[Salem witches, flying brooms, and synthetic drugs].

Science.gov (United States)

Castellanos Tejero, Manuel; Castellanos Tejero, M de los Angeles

2002-10-01

As supplementary material to Health Education programs about synthetic drugs, the authors present a historical summary on LSD, stramonium and khat. "Tripis", Special K and other synthetic pills contain these substances and are being widely used by youths. The history of these main hallucinogenic active ingredients has a strong tie to the mythology of witchcraft and witches: a historically interesting time period bearing a large amount of religious intolerance. The objective of this review is to end the belief today's youth have that they are taking new substances which have no risks.

Risk control and rational recreation: A qualitative analysis of synthetic drug use among young urbanites in China.

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Lin, Shaozhen; Zhang, Yong-an

2014-07-01

To fight against the rapid growth of synthetic drugs, the Chinese government has strengthened the controls and regulation, incorporated synthetic drugs into the new detoxification system, and changed the inconsistent governance of synthetic and traditional drugs. This, however, has not stopped the spread of synthetic drugs among young urbanites. While scholars have focused on the loopholes and defects of specific drug control regulations, ethnographic inquiries illustrate how and why control does not work, or is even resisted by young drug users. In-depth qualitative interviews were conducted with 28 individuals aged between 20 and 35, recruited from a cohort of synthetic drug users in a Shanghai drug rehabilitation centre. Audio-recorded interviews elicited accounts of their daily experiences of drug use as well as their perspectives on the impact of the government's new drug control policies. The main themes voiced by our respondents include: (1) synthetic drugs are not addictive, and are used to feel 'high'; (2) synthetic drugs are used to achieve their goals, which are otherwise impossible through mainstream means; (3) users are confident that they will be able to manage the use of synthetic drugs without harm to themselves; (4) their worries concern administrative punishment rather than consequences to health. The participants of this study did not support the government's attempts to control the use of synthetic drugs. They viewed their use as rational recreation under the perceived boundaries of 'acceptable risks'. Even in the context of severe control, synthetic drugs have strong appeal to youths. Drug policy should acknowledge the experiences of users and consider the socio-cultural contexts of youth drug-taking. The personal experience of participants could help improve the Chinese Drug Control Act and regulations. Copyright © 2014 Elsevier B.V. All rights reserved.

Natural and synthetic biomaterials for controlled drug delivery.

Science.gov (United States)

Kim, Jang Kyoung; Kim, Hyung Jin; Chung, Jee-Young; Lee, Jong-Hwan; Young, Seok-Beom; Kim, Yong-Hee

2014-01-01

A wide variety of delivery systems have been developed and many products based on the drug delivery technology are commercially available. The development of controlled-release technologies accelerated new dosage form design by altering pharmacokinetic and pharmacodynamics profiles of given drugs, resulting in improved efficacy and safety. Various natural or synthetic polymers have been applied to make matrix, reservoir or implant forms due to the characteristics of polymers, especially ease of control for modifications of biocompatibility, biodegradation, porosity, charge, mechanical strength and hydrophobicity/hydrophilicity. Hydrogel is a hydrophilic, polymeric network capable of imbibing large amount of water and biological fluids. This review article introduces various applications of natural and synthetic polymer-based hydrogels from pharmaceutical, biomedical and bioengineering points of view.

A Randomized Trial of Employment-Based Reinforcement of Cocaine Abstinence in Injection Drug Users

OpenAIRE

Silverman, Kenneth; Wong, Conrad J; Needham, Mick; Diemer, Karly N; Knealing, Todd; Crone-Todd, Darlene; Fingerhood, Michael; Nuzzo, Paul; Kolodner, Kenneth

2007-01-01

High-magnitude and long-duration abstinence reinforcement can promote drug abstinence but can be difficult to finance. Employment may be a vehicle for arranging high-magnitude and long-duration abstinence reinforcement. This study determined if employment-based abstinence reinforcement could increase cocaine abstinence in adults who inject drugs and use cocaine during methadone treatment. Participants could work 4 hr every weekday in a workplace where they could earn about $10.00 per hour in ...

Evaluation of clay hybrid nanocomposites of different chain length as reinforcing agent for natural and synthetic rubbers

International Nuclear Information System (INIS)

Yehia, A.A.; Akelah, A.M.; Rehab, A.; El-Sabbagh, S.H.; El Nashar, D.E.; Koriem, A.A.

2012-01-01

Highlights: → The modified organo-clay (MMT-ATBN) markedly reinforce natural and synthetic rubbers. → The reinforcing efficiency of the organo-clay is much higher than HAF carbon black. → The reinforcing efficiency of MMT modified with different alkylamines greatly depend on the chain length. → The good compatibility of modified organo-clay with NBR can be attributed to the chemical nature. -- Abstract: Polymer nanocomposites are one of the highly discussed research topics in recent time. It has been reported in the present paper the preparation and the properties of different nanoclays based on sodium montmorillonite (bentonite) and some organic amines of varying chain lengths (dodecylamine, hexadecylamine and octadecylamine) beside amine-terminated butadiene-acrylonitrile copolymer (ATBN). The hybrid clays have been characterized with the help of Fourier Transform Infrared spectroscopy (FTIR). Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), Wide angle X-ray diffractions (WXRD), and Thermogravimetric analysis (TGA). X-ray results showed that the intergallery distance of the clay is increased as a result of the intercalation of the amines and ATBN. The nanocomposite clays were incorporated in natural and synthetic rubbers (NR, SBR and NBR). The physico-mechanical properties are greatly improved with loading low concentrations of the nanocomposite clays compared with carbon black.

Dynamics of synthetic drugs transmission model with psychological addicts and general incidence rate

Science.gov (United States)

Ma, Mingju; Liu, Sanyang; Xiang, Hong; Li, Jun

2018-02-01

Synthetic drugs are replacing traditional ones and becoming the main popular ones gradually, which have given rise to serious social issues in recent years. In this paper, a synthetic drugs transmission model with psychological addicts and general contact rate is proposed. The local and global stabilities are decided by the basic reproduction number R0. By analyzing the sensitivity of parameters, we obtain that controlling psychological addiction is better than drugs treatment. These results are verified by numerical simulations.

Caffeine increases the motivation to obtain non-drug reinforcers in rats

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Sheppard, A. Brianna; Gross, Skyler C.; Pavelka, Sarah A.; Hall, Melanie J.; Palmatier, Matthew I.

2012-01-01

BACKGROUND Caffeine is widely considered to be a reinforcer in humans, but this effect is difficult to measure in non-human animals. We hypothesized that caffeine may have dual reinforcing effects comparable to nicotine - limited primary reinforcing effects, but potent reinforcement enhancing effects. The present studies tested this hypothesis by investigating the effect of caffeine on responding for non-drug rewards. METHODS In two experiments, rats were shaped to respond on a progressive ratio (PR) schedule for sucrose solution (20% w/v; Experiment 1) or a fixed ratio 2 (FR2) schedule for a moderately reinforcing visual stimulus (VS; Experiment 2). Pretreatment with various doses of caffeine (0–50 mg/kg, intraperitoneal injection) were administered prior to tests over successive week days (M-F). In Experiment 1, acute administration of low-moderate caffeine doses (6.25–25 mg/kg) increased responding for sucrose under the PR schedule. This effect of caffeine declined over the initial 15 test days. In Experiment 2, only acute pretreatment with 12.5 mg/kg caffeine increased responding for the visual stimulus and complete tolerance to this effect of caffeine was observed over the 15 days of testing. In follow up tests we found that abstinence periods of 4 and 8 days resulted in incomplete recovery of the enhancing effects of caffeine. CONCLUSION The findings suggest that caffeine enhances the reinforcing effects of non-drug stimuli, but that the pharmacological profile of these effects may differ from other psychomotor stimulants. PMID:22336397

Adherence to synthetic disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: Results of the OBSERVAR Study.

Science.gov (United States)

Juan Mas, Antonio; Castañeda, Santos; Cantero Santamaría, José I; Baquero, José L; Del Toro Santos, Francisco J

2017-12-27

Treatment compliance with disease-modifying antirheumatic drugs (DMARD) is essential to achieve the therapeutic goals in rheumatoid arthritis (RA). However, despite the need for good compliance, there is evidence that patients with RA frequently fail to use DMARD for the control of RA. Thus, the main objective of the OBSERVAR study is to evaluate the reasons for the lack of therapeutic adherence to synthetic DMARD in these patients. A Delphi process involving 18 randomly selected Spanish rheumatologists determined the level of agreement with 66 causes of noncompliance selected from the literature in relation to synthetic DMARD in RA. The reasons for noncompliance were consistent in 75.7%, although 3 reasons (4.5%) were highly consistent: 1) not knowing what to do in the case of an adverse event with DMARD; 2) not having undergone adherence screening by health personnel for early detection of "noncompliant patients"; and 3) not having undergone interventions or strategies that improve adherence. In order to improve adherence to RA treatment with synthetic DMARD, the patient should be adequately informed of each new treatment introduced, the patient's compliance profile should be incorporated into the clinical routine and the patient's motivation for therapeutic compliance be reinforced through the methods available to us. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Immunomodulating activities of soluble synthetic polymer-bound drugs.

Science.gov (United States)

Ríhová, Blanka

2002-09-13

The introduction of a synthetic material into the body always affects different body systems, including the defense system. Synthetic polymers are usually thymus-independent antigens with only a limited ability to elicit antibody formation or to induce a cellular immune response against them. However, there are many other ways that they influence or can be used to influence the immune system of the host. Low-immunogenic water-soluble synthetic polymers sometimes exhibit significant immunomodulating activity, mainly concerning the activation/suppression of NK cells, LAK cells and macrophages. Some of them, such as poly(ethylene glycol) and poly[N-(2-hydroxypropyl)methacrylamide], can be used as effective protein carriers, as they are able to reduce the immunogenicity of conjugated proteins and/or to reduce non-specific uptake of liposome/nanoparticle-entrapped drugs and other therapeutic agents. Recently, the development of vaccine delivery systems prepared from biodegradable and biocompatible water-soluble synthetic polymers, microspheres, liposomes and/or nanoparticles has received considerable attention, as they can be tailored to meet the specific physical, chemical, and immunogenic requirements of a particular antigen and some of them can also act as adjuvants. Copyright 2002 Elsevier Science B.V.

[New polymer-drug systems based on natural and synthetic polymers].

Science.gov (United States)

Racoviţă, Stefania; Vasiliu, Silvia; Foia, Liliana

2010-01-01

The great versatility of polymers makes them very useful in the biomedical and pharmaceutical fields. The combination of natural and synthetic polymers leads to new materials with tailored functional properties. The aim of this work consists in the preparation of new drug delivery system based on chitosan (natural polymer) and polybetaines (synthetic polymers), by a simple process, well known in the literature as complex coacervation methods. Also, the adsorption and release studies of two antibiotics as well as the preservation of their bactericidal capacities were performed.

Traceability of synthetic drugs by position-specific deuterium isotope ratio analysis

Energy Technology Data Exchange (ETDEWEB)

Brenna, Elisabetta [Dipartimento di Chimica, Materiali e di Ingegneria Chimica del Politecnico di Milano and Istituto CNR per la Chimica del Riconoscimento Molecolare, Via Mancinelli 7, Milan I-20131 (Italy)], E-mail: elisabetta.brenna@polimi.it; Fronza, Giovanni [Dipartimento di Chimica, Materiali e di Ingegneria Chimica del Politecnico di Milano (Italy) and Instituto CNR per la Chimica del Riconoscimento Molecolare, Via Mancinelli 7, Milan I-20131 (Italy)], E-mail: giovanni.fronza@polimi.it; Fuganti, Claudio [Dipartimento di Chimica, Materiali e di Ingegneria Chimica del Politecnico di Milano (Italy) and Istituto CNR per la Chimica del Riconoscimento Molecolare, Via Mancinelli 7, Milan I-20131 (Italy)

2007-10-10

Samples of fluoxetine of different origin were submitted to natural abundance {sup 2}H NMR spectroscopy. The deuterium content at the various sites of the molecule was found to depend on its synthetic history. Hints on the synthetic procedure can be obtained by comparison with standard compounds, whose synthesis is known. These preliminary results give an idea of the potential of site-specific isotope ratio analysis in the fight against patent infringement and drug counterfeiting.

Traceability of synthetic drugs by position-specific deuterium isotope ratio analysis

International Nuclear Information System (INIS)

Brenna, Elisabetta; Fronza, Giovanni; Fuganti, Claudio

2007-01-01

Samples of fluoxetine of different origin were submitted to natural abundance 2 H NMR spectroscopy. The deuterium content at the various sites of the molecule was found to depend on its synthetic history. Hints on the synthetic procedure can be obtained by comparison with standard compounds, whose synthesis is known. These preliminary results give an idea of the potential of site-specific isotope ratio analysis in the fight against patent infringement and drug counterfeiting

Employment-based abstinence reinforcement promotes opiate and cocaine abstinence in out-of-treatment injection drug users.

Science.gov (United States)

Holtyn, August F; Koffarnus, Mikhail N; DeFulio, Anthony; Sigurdsson, Sigurdur O; Strain, Eric C; Schwartz, Robert P; Silverman, Kenneth

2014-01-01

We examined the use of employment-based abstinence reinforcement in out-of-treatment injection drug users, in this secondary analysis of a previously reported trial. Participants (N = 33) could work in the therapeutic workplace, a model employment-based program for drug addiction, for 30 weeks and could earn approximately $10 per hr. During a 4-week induction, participants only had to work to earn pay. After induction, access to the workplace was contingent on enrollment in methadone treatment. After participants met the methadone contingency for 3 weeks, they had to provide opiate-negative urine samples to maintain maximum pay. After participants met those contingencies for 3 weeks, they had to provide opiate- and cocaine-negative urine samples to maintain maximum pay. The percentage of drug-negative urine samples remained stable until the abstinence reinforcement contingency for each drug was applied. The percentage of opiate- and cocaine-negative urine samples increased abruptly and significantly after the opiate- and cocaine-abstinence contingencies, respectively, were applied. These results demonstrate that the sequential administration of employment-based abstinence reinforcement can increase opiate and cocaine abstinence among out-of-treatment injection drug users. © Society for the Experimental Analysis of Behavior.

Longer treatment with alternative non-drug reinforcement fails to reduce resurgence of cocaine or alcohol seeking in rats.

Science.gov (United States)

Nall, Rusty W; Craig, Andrew R; Browning, Kaitlyn O; Shahan, Timothy A

2018-04-02

Provision of alternative non-drug reinforcement is among the most effective methods for treating substance use disorders. However, when alternative reinforcers become unavailable during treatment interruptions or upon cessation of treatment, relapse often occurs. Relapse following the loss of alternative reinforcement is known as resurgence. One factor that could reduce resurgence is longer duration of treatment with alternative reinforcement, but the available data are mixed. Further, the effects of length of treatment have previously only been examined with food seeking. The present experiments directly examined if duration of treatment impacted the magnitude of resurgence of cocaine or alcohol seeking in rats. First, rats were trained to self-administer cocaine (Experiment 1) or alcohol (Experiment 2) by performing a target behavior. Second, target behavior was extinguished and performing an alternative behavior produced an alternative non-drug (i.e., food) reinforcer. Finally, resurgence was assessed following removal of alternative reinforcement after either 5 or 20 sessions of treatment. Treatment duration did not differentially affect resurgence of cocaine seeking in Experiment 1 or Alcohol seeking in Experiment 2. These results suggest that extended treatment with alternative non-drug reinforcement may not decrease propensity to relapse. Further, these results may have implications for treatment of substance use disorders and for theories of resurgence. Copyright © 2017 Elsevier B.V. All rights reserved.

A randomized trial of employment-based reinforcement of cocaine abstinence in injection drug users.

Science.gov (United States)

Silverman, Kenneth; Wong, Conrad J; Needham, Mick; Diemer, Karly N; Knealing, Todd; Crone-Todd, Darlene; Fingerhood, Michael; Nuzzo, Paul; Kolodner, Kenneth

2007-01-01

High-magnitude and long-duration abstinence reinforcement can promote drug abstinence but can be difficult to finance. Employment may be a vehicle for arranging high-magnitude and long-duration abstinence reinforcement. This study determined if employment-based abstinence reinforcement could increase cocaine abstinence in adults who inject drugs and use cocaine during methadone treatment. Participants could work 4 hr every weekday in a workplace where they could earn about $10.00 per hour in vouchers; they were required to provide routine urine samples. Participants who attended the workplace and provided cocaine-positive urine samples during the initial 4 weeks were invited to work 26 weeks and were randomly assigned to an abstinence-and-work (n = 28) or work-only (n = 28) group. Abstinence-and-work participants had to provide urine samples showing cocaine abstinence to work and maintain maximum pay. Work-only participants could work independent of their urinalysis results. Abstinence-and-work participants provided more (p = .004; OR = 5.80, 95% CI = 2.03-16.56) cocaine-negative urine samples (29%) than did work-only participants (10%). Employment-based abstinence reinforcement can increase cocaine abstinence.

Use of synthetic cathinones and cannabimimetics among injection drug users in San Diego, California.

Science.gov (United States)

Wagner, Karla D; Armenta, Richard F; Roth, Alexis M; Maxwell, Jane C; Cuevas-Mota, Jazmine; Garfein, Richard S

2014-08-01

Use of synthetic cathinones (SC) and cannabimimetics (i.e., "THC homologues" [TH]) is associated with adverse health effects. We investigated the epidemiology of synthetic drug use among a cohort of injection drug users (IDUs) in San Diego, California. We used logistic regression analysis to identify correlates of SC and TH use among 485 IDUs enrolled from June 2012 to September 2013. Seven percent of participants reported ever using SC and 30% reported ever using TH. In multivariate logistic regression, age and recent hospitalization were significantly associated with odds of SC use (Adjusted Odds Ratio [AOR] 0.93, 95% Confidence Interval [C.I.] 0.90, 0.97; and AOR 2.34 95% C.I. 1.00, 5.49, respectively) and TH use (AOR 0.96, 95% C.I. 0.94, 0.98; and AOR 2.62, 95% C.I. 1.47, 4.68, respectively). Use of methamphetamine (AOR 9.35, 95% C.I. 1.20, 72.79) and club drugs in the past six months (AOR 3.38, 95% C.I. 1.17, 9.76) were significantly associated with SC use. Being on probation/parole (AOR 2.42, 95% C.I. 1.44, 4.07), initiating injection drug use with stimulants (AOR 1.89 95% C.I. 1.13, 3.16), and past six-month marijuana (AOR 9.22, 95% C.I. 4.49, 18.96) and prescription drug use (AOR 1.98, 95% C.I. 1.20, 3.27) were significantly associated with TH use. A considerable proportion of IDU use synthetic drugs and may experience harms associated with their use. Findings have implications for criminal justice system management. Prevention efforts should emphasize the risks associated with rapidly changing synthetic formulations, and the potential harms associated with polydrug use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Synthetic Nano-Low Density Lipoprotein as Targeted Drug DeliveryVehicle for Glioblastoma Multiforme

Energy Technology Data Exchange (ETDEWEB)

Nikanjam, Mina; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Shu,Xiao; Budinger, Thomas F.; Forte, Trudy M.

2006-06-14

This paper discribes a synthetic low density lipoprotein(LDL) made by complexing a 29 amino acid that consists of a lipid bindingdomain and the LDL receptor binding domain with a lipid microemulsion.The nano-LDL particles were intermdiate in size between LDL and HDL andbound to LDL receptors on GBM brain tumor cells. Synthetic nano-LDLuptake by GBM cells was LDL receptor specific and dependent on cellreceptor number. It is suggested that these synthetic particles can serveas a delivery vehicle for hydophobic anti-tumor drugs by targeting theLDL receptor.

Natural and Synthetic Polymers as Inhibitors of Drug Efflux Pumps

Science.gov (United States)

2007-01-01

Inhibition of efflux pumps is an emerging approach in cancer therapy and drug delivery. Since it has been discovered that polymeric pharmaceutical excipients such as Tweens® or Pluronics® can inhibit efflux pumps, various other polymers have been investigated regarding their potential efflux pump inhibitory activity. Among them are polysaccharides, polyethylene glycols and derivatives, amphiphilic block copolymers, dendrimers and thiolated polymers. In the current review article, natural and synthetic polymers that are capable of inhibiting efflux pumps as well as their application in cancer therapy and drug delivery are discussed. PMID:17896100

Evaluation of synthetic zeolites as oral delivery vehicle for anti-inflammatory drugs

Directory of Open Access Journals (Sweden)

Elham Khodaverdi

2014-05-01

Full Text Available Objective(s: In this research, zeolite X and zeolite Y were used as vehicle to prepare intestine targeted oral delivery systems of indomethacin and ibuprofen. Materials and Methods: A soaking procedure was implemented to encapsulate indomethacin or ibuprofen within synthetic zeolites. Gravimetric methods and IR spectra of prepared formulations were used to assess drug loading efficiencies into zeolite structures. Scanning Electron Microscopy (SEM was also utilized to determine morphologies changes in synthetic zeolites after drug loading. At the next stage, dissolution studies were used to predict the in vivo performance of prepared formulations at HCl 0.1 N and PBS pH 6.5 as simulated gastric fluid (SGF and simulated intestine fluid (SIF, respectively. Results: Drug loadings of prepared formulations was determined between 24-26 % w/w. Dissolution tests at SGF were shown that zeolites could retain acidic model drugs in their porous structures and can be able to limit their release into the stomach. On the other hand, all prepared formulations completely released model drugs during 3 hr in simulated intestine fluid. Conclusion: Obtained results indicated zeolites could potentially be able to release indomethacin and ibuprofen in a sustained and controlled manner and reduced adverse effects commonly accompanying oral administrations of NSAIDs.

Developing and implementing a positive behavioral reinforcement intervention in prison-based drug treatment: Project BRITE.

Science.gov (United States)

Burdon, William M; St De Lore, Jef; Prendergast, Michael L

2011-09-01

Within prison settings, the reliance on punishment for controlling inappropriate or noncompliant behavior is self-evident. What is not so evident is the similarity between this reliance on punishment and the use of positive reinforcements to increase desired behaviors. However, seldom do inmates receive positive reinforcement for engaging in prosocial behaviors or, for inmates receiving drug treatment, behaviors that are consistent with or support their recovery. This study provides an overview of the development and implementation of a positive behavioral reinforcement intervention in male and female prison-based drug treatment programs. The active involvement of institutional staff, treatment staff, and inmates enrolled in the treatment programs in the development of the intervention along with the successful branding of the intervention were effective at promoting support and participation. However, these factors may also have ultimately impacted the ability of the randomized design to reliably demonstrate the effectiveness of the intervention.

The relevance of polymeric synthetic membranes in topical formulation assessment and drug diffusion study.

Science.gov (United States)

Ng, Shiow-Fern; Rouse, Jennifer J; Sanderson, Francis D; Eccleston, Gillian M

2012-03-01

Synthetic membranes are composed of thin sheets of polymeric macromolecules that can control the passage of components through them. Generally, synthetic membranes used in drug diffusion studies have one of two functions: skin simulation or quality control. Synthetic membranes for skin simulation, such as the silicone-based membranes polydimethylsiloxane and Carbosil, are generally hydrophobic and rate limiting, imitating the stratum corneum. In contrast, synthetic membranes for quality control, such as cellulose esters and polysulfone, are required to act as a support rather than a barrier. These synthetic membranes also often contain pores; hence, they are called porous membranes. The significance of Franz diffusion studies and synthetic membranes in quality control studies involves an understanding of the fundamentals of synthetic membranes. This article provides a general overview of synthetic membranes, including a brief background of the history and the common applications of synthetic membranes. This review then explores the types of synthetic membranes, the transport mechanisms across them, and their relevance in choosing a synthetic membrane in Franz diffusion cell studies for formulation assessment purposes.

Three-dimensional fabric reinforced concrete finds first use in reactor building

International Nuclear Information System (INIS)

Akihama, S.; Nakagava, H.

1989-01-01

It is reported about creation of concrete reinforced with synthetic fibers by Japanese firm Kadzima. Synthetic material with three-dimensional orientation of fibers is produced of roving impreganted with synthetic resin. The reinforcement produced is submerged into the concrete matrix. The compression strength of such a material makes up 58 MPa. The new material is used for constructing the nuclear reactor shielding containers

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

Oral Fluid vs. Urine Analysis to Monitor Synthetic Cannabinoids and Classic Drugs Recent Exposure.

Science.gov (United States)

Blandino, Vincent; Wetzel, Jillian; Kim, Jiyoung; Haxhi, Petrit; Curtis, Richard; Concheiro, Marta

2017-01-01

Urine is a common biological sample to monitor recent drug exposure, and oral fluid is an alternative matrix of increasing interest in clinical and forensic toxicology. Limited data are available about oral fluid vs. urine drug disposition, especially for synthetic cannabinoids. To compare urine and oral fluid as biological matrices to monitor recent drug exposure among HIV-infected homeless individuals. Seventy matched urine and oral fluid samples were collected from 13 participants. Cannabis, amphetamines, benzodiazepines, cocaine and opiates were analyzed in urine by the enzyme-multipliedimmunoassay- technique and in oral fluid by liquid chromatography tandem mass spectrometry (LCMSMS). Eleven synthetic cannabinoids were analyzed in urine and in oral fluid by LC-MSMS. Five oral fluid samples were positive for AB-FUBINACA. In urine, 4 samples tested positive for synthetic cannabinoids PB-22, 5-Fluoro-PB-22, AB-FUBINACA, and metabolites UR-144 5-pentanoic acid and UR-144 4-hydroxypentyl. In only one case, oral fluid and urine results matched, both specimens being AB-FUBINACA positive. For cannabis, 40 samples tested positive in urine and 30 in oral fluid (85.7% match). For cocaine, 37 urine and 52 oral fluid samples were positive (75.7% match). Twenty-four urine samples were positive for opiates, and 25 in oral fluid (81.4% match). For benzodiazepines, 23 samples were positive in urine and 25 in oral fluid (85.7% match). These results offer new information about drugs disposition between urine and oral fluid. Oral fluid is a good alternative matrix to urine for monitoring cannabis, cocaine, opiates and benzodiazepines recent use; however, synthetic cannabinoids showed mixed results. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Differential physiological and behavioral cues observed in individuals smoking botanical marijuana versus synthetic cannabinoid drugs.

Science.gov (United States)

Chase, Peter B; Hawkins, Jeff; Mosier, Jarrod; Jimenez, Ernest; Boesen, Keith; Logan, Barry K; Walter, Frank G

2016-01-01

Synthetic cannabinoid use has increased in many states, and medicinal and/or recreational marijuana use has been legalized in some states. These changes present challenges to law enforcement drug recognition experts (DREs) who determine whether drivers are impaired by synthetic cannabinoids or marijuana, as well as to clinical toxicologists who care for patients with complications from synthetic cannabinoids and marijuana. Our goal was to compare what effects synthetic cannabinoids and marijuana had on performance and behavior, including driving impairment, by reviewing records generated by law enforcement DREs who evaluated motorists arrested for impaired driving. Data were from a retrospective, convenience sample of de-identified arrest reports from impaired drivers suspected of using synthetic cannabinoids (n = 100) or marijuana (n = 33). Inclusion criteria were arrested drivers who admitted to using either synthetic cannabinoids or marijuana, or who possessed either synthetic cannabinoids or marijuana; who also had a DRE evaluation at the scene; and whose blood screens were negative for alcohol and other drugs. Exclusion criteria were impaired drivers arrested with other intoxicants found in their drug or alcohol blood screens. Blood samples were analyzed for 20 popular synthetic cannabinoids by using liquid chromatography-tandem mass spectrometry. Delta-9-tetrahydrocannabinol (THC) and THC-COOH were quantified by gas chromatography-mass spectrometry. Statistical significance was determined by using Fisher's exact test or Student's t-test, where appropriate, to compare the frequency of characteristics of those in the synthetic cannabinoid group versus those in the marijuana group. 16 synthetic cannabinoid and 25 marijuana records met selection criteria; the drivers of these records were arrested for moving violations. Median age for the synthetic cannabinoid group (n = 16, 15 males) was 20 years (IQR 19-23 years). Median age for the marijuana group (n = 25, 21

Learning from biology: synthetic lipoproteins for drug delivery.

Science.gov (United States)

Huang, Huang; Cruz, William; Chen, Juan; Zheng, Gang

2015-01-01

Synthetic lipoproteins represent a relevant tool for targeted delivery of biological/chemical agents (chemotherapeutics, siRNAs, photosensitizers, and imaging contrast agents) into various cell types. These nanoparticles offer a number of advantages for drugs delivery over their native counterparts while retaining their natural characteristics and biological functions. Their ultra-small size (lipoprotein receptors, i.e., low-density lipoprotein receptor (LDLR) and Scavenger receptor class B member 1 (SRB1) that are found in a number of pathological conditions (e.g., cancer, atherosclerosis), make them superior delivery strategies when compared with other nanoparticle systems. We review the various approaches that have been developed for the generation of synthetic lipoproteins and their respective applications in vitro and in vivo. More specifically, we summarize the approaches employed to address the limitation on use of reconstituted lipoproteins by means of natural or recombinant apolipoproteins, as well as apolipoprotein mimetic molecules. Finally, we provide an overview of the advantages and disadvantages of these approaches and discuss future perspectives for clinical translation of these nanoparticles. © 2014 Wiley Periodicals, Inc.

Kronic hysteria: exploring the intersection between Australian synthetic cannabis legislation, the media, and drug-related harm.

