigeria is included. Globally occurring emerging parasitic diseases are also outlined. Emerging and re-emerging infections can be brought about by many factors including climate change and global warming, changes in biodiversity, population mobility, movement of animals, globalisation of commerce/trade and food supply, social and cultural factors such as food eating habits, religious beliefs, farming practices, trade of infected healthy animals, reduction in the available land for animals, immune-suppressed host and host density and misuse or over use of some drugs leading to drug resistance. PMID:25328553
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DRUG POLICY AND DRUG ADDICTION IN TURKEY
İLHAN, Mustafa Necmi
2018-01-01
The NationalStrategy Document on Drugs and Emergency Action Plan started with thecontributions of all the relevant institutions within the year of 2014 wasprepared and after that in accordance with the Prime Ministry Notice entitledFight Against Drugs published within this scope, the committees for FightAgainst Drugs were established (under the presidency of Deputy Prime Ministerand with the help of Ministry of Health, Ministry of Justice, Ministry of Laborand Social Security, Ministry of Fam...
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Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents.
Ververis, Katherine; Hiong, Alison; Karagiannis, Tom C; Licciardi, Paul V
2013-01-01
Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza) and depsipeptide (romidepsin, Istodax). More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while
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International Nuclear Information System (INIS)
Lupattelli, Tommaso; Garaci, Francesco Giuseppe; Basile, Antonio; Minnella, Daniela Paola; Casini, Andrea; Clerissi, Jacques
2009-01-01
Mycotic false aneurysm caused by local arterial injury from attempted intravenous injections in drug addicts remains a challenging clinical problem. The continued increase in drug abuse has resulted in an increased incidence of this problem, particularly in high-volume urban centres. In the drug-abusing population, mycotic arterial pseudoaneurysms most often occur because of missed venous injection and are typically seen in the groin, axilla, and antecubital fossa. Mycotic aneurysms may lead to life-threatening haemorrhage, limb loss, sepsis, and even death. Any soft-tissue swelling in the vicinity of a major artery in an intravenous drug abuser should be suspected of being a false aneurysm until proven otherwise and should prompt immediate referral to a vascular surgeon for investigation and management. We report a case of rupturing mycotic pseudoaneurysm of the left common femoral artery treated by surgical resection followed by vessel reconstruction with autologous material. Unfortunately, at the time of discharge a sudden leakage from the vein graft anastomosis occurred, with subsequent massive bleeding, and required emergent endovascular covered stenting. To the best of our knowledge, this is the first reported case of femoral artery bleeding in a drug abuser treated by stent graft placement.
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Agrawal, Mukta; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G; Chougule, Mahavir Bhupal; Shoyele, Sunday A; Alexander, Amit
2018-05-23
According to the Alzheimer Association Report (2017), Alzheimer's disease (AD) is the 6th primary cause of death in the USA, which affects nearly 5.5 million people. In the year 2017 itself, the cost of AD treatment in the USA has been reported to rise to $259 billion. This statistic shows the severity of the disease in the USA which is very much similar across the globe. On the other hand, the treatment remains limited to a few conventional oral medications (approved by FDA). These are mainly acting superficially from mild to the moderate AD. The therapeutic efficacy of the drug is not only affected by its reduced concentration in the brain owing to the existence of blood-brain-barrier (BBB) but also due to its low brain permeability. In this context, the intranasal (IN) route of drug administration has emerged as an alternative route over the systemic (oral and parenteral) drug delivery to the brain. The delivery of the drug via an IN route offers various advantages over systemic drug delivery system, as it directly delivers the drug into the brain via olfactory route. Presence of drug in the olfactory bulb, in turn, increases the drug bioavailability in the brain and reduces the drug degradation as well as wastage of the drug through` systemic clearance. However, there is also some limitation associated with IN like poor drug permeation through the nasal mucosa and mucociliary clearance. The delivery system various through novel strategies (nano drug carrier system, colloidal carriers, mucoadhesive devices, controlled delivery system, pro-drug, etc.) are adapted to overcome the above-stated limitations. Although, after all, such successful research claims, very few of the nose-to-brain drug delivery of anti-AD drugs have gained market approval due to lack of sufficient clinical evidence. Onzetra Xsail® is one such marketed preparations approved for IN delivery used for the treatment of a brain disorder; migraine. In the field of patents also, no work is found
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Islam, Nazrul; Richard, Derek
2018-05-24
Local delivery of drug to the target organ via inhalation offers enormous benefits in the management of many diseases. Lung cancer is the most common of all cancers and it is the leading cause of death worldwide. Currently available treatment systems (intravenous or oral drug delivery) are not efficient in accumulating the delivered drug into the target tumor cells and are usually associated with various systemic and dose-related adverse effects. The pulmonary drug delivery technology would enable preferential accumulation of drug within the cancer cell and thus be superior to intravenous and oral delivery in reducing cancer cell proliferation and minimising the systemic adverse effects. Site-specific drug delivery via inhalation for the treatment of lung cancer is both feasible and efficient. The inhaled drug delivery system is non-invasive, produces high bioavailability at low dose and avoids first pass metabolism of the delivered drug. Various anticancer drugs including chemotherapeutics, proteins and genes have been investigated for inhalation in lung cancers with significant outcomes. Pulmonary delivery of drugs from dry powder inhaler (DPI) formulation is stable and has high patient compliance. Herein, we report the potential of pulmonary drug delivery from dry powder inhaler (DPI) formulations inhibiting lung cancer cell proliferation at very low dose with reduced unwanted adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Ward, Mark G; Irving, Peter M; Sparrow, Miles P
2015-10-28
In the last 15 years the management of inflammatory bowel disease has evolved greatly, largely through the increased use of immunomodulators and, especially, anti-tumor necrosis factor (anti-TNF) biologic agents. Within this time period, confidence in the use of anti-TNFs has increased, whilst, especially in recent years, the efficacy and safety of thiopurines has been questioned. Yet despite recent concerns regarding the risk: benefit profile of thiopurines, combination therapy with an immunomodulator and an anti-TNF has emerged as the recommended treatment strategy for the majority of patients with moderate-severe disease, especially those who are recently diagnosed. Concurrently, therapeutic drug monitoring has emerged as a means of optimizing the dosage of both immunomodulators and anti-TNFs. However the recommended therapeutic target levels for both drug classes were largely derived from studies of monotherapy with either agent, or studies underpowered to analyze outcomes in combination therapy patients. It has been assumed that these target levels are applicable to patients on combination therapy also, however there are few data to support this. Similarly, the timing and duration of treatment with immunomodulators when used in combination therapy remains unknown. Recent attention, including post hoc analyses of the pivotal registration trials, has focused on the optimization of anti-TNF agents, when used as either monotherapy or combination therapy. This review will instead focus on how best to optimize immunomodulators when used in combination therapy, including an evaluation of recent data addressing unanswered questions regarding the optimal timing, dosage and duration of immunomodulator therapy in combination therapy patients.
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Kratom, an Emerging Drug of Abuse: A Case Report of Overdose and Management of Withdrawal.
Diep, Jack; Chin, David Tian; Gupta, Somdatta; Syed, Faraz; Xiong, Ming; Cheng, Jianguo
2018-04-15
Kratom is an herb indigenous to Southeast Asia with psychoactive opioid compounds, often used as a treatment for chronic pain or opiate withdrawal symptoms. It is legally and readily available via Internet sales and has been identified as an emerging drug of abuse in the United States. Kratom use has been associated with psychosis, seizures, and even death. At lower doses, kratom acts as a stimulant, while at higher doses, it produces analgesia and euphoria. Here, we describe the successful management of kratom overdose and withdrawal in a young man with negative toxicology screens.
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[Development of antituberculous drugs: current status and future prospects].
Tomioka, Haruaki; Namba, Kenji
2006-12-01
Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. One-third of the world's population is infected with Mycobacterium tuberculosis (MTB), the etiologic agent of TB. The World Health Organization estimates that about eight to ten million new TB cases occur annually worldwide and the incidence of TB is currently increasing. In this context, TB is in the top three, with malaria and HIV being the leading causes of death from a single infectious agent, and approximately two million deaths are attributable to TB annually. In particular, pulmonary TB, the most common form of TB, is a highly contagious and life-threatening infection. Moreover, enhanced susceptibility to TB in HIV-infected populations is another serious health problem throughout the world. In addition, multidrug-resistant TB (MDR-TB) has been increasing in incidence in many areas, not only in developing countries but industrialized countries as well, during the past decade. These situations, particularly the global resurgence of TB and the rapid emergence of MDR-TB, underscore the importance of the development of new antituberculous drugs and new protocols for efficacious clinical control of TB patients using ordinary antimycobacterial drugs. Concerning the development of new antituberculous drugs, the following points are of particular importance. (1) Development of drugs which display lasting antimycobacterial activity in vivo is desirable, since they can be administered with long intervals and consequently facilitate directly observed therapy and enhance patient compliance. (2) Development of novel antituberculosis compounds to combat MDR-TB is urgently needed. (3) The eradication of slowly metabolizing and, if possible, dormant populations of MTB organisms that cause relapse, using new classes of anti-TB drugs is very promising for prevention of TB incidence, because it will markedly reduce the incidence of active TB from persons who are
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Soller, Brian; Lee, Juliet P.
2010-01-01
This article examines why Southeast Asian American adolescents and emerging adults in two urban settings prefer to use "blunts," or hollowed-out cigars filled with marijuana, over other methods of drug intake. Rationales for preferring blunts were both instrumental and social. Blunts allowed users to more easily share marijuana, the preferred drug…
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Frank, Matthew G; Watkins, Linda R; Maier, Steven F
2011-06-01
Stress and stress-induced glucocorticoids (GCs) sensitize drug abuse behavior as well as the neuroinflammatory response to a subsequent pro-inflammatory challenge. Stress also predisposes or sensitizes individuals to develop substance abuse. There is an emerging evidence that glia and glia-derived neuroinflammatory mediators play key roles in the development of drug abuse. Drugs of abuse such as opioids, psychostimulants, and alcohol induce neuroinflammatory mediators such as pro-inflammatory cytokines (e.g. interleukin (IL)-1β), which modulate drug reward, dependence, and tolerance as well as analgesic properties. Drugs of abuse may directly activate microglial and astroglial cells via ligation of Toll-like receptors (TLRs), which mediate the innate immune response to pathogens as well as xenobiotic agents (e.g. drugs of abuse). The present review focuses on understanding the immunologic mechanism(s) whereby stress primes or sensitizes the neuroinflammatory response to drugs of abuse and explores whether stress- and GC-induced sensitization of neuroimmune processes predisposes individuals to drug abuse liability and the role of neuroinflammatory mediators in the development of drug addiction. Copyright © 2011 Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
Jeane Freitas de Oliveira
2010-09-01
consumo de drogas como un problema de salud para el grupo estudiado.This paper discusses on the social representations of community health agents (CHAs about drug use as part of a qualitative, ethnographic study with data collected by means of a set of research techniques among health professionals including 22 CHAs in a basic health unit in Salvador, Bahia (Brazil from January, 2006 to January, 2007. The Theory of Social Representations was adopted as the theoretical framework whereas gender was the chosen analytical category. CHAs were found to recognize the women's proximity and participation in the drug phenomenon in the community where they live and act, although they take no professional measures towards such an issue. Their social representations were shown to reproduce stereotypes and prejudices towards drug users and drug use, especially gender- and social class-related, while highlighting the invisibility of drug use as a health problem for the population under study.
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Early Observations on Possible Defenses by the Emerging Threat Agent Project
2011-01-01
approach would involve the following: • Seek to dissuade adversary development of new CB capabilities. Dissuasion seeks to affect the adversary’s... fruit , it would be unwise in the short term to divert much funding from the agent-specific approach to the second track. The track 2 mechanistic...agents to enhance their effectiveness – genetic manipulation of innocuous (and perhaps ubiquitous) bacteria, viruses, or fungi to make them dangerous
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Targeted Drug-Carrying Bacteriophages as Antibacterial Nanomedicines▿
Yacoby, Iftach; Bar, Hagit; Benhar, Itai
2007-01-01
While the resistance of bacteria to traditional antibiotics is a major public health concern, the use of extremely potent antibacterial agents is limited by their lack of selectivity. As in cancer therapy, antibacterial targeted therapy could provide an opportunity to reintroduce toxic substances to the antibacterial arsenal. A desirable targeted antibacterial agent should combine binding specificity, a large drug payload per binding event, and a programmed drug release mechanism. Recently, we presented a novel application of filamentous bacteriophages as targeted drug carriers that could partially inhibit the growth of Staphylococcus aureus bacteria. This partial success was due to limitations of drug-loading capacity that resulted from the hydrophobicity of the drug. Here we present a novel drug conjugation chemistry which is based on connecting hydrophobic drugs to the phage via aminoglycoside antibiotics that serve as solubility-enhancing branched linkers. This new formulation allowed a significantly larger drug-carrying capacity of the phages, resulting in a drastic improvement in their performance as targeted drug-carrying nanoparticles. As an example for a potential systemic use for potent agents that are limited for topical use, we present antibody-targeted phage nanoparticles that carry a large payload of the hemolytic antibiotic chloramphenicol connected through the aminoglycoside neomycin. We demonstrate complete growth inhibition toward the pathogens Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli with an improvement in potency by a factor of ∼20,000 compared to the free drug. PMID:17404004
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Drug treatment and novel drug target against Cryptosporidium
Directory of Open Access Journals (Sweden)
Gargala G.
2008-09-01
Full Text Available Cryptosporidiosis emergence triggered the screening of many compounds for potential anti-cryptosporidial activity in which the majority were ineffective. The outbreak of cryptosporidiosis which occurred in Milwaukee in 1993 was not only the first significant emergence of Cryptosporidium spp. as a major human pathogen but also a huge waterborne outbreak thickening thousands of people from a major city in North America. Since then, outbreaks of cryptosporidiosis are regularly occurring throughout the world. New drugs against this parasite became consequently urgently needed. Among the most commonly used treatments against cryptosporidiosis are paromomycin, and azithromycin, which are partially effective. Nitazoxanide (NTZ’s effectiveness was demonstrated in vitro, and in vivo using several animal models and finally in clinical trials. It significantly shortened the duration of diarrhea and decreased mortality in adults and in malnourished children. NTZ is not effective without an appropriate immune response. In AIDS patients, combination therapy restoring immunity along with antimicrobial treatment of Cryptosporidium infection is necessary. Recent investigations focused on the potential of molecular-based immunotherapy against this parasite. Others tested the effects of probiotic bacteria, but were unable to demonstrate eradication of C. parvum. New synthetic isoflavone derivatives demonstrated excellent activity against C. parvum in vitro and in a gerbil model of infection. Newly synthesized nitroor non nitro- thiazolide compounds, derived from NTZ, have been recently shown to be at least as effective as NTZ against C. parvum in vitro development and are promising new therapeutic agents.
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Emerging infectious diseases of wildlife: a critical perspective.
Tompkins, Daniel M; Carver, Scott; Jones, Menna E; Krkošek, Martin; Skerratt, Lee F
2015-04-01
We review the literature to distinguish reports of vertebrate wildlife disease emergence with sufficient evidence, enabling a robust assessment of emergence drivers. For potentially emerging agents that cannot be confirmed, sufficient data on prior absence (or a prior difference in disease dynamics) are frequently lacking. Improved surveillance, particularly for neglected host taxa, geographical regions and infectious agents, would enable more effective management should emergence occur. Exposure to domestic sources of infection and human-assisted exposure to wild sources were identified as the two main drivers of emergence across host taxa; the domestic source was primary for fish while the wild source was primary for other taxa. There was generally insufficient evidence for major roles of other hypothesized drivers of emergence. Copyright © 2015 Elsevier Ltd. All rights reserved.
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International Nuclear Information System (INIS)
Chen Dengke; Zhang Dafa; Jiang Wei; Chen Yonghong
2007-01-01
Emergency decision-making to Marine Pressurized-Water Reactor (MPWR) was severely restricted by the complex environment. To enhance the emergency decision-making ability of MPWR, reducing the effect of emergencies, an emergency Decision-making Support System (DSS) which based on Multi-agent System (MAS) was presented. In the system, the HLA/RTI was used as the support environment, and the structure and the Control Agent (SCA), Analyse Agent (AA), Countermeasure Agent (CA), Evaluation Agent (EVA) and Environment Agent (ENA) were designed. The MAS were with the characteristics of autonomy, reactivity and initiative, which were fully used in the system to make effective decision for emergencies. (authors)
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Intestinal transport of gentamicin with a novel, glycosteroid drug transport agent
Axelrod, H. R.; Kim, J. S.; Longley, C. B.; Lipka, E.; Amidon, G. L.; Kakarla, R.; Hui, Y. W.; Weber, S. J.; Choe, S.; Sofia, M. J.
1998-01-01
PURPOSE: The objective was to investigate the ability of a glycosteroid (TC002) to increase the oral bioavailability of gentamicin. METHODS: Admixtures of gentamicin and TC002 were administered to the rat ileum by injection and to dogs by ileal or jejunal externalized ports, or PO. Bioavailability of gentamicin was determined by HPLC. 3H-TC002 was injected via externalized cannulas into rat ileum or jejunum, or PO and its distribution and elimination was determined. The metabolism of TC002 in rats was evaluated by solid phase extraction and HPLC analysis of plasma, urine and feces following oral or intestinal administration. RESULTS: The bioavailability of gentamicin was substantially increased in the presence of TC002 in both rats and dogs. The level of absorption was dependent on the concentration of TC002 and site of administration. Greatest absorption occurred following ileal orjejunal administration. TC002 was significantly more efficacious than sodium taurocholate, but similar in cytotoxicity. TC002 remained primarily in the GI tract following oral or intestinal administration and cleared rapidly from the body. It was only partly metabolized in the GI tract, but was rapidly and completely converted to its metabolite in plasma and urine. CONCLUSIONS: TC002 shows promise as a new drug transport agent for promoting intestinal absorption of polar molecules such as gentamicin.
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Fithawati, Garnis; Budianto, Emil
2018-04-01
Common treatment for Helicobacter pylori by repeated oral consumption of amoxicillin trihydrate is not effective. Amoxicillin trihydrate has a very short residence time in stomach which leads into its ineffectiveness. Residence time of amoxicillin trihydrate can be improved by encapsulating amoxicillin trihydrate into a floating drug delivery system. In this study, amoxicillin trihydrate is encapsulated into hydrogel semi-IPN chitosan methyl cellulose matrix as a floating drug delivery system and then treated with 20% KHCO3 as pore forming agent. Drug loading process used are in-situ loading and post loading. In-situ loading process has higher efficiency percentage and dissolution percentage than post loading process. In-situ loading process resulted 100% efficiency with 92,70% dissolution percentage. Post loading process resulted 98,7% efficiency with 90,42% dissolution percentage. Mechanism of drug dissolution study by kinetics approach showed both in-situ loading process and post loading process are diffusion and degradation process (n=0,4913) and (n=0,4602) respectively. These results are supported by characterization data from optical microscope and scanning electron microscopy (SEM). Data from optical microscope showed both loading process resulted in coarser hydrogel surface. Characterization using SEM showed elongated pores in both loading process after dissolution test.
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Directory of Open Access Journals (Sweden)
Dhanan Sarwo Utomo
2012-01-01
Full Text Available This study is motivated by the reality that school choice programs that is currently implemented in Bandung that, always resulting student deficit (lack of student in some schools. In this study, a mechanism that can describe how the enrollment pattern in a school choice program emerge as a result of individual preferences of the prospective students, is constructed. Using computer simulation, virtual experiments are conducted. In these experiments, the enrollment patterns and the number of student deficit that were resulted by various school choice program configurations are analyzed. Based on the experiment results, modification of the current program that can minimize the number of student deficit can be purposed.Keywords: agent-based simulation, school choice, computer simulation
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Cardiovascular drugs inducing QT prolongation: facts and evidence.
Taira, Carlos A; Opezzo, Javier A W; Mayer, Marcos A; Höcht, Christian
2010-01-01
Acquired QT syndrome is mainly caused by the administration of drugs that prolong ventricular repolarization. On the other hand, the risk of drug-induced torsades de pointes is increased by numerous predisposing factors, such as genetic predisposition, female sex, hypokalemia and cardiac dysfunction. This adverse reaction is induced by different chemical compounds used for the treatment of a variety of pathologies, including arrhythmias. As it is known, antiarrhythmic agents and other cardiovascular drugs can prolong the QT interval, causing this adverse reaction. Of the 20 most commonly reported drugs, 10 were cardiovascular agents and these appeared in 348 of the reports (46%). Class Ia antiarrhythmic agents have frequently been linked to inducing arrhythmia, including torsades de pointes. Sotalol and amiodarone, class III antiarrhythmics, are known to prolong the QT interval by blocking I(Kr). Due to the severity of events caused by the therapeutic use of these drugs, in this work of revision the cardiovascular drugs that present this property and the factors and evidence will be mentioned.