Science.gov (United States)

Bright, Stephen J; Bishop, Brian; Kane, Robert; Marsh, Ali; Barratt, Monica J

2013-05-01

Having first appeared in Europe, synthetic cannabis emerged as a drug of concern in Australia during 2011. Kronic is the most well-known brand of synthetic cannabis in Australia and received significant media attention. Policy responses were reactive and piecemeal between state and federal governments. In this paper we explore the relationship between media reports, policy responses, and drug-related harm. Google search engine applications were used to produce time-trend graphs detailing the volume of media stories being published online about synthetic cannabis and Kronic, and also the amount of traffic searching for these terms. A discursive analysis was then conducted on those media reports that were identified by Google as 'key stories'. The timing of related media stories was also compared with self-reported awareness and month of first use, using previously unpublished data from a purposive sample of Australian synthetic cannabis users. Between April and June 2011, mentions of Kronic in the media increased. The number of media stories published online connected strongly with Google searches for the term Kronic. These stories were necessarily framed within dominant discourses that served to construct synthetic cannabis as pathogenic and created a 'moral panic'. Australian state and federal governments reacted to this moral panic by banning individual synthetic cannabinoid agonists. Manufacturers subsequently released new synthetic blends that they claimed contained new unscheduled chemicals. Policies implemented within in the context of 'moral panic', while well-intended, can result in increased awareness of the banned product and the use of new yet-to-be-scheduled drugs with unknown potential for harm. Consideration of regulatory models should be based on careful examination of the likely intended and unintended consequences. Such deliberation might be limited by the discursive landscape. Copyright © 2012 Elsevier B.V. All rights reserved.

Synthetic Cannabinoids

Directory of Open Access Journals (Sweden)

Aslihan Okan Ibiloglu

2017-09-01

Full Text Available Synthetic cannabinoids which is a subgroup of cannabinoids are commonly used for recreational drug use throughout the whole world. Although both marijuana and synthetic cannabinoids stimulate the same receptors, cannabinoid receptor 1 (CB1 and cannabinoid receptor 2 (CB2, studies have shown that synthetic cannabinoids are much more potent than marijuana. The longer use of synthetic cannabinoids can cause severe physical and psychological symptoms that might even result in death, similar to many known illicit drugs. Main treatment options mostly involve symptom management and supportive care. The aim of this article is to discuss clinical and pharmacological properties of the increasingly used synthetic cannabinoids. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2017; 9(3.000: 317-328

Can reinforcement-based interventions to reduce drug use successfully be adapted to routine opioid maintenance treatment?

Directory of Open Access Journals (Sweden)

Michael Specka

2013-12-01

Full Text Available INTRODUCTION: Comorbid substance related disorders are a major health problem for patients in opioid maintenance treatment (OMT. It was investigated whether a reinforcement scheme adapted to the regulatory and financial restrictions of routine treatment reduces concomitant drug use. METHODS: OMT patients from 7 clinics who were using cocaine, benzodiazepines, heroin or amphetamines were randomly allocated to either treatment as usual (n = 64 or treatment with an additional escalating reinforcement scheme (n = 72 in which a patient's number of weekly take-home dosages was increased after 1, 4, 8 and 12 consecutive weeks with drug-free urine specimens. Trial duration was 26 weeks. RESULTS: Completion rates were 64% for controls and 62.5% in the experimental group. Mean number of drug-free weeks was 11.3 (SD 8.5 for the control group and 9.8 (8.9 for the experimental group (p = 0.30. CONCLUSION: The intervention was not effective compared to routine treatment. Additional features might be necessary to achieve an effect, e.g. a higher frequency of urine sampling or use of other reinforcers. It has to be further investigated how interventions which have been proven effective in experimental studies can successfully be adapted to routine care conditions.

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

Directory of Open Access Journals (Sweden)

Marcus Baumann

2013-10-01

Full Text Available This review which is the second in this series summarises the most common synthetic routes as applied to the preparation of many modern pharmaceutical compounds categorised as containing a six-membered heterocyclic ring. The reported examples are based on the top retailing drug molecules combining synthetic information from both scientific journals and the wider patent literature. It is hoped that this compilation, in combination with the previously published review on five-membered rings, will form a comprehensive foundation and reference source for individuals interested in medicinal, synthetic and preparative chemistry.

Preparation of reinforced poly(ethylene oxide) blend hydrogel films containing a drug and assessment of their properties

International Nuclear Information System (INIS)

Yang Zhanshan; Zhu Nankang; Yang Shuqin

1999-01-01

Reinforced poly(ethylene oxide) blend hydrogen films containing mafenide acetate were prepared by using two freezing-thawing cycles and the irradiation crosslinking technique, and their properties and the drug release were assessed. The results showed that the tensile strength of the reinforced PEO blend hydrogel films increased significantly (p < 0.01), the gel fraction and the elongation at break of the films increased slightly as compared with those formed by the irradiation without the freezing-thawing treatment, indicating that the mechanical properties of the PEO blend hydrogel films can be improved by the freezing-thawing cycles. The reinforced films possessed an ideal flexibility, crosslinking density and elasticity as wound dressings. Swelling studies showed that the equilibrium water content of the hydrogel films expressed in the degree of swelling decreased significantly (p < 0.01), suggesting that a significant structural rearrangement of the films occurred during the freezing process. The structural densification resulted in the increase of the mechanical strength of the hydrogel films. The hydrogels formed by the irradiation at doses of 40 kGy were comparatively stronger. Release studies were run on the reinforced hydrogels with mafenide acetate which was incorporated before the freezing-thawing treatment. Release was followed over seven days. The drug transport was controlled by a regular diffusion model

Advanced Drug Delivery Systems - a Synthetic and Biological Applied Evaluation

DEFF Research Database (Denmark)

Bjerg, Lise Nørkjær

function as the targeting moiety on the surface of the liposomes. Several examples of synthetic procedures known from the literature are presented. The chapter is completed with a study covering the conjugation efficiencies of a variety of chemical functionalities. Large differences are revealed between...... to guide the uptake, in addition to an enzymatically cleavable peptide sequence, whose cleavage would result in removal of the polymer layer as well as uncovering cationic charges on the liposomal surface. These systems were shown to have superior drug efficacy in vitro....

Synthetic LDL as targeted drug delivery vehicle

Science.gov (United States)

Forte, Trudy M [Berkeley, CA; Nikanjam, Mina [Richmond, CA

2012-08-28

The present invention provides a synthetic LDL nanoparticle comprising a lipid moiety and a synthetic chimeric peptide so as to be capable of binding the LDL receptor. The synthetic LDL nanoparticle of the present invention is capable of incorporating and targeting therapeutics to cells expressing the LDL receptor for diseases associated with the expression of the LDL receptor such as central nervous system diseases. The invention further provides methods of using such synthetic LDL nanoparticles.

Habituation of reinforcer effectiveness

Directory of Open Access Journals (Sweden)

David R Lloyd

2014-01-01

Full Text Available In this paper we propose an integrative model of habituation of reinforcer effectiveness (HRE that links behavioral and neural based explanations of reinforcement. We argue that habituation of reinforcer effectiveness (HRE is a fundamental property of reinforcing stimuli. Most reinforcement models implicitly suggest that the effectiveness of a reinforcer is stable across repeated presentations. In contrast, an HRE approach predicts decreased effectiveness due to repeated presentation. We argue that repeated presentation of reinforcing stimuli decreases their effectiveness and that these decreases are described by the behavioral characteristics of habituation (McSweeney and Murphy, 2009;Rankin et al., 2009. We describe a neural model that postulates a positive association between dopamine neurotransmission and HRE. We present evidence that stimulant drugs, which artificially increase dopamine neurotransmission, disrupt (slow normally occurring HRE and also provide evidence that stimulant drugs have differential effects on operant responding maintained by reinforcers with rapid vs. slow HRE rates. We hypothesize that abnormal HRE due to genetic and/or environmental factors may underlie some behavioral disorders. For example, recent research indicates that slow-HRE is predictive of obesity. In contrast ADHD may reflect ‘accelerated-HRE’. Consideration of HRE is important for the development of effective reinforcement based treatments. Finally, we point out that most of the reinforcing stimuli that regulate daily behavior are non-consumable environmental/social reinforcers which have rapid-HRE. The almost exclusive use of consumable reinforcers with slow-HRE in pre-clinical studies with animals may have caused the importance of HRE to be overlooked. Further study of reinforcing stimuli with rapid-HRE is needed in order to understand how habituation and reinforcement interact and regulate behavior.

Habituation of reinforcer effectiveness.

Science.gov (United States)

Lloyd, David R; Medina, Douglas J; Hawk, Larry W; Fosco, Whitney D; Richards, Jerry B

2014-01-09

In this paper we propose an integrative model of habituation of reinforcer effectiveness (HRE) that links behavioral- and neural-based explanations of reinforcement. We argue that HRE is a fundamental property of reinforcing stimuli. Most reinforcement models implicitly suggest that the effectiveness of a reinforcer is stable across repeated presentations. In contrast, an HRE approach predicts decreased effectiveness due to repeated presentation. We argue that repeated presentation of reinforcing stimuli decreases their effectiveness and that these decreases are described by the behavioral characteristics of habituation (McSweeney and Murphy, 2009; Rankin etal., 2009). We describe a neural model that postulates a positive association between dopamine neurotransmission and HRE. We present evidence that stimulant drugs, which artificially increase dopamine neurotransmission, disrupt (slow) normally occurring HRE and also provide evidence that stimulant drugs have differential effects on operant responding maintained by reinforcers with rapid vs. slow HRE rates. We hypothesize that abnormal HRE due to genetic and/or environmental factors may underlie some behavioral disorders. For example, recent research indicates that slow-HRE is predictive of obesity. In contrast ADHD may reflect "accelerated-HRE." Consideration of HRE is important for the development of effective reinforcement-based treatments. Finally, we point out that most of the reinforcing stimuli that regulate daily behavior are non-consumable environmental/social reinforcers which have rapid-HRE. The almost exclusive use of consumable reinforcers with slow-HRE in pre-clinical studies with animals may have caused the importance of HRE to be overlooked. Further study of reinforcing stimuli with rapid-HRE is needed in order to understand how habituation and reinforcement interact and regulate behavior.

Synthetic Biology and Personalized Medicine

Science.gov (United States)

Jain, K.K.

2013-01-01

Synthetic biology, application of synthetic chemistry to biology, is a broad term that covers the engineering of biological systems with structures and functions not found in nature to process information, manipulate chemicals, produce energy, maintain cell environment and enhance human health. Synthetic biology devices contribute not only to improve our understanding of disease mechanisms, but also provide novel diagnostic tools. Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs. The potential of synthetic genome, using an expanded genetic code that is designed for specific drug synthesis as well as delivery and activation of the drug in vivo by a pathological signal, was already pointed out during a lecture delivered at Kuwait University in 2005. Of two approaches to synthetic biology, top-down and bottom-up, the latter is more relevant to the development of personalized medicines as it provides more flexibility in constructing a partially synthetic cell from basic building blocks for a desired task. PMID:22907209

Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids.

Science.gov (United States)

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.

21 CFR 73.1200 - Synthetic iron oxide.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Synthetic iron oxide. 73.1200 Section 73.1200 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1200 Synthetic iron oxide. (a) Identity. (1) The color additive synthetic iron oxide consists of any one or any combination of synthetically prepared...

From "herbal highs" to the "heroin of cannabis": Exploring the evolving discourse on synthetic cannabinoid use in a Norwegian Internet drug forum.

Science.gov (United States)

Bilgrei, Ola Røed

2016-03-01

In the early 2000s, online vendors began selling an array of so-called "legal highs"--apparently organic produce made from exotic herbs. Simultaneously, members of online drug discussion forums began to debate the alleged effects of the new drugs, creating an enormous base of user-derived information based on personal experiences. This study combines the historical data spanning a seven-year period derived from a Norwegian drug discussion forum about synthetic cannabinoids and interviews with 14 male forum members who all had experience with the drug. By combining the two sources, this study reveals not only the evolving discourse on synthetic cannabinoid use but also how forum members related to the online information that they gathered and co-produced. Analysis of the evolving online discourse revealed three distinct phases. The first was an enthusiastic phase, with users embracing the new drugs. The second was a phase characterized by growing ambivalence and scepticism towards use of the drugs. The third was one in which members of the community rejected the new drugs based on negative reviews from users. The analysis displays the communal process whereby members co-operate in the exchange of an extensive body of knowledge accumulated about synthetic cannabinoids, and the way in which this evolving discourse influences members of the forum in their views and representations of the drugs. Paradoxically, the online discussions of synthetic cannabinoids, which had great significance for their proliferation when they were initially introduced to the market, now seem to be a deterrent. The role of online drug communities in the development of new drug trends should receive renewed attention. Copyright © 2016 Elsevier B.V. All rights reserved.

A new synthetic drug 5-(2-aminopropyl)indole (5-IT) induces rewarding effects and increases dopamine D1 receptor and dopamine transporter mRNA levels.

Science.gov (United States)

Botanas, Chrislean Jun; Yoon, Seong Shoon; de la Peña, June Bryan; Dela Peña, Irene Joy; Kim, Mikyung; Custodio, Raly James; Woo, Taeseon; Seo, Joung-Wook; Jang, Choon-Gon; Yang, Ji Seul; Yoon, Yoon Mi; Lee, Yong Sup; Kim, Hee Jin; Cheong, Jae Hoon

2018-04-02

In recent years, there has been a marked increase in the use of recreational synthetic psychoactive substances, which is a cause of concern among healthcare providers and legal authorities. In particular, there have been reports on the misuse of 5-(2-aminopropyl)indole (5-API; 5-IT), a new synthetic drug, and of fatal and non-fatal intoxication. Despite these reports, little is known about its psychopharmacological effects and abuse potential. Here, we investigated the abuse potential of 5-IT by evaluating its rewarding and reinforcing effects through conditioned place preference (CPP) (1, 10, and 30 mg/kg, i.p.) in mice and self-administration test (0.1, 0.3, 1, and 3 mg/kg/inf., i.v.) in rats. We also examined whether 5-IT (1, 3, and 10 mg/kg, i.p.) induces locomotor sensitization in mice following a 7-day treatment and drug challenge. Then, we explored the effects of 5-IT (10 mg/kg, i.p.) on dopamine-related genes in the striatum, prefrontal cortex (PFC), and substantia nigra pars compacta (SNc)/ventral tegmental (VTA) of mice by quantitative real-time polymerase chain reaction. 5-IT produced CPP in mice but was not reliably self-administered by rats. 5-IT also induced locomotor sensitization following repeated administration and drug challenge. Moreover, 5-IT increased mRNA levels of dopamine D1 receptor in the striatum and PFC and dopamine transporter in the SNc/VTA of mice. These results indicate that 5-IT has psychostimulant and rewarding properties, which may be attributed to its ability to affect the dopaminergic system in the brain. These findings suggest that 5-IT poses a substantial risk for abuse and addiction in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

EMPLOYMENT-BASED ABSTINENCE REINFORCEMENT PROMOTES OPIATE AND COCAINE ABSTINENCE IN OUT-OF-TREATMENT INJECTION DRUG USERS

OpenAIRE

Holtyn, August F.; Koffarnus, Mikhail N.; DeFulio, Anthony; Sigurdsson, Sigurdur O.; Strain, Eric C.; Schwartz, Robert P.; Silverman, Kenneth

2014-01-01

We examined the use of employment-based abstinence reinforcement in out-of-treatment injection drug users, in this secondary analysis of a previously reported trial. Participants (N = 33) could work in the therapeutic workplace, a model employment-based program for drug addiction, for 30 weeks and could earn approximately $10 per hr. During a 4-week induction, participants only had to work to earn pay. After induction, access to the workplace was contingent on enrollment in methadone treatmen...

Synthetic biology: Emerging bioengineering in Indonesia

Science.gov (United States)

Suhandono, Sony

2017-05-01

The development of synthetic biology will shape the new era of science and technology. It is an emerging bioengineering technique involving genetic engineering which can alter the phenotype and behavior of the cell or the new product. Synthetic biology may produce biomaterials, drugs, vaccines, biosensors, and even a recombinant secondary metabolite used in herbal and complementary medicine, such as artemisinin, a malaria drug which is usually extracted from the plant Artemisia annua. The power of synthetic biology has encouraged scientists in Indonesia, and is still in early development. This paper also covers some research from an Indonesian research institute in synthetic biology such as observing the production of bio surfactants and the enhanced production of artemisinin using a transient expression system. Synthetic biology development in Indonesia may also be related to the iGEM competition, a large synthetic biology research competition which was attended by several universities in Indonesia. The application of synthetic biology for drug discovery will be discussed.

Effects of reinforcer magnitude on data-entry productivity in chronically unemployed drug abusers participating in a Therapeutic Workplace.

Science.gov (United States)

Wong, Conrad J; Sheppard, Jeannie-Marie; Dallery, Jesse; Bedient, Guy; Robles, Elias; Svikis, Dace; Silverman, Kenneth

2003-02-01

The Therapeutic Workplace is a substance abuse treatment wherein patients are hired and paid to work in a job contingent on daily drug-free urine samples. The present study examined data-entry productivity of 6 unemployed methadone patients who demonstrated relatively variable and low data-entry response rates. A within-subject reversal design was used to determine whether increasing reinforcement magnitude tenfold could increase response rates. Four of the 6 participants showed the highest rates of responding in the high magnitude reinforcement condition. Two participants, who had the lowest overall response rates, showed less robust changes to the magnitude manipulation. The results suggest that reinforcement magnitude can be used to improve productivity in Therapeutic Workplace participants.

Fiber-reinforced neutron shielding mortar concrete

International Nuclear Information System (INIS)

Kaji, Keisuke; Okazaki, Masaki; Ohigashi, Toshihide; Mayahara, Mitsuro.

1989-01-01

To improve the moldability, durability and economicity by adding cement curing promotors and reinforcing fibers to cement and boron compound which has been considered difficult so far, thereby enabling to add a great amount of the boron compound. The boron compound is added by from 5 to 200% by weight of powder of colemanite or borocarcite as natural ores or boric acid, borax or titanium boride, etc. as synthesis products and lithium hydroxide. calcium aluminate, etc. is added by more than 0.1% x boron compound blending ration (%) as the curing promoter. 0.3 to 5% by weight of polyvinyl alcohol type synthetic fibers, polyacrilonitrile type synthetic fibers or carbon fibers, etc. are added as the reinforcing fibers. This can prevent instantaneous coagulation, curing delay, etc. due to sulfur ions, enable easy application and molding and improve the durability and economicity. (T.M.)

An experimental study of mechanical behavior of natural fiber reinforced polymer matrix composites

Science.gov (United States)

Ratna, Sanatan; Misra, Sheelam

2018-05-01

Fibre-reinforced polymer composites have played a dominant role for a long time in a variety of applications for their high specific strength and modulus. The fibre which serves as a reinforcement in reinforced plastics may be synthetic or natural. Past studies show that only synthetic fibres such as glass, carbon etc., have been used in fibre reinforced plastics. Although glass and other synthetic fibre-reinforced plastics possess high specific strength, their fields of application are very limited because of their inherent higher cost of production. In this connection, an investigation has been carried out to make use of horse hair, an animal fibre abundantly available in India. Animal fibres are not only strong and lightweight but also relatively very cheaper than mineral fibre. The present work describes the development and characterization of a new set of animal fiber based polymer composites consisting of horse hair as reinforcement and epoxy resin. The newly developed composites are characterized with respect to their mechanical characteristics. Experiments are carried out to study the effect of fibre length on mechanical behavior of these epoxy based polymer composites. Composite made form horse hair can be used as a potential reinforcing material for many structural and non-structural applications. This work can be further extended to study other aspects of such composites like effect of fiber content, loading pattern, fibre treatment on mechanical behavior of horse hair based polymer horse hair.

Study of the internal confinement of concrete reinforced (in civil engineering) with woven reinforcement

Science.gov (United States)

Dalal, M.; Goumairi, O.; El Malik, A.

2017-10-01

Concrete is generally the most used material in the field of construction. Despite its extensive use in structures, it represents some drawbacks related to its properties including its low tensile strength and low ductility. To solve this problem, the use of steel reinforcement in concrete structures is possible. Another possibility is the introduction of different types of continuous fibre / staple in the concrete, such as steel fibres or synthetic fibres, to obtain ″Concretes bundles″. Many types of fibre concrete, which have been developed and for many of them, the gain provided by the fibre was rather low and no significant improvement in tensile strength was really reaching. By cons, the ductility was higher than that of ordinary concrete. The objective of this study is to examine concrete reinforcement by inserting reinforcements woven polyester. These are either woven bidirectional (2D) or three-dimensional woven (3D). So we will report the properties of each type of reinforcement and the influence of the method of weaving on the strength reinforcements and on the strength of concrete in which they are incorporated. Such influence should contribute to improving the sustainability and enhancement of reinforcement

A new strategy to deliver synthetic protein drugs: self-reproducible biologics using minicircles.

Science.gov (United States)

Yi, Hyoju; Kim, Youngkyun; Kim, Juryun; Jung, Hyerin; Rim, Yeri Alice; Jung, Seung Min; Park, Sung-Hwan; Ju, Ji Hyeon

2014-08-05

Biologics are the most successful drugs used in anticytokine therapy. However, they remain partially unsuccessful because of the elevated cost of their synthesis and purification. Development of novel biologics has also been hampered by the high cost. Biologics are made of protein components; thus, theoretically, they can be produced in vivo. Here we tried to invent a novel strategy to allow the production of synthetic drugs in vivo by the host itself. The recombinant minicircles encoding etanercept or tocilizumab, which are synthesized currently by pharmaceutical companies, were injected intravenously into animal models. Self-reproduced etanercept and tocilizumab were detected in the serum of mice. Moreover, arthritis subsided in mice that were injected with minicircle vectors carrying biologics. Self-reproducible biologics need neither factory facilities for drug production nor clinical processes, such as frequent drug injection. Although this novel strategy is in its very early conceptual stage, it seems to represent a potential alternative method for the delivery of biologics.

Synthetic Cathinones ("Bath Salts")

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Reinforcing the membrane-mediated mechanism of action of the anti-tuberculosis candidate drug thioridazine with molecular simulations

DEFF Research Database (Denmark)

Kopec, Wojciech; Khandelia, Himanshu

2014-01-01

Thioridazine is a well-known dopamine-antagonist drug with a wide range of pharmacological properties ranging from neuroleptic to antimicrobial and even anticancer activity. Thioridazine is a critical component of a promising multi-drug therapy against M. tuberculosis. Amongst the various propose......-membrane interactions, and reinforce the wider, emerging view of action of many small, bioactive compounds....... mechanisms of action, the cell membrane-mediated one is peculiarly tempting due to the distinctive feature of phenothiazine drug family to accumulate in selected body tissues. In this study, we employ long-scale molecular dynamics simulations to investigate the interactions of three different concentrations...

Trends in Deaths Involving Heroin and Synthetic Opioids Excluding Methadone, and Law Enforcement Drug Product Reports, by Census Region - United States, 2006-2015.

Science.gov (United States)

O'Donnell, Julie K; Gladden, R Matthew; Seth, Puja

2017-09-01

Opioid overdose deaths quadrupled from 8,050 in 1999 to 33,091 in 2015 and accounted for 63% of drug overdose deaths in the United States in 2015. During 2010-2015, heroin overdose deaths quadrupled from 3,036 to 12,989 (1). Sharp increases in the supply of heroin and illicitly manufactured fentanyl (IMF) are likely contributing to increased deaths (2-6). CDC examined trends in unintentional and undetermined deaths involving heroin or synthetic opioids excluding methadone (i.e., synthetic opioids)* by the four U.S. Census regions during 2006-2015. Drug exhibits (i.e., drug products) obtained by law enforcement and reported to the Drug Enforcement Administration's (DEA's) National Forensic Laboratory Information System (NFLIS) that tested positive for heroin or fentanyl (i.e., drug reports) also were examined. All U.S. Census regions experienced substantial increases in deaths involving heroin from 2006 to 2015. Since 2010, the South and West experienced increases in heroin drug reports, whereas the Northeast and Midwest experienced steady increases during 2006-2015. † In the Northeast, Midwest, and South, deaths involving synthetic opioids and fentanyl drug reports increased considerably after 2013. These broad changes in the U.S. illicit drug market highlight the urgent need to track illicit drugs and enhance public health interventions targeting persons using or at high risk for using heroin or IMF.

Employment-Based Reinforcement of Adherence to Oral Naltrexone Treatment in Unemployed Injection Drug Users

OpenAIRE

Dunn, Kelly; Defulio, Anthony; Everly, Jeffrey J.; Donlin, Wendy D.; Aklin, Will M.; Nuzzo, Paul A.; Leoutsakos, Jeannie-Marie S.; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E.; Silverman, Kenneth

2012-01-01

Naltrexone has high potential for use as a relapse prevention pharmacotherapy for opiate dependence; however suffers from notoriously poor adherence when prescribed for oral self-administration. This study evaluated whether entry to a therapeutic workplace could be used to reinforce adherence with oral naltrexone. Opiate-dependent and cocaine-using injection drug users were detoxified, inducted onto oral naltrexone, and randomly assigned to a Contingency (n=35) or Prescription (n=32) group fo...

Blends of synthetic and natural polymers as drug delivery systems for growth hormone.

Science.gov (United States)

Cascone, M G; Sim, B; Downes, S

1995-05-01

In order to overcome the biological deficiencies of synthetic polymers and to enhance the mechanical characteristics of natural polymers, two synthetic polymers, poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA) were blended, in different ratios, with two biological polymers, collagen (C) and hyaluronic acid (HA). These blends were used to prepare films, sponges and hydrogels which were loaded with growth hormone (GH) to investigate their potential use as drug delivery systems. The GH release was monitored in vitro using a specific enzyme-linked immunosorbent assay. The results show that GH can be released from HA/PAA sponges and from HA/PVA and C/PVA hydrogels. The initial GH concentration used for sample loading affected the total quantity of GH released but not the pattern of release. The rate and quantity of GH released was significantly dependent on the HA or C content of the polymers.

Glutamatergic transmission in drug reward: implications for drug addiction

OpenAIRE

D'Souza, Manoranjan S.

2015-01-01

Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding) effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society. Over the last two decades...

Mammalian synthetic biology: emerging medical applications.

Science.gov (United States)

Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

2015-05-06

In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Epidemics of HIV, HCV and syphilis infection among synthetic drugs only users, heroin-only users and poly-drug users in Southwest China.

Science.gov (United States)

Su, Shu; Mao, Limin; Zhao, Jinxian; Chen, Liang; Jing, Jun; Cheng, Feng; Zhang, Lei

2018-04-26

The number of poly-drug users who mix use heroin and synthetic drugs (SD) is increasing worldwide. The objective of this study is to measure the risk factors for being infected with hepatitis C (HCV), human immunodeficiency virus (HIV) and syphilis among SD-only users, heroin-only users and poly-drug users. A cross-sectional study was conducted in 2015 from a national HIV surveillance site in Southwest China, 447 poly-drug, 526 SD-only and 318 heroin-only users were recruited. Poly-drug users have higher drug-use frequency, higher rates of drug-sharing and unsafe sexual acts than other users (p users experienced sexual arousal due to drug effects, which is higher than the rate among other drug users. Poly-drug users had the highest prevalence of HIV (10.5%) and syphilis (3.6%), but heroin-only users had the highest prevalence of HCV (66.0%) (all p users, having sex following drug consumption and using drugs ≥1/day were the major risk factors for both HIV (Adjusted odds ratio (AOR) = 2.4, 95% CI [1.8-3.4]; 2.3, [1.6-3.1]) and syphilis infection (AOR = 4.1, [2.1-6.9]; 3.9, [1.8-5.4]). Elevated risk of both HIV and syphilis infection have been established among poly-drug users.

21 CFR 874.3620 - Ear, nose, and throat synthetic polymer material.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ear, nose, and throat synthetic polymer material. 874.3620 Section 874.3620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., and throat synthetic polymer material. (a) Identification. Ear, nose, and throat synthetic polymer...

Polyethylenimine-mediated synthetic insertion of gold nanoparticles into mesoporous silica nanoparticles for drug loading and biocatalysis.

Science.gov (United States)

Pandey, Prem C; Pandey, Govind; Narayan, Roger J

2017-03-27

Mesoporous silica nanoparticles (MSNPs) have been used as an efficient and safe carrier for drug delivery and biocatalysis. The surface modification of MSNPs using suitable reagents may provide a robust framework in which two or more components can be incorporated to give multifunctional capabilities (e.g., synthesis of noble metal nanoparticles within mesoporous architecture along with loading of a bioactive molecule). In this study, the authors reported on a new synthetic route for the synthesis of gold nanoparticles (AuNPs) within (1) unmodified MSNPs and (2) 3-trihydroxysilylpropyl methylphosphonate-modified MSNPs. A cationic polymer, polyethylenimine (PEI), and formaldehyde were used to mediate synthetic incorporation of AuNPs within MSNPs. The AuNPs incorporated within the mesoporous matrix were characterized by transmission electron microscopy, energy dispersive x-ray analysis, and high-resolution scanning electron microscopy. PEI in the presence of formaldehyde enabled synthetic incorporation of AuNPs in both unmodified and modified MSNPs. The use of unmodified MSNPs was associated with an increase in the polycrystalline structure of the AuNPs within the MSNPs. The AuNPs within modified MSNPs showed better catalytic activity than those within unmodified MSNPs. MSNPs with an average size of 200 nm and with a pore size of 4-6 nm were used for synthetic insertion of AuNPs. It was found that the PEI coating enabled AuNPs synthesis within the mesopores in the presence of formaldehyde or tetrahydrofuran hydroperoxide at a temperature between 10 and 25 °C or at 60 °C in the absence of organic reducing agents. The as-made AuNP-inserted MSNPs exhibited enhanced catalytic activity. For example, these materials enabled rapid catalytic oxidation of the o-dianisidine substrate to produce a colored solution in proportion to the amount of H 2 O 2 generated as a function of glucose oxidase-catalyzed oxidation of glucose; a linear concentration range from 80 to

Employment-based Reinforcement of Adherence to Oral Naltrexone in Unemployed Injection Drug Users: 12-month Outcomes

OpenAIRE

Dunn, Kelly; DeFulio, Anthony; Everly, Jeffrey J.; Donlin, Wendy D.; Aklin, Will M.; Nuzzo, Paul A.; Leoutsakos, Jeannie-Marie S.; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E.; Silverman, Kenneth

2014-01-01

Oral naltrexone could be a promising relapse prevention pharmacotherapy for recently detoxified opioid-dependent patients, however interventions are often needed to promote adherence with this treatment approach. We recently conducted a study to evaluate a 26-week employment-based reinforcement intervention of oral naltrexone in unemployed injection drug users (Dunn et al., 2013). Participants were randomly assigned into a Contingency (n=35) group required to ingest naltrexone under staff obs...