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Bactericidal assessment of nano-silver on emerging and re-emerging human pathogens.
Anuj, Samir A; Gajera, Harsukh P; Hirpara, Darshna G; Golakiya, Baljibhai A
2018-04-24
With the threat of the growing number of bacteria resistant to antibiotics, the re-emergence of previously deadly infections and the emergence of new infections, there is an urgent need for novel therapeutic agent. Silver in the nano form, which is being used increasingly as antibacterial agents, may extend its antibacterial application to emerging and re-emerging multidrug-resistant pathogens, the main cause of nosocomial diseases worldwide. In the present study, a completely bottom up method to prepare green nano-silver was used. To explore the action of nano-silver on emerging Bacillus megaterium MTCC 7192 and re-emerging Pseudomonas aeruginosa MTCC 741 pathogenic bacteria, the study includes an analysis of the bacterial membrane damage through Scanning Electron Microscope (SEM) as well as alternation of zeta potential and intracellular leakages. In this work, we observed genuine bactericidal property of nano-silver as compare to broad spectrum antibiotics against emerging and re-emerging mode. After being exposed to nano-silver, the membrane becomes scattered from their original ordered arrangement based on SEM observation. Moreover, our results also suggested that alternation of zeta potential enhanced membrane permeability, and beyond a critical point, it leads to cell death. The leakages of intracellular constituents were confirmed by Gas Chromatography-Mass Spectrometry (GC-MS). In conclusion, the combine results suggested that at a specific dose, nano-silver may destroy the structure of bacterial membrane and depress its activity, which causes bacteria to die eventually. Copyright © 2018 Elsevier GmbH. All rights reserved.
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Review of new insights into antimicrobial agents.
Dehghan Esmatabadi, M J; Bozorgmehr, A; Hajjari, S N; Sadat Sombolestani, A; Malekshahi, Z V; Sadeghizadeh, M
2017-02-28
People have known the bacteria and have used various ways to deal with them, from a long time ago. Perhaps, natural antibiotics with have been the first step in fighting against pathogens. However, several factors, such as dealing with unfamiliar bacteria or emergence of drug-resistant species, have motivated us to discover new antibiotics or even change previous types. In this regard, a variety of natural and synthetic antibiotics with different origins, mechanism of action, structures and functional spectrum, have been developed and used. Some impact on the synthesis of nucleic acids and some affect protein synthesis so destroy bacteria. There is a ring in the structure of most of the antibiotics which gives them special properties. However, despite their numerous advantages, antibiotics also have drawbacks ehich limit their use in all situations. Therefore, other approaches such as photodynamic therapy (PDT) and antibacterial peptides were considered as alternatives. Photodynamic therapy (PDT) is a treatment that uses photosensitizing agents, along with light, to kill bacteria. The photosensitizing agents only work after they have been activated by certain kinds of light. Antibacterial peptides are a unique and diverse group of molecules which have between 12 and 50 amino acids in general. In this paper, will reviewt hree mentioned topics, namely antibiotics, photodynamic therapy and antibacterial peptides and will discuss the advantages and disadvantages of each approach briefly.
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Lifescience Database Archive (English)
Full Text Available C4H6O6 D06282.gif ... Neuropsychiatric agent ... DG01571 ... Nicotinic cholinergic receptor partial agonist Other ... DG01718 ... Drugs... for addictive disorder ... DG01715 ... Drugs for nicotine dependence Therapeutic category: 7990 A
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International Nuclear Information System (INIS)
Asmis, Lars; Tanner, Felix C.; Sudano, Isabella; Luescher, Thomas F.; Camici, Giovanni G.
2010-01-01
Background: DMSO is routinely infused together with hematopoietic cells in patients undergoing myeloablative therapy and was recently found to inhibit smooth muscle cells proliferation and arterial thrombus formation in the mouse by preventing tissue factor (TF), a key activator of the coagulation cascade. This study was designed to investigate whether DMSO prevents platelet activation and thus, whether it may represent an interesting agent to be used on drug eluting stents. Methods and results: Human venous blood from healthy volunteers was collected in citrated tubes and platelet activation was studied by cone and platelet analyzer (CPA) and rapid-platelet-function-assay (RPFA). CPA analysis showed that DMSO-treated platelets exhibit a lower adherence in response to shear stress (-15.54 ± 0.9427%, n = 5, P < 0.0001 versus control). Additionally, aggregometry studies revealed that DMSO-treated, arachidonate-stimulated platelets had an increased lag phase (18.0% ± 4.031, n = 9, P = 0.0004 versus control) as well as a decreased maximal aggregation (-6.388 ± 2.212%, n = 6, P = 0.0162 versus control). Inhibitory action of DMSO could be rescued by exogenous thromboxane A2 and was mediated, at least in part, by COX-1 inhibition. Conclusions: Clinically relevant concentrations of DMSO impair platelet activation by a thromboxane A2-dependent, COX-1-mediated effect. This finding may be crucial for the previously reported anti-thrombotic property displayed by DMSO. Our findings support a role for DMSO as a novel drug to prevent not only proliferation, but also thrombotic complications of drug eluting stents.
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Synthesis of radiolabeled racemic and enantiomeric antiarrhythmic agents
Energy Technology Data Exchange (ETDEWEB)
Stolle, W.T.; Stelzer, L.S.; Hester, J.B.; Perricone, S.C.; Hsi, R.S.P. (Upjohn Co., Kalamazoo, MI (United States))
1994-10-01
Ibutilide fumarate, racemic N-[4-[4-(ethyl-n-heptylamino)-hydroxybutyl]phenyl]methanesulfonamide hemifumarate, and artilide, the R-(+)-enantiomer of N-[4-[4-(ethyl-n-heptylamino)-hydroxybutyl]phenyl]methanesulfonamide hemifumerate, are under clinical investigation as Class III antiarrhythmic agents. For conducting drug disposition studies, we synthesized carbon-14 labeled ibutilide, as well as its two enantiomeric forms. In addition, high specific activity tritium labeled ibutilide was also prepared to facilitate development of a radioimmunoassay and for studying receptor site characteristics of this agent. Results of metabolism studies with [[sup 14]C]ibutilide led us to prepare tritium labeled artilide, which is more readily accessible than the C-14 labeled drug. The optical antipode of artilide was also labeled with tritium for comparative drug disposition investigations on the two enantiomers. (author).
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Full Text Available ... RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/ ...
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Full Text Available ... Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens ... Substance Use and SUDs in LGBT Populations Treatment Trends & Statistics Women and Drugs Publications Search Publications Orderable ...
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Speck, Ulrich; Scheller, Bruno; Rutsch, Wolfgang; Laule, Michael; Stangl, Verena
2011-05-01
Our initial investigations into restenosis inhibition by local drug delivery were prompted by reports on an improved outcome of coronary interventions, including a lower rate of target lesion revascularisation, when the intervention was performed with an ionic instead of non-ionic contrast medium. Although this was not confirmed in an animal study, the short exposure of the vessel wall to paclitaxel dissolved in contrast agent or coated on balloons proved to be efficacious. A study comparing three methods of local drug delivery to the coronary artery in pigs indicated the following order of efficacy in inhibiting neointimal proliferation: paclitaxel-coated balloons > sirolimus-eluting stents, sustained drug release > paclitaxel in contrast medium. Cell culture experiments confirmed that cell proliferation can be inhibited by very short exposure to the drug. Shorter exposure times require higher drug concentrations. Effective paclitaxel concentrations in porcine arteries are achieved when the drug is dissolved in contrast medium or coated on balloons. Paclitaxel is an exceptional drug in that it stays in the treated tissue for a long time. This may explain the long-lasting efficacy of paclitaxel-coated balloons, but does not disprove the hypothesis that the agent blocks a process initiating long-lasting excessive neointimal proliferation, which occurs early after vessel injury.
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Lifescience Database Archive (English)
Full Text Available )2. Ca D02780.gif ... Neuropsychiatric agent ... DG01498 ... NMDA receptor antagonist Other ... DG01718 ... Drugs for add...ictive disorder ... DG01716 ... Drugs for alcohol dependence Therapeutic category: 1190 ATC code: N07BB03 Chemica
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2016-05-01
Hair loss can have major psychological consequences. It can be due to a wide variety of causes, including hormonal disorders, dietary factors, infections, inflammation, trauma, emotional factors, and cancer. Drugs can also induce hair loss, by interacting with the hair growth cycle. Drug-induced hair loss may be immediate or delayed, sudden or gradual, and diffuse or localised. It is usually reversible after drug discontinuation. The drugs most often implicated in hair loss are anticancer agents, interferon, azole antifungals, lithium, immunosuppressants, and many other drugs belonging to a variety of pharmacological classes.
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Directory of Open Access Journals (Sweden)
Alaíde Braga de Oliveira
2009-08-01
Full Text Available Malaria is still the most destructive and dangerous parasitic infection in many tropical and subtropical countries. The burden of this disease is getting worse, mainly due to the increasing resistance of Plasmodium falciparum against the widely available antimalarial drugs. There is an urgent need for new, more affordable and accessible antimalarial agents possessing original modes of action. Natural products have played a dominant role in the discovery of leads for the development of drugs to treat human diseases, and this fact anticipates that new antimalarial leads may certainly emerge from tropical plant sources. This present review covers most of the recently-published non-alkaloidal natural compounds from plants with antiplasmodial and antimalarial properties, belonging to the classes of terpenes, limonoids, flavonoids, chromones, xanthones, anthraquinones, miscellaneous and related compounds, besides the majority of papers describing antiplasmodial crude extracts published in the last five years not reviewed before. In addition, some perspectives and remarks on the development of new drugs and phytomedicines for malaria are succinctly discussed.
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Emerging migraine treatments and drug targets
DEFF Research Database (Denmark)
Olesen, Jes; Ashina, Messoud
2011-01-01
Migraine has a 1-year prevalence of 10% and high socioeconomic costs. Despite recent drug developments, there is a huge unmet need for better pharmacotherapy. In this review we discuss promising anti-migraine strategies such as calcitonin gene-related peptide (CGRP) receptor antagonists and 5......-hydroxytrypamine (5-HT)(1F) receptor agonists, which are in late-stage development. Nitric oxide antagonists are also in development. New forms of administration of sumatriptan might improve efficacy and reduce side effects. Botulinum toxin A has recently been approved for the prophylaxis of chronic migraine....... Tonabersat, a cortical spreading depression inhibitor, has shown efficacy in the prophylaxis of migraine with aura. Several new drug targets such as nitric oxide synthase, the 5-HT(1D) receptor, the prostanoid receptors EP(2) and EP(4), and the pituitary adenylate cyclase receptor PAC1 await development...
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Lung Damage due to Chemotherapeutic Agents
Directory of Open Access Journals (Sweden)
Serdar Kalemci
2014-12-01
Full Text Available Chemotherapeutic drug-induced pulmonary toxicity not only emerges in cumulative doses, but also can be observed even at low dosages. Combined administration of many drugs, concurrent radiotherapy applications, opportunistic infections, lymphangitic tumor extension and pleural metastases complicate the disease diagnosis.
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Thymoquinone: an emerging natural drug with a wide range of medical applications
Directory of Open Access Journals (Sweden)
Mohannad Khader
2015-12-01
Full Text Available Nigella sativa has attracted healers in ancient civilizations and researchers in recent times. Traditionally, it has been used in different forms to treat many diseases including asthma, hypertension, diabetes, inflammation, cough, bronchitis, headache, eczema, fever, dizziness and influenza. Experimentally, it has been demonstrated that N. sativa extracts and the main constituent of their volatile oil, thymoquinone, possess antioxidant, anti-inflammatory and hepatoprotective properties. In this review we aimed at summarizing the most recent investigations related to a few and most important effects of thymoquinone. It is concluded that thymoquinone has evidently proved its activity as hepatoprotective, anti-inflammatory, antioxidant, cytotoxic and anti-cancer chemical, with specific mechanisms of action, which provide support to consider this compound as an emerging drug. Further research is required to make thymoquinone a pharmaceutical preparation ready for clinical trials.
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Variations on agent-oriented programming
Directory of Open Access Journals (Sweden)
Dalia Baziukė
2017-12-01
Full Text Available Occurrence of the agent paradigm and its further applications have stimulated the emergence of new concepts and methodologies in computer science. Today terms like multi-agent system, agent-oriented methodology, and agent-oriented programming (AOP are widely used. The aim of this paper is to clarify the validity of usage of the terms AOP and AOP language. This is disclosed in two phases of an analysis process. Determining to which concepts, terms like agent, programming, object-oriented analysis and design, object-oriented programming, and agent-oriented analysis and design correspond is accomplished in the first phase. Analysis of several known agent system engineering methodologies in terms of key concepts used, final resulting artifacts, and their relationship with known programming paradigms and modern tools for agent system development is performed in the second phase. The research shows that in most cases in the final phase of agent system design and in the coding stage, the main artifact is an object, defined according to the rules of the object-oriented paradigm. Hence, we say that the computing society still does not have AOP owing to the lack of an AOP language. Thus, the term AOP is very often incorrectly assigned to agent system development frameworks that in most cases, transform agents into objects.DOI: 10.15181/csat.v5i1.1361
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Exploring drug-target interaction networks of illicit drugs
Atreya, Ravi V; Sun, Jingchun; Zhao, Zhongming
2013-01-01
Background Drug addiction is a complex and chronic mental disease, which places a large burden on the American healthcare system due to its negative effects on patients and their families. Recently, network pharmacology is emerging as a promising approach to drug discovery by integrating network biology and polypharmacology, allowing for a deeper understanding of molecular mechanisms of drug actions at the systems level. This study seeks to apply this approach for investigation of illicit dru...
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Filled carbon nanotubes in biomedical imaging and drug delivery.
Martincic, Markus; Tobias, Gerard
2015-04-01
Carbon nanotubes have been advocated as promising candidates in the biomedical field in the areas of diagnosis and therapy. In terms of drug delivery, the use of carbon nanotubes can overcome some limitations of 'free' drugs by improving the formulation of poorly water-soluble drugs, allowing targeted delivery and even enabling the co-delivery of two or more drugs for combination therapy. Two different approaches are currently being explored for the delivery of diagnostic and therapeutic agents by carbon nanotubes, namely attachment of the payload to the external sidewalls or encapsulation into the inner cavities. Although less explored, the latter confers additional stability to the chosen diagnostic or therapeutic agents, and leaves the backbone structure of the nanotubes available for its functionalization with dispersing and targeting moieties. Several drug delivery systems and diagnostic agents have been developed in the last years employing the inner tubular cavities of carbon nanotubes. The research discussed in this review focuses on the use of carbon nanotubes that contain in their interior drug molecules and diagnosis-related compounds. The approaches employed for the development of such nanoscale vehicles along with targeting and releasing strategies are discussed. The encapsulation of both biomedical contrast agents and drugs inside carbon nanotubes is further expanding the possibilities to allow an early diagnosis and treatment of diseases.
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Directory of Open Access Journals (Sweden)
Garduño-Espinosa J
2002-05-01
Full Text Available Abstract Background Several neuromuscular blocking (NMB agents are available for clinical use in anesthesia. The present study was performed in order to identify preferences and behaviors of anesthesiologists for using vecuronium, rocuronium or other NMB agents in their clinical practice. Material and methods The cross-sectional survey was applied at the Updated Course of the Colegio Mexicano de Anestesiología performed last year. Of 989, 282 (28.5% surveys were returned. Results Most anesthesiologists were working at both public and private hospitals, performed anesthetic procedures for hospitalized and ambulatory patients, and anesthetized children as well as adults. Respondents did not consider mechanomyography as the gold standard method for neuromuscular monitoring. The T25 was not recognized as a pharmacodynamic parameter that represents the clinical duration of the neuromuscular block. Most answered that vecuronium induces less histamine release than rocuronium, had never used any neuromuscular monitor, did not know the cost of vecuronium and rocuronium, and preferred rocuronium in multiple-sampling vials and vecuronium in either a vial for single or multiple sampling. Rocuronium was preferred for emergency surgery in patients with full stomach only. Almost all of anesthesiologists that conserve the unused drug did it without refrigeration and more than 30% conserve the unused drug in one syringe for further use. Conclusion Vecuronium was preferred for most clinical situations, and the decision for this choice was not based on costs. Storage of unused drugs without refrigeration in a single syringe for purpose of future use in several patients represented a dangerous common practice.
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An emerging platform for drug delivery: aerogel based systems.
Ulker, Zeynep; Erkey, Can
2014-03-10
Over the past few decades, advances in "aerogel science" have provoked an increasing interest for these materials in pharmaceutical sciences for drug delivery applications. Because of their high surface areas, high porosities and open pore structures which can be tuned and controlled by manipulation of synthesis conditions, nanostructured aerogels represent a promising class of materials for delivery of various drugs as well as enzymes and proteins. Along with biocompatible inorganic aerogels and biodegradable organic aerogels, more complex systems such as surface functionalized aerogels, composite aerogels and layered aerogels have also been under development and possess huge potential. Emphasis is given to the details of the aerogel synthesis and drug loading methods as well as the influence of synthesis parameters and loading methods on the adsorption and release of the drugs. Owing to their ability to increase the bioavailability of low solubility drugs, to improve both their stability and their release kinetics, there are an increasing number of research articles concerning aerogels in different drug delivery applications. This review presents an up to date overview of the advances in all kinds of aerogel based drug delivery systems which are currently under investigation. Copyright © 2014 Elsevier B.V. All rights reserved.
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Emerging drugs for gastroesophageal reflux disease
Boeckxstaens, G. E.
2009-01-01
Proton pump inhibitors (PPIs) are very effective and safe drugs for the treatment of erosive and non-erosive gastroesophageal reflux disease (GERD). Nevertheless, a significant proportion of GERD patients (30 - 40%) continue to suffer from symptoms during PPI treatment, which has stimulated the
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Targeted Drug-Carrying Bacteriophages as Antibacterial Nanomedicines▿
Yacoby, Iftach; Bar, Hagit; Benhar, Itai
2007-01-01
While the resistance of bacteria to traditional antibiotics is a major public health concern, the use of extremely potent antibacterial agents is limited by their lack of selectivity. As in cancer therapy, antibacterial targeted therapy could provide an opportunity to reintroduce toxic substances to the antibacterial arsenal. A desirable targeted antibacterial agent should combine binding specificity, a large drug payload per binding event, and a programmed drug release mechanism. Recently, w...
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21 CFR 178.3130 - Antistatic and/or anti-fogging agents in food-packaging materials.
2010-04-01
...-packaging materials. 178.3130 Section 178.3130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF.../or anti-fogging agents in food-packaging materials. The substances listed in paragraph (b) of this section may be safely used as antistatic and/or antifogging agents in food-packaging materials, subject to...
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Bedaquiline resistance: Its emergence, mechanism and prevention.
Nguyen, Thi Van Anh; Anthony, Richard M; Bañuls, Anne-Laure; Vu, Dinh Hoa; Alffenaar, Jan-Willem C
2017-01-01
Bedaquiline, a new anti-tuberculosis drug, has already been used in more than 50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This paper aims to review currently identified mechanisms of resistance, the emergence of bedaquiline
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Innovative agents in cancer prevention.