Role of various natural, synthetic and semi-synthetic polymers on drug release kinetics of losartan potassium oral controlled release tablets.

Science.gov (United States)

Jayasree, J; Sivaneswari, S; Hemalatha, G; Preethi, N; Mounika, B; Murthy, S Vasudeva

2014-10-01

The objective of the present work was to formulate and to characterize controlled release matrix tablets of losartan potassium in order to improve bioavailability and to minimize the frequency of administration and increase the patient compliance. Losartan potassium controlled release matrix tablets were prepared by direct compression technique by the use of different natural, synthetic and semisynthetic polymers such as gum copal, gum acacia, hydroxypropyl methyl cellulose K100 (HPMC K100), eudragit RL 100 and carboxy methyl ethyl cellulose (CMEC) individually and also in combination. Studies were carried out to study the influence of type of polymer on drug release rate. All the formulations were subjected to physiochemical characterization such as weight variation, hardness, thickness, friability, drug content, and swelling index. In vitro dissolution studies were carried out simulated gastric fluid (pH 1.2) for first 2 h and followed by simulated intestinal fluid (pH 6.8) up to 24 h, and obtained dissolution data were fitted to in vitro release kinetic equations in order to know the order of kinetics and mechanism of drug release. Results of physiochemical characterization of losartan potassium matrix tablets were within acceptable limits. Formulation containing HPMC K100 and CMEC achieved the desired drug release profile up to 24 h followed zero order kinetics, release pattern dominated by Korsmeyer - Peppas model and mechanism of drug release by nonfickian diffusion. The good correlation obtained from Hixson-Crowell model indicates that changes in surface area of the tablet also influences the drug release. Based on the results, losartan potassium controlled release matrix tablets prepared by employing HPMC K100 and CMEC can attain the desired drug release up to 24 h, which results in maintaining steady state concentration and improving bioavailability.

21 CFR 73.200 - Synthetic iron oxide.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Synthetic iron oxide. 73.200 Section 73.200 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.200 Synthetic iron oxide. (a) Identity. (1) The color additive synthetic iron oxide consists of any one or any combination of synthetically prepared...

21 CFR 172.888 - Synthetic petroleum wax.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Synthetic petroleum wax. 172.888 Section 172.888... CONSUMPTION Multipurpose Additives § 172.888 Synthetic petroleum wax. Synthetic petroleum wax may be safely used in or on foods in accordance with the following conditions: (a) Synthetic petroleum wax is a...

Synthetic biology: programming cells for biomedical applications.

Science.gov (United States)

Hörner, Maximilian; Reischmann, Nadine; Weber, Wilfried

2012-01-01

The emerging field of synthetic biology is a novel biological discipline at the interface between traditional biology, chemistry, and engineering sciences. Synthetic biology aims at the rational design of complex synthetic biological devices and systems with desired properties by combining compatible, modular biological parts in a systematic manner. While the first engineered systems were mainly proof-of-principle studies to demonstrate the power of the modular engineering approach of synthetic biology, subsequent systems focus on applications in the health, environmental, and energy sectors. This review describes recent approaches for biomedical applications that were developed along the synthetic biology design hierarchy, at the level of individual parts, of devices, and of complex multicellular systems. It describes how synthetic biological parts can be used for the synthesis of drug-delivery tools, how synthetic biological devices can facilitate the discovery of novel drugs, and how multicellular synthetic ecosystems can give insight into population dynamics of parasites and hosts. These examples demonstrate how this new discipline could contribute to novel solutions in the biopharmaceutical industry.

What Are Synthetic Cannabinoids?

Science.gov (United States)

... years, synthetic cannabinoid mixtures have been easy to buy in drug paraphernalia shops, novelty stores, gas stations, and over ... abuse, authorities have made it illegal to sell, buy, or possess some of ... use is that standard drug tests cannot easily detect many of the chemicals ...

Application of Minicircle Technology of Self-Reproducing Synthetic Protein Drugs in Preventing Skin Allograft Rejection.

Science.gov (United States)

Lim, Sun Woo; Kim, Young Kyun; Park, Narae; Jin, Long; Jin, Jian; Doh, Kyoung Chan; Ju, Ji Hyeon; Yang, Chul Woo

2015-07-30

Recently, it has been reported that minicircle vectors could allow the expression of transgenes using the protein synthesis system of the host. Here, we tested a novel strategy to permit the production of synthetic biologics using minicircle technology and evaluated their feasibility as a therapeutic tool in a skin allograft model. We engineered vectors to carry cassette sequences for tocilizumab [anti-soluble interleukin-6 receptor (sIL-6R) antibody] and/or etanercept [tumor necrosis factor receptor 2 (TNFR2)-Fc fusion protein], and then isolated minicircle vectors from the parent vectors. We verified the production of proteins from minicircles and their duration in HEK293T cells and mice. We also evaluated whether these proteins were expressed at levels sufficient to ameliorate skin allograft rejection in mice. Each minicircle transfected into cells was detectable for at least 30 days. In mice, the drugs were mainly expressed in the liver and were detectable for at least 10 days after a single injection. These drugs were also detected in the blood. Treatment of mice with minicircles prolonged skin allograft survival, which was accompanied by a reduction of the number of interferon-γ+ or interleukin-17+ lymphocytes and an induction of forkhead box P3 expression. These findings suggest that blocking of sIL-6R and/or TNF-α using minicircles encoding tocilizumab and/or etanercept was functionally active and relevant for preventing acute allograft rejection. Self-reproducing synthetic protein drugs produced using minicircle technology are potentially powerful tools for preventing acute rejection in transplantation.

The Effect of Health Education based on Health Belief Model on Preventive Actions of Synthetic Drugs Dependence in Male Students of Kerman, Iran

Directory of Open Access Journals (Sweden)

Seyed Saeed Mazloomy Mahmoodabad

2017-06-01

Conclusion: Findings indicated that by increase of HBM components' average scores, the average score of synthetic drug dependence preventive actions increased too. Therefore, results of the research confirm the effect and efficiency of HBM in making preventive actions of drug dependence. 

Evaluation of mechanical properties of hybrid fiber (hemp, jute, kevlar) reinforced composites

Science.gov (United States)

Suresha, K. V.; Shivanand, H. K.; Amith, A.; Vidyasagar, H. N.

2018-04-01

In today's world composites play wide role in all the engineering fields. The reinforcement of composites decides the properties of the material. Natural fiber composites compared to synthetic fiber possesses poor mechanical properties. The solution for this problem is to use combination of natural fiber and synthetic fiber. Hybridization helps to improve the overall mechanical properties of the material. In this study, hybrid reinforced composites of Hemp fabric/Kevlar fabric/Epoxy and Jute fabric/ Kevlar fabric/Epoxy composites are fabricated using Simple hand layup technique followed by Vacuum bagging process. Appropriate test methods as per standards and guidelines are followed to analyze mechanical behavior of the composites. The mechanical characteristics like tensile, compression and flexural properties of the hybrid reinforced composites are tested as per the ASTM standards by series of tensile test; compression test and three point bending tests were conducted on the hybrid composites. A quantitative relationship between the Hemp fabric/Kevlar fabric/Epoxy and Jute/ Kevlar fabric/Epoxy has been established with constant thickness.

The therapeutic workplace to promote treatment engagement and drug abstinence in out-of-treatment injection drug users: a randomized controlled trial.

Science.gov (United States)

Holtyn, August F; Koffarnus, Mikhail N; DeFulio, Anthony; Sigurdsson, Sigurdur O; Strain, Eric C; Schwartz, Robert P; Leoutsakos, Jeannie-Marie S; Silverman, Kenneth

2014-11-01

Determine if employment-based reinforcement can increase methadone treatment engagement and drug abstinence in out-of-treatment injection drug users. This study was conducted from 2008 to 2012 in a therapeutic workplace in Baltimore, MD. After a 4-week induction, participants (N=98) could work and earn pay for 26 weeks and were randomly assigned to Work Reinforcement, Methadone & Work Reinforcement, and Abstinence, Methadone & Work Reinforcement conditions. Work Reinforcement participants had to work to earn pay. Methadone & Work Reinforcement and Abstinence, Methadone, & Work Reinforcement participants had to enroll in methadone treatment to work and maximize pay. Abstinence, Methadone, & Work Reinforcement participants had to provide opiate- and cocaine-negative urine samples to maximize pay. Most participants (92%) enrolled in methadone treatment during induction. Drug abstinence increased as a graded function of the addition of the methadone and abstinence contingencies. Abstinence, Methadone & Work Reinforcement participants provided significantly more urine samples negative for opiates (75% versus 54%) and cocaine (57% versus 32%) than Work Reinforcement participants. Methadone & Work Reinforcement participants provided significantly more cocaine-negative samples than Work Reinforcement participants (55% versus 32%). The therapeutic workplace can promote drug abstinence in out-of-treatment injection drug users. Clinical trial registration number: NCT01416584. Copyright © 2014 Elsevier Inc. All rights reserved.

A State-of-the-Art Review on Soil Reinforcement Technology Using Natural Plant Fiber Materials: Past Findings, Present Trends and Future Directions.

Science.gov (United States)

Gowthaman, Sivakumar; Nakashima, Kazunori; Kawasaki, Satoru

2018-04-04

Incorporating sustainable materials into geotechnical applications increases day by day due to the consideration of impacts on healthy geo-environment and future generations. The environmental issues associated with conventional synthetic materials such as cement, plastic-composites, steel and ashes necessitate alternative approaches in geotechnical engineering. Recently, natural fiber materials in place of synthetic material have gained momentum as an emulating soil-reinforcement technique in sustainable geotechnics. However, the natural fibers are innately different from such synthetic material whereas behavior of fiber-reinforced soil is influenced not only by physical-mechanical properties but also by biochemical properties. In the present review, the applicability of natural plant fibers as oriented distributed fiber-reinforced soil (ODFS) and randomly distributed fiber-reinforced soil (RDFS) are extensively discussed and emphasized the inspiration of RDFS based on the emerging trend. Review also attempts to explore the importance of biochemical composition of natural-fibers on the performance in subsoil reinforced conditions. The treatment methods which enhances the behavior and lifetime of fibers, are also presented. While outlining the current potential of fiber reinforcement technology, some key research gaps have been highlighted at their importance. Finally, the review briefly documents the future direction of the fiber reinforcement technology by associating bio-mediated technological line.

A State-of-the-Art Review on Soil Reinforcement Technology Using Natural Plant Fiber Materials: Past Findings, Present Trends and Future Directions

Directory of Open Access Journals (Sweden)

Sivakumar Gowthaman

2018-04-01

Full Text Available Incorporating sustainable materials into geotechnical applications increases day by day due to the consideration of impacts on healthy geo-environment and future generations. The environmental issues associated with conventional synthetic materials such as cement, plastic-composites, steel and ashes necessitate alternative approaches in geotechnical engineering. Recently, natural fiber materials in place of synthetic material have gained momentum as an emulating soil-reinforcement technique in sustainable geotechnics. However, the natural fibers are innately different from such synthetic material whereas behavior of fiber-reinforced soil is influenced not only by physical-mechanical properties but also by biochemical properties. In the present review, the applicability of natural plant fibers as oriented distributed fiber-reinforced soil (ODFS and randomly distributed fiber-reinforced soil (RDFS are extensively discussed and emphasized the inspiration of RDFS based on the emerging trend. Review also attempts to explore the importance of biochemical composition of natural-fibers on the performance in subsoil reinforced conditions. The treatment methods which enhances the behavior and lifetime of fibers, are also presented. While outlining the current potential of fiber reinforcement technology, some key research gaps have been highlighted at their importance. Finally, the review briefly documents the future direction of the fiber reinforcement technology by associating bio-mediated technological line.

Ballistic Performance of Mallow and Jute Natural Fabrics Reinforced Epoxy Composites in Multilayered Armor

OpenAIRE

Nascimento, Lucio Fabio Cassiano; Louro, Luis Henrique Leme; Monteiro, Sergio Neves; Gomes, Alaelson Vieira; Marçal, Rubens Lincoln Santana Blazutti; Lima Júnior, Édio Pereira; Margem, Jean Igor

2017-01-01

Natural fiber reinforced polymer composites have recently been investigated as a component of multilayered armor system (MAS). These composites were found to present advantages when replacing conventional high strength synthetic aramid fabric laminate composite (KevlarTM, with same thickness, as MAS second layer. Continuous and loose natural fibers were up to now mostly used to reinforce these ballistic composites. Only two natural fabrics reinforced polymer composite were so far used with sa...

Designer Drugs: A Synthetic Catastrophe

OpenAIRE

Fratantonio, James; Andrade, Lawrence; Febo, Marcelo

2015-01-01

Synthetic stimulants can cause hallucinations, aggressive behaviors, death and are sometimes legal. These substances are sold as plant food and bath salts that are "Not for Human Consumption", therefore skirting the 1986 Federal Analogue Act and giving a false pretense of safety. Studies have proved that these substances are toxic, have a high abuse potential, and are becoming extremely prevalent in the United States. This creates a dilemma for law enforcement agents, hospitals, and substance...

Electrochemical corrosion of carbon-fiber-reinforced plastic-metal electrode couples in corrosion media

International Nuclear Information System (INIS)

Chukalovskaya, T.V.; Shcherbakov, A.I.; Chigirinskaya, L.A.; Bandurkin, V.V.; Medova, I.L.; Chukalovskij, P.A.

1995-01-01

Polarization diagrams, obtained for carbon-fiber-reinforced plastic(cathode)-metallic material(anode) contact couples are analyzed to predict the corrosion behaviour of some technical metals and alloys (carbon steel, stainless steels, brass, aluminium, titanium) in contact with carbon-fiber-reinforced plastic in differen agressive media (H 2 SO 4 , HCl, H 3 PO 4 , NaOH solutions in wide temperature and concentration range, synthetic seawater at 30 and 50 deg C). The predicted behaviour was supported by direct investigation into carbon-fiber-reinforced plastic-titanium and carbon-fiber-reinforced plastic-aluminium contact couples at different square ratios. 6 refs.; 4 figs

Bamboo reinforced polymer composite - A comprehensive review

Science.gov (United States)

Roslan, S. A. H.; Rasid, Z. A.; Hassan, M. Z.

2018-04-01

Bamboo has greatly attention of researchers due to their advantages over synthetic polymers. It is entirely renewable, environmentally-friendly, non-toxic, cheap, non-abrasive and fully biodegradable. This review paper summarized an oveview of the bamboo, fiber extraction and mechanical behavior of bamboo reinforced composites. A number of studies proved that mechanical properties of bamboo fibers reinforced reinforced polymer composites are excellent and competent to be utilized in high-tech applications. The properties of the laminate are influenced by the fiber loading, fibre orientation, physical and interlaminar adhesion between fibre and matrix. In contrast, the presence of chemical constituents such as cellulose, lignin, hemicellulose and wax substances in natural fibres preventing them from firmly binding with polymer resin. Thus, led to poor mechanical properties for composites. Many attempt has been made in order to overcome this issue by using the chemical treatment.

THERMOMECHANICAL PROPERTIES OF JUTE/BAGASSE HYBRID FIBRE REINFORCED EPOXY THERMOSET COMPOSITES

OpenAIRE

Sudhir Kumar Saw; Chandan Datta

2009-01-01

Natural fibres are partly replacing currently used synthetic fibres as reinforcement for polymer composites. Jute fibre bundles were high-cellulose-content modified by alkali treatment, while the bagasse fibre bundles were modified by creating quinones in the lignin portions of fibre surfaces and reacting them with furfuryl alcohol (FA) to increase their adhesiveness. The effects of different fibre bundle loading and modification of bagasse fibre surfaces in hybrid fibre reinforced epoxy comp...

A Comparison of Escalating versus Fixed Reinforcement Schedules on Undergraduate Quiz Taking

Science.gov (United States)

Mahoney, Amanda

2017-01-01

Drug abstinence studies indicate that escalating reinforcement schedules maintain abstinence for longer periods than fixed reinforcement schedules. The current study evaluated whether escalating reinforcement schedules would maintain more quiz taking than fixed reinforcement schedules. During baseline and for the control group, bonus points were…

Reinforcement magnitude modulation of rate dependent effects in pigeons and rats.

Science.gov (United States)

Ginsburg, Brett C; Pinkston, Jonathan W; Lamb, R J

2011-08-01

Response rate can influence the behavioral effects of many drugs. Reinforcement magnitude may also influence drug effects. Further, reinforcement magnitude can influence rate-dependent effects. For example, in an earlier report, we showed that rate-dependent effects of two antidepressants depended on reinforcement magnitude. The ability of reinforcement magnitude to interact with rate-dependency has not been well characterized. It is not known whether our previous results are specific to antidepressants or generalize to other drug classes. Here, we further examine rate-magnitude interactions by studying effects of two stimulants (d-amphetamine [0.32-5.6 mg/kg] and cocaine [0.32-10 mg/kg]) and two sedatives (chlordiazepoxide [1.78-32 mg/kg] and pentobarbital [1.0-17.8 mg/kg]) in pigeons responding under a 3-component multiple fixed-interval (FI) 300-s schedule maintained by 2-, 4-, or 8-s of food access. We also examine the effects of d-amphetamine [0.32-3.2 mg/kg] and pentobarbital [1.8-10 mg/kg] in rats responding under a similar multiple FI300-s schedule maintained by 2- or 10- food pellet (45 mg) delivery. In pigeons, cocaine and, to a lesser extent, chlordiazepoxide exerted rate-dependent effects that were diminished by increasing durations of food access. The relationship was less apparent for pentobarbital, and not present for d-amphetamine. In rats, rate-dependent effects of pentobarbital and d-amphetamine were not modulated by reinforcement magnitude. In conclusion, some drugs appear to exert rate-dependent effect which are diminished when reinforcement magnitude is relatively high. Subsequent analysis of the rate-dependency data suggest the effects of reinforcement magnitude may be due to a diminution of drug-induced increases in low-rate behavior that occurs early in the fixed-interval. (c) 2011 APA, all rights reserved.

Biosynthesis of therapeutic natural products using synthetic biology.

Science.gov (United States)

Awan, Ali R; Shaw, William M; Ellis, Tom

2016-10-01

Natural products are a group of bioactive structurally diverse chemicals produced by microorganisms and plants. These molecules and their derivatives have contributed to over a third of the therapeutic drugs produced in the last century. However, over the last few decades traditional drug discovery pipelines from natural products have become far less productive and far more expensive. One recent development with promise to combat this trend is the application of synthetic biology to therapeutic natural product biosynthesis. Synthetic biology is a young discipline with roots in systems biology, genetic engineering, and metabolic engineering. In this review, we discuss the use of synthetic biology to engineer improved yields of existing therapeutic natural products. We further describe the use of synthetic biology to combine and express natural product biosynthetic genes in unprecedented ways, and how this holds promise for opening up completely new avenues for drug discovery and production. Copyright © 2016 Elsevier B.V. All rights reserved.

Employment-based reinforcement of adherence to oral naltrexone in unemployed injection drug users: 12-month outcomes.

Science.gov (United States)

Dunn, Kelly; DeFulio, Anthony; Everly, Jeffrey J; Donlin, Wendy D; Aklin, Will M; Nuzzo, Paul A; Leoutsakos, Jeannie-Marie S; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E; Silverman, Kenneth

2015-06-01

Oral naltrexone could be a promising relapse-prevention pharmacotherapy for recently detoxified opioid-dependent patients; however, interventions are often needed to promote adherence with this treatment approach. We recently conducted a study to evaluate a 26-week employment-based reinforcement intervention of oral naltrexone in unemployed injection drug users (Dunn et al., 2013). Participants were randomly assigned into a contingency (n = 35) group required to ingest naltrexone under staff observation to gain entry into a therapeutic workplace or a prescription (n = 32) group given a take-home supply of oral naltrexone and access to the workplace without observed ingestion. Monthly urine samples were collected and analyzed for evidence for naltrexone adherence, opioid use, and cocaine use. As previously reported, contingency participants provided significantly more naltrexone-positive urine samples than prescription participants during the 26-week intervention period. The goal of this current study is to report the 12-month outcomes, which occurred 6 months after the intervention ended. Results at the 12-month visit showed no between-groups differences in naltrexone-positive, opioid-negative, or cocaine-negative urine samples and no participant self-reported using naltrexone at the follow-up visit. These results show that even after a period of successfully reinforced oral naltrexone adherence, longer-term naltrexone use is unlikely to be maintained after reinforcement contingencies are discontinued. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

LACTIC ACIDOSIS: A RARE MANIFESTATION OF SYNTHETIC MARIJUANA INTOXICATION.

Science.gov (United States)

Antill, T; Jakkoju, A; Dieguez, J; Laskhmiprasad, L

2015-01-01

Synthetic cannabinoids are designer drugs that mimic the effect of cannabis, which has become popular with young drug users. These drugs have a similar chemical structure and pharmacologic effects as marijuana, but seem to be more potent. These substances have been banned by the US Drug Enforcement Agency in 2010. Prior to 2010, these drugs were perceived as "safer" by the general population. Synthetic cannabinoids cause effects similar to marijuana making the subjects euphoric. However, they act as full, rather than partial, agonist at the receptor sites causing more severe side effects such as severe agitation, seizures, acute renal failure, and lactic acidosis.

Miracle drug: Brazil approves never-tested cancer medicine.

Science.gov (United States)

Kuchenbecker, Ricardo S; Mota, Daniel M

2017-07-01

Background Brazil recently approved synthetic phosphoetanolamine, a popularly dubbed 'cancer pill', a substance that has been shown to kill cancer cells in lab animal models but was not yet formally accessed in humans, and thus despite the existence of any evidence of its efficacy and safety. Methods The authors describe the recent decision of Brazil to aprove phosphoetanolamine in the context of growing 'judicialization' to promote access to medicines and thus reinforcing a growing sense of legal uncertainty. Results The approval of phosphoetanolamine despite the existence of any evidence of its efficacy and safety represents to the authors one of the saddest and surrealistic episodes in Brazil's recent public health history. Brazil's current economic crisis is fueling the 'judicialization' to promote access to medicines and thus reinforcing a growing sense of legal uncertainty in the context of rising economic constrains and a progressive failing state. The authors state that the Phosphoetanolamine's approval bill violates current legal prohibition of commercialisation of drugs without the Brazilian national drug regulatory agency's approval and thus may represent a potential menace to Brazil's pharmacogovernance and the country's governance to health technology assessment at the Brazilian national health systems. Conclusion Phosphoetanolamine's approval illustrates that the combination of flawed decision making, economic crisis and political interference may threaten weak governance mechanisms for drug regulation and health technology assessment and thus representing an extra burden in the sustainability of universal access-based national health systems.

Controlled release of cortisone drugs from block copolymers synthetized by ATRP

Science.gov (United States)

Valenti, G.; La Carta, S.; Mazzotti, G.; Rapisarda, M.; Perna, S.; Di Gesù, R.; Giorgini, L.; Carbone, D.; Recca, G.; Rizzarelli, P.

2016-05-01

Diseases affecting posterior eye segment, like macular edema, infection and neovascularization, may cause visual impairment. Traditional treatments, such as steroidal-drugs intravitreal injections, involve chronic course of therapy usually over a period of years. Moreover, they can require frequent administrations of drug in order to have an adequately disease control. This dramatically reduce patient's compliance. Efforts have been made to develop implantable devices that offer an alternative therapeutic approach to bypass many challenges of conventional type of therapy. Implantable drug delivery systems (DDS) have been developed to optimize therapeutic properties of drugs and ensure their slow release in the specific site. Polymeric materials can play an essential role in modulating drug delivery and their use in such field has become indispensable. During last decades, acrylic polymers have obtained growing interest. Biocompatibility and chemical properties make them extremely versatile, allowing their use in many field such as biomedical. In particular, block methacrylate copolymer with a balance of hydrophilic and hydrophobic properties can be suitable for prolonged DDS in biomedical devices. In this work, we focused on the realization of a system for controlled and long term release of betamethasone 17,21-dipropionate (BDP), a cortisone drug, from methacrylic block copolymers, to be tested in the treatment of the posterior eye's diseases. Different series of methyl methacrylate/hydroxyethyl methacrylate (MMA/HEMA) block and random copolymers, with different monomer compositions (10-60% HEMA), were synthetized by Atom Transfer Radical Polymerization (ATRP) to find the best hydrophilic/hydrophobic ratio, able to ensure optimal kinetic release. Copolymer samples were characterized by NMR spectroscopy (1H-NMR, 13C-NMR, CosY), SEC, TGA and DSC. Monitoring of drug release from films loaded with BDP was carried out by HPLC analysis. Evaluation of different kinetic

Controlled release of cortisone drugs from block copolymers synthetized by ATRP

Energy Technology Data Exchange (ETDEWEB)

Valenti, G.; La Carta, S.; Rapisarda, M.; Carbone, D.; Recca, G.; Rizzarelli, P., E-mail: paola.rizzarelli@cnr.it [Istituto per i Polimeri, Compositi e Biomateriali, Consiglio Nazionale delle Ricerche Via P. Gaifami 18, 95129 Catania (Italy); Mazzotti, G.; Giorgini, L. [Dipartimento di Chimica Industriale «Toso Montanari», Università di Bologna Via Risorgimento 4, 40136 Bologna (Italy); Perna, S. [ST Microelectronics Srl, Stradale Primosole, 50–95121 Catania (Italy); Di Gesù, R. [Merck Serono S.p.A., Via L. Einaudi, 11–00012 Guidonia Montecelio, Rome (Italy)

2016-05-18

Diseases affecting posterior eye segment, like macular edema, infection and neovascularization, may cause visual impairment. Traditional treatments, such as steroidal-drugs intravitreal injections, involve chronic course of therapy usually over a period of years. Moreover, they can require frequent administrations of drug in order to have an adequately disease control. This dramatically reduce patient’s compliance. Efforts have been made to develop implantable devices that offer an alternative therapeutic approach to bypass many challenges of conventional type of therapy. Implantable drug delivery systems (DDS) have been developed to optimize therapeutic properties of drugs and ensure their slow release in the specific site. Polymeric materials can play an essential role in modulating drug delivery and their use in such field has become indispensable. During last decades, acrylic polymers have obtained growing interest. Biocompatibility and chemical properties make them extremely versatile, allowing their use in many field such as biomedical. In particular, block methacrylate copolymer with a balance of hydrophilic and hydrophobic properties can be suitable for prolonged DDS in biomedical devices. In this work, we focused on the realization of a system for controlled and long term release of betamethasone 17,21-dipropionate (BDP), a cortisone drug, from methacrylic block copolymers, to be tested in the treatment of the posterior eye’s diseases. Different series of methyl methacrylate/hydroxyethyl methacrylate (MMA/HEMA) block and random copolymers, with different monomer compositions (10–60% HEMA), were synthetized by Atom Transfer Radical Polymerization (ATRP) to find the best hydrophilic/hydrophobic ratio, able to ensure optimal kinetic release. Copolymer samples were characterized by NMR spectroscopy ({sup 1}H-NMR, {sup 13}C-NMR, CosY), SEC, TGA and DSC. Monitoring of drug release from films loaded with BDP was carried out by HPLC analysis. Evaluation of

Controlled release of cortisone drugs from block copolymers synthetized by ATRP

International Nuclear Information System (INIS)

Valenti, G.; La Carta, S.; Rapisarda, M.; Carbone, D.; Recca, G.; Rizzarelli, P.; Mazzotti, G.; Giorgini, L.; Perna, S.; Di Gesù, R.

2016-01-01

Diseases affecting posterior eye segment, like macular edema, infection and neovascularization, may cause visual impairment. Traditional treatments, such as steroidal-drugs intravitreal injections, involve chronic course of therapy usually over a period of years. Moreover, they can require frequent administrations of drug in order to have an adequately disease control. This dramatically reduce patient’s compliance. Efforts have been made to develop implantable devices that offer an alternative therapeutic approach to bypass many challenges of conventional type of therapy. Implantable drug delivery systems (DDS) have been developed to optimize therapeutic properties of drugs and ensure their slow release in the specific site. Polymeric materials can play an essential role in modulating drug delivery and their use in such field has become indispensable. During last decades, acrylic polymers have obtained growing interest. Biocompatibility and chemical properties make them extremely versatile, allowing their use in many field such as biomedical. In particular, block methacrylate copolymer with a balance of hydrophilic and hydrophobic properties can be suitable for prolonged DDS in biomedical devices. In this work, we focused on the realization of a system for controlled and long term release of betamethasone 17,21-dipropionate (BDP), a cortisone drug, from methacrylic block copolymers, to be tested in the treatment of the posterior eye’s diseases. Different series of methyl methacrylate/hydroxyethyl methacrylate (MMA/HEMA) block and random copolymers, with different monomer compositions (10–60% HEMA), were synthetized by Atom Transfer Radical Polymerization (ATRP) to find the best hydrophilic/hydrophobic ratio, able to ensure optimal kinetic release. Copolymer samples were characterized by NMR spectroscopy ("1H-NMR, "1"3C-NMR, CosY), SEC, TGA and DSC. Monitoring of drug release from films loaded with BDP was carried out by HPLC analysis. Evaluation of different

Prior methylphenidate self-administration alters the subsequent reinforcing effects of methamphetamine in rats.