Manson, Margaret M; Farmer, Peter B; Gescher, Andreas; Steward, William P
2005-01-01
There are many facets to cancer prevention: a good diet, weight control and physical activity, a healthy environment, avoidance of carcinogens such as those in tobacco smoke, and screening of populations at risk to allow early detection. But there is also the possibility of using drugs or naturally occurring compounds to prevent initiation of, or to suppress, tumour growth. Only a few such agents have been used to date in the clinic with any success, and these include non-steroidal anti-inflammatory drugs for colon, finasteride for prostate and tamoxifen or raloxifene for breast tumours. An ideal chemopreventive agent would restore normal growth control to a preneoplastic or cancerous cell population by modifying aberrant signalling pathways or inducing apoptosis (or both) in cells beyond repair. Characteristics for such an agent include selectivity for damaged or transformed cells, good bioavailability and more than one mechanism of action to foil redundancy or crosstalk in signalling pathways. As more research effort is being targeted towards this area, the distinction between chemotherapeutic and chemopreventive agents is blurring. Chemotherapeutic drugs are now being designed to target over- or under-active signalling molecules within cancer cells, a philosophy which is just as relevant in chemoprevention. Development of dietary agents is particularly attractive because of our long-standing exposure to them, their relative lack of toxicity, and encouraging indications from epidemiology. The carcinogenic process relies on the cell's ability to proliferate abnormally, evade apoptosis, induce angiogenesis and metastasise to distant sites. In vitro studies with a number of different diet-derived compounds suggest that there are molecules capable of modulating each of these aspects of tumour growth. However, on the negative side many of them have rather poor bioavailability. The challenge is to uncover their multiple mechanisms of action in order to predict their
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Zhang, Jie; Zhang, Yu; Liu, Junxi; Li, Guozhong; Wen, Zhaohui; Zhao, Yue; Zhang, Xiangyu; Liu, Fenghua
2017-10-01
The application of ultrasound contrast agents not only is confined to the enhancement of ultrasound imaging but also has started to be used as a drug system for diagnosis and treatment. In this paper, Span60 and PEG1500 were used as membrane materials, and a new targeting and drug-loading multifunctional ultrasound contrast agent microbubble enveloping the FA-CNTs-PTX complex was successfully prepared by acoustic cavitation. With the breast cancer cell line MCF7 as the research target, the effects of the microbubble with FA-CNTs-PTX on the proliferation and toxicity of MCF7 cells were studied using a CCK-8 and AO/EB double-staining method. The influences of the microbubbles with FA-CNTs-PTX on the cellular morphology and apoptosis period of the MCF7 cells were detected using an inverted fluorescence microscope. The apoptosis of MCF7 cells induced by the microbubbles with FA-CNTs-PTX was investigated with flow cytometry and an annexin and PI double staining fluorescence quantitative analysis. The results indicated that the ultrasound contrast agent microbubble with FA-CNTs-PTX remarkably inhibited the proliferation of MCF7 cells, which was mainly controlled by the drug loading rate and the nanometer size of the microbubbles. Moreover, the proliferative inhibition rate of the microbubbles with FA-CNTs-PTX was related to the cell apoptosis period of MCF7 cells. Its inhibition degree on the proliferation of MCF7 cells was higher than that of the hepatoma HepG2 cells. The apoptosis rate of MCF7 cells induced by the microbubbles with FA-CNTs-PTX was higher than that of normal human umbilical vein endothelial cells (HUVECs), and the microbubbles with FA-CNTs-PTX could target the MCF7 cells. Copyright © 2017 Elsevier B.V. All rights reserved.
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Recreational drug discovery: natural products as lead structures for the synthesis of smart drugs.
Appendino, Giovanni; Minassi, Alberto; Taglialatela-Scafati, Orazio
2014-07-01
Covering: up to December 2013. Over the past decade, there has been a growing transition in recreational drugs from natural materials (marijuana, hashish, opium), natural products (morphine, cocaine), or their simple derivatives (heroin), to synthetic agents more potent than their natural prototypes, which are sometimes less harmful in the short term, or that combine properties from different classes of recreational prototypes. These agents have been named smart drugs, and have become popular both for personal consumption and for collective intoxication at rave parties. The reasons for this transition are varied, but are mainly regulatory and commercial. New analogues of known illegal intoxicants are invisible to most forensic detection techniques, while the alleged natural status and the lack of avert acute toxicity make them appealing to a wide range of users. On the other hand, the advent of the internet has made possible the quick dispersal of information among users and the on-line purchase of these agents and/or the precursors for their synthesis. Unlike their natural products chemotypes (ephedrine, mescaline, cathinone, psilocybin, THC), most new drugs of abuse are largely unfamiliar to the organic chemistry community as well as to health care providers. To raise awareness of the growing plague of smart drugs we have surveyed, in a medicinal chemistry fashion, their development from natural products leads, their current methods of production, and the role that clandestine home laboratories and underground chemists have played in the surge of popularity of these drugs.
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Drug shortages: Implications for medical toxicology.
Mazer-Amirshahi, Maryann; Hawley, Kristy L; Zocchi, Mark; Fox, Erin; Pines, Jesse M; Nelson, Lewis S
2015-07-01
Drug shortages have significantly increased over the past decade. There are limited data describing how shortages impact medical toxicology of drugs. To characterize drug shortages affecting the management of poisoned patients. Drug shortage data from January 2001 to December 2013 were obtained from the University of Utah Drug Information Service. Shortage data for agents used to treat poisonings were analyzed. Information on drug type, formulation, reason for shortage, shortage duration, marketing, and whether the drug was available from a single source was collected. The availability of a substitute therapy and whether substitutes were in shortage during the study period were also investigated. Of 1,751 shortages, 141 (8.1%) impacted drugs used to treat poisoned patients, and as of December 2013, 21 (14.9%) remained unresolved. New toxicology shortages increased steadily from the mid-2000s, reaching a high of 26 in 2011. Median shortage duration was 164 days (interquartile range: 76-434). Generic drugs were involved in 85.1% of shortages and 41.1% were single-source products. Parenteral formulations were often involved in shortages (89.4%). The most common medications in shortage were sedative/hypnotics (15.6%). An alternative agent was available for 121 (85.8%) drugs; however, 88 (72.7%) alternatives were also affected by shortages at some point during the study period. When present, the most common reasons reported were manufacturing delays (22.0%) and supply/demand issues (17.0%). Shortage reason was not reported for 48.2% of drugs. Toxicology drug shortages are becoming increasingly prevalent, which can result in both suboptimal treatment and medication errors from using less familiar alternatives. Drug shortages affected a substantial number of critical agents used in the management of poisoned patients. Shortages were often of long duration and for drugs without alternatives. Providers caring for poisoned patients should be aware of current shortages and
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Llorach-Pares, Laura; Nonell-Canals, Alfons; Sanchez-Martinez, Melchor; Avila, Conxita
2017-11-27
Computer-aided drug discovery/design (CADD) techniques allow the identification of natural products that are capable of modulating protein functions in pathogenesis-related pathways, constituting one of the most promising lines followed in drug discovery. In this paper, we computationally evaluated and reported the inhibitory activity found in meridianins A-G, a group of marine indole alkaloids isolated from the marine tunicate Aplidium , against various protein kinases involved in Alzheimer's disease (AD), a neurodegenerative pathology characterized by the presence of neurofibrillary tangles (NFT). Balance splitting between tau kinase and phosphate activities caused tau hyperphosphorylation and, thereby, its aggregation and NTF formation. Inhibition of specific kinases involved in its phosphorylation pathway could be one of the key strategies to reverse tau hyperphosphorylation and would represent an approach to develop drugs to palliate AD symptoms. Meridianins bind to the adenosine triphosphate (ATP) binding site of certain protein kinases, acting as ATP competitive inhibitors. These compounds show very promising scaffolds to design new drugs against AD, which could act over tau protein kinases Glycogen synthetase kinase-3 Beta (GSK3β) and Casein kinase 1 delta (CK1δ, CK1D or KC1D), and dual specificity kinases as dual specificity tyrosine phosphorylation regulated kinase 1 (DYRK1A) and cdc2-like kinases (CLK1). This work is aimed to highlight the role of CADD techniques in marine drug discovery and to provide precise information regarding the binding mode and strength of meridianins against several protein kinases that could help in the future development of anti-AD drugs.
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Microtubule destabilising agents: far more than just antimitotic anticancer drugs
Bates, Darcy; Eastman, Alan
2016-01-01
Vinca alkaloids have been approved as anticancer drugs for more than 50 years. They have been classified as cytotoxic chemotherapy drugs that act during cellular mitosis, enabling them to target fast growing cancer cells. With the evolution of cancer drug development there has been a shift towards new “targeted” therapies to avoid the side effects and general toxicities of “cytotoxic chemotherapies” such as the vinca alkaloids. Due to their original classification, many have overlooked the fa...
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Cardiovascular Effects of Performance-Enhancing Drugs.
La Gerche, André; Brosnan, Maria J
2017-01-03
Exercise and competitive sports should be associated with a wide range of health benefits with the potential to inspire a positive community health legacy. However, the reputation of sports is being threatened by an ever-expanding armamentarium of agents with real or perceived benefits in performance enhancement. In addition to the injustice of unfair advantage for dishonest athletes, significant potential health risks are associated with performance-enhancing drugs. Performance-enhancing drugs may have an effect on the cardiovascular system by means of directly altering the myocardium, vasculature, and metabolism. However, less frequently considered is the potential for indirect effects caused through enabling athletes to push beyond normal physiological limits with the potential consequence of exercise-induced arrhythmias. This review will summarize the known health effects of PEDs but will also focus on the potentially greater health threat posed by the covert search for performance-enhancing agents that have yet to be recognized by the World Anti-Doping Agency. History has taught us that athletes are subjected to unmonitored trials with experimental drugs that have little or no established efficacy or safety data. One approach to decrease drug abuse in sports would be to accept that there is a delay from when athletes start experimenting with novel agents to the time when authorities become aware of these drugs. This provides a window of opportunity for athletes to exploit with relative immunity. It could be argued that all off-label use of any agent should be deemed illegal. © 2016 American Heart Association, Inc.
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Arrhythmogenic effects of illicit drugs in athletes.
Furlanello, Francesco; Bentivegna, Stefano; Cappato, Riccardo; De Ambroggi, Luigi
2003-12-01
Cardiac arrhythmias are among the most important causes of non-eligibility to sports activities, and may be due to different causes (cardiomyopathies, myocarditis, coronary abnormalities, valvular diseases, primary electrical disorders, abuse of illicit drugs). The list of illicit drugs banned by the International Olympic Committee and yearly updated by the World Anti-Doping Agency includes the following classes: stimulants, narcotics, anabolic agents (androgenic steroids and others such as beta-2 stimulants), peptide hormones, mimetics and analogues, diuretics, agents with an antiestrogenic activity, masking agents. Almost all illicit drugs may cause, through a direct or indirect arrhythmogenic effect, in the short, medium or long term, a wide range of cardiac arrhythmias (focal or reentry type, supraventricular and/or ventricular), lethal or not, even in healthy subjects with no previous history of cardiac diseases. Therefore, given the widespread abuse of illicit drugs among athletes, in the management of arrhythmic athletes the cardiologist should always take into consideration the possibility that the arrhythmias be due to the assumption of illicit drugs (sometimes more than one type), especially if no signs of cardiac diseases are present. On the other hand, in the presence of latent underlying arrhythmogenic heart disease including some inherited cardiomyopathies at risk of sudden cardiac death, illicit drugs could induce severe cardiac arrhythmic effects.
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Wu, Lingjie; Wu, Ming; Zeng, Yongyi; Zhang, Da; Zheng, Aixian; Liu, Xiaolong; Liu, Jingfeng
2015-01-01
The combination of a multi-therapeutic mode with a controlled fashion is a key improvement in nanomedicine. Here, we synthesized polyethylene glycol (PEG)-modified doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) @CuS nanohybrids as efficient drug delivery carriers, combined with photothermal therapy and chemotherapy to enhance the therapeutic efficacy on hepatocellular carcinoma (HCC). The physical properties of the nanohybrids were characterized by transmission electron microscopy (TEM), N2 adsorption and desorption experiments and by the Vis-NIR absorption spectra. The results showed that the doxorubicin could be stored in the inner pores of mesoporous silica nanoparticles; the CuS nanoparticles, which are coated on the surface of a mesoporous silica nanoparticle, could serve as efficient photothermal therapy (PTT) agents; the loaded drug release could be easily triggered by NIR irradiation. The combination of the PTT treatment with controlled chemotherapy could further enhance the cancer ablation ability compared to any of the single approaches alone. Hence, the reported PEG-modified DOX-loaded mesoporous silica nanoparticle@CuS nanohybrids might be very promising therapeutic agents for HCC treatment.
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Full Text Available ... Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs ... from the Director of the National Institute on Drug Abuse, Dr. Nora D. Volkow. Message from the Director ...
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Boutroy, M J
1994-01-01
Drugs have been in the past and will in the future still be liable to induce apnea in neonates, infants and older children. At these different stages of development, the child may be abnormally vulnerable to respiratory disorders and apnea, and doses of drugs, without any abnormal side effects in adult patients, can be harmful in younger subjects. Drugs responsible for apnea during development are numerous, but more than half of the problems are induced by sedatives and hypnotics, among which phenothiazines, barbiturates, benzodiazepines (included transplacentally acquired) and general anesthetics are a few. Other pharmacological families are apnea inducers in the neonatal period and childhood: analgesics and opioid narcotics, agents acting at the levels of neuromuscular function and autonomic ganglia, and cardiovascular agents. The pathogenesis of these apneas depends on the disturbance of any mechanism responsible for the respiratory activity: medullary centers and brain stem structures, afferent influx to CNS, sleep stages, upper airways, lungs and respiratory muscles. At key stages such as birth and infancy, drugs may emphasize the particular sensitivity of the mechanisms responsible for inducing apnea. This might explain unexpected respiratory disorders during development.
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Polymeric drugs: Advances in the development of pharmacologically active polymers
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
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Phytosterols and anabolic agents versus designer drugs
Energy Technology Data Exchange (ETDEWEB)
Brabander, H.F. de [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium)]. E-mail: Hubert.DeBrabander@UGent.be; Verheyden, K. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium); Mortier, V. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium); Le Bizec, B. [LABERCA, Ecole Nationale Veterinaire de Nantes, BP 50707, F-44087 Nantes Cedex 03 (France); Verbeke, W. [Ghent University, Department of Agricultural Economics, Coupure links 653, B-9000 Ghent (Belgium); Courtheyn, D. [Federal Feed and Food Laboratory, Braemkasteelstraat 59, B-9050 Ghentbruges (Belgium); Noppe, H. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium)
2007-03-14
Cholesterol is a well-known component in fats of animal origin and it also is the precursor of natural hormones. Phytosterols appear in plants and only differ slightly in structure from cholesterol. An important difference however is the low absorption in the gut of phytosterols and their saturated derivatives, the phytostanols. As a result, there is time for all kind of reactions in faecal material inside and outside of the gut. Determination of the abuse of natural hormones may be based on gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Abuse of natural hormones changes the {sup 13}C/{sup 12}C ratio of some metabolites during a relatively long time. The formation of (natural) hormones in the gut may interfere with this method. Designer drugs are mainly known from sports doping. In animal fattening, designer drugs may be used as well. Small changes in the structure of (natural) hormones may lead to a new group of substances asking for new strategies for their detection and the constatation of their abuse.
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Phytosterols and anabolic agents versus designer drugs
International Nuclear Information System (INIS)
Brabander, H.F. de; Verheyden, K.; Mortier, V.; Le Bizec, B.; Verbeke, W.; Courtheyn, D.; Noppe, H.
2007-01-01
Cholesterol is a well-known component in fats of animal origin and it also is the precursor of natural hormones. Phytosterols appear in plants and only differ slightly in structure from cholesterol. An important difference however is the low absorption in the gut of phytosterols and their saturated derivatives, the phytostanols. As a result, there is time for all kind of reactions in faecal material inside and outside of the gut. Determination of the abuse of natural hormones may be based on gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Abuse of natural hormones changes the 13 C/ 12 C ratio of some metabolites during a relatively long time. The formation of (natural) hormones in the gut may interfere with this method. Designer drugs are mainly known from sports doping. In animal fattening, designer drugs may be used as well. Small changes in the structure of (natural) hormones may lead to a new group of substances asking for new strategies for their detection and the constatation of their abuse
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Directory of Open Access Journals (Sweden)
Kênnia Stephanie Morais Oliveira
2018-04-01
Full Text Available OBJETIVO: Expor a prática de uma atividade de extensão realizada no intuito capacitar os agentes penitenciários da Penitenciária Federal de Mossoró/RN. MÉTODOS: Para aplicação do Suporte Básico de Vida (SBV em situações de urgência/emergência. A atividade aconteceu no período de novembro de 2012 a setembro de 2013, coordenado por um docente, com a participação de 09 discentes da Faculdade de Enfermagem da Universidade do Estado do Rio Grande do Norte. RESULTADOS: A realização deste trabalho permitiu aos agentes penitenciários aperfeiçoar noções prévias acerca da temática, bem como adquirir novos conhecimentos, tendo em vista a possibilidade de aplicá-los no seu cotidiano no âmbito profissional, como também pessoal. CONCLUSÃO: Nesse sentido, os objetivos do projeto foram contemplados na medida em que foram evidenciados os avanços durante as etapas do ensino-aprendizagem.
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Portable Sensor for Chemical Nerve Agents and Organophosphorus Compounds
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...biomedical applications such as: tissue engineering, wound dressing materials, molecular imprinting, drug delivery, etc. In this experiment the hydrogel...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
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Heterocyclic Scaffolds: Centrality in Anticancer Drug Development.
Ali, Imran; Lone, Mohammad Nadeem; Al-Othman, Zeid A; Al-Warthan, Abdulrahman; Sanagi, Mohd Marsin
2015-01-01
Cancer has been cursed for human beings for long time. Millions people lost their lives due to cancer. Despite of the several anticancer drugs available, cancer cannot be cured; especially at the late stages without showing any side effect. Heterocyclic compounds exhibit exciting medicinal properties including anticancer. Some market selling heterocyclic anticancer drugs include 5-flourouracil, methortrexate, doxorubicin, daunorubicin, etc. Besides, some natural products such as vinblastine and vincristine are also used as anticancer drugs. Overall, heterocyclic moeities have always been core parts in the expansion of anticancer drugs. This article describes the importance of heterocyclic nuclei in the development of anticancer drugs. Besides, the attempts have been made to discuss both naturally occurring and synthetic heterocyclic compounds as anticancer agents. In addition, some market selling anticancer heterocyclic compounds have been described. Moreover, the efforts have been made to discuss the mechanisms of actions and recent advances in heterocyclic compounds as anticancer agents. The current challenges and future prospectives of heterocyclic compounds have also been discussed. Finally, the suggestions for syntheses of effective, selective, fast and human friendly anticancer agents are discussed into the different sections.
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Multi-Agent System-Based Microgrid Operation Strategy for Demand Response
Directory of Open Access Journals (Sweden)
Hee-Jun Cha
2015-12-01
Full Text Available The microgrid and demand response (DR are important technologies for future power grids. Among the variety of microgrid operations, the multi-agent system (MAS has attracted considerable attention. In a microgrid with MAS, the agents installed on the microgrid components operate optimally by communicating with each other. This paper proposes an operation algorithm for the individual agents of a test microgrid that consists of a battery energy storage system (BESS and an intelligent load. A microgrid central controller to manage the microgrid can exchange information with each agent. The BESS agent performs scheduling for maximum benefit in response to the electricity price and BESS state of charge (SOC through a fuzzy system. The intelligent load agent assumes that the industrial load performs scheduling for maximum benefit by calculating the hourly production cost. The agent operation algorithm includes a scheduling algorithm using day-ahead pricing in the DR program and a real-time operation algorithm for emergency situations using emergency demand response (EDR. The proposed algorithm and operation strategy were implemented both by a hardware-in-the-loop simulation test using OPAL-RT and an actual hardware test by connecting a new distribution simulator.
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Multi-drug resistant Staphylococcus aureus isolated from emergency ...
African Journals Online (AJOL)
Purpose: To study the prevalence of resistant strains of S. aureus isolated from surfaces, beds and various equipment of an Iranian hospital emergency ward. Methods: Two hundred swab samples were collected from the surfaces, beds, trolleys, surgical equipment and diagnostic medical devices in emergency ward.
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Allosteric cross-talk in chromatin can mediate drug-drug synergy
Adhireksan, Zenita; Palermo, Giulia; Riedel, Tina; Ma, Zhujun; Muhammad, Reyhan; Rothlisberger, Ursula; Dyson, Paul J.; Davey, Curt A.
2017-03-01
Exploitation of drug-drug synergism and allostery could yield superior therapies by capitalizing on the immensely diverse, but highly specific, potential associated with the biological macromolecular landscape. Here we describe a drug-drug synergy mediated by allosteric cross-talk in chromatin, whereby the binding of one drug alters the activity of the second. We found two unrelated drugs, RAPTA-T and auranofin, that yield a synergistic activity in killing cancer cells, which coincides with a substantially greater number of chromatin adducts formed by one of the compounds when adducts from the other agent are also present. We show that this occurs through an allosteric mechanism within the nucleosome, whereby defined histone adducts of one drug promote reaction of the other drug at a distant, specific histone site. This opens up possibilities for epigenetic targeting and suggests that allosteric modulation in nucleosomes may have biological relevance and potential for therapeutic interventions.
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Systemic Antifungal Agents: Current Status and Projected Future Developments
Seyedmousavi, S.; Rafati, H.; Ilkit, M.; Tolooe, A.; Hedayati, M.T.; Verweij, P.E.