Science.gov (United States)

Baladi, Michelle G; Nielsen, Shannon M; Umpierre, Anthony; Hanson, Glen R; Fleckenstein, Annette E

2014-12-01

Methylphenidate (MPD) is clinically effective in treating the symptoms of attention-deficit hyperactivity disorder; however, its relatively widespread availability has raised public health concerns on nonmedical use of MPD among certain adult populations. Most preclinical studies investigate whether presumed therapeutically relevant doses of MPD alter sensitivity to the reinforcing effects of other drugs, but it remains unclear whether doses of MPD likely exceeding therapeutic relevance impact the subsequent reinforcing effects of drugs. To begin to address this question, the effect of prior MPD self-administration (0.56 mg/kg/infusion) on the subsequent reinforcing effects of methamphetamine (METH, 0.032 or 0.1 mg/kg/infusion) was investigated in male Sprague-Dawley rats. For comparison, it was also determined whether prior experimenter-administered MPD, injected daily at a presumed therapeutically relevant dose (2 mg/kg), altered the subsequent reinforcing effects of METH. Results indicated that, under the current conditions, only a history of MPD self-administration increased sensitivity to the subsequent reinforcing effects of METH. Furthermore, MPD did not impact food-maintained responding, suggesting that the effect of MPD might be specific to drug reinforcers. These data suggest that short-term, nonmedical use of MPD might alter the positive reinforcing effects of METH in a manner relevant to vulnerability to drug use in humans.

Reinforcement and recovery of timber structures

Directory of Open Access Journals (Sweden)

Antonio Alves Dias

2006-02-01

Full Text Available Preservation of timber structures is a reason for constant concern because their deterioration often involves compromising the historical patrimony, besides endangering the safety of the structure, and consequently, of their users. Many are the examples of churches, residences or other constructions where this manifestation is a fact. The technique of reinforcing structurally endangered pieces with the addition of natural or synthetic fibers, is an alternative that has been researched. In the group of synthetic fibers, fiberglass, carbon and aramid ones are included. On the other hand, it has been frequent in the restoration of old buildings, especially in Europe, the employment of materials that were not available in the past, aiming to achieve structural, acoustic and aesthetic benefits. On an existing timber structure floor, a concrete slab has been carried out, with an appropriate connection system among the parts, constituting the composite timber-concrete structures. This alternative has been considered as extraordinarily viable, because it gathers a series of convenience related with the durability and it presents better mechanic performance than conventional timber structures. In this work, the state-of-the-art of the use of fibers as structural reinforcement and of the timber-concrete composite structures, is presented.

Drug specificity in drug versus food choice in male rats.

Science.gov (United States)

Tunstall, Brendan J; Riley, Anthony L; Kearns, David N

2014-08-01

Although different classes of drug differ in their mechanisms of reinforcement and effects on behavior, little research has focused on differences in self-administration behaviors maintained by users of these drugs. Persistent drug choice despite available reinforcement alternatives has been proposed to model behavior relevant to addiction. The present study used a within-subjects procedure, where male rats (Long-Evans, N = 16) were given a choice between cocaine (1.0 mg/kg/infusion) and food (a single 45-mg grain pellet) or between heroin (0.02 mg/kg/infusion) and food in separate phases (drug order counterbalanced). All rats were initially trained to self-administer each drug, and the doses used were based on previous studies showing that small subsets of rats tend to prefer drug over food reinforcement. The goal of the present study was to determine whether rats that prefer cocaine would also prefer heroin. Choice sessions consisted of 2 forced-choice trials with each reinforcer, followed by 14 free-choice trials (all trials separated by 10-min intertrial interval). Replicating previous results, small subsets of rats preferred either cocaine (5 of the 16 rats) or heroin (2 of the 16 rats) to the food alternative. Although 1 of the 16 rats demonstrated a preference for both cocaine and heroin to the food alternative, there was no relationship between degree of cocaine and heroin preference in individual rats. The substance-specific pattern of drug preference observed suggests that at least in this animal model, the tendencies to prefer cocaine or heroin in preference to a nondrug alternative are distinct behavioral phenomena.

Tensile Capacity of U-bar Loop Connections with Precast Fiber Reinforced Dowels

DEFF Research Database (Denmark)

Sørensen, Jesper Harrild; Hoang, Linh Cao; Olesen, John Forbes

2016-01-01

This paper describes an investigation of the tensile capacity of in-situ cast U-bar loop connections between precast concrete elements. The basic idea is to introduce a small precast cylindrical dowel of fiber reinforced mortar that fits into the bend diameter of the overlapping U...... that use of a precast fiber reinforced dowel performs at a slightly lower load level, as compared to a connection grouted solely with regular mortar and reinforced with the same amount of transverse reinforcement. However, the load-displacement response of specimens with a fiber reinforced dowel is closer......-bars. The remaining part of the connection is cast in-situ with a regular mortar, which then encapsulates the precast dowel. Different dowel configurations have been investigated, including the use of steel or synthetic fibers with or without lacer bars placed within the precast dowel. The experimental results show...

DNA sequence analyses of blended herbal products including synthetic cannabinoids as designer drugs.

Science.gov (United States)

Ogata, Jun; Uchiyama, Nahoko; Kikura-Hanajiri, Ruri; Goda, Yukihiro

2013-04-10

In recent years, various herbal products adulterated with synthetic cannabinoids have been distributed worldwide via the Internet. These herbal products are mostly sold as incense, and advertised as not for human consumption. Although their labels indicate that they contain mixtures of several potentially psychoactive plants, and numerous studies have reported that they contain a variety of synthetic cannabinoids, their exact botanical contents are not always clear. In this study, we investigated the origins of botanical materials in 62 Spice-like herbal products distributed on the illegal drug market in Japan, by DNA sequence analyses and BLAST searches. The nucleotide sequences of four regions were analyzed to identify the origins of each plant species in the herbal mixtures. The sequences of "Damiana" (Turnera diffusa) and Lamiaceae herbs (Mellissa, Mentha and Thymus) were frequently detected in a number of products. However, the sequences of other plant species indicated on the packaging labels were not detected. In a few products, DNA fragments of potent psychotropic plants were found, including marijuana (Cannabis sativa), "Diviner's Sage" (Salvia divinorum) and "Kratom" (Mitragyna speciosa). Their active constituents were also confirmed using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), although these plant names were never indicated on the labels. Most plant species identified in the products were different from the plants indicated on the labels. The plant materials would be used mainly as diluents for the psychoactive synthetic compounds, because no reliable psychoactive effects have been reported for most of the identified plants, with the exception of the psychotropic plants named above. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

[Designer drugs in Jutland].

Science.gov (United States)

Simonsen, K W; Kaa, E

2001-04-16

The aim of this investigation was to examine illegal tablets and capsules seized in Jutland, the western part of Denmark, during the period 1995-1999. The drugs are described according to technical appearance (colour, logo, score, diameter) and content of synthetic drugs. All illegal tablets and capsules received during the period 1995-1999 (109 cases containing 192 different samples) were examined. MDMA was the most common drug and was seen during the entire period. Amphetamine was the second most common drug and has been frequently detected during the the last two years. Drugs like MDE, MBDB, BDB, and 2-CB were rarely seen and they disappeared quickly from the illegal market. MDA appeared on the market at the end of 1999. Only 53% of the tablets contained MDMA as the sole drug. Eighty-one percent of the tablets/capsules contained only one synthetic drug, whereas 13% contained a mixture of two or more synthetic drugs. Six per cent of the samples did not contain a euphoric drug/designer drug. The content of MDMA, MDE, and amphetamine in the tablets varied greatly. MDMA is apparently the drug preferred by the users, but still only half of the tablets contained MDMA as the only drug. The rest of the tablets contained either another synthetic drug or a mixture of drugs. In conclusion, the increasing supply of various drugs with different and unpredictable effects and of miscellaneous quality brings about the risk of serious and complicated intoxications.

Soil reinforcement with recycled carpet wastes.

Science.gov (United States)

Ghiassian, Hossein; Poorebrahim, Gholamreza; Gray, Donald H

2004-04-01

A root or fibre-reinforced soil behaves as a composite material in which fibres of relatively high tensile strength are embedded in a matrix of relatively plastic soil. Shear stresses in the soil mobilize tensile resistance in the fibres, which in turn impart greater strength to the soil. A research project has been undertaken to study the influence of synthetic fibrous materials for improving the strength characteristics of a fine sandy soil. One of the main objectives of the project is to explore the conversion of fibrous carpet waste into a value-added product for soil reinforcement. Drained triaxial tests were conducted on specimens, which were prepared in a cylindrical mould and compacted at their optimum water contents. The main test variables included the aspect ratio and the weight percentage of the fibrous strips. The results clearly show that fibrous inclusions derived from carpet wastes improve the shear strength of silty sands. A model developed to simulate the effect of the fibrous inclusions accurately predicts the influence of strip content, aspect ratio and confining pressure on the shear strength of reinforced sand.

21 CFR 172.275 - Synthetic paraffin and succinic derivatives.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Synthetic paraffin and succinic derivatives. 172... FOOD FOR HUMAN CONSUMPTION Coatings, Films and Related Substances § 172.275 Synthetic paraffin and succinic derivatives. Synthetic paraffin and succinic derivatives identified in this section may be safely...

Drug decriminalization and the price of illicit drugs.

Science.gov (United States)

Félix, Sónia; Portugal, Pedro

2017-01-01

This study is an empirical assessment of the impact of the drug decriminalization policy followed by Portugal in July 2001, on the price of illicit drugs. The analysis is performed using a difference-in-differences approach and the Synthetic Control Method in order to construct a synthetic control unit from a convex combination of countries. The results suggest that the prices of opiates and cocaine in the post-treatment period did not decrease in the sequence of the policy change. We conclude that the drug decriminalization policy seems to have caused no harm through lower illicit drugs prices, which would lead to higher drug usage and dependence. Copyright © 2016 Elsevier B.V. All rights reserved.

Naloxone and rimonabant reduce the reinforcing properties of exercise in rats.

Science.gov (United States)

Rasmussen, Erin B; Hillman, Conrad

2011-12-01

Naloxone and rimonabant block neurotransmitter action of some drugs of abuse (such as ethanol, opiates, and nicotine), and thereby reduce drug seeking and self-administration by suppressing the drugs' reinforcing properties. The present study represents an attempt to elucidate whether these drugs may also reduce rewarding properties of other events, in this case, activity-based reinforcement. In Experiment 1, 10 obese and 10 lean Zucker rats pressed a locked door under a progressive ratio schedule of reinforcement that, when unlocked, provided access to a running wheel for 2-min intervals. After baseline breakpoints were established, doses of naloxone (0.3-10 mg/kg) were administered prior to experimental sessions. Obese rats exhibited lower baseline breakpoints for wheel activity, lower response rates, and fewer revolutions compared to lean rats. Naloxone decreased revolutions and response rates for lean and obese rats, but did not reduce breakpoints. In Experiment 2, five Long-Evans rats pressed a door to unlock a wheel for 20 s of wheel activity. Doses of rimonabant (1-10 mg/kg) were administered before some experimental sessions. The highest dose of rimonabant suppressed breakpoints and response rates, but did not affect revolutions. These data suggest that both drugs reduce the reinforcing properties of wheel running, but do so in different manners: naloxone may suppress wheel-based activity (consummatory behavior), but not seeking (appetitive behavior), and rimonabant does the converse. The data also support the role of endocannabinoids in the reinforcing properties of exercise, an implication that is important in terms of CB1 antagonists as a type of pharmacotherapy.

Characteristic Trends in Prevalence and Use of New Synthetic "Designer" Drugs over the Territory of the Republic of Bashkortostan

Science.gov (United States)

Asadullin, Azat R.; Yuldashev, Vladimir L.; Galeeva, Elena Kh.; Achmetova, Elvina A.; Nikolaev, Ivan V.

2016-01-01

The urgency of this study has become vivid in the light of the growing problem of prevalence and use of new synthetic drug types, incidence rate of comorbid states, and pathomorphism of psychoactive substances consumption. The aim of this paper consists in analysis and disclosure of the research data obtained on consumption of such designer drugs…

The Development and Validation of an In Vitro Airway Model to Assess Realistic Airway Deposition and Drug Permeation Behavior of Orally Inhaled Products Across Synthetic Membranes.

Science.gov (United States)

Huynh, Bao K; Traini, Daniela; Farkas, Dale R; Longest, P Worth; Hindle, Michael; Young, Paul M

2018-04-01

Current in vitro approaches to assess lung deposition, dissolution, and cellular transport behavior of orally inhaled products (OIPs) have relied on compendial impactors to collect drug particles that are likely to deposit in the airway; however, the main drawback with this approach is that these impactors do not reflect the airway and may not necessarily represent drug deposition behavior in vivo. The aim of this article is to describe the development and method validation of a novel hybrid in vitro approach to assess drug deposition and permeation behavior in a more representative airway model. The medium-sized Virginia Commonwealth University (VCU) mouth-throat (MT) and tracheal-bronchial (TB) realistic upper airway models were used in this study as representative models of the upper airway. The TB model was modified to accommodate two Snapwell ® inserts above the first TB airway bifurcation region to collect deposited nebulized ciprofloxacin-hydrochloride (CIP-HCL) droplets as a model drug aerosol system. Permeation characteristics of deposited nebulized CIP-HCL droplets were assessed across different synthetic membranes using the Snapwell test system. The Snapwell test system demonstrated reproducible and discriminatory drug permeation profiles for already dissolved and nebulized CIP-HCL droplets through a range of synthetic permeable membranes under different test conditions. The rate and extent of drug permeation depended on the permeable membrane material used, presence of a stirrer in the receptor compartment, and, most importantly, the drug collection method. This novel hybrid in vitro approach, which incorporates a modified version of a realistic upper airway model, coupled with the Snapwell test system holds great potential to evaluate postairway deposition characteristics, such as drug permeation and particle dissolution behavior of OIPs. Future studies will expand this approach using a cell culture-based setup instead of synthetic membranes, within a

A Comparison of Real-Time and Endpoint Cell Viability Assays for Improved Synthetic Lethal Drug Validation.

Science.gov (United States)

Single, Andrew; Beetham, Henry; Telford, Bryony J; Guilford, Parry; Chen, Augustine

2015-12-01

Cell viability assays fulfill a central role in drug discovery studies. It is therefore important to understand the advantages and disadvantages of the wide variety of available assay methodologies. In this study, we compared the performance of three endpoint assays (resazurin reduction, CellTiter-Glo, and nuclei enumeration) and two real-time systems (IncuCyte and xCELLigence). Of the endpoint approaches, both the resazurin reduction and CellTiter-Glo assays showed higher cell viabilities when compared directly to stained nuclei counts. The IncuCyte and xCELLigence real-time systems were comparable, and both were particularly effective at tracking the effects of drug treatment on cell proliferation at sub-confluent growth. However, the real-time systems failed to evaluate contrasting cell densities between drug-treated and control-treated cells at full growth confluency. Here, we showed that using real-time systems in combination with endpoint assays alleviates the disadvantages posed by each approach alone, providing a more effective means to evaluate drug toxicity in monolayer cell cultures. Such approaches were shown to be effective in elucidating the toxicity of synthetic lethal drugs in an isogenic pair of MCF10A breast cell lines. © 2015 Society for Laboratory Automation and Screening.

Deletion of the δ opioid receptor gene impairs place conditioning but preserves morphine reinforcement.

Science.gov (United States)

Le Merrer, Julie; Plaza-Zabala, Ainhoa; Del Boca, Carolina; Matifas, Audrey; Maldonado, Rafael; Kieffer, Brigitte L

2011-04-01

Converging experimental data indicate that δ opioid receptors contribute to mediate drug reinforcement processes. Whether their contribution reflects a role in the modulation of drug reward or an implication in conditioned learning, however, has not been explored. In the present study, we investigated the impact of δ receptor gene knockout on reinforced conditioned learning under several experimental paradigms. We assessed the ability of δ receptor knockout mice to form drug-context associations with either morphine (appetitive)- or lithium (aversive)-induced Pavlovian place conditioning. We also examined the efficiency of morphine to serve as a positive reinforcer in these mice and their motivation to gain drug injections, with operant intravenous self-administration under fixed and progressive ratio schedules and at two different doses. Mutant mice showed impaired place conditioning in both appetitive and aversive conditions, indicating disrupted context-drug association. In contrast, mutant animals displayed intact acquisition of morphine self-administration and reached breaking-points comparable to control subjects. Thus, reinforcing effects of morphine and motivation to obtain the drug were maintained. Collectively, the data suggest that δ receptor activity is not involved in morphine reinforcement but facilitates place conditioning. This study reveals a novel aspect of δ opioid receptor function in addiction-related behaviors. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

National Institute on Drug Abuse

Science.gov (United States)

... Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription Drugs & Cold Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

The new pattern of drug abuse in China.

Science.gov (United States)

Sun, Hong-qiang; Bao, Yan-ping; Zhou, Shuang-jiang; Meng, Shi-qiu; Lu, Lin

2014-07-01

Drug abuse has resulted in a huge burden on public health and the economy in China. Since the reemergence of drug abuse in China in the 1980s, the number of drug addicts has increased dramatically, especially the proportion of users of synthetic drugs, such as amphetamine-type stimulant (ATS). Further, the proportion of opiate addicts has decreased among the new initiates. This review describes the new pattern of drug abuse and the resultant intervention strategy in China. The demographics regarding drug abuse in China point to a trend of younger users, and indicate that Internet and telephone are facilitating drug trafficking. Furthermore, polydrug use is common. Many heroin addicts have used ATS and other synthetic drugs, and some synthetic drug abusers have used opiate drugs too. HIV infection and psychosis comorbidity are primarily associated with drug abuse in China. Although opiate drug use and its associated harm have been controlled effectively in some areas, the synthetic drugs and new designer drugs have complicated the drug abuse scene. A national system of management and intervention for synthetic drugs and associated diseases urgently needs to be established in China.

Incorporation of photosenzitizer hypericin into synthetic lipid-based nano-particles for drug delivery and large unilamellar vesicles with different content of cholesterol

Science.gov (United States)

Joniova, Jaroslava; Blascakova, Ludmila; Jancura, Daniel; Nadova, Zuzana; Sureau, Franck; Miskovsky, Pavol

2014-08-01

Low-density lipoproteins (LDL) and high-density lipoproteins (HDL) are attractive natural occurring vehicles for drug delivery and targeting to cancer tissues. The capacity of both types of the lipoproteins to bind hydrophobic drugs and their functionality as drug carriers have been examined in several studies and it has been also shown that mixing of anticancer drugs with LDL or HDL before administration led to an increase of cytotoxic effects of the drugs in the comparison when the drugs were administered alone. However, a difficult isolation of the lipoproteins in large quantity from a biological organism as well as a variability of the composition and size of these molecules makes practical application of LDL and HDL as drug delivery systems quite complicated. Synthetic LDL and HDL and large unilamellar vesicles (LUV) are potentially suitable candidates to substitute the native lipoproteins for targeted and effective drug delivery. In this work, we have studied process of an association of potent photosensitizer hypericin (Hyp) with synthetic lipid-based nano-particles (sLNP) and large unilamellar vesicles (LUV) containing various amount of cholesterol. Cholesterol is one of the main components of both LDL and HDL particles and its presence in biological membranes is known to be a determining factor for membrane properties. It was found that the behavior of Hyp incorporation into sLNP particles with diameter ca ~ 90 nm is qualitatively very similar to that of Hyp incorporation into LDL (diameter ca. 22 nm) and these particles are able to enter U-87 MG cells by endocytosis. The presence of cholesterol in LUV influences the capacity of these vesicles to incorporate Hyp into their structure.

Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction.

Science.gov (United States)

Elsheshtawy, Moustafa; Sriganesh, Priatharsini; Virparia, Vasudev; Patel, Falgun; Khanna, Ashok

2016-01-01

Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools.

Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction

OpenAIRE

Moustafa Elsheshtawy; Priatharsini Sriganesh; Vasudev Virparia; Falgun Patel; Ashok Khanna

2016-01-01

Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools.

Aerobic exercise decreases the positive-reinforcing effects of cocaine.

Science.gov (United States)

Smith, Mark A; Schmidt, Karl T; Iordanou, Jordan C; Mustroph, Martina L

2008-11-01

Aerobic exercise can serve as an alternative, non-drug reinforcer in laboratory animals and has been recommended as a potential intervention for substance abusing populations. Unfortunately, relatively little empirical data have been collected that specifically address the possible protective effects of voluntary, long-term exercise on measures of drug self-administration. The purpose of the present study was to examine the effects of chronic exercise on sensitivity to the positive-reinforcing effects of cocaine in the drug self-administration procedure. Female rats were obtained at weaning and immediately divided into two groups. Sedentary rats were housed individually in standard laboratory cages that permitted no exercise beyond normal cage ambulation; exercising rats were housed individually in modified cages equipped with a running wheel. After 6 weeks under these conditions, rats were surgically implanted with venous catheters and trained to self-administer cocaine on a fixed-ratio schedule of reinforcement. Once self-administration was acquired, cocaine was made available on a progressive ratio schedule and breakpoints were obtained for various doses of cocaine. Sedentary and exercising rats did not differ in the time to acquire cocaine self-administration or responding on the fixed-ratio schedule of reinforcement. However, on the progressive ratio schedule, breakpoints were significantly lower in exercising rats than sedentary rats when responding was maintained by both low (0.3mg/kg/infusion) and high (1.0mg/kg/infusion) doses of cocaine. In exercising rats, greater exercise output prior to catheter implantation was associated with lower breakpoints at the high dose of cocaine. These data indicate that chronic exercise decreases the positive-reinforcing effects of cocaine and support the possibility that exercise may be an effective intervention in drug abuse prevention and treatment programs.

Drugged Driving

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Club Drugs

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction

Directory of Open Access Journals (Sweden)

Moustafa Elsheshtawy

2016-01-01

Full Text Available Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools.

Neurobiology of dysregulated motivational systems in drug addiction

Science.gov (United States)

Edwards, Scott; Koob, George F

2010-01-01

The progression from recreational drug use to drug addiction impacts multiple neurobiological processes and can be conceptualized as a transition from positive to negative reinforcement mechanisms driving both drug-taking and drug-seeking behaviors. Neurobiological mechanisms for negative reinforcement, defined as drug taking that alleviates a negative emotional state, involve changes in the brain reward system and recruitment of brain stress (or antireward) systems within forebrain structures, including the extended amygdala. These systems are hypothesized to be dysregulated by excessive drug intake and to contribute to allostatic changes in reinforcement mechanisms associated with addiction. Points of intersection between positive and negative motivational circuitry may further drive the compulsivity of drug addiction but also provide a rich neurobiological substrate for therapeutic intervention. PMID:20563312

Comparison of outcome expectancies for synthetic cannabinoids and botanical marijuana.

Science.gov (United States)

Lauritsen, Kirstin J; Rosenberg, Harold

2016-07-01

Although initially developed for medical purposes, synthetic cannabinoids have also been consumed for recreational purposes. To evaluate whether agreement with positive and negative outcome expectancies differed for synthetic cannabinoids versus botanical marijuana, and assess reported reasons for using synthetic cannabinoids. Using a web-based recruitment and data collection procedure, 186 adults who had used both synthetic cannabinoids and botanical marijuana and 181 adults who had used botanical marijuana but not synthetic cannabinoids, completed measures of outcome expectancies and other relevant questionnaires. A significant interaction revealed that participants who had used both synthetic cannabinoids and botanical marijuana indicated lower agreement with positive expectancies for synthetic cannabinoids, and higher agreement with positive expectancies for botanical marijuana, than did those participants who used only botanical marijuana. There was no interaction between type of drug and use history on agreement with negative expectancies, and participants agreed more strongly with negative outcome expectancies for synthetic cannabinoids than for botanical marijuana whether they had used one or both types of these drugs. The most frequently provided reasons for using synthetic cannabinoids included availability, perceived legality, cost, curiosity, and social interaction. Given growing public acceptance of recreational and medical marijuana, coupled with negative perceptions and increasing regulation of synthetic cannabinoid compounds, botanical marijuana is likely to remain more available and more popular than synthetic cannabinoids.

Reinforcer magnitude and rate dependency: evaluation of resistance-to-change mechanisms.

Science.gov (United States)

Pinkston, Jonathan W; Ginsburg, Brett C; Lamb, Richard J

2014-10-01

Under many circumstances, reinforcer magnitude appears to modulate the rate-dependent effects of drugs such that when schedules arrange for relatively larger reinforcer magnitudes rate dependency is attenuated compared with behavior maintained by smaller magnitudes. The current literature on resistance to change suggests that increased reinforcer density strengthens operant behavior, and such strengthening effects appear to extend to the temporal control of behavior. As rate dependency may be understood as a loss of temporal control, the effects of reinforcer magnitude on rate dependency may be due to increased resistance to disruption of temporally controlled behavior. In the present experiments, pigeons earned different magnitudes of grain during signaled components of a multiple FI schedule. Three drugs, clonidine, haloperidol, and morphine, were examined. All three decreased overall rates of key pecking; however, only the effects of clonidine were attenuated as reinforcer magnitude increased. An analysis of within-interval performance found rate-dependent effects for clonidine and morphine; however, these effects were not modulated by reinforcer magnitude. In addition, we included prefeeding and extinction conditions, standard tests used to measure resistance to change. In general, rate-decreasing effects of prefeeding and extinction were attenuated by increasing reinforcer magnitudes. Rate-dependent analyses of prefeeding showed rate-dependency following those tests, but in no case were these effects modulated by reinforcer magnitude. The results suggest that a resistance-to-change interpretation of the effects of reinforcer magnitude on rate dependency is not viable.

From bricolage to BioBricks™: Synthetic biology and rational design.

Science.gov (United States)

Lewens, Tim

2013-12-01

Synthetic biology is often described as a project that applies rational design methods to the organic world. Although humans have influenced organic lineages in many ways, it is nonetheless reasonable to place synthetic biology towards one end of a continuum between purely 'blind' processes of organic modification at one extreme, and wholly rational, design-led processes at the other. An example from evolutionary electronics illustrates some of the constraints imposed by the rational design methodology itself. These constraints reinforce the limitations of the synthetic biology ideal, limitations that are often freely acknowledged by synthetic biology's own practitioners. The synthetic biology methodology reflects a series of constraints imposed on finite human designers who wish, as far as is practicable, to communicate with each other and to intervene in nature in reasonably targeted and well-understood ways. This is better understood as indicative of an underlying awareness of human limitations, rather than as expressive of an objectionable impulse to mastery over nature. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structural analysis of protein-ligand interactions: the binding of endogenous compounds and of synthetic drugs.

Science.gov (United States)

Gallina, Anna M; Bork, Peer; Bordo, Domenico

2014-02-01

The large number of macromolecular structures deposited with the Protein Data Bank (PDB) describing complexes between proteins and either physiological compounds or synthetic drugs made it possible a systematic analysis of the interactions occurring between proteins and their ligands. In this work, the binding pockets of about 4000 PDB protein-ligand complexes were investigated and amino acid and interaction types were analyzed. The residues observed with lowest frequency in protein sequences, Trp, His, Met, Tyr, and Phe, turned out to be the most abundant in binding pockets. Significant differences between drug-like and physiological compounds were found. On average, physiological compounds establish with respect to drugs about twice as many hydrogen bonds with protein atoms, whereas drugs rely more on hydrophobic interactions to establish target selectivity. The large number of PDB structures describing homologous proteins in complex with the same ligand made it possible to analyze the conservation of binding pocket residues among homologous protein structures bound to the same ligand, showing that Gly, Glu, Arg, Asp, His, and Thr are more conserved than other amino acids. Also in the cases in which the same ligand is bound to unrelated proteins, the binding pockets showed significant conservation in the residue types. In this case, the probability of co-occurrence of the same amino acid type in the binding pockets could be up to thirteen times higher than that expected on a random basis. The trends identified in this study may provide an useful guideline in the process of drug design and lead optimization. Copyright © 2014 John Wiley & Sons, Ltd.

Designing bioinspired composite reinforcement architectures via 3D magnetic printing

Science.gov (United States)

Martin, Joshua J.; Fiore, Brad E.; Erb, Randall M.

2015-10-01

Discontinuous fibre composites represent a class of materials that are strong, lightweight and have remarkable fracture toughness. These advantages partially explain the abundance and variety of discontinuous fibre composites that have evolved in the natural world. Many natural structures out-perform the conventional synthetic counterparts due, in part, to the more elaborate reinforcement architectures that occur in natural composites. Here we present an additive manufacturing approach that combines real-time colloidal assembly with existing additive manufacturing technologies to create highly programmable discontinuous fibre composites. This technology, termed as `3D magnetic printing', has enabled us to recreate complex bioinspired reinforcement architectures that deliver enhanced material performance compared with monolithic structures. Further, we demonstrate that we can now design and evolve elaborate reinforcement architectures that are not found in nature, demonstrating a high level of possible customization in discontinuous fibre composites with arbitrary geometries.