2017-01-01
By definition, an antifungal agent is a drug that selectively destroys fungal pathogens with minimal side effects to the host. Despite an increase in the prevalence of fungal infections particularly in immunocompromised patients, only a few classes of antifungal drugs are available for therapy, and
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Adult Status Epilepticus: A Review of the Prehospital and Emergency Department Management
Billington, Michael; Kandalaft, Osama R.; Aisiku, Imoigele P.
2016-01-01
Seizures are a common presentation in the prehospital and emergency department setting and status epilepticus represents an emergency neurologic condition. The classification and various types of seizures are numerous. The objectives of this narrative literature review focuses on adult patients with a presentation of status epilepticus in the prehospital and emergency department setting. In summary, benzodiazepines remain the primary first line therapeutic agent in the management of status epilepticus, however, there are new agents that may be appropriate for the management of status epilepticus as second- and third-line pharmacological agents. PMID:27563928
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Advantage and limitations of nitrofurantoin in multi-drug resistant Indian scenario
Directory of Open Access Journals (Sweden)
Laishram Shakti
2015-01-01
Full Text Available Infections caused by antibiotic resistant pathogens are of significant concern and are associated with higher mortality and morbidity. Nitrofurantoin is a broad-spectrum bactericidal antibiotic and is effectively used to treat urinary tract infections (UTIs caused by E. coli, Klebsiella sp., Enterobacter sp., Enterococcus sp. and Staphylococcus aureus. It interfere with the synthesis of cell wall, bacterial proteins and DNA of both Gram positive and Gram negative pathogens. Nitrofurantoin has been used successfully for treatment and prophylaxis of acute lower urinary tract infections. With the emergence of antibiotic resistance, nitrofurantoin has become the choice of agent for treating UTIs caused by multi-drug resistant pathogens.
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Seely, Kathryn A; Lapoint, Jeff; Moran, Jeffery H; Fattore, Liana
2012-12-03
"K2" and "Spice" drugs (collectively hereafter referred to as Spice) represent a relatively new class of designer drugs that have recently emerged as popular alternatives to marijuana, otherwise characterized as "legal highs". These drugs are readily available on the Internet and sold in many head shops and convenience stores under the disguise of innocuous products like herbal blends, incense, or air fresheners. Although package labels indicate "not for human consumption", the number of intoxicated people presenting to emergency departments is dramatically increasing. The lack of validated and standardized human testing procedures and an endless supply of potential drugs of abuse are primary reasons why researchers find it difficult to fully characterize clinical consequences associated with Spice. While the exact chemical composition and toxicology of Spice remains to be determined, there is mounting evidence identifying several synthetic cannabinoids as causative agents responsible for psychoactive and adverse physical effects. This review provides updates of the legal status of common synthetic cannabinoids detected in Spice and analytical procedures used to test Spice products and human specimens collected under a variety of clinical circumstances. The pharmacological and toxicological consequences of synthetic cannabinoid abuse are also reviewed to provide a future perspective on potential short- and long-term implications. Copyright © 2012 Elsevier Inc. All rights reserved.
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Organic molecule-based photothermal agents: an expanding photothermal therapy universe.
Jung, Hyo Sung; Verwilst, Peter; Sharma, Amit; Shin, Jinwoo; Sessler, Jonathan L; Kim, Jong Seung
2018-04-03
Over the last decade, organic photothermal therapy (PTT) agents have attracted increasing attention as a potential complement for, or alternative to, classical drugs and sensitizers involving inorganic nanomaterials. In this tutorial review, we provide a structured description of the main classes of organic photothermal agents and their characteristics. Representative agents that have been studied in the context of photothermal therapy since 2000 are summarized and recent advances in using PTT agents to address various cancers indications are highlighted.
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2013-04-04
... foundations, emerging technologies and innovations in regulatory science, as well as the current quality and... strategies, while industry professionals from some of today's leading pharmaceutical companies present case.... Drug Safety. Emerging Active Pharmaceutical Ingredients (API) Regulations. Investigations. Emerging API...
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Fimantari, Khansa; Budianto, Emil
2018-04-01
Helicobacterpylori infection can be treated using trihydrate amoxicillin. However, this treatment is not effective enough, as the conventional dosage treatment has a relatively short retention time in the human stomach. In the present study, the amoxicillin trihydrate drug will be encapsulated into a semi-IPN K-PNVP hydrogel matrix with 7,5% KHCO3 as a pore-forming agent. The encapsulated drug is tested with in vitro method to see the efficiency of its encapsulation and dissolution. The hydrogel in situ loading produces an encapsulation efficiency value. The values of the encapsulation efficiency are 95% and 98%, while post loading hydrogel yields an encapsulation efficiency value is 77% and the dissolution is 84%. The study of drug dissolution mechanism was done by using mathematical equation model to know its kinetics and its mechanism of dissolution. The post loading hydrogel was done by using thefirst-order model, while hydrogel in situ loading used Higuchi model. The Korsmeyer-Peppas model shows that post loading hydrogel dissolution mechanism is a mixture of diffusion and erosion, and in situ loading hydrogel in the form of diffusion. It is supported by the results of hydrogel characterization, before and after dissolution test with an optical microscope. The results of the optical microscope show that the hydrogel surface before and after the dissolution tested for both methods shows the change becomes rougher.
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Oncogenic targets, magnitude of benefit, and market pricing of antineoplastic drugs.
Amir, Eitan; Seruga, Bostjan; Martinez-Lopez, Joaquin; Kwong, Ryan; Pandiella, Atanasio; Tannock, Ian F; Ocaña, Alberto
2011-06-20
The relationship between market pricing of new anticancer drugs and the magnitude of clinical benefit caused by them has not been reported. Randomized clinical trials (RCTs) that evaluated approved new agents for solid tumors by the U.S. Food and Drug administration since the year 2000 were assessed. Hazard ratios (HRs) and 95% CIs were extracted for time-to-event end points described for each RCT. HRs were pooled for three groups: agents directed against a specific molecular target, for which the target population is selected by a biomarker (group A); less specific biologic targeted agents (group B); and chemotherapeutic agents (group C). Monthly market prices of these different drugs were compared. For overall survival (OS), the pooled HR was 0.69 (95% CI, 0.59 to 0.81) for group A (six drugs, six trials); it was 0.78 (95% CI, 0.74 to 0.83) for group B (seven drugs, 14 trials); and it was 0.84 (95% CI, 0.79 to 0.90) for group C (eight drugs, 12 trials). For progression-free survival (PFS), the pooled HR was 0.42 (95% CI, 0.36 to 0.49) for group A (six drugs, seven trials); it was 0.57 (95% CI, 0.51 to 0.64) for group B (seven drugs, 14 trials); and it was 0.75 (95% CI, 0.66 to 0.85) for group C (six drugs, 10 trials). Tests for heterogeneity between subgroups were highly significant for PFS (P targets are clinically the most beneficial, but their monthly market prices are not significantly different from those of other anticancer agents.
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Emerging infectious diseases: a guide to diseases, causative agents, and surveillance
National Research Council Canada - National Science Library
Beltz, Lisa A
2011-01-01
"This important resource offers a comprehensive introduction to emerging and reemerging infectious disease, including the underlying mechanisms of microbial emergence, the technology used to detect...
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Full Text Available ... Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl ... groups of young people, guiding the use of technology, the discussion between friends, and the importance of ...
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Full Text Available ... Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl ... AIDS (acquired immune deficiency syndrome). AIDS is a disease of the immune system for which there is ...
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Full Text Available ... Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana ... person at risk for getting HIV. Drug and alcohol intoxication affect judgment and can lead to unsafe ...
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Drug-Target Kinetics in Drug Discovery.
Tonge, Peter J
2018-01-17
The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.
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Neuroprotection for Nerve Agent-Induced Brain Damage
National Research Council Canada - National Science Library
Newmark, Jonathan; Ballough, Gerald P; Filbert, Margaret G
2002-01-01
... secondary to exposure to nerve agents. Preliminary work in this laboratory has demonstrated proof of concept using a compound not yet approved for clinical use by the US Food and Drug Administration...
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A comparative study on the cost of new antibiotics and drugs of other therapeutic categories.
Falagas, Matthew E; Fragoulis, Konstantinos N; Karydis, Ioannis
2006-12-20
Drug treatment is becoming more expensive due to the increased cost for the introduction of new drugs, and there seems to be an uneven distribution of medication cost for different therapeutic categories. We hypothesized that the cost of new antimicrobial agents may differ from that of other therapeutic categories and this may play a role in the stagnation of development of new antibiotics. We performed a pharmaco-economical comparative analysis of the drug cost of treatment for new agents introduced in the United States drug market in various therapeutic categories. We calculated the drug cost (in US dollars) of a ten-day treatment of all new drugs approved by the FDA during the period between January 1997 and July 2003, according to the 2004 Red Book Pharmacy's Fundamental Reference. New anti-neoplastic agents were found to be the most expensive drugs in comparison to all other therapeutic categories, with a median ten-day drug-treatment cost of US$848 compared to the median ten-day drug-treatment costs of all other categories ranging from US$29 to US$301. On the other hand, new antimicrobial drugs were found to be much less expensive, with a median ten-day drug-treatment cost of US$137 and $US85 for all anti-microbial agents and for anti-microbial agents excluding anti-HIV medications, respectively. The drug-treatment cost of new medications varies considerably by different therapeutic categories. This fact may influence industry decisions regarding the development of new drugs and may play a role in the shortage of new antimicrobial agents in the fight against the serious problem of antimicrobial resistance.
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A Distributed Intelligent System for Emergency Convoy
Directory of Open Access Journals (Sweden)
Mohammed Benalla
2016-09-01
Full Text Available The general problem that guides this research is the ability to design a distributed intelligent system for guiding the emergency convoys; a solution that will be based on a group of agents and on the analysis of traffic in order to generate collective functional response. It fits into the broader issue of Distributed Artificial System (DAI, which is to operate a cooperatively computer agent into multi-agents system (MAS. This article describes conceptually two fundamental questions of emergency convoys. The first question is dedicated to find a response to the traffic situation (i.e. fluid way, while the second is devoted to the convoy orientation; while putting the point on the distributed and cooperative resolution for the general problem.
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Full Text Available ... Twitter YouTube Flickr RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts ... to HIV and progression of AIDS. Drugs of abuse and HIV both affect the brain. Research has ...