Designing bioinspired composite reinforcement architectures via 3D magnetic printing.

Science.gov (United States)

Martin, Joshua J; Fiore, Brad E; Erb, Randall M

2015-10-23

Discontinuous fibre composites represent a class of materials that are strong, lightweight and have remarkable fracture toughness. These advantages partially explain the abundance and variety of discontinuous fibre composites that have evolved in the natural world. Many natural structures out-perform the conventional synthetic counterparts due, in part, to the more elaborate reinforcement architectures that occur in natural composites. Here we present an additive manufacturing approach that combines real-time colloidal assembly with existing additive manufacturing technologies to create highly programmable discontinuous fibre composites. This technology, termed as '3D magnetic printing', has enabled us to recreate complex bioinspired reinforcement architectures that deliver enhanced material performance compared with monolithic structures. Further, we demonstrate that we can now design and evolve elaborate reinforcement architectures that are not found in nature, demonstrating a high level of possible customization in discontinuous fibre composites with arbitrary geometries.

Glutamatergic transmission in drug reward: implications for drug addiction.

Science.gov (United States)

D'Souza, Manoranjan S

2015-01-01

Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding) effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society. Over the last two decades, there has been an increasing focus on the role of the excitatory neurotransmitter glutamate in drug addiction. In this review, pharmacological and genetic evidence supporting the role of glutamate in mediating the rewarding effects of the above described drugs of abuse will be discussed. Further, the review will discuss the role of glutamate transmission in two complex heterogeneous brain regions, namely the nucleus accumbens (NAcc) and the ventral tegmental area (VTA), which mediate the rewarding effects of drugs of abuse. In addition, several medications approved by the Food and Drug Administration that act by blocking glutamate transmission will be discussed in the context of drug reward. Finally, this review will discuss future studies needed to address currently unanswered gaps in knowledge, which will further elucidate the role of glutamate in the rewarding effects of drugs of abuse.

Optimization of Recycled Glass Fibre-Reinforced Plastics Gear via Integration of the Taguchi Method and Grey Relational Analysis

Science.gov (United States)

Mizamzul Mehat, Nik; Syuhada Zakarria, Noor; Kamaruddin, Shahrul

2018-03-01

The increase in demand for industrial gears has resulted in the increase in usage of plastic-matrix composites particularly glass fibre-reinforced plastics as the gear materials. The usage of these synthetic fibers is to enhance the mechanical strength and the thermal resistance of the plastic gears. Nevertheless, the production of large quantities of these synthetic fibre-reinforced composites poses a serious threat to the ecosystem. Comprehending to this fact, the present work aimed at investigating the effects of incorporating recycled glass fibre-reinforced plastics in various compositions particularly on dimensional stability and mechanical properties of gear produced with diverse injection moulding processing parameters setting. The integration of Grey relational analysis (GRA) and Taguchi method was adopted to evaluate the influence of recycled glass fibre-reinforced plastics and variation in processing parameters on gear quality. From the experimental results, the blending ratio was found as the most influential parameter of 56.0% contribution in both improving tensile properties as well as in minimizing shrinkage, followed by mould temperature of 24.1% contribution and cooling time of 10.6% contribution. The results obtained from the aforementioned work are expected to contribute to accessing the feasibility of using recycled glass fibre-reinforced plastics especially for gear application.

Tensile Mechanical Property of Oil Palm Empty Fruit Bunch Fiber Reinforced Epoxy Composites

Science.gov (United States)

Ghazilan, A. L. Ahmad; Mokhtar, H.; Shaik Dawood, M. S. I.; Aminanda, Y.; Ali, J. S. Mohamed

2017-03-01

Natural, short, untreated and randomly oriented oil palm empty fruit bunch fiber reinforced epoxy composites were manufactured using vacuum bagging technique with 20% fiber volume composition. The performance of the composite was evaluated as an alternative to synthetic or conventional reinforced composites. Tensile properties such as tensile strength, modulus of elasticity and Poisson’s ratio were compared to the tensile properties of pure epoxy obtained via tensile tests as per ASTM D 638 specifications using Universal Testing Machine INSTRON 5582. The tensile properties of oil palm empty fruit bunch fiber reinforced epoxy composites were lower compared to plain epoxy structure with the decrement in performances of 38% for modulus of elasticity and 61% for tensile strength.

Hypocretin / orexin involvement in reward and reinforcement

Science.gov (United States)

España, Rodrigo A.

2015-01-01

Since the discovery of the hypocretins/orexins, a series of observations have indicated that these peptides influence a variety of physiological processes including feeding, sleep/wake function, memory, and stress. More recently, the hypocretins have been implicated in reinforcement and reward-related processes via actions on the mesolimbic dopamine system. Although investigation into the relationship between the hypocretins and reinforcement/reward remains in relatively early stages, accumulating evidence suggests that continued research into this area may offer new insights into the addiction process and provide the foundation to generate novel pharmacotherapies for drug abuse. The current chapter will focus on contemporary perspectives of hypocretin regulation of cocaine reward and reinforcement via actions on the mesolimbic dopamine system. PMID:22640614

DrugFacts: Heroin

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

The Effect of Pre-Tension on Deformation Behaviour of Natural Fabric Reinforced Composite

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Paulė BEKAMPIENĖ

2011-03-01

Full Text Available In the fiber-reinforced composites industry together with the promotion of environmental friendly production, synthetic materials are attempted to be replaced by renewable, biodegradable and recyclable materials. The most important challenge is to improve strength and durability of these materials. Matrix that supports the fiber-reinforcement in composite generally is brittle and deformation causes fragmentation of the matrix. Pre-tension of reinforcement is a well-known method to increase tensile strength of woven material. The current study develops the idea to use pre-tension of woven fabric in order to improve quality and strength properties of the obtained composite. Natural (cotton fiber and synthetic (glass fiber woven fabrics were investigated. The pressure forming operation was carried out in order to study clamping imposed strain variation across the surface of woven fabric. The uniaxial tension test of single-layer composite specimens with and without pre-tension was performed to study the effect of pre-tension on strength properties of composite. The results have shown that pre-tension imposed by clamping is an effective method to improve the quality of shaped composite parts (more smoothed contour is obtained and to increase the strength properties of composite reinforced by woven natural fabric. After pre-tension the tensile strength at break increased in 12 % in warp direction, in 58 % in weft direction and in 39 % in bias direction.http://dx.doi.org/10.5755/j01.ms.17.1.250

A Synthetic Biology Project - Developing a single-molecule device for screening drug-target interactions.

Science.gov (United States)

Firman, Keith; Evans, Luke; Youell, James

2012-07-16

This review describes a European-funded project in the area of Synthetic Biology. The project seeks to demonstrate the application of engineering techniques and methodologies to the design and construction of a biosensor for detecting drug-target interactions at the single-molecule level. Production of the proteins required for the system followed the principle of previously described "bioparts" concepts (a system where a database of biological parts - promoters, genes, terminators, linking tags and cleavage sequences - is used to construct novel gene assemblies) and cassette-type assembly of gene expression systems (the concept of linking different "bioparts" to produce functional "cassettes"), but problems were quickly identified with these approaches. DNA substrates for the device were also constructed using a cassette-system. Finally, micro-engineering was used to build a magnetoresistive Magnetic Tweezer device for detection of single molecule DNA modifying enzymes (motors), while the possibility of constructing a Hall Effect version of this device was explored. The device is currently being used to study helicases from Plasmodium as potential targets for anti-malarial drugs, but we also suggest other potential uses for the device. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Synthetic cannabinoid: prevalence, mechanisms of addiction development, mental disorders associated with the use of synthetic cannabinoid

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Antsyborov A.V.

2017-04-01

Full Text Available according to the authors among the new psychoactive substances, the number of which is growing every year, despite the measures aimed at the obstacles to their dissemination there discovered the most frequent violations of psychotic conditions associated with use of synthetic cannabinoid in clinical practice. On the black market, they are distributed through online shops, under the guise of herbal mixtures for Smoking. When ingested, this group of drugs at the peak of intoxication raises a number of mental (different according to the depth of impaired consciousness, auditory and visual hallucinations, panic attacks, acute psychotic paranoid disorders, catatonic stupor, polar affective disorders, acute polythematic delusional symptoms and somatic disorders (disorders of heart rhythm and conduction, acute ischemic disorders, hypertension, depression of respiratory activity, violation of thermoregulation, development of acute renal failure, vomiting, expressed cephalgia, clinic of hypokalemia. In the reviewed literature and authors own observations there have been discovered some cases of mental addiction development to synthetic cannabinoids. The analysis of new literature data and own clinical observations helped the authors to compare the psychotropic effects caused by this group of drugs, relative to other known surfactants. The toxic effects of CSC on the body greatly exceeds the use of plant cannabinoids, and it has almost the same effects as the synthetic cathinone’s. The speed of formation of psychological dependence is lower compared to synthetic cathinone. Developing current strategies for diagnosis, treatment, and rehabilitation of patients who use synthetic cannabinoids remains an important task for practical healthcare.

Fique Fabric: A Promising Reinforcement for Polymer Composites

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Sergio Neves Monteiro

2018-02-01

Full Text Available A relatively unknown natural fiber extracted from the leaves of the fique plant, native of the South American Andes, has recently shown potential as reinforcement of polymer composites for engineering applications. Preliminary investigations indicated a promising substitute for synthetic fibers, competing with other well-known natural fibers. The fabric made from fique fibers have not yet been investigated as possible composite reinforcement. Therefore, in the present work a more thorough characterization of fique fabric as a reinforcement of composites with a polyester matrix was performed. Thermal mechanical properties of fique fabric composites were determined by dynamic mechanical analysis (DMA. The ballistic performance of plain woven fique fabric-reinforced polyester matrix composites was investigated as a second layer in a multilayered armor system (MAS. The results revealed a sensible improvement in thermal dynamic mechanical behavior. Both viscoelastic stiffness and glass transition temperature were increased with the amount of incorporated fique fabric. In terms of ballistic results, the fique fabric composites present a performance similar to that of the much stronger KevlarTM as an MAS second layer with the same thickness. A cost analysis indicated that armor vests with fique fabric composites as an MAS second layer would be 13 times less expensive than a similar creation made with Kevlar™.

Towards reinforcement solutions for urban fibre/fabric waste using bio-based biodegradable resins.

Science.gov (United States)

Agrawal, Pramod; Hermes, Alina; Bapeer, Solaf; Luiken, Anton; Bouwhuis, Gerrit; Brinks, Ger

2017-10-01

The main research question is how to systematically define and characterize urban textile waste and how to effectively utilise it to produce reinforcement(s) with selected bio-based biodegradable resin(s). Several composite samples have been produced utilising predominantly natural and predominantly synthetic fibres by combining loose fibres with PLA, nonwoven fabric with PLA, woven fabric with PLA, two-layer composite & four-layer composite samples. Physio-chemical characterisations according to the established standards have been conducted. The present work is a step toward the circular economy and closing the loop in textile value chain.

The development and maintenance of drug addiction.

Science.gov (United States)

Wise, Roy A; Koob, George F

2014-01-01

What is the defining property of addiction? We dust off a several-decades-long debate about the relative importance of two forms of reinforcement—positive reinforcement, subjectively linked to drug-induced euphoria, and negative reinforcement, subjectively linked to the alleviation of pain—both of which figure importantly in addiction theory; each of these forms has dominated addiction theory in its time. We agree that addiction begins with the formation of habits through positive reinforcement and that drug-opposite physiological responses often establish the conditions for negative reinforcement to come into play at a time when tolerance, in the form of increasing reward thresholds, appears to develop into positive reinforcement. Wise’s work has tended to focus on positive-reinforcement mechanisms that are important for establishing drug-seeking habits and reinstating them quickly after periods of abstinence, whereas Koob’s work has tended to focus on the negative-reinforcement mechanisms that become most obvious in the late stages of sustained addiction. While we tend to agree with each other about the early and late stages of addiction, we hold different views as to (i) the point between early and late at which the diagnosis of ‘addiction’ should be invoked, (ii) the relative importance of positive and negative reinforcement leading up to this transition, and (iii) the degree to which the specifics of negative reinforcement can be generalized across the range of addictive agents.

Glutamatergic transmission in drug reward: Implications for drug addiction

Directory of Open Access Journals (Sweden)

Manoranjan S Dsouza

2015-11-01

Full Text Available Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society. Over the last two decades, there has been an increasing focus on the role of the excitatory neurotransmitter glutamate in drug addiction. In this review, pharmacological and genetic evidence supporting the role of glutamate in mediating the rewarding effects of the above described drugs of abuse will be discussed. Further, the review will discuss the role of glutamate transmission in two complex heterogeneous brain regions, namely the nucleus accumbens (NAcc and the ventral tegmental area (VTA, which mediate the rewarding effects of drugs of abuse. In addition, several medications approved by the Food and Drug Administration that act by blocking glutamate transmission will be discussed in the context of drug reward. Finally, this review will discuss future studies needed to address currently unanswered gaps in knowledge, which will further elucidate the role of glutamate in the rewarding effects of drugs of abuse.

Bending test in epoxy composites reinforced with continuous and aligned PALF fibers

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Gabriel Oliveira Glória

2017-10-01

Full Text Available Sustainable actions aiming to prevent increasing worldwide pollution are motivating the substitution of environmentally friendly materials for conventional synthetic ones. A typical example is the use of natural lignocellulosic fiber (LCF as reinforcement of polymer composites that have traditionally been reinforced with glass fiber. Both scientific research and engineering applications support the use of numerous LCFs composites. The pineapple fiber (PALF, extracted from the leaves of Ananas comosus, is considered a LCF with potential for composite reinforcement. However, specific mechanical properties and microstructural characterization are still necessary for this purpose. Therefore, the objective of this short work is to evaluate the flexural properties, by means of three points, bend tests, of epoxy composites incorporated with up to 30 vol% of PALF. Results reveal that continuous and aligned fibers significantly increase the flexural strength. Scanning electron microscopy disclosed the fracture mechanism responsible for this reinforcement. Keywords: Pineapple fibers, PALF, Flexural properties, Bending test, Epoxy composites, Fracture mechanism

Synthetic cathinone “bath salts”: the mechanism of action, toxicological aspects, clinic, dependence development

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Antsyborov A.V.

2017-05-01

Full Text Available according to the authors synthetic cathinone is a new class of designer drugs with psychoactive effect at the peak of intoxication which can cause hallucinatory disorders, acute paranoid disorders of psychotic level, the development of delirious disorders, affective disorders comparable to cocaine, methylenedioxymethamphetamine (MDMA and other drugs with amphetamine-like effect. The first reports of synthetic cathinone appeared in early 2009. On the black market, these substances were marketed as «bath salts». The legislation of the European countries have been carrying these substances to the drug since 2010, in the United States synthetic cathinone has been included in the list of narcotic substances since 2011, in the Russian Federation, these substances can be attributed to narcotic according to the Decree of the RF Government dated 31 December 2009 №1186 «About modification of some resolutions of the Government of the Russian Federation on issues related to trafficking in narcotic drugs». Recent clinical studies indicate dysregulation effect of synthetic cathinone’s on central monoamine system, which is one of the main mechanisms of synthetic cathinone’s action, and is the basis of behavioral disorders due to use. The review provides data about the chemical structure of synthetic cathinone’s, mechanisms of addiction, toxicology, clinical aspects of use.

Preparation and characterization of corn reinforced polymer sheet of fibers

International Nuclear Information System (INIS)

Moreira, Tatiana Martinez; Seo, Emilia Satoshi Miyamaru

2016-01-01

There is a global trend in seeking plant fibers to replace the synthetic fibers to obtain reinforced composites aimed at the use of renewable resources. In this context, this paper aims to develop the process of preparing maize leaf fibers, characterizing them and adapting them for applications in the construction industry and develop a reinforced polymer composite with these fibers. Corn leaves were dried in environmental temperature, treated by mercerizing, then neutralized with acid solution and washed in running water. The characterization of the corn leaf fibers was carried out by X-ray diffraction, X-ray fluorescence, scanning electron microscopy, specific surface area, thermogravimetry and specific mass. The mercerizing treatment was effective, because the maize fibers have characteristics similar to synthetic fibers, leading to a possibility of new technological uses. The polymeric composite material was developed by extrusion processes and injection and tested for tensile testing, differential scanning calorimetry and scanning electron microscopy, thus reused an organic waste that would be disposed of by inserting it in a technological process, contributing to the research and development of new polymeric materials as well as to reduce waste discarded as scrap. (author)

Synthetic approaches to the 2009 new drugs.

Science.gov (United States)

Liu, Kevin K-C; Sakya, Subas M; O'Donnell, Christopher J; Flick, Andrew C; Li, Jin

2011-02-01

New drugs are introduced to the market every year and each individual drug represents a privileged structure for its biological target. These new chemical entities (NCEs) provide insights into molecular recognition and also serve as leads for designing future new drugs. This review covers the syntheses of 21 NCEs marketed in 2009. Copyright © 2011 Elsevier Ltd. All rights reserved.

Antitheilerial Chemical Drugs: A Review | Hayat | Bulletin of Animal ...

African Journals Online (AJOL)

Synthetic or semi synthetic chemical drugs were used for treatment of Theileria species. These drugs include antimalarial, trypanocides and antibiotics, antiviral, etc. The aim of this study was to over-view chemical drugs tested for treatment of theileriosis. Keywords: Theileria, treatment, chemical drug ...

Physical dependence increases the relative reinforcing effects of caffeine versus placebo.

Science.gov (United States)

Garrett, B E; Griffiths, R R

1998-10-01

Using a within-subject cross-over design, this study examined the role of physical dependence in caffeine reinforcement by experimentally manipulating physical dependence. Each subject was exposed to two chronic drug phases (300 mg/70 kg/day caffeine and placebo) for 9-12 days, with order of phases counterbalanced across subjects. On 2 separate days immediately following each of the chronic drug exposures, subjects received acute doses of either caffeine (300 mg/70 kg) or placebo in counterbalanced order. The reinforcing effects of these drugs were then determined by using a multiple-choice procedure in which subjects made a series of discrete choices between receiving varying amounts of money or receiving the drug again, and a choice between the two drugs. To ensure that subjects completed the form carefully, following exposure to both of the acute drug administrations, one of the subject's previous choices from the multiple-choice form was randomly selected and the consequence of that choice was implemented. When subjects were maintained on chronic caffeine, they were willing to forfeit significantly more money and showed significant increases in typical withdrawal symptoms (e.g. fatigue, mood disturbance) after receiving placebo as compared to the other three conditions. When subjects were maintained on chronic caffeine, they also chose to receive caffeine over placebo twice as often than when they were maintained on chronic placebo. These findings provide the strongest evidence to date indicating that caffeine physical dependence increases the relative reinforcing effects of caffeine versus placebo.

A New Drug Release Method in Early Development of Transdermal Drug Delivery Systems

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Bing Cai

2012-01-01

Full Text Available In vitro drug release tests are a widely used tool to measure the variance between transdermal product performances and required by many authorities. However, the result cannot provide a good estimation of the in vivo drug release. In the present work, a new method for measuring drug release from patches has been explored and compared with the conventional USP apparatus 2 and 5 methods. Durogesic patches, here used as a model patch, were placed on synthetic skin simulator and three moisture levels (29, 57, 198 μL cm−2 were evaluated. The synthetic skin simulators were collected after 1, 2, 3, 4, 6, and 24 hours and extracted with pH 1.0 hydrochloric acid solution. The drug concentrations in the extractions were measured by isocratic reverse phase high-pressure liquid chromatography. The results showed that, with the increasing moisture level on the synthetic skin simulator, the drug release rate increased. In comparison with the conventional USP method, the drug release results performed by the new method were in more correlation to the release rate claimed in the product label. This new method could help to differentiate the drug release rates among assorted formulations of transdermal drug delivery systems in the early stage of development.

Influence of cellulose fibers on structure and properties of fiber reinforced foam concrete

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Fedorov Valeriy

2018-01-01

Full Text Available One of the promising means of foamed concrete quality improvement is micro-reinforcement by adding synthetic and mineral fibers to the base mix. This research is the first to investigate peculiarities of using recycled cellulose fiber extracted from waste paper for obtaining fiber reinforced foam concrete. The paper presents results of experimental research on the influence of cellulose fibers on structure and properties of fiber reinforced foam concrete by using methods of chemical analysis and scanning electron microscopy. The research determines peculiarities of new formations appearance and densification of binder hydration products in the contact zone between fiber and cement matrix, which boost mechanical strength of fiber reinforced foam concrete. Physico-mechanical properties of fiber reinforced foam concrete were defined depending on the amount of recycled cellulose fiber added to the base mix. It was found that the use of recycled cellulose fibers allows obtaining structural thermal insulating fiber reinforced foam concretes of non-autoclaved hardening of brand D600 with regard to mean density with the following improved properties: compressive strength increased by 35% compared to basic samples, higher stability of foamed concrete mix and decreased shrinkage deformation.

Synthetic cathinones: a new public health problem.

Science.gov (United States)

Karila, Laurent; Megarbane, Bruno; Cottencin, Olivier; Lejoyeux, Michel

2015-01-01

New psychoactive substances (NPS) have completely modified the drug scene and the current landscape of addiction. Synthetic substances, such as substituted or synthetic cathinones, also known as « legal highs », are often produced and used to mimic the effects of controlled drugs such as cocaine, methylenedioxymethamphetamine (MDMA, ecstasy), and methamphetamine. The overwhelming majority of synthetic cathinones are produced in China and South East Asian countries. The Internet has emerged as the new marketplace for NPS, playing a major role in providing information on acquisition, synthesis, extraction, identification, and substance use. All these compounds are intentionally mislabeled and sold on-line under slang terms such as bath salts, plant food, plant feeders and research chemicals. They are sometimes labeled « not for human use » or « not tested for hazards or toxicity ». The rapid spread of NPS forces member countries of the European Union to adapt their response to the potential new dangers that may cause. To date, not only health actors but also the general public need to be clearly informed and aware of dangers resulting from NPS spread and use. Here, we review the major clinical effects of synthetic cathinones to highlight their impact on public health. A literature search was conducted from 2009 to 2014 based on PubMed, Google Scholar, Erowid, and governmental websites, using the following keywords alone or in combination: "new psychoactive substances", "synthetic cathinones", "substituted cathinones", "mephedrone", "methylone", "MDPV", "4-MEC", "addiction", and "substance use disorder".

Drug Facts: Anabolic Steroids

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Drugged Driving

Science.gov (United States)

... Survey Results Synthetic Cannabinoids (K2/Spice) Unpredictable Danger Drug and Alcohol Use in College-Age Adults in 2016 Monitoring the Future 2016 Survey Results Drug and Alcohol Use in College-Age Adults in 2015 View All NIDA Home ...

Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement.

Science.gov (United States)

Griffiths, R R; Chausmer, A L

2000-11-01

Caffeine is an excellent model compound for understanding drugs of abuse/dependence. The results of self-administration and choice studies in humans clearly demonstrate the reinforcing effects of low and moderate doses of caffeine. Caffeine reinforcement has been demonstrated in about 45% of normal subjects with histories of moderate and heavy caffeine use. Recent studies provide compelling evidence that caffeine physical dependence potentiates the reinforcing effects of caffeine through the mechanism of withdrawal symptom avoidance. Tolerance to the subjective and sleep-disrupting effects of caffeine in humans has been demonstrated. Physical dependence as reflected in a withdrawal syndrome in humans has been repeatedly demonstrated in adults and recently demonstrated in children. Withdrawal severity is an increasing function of caffeine maintenance dose, with withdrawal occurring at doses as low as 100 mg per day. Increased cerebral blood flow may be the physiological mechanism for caffeine withdrawal headache. Case studies in adults and adolescents clearly demonstrate that some individuals meet DSM-IV diagnostic criteria for a substance dependence syndrome on caffeine, including feeling compelled to continue caffeine use despite desires and recommendations to the contrary. Survey data suggest that 9% to 30% percent of caffeine consumers may be caffeine dependent according to DSM-IV criteria.

Improving the drug delivery characteristics of graphene oxide based polymer nanocomposites through the “one-pot” synthetic approach of single-electron-transfer living radical polymerization

Energy Technology Data Exchange (ETDEWEB)

Gao, Peng; Liu, Meiying; Tian, Jianwen; Deng, Fengjie [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wang, Ke [Department of Chemistry and the Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing 100084 (China); Xu, Dazhuang [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Liu, Liangji [Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006 (China); Zhang, Xiaoyong, E-mail: xiaoyongzhang1980@gmail.com [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wei, Yen, E-mail: weiyen@tsinghua.edu.cn [Department of Chemistry and the Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing 100084 (China)

2016-08-15

Graphical abstract: The PEGylated graphene oxides with high water dispersibility, good biocompatibility as well as high drug loading capability were fabricated via “one-pot” SET-LRP. - Highlights: • Surface modification of graphene oxide with polymers. • One-pot single-electron-transfer living radical polymerization. • Improving drug delivery characteristics. • The synthetic approach is rather simple, universal and effective. - Abstract: Graphene oxide (GO) based polymer nanocomposites have attracted extensive research interest recently for their outstanding physicochemical properties and potential applications. However, surface modification of GO with synthetic polymers has demonstrated to be trouble for most polymerization procedures are occurred under non-aqueous solution, which will in turn lead to the restacking of GO. In this work, a facile and efficient “one-pot” strategy has been developed for surface modification of GO with synthetic polymers through single-electron-transfer living radical polymerization (SET-LRP). The GO based polymer nanocomposites were obtained via SET-LRP in aqueous solution using poly(ethylene glycol) methyl ether methacrylate (PEGMA) as the monomer and 11-bromoundecanoic acid as the initiator, which could be effectively adsorbed on GO through hydrophobic interaction. The successful preparation of GO based polymer nanocomposites was confirmed by a series of characterization techniques such as {sup 1}H nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermogravimetric analysis, transmission electron microscopy and X-ray photoelectron spectroscopy. The resultant products exhibit high water disperisibility, excellent biocompatibility and high efficient drug loading capability, making these PEGylated GO nanocomposites promising candidates for biomedical applications.

Application of ceramic short fiber reinforced Al alloy matrix composite on piston for internal combustion engines

Directory of Open Access Journals (Sweden)

Wu Shenqing

2010-11-01

Full Text Available The preparation and properties of ceramic short fiber reinforced Al-Si alloy matrix composite and it’s application on the piston for internal combustion engines are presented. Alumina or aluminosilicate fibers reinforced Al-Si alloy matrix composite has more excellent synthetical properties at elevated temperature than the matrix alloys. A partially reinforced Al-Si alloy matrix composite piston produced by squeeze casting technique has a firm interface between reinforced and unreinforced areas, low reject rate and good technical tolerance. As a new kind of piston material, it has been used for mass production of about 400,000 pieces of automobile engines piston. China has become one of a few countries in which aluminum alloy matrix composite materials have been used in automobile industry and attained industrialization.

Wheel running decreases the positive reinforcing effects of heroin.

Science.gov (United States)

Smith, Mark A; Pitts, Elizabeth G

2012-01-01

The purpose of this study was to examine the effects of voluntary wheel running on the positive reinforcing effects of heroin in rats with an established history of drug self-administration. Rats were assigned to sedentary (no wheel) and exercise (wheel) conditions and trained to self-administer cocaine under positive reinforcement contingencies. Rats acquiring cocaine self-administration were then tested with various doses of heroin during daily test sessions. Sedentary rats self-administered more heroin than exercising rats, and this effect was greatest at low and moderate doses of heroin. These data suggest that voluntary wheel running decreases the positive reinforcing effects of heroin.

Understanding the Growing Threat of Synthetic Cannabinoids and Its Implications on University-Based Counselors

Science.gov (United States)

Golubovic, Nedeljko; Dew, Brian J.

2017-01-01

The rise in synthetic cannabinoid use has been one of the nation's most alarming drug-related trends. Considering the popularity of use among young adults, college counselors are likely to be among the 1st professionals to treat clients who use these drugs. In this article, the unique aspects of synthetic cannabinoids are reviewed, implications…

Influence of sulfates on chloride diffusion and chloride-induced reinforcement corrosion in limestone cement materials at low temperature

Czech Academy of Sciences Publication Activity Database

Sotiriadis, Konstantinos; Rakanta, E.; Mitzithra, M. E.; Batis, G.; Tsivilis, S.

2017-01-01

Roč. 29, č. 8 (2017), č. článku 04017060. ISSN 0899-1561 R&D Projects: GA MŠk(CZ) LO1219 Keywords : limestone cement * chloride diffusion * reinforcement corrosion * sulfate attack * low temperature Subject RIV: JN - Civil Engineering OBOR OECD: Composites (including laminates, reinforced plastics, cermets, combined natural and synthetic fibre fabrics Impact factor: 1.644, year: 2016 http://ascelibrary.org/doi/abs/10.1061/%28ASCE%29MT.1943-5533.0001895

The Pharmacologic and Clinical Effects of Illicit Synthetic Cannabinoids.

Science.gov (United States)

White, C Michael

2017-03-01

This article presents information on illicitly used synthetic cannabinoids. Synthetic cannabinoids are structurally heterogeneous and commonly used drugs of abuse that act as full agonists of the cannabinoid type-1 receptor but have a variety of additional pharmacologic effects. There are numerous cases of patient harm and death in the United States, Europe, and Australia with many psychological, neurological, cardiovascular, pulmonary, and renal adverse events. Although most users prefer using cannabis, there are convenience, legal, and cost reasons driving the utilization of synthetic cannabinoids. Clinicians should be aware of pharmacologic and clinical similarities and differences between synthetic cannabinoid and cannabis use, the limited ability to detect synthetic cannabinoids in the urine or serum, and guidance to treat adverse events. © 2016, The American College of Clinical Pharmacology.