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Directory of Open Access Journals (Sweden)
Xingquan Zhang
2016-01-01
Full Text Available Unlike human immunodeficiency virus (HIV and hepatitis B virus (HBV, hepatitis C virus (HCV infection is a curable disease. Current direct antiviral agent (DAA targets are focused on HCV NS3/4A protein (protease, NS5B protein (polymerase and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi, simeprevir (Olysio, and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the “cure HCV” goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others.
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In Vitro Drug Metabolism by Human Carboxylesterase 1
DEFF Research Database (Denmark)
Thomsen, Ragnar; Rasmussen, Henrik B; Linnet, Kristian
2014-01-01
Carboxylesterase 1 (CES1) is the major hydrolase in human liver. The enzyme is involved in the metabolism of several important therapeutic agents, drugs of abuse, and endogenous compounds. However, no studies have described the role of human CES1 in the activation of two commonly prescribed...... a panel of therapeutic drugs and drugs of abuse to assess their inhibition of the hydrolysis of p-nitrophenyl acetate by recombinant CES1 and human liver microsomes. The screening assay confirmed several known inhibitors of CES1 and identified two previously unreported inhibitors: the dihydropyridine...... calcium antagonist, isradipine, and the immunosuppressive agent, tacrolimus. CES1 plays a role in the metabolism of several drugs used in the treatment of common conditions, including hypertension, congestive heart failure, and diabetes mellitus; thus, there is a potential for clinically relevant drug-drug...
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Neuromuscular transmission: new concepts and agents.
Boer, H.D. de
2009-01-01
Sugammadex is the first selective relaxant binding agent which was originally designed to reverse the steroidal NMB drug rocuronium. The results of recent studies demonstrate that sugammadex is effective for reversal of rocuronium and vecuronium-induced neuromuscular block without apparent
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Hypoglycaemia from misuse of oral hypoglycaemic agent in patients ...
African Journals Online (AJOL)
In conclusion, misuse of oral hypoglycaemic agents (OHA) to treat LUTS with subsequent presentation in hypoglycaemic coma should be of concern to the health care provider especially the urologist. It is of no benefit and constitutes drug abuse that should be discouraged. Keywords: drug abuse, hypoglycaemia, lower ...
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Exploiting Specific Interactions toward Next-Generation Polymeric Drug Transporters
Wieczorek, Sebastian; Krause, Eberhard; Hackbarth, Steffen; Roeder, Beate; Hirsch, Anna K. H.; Boerner, Hans G.
2013-01-01
A generic method describes advanced tailoring of polymer drug carriers based on polymer-block-peptides. Combinatorial means are used to select suitable peptide segments to specifically complex small-molecule drugs. The resulting specific drug formulation agents render insoluble drugs water-soluble
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Detoxifying antitumoral drugs via nanoconjugation: the case of gold nanoparticles and cisplatin.
Directory of Open Access Journals (Sweden)
Joan Comenge
Full Text Available Nanoparticles (NPs have emerged as a potential tool to improve cancer treatment. Among the proposed uses in imaging and therapy, their use as a drug delivery scaffold has been extensively highlighted. However, there are still some controversial points which need a deeper understanding before clinical application can occur. Here the use of gold nanoparticles (AuNPs to detoxify the antitumoral agent cisplatin, linked to a nanoparticle via a pH-sensitive coordination bond for endosomal release, is presented. The NP conjugate design has important effects on pharmacokinetics, conjugate evolution and biodistribution and results in an absence of observed toxicity. Besides, AuNPs present unique opportunities as drug delivery scaffolds due to their size and surface tunability. Here we show that cisplatin-induced toxicity is clearly reduced without affecting the therapeutic benefits in mice models. The NPs not only act as carriers, but also protect the drug from deactivation by plasma proteins until conjugates are internalized in cells and cisplatin is released. Additionally, the possibility to track the drug (Pt and vehicle (Au separately as a function of organ and time enables a better understanding of how nanocarriers are processed by the organism.
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Fluorine-Containing Taxoid Anticancer Agents and Their Tumor-Targeted Drug Delivery
Seitz, Joshua; Vineberg, Jacob G.; Zuniga, Edison S.; Ojima, Iwao
2013-01-01
A long-standing problem of conventional chemotherapy is the lack of tumor-specific treatments. Traditional chemotherapy relies on the premise that rapidly proliferating cancer cells are more likely to be killed by a cytotoxic agent. In reality, however, cytotoxic agents have very little or no specificity, which leads to systemic toxicity, causing undesirable severe side effects. Consequently, various “molecularly targeted cancer therapies” have been developed for use in specific cancers, incl...
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Grund, Jean-Paul C; Latypov, Alisher; Harris, Magdalena
2013-07-01
Krokodil, a homemade injectable opioid, gained its moniker from the excessive harms associated with its use, such as ulcerations, amputations and discolored scale-like skin. While a relatively new phenomenon, krokodil use is prevalent in Russia and the Ukraine, with at least 100,000 and around 20,000 people respectively estimated to have injected the drug in 2011. In this paper we review the existing information on the production and use of krokodil, within the context of the region's recent social history. We searched PubMed, Google Advanced Search, Google Scholar, YouTube and the media search engine www.Mool.com for peer reviewed or media reports, grey literature and video reports. Survey data from HIV prevention and treatment NGOs was consulted, as well as regional experts and NGO representatives. Krokodil production emerged in an atypical homemade drug production and injecting risk environment that predates the fall of communism. Made from codeine, the active ingredient is reportedly desomorphine, but - given the rudimentary 'laboratory' conditions - the solution injected may include various opioid alkaloids as well as high concentrations of processing chemicals, responsible for the localized and systemic injuries reported here. Links between health care and law enforcement, stigma and maltreatment by medical providers are likely to thwart users seeking timely medical help. A comprehensive response to the emergence of krokodil and associated harms should focus both on the substance itself and its rudimentary production methods, as well as on its micro and macro risk environments - that of the on-going syndemic of drug injecting, HIV, HCV, TB and STIs in the region and the recent upheaval in local and international heroin supply. The feasibility of harm reduction strategies for people who inject krokodil may depend more on political will than on the practical implementation of interventions. The legal status of opioid substitution treatment in Russia is a point
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Effect of Erythropoiesis-Stimulating Agent Policy Decisions
U.S. Department of Health & Human Services — Erythropoiesis-stimulating agents (ESAs) are used as a treatment for anemia in myelodysplastic syndromes (MDS) patients. In early 2007, the U.S. Food and Drug...
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P-glycoprotein targeted nanoscale drug carriers
Li, Wengang; Abu Samra, Dina Bashir Kamil; Merzaban, Jasmeen; Khashab, Niveen M.
2013-01-01
Multi-drug resistance (MDR) is a trend whereby tumor cells exposed to one cytotoxic agent develop cross-resistance to a range of structurally and functionally unrelated compounds. P -glycoprotein (P -gp) efflux pump is one of the mostly studied drug
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Radiation protective agents possessing anti-oxidative properties
Energy Technology Data Exchange (ETDEWEB)
Anzai, Kazunori; Ueno, Emi; Yoshida, Akira; Furuse, Masako; Ikota, Nobuo [National Inst. of Radiological Sciences, Research Center for Radiation Safety, Chiba, Chiba (Japan)
2005-11-15
The purpose of studies is to see mechanisms of radiation protection of agents possessing anti-oxidative properties because the initial step resulting in radiation hazard is the formation of radicals by water radiolysis. Agents were commercially available or synthesized proxyl derivatives (spin prove agents), commercially available spin-trapping agents, edaravone and TMG (a tocopherol glycoside). Mice and cultured cells were X-irradiated by Shimadzu Pantak HF-320 or 320S. Survivals of cells were determined by colony assay and of mice, to which the agents were given intraperitoneally before or after X-irradiation, within 30 days post irradiation. Plasma and marrow concentrations of proxyls were estimated by electron spin resonance (ESR) spectrometry. Mechanisms of their radiation protective effects were shown different from agent to agent. TMG was found effective even post irradiation, which suggests a possibility for a new drug development. Some (spin trapping agents and TMG), virtually ineffective at the cell level, were found effective in the whole body, suggesting the necessity of studies on their disposition and metabolism. (S.I.)
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Radiation protective agents possessing anti-oxidative properties
International Nuclear Information System (INIS)
Anzai, Kazunori; Ueno, Emi; Yoshida, Akira; Furuse, Masako; Ikota, Nobuo
2005-01-01
The purpose of studies is to see mechanisms of radiation protection of agents possessing anti-oxidative properties because the initial step resulting in radiation hazard is the formation of radicals by water radiolysis. Agents were commercially available or synthesized proxyl derivatives (spin prove agents), commercially available spin-trapping agents, edaravone and TMG (a tocopherol glycoside). Mice and cultured cells were X-irradiated by Shimadzu Pantak HF-320 or 320S. Survivals of cells were determined by colony assay and of mice, to which the agents were given intraperitoneally before or after X-irradiation, within 30 days post irradiation. Plasma and marrow concentrations of proxyls were estimated by electron spin resonance (ESR) spectrometry. Mechanisms of their radiation protective effects were shown different from agent to agent. TMG was found effective even post irradiation, which suggests a possibility for a new drug development. Some (spin trapping agents and TMG), virtually ineffective at the cell level, were found effective in the whole body, suggesting the necessity of studies on their disposition and metabolism. (S.I.)
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Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma
International Nuclear Information System (INIS)
Maes, Ken; Menu, Eline; Van Valckenborgh, Els; Van Riet, Ivan; Vanderkerken, Karin; De Bruyne, Elke
2013-01-01
Multiple myeloma (MM) is an incurable B-cell malignancy. Therefore, new targets and drugs are urgently needed to improve patient outcome. Epigenetic aberrations play a crucial role in development and progression in cancer, including MM. To target these aberrations, epigenetic modulating agents, such as DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi), are under intense investigation in solid and hematological cancers. A clinical benefit of the use of these agents as single agents and in combination regimens has been suggested based on numerous studies in pre-clinical tumor models, including MM models. The mechanisms of action are not yet fully understood but appear to involve a combination of true epigenetic changes and cytotoxic actions. In addition, the interactions with the BM niche are also affected by epigenetic modulating agents that will further determine the in vivo efficacy and thus patient outcome. A better understanding of the molecular events underlying the anti-tumor activity of the epigenetic drugs will lead to more rational drug combinations. This review focuses on the involvement of epigenetic changes in MM pathogenesis and how the use of DNMTi and HDACi affect the myeloma tumor itself and its interactions with the microenvironment