Employment-based abstinence reinforcement following inpatient detoxification in HIV-positive opioid and/or cocaine-dependent patients

OpenAIRE

Dunn, Kelly; Fingerhood, Michael; Wong, Conrad J.; Svikis, Dace S.; Nuzzo, Paul; Silverman, Kenneth

2014-01-01

Employment-based reinforcement interventions have been used to promote abstinence from drugs among chronically unemployed injection drug users. The current study utilized an employment-based reinforcement intervention to promote opiate and cocaine abstinence among opioid-dependent, HIV-positive participants who had recently completed a brief inpatient detoxification. Participants (n=46) were randomly assigned to an Abstinence & Work group that was required to provide negative urine samples in...

The Effects of Cannabinoids on Executive Functions: Evidence from Cannabis and Synthetic Cannabinoids—A Systematic Review

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Koby Cohen

2018-02-01

Full Text Available Background—Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short and long-term range of adverse effects. Recently, new types of designer-drugs containing synthetic cannabinoids have been widespread. These synthetic cannabinoid drugs are associated with undesired adverse effects similar to those seen with cannabis use, yet, in more severe and long-lasting forms. Method—A literature search was conducted using electronic bibliographic databases up to 31 December 2017. Specific search strategies were employed using multiple keywords (e.g., “synthetic cannabinoids AND cognition,” “cannabis AND cognition” and “cannabinoids AND cognition”. Results—The search has yielded 160 eligible studies including 37 preclinical studies (5 attention, 25 short-term memory, 7 cognitive flexibility and 44 human studies (16 attention, 15 working memory, 13 cognitive flexibility. Both pre-clinical and clinical studies demonstrated an association between synthetic cannabinoids and executive-function impairment either after acute or repeated consumptions. These deficits differ in severity depending on several factors including the type of drug, dose of use, quantity, age of onset and duration of use. Conclusions—Understanding the nature of the impaired executive function following consumption of synthetic cannabinoids is crucial in view of the increasing use of these drugs.

Effect of waste synthetic bag pieces on the CBR value of expansive Soil

Directory of Open Access Journals (Sweden)

Ajay Kumar Agarwal

2015-03-01

Full Text Available Expansive soils such as black cotton soil which are widely distributed in India have a tendency for volume changes due to change in moisture content. Also exhibits very low bearing capacity and high compressibility. Stabilization of such soil by admixture is used commonly now days. But no mix is suitable to improve all the types of soil. But it is obvious that depending on type of soil & type of admixture the optimum mix can be designed.  In this paper a mix has been designed to improve the bearing capacity of soil by using fly ash and lime mixture, reinforced with waste synthetic bag pieces. Various tests are carried out to determine the CBR value and other soil properties with and without using any admixture and reinforcement. The maximum value of CBR was found to be23.82% for 2.5 mm penetration and 22.21% for 5 mm penetration, when waste synthetic bag pieces of size 2 cm * 2 cm were used at a proportion of 0.1%.

PERFORMANCE OF RC AND FRC WALL PANELS REINFORCED WITH MILD STEEL AND GFRP COMPOSITES IN BLAST EVENTS

Energy Technology Data Exchange (ETDEWEB)

Timothy Garfield; William D. Richins; Thomas K. Larson; Chris P. Pantelides; James E. Blakeley

2011-06-01

The structural integrity of reinforced concrete structures in blast events is important for critical facilities. This paper presents experimental data generated for calibrating detailed finite element models that predict the performance of reinforced concrete wall panels with a wide range of construction details under blast loading. The test specimens were 1.2 m square wall panels constructed using Normal Weight Concrete (NWC) or Fiber Reinforced Concrete (FRC). FRC consists of macro-synthetic fibers dispersed in NWC. Five types of panels were tested: NWC panels with steel bar reinforcement (Type A); FRC panels without additional reinforcement (Type B); FRC panels with steel bar reinforcement (Type C); NWC panels with glass fiber reinforced polymer (GFRP) bar reinforcement (Type D); and NWC panels reinforced with steel bar reinforcement and external bidirectional GFRP overlays on both faces (Type E). An additional three Type C panels were used as control specimens (CON). Each panel type was constructed with three thicknesses: 152 mm, 254 mm, and 356 mm. The panels were instrumented with strain gauges, and accelerometers; in addition, pressure sensors and high speed videos were employed during the blast events. Panel types C and E had the best performance, whereas panel type B did not perform well. Preliminary dynamic simulations show crack patterns similar to the experimental results.

The dopamine motive system: implications for drug and food addiction.

Science.gov (United States)

Volkow, Nora D; Wise, Roy A; Baler, Ruben

2017-11-16

Behaviours such as eating, copulating, defending oneself or taking addictive drugs begin with a motivation to initiate the behaviour. Both this motivational drive and the behaviours that follow are influenced by past and present experience with the reinforcing stimuli (such as drugs or energy-rich foods) that increase the likelihood and/or strength of the behavioural response (such as drug taking or overeating). At a cellular and circuit level, motivational drive is dependent on the concentration of extrasynaptic dopamine present in specific brain areas such as the striatum. Cues that predict a reinforcing stimulus also modulate extrasynaptic dopamine concentrations, energizing motivation. Repeated administration of the reinforcer (drugs, energy-rich foods) generates conditioned associations between the reinforcer and the predicting cues, which is accompanied by downregulated dopaminergic response to other incentives and downregulated capacity for top-down self-regulation, facilitating the emergence of impulsive and compulsive responses to food or drug cues. Thus, dopamine contributes to addiction and obesity through its differentiated roles in reinforcement, motivation and self-regulation, referred to here as the 'dopamine motive system', which, if compromised, can result in increased, habitual and inflexible responding. Thus, interventions to rebalance the dopamine motive system might have therapeutic potential for obesity and addiction.

Drug use as consumer behavior.

Science.gov (United States)

Foxall, Gordon Robert; Sigurdsson, Valdimar

2011-12-01

Seeking integration of drug consumption research by a theory of memory function and emphasizing drug consumption rather than addiction, Müller & Schumann (M&S) treat drug self-administration as part of a general pattern of consumption. This insight is located within a more comprehensive framework for understanding drug use as consumer behavior that explicates the reinforcement contingencies associated with modes of drug consumption.

Assessing the effectiveness of synthetic and biologic disease-modifying antirheumatic drugs in psoriatic arthritis – a systematic review

Directory of Open Access Journals (Sweden)

Kingsley GH

2015-05-01

Full Text Available Gabrielle H Kingsley, David L Scott Rheumatology Unit, Kings College London, London, UK Background: Psoriatic arthritis is an inflammatory arthritis the primary manifestations of which are locomotor and skin disease. Although a number of guidelines have been published citing strategies for reducing disease progression, the evidence base for disease-modifying agents is unclear. This forms the focus of this systematic review. Methods: The systematic review was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 checklist. We selected randomized controlled trials (RCTs that looked at the impact of interventions with disease-modifying agents, either synthetic drugs or biologics on musculoskeletal outcomes, notably American College of Rheumatology 20 percent responders. Results were analyzed using Review Manager 5.1.6 (Cochrane Collaboration, Oxford, UK. Whilst our primary focus was on published trials, we also looked at new trials presented in abstract form in 2013–2014 that were not yet published to avoid omitting important and up-to-date information on developing treatments. Results: Our in-depth analysis included 28 trials overall enrolling 5,177 patients published between the 1980s and now as well as limited analysis of some studies in abstract form as described earlier. The most frequently available locomotor outcome measure was the American College of Rheumatology 20 percent responders. The risk ratio for achieving an American College of Rheumatology 20 percent responders response was positive in favor of treatment (risk ratio 2.30; 95% confidence interval 1.78–2.96; however, there was evidence of considerable heterogeneity between trials. Overall randomized controlled trials of established synthetic disease-modifying agents were largely negative (methotrexate, ciclosporin and sulfasalazine though leflunomide showed a small positive effect. A new synthetic agent, apremilast, did show a

Investigation of mechanical properties of kenaf, hemp and E-glass fiber reinforced composites

Science.gov (United States)

Dinesh, Veena; Shivanand, H. K.; Vidyasagar, H. N.; Chari, V. Srinivasa

2018-04-01

Recently the use of fiber reinforced polymer composite in the automobile, aerospace overwhelming designing sectors has increased tremendously due to the ecological issues and health hazard possessed by the synthetic fiber during disposal and manufacturing. The paper presents tensile strength, flexural strength and hardness of kenaf-E glass-kenaf, hemp-E glass-hemp and kenaf-E glass-hemp fiber reinforced polyester composites. The composite plates are shaped according to the standard geometry and uni-axially loaded in order to investigate the tensile responses of each combination. In addition to the physical and mechanical properties, processing methods and application of kenaf and hemp fiber composites is also discussed.

Treatment Approaches for Drug Addiction

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Health Consequences of Drug Misuse

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Understanding Drug Use and Addiction

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

77 FR 58915 - Presidential Determination on Major Illicit Drug Transit or Major Illicit Drug Producing...

Science.gov (United States)

2012-09-24

... initiatives specifically intended to fight the trafficking of marijuana and synthetic drugs. As detailed in... countries. For example, Canada has taken effective steps to stem the flow of synthetic MDMA (ecstasy) across...

Behavior of reinforced concrete beams reinforced with GFRP bars

Directory of Open Access Journals (Sweden)

D. H. Tavares

Full Text Available The use of fiber reinforced polymer (FRP bars is one of the alternatives presented in recent studies to prevent the drawbacks related to the steel reinforcement in specific reinforced concrete members. In this work, six reinforced concrete beams were submitted to four point bending tests. One beam was reinforced with CA-50 steel bars and five with glass fiber reinforced polymer (GFRP bars. The tests were carried out in the Department of Structural Engineering in São Carlos Engineering School, São Paulo University. The objective of the test program was to compare strength, reinforcement deformation, displacement, and some anchorage aspects between the GFRP-reinforced concrete beams and the steel-reinforced concrete beam. The results show that, even though four GFRP-reinforced concrete beams were designed with the same internal tension force as that with steel reinforcement, their capacity was lower than that of the steel-reinforced beam. The results also show that similar flexural capacity can be achieved for the steel- and for the GFRP-reinforced concrete beams by controlling the stiffness (reinforcement modulus of elasticity multiplied by the bar cross-sectional area - EA and the tension force of the GFRP bars.

Acute Intoxications Involving Synthetic Psychoactive Substances

Directory of Open Access Journals (Sweden)

Sergey A. Vasil'ev

2018-01-01

Full Text Available The purpose of this study was to evaluate the effectiveness of a succinic acid derivate, a substrate metabolic agent cytoflavin in patients with acute poisoning with synthetic psychoactive drugs.Materials and methods. A retrospective evaluation of effectiveness of a combined intensive care treatment protocol for 622 patients with acute narcotic poisoning (methadone and synthetic cannabinoids was carried out. All patients were divided into two groups. The main group (112 patients, median age 38.2±12.0 years included patients who, in addition to the basic treatment, received cytoflavin by intravenous drop infusion, 20–40 ml diluted in 400–500 ml of 10% glucose, for 5 days. Patients of the reference group (510 subjects, median age 37.6±14.1 years received treatment according to the «classical scheme». In addition to conventional examination, all patients underwent duplex scanning of cerebral vessels, examination of changes in the cerebral blood circulation and electroencephalogram findings. The severity of somatic disorders was assessed using criteria of the Glasgow coma scale. The severity of the asthenic syndrome was assessed according to the MFI-20 scale.Results. Compared to patients who received a standard therapy, patients of the main group had a significantly more rapid recovery from coma (by 1.5-fold: 23.5±3.1 days, versus 15.1±3.0 days, respectively, P0.05; the duration of psychotic disorders was shorter (by 1.8-fold: 15.5±4.2 hours vs 8.3±2.5 hours., respectively, P0.05, and the intensity of asthenic syndrome (by 2.8-fold: 64.1±3.3 rel. units vs 23.0±4,9 rel. units, respectively, P0.05 was also lower.Conclusion. Inclusion of cytoflavin in a protocol of a complex treatment of patients with synthetic drugs poisoning increased the effectiveness of the therapy. Data demonstrate that inclusion of the drug can be recommended for treatment of acute synthetic narcotic poisoning. 

The Wide and Unpredictable Scope of Synthetic Cannabinoids Toxicity

Directory of Open Access Journals (Sweden)

Jose Orsini

2015-01-01

Full Text Available Drug use and abuse continue to be a large public health concern worldwide. Over the past decade, novel or atypical drugs have emerged and become increasingly popular. In the recent past, compounds similar to tetrahydrocannabinoid (THC, the active ingredient of marijuana, have been synthetically produced and offered commercially as legal substances. Since the initial communications of their abuse in 2008, few case reports have been published illustrating the misuse of these substances with signs and symptoms of intoxication. Even though synthetic cannabinoids have been restricted, they are still readily available across USA and their use has been dramatically increasing, with a concomitant increment in reports to poison control centers and emergency department (ED visits. We describe a case of acute hypoxemic/hypercapnic respiratory failure as a consequence of acute congestive heart failure (CHF developed from myocardial stunning resulting from a non-ST-segment elevation myocardial infarction (MI following the consumption of synthetic cannabinoids.

Anti-Cancer Drug Discovery Using Synthetic Lethal Chemogenetic (SLC) Analysis

National Research Council Canada - National Science Library

Bellows, David S

2004-01-01

I am developing a novel cell-based small-molecule screening approach that can identify inhibitors of any non-essential protein function through a surrogate synthetic lethal phenotype in the baker's...

Anti-Cancer Drug Discovery Using Synthetic Lethal Chemogenetic (SLC) Analysis

National Research Council Canada - National Science Library

Bellows, David S

2006-01-01

I am developing a novel cell-based small-molecule screening approach that can identify inhibitors of any non-essential protein function through a surrogate synthetic lethal phenotype in the baker's...

Drugs + HIV, Learn the Link

Medline Plus

Full Text Available ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Synergistic Synthetic Biology: Units in Concert

Science.gov (United States)

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications. PMID:25022769

Synergistic Synthetic Biology: Units in Concert

International Nuclear Information System (INIS)

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

Mallow Fiber-Reinforced Epoxy Composites in Multilayered Armor for Personal Ballistic Protection

Science.gov (United States)

Nascimento, Lucio Fábio Cassiano; Louro, Luis Henrique Leme; Monteiro, Sergio Neves; Lima, Édio Pereira; da Luz, Fernanda Santos

2017-10-01

Lighter and less expensive polymer composites reinforced with natural fibers have been investigated as possible components of a multilayered armor system (MAS) for personal protection against high-velocity ammunition. Their ballistic performance was consistently found comparable with that of conventional Kevlar® synthetic aramid fiber. Among the numerous existing natural fibers with the potential for reinforcing polymer composites to replace Kevlar® in MAS, mallow fiber has not been fully investigated. Thus, the objective of this work is to evaluate the ballistic performance of epoxy composites reinforced with 30 vol.% of aligned mallow fibers as a second MAS layer backing a front ceramic plate. The results using high-velocity 7.62 ammunition show a similar indentation to a Kevlar® layer with the same thickness. An impedance matching calculation supports the similar ballistic performance of mallow fiber composite and Kevlar®. Reduced MAS costs associated with the mallow fiber composite are practical advantages over Kevlar®.

Synthetic neurosteroids on brain protection

Directory of Open Access Journals (Sweden)

Mariana Rey

2015-01-01

Full Text Available Neurosteroids, like allopregnanolone and pregnanolone, are endogenous regulators of neuronal excitability. Inside the brain, they are highly selective and potent modulators of GABA A receptor activity. Their anticonvulsant, anesthetics and anxiolytic properties are useful for the treatments of several neurological and psychiatric disorders via reducing the risks of side effects obtained with the commercial drugs. The principal disadvantages of endogenous neurosteroids administration are their rapid metabolism and their low oral bioavailability. Synthetic steroids analogues with major stability or endogenous neurosteroids stimulation synthesis might constitute promising novel strategies for the treatment of several disorders. Numerous studies indicate that the 3α-hydroxyl configuration is the key for binding and activity, but modifications in the steroid nucleus may emphasize different pharmacophores. So far, several synthetic steroids have been developed with successful neurosteroid-like effects. In this work, we summarize the properties of various synthetic steroids probed in trials throughout the analysis of several neurosteroids-like actions.

Variability in prescription opioid intake and reinforcement amongst 129 substrains.

Science.gov (United States)

Jimenez, S M; Healy, A F; Coelho, M A; Brown, C N; Kippin, T E; Szumlinski, K K

2017-09-01

Opioid abuse in the United States has reached epidemic proportions, with treatment admissions and deaths associated with prescription opioid abuse quadrupling over the past 10 years. Although genetics are theorized to contribute substantially to inter-individual variability in the development, severity and treatment outcomes of opioid abuse/addiction, little direct preclinical study has focused on the behavioral genetics of prescription opioid reinforcement and drug-taking. Herein, we employed different 129 substrains of mice currently available from The Jackson Laboratory (129S1/SvlmJ, 129X1/SvJ, 129S4/SvJaeJ and 129P3/J) as a model system of genetic variation and assayed mice for oral opioid intake and reinforcement, as well as behavioral and somatic signs of dependence. All substrains exhibited a dose-dependent increase in oral oxycodone and heroin preference and intake under limited-access procedures and all, but 129S1/SvlmJ mice, exhibited oxycodone reinforcement. Relative to the other substrains, 129P3/J mice exhibited higher heroin and oxycodone intake. While 129X1/SvJ exhibited the highest anxiety-like behavior during natural opioid withdrawal, somatic and behavior signs of precipitated withdrawal were most robust in 129P3/J mice. These results demonstrate the feasibility and relative sensitivity of our oral opioid self-administration procedures for detecting substrain differences in drug reinforcement/intake among 129 mice, of relevance to the identification of genetic variants contributing to high vs. low oxycodone reinforcement and intake. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Synthetic biology era: Improving antibiotic's world.

Science.gov (United States)

Guzmán-Trampe, Silvia; Ceapa, Corina D; Manzo-Ruiz, Monserrat; Sánchez, Sergio

2017-06-15

The emergence of antibiotic-resistant pathogen microorganisms is problematic in the context of the current spectrum of available medication. The poor specificity and the high toxicity of some available molecules have made imperative the search for new strategies to improve the specificity and to pursue the discovery of novel compounds with increased bioactivity. Using living cells as platforms, synthetic biology has counteracted this problem by offering novel pathways to create synthetic systems with improved and desired functions. Among many other biotechnological approaches, the advances in synthetic biology have made it possible to design and construct novel biological systems in order to look for new drugs with increased bioactivity. Advancements have also been made in the redesigning of RNA and DNA molecules in order to engineer antibiotic clusters for antibiotic overexpression. As for the production of these antibacterial compounds, yeasts and filamentous fungi as well as gene therapy are utilized to enhance protein solubility. Specific delivery is achieved by creating chimeras using plant genes into bacterial hosts. Some of these synthetic systems are currently in clinical trials, proving the proficiency of synthetic biology in terms of both pharmacological activities as well as an increase in the biosafety of treatments. It is possible that we may just be seeing the tip of the iceberg, and synthetic biology applications will overpass expectations beyond our present knowledge. Copyright © 2017. Published by Elsevier Inc.

Ischemic stroke after use of the synthetic marijuana "spice".

Science.gov (United States)

Freeman, Melissa J; Rose, David Z; Myers, Martin A; Gooch, Clifton L; Bozeman, Andrea C; Burgin, W Scott

2013-12-10

To report and associate acute cerebral infarctions in 2 young, previously healthy siblings with use of the street drug known as "spice" (a synthetic marijuana product, also known as "K2"), which they independently smoked before experiencing acute embolic-appearing ischemic strokes. We present history, physical examination, laboratory data, cerebrovascular imaging, echocardiogram, ECG, and hospital course of these patients. We found that in both siblings spice was obtained from the same source. The drug was found to contain the schedule I synthetic cannabinoid JWH-018. Full stroke workup was unrevealing of a stroke etiology; urine drug screen was positive for marijuana. We found that our 2 patients who smoked the street drug spice had a temporal association with symptoms of acute cerebral infarction. This association may be confounded by contaminants in the product consumed (i.e., marijuana or an unidentified toxin) or by an unknown genetic mechanism. The imaging of both patients suggests an embolic etiology, which is consistent with reports of serious adverse cardiac events with spice use, including tachyarrhythmias and myocardial infarctions.

Synthetic biology approaches in drug discovery and pharmaceutical biotechnology.

Science.gov (United States)

Neumann, Heinz; Neumann-Staubitz, Petra

2010-06-01

Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology.

CYP3A4 Mediates Oxidative Metabolism of the Synthetic Cannabinoid AKB-48

OpenAIRE

Holm, Niels Bjerre; Nielsen, Line Marie; Linnet, Kristian

2015-01-01

Synthetic cannabinoid designer drugs have emerged as drugs of abuse during the last decade, and acute intoxication cases are documented in the scientific literature. Synthetic cannabinoids are extensively metabolized, but our knowledge of the involved enzymes is limited. Here, we investigated the metabolism of N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48), a compound identified in herbal blends from 2012 and onwards. We screened for metabolite formation using a panel of nine rec...

International Drug Control Policy

Science.gov (United States)

2009-08-24

Common illegal drugs include cannabis, cocaine, opiates, and synthetic drugs. International trade in these drugs represents a lucrative and what...into effect, decriminalizing “personal use” amounts of marijuana , heroin, cocaine, methamphetamine, and other internationally sanctioned drugs.15 While...President Calls for Legalizing Marijuana ,”CNN.com, May 13, 2009. 15 “Mexico Legalizes Drug Possession,” Associated Press, August 21, 2009. 16 In support

21 CFR 864.2220 - Synthetic cell and tissue culture media and components.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Synthetic cell and tissue culture media and components. 864.2220 Section 864.2220 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Cell And Tissue Culture...

DrugFacts: Electronic Cigarettes (e-Cigarettes)

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Probing the Behavioral and Neurophysiological Effects of Acute Smoking Abstinence on Drug and Nondrug Reinforcement During a Cognitive Task.

Science.gov (United States)

Schlienz, Nicolas J; Hawk, Larry W

2017-06-01

Smoking abstinence is theorized to increase smoking reinforcement and decrease nondrug reinforcement. A separate literature demonstrates the detrimental effects of abstinence on cognition. The present study integrates these two areas by examining the separate and combined effects of reinforcement and smoking abstinence on behavior and a neurophysiological index of response monitoring (ie, error-related negativity [ERN]) during a cognitive task. After a screening visit, adult smokers attended two laboratory visits, once while smoking and once while abstinent. Participants completed a flanker task under cigarette-, money-, and no-reinforcement conditions. The initial 15 participants had an easier reaction time (RT) requirement; to ensure sufficient error rates for ERN computation, a harder RT deadline was employed for the remaining 21 participants. Smoking abstinence reduced speeded accuracy and ERN amplitude only among participants tested with the harder RT deadline. Cigarette and money reinforcement each increased speeded accuracy and ERN amplitude compared to no reinforcement. The effect of cigarette reinforcement tended to be greater during abstinence for speeded accuracy but not the ERN. The effect of money reinforcement was unaffected by abstinence. The impact of smoking abstinence on reinforcement may depend on task demands. However, the effects of cigarette and money reinforcement generalize well from operant paradigms to cognitive tasks, fostering integration between the two literatures. Results provided modest evidence of abstinence-induced increases in smoking reinforcement; the absence of abstinence-induced reductions in nondrug reinforcement is consistent with recent work in suggesting that such effects are limited to a subset of sensory reinforcers. This study draws attention to the need for greater integration of reinforcement and cognition to better understand the mechanisms that contribute to smoking relapse. Results emphasize thoughtful

Fracture Behavior and Properties of Functionally Graded Fiber-Reinforced Concrete

International Nuclear Information System (INIS)

Roesler, Jeffery; Bordelon, Amanda; Gaedicke, Cristian; Park, Kyoungsoo; Paulino, Glaucio

2008-01-01

In concrete pavements, a single concrete mixture design is selected to resist mechanical loading without attempting to adversely affect the concrete pavement shrinkage, ride quality, or noise attenuation. An alternative approach is to design distinct layers within the concrete pavement surface which have specific functions thus achieving higher performance at a lower cost. The objective of this research was to address the structural benefits of functionally graded concrete materials (FGCM) for rigid pavements by testing and modeling the fracture behavior of different combinations of layered plain and synthetic fiber-reinforced concrete materials. Fracture parameters and the post-peak softening behavior were obtained for each FGCM beam configuration by the three point bending beam test. The peak loads and initial fracture energy between the plain, fiber-reinforced, and FGCM signified similar crack initiation. The total fracture energy indicated improvements in fracture behavior of FGCM relative to full-depth plain concrete. The fracture behavior of FGCM depended on the position of the fiber-reinforced layer relative to the starter notch. The fracture parameters of both fiber-reinforced and plain concrete were embedded into a finite element-based cohesive zone model. The model successfully captured the experimental behavior of the FGCMs and predicted the fracture behavior of proposed FGCM configurations and structures. This integrated approach (testing and modeling) demonstrates the viability of FGCM for designing layered concrete pavements system

Braided reinforced composite rods for the internal reinforcement of concrete

Science.gov (United States)

Gonilho Pereira, C.; Fangueiro, R.; Jalali, S.; Araujo, M.; Marques, P.

2008-05-01

This paper reports on the development of braided reinforced composite rods as a substitute for the steel reinforcement in concrete. The research work aims at understanding the mechanical behaviour of core-reinforced braided fabrics and braided reinforced composite rods, namely concerning the influence of the braiding angle, the type of core reinforcement fibre, and preloading and postloading conditions. The core-reinforced braided fabrics were made from polyester fibres for producing braided structures, and E-glass, carbon, HT polyethylene, and sisal fibres were used for the core reinforcement. The braided reinforced composite rods were obtained by impregnating the core-reinforced braided fabric with a vinyl ester resin. The preloading of the core-reinforced braided fabrics and the postloading of the braided reinforced composite rods were performed in three and two stages, respectively. The results of tensile tests carried out on different samples of core-reinforced braided fabrics are presented and discussed. The tensile and bending properties of the braided reinforced composite rods have been evaluated, and the results obtained are presented, discussed, and compared with those of conventional materials, such as steel.

Drugs from the Oceans: Marine Natural Products as Leads for Drug Discovery.

Science.gov (United States)

Altmann, Karl-Heinz

2017-10-25

The marine environment harbors a vast number of species that are the source of a wide array of structurally diverse bioactive secondary metabolites. At this point in time, roughly 27'000 marine natural products are known, of which eight are (were) at the origin of seven marketed drugs, mostly for the treatment of cancer. The majority of these drugs and also of drug candidates currently undergoing clinical evaluation (excluding antibody-drug conjugates) are unmodified natural products, but synthetic chemistry has played a central role in the discovery and/or development of all but one of the approved marine-derived drugs. More than 1000 new marine natural products have been isolated per year over the last decade, but the pool of new and unique structures is far from exhausted. To fully leverage the potential offered by the structural diversity of marine-produced secondary metabolites for drug discovery will require their broad assessment for different bioactivities and the productive interplay between new fermentation technologies, synthetic organic chemistry, and medicinal chemistry, in order to secure compound supply and enable lead optimization.

Electrochemical and spectroscopic characterisation of amphetamine-like drugs: Application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors

International Nuclear Information System (INIS)

Milhazes, Nuno; Martins, Pedro; Uriarte, Eugenio; Garrido, Jorge; Calheiros, Rita; Marques, M. Paula M.; Borges, Fernanda

2007-01-01

A complete physicochemical characterisation of MDMA and its synthetic precursors MDA, 3,4-methylenedioxybenzaldehyde (piperonal) and 3,4-methylenedioxy-β-methyl-β-nitrostyrene was carried out through voltammetric assays and Raman spectroscopy combined with theoretical (DFT) calculations. The former provided important analytical redox data, concluding that the oxidative mechanism of the N-demethylation of MDMA involves the removal of an electron from the amino-nitrogen atom, leading to the formation of a primary amine and an aldehyde. The vibrational spectroscopic experiments enable to afford a rapid and reliable detection of this type of compounds, since they yield characteristic spectral patterns that lead to an unequivocal identification. Moreover, the rational synthesis of the drug of abuse 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') from one of its most relevant precursors 3,4-methylene-dioxyamphetamine (MDA), is reported. In addition, several approaches for the N-methylation of MDA, a limiting synthetic step, were attempted and the overall yields compared

Electrochemical and spectroscopic characterisation of amphetamine-like drugs: Application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors

Energy Technology Data Exchange (ETDEWEB)

Milhazes, Nuno [CEQOFFUP, Faculdade de Farmacia, Universidade do Porto (Portugal); Departamento de Quimica Organica, Faculdade de Farmacia, Universidade do Porto (Portugal); Instituto Superior de Ciencias da Saude-Norte, Gandra, Paredes (Portugal); Martins, Pedro [Departamento de Quimica Organica, Facultade de Farmacia, Universidad de Santiago de Compostela (Spain); Uriarte, Eugenio [Departamento de Quimica Organica, Facultade de Farmacia, Universidad de Santiago de Compostela (Spain); Garrido, Jorge [Unidade I and D ' Quimica-Fisica Molecular' (Portugal); Departamento de Engenharia Quimica, ISEP, Instituto Politecnico do Porto (Portugal); Calheiros, Rita [Unidade I and D ' Quimica-Fisica Molecular' (Portugal); Marques, M. Paula M. [Unidade I and D ' Quimica-Fisica Molecular' (Portugal); Departamento de Bioquimica, Faculdade de Ciencias e Tecnologia, Universidade de Coimbra (Portugal); Borges, Fernanda [Departamento de Quimica Organica, Faculdade de Farmacia, Universidade do Porto (Portugal) and Unidade I and D ' Quimica-Fisica Molecular' (Portugal)]. E-mail: fborges@ff.up.pt

2007-07-23

A complete physicochemical characterisation of MDMA and its synthetic precursors MDA, 3,4-methylenedioxybenzaldehyde (piperonal) and 3,4-methylenedioxy-{beta}-methyl-{beta}-nitrostyrene was carried out through voltammetric assays and Raman spectroscopy combined with theoretical (DFT) calculations. The former provided important analytical redox data, concluding that the oxidative mechanism of the N-demethylation of MDMA involves the removal of an electron from the amino-nitrogen atom, leading to the formation of a primary amine and an aldehyde. The vibrational spectroscopic experiments enable to afford a rapid and reliable detection of this type of compounds, since they yield characteristic spectral patterns that lead to an unequivocal identification. Moreover, the rational synthesis of the drug of abuse 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') from one of its most relevant precursors 3,4-methylene-dioxyamphetamine (MDA), is reported. In addition, several approaches for the N-methylation of MDA, a limiting synthetic step, were attempted and the overall yields compared.

Electrochemical and spectroscopic characterisation of amphetamine-like drugs: application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors.

Science.gov (United States)

Milhazes, Nuno; Martins, Pedro; Uriarte, Eugenio; Garrido, Jorge; Calheiros, Rita; Marques, M Paula M; Borges, Fernanda

2007-07-23

A complete physicochemical characterisation of MDMA and its synthetic precursors MDA, 3,4-methylenedioxybenzaldehyde (piperonal) and 3,4-methylenedioxy-beta-methyl-beta-nitrostyrene was carried out through voltammetric assays and Raman spectroscopy combined with theoretical (DFT) calculations. The former provided important analytical redox data, concluding that the oxidative mechanism of the N-demethylation of MDMA involves the removal of an electron from the amino-nitrogen atom, leading to the formation of a primary amine and an aldehyde. The vibrational spectroscopic experiments enable to afford a rapid and reliable detection of this type of compounds, since they yield characteristic spectral patterns that lead to an unequivocal identification. Moreover, the rational synthesis of the drug of abuse 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") from one of its most relevant precursors 3,4-methylene-dioxyamphetamine (MDA), is reported. In addition, several approaches for the N-methylation of MDA, a limiting synthetic step, were attempted and the overall yields compared.

New drugs of abuse.

Science.gov (United States)

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.

Flexural reinforced concrete member with FRP reinforcement

OpenAIRE

Putzolu, Mariana

2017-01-01

One of the most problematic point in construction is the durability of the concrete especially related to corrosion of the steel reinforcement. Due to this problem the construction sector, introduced the use of Fiber Reinforced Polymer, the main fibers used in construction are Glass, Carbon and Aramid. In this study, the author aim to analyse the flexural behaviour of concrete beams reinforced with FRP. This aim is achieved by the analysis of specimens reinforced with GFRP bars, with theoreti...

Efficacy of conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids and tofacitinib: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis

NARCIS (Netherlands)

Gaujoux-Viala, Cécile; Nam, Jackie; Ramiro, Sofia; Landewé, Robert; Buch, Maya H.; Smolen, Josef S.; Gossec, Laure

2014-01-01

To update a previous systematic review assessing the efficacy of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in rheumatoid arthritis (RA). Two systematic reviews of the literature using PubMed, Embase and the Cochrane library were performed from 2009 until January 2013 to

Radiation techniques in the formulation of synthetic biomaterials

International Nuclear Information System (INIS)

Kaetsu, Isao

1992-01-01

This chapter reviews the uses of various radiation techniques, such as radiation polymerization, grafting, and crosslinking, for the formulation of synthetic biomaterials. The biomaterials are divided into four categories: Biocompatible polymers, immobilized proteins, immobilized cells, and drug delivery systems. The recent achievements in each category are described, and the contributions of novel radiation techniques to this field are discussed. Work on drug delivery systemsis also reviewed, and the status of the practical applications of drug delivery systems for therapy is summarized. Future trends in the field of radiation-synthesized biomaterials are indicated. (orig.)

Local hippocampal methamphetamine-induced reinforcement

Directory of Open Access Journals (Sweden)

Ulises M Ricoy

2009-11-01

Full Text Available Drug abuse and addiction are major problems in the United States. In particular methamphetamine (METH use has increased dramatically. A greater understanding of how METH acts on the brain to induce addiction may lead to better therapeutic targets for this problem. The hippocampus is recognized as an important structure in learning and memory, but is not typically associated with drug reinforcement or reward processes. Here, the focus is on the hippocampus which has been largely ignored in the addiction literature as compared to the nucleus accumbens (NAc, ventral tegmental area (VTA, and prefrontal cortex (PFC. The results show that METH administered unilaterally via a microdialysis probe to rats’ right dorsal hippocampus will induce drug-seeking (place preference and drug-taking (lever-pressing behavior. Furthermore, both of these responses are dependent on local dopamine (DA receptor activation, as they are impaired by a selective D1/D5 receptor antagonist. The results suggest that the hippocampus is part of the brain’s reward circuitry that underlies addiction.

Employment-based reinforcement of adherence to oral naltrexone treatment in unemployed injection drug users.

Science.gov (United States)

Dunn, Kelly E; Defulio, Anthony; Everly, Jeffrey J; Donlin, Wendy D; Aklin, Will M; Nuzzo, Paul A; Leoutsakos, Jeannie-Marie S; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E; Silverman, Kenneth

2013-02-01

Oral naltrexone has high potential for use as a relapse prevention pharmacotherapy for opiate dependence yet suffers from notoriously poor adherence. This study evaluated whether entry to a therapeutic workplace could reinforce adherence with oral naltrexone. Opiate-dependent and cocaine-using injection drug users were detoxified, inducted onto oral naltrexone, and randomly assigned to a contingency (n = 35) or prescription (n = 32) group for a 26-week period. Contingency participants were required to ingest naltrexone under staff observation to gain access to the therapeutic workplace. Prescription participants received a take-home supply of naltrexone and could access the workplace independent of naltrexone ingestion. Primary outcome measures were percent of urine samples positive for naltrexone at 30-day assessments and negative for opiates and cocaine at 30-day assessments. Contingency participants provided significantly more urine samples that were positive for naltrexone compared with prescription participants (72% vs. 21%, p workplace significantly promoted adherence to oral naltrexone, and that the majority of opiate use occurred in conjunction with cocaine use, suggesting that untreated cocaine use may limit the effectiveness of oral naltrexone in promoting opiate abstinence. (c) 2013 APA, all rights reserved.

Emergency Physicians' Knowledge of Cannabinoid Designer Drugs

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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.

A Synthetic Serine Protease Inhibitor, Nafamostat Mesilate, Is a Drug Potentially Applicable to the Treatment of Ebola Virus Disease.

Science.gov (United States)

Nishimura, Hidekazu; Yamaya, Mutsuo

2015-09-01

Ebola virus disease (EVD) has been a great concern worldwide because of its high mortality. EVD usually manifests with fever, diarrhea and vomiting, as well as disseminated intravascular coagulation (DIC). To date, there is neither a licensed Ebola vaccine nor a promising therapeutic agent, although clinical trials are ongoing. For replication inside the cell, Ebola virus (EBOV) must undergo the proteolytic processing of its surface glycoprotein in the endosome by proteases including cathepsin B (CatB), followed by the fusion of the viral membrane and host endosome. Thus, the proteases have been considered as potential targets for drugs against EVD. However, no protease inhibitor has been presented as effective clinical drug against it. A synthetic serine protease inhibitor, nafamostat mesilate (NM), reduced the release of CatB from the rat pancreas. Furthermore, it has anticoagulant activities, such as inhibition of the factor VIIa complex, and has been used for treating DIC in Japan. Thus, NM could be considered as a drug candidate for the treatment of DIC induced by EBOV infection, as well as for the possible CatB-related antiviral action. Moreover, the drug has a history of large-scale production and clinical use, and the issues of safety and logistics might have been cleared. We advocate in vitro and in vivo experiments using active EBOV to examine the activities of NM against the infection and the DIC induced by the infection. In addition, we suggest trials for comparison among anti-DIC drugs including the NM in EVD patients, in parallel with the experiments.

Stereocomplex-Reinforced PEGylated Polylactide Micelle for Optimized Drug Delivery

Directory of Open Access Journals (Sweden)

Chunsheng Feng

2016-04-01

Full Text Available The instability of PEGylated polylactide micelles is a challenge for drug delivery. Stereocomplex interaction between racemic polylactide chains with different configurations provides an effective strategy to enhance the stability of micelles as the nanocarriers of drugs. In this work, a stereocomplex micelle (SCM self-assembled from the amphiphilic triblock copolymers comprising poly(ethylene glycol (PEG, and dextrorotatory and levorotatory polylactides (PDLA and PLLA was applied for efficient drug delivery. The spherical SCM showed the smallest scale and the lowest critical micelle concentration (CMC than the micelles with single components attributed to the stereocomplex interaction between PDLA and PLLA. 10-Hydroxycamptothecin (HCPT as a model antitumor drug was loaded into micelles. Compared with the loading micelles from individual PDLA and PLLA, the HCPT-loaded SCM exhibited the highest drug loading efficiency (DLE and the slowest drug release in phosphate-buffered saline (PBS at pH 7.4, indicating its enhanced stability in circulation. More fascinatingly, the laden SCM was demonstrated to have the highest cellular uptake of HCPT and suppress malignant cells most effectively in comparison to the HCPT-loaded micelles from single copolymer. In summary, the stereocomplex-enhanced PLA–PEG–PLA micelle may be promising for optimized drug delivery in the clinic.

Ischemic stroke after use of the synthetic marijuana “spice”

Science.gov (United States)

Freeman, Melissa J.; Rose, David Z.; Myers, Martin A.; Gooch, Clifton L.; Bozeman, Andrea C.

2013-01-01

Objectives: To report and associate acute cerebral infarctions in 2 young, previously healthy siblings with use of the street drug known as “spice” (a synthetic marijuana product, also known as “K2”), which they independently smoked before experiencing acute embolic-appearing ischemic strokes. Methods: We present history, physical examination, laboratory data, cerebrovascular imaging, echocardiogram, ECG, and hospital course of these patients. Results: We found that in both siblings spice was obtained from the same source. The drug was found to contain the schedule I synthetic cannabinoid JWH-018. Full stroke workup was unrevealing of a stroke etiology; urine drug screen was positive for marijuana. Conclusions: We found that our 2 patients who smoked the street drug spice had a temporal association with symptoms of acute cerebral infarction. This association may be confounded by contaminants in the product consumed (i.e., marijuana or an unidentified toxin) or by an unknown genetic mechanism. The imaging of both patients suggests an embolic etiology, which is consistent with reports of serious adverse cardiac events with spice use, including tachyarrhythmias and myocardial infarctions. PMID:24212384

Enhancement of Curcumin Bioavailability Using Nanocellulose Reinforced Chitosan Hydrogel

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Thennakoon M. Sampath Udeni Gunathilake

2017-02-01

Full Text Available A unique biodegradable, superporous, swellable and pH sensitive nanocellulose reinforced chitosan hydrogel with dynamic mechanical properties was prepared for oral administration of curcumin. Curcumin, a less water-soluble drug was used due to the fact that the fast swellable, superporous hydrogel could release a water-insoluble drug to a great extent. CO2 gas foaming was used to fabricate hydrogel as it eradicates using organic solvents. Field emission scanning electron microscope images revealed that the pore size significantly increased with the formation of widely interconnected porous structure in gas foamed hydrogels. The maximum compression of pure chitosan hydrogel was 25.9 ± 1 kPa and it increased to 38.4 ± 1 kPa with the introduction of 0.5% cellulose nanocrystals. In vitro degradation of hydrogels was found dependent on the swelling ratio and the amount of CNC of the hydrogel. All the hydrogels showed maximum swelling ratios greater than 300%. The 0.5% CNC-chitosan hydrogel showed the highest swelling ratio of 438% ± 11%. FTIR spectrum indicated that there is no interaction between drug and ingredients present in hydrogels. The drug release occurred in non-Fickian (anomalous manner in simulated gastric medium. The drug release profiles of hydrogels are consistent with the data obtained from the swelling studies. After gas foaming of the hydrogel, the drug loading efficiency increased from 41% ± 2.4% to 50% ± 2.0% and release increased from 0.74 to 1.06 mg/L. The drug release data showed good fitting to Ritger-Peppas model. Moreover, the results revealed that the drug maintained its chemical activity after in vitro release. According to the results of this study, CNC reinforced chitosan hydrogel can be suggested to improve the bioavailability of curcumin for the absorption from stomach and upper intestinal tract.

Investigation of the in vitro toxicological properties of the synthetic cannabimimetic drug CP-47,497-C8

Energy Technology Data Exchange (ETDEWEB)

Koller, Verena J., E-mail: verena.koller@meduniwien.ac.at [Institute of Cancer Research, Department of Internal Medicine 1, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna (Austria); Auwärter, Volker [Institute of Forensic Medicine, University Medical Center Freiburg, Albertstraße 9, 79104 Freiburg (Germany); Grummt, Tamara [German Federal Environmental Agency, Heinrich-Heine-Str., 12, 08645 Bad Elster (Germany); Moosmann, Bjoern [Institute of Forensic Medicine, University Medical Center Freiburg, Albertstraße 9, 79104 Freiburg (Germany); Mišík, Miroslav [Institute of Cancer Research, Department of Internal Medicine 1, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna (Austria); Knasmüller, Siegfried [Institute of Cancer Research, Department of Internal Medicine 1, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna (Austria)

2014-06-01

Cannabicyclohexanol (CP-47,497-C8) is a representative of a group of cannabimimetic cyclohexylphenols which is added to herbal mixtures as a cannabis substitute since 2008. Although in the beginning CP-47,497-C8 was the main ingredient of “Spice” and similar products, it was partly replaced by aminoalkylindole-type cannabinoid receptor agonists like JWH-018, JWH-073 or JWH-250, but never completely disappeared from the market. Since information on its toxicological properties is scarce, we investigated the effects of the drug in human derived cell lines. The cytotoxic effects were studied in a panel of assays (SRB, XTT, LDHe and NR tests) in a buccal derived (TR146) and a liver derived (HepG2) cell line. The strongest effects were seen in the two former assays at levels ≥ 7.5 μM indicating that the compound interferes with protein synthesis and causes membrane damage. In additional comet assays, DNA damage was detected at levels ≥ 10 μM. Experiments with lesion specific enzymes showed that these effects are not due to oxidative damage of DNA bases. The negative findings obtained in Salmonella/microsome assays and the positive results of micronucleus tests with the cell lines indicate that the compound does not cause gene mutations but acts on the chromosomal level. In contrast to other synthetic cannabinoids, no indication for estrogenic/antiestrogenic properties was seen in a luciferase assay with bone marrow derived U2-OS cells. In conclusion, our findings show that the drug has only weak cytotoxic properties. However, the induction of chromosomal damage indicates that it may cause adverse effects in users due to its impact on the stability of the genetic material. - Highlights: • We tested the toxic properties of a synthetic cannabinoid. • Acute cytotoxic effects were detected with doses ≥ 7 μM. • No hormonal effects were found. • DNA damage was detected at levels ≥ 10 μM in comet assay and micronucleus tests. • Effects in directly

Investigation of the in vitro toxicological properties of the synthetic cannabimimetic drug CP-47,497-C8

International Nuclear Information System (INIS)

Koller, Verena J.; Auwärter, Volker; Grummt, Tamara; Moosmann, Bjoern; Mišík, Miroslav; Knasmüller, Siegfried

2014-01-01

Cannabicyclohexanol (CP-47,497-C8) is a representative of a group of cannabimimetic cyclohexylphenols which is added to herbal mixtures as a cannabis substitute since 2008. Although in the beginning CP-47,497-C8 was the main ingredient of “Spice” and similar products, it was partly replaced by aminoalkylindole-type cannabinoid receptor agonists like JWH-018, JWH-073 or JWH-250, but never completely disappeared from the market. Since information on its toxicological properties is scarce, we investigated the effects of the drug in human derived cell lines. The cytotoxic effects were studied in a panel of assays (SRB, XTT, LDHe and NR tests) in a buccal derived (TR146) and a liver derived (HepG2) cell line. The strongest effects were seen in the two former assays at levels ≥ 7.5 μM indicating that the compound interferes with protein synthesis and causes membrane damage. In additional comet assays, DNA damage was detected at levels ≥ 10 μM. Experiments with lesion specific enzymes showed that these effects are not due to oxidative damage of DNA bases. The negative findings obtained in Salmonella/microsome assays and the positive results of micronucleus tests with the cell lines indicate that the compound does not cause gene mutations but acts on the chromosomal level. In contrast to other synthetic cannabinoids, no indication for estrogenic/antiestrogenic properties was seen in a luciferase assay with bone marrow derived U2-OS cells. In conclusion, our findings show that the drug has only weak cytotoxic properties. However, the induction of chromosomal damage indicates that it may cause adverse effects in users due to its impact on the stability of the genetic material. - Highlights: • We tested the toxic properties of a synthetic cannabinoid. • Acute cytotoxic effects were detected with doses ≥ 7 μM. • No hormonal effects were found. • DNA damage was detected at levels ≥ 10 μM in comet assay and micronucleus tests. • Effects in directly

Double network physical gels from elastin-like polypeptide block copolymers: nanoscale control of thermoresponsive reinforcement

Science.gov (United States)

Glassman, Matthew; Olsen, Bradley

2014-03-01

Triblock copolymers with associative protein midblocks and thermoresponsive endblocks form shear thinning hydrogels with a low yield stress at low temperatures, but can be reinforced by a self-assembled network of the endblock aggregates. Here, we compare the use of bioengineered elastin-like polypeptides (ELPs) to synthetic poly(N-isopropylacrylamide) (PNIPAM) as endblocks to control the self-assembly of the reinforcing network. The temperature dependence of the mechanics of these hydrogels is a strong function of the domain size and morphology in the endblock network. Despite the architectural similarities, triblock ELP fusions and PNIPAM bioconjugates exhibit distinct reinforcement maxima at fixed block composition and polymer concentration, and these differences can be attributed to the nanostructural features of the two systems. Furthermore, in ELP fusions, the amino acid sequence can be readily modified to manipulate the solvation kinetics of the endblock domains. Finally, various endblocks have been combined to form triblock terpolymer hydrogels, demonstrating how the choice of thermoresponsive blocks can be used to tune the reinforcement of shear thinning hydrogels.

Drug Use and Viral Infections (HIV, Hepatitis)

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Family Checkup: Positive Parenting Prevents Drug Abuse

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Study on reinforced concrete beams with helical transverse reinforcement

Science.gov (United States)

Kaarthik Krishna, N.; Sandeep, S.; Mini, K. M.

2018-02-01

In a Reinforced Concrete (R.C) structure, major reinforcement is used for taking up tensile stresses acting on the structure due to applied loading. The present paper reports the behavior of reinforced concrete beams with helical reinforcement (transverse reinforcement) subjected to monotonous loading by 3-point flexure test. The results were compared with identically similar reinforced concrete beams with rectangular stirrups. During the test crack evolution, load carrying capacity and deflection of the beams were monitored, analyzed and compared. Test results indicate that the use of helical reinforcement provides enhanced load carrying capacity and a lower deflection proving to be more ductile, clearly indicating the advantage in carrying horizontal loads. An analysis was also carried out using ANSYS software in order to compare the test results of both the beams.

DESIGN AND EVALUATION OF LOSARTAN POTASSIUM MATRIX TABLETS WITH NATURAL AND SYNTHETIC POLYMERS

OpenAIRE

R. L. C. Sasidhar et al.

2012-01-01

The objective of the study was to formulate controlled release matrix tablets of losartan Potassium by using a combination of hydrophilic synthetic polymer like poly (ethylene oxides) and natural gums like xanthan gum, karaya gum and guar gum. A combination of synthetic hydrophobic polymers like methacrylates with synthetic hydrophilic polymer like poly (ethylene oxide) was also used in the preparation of matrix tablets and evaluated for their influence on controlled drug release. The matrix ...

Patient Counseling about Herbal-Drug Interactions | Hussain ...

African Journals Online (AJOL)

The multitude of pharmacologically active compounds obviously increases the likelihood of interactions taking place. Hence, the likelihood of herb-drug interactions is theoretically higher than drug-drug interactions because synthetic drugs usually contain single chemical entity. Case reports and clinical studies have ...

REINFORCED COMPOSITE PANEL

DEFF Research Database (Denmark)

2003-01-01

A composite panel having front and back faces, the panel comprising facing reinforcement, backing reinforcement and matrix material binding to the facing and backing reinforcements, the facing and backing reinforcements each independently comprising one or more reinforcing sheets, the facing rein...... by matrix material, the facing and backing reinforcements being interconnected to resist out-of-plane relative movement. The reinforced composite panel is useful as a barrier element for shielding structures, equipment and personnel from blast and/or ballistic impact damage....

Behavioral Perspectives on the Neuroscience of Drug Addiction

Science.gov (United States)

Winger, Gail; Woods, James H.; Galuska, Chad M.; Wade-Galuska, Tammy

2005-01-01

Neuroscientific approaches to drug addiction traditionally have been based on the premise that addiction is a process that results from brain changes that in turn result from chronic administration of drugs of abuse. An alternative approach views drug addiction as a behavioral disorder in which drugs function as preeminent reinforcers. Although…

Effect of Different Fillers on Adhesive Wear Properties of Glass Fiber Reinforced Polyester Composites

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E. Feyzullahoğlu

2017-12-01

Full Text Available Polymeric composites are used for different aims as substitute of traditional materials such as metals; due to their improved strength at small specific weight. The fiber reinforced polymer (FRP composite material consists of polymeric matrix and reinforcing material. Polymeric materials are commonly reinforced with synthetic fibers such as glass and carbon. The glass fiber reinforced polyester (GFRP composites are used with different filler materials. The aim of this study is to investigate the effects of different filler materials on adhesive wear behavior of GFRP. In this experimental study; polymetilmetacrilat (PMMA, Glass beads (GB and Glass sand (GS were used as filling material in GFRP composite samples. The adhesive wear behaviors of samples were carried out using ball on disc type tribometer. The friction force and coefficient of friction were measured during the test. The volume loss and wear rate values of samples were calculated according to test results. Barcol hardness values of samples were measured. The densities of samples were measured. Results show that the wear resistance of GB filled GFRP composite samples was much more than non-filled and PMMA filled GFRP composite samples.

Polymer architecture and drug delivery.

Science.gov (United States)

Qiu, Li Yan; Bae, You Han

2006-01-01

Polymers occupy a major portion of materials used for controlled release formulations and drug-targeting systems because this class of materials presents seemingly endless diversity in topology and chemistry. This is a crucial advantage over other classes of materials to meet the ever-increasing requirements of new designs of drug delivery formulations. The polymer architecture (topology) describes the shape of a single polymer molecule. Every natural, seminatural, and synthetic polymer falls into one of categorized architectures: linear, graft, branched, cross-linked, block, star-shaped, and dendron/dendrimer topology. Although this topic spans a truly broad area in polymer science, this review introduces polymer architectures along with brief synthetic approaches for pharmaceutical scientists who are not familiar with polymer science, summarizes the characteristic properties of each architecture useful for drug delivery applications, and covers recent advances in drug delivery relevant to polymer architecture.

[Advance in flavonoids biosynthetic pathway and synthetic biology].

Science.gov (United States)

Zou, Li-Qiu; Wang, Cai-Xia; Kuang, Xue-Jun; Li, Ying; Sun, Chao

2016-11-01

Flavonoids are the valuable components in medicinal plants, which possess a variety of pharmacological activities, including anti-tumor, antioxidant and anti-inflammatory activities. There is an unambiguous understanding about flavonoids biosynthetic pathway, that is,2S-flavanones including naringenin and pinocembrin are the skeleton of other flavonoids and they can transform to other flavonoids through branched metabolic pathway. Elucidation of the flavonoids biosynthetic pathway lays a solid foundation for their synthetic biology. A few flavonoids have been produced in Escherichia coli or yeast with synthetic biological technologies, such as naringenin, pinocembrin and fisetin. Synthetic biology will provide a new way to get valuable flavonoids and promote the research and development of flavonoid drugs and health products, making flavonoids play more important roles in human diet and health. Copyright© by the Chinese Pharmaceutical Association.

Self-Healing Capability of Fiber-Reinforced Cementitious Composites for Recovery of Watertightness and Mechanical Properties

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Tomoya Nishiwaki

2014-03-01

Full Text Available Various types of fiber reinforced cementitious composites (FRCCs were experimentally studied to evaluate their self-healing capabilities regarding their watertightness and mechanical properties. Cracks were induced in the FRCC specimens during a tensile loading test, and the specimens were then immersed in static water for self-healing. By water permeability and reloading tests, it was determined that the FRCCs containing synthetic fiber and cracks of width within a certain range (<0.1 mm exhibited good self-healing capabilities regarding their watertightness. Particularly, the high polarity of the synthetic fiber (polyvinyl alcohol (PVA series and hybrid fiber reinforcing (polyethylene (PE and steel code (SC series showed high recovery ratio. Moreover, these series also showed high potential of self-healing of mechanical properties. It was confirmed that recovery of mechanical property could be obtained only in case when crack width was sufficiently narrow, both the visible surface cracks and the very fine cracks around the bridging of the SC fibers. Recovery of the bond strength by filling of the very fine cracks around the bridging fibers enhanced the recovery of the mechanical property.

Physical and Mechanical Properties of Jute Mat Reinforced Epoxy Composites

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S.M Sadaf

2011-11-01

Full Text Available Cellulose jute fibre offers a number of benefits as reinforcement for synthetic polymers since it has a high specific strength and stiffness, low hardness, relatively low density and biodegradability. To reduce moisture uptake and hence to improve the mechanical properties of the composites, bleached jute mats were incorporated as reinforcing elements in the epoxy matrix. Composites at varying volume fractions and different orientations of jute mat were fabricated by hot compression machine under specific pressures and temperatures. Tensile, flexure, impact and water absorption tests of composites were conducted. Jute mat oriented at (0 ± 45–90° composites showed reduced strength compared to (0–90° fibre mat composites. Impact strength and water uptake of high volume fraction jute mat reinforced composites was higher compared to that of lower volume fraction composites. Fracture surfaces of jute mat composites were analyzed under SEM. Fracture surface of (0–90° jute mat oriented composites showed twisted fibres, while (0 ± 45–90° jute mat oriented composites had fibre pull-out without any twisting. Overall, composites containing 52% jute mat at orientations of (0–90° showed better properties compared to other fabricated composites.

Landslide rehabilitation with geo synthetics in open coal mine Oslomej

International Nuclear Information System (INIS)

Dimitrievski, Ljupcho; Ilievska, Frosina; Ilievski, Darko

2004-01-01

In November 2002 stability is violated and landslides are registered in open coal mine Oslomej, Republic of Macedonia. Around the profile IV existing open irrigation channel was interrupted and landslide was extended to the regional way R421 Kicevo - Oslomej. The landslide was classified like big and dangerous, including danger for disruption of the regional road and pipeline Studencica - Oslomej for supplying of thermal power plant Oslomej with technical water. According to the proposed solution, main project design for landslide rehabilitation was prepared with using geo synthetics Stabilenka 200/45. In fill is local soil material which had been placed and compacted in layers, it had formed a composite construction. Stabilenka acts as a reinforcement due to its ability to absorb tensile forces. With the design solution two retaining walls of reinforced soil and complete drainage system of geo composite materials had been constructed This paper deals with details of the design and the construction. (Author)

Synthetic biology, inspired by synthetic chemistry.

Science.gov (United States)

Malinova, V; Nallani, M; Meier, W P; Sinner, E K

2012-07-16

The topic synthetic biology appears still as an 'empty basket to be filled'. However, there is already plenty of claims and visions, as well as convincing research strategies about the theme of synthetic biology. First of all, synthetic biology seems to be about the engineering of biology - about bottom-up and top-down approaches, compromising complexity versus stability of artificial architectures, relevant in biology. Synthetic biology accounts for heterogeneous approaches towards minimal and even artificial life, the engineering of biochemical pathways on the organismic level, the modelling of molecular processes and finally, the combination of synthetic with nature-derived materials and architectural concepts, such as a cellular membrane. Still, synthetic biology is a discipline, which embraces interdisciplinary attempts in order to have a profound, scientific base to enable the re-design of nature and to compose architectures and processes with man-made matter. We like to give an overview about the developments in the field of synthetic biology, regarding polymer-based analogs of cellular membranes and what questions can be answered by applying synthetic polymer science towards the smallest unit in life, namely a cell. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Drug versus sweet reward: greater attraction to and preference for sweet versus drug cues.

Science.gov (United States)

Madsen, Heather B; Ahmed, Serge H

2015-05-01

Despite the unique ability of addictive drugs to directly activate brain reward circuits, recent evidence suggests that drugs induce reinforcing and incentive effects that are comparable to, or even lower than some nondrug rewards. In particular, when rats have a choice between pressing a lever associated with intravenous cocaine or heroin delivery and another lever associated with sweet water delivery, most respond on the latter. This outcome suggests that sweet water is more reinforcing and attractive than either drug. However, this outcome may also be due to the differential ability of sweet versus drug levers to elicit Pavlovian feeding-like conditioned responses that can cause involuntary lever pressing, such as pawing and biting the lever. To test this hypothesis, rats first underwent Pavlovian conditioning to associate one lever with sweet water (0.2% saccharin) and a different lever with intravenous cocaine (0.25 mg) or heroin (0.01 mg). Choice between these two levers was then assessed under two operant choice procedures: one that permitted the expression of Pavlovian-conditioned lever press responses during choice, the other not. During conditioning, Pavlovian-conditioned lever press responses were considerably higher on the sweet lever than on either drug lever, and slightly greater on the heroin lever than on the cocaine lever. Importantly, though these differences in Pavlovian-conditioned behavior predicted subsequent preference for sweet water during choice, they were not required for its expression. Overall, this study confirms that rats prefer the sweet lever because sweet water is more reinforcing and attractive than cocaine or heroin. © 2014 Society for the Study of Addiction.

Synthesis and Properties of Carbon Nanotube-Grafted Silica Nanoarchitecture-Reinforced Poly(Lactic Acid

Directory of Open Access Journals (Sweden)

Yao-Wen Hsu

2017-07-01

Full Text Available A novel nanoarchitecture-reinforced poly(lactic acid (PLA nanocomposite was prepared using multi-walled carbon nanotube (MWCNT-grafted silica nanohybrids as reinforcements. MWCNT-grafted silica nanohybrids were synthesized by the generation of silica nanoparticles on the MWCNT surface through the sol-gel technique. This synthetic method involves organo-modified MWCNTs that are dispersed in tetrahydrofuran, which incorporates tetraethoxysilane that undergoes an ultrasonic sol-gel process. Gelation yielded highly dispersed silica on the organo-modified MWCNTs. The structure and properties of the nanohybrids were established using 29Si nuclear magnetic resonance, Raman spectroscopy, wide-angle X-ray diffraction, thermogravimetric analysis, and transmission electron microscopy. The resulting MWCNT nanoarchitectures were covalently assembled into silica nanoparticles, which exhibited specific and controllable morphologies and were used to reinforce biodegradable PLA. The tensile strength and the heat deflection temperature (HDT of the PLA/MWCNT-grafted silica nanocomposites increased when the MWCNT-grafted silica was applied to the PLA matrix; by contrast, the surface resistivity of the PLA/MWCNT-grafted silica nanocomposites appeared to decline as the amount of MWCNT-grafted silica in the PLA matrix increased. Overall, the reinforcement of PLA using MWCNT-grafted silica nanoarchitectures was efficient and improved its mechanical properties, heat resistance, and electrical resistivity.

Drug monitoring and individual dose optimization of antimicrobial drugs : oxazolidinones

NARCIS (Netherlands)

Cattaneo, Dario; Alffenaar, Jan-Willem; Neely, Michael

INTRODUCTION: Oxazolidinones are synthetic antibiotics with bacteriostatic activity against Gram-positive pathogens. Linezolid, the first marketed oxazolidinone, has shown also activity against Mycobaterium tuberculosis, including multidrug-resistant and extensively drug-resistant strains. Recently,

21 CFR 172.866 - Synthetic glycerin produced by the hydrogenolysis of carbohydrates.

Science.gov (United States)

2010-04-01

... of carbohydrates. 172.866 Section 172.866 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... produced by the hydrogenolysis of carbohydrates. Synthetic glycerin produced by the hydrogenolysis of carbohydrates may be safely used in food, subject to the provisions of this section: (a) It shall contain not in...

Which Classes of Prescription Drugs Are Commonly Misused?

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Seeking Drug Abuse Treatment: Know What to Ask

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Drugs, Brains, and Behavior: The Science of Addiction

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Reinforcement Magnitude: An Evaluation of Preference and Reinforcer Efficacy

OpenAIRE

Trosclair-Lasserre, Nicole M; Lerman, Dorothea C; Call, Nathan A; Addison, Laura R; Kodak, Tiffany

2008-01-01

Consideration of reinforcer magnitude may be important for maximizing the efficacy of treatment for problem behavior. Nonetheless, relatively little is known about children's preferences for different magnitudes of social reinforcement or the extent to which preference is related to differences in reinforcer efficacy. The purpose of the current study was to evaluate the relations among reinforcer magnitude, preference, and efficacy by drawing on the procedures and results of basic experimenta...

Tofacitinib with conventional synthetic disease‐modifying antirheumatic drugs in Chinese patients with rheumatoid arthritis: Patient‐reported outcomes from a Phase 3 randomized controlled trial

OpenAIRE

Li, Zhanguo; An, Yuan; Su, Houheng; Li, Xiangpei; Xu, Jianhua; Zheng, Yi; Li, Guiye; Kwok, Kenneth; Wang, Lisy; Wu, Qizhe

2018-01-01

Abstract Aim Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We assess the effect of tofacitinib + conventional synthetic disease‐modifying anti rheumatic drugs (csDMARDs) on patient‐reported outcomes in Chinese patients with RA and inadequate response to DMARDs. Methods This analysis of data from the Phase 3 study ORAL Sync included Chinese patients randomized 4 : 4 : 1 : 1 to receive tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, p...

Rapid identification of illegal synthetic adulterants in herbal anti-diabetic medicines using near infrared spectroscopy

Science.gov (United States)

Feng, Yanchun; Lei, Deqing; Hu, Changqin

We created a rapid detection procedure for identifying herbal medicines illegally adulterated with synthetic drugs using near infrared spectroscopy. This procedure includes a reverse correlation coefficient method (RCCM) and comparison of characteristic peaks. Moreover, we made improvements to the RCCM based on new strategies for threshold settings. Any tested herbal medicine must meet two criteria to be identified with our procedure as adulterated. First, the correlation coefficient between the tested sample and the reference must be greater than the RCCM threshold. Next, the NIR spectrum of the tested sample must contain the same characteristic peaks as the reference. In this study, four pure synthetic anti-diabetic drugs (i.e., metformin, gliclazide, glibenclamide and glimepiride), 174 batches of laboratory samples and 127 batches of herbal anti-diabetic medicines were used to construct and validate the procedure. The accuracy of this procedure was greater than 80%. Our data suggest that this protocol is a rapid screening tool to identify synthetic drug adulterants in herbal medicines on the market.

THE USE OF SISAL FIBRE AS REINFORCEMENT IN CEMENT BASED COMPOSITES

Directory of Open Access Journals (Sweden)

Romildo Dias Tolêdo Filho

1999-08-01

Full Text Available ABSTRACT The inclusion of fibre reinforcement in concrete, mortar and cement paste can enhance many of the engineering properties of the basic materials, such as fracture toughness, flexural strength and resistance to fatigue, impact, thermal shock and spalling. In recent years, a great deal of interest has been created worldwide on the potential applications of natural fibre reinforced, cement based composites. Investigations have been carried out in many countries on various mechanical properties, physical performance and durability of cement based matrices reinforced with naturally occurring fibres including sisal, coconut, jute, bamboo and wood fibres. These fibres have always been considered promising as reinforcement of cement based matrices because of their availability, low cost and low consumption of energy. In this review, the general properties of the composites are described in relation to fibre content, length, strength and stiffness. A chronological development of sisal fibre reinforced, cement based matrices is reported and experimental data are provided to illustrate the performance of sisal fibre reinforced cement composites. A brief description on the use of these composite materials as building products has been included. The influence of sisal fibres on the development of plastic shrinkage in the pre-hardened state, on tensile, compressive and bending strength in the hardened state of mortar mixes is discussed. Creep and drying shrinkage of the composites and the durability of natural fibres in cement based matrices are of particular interest and are also highlighted. The results show that the composites reinforced with sisal fibres are reliable materials to be used in practice for the production of structural elements to be used in rural and civil construction. This material could be a substitute asbestos-cement composite, which is a serious hazard to human and animal health and is prohibited in industrialized countries. The

SIMULTANEOUS DETERMINATION OF 32 NEW SYNTHETIC CANNABINOIDS IN HUMAN URINE AND HAIR BY LC-MS/MS

OpenAIRE

WANG, Chung-Feng

2018-01-01

The extraction procedure and detectionmethods of new Synthetic Cannabinoids (ex: BB-22, SDB-005, THJ-018,JZL-195……etc.) for human urine and hair samples are in great need due to thesenew drugs are abused severely in recent years all over the world. Highlysensitive analytical techniques are therefore required for trace-levelidentification and quantification of these kinds of drugs. We report a fullyvalidated method here developed by our team which could simultaneouslydetermine 32 new Synthetic...

Atomic force microscopy analysis of synthetic membranes applied in release studies

Energy Technology Data Exchange (ETDEWEB)

Olejnik, Anna, E-mail: annamar@amu.edu.pl; Nowak, Izabela

2015-11-15

Graphical abstract: - Highlights: • We compare eight synthetic membranes by atomic force microscopy. • We predict the behavior of membranes in the release experiments. • The polymeric synthetic membranes varied in shape and size. • We detect substructures in pores of cellulose esters and nylon membranes. • Substructures limit the release rate of active compound. - Abstract: Synthetic membranes are commonly used in drug release studies and are applied mostly in quality control. They contain pores through which the drug can be diffused directly into the receptor fluid. Investigation of synthetic membranes permits determination of their structure and characterization of their properties. We suggest that the preliminary characterization of the membranes can be relevant to the interpretation of the release results. The aim of this study was to compare eight synthetic membranes by using atomic force microscopy in order to predict and understand their behavior in the release experiments. The results proved that polytetrafluoroethylene membrane was not suitable for the release study of tetrapeptide due to its hydrophobic nature, thickness and the specific structure with high trapezoid shaped blocks. The additional substructures in pores of mixed cellulose esters and nylon membranes detected by AFM influenced the diffusion rate of the active compound. These findings indicate that the selection of the membrane for the release studies should be performed cautiously by taking into consideration the membrane properties and by analyzing them prior the experiment.

Atomic force microscopy analysis of synthetic membranes applied in release studies

International Nuclear Information System (INIS)

Olejnik, Anna; Nowak, Izabela

2015-01-01

Graphical abstract: - Highlights: • We compare eight synthetic membranes by atomic force microscopy. • We predict the behavior of membranes in the release experiments. • The polymeric synthetic membranes varied in shape and size. • We detect substructures in pores of cellulose esters and nylon membranes. • Substructures limit the release rate of active compound. - Abstract: Synthetic membranes are commonly used in drug release studies and are applied mostly in quality control. They contain pores through which the drug can be diffused directly into the receptor fluid. Investigation of synthetic membranes permits determination of their structure and characterization of their properties. We suggest that the preliminary characterization of the membranes can be relevant to the interpretation of the release results. The aim of this study was to compare eight synthetic membranes by using atomic force microscopy in order to predict and understand their behavior in the release experiments. The results proved that polytetrafluoroethylene membrane was not suitable for the release study of tetrapeptide due to its hydrophobic nature, thickness and the specific structure with high trapezoid shaped blocks. The additional substructures in pores of mixed cellulose esters and nylon membranes detected by AFM influenced the diffusion rate of the active compound. These findings indicate that the selection of the membrane for the release studies should be performed cautiously by taking into consideration the membrane properties and by analyzing them prior the experiment.

Reinforced sulphur concrete

NARCIS (Netherlands)

2014-01-01

Reinforced sulphur concrete wherein one or more metal reinforcing members are in contact with sulphur concrete is disclosed. The reinforced sulphur concrete comprises an adhesion promoter that enhances the interaction between the sulphur and the one or more metal reinforcing members.

A Study of Nanoclay Reinforcement of Biocomposites Made by Liquid Composite Molding

Directory of Open Access Journals (Sweden)

Farida Bensadoun

2011-01-01

Full Text Available Liquid composite molding (LCM processes are widely used to manufacture composite parts for the automotive industry. An appropriate selection of the materials and proper optimization of the manufacturing parameters are keys to produce parts with improved mechanical properties. This paper reports on a study of biobased composites reinforced with nanoclay particles. A soy-based unsaturated polyester resin was used as synthetic matrix, and glass and flax fiber fabrics were used as reinforcement. This paper aims to improve mechanical and flammability properties of reinforced composites by introducing nanoclay particles in the unsaturated polyester resin. Four different mixing techniques were investigated to improve the dispersion of nanoclay particles in the bioresin in order to obtain intercalated or exfoliated structures. An experimental study was carried out to define the adequate parameter combinations between vacuum pressure, filling time, and resin viscosity. Two manufacturing methods were investigated and compared: RTM and SCRIMP. Mechanical properties, such as flexural modulus and ultimate strength, were evaluated and compared for conventional glass fiber composites (GFC and flax fiber biocomposites (GFBiores-C. Finally, smoke density analysis was performed to demonstrate the effects and advantages of using an environment-friendly resin combined with nanoclay particles.

Intranasal oxytocin enhances socially-reinforced learning in rhesus monkeys

Directory of Open Access Journals (Sweden)

Lisa A Parr

2014-09-01

Full Text Available There are currently no drugs approved for the treatment of social deficits associated with autism spectrum disorders (ASD. One hypothesis for these deficits is that individuals with ASD lack the motivation to attend to social cues because those cues are not implicitly rewarding. Therefore, any drug that could enhance the rewarding quality of social stimuli could have a profound impact on the treatment of ASD, and other social disorders. Oxytocin (OT is a neuropeptide that has been effective in enhancing social cognition and social reward in humans. The present study examined the ability of OT to selectively enhance learning after social compared to nonsocial reward in rhesus monkeys, an important species for modeling the neurobiology of social behavior in humans. Monkeys were required to learn an implicit visual matching task after receiving either intranasal (IN OT or Placebo (saline. Correct trials were rewarded with the presentation of positive and negative social (play faces/threat faces or nonsocial (banana/cage locks stimuli, plus food. Incorrect trials were not rewarded. Results demonstrated a strong effect of socially-reinforced learning, monkeys’ performed significantly better when reinforced with social versus nonsocial stimuli. Additionally, socially-reinforced learning was significantly better and occurred faster after IN-OT compared to placebo treatment. Performance in the IN-OT, but not Placebo, condition was also significantly better when the reinforcement stimuli were emotionally positive compared to negative facial expressions. These data support the hypothesis that OT may function to enhance prosocial behavior in primates by increasing the rewarding quality of emotionally positive, social compared to emotionally negative or nonsocial images. These data also support the use of the rhesus monkey as a model for exploring the neurobiological basis of social behavior and its impairment.

Beyond Cost-Benefit Analysis in the Governance of Synthetic Biology.

Science.gov (United States)

Wallach, Wendell; Saner, Marc; Marchant, Gary

2018-01-01

For many innovations, oversight fits nicely within existing governance mechanisms; nevertheless, others pose unique public health, environmental, and ethical challenges. Synthetic artemisinin, for example, has many precursors in laboratory-developed drugs that emulate natural forms of the same drug. The policy challenges posed by synthetic artemisinin do not differ significantly in kind from other laboratory-formulated drugs. Synthetic biofuels and gene drives, however, fit less clearly into existing governance structures. How many of the new categories of products require new forms of regulatory oversight, or at least extensive forms of testing, remains unclear. Any effort to improve the governance of synthetic biology should start with a rich understanding of the different possible science-policy interfaces that could help to inform governance. CBA falls into a subset of the overall range of possibilities, and which interface is appropriate may turn out to depend on context, on the demands of the decision at hand. In what follows, we lay out a typology of interfaces. After that, we turn to the question of how to draw upon the range of possible interfaces and effectively address the factual and moral complexities of emerging technologies. We propose a governance model built around structures that we call "governance coordinating committees." GCCs are intended to be mechanisms for accommodating the complexities of innovations that have far-ranging societal impacts. The production of biofuels, for example, could contaminate water supplies and have a destructive environmental impact if not managed correctly. The introduction of a gene drive could have economic and environmental impacts that are not restricted to one nation. Forging appropriate means for determining and evaluating those societal impacts, to the best of a corporation's, industry's, or government's ability, is central to responsible research and innovation. Public policy must be shaped in a manner that

Emerging drugs of abuse.

Science.gov (United States)

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.

Reinforcement Magnitude: An Evaluation of Preference and Reinforcer Efficacy

Science.gov (United States)

Trosclair-Lasserre, Nicole M.; Lerman, Dorothea C.; Call, Nathan A.; Addison, Laura R.; Kodak, Tiffany

2008-01-01

Consideration of reinforcer magnitude may be important for maximizing the efficacy of treatment for problem behavior. Nonetheless, relatively little is known about children's preferences for different magnitudes of social reinforcement or the extent to which preference is related to differences in reinforcer efficacy. The purpose of the current…

Autoshaping Chicks with Heat Reinforcement: The Role of Stimulus-Reinforcer and Response-Reinforcer Relations

Science.gov (United States)

Wasserman, Edward A.; And Others

1975-01-01

The present series of experiments attempted to analyze more fully the contributions of stimulus-reinforcer and response-reinforcer relations to autoshaping within a single conditioning situation. (Author)

Synthetic Genetic Targeting of Genome Instability in Cancer

International Nuclear Information System (INIS)

Sajesh, Babu V.; Guppy, Brent J.; McManus, Kirk J.

2013-01-01

Cancer is a leading cause of death throughout the World. A limitation of many current chemotherapeutic approaches is that their cytotoxic effects are not restricted to cancer cells, and adverse side effects can occur within normal tissues. Consequently, novel strategies are urgently needed to better target cancer cells. As we approach the era of personalized medicine, targeting the specific molecular defect(s) within a given patient’s tumor will become a more effective treatment strategy than traditional approaches that often target a given cancer type or sub-type. Synthetic genetic interactions are now being examined for their therapeutic potential and are designed to target the specific genetic and epigenetic phenomena associated with tumor formation, and thus are predicted to be highly selective. In general, two complementary approaches have been employed, including synthetic lethality and synthetic dosage lethality, to target aberrant expression and/or function associated with tumor suppressor genes and oncogenes, respectively. Here we discuss the concepts of synthetic lethality and synthetic dosage lethality, and explain three general experimental approaches designed to identify novel genetic interactors. We present examples and discuss the merits and caveats of each approach. Finally, we provide insight into the subsequent pre-clinical work required to validate novel candidate drug targets

Treat Jail Detainees' Drug Abuse to Lower HIV Transmission

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Abuse of Prescription (Rx) Drugs Affects Young Adults Most

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

A Novel Application of Synthetic Biology and Directed Evolution to Engineer Phage-based Antibiotics

Energy Technology Data Exchange (ETDEWEB)

Wu, Meiye [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

2014-09-01

The emergence of multiple drug resistant bacteria poses threats to human health, agriculture and food safety. Annually over 100,000 deaths and up to $20 billion loss to the U.S. economy are attributed to multiple drug resistant bacteria. With only four new chemical antibiotics in the drug development pipeline, we are in dire need of new solutions to address the emerging threat of multiple drug resistance. We propose a paradigm-changing approach to address the multi-drug resistant bacteria problem by utilizing Synthetic Biology (SynBio) methodologies to create and evolve “designer” bacteriophages or phages – viruses that specifically infect bacteria – to infect and kill newly emerging pathogenic bacterial strains WITHOUT the need for chemical antibiotics. A major advantage of using phage to combat pathogenic bacteria is that phages can co-evolve with their bacterial host, and Sandia can be the first in the world to establish an industrial scale Synthetic Biology pipeline for phage directed evolution for safe, targeted, customizable solution to bacterial drug resistance. Since there is no existing phage directed evolution effort within or outside of Sandia, this proposal is suitable as a high-risk LDRD effort to create the first pipeline for such an endeavor. The high potential reward nature of this proposal will be the immediate impact in decontamination and restoration of surfaces and infrastructure, with longer term impact in human or animal therapeutics. The synthetic biology and screening approaches will lead to fundamental knowledge of phage/bacteria co-evolution, making Sandia a world leader in directed evolution of bacteriophages.

Comparison of self-administration behavior and responsiveness to drug-paired cues in rats running an alley for intravenous heroin and cocaine.

Science.gov (United States)

Su, Zu-In; Wenzel, Jennifer; Baird, Rebeccah; Ettenberg, Aaron

2011-04-01

Evidence suggests that responsiveness to a drug-paired cue is predicted by the reinforcing magnitude of the drug during prior self-administration. It remains unclear, however, if this principle holds true when comparisons are made across drug reinforcers. The current study was therefore devised to test the hypothesis that differences in the animals' responsiveness to a cocaine- or heroin-paired cue presented during extinction would reflect differences in the patterns of prior cocaine and heroin runway self-administration. Rats ran a straight alley for single intravenous injections of either heroin (0.1 mg/kg/inj) or cocaine (1.0 mg/kg/inj) each paired with a distinct olfactory cue. Animals experienced 15 trials with each drug reinforcer in a counterbalanced manner. Start latencies, run times, and retreat behaviors (a form of approach-avoidance conflict) provided behavioral indices of the subjects' motivation to seek the reinforcer on each trial. Responsiveness to each drug-paired cue was assessed after 7, 14, or 21 days of non-reinforced extinction trials. Other animals underwent conditioned place preference (CPP) testing to ensure that the two drug reinforcers were capable of producing drug-cue associations. While both drugs produced comparable CPPs, heroin served as a stronger incentive stimulus in the runway as evidenced by faster start and run times and fewer retreats. In contrast, cocaine- but not heroin-paired cues produced increases in drug-seeking behavior during subsequent extinction trials. The subjects' responsiveness to drug-paired cues during extinction was not predicted by differences in the motivation to seek heroin versus cocaine during prior drug self-administration.

Application of LC-ESI-MS-MS for detection of synthetic adulterants in herbal remedies.

Science.gov (United States)

Bogusz, Maciej J; Hassan, Huda; Al-Enazi, Eid; Ibrahim, Zuhour; Al-Tufail, Mohammed

2006-05-03

Adulteration of allegedly "natural herbal medicines" with undeclared synthetic drugs is a common and dangerous phenomenon of alternative medicine. The purpose of the study was to develop a procedure for detection of most common synthetic adulterants in herbal remedies, using high-pressure liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS-MS). Eighty drugs belonging to various pharmacological classes were included in the study. For most drugs two transitions were monitored, using protonated or deprotonated molecules as precursor ions. The drugs were isolated from herbal remedies using simple methanol extraction. Chromatographic separation was done in gradient of acetonitrile-10 mM ammonium formate buffer (pH 3.0). Drugs tested were grouped in suites, comprising analgesic drugs, antibiotics, antidiabetic drugs, antiepileptic drugs, aphrodisiacs, hormones and anabolic drugs, psychotropic drugs, and weight reducing compounds. These suites were used according to the declared benefits of examined preparations. Limits of detection ranged from 5 pg to 1 ng per injected sample. Drug-free herbal remedy spiked with eight various pharmaceuticals occurring in adulterated herbal preparations was used for internal proficiency testing. The recoveries of spiked drugs ranged from 63 to 100%. The procedure was applied in everyday casework. Several undeclared drugs were identified in "herbal" remedies, like e.g. sildenafil, tadalafil, testosterone, or glibenclamide. Pharmacological properties of detected drugs always corresponded with the claims of the "natural" remedies. The method presents a valuable extension of standard GC-MS screening used for this purpose.

Long-term successful arthroscopic repair of large and massive rotator cuff tears with a functional and degradable reinforcement device.

Science.gov (United States)

Proctor, Christopher S

2014-10-01

Rotator cuff repair is a procedure with varying outcomes, and there has been subsequent interest in devices that reinforce the repair and enhance structural and functional outcomes. The objective of this study was to determine these outcomes for arthroscopic repair of large and massive rotator cuff tears augmented with a synthetic absorbable mesh designed specifically for reinforcement of tendon repair by imaging and clinical assessments. Consecutive arthroscopic repairs were performed on 18 patients with large to massive rotator cuff tears by use of a poly-l-lactic acid synthetic patch as a reinforcement device and fixation with 4 sutures. Patients were assessed preoperatively and at 6 months, 12 months, and a mean of 42 months after surgery by the American Shoulder and Elbow Surgeons (ASES) shoulder score to evaluate clinical performance and at 12 months by ultrasound to assess structural repair. Ultrasound showed that 15 of 18 patients had intact rotator cuff repair at 12 months; at 42 months, an additional patient had a failed repair. Patients showed improvement in the ASES shoulder score from 25 preoperatively to 71 at 12 months and 70 at 42 months after surgery. Patients with intact rotator cuff (n = 14) at 42 months had an ASES shoulder score of 82. The poly-l-lactic acid bioabsorbable patch designed specifically to reinforce the surgical repair of tendons supported successful repair of large to massive rotator cuff tears in 83% of patients at 12 months after surgery and 78% of patients at 42 months after surgery, with substantial functional improvement. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Differential vulnerability to the punishment of cocaine related behaviours: effects of locus of punishment, cocaine taking history and alternative reinforcer availability.

Science.gov (United States)

Pelloux, Yann; Murray, Jennifer E; Everitt, Barry J

2015-01-01

The availability of alternative reinforcement has been shown to reduce drug use, but it remains unclear whether it facilitates a reduction or cessation of drug seeking or taking. We compared the effects of punishment of cocaine seeking or taking behaviour after brief or extended cocaine-taking histories when behavioural reallocation was facilitated or not by making available an alternative ingestive reinforcer (sucrose). In the first experiment, punishment of either seeking or taking responses was introduced immediately after training on the seeking-taking chained schedule. In the second experiment, punishment of cocaine seeking was introduced after 12 additional days of either 1 or 6 h daily access to cocaine self-administration. In both experiments, beginning 1 week before the introduction of punishment, a subset of rats had concurrent nose poke access to sucrose while seeking or taking cocaine. The presence of an alternative source of reinforcement markedly facilitated behavioural reallocation from punished cocaine taking after acquisition. It also facilitated punishment-induced suppression of cocaine seeking after an extensive cocaine self-administration history likely by prompting goal-directed motivational control over drug use. However, a significant proportion of rats were deemed compulsive-maintaining drug use after an extensive cocaine history despite the presence of abstinence-promoting positive and negative incentives. Making available an alternative reinforcer facilitates disengagement from punished cocaine use through at least two different processes but remains ineffective in a subpopulation of vulnerable animals, which continued to seek cocaine despite the aversive consequence of punishment and the presence of the alternative positive reinforcer.

Genomic Signatures of Reinforcement

Directory of Open Access Journals (Sweden)

Austin G. Garner

2018-04-01

Full Text Available Reinforcement is the process by which selection against hybridization increases reproductive isolation between taxa. Much research has focused on demonstrating the existence of reinforcement, yet relatively little is known about the genetic basis of reinforcement or the evolutionary conditions under which reinforcement can occur. Inspired by reinforcement’s characteristic phenotypic pattern of reproductive trait divergence in sympatry but not in allopatry, we discuss whether reinforcement also leaves a distinct genomic pattern. First, we describe three patterns of genetic variation we expect as a consequence of reinforcement. Then, we discuss a set of alternative processes and complicating factors that may make the identification of reinforcement at the genomic level difficult. Finally, we consider how genomic analyses can be leveraged to inform if and to what extent reinforcement evolved in the face of gene flow between sympatric lineages and between allopatric and sympatric populations of the same lineage. Our major goals are to understand if genome scans for particular patterns of genetic variation could identify reinforcement, isolate the genetic basis of reinforcement, or infer the conditions under which reinforcement evolved.

Genomic Signatures of Reinforcement

Science.gov (United States)

Goulet, Benjamin E.

2018-01-01

Reinforcement is the process by which selection against hybridization increases reproductive isolation between taxa. Much research has focused on demonstrating the existence of reinforcement, yet relatively little is known about the genetic basis of reinforcement or the evolutionary conditions under which reinforcement can occur. Inspired by reinforcement’s characteristic phenotypic pattern of reproductive trait divergence in sympatry but not in allopatry, we discuss whether reinforcement also leaves a distinct genomic pattern. First, we describe three patterns of genetic variation we expect as a consequence of reinforcement. Then, we discuss a set of alternative processes and complicating factors that may make the identification of reinforcement at the genomic level difficult. Finally, we consider how genomic analyses can be leveraged to inform if and to what extent reinforcement evolved in the face of gene flow between sympatric lineages and between allopatric and sympatric populations of the same lineage. Our major goals are to understand if genome scans for particular patterns of genetic variation could identify reinforcement, isolate the genetic basis of reinforcement, or infer the conditions under which reinforcement evolved. PMID:29614048

Synthetic Biology to Engineer Bacteriophage Genomes.

Science.gov (United States)

Rita Costa, Ana; Milho, Catarina; Azeredo, Joana; Pires, Diana Priscila

2018-01-01

Recent advances in the synthetic biology field have enabled the development of new molecular biology techniques used to build specialized bacteriophages with new functionalities. Bacteriophages have been engineered towards a wide range of applications including pathogen control and detection, targeted drug delivery, or even assembly of new materials.In this chapter, two strategies that have been successfully used to genetically engineer bacteriophage genomes are addressed: a yeast-based platform and bacteriophage recombineering of electroporated DNA.

Effect of UV and water spraying on the mechanical properties of flax fabric reinforced polymer composites used for civil engineering applications

International Nuclear Information System (INIS)

Yan, Libo; Chouw, Nawawi; Jayaraman, Krishnan

2015-01-01

Highlights: • UV weathering degraded mechanical properties of flax/epoxy composites. • SEM confirmed degradation in fibre/matrix interfacial bonding. • UV weathering caused discolouration, matrix erosion, microcracking. - Abstract: The lack of data related to durability is one major challenge that needed to be addressed prior to the widespread acceptance of natural fibre reinforced polymer composites for engineering applications. In this work, the combined effect of ultraviolet (UV) radiation and water spraying on the mechanical properties of flax fabric reinforced epoxy composite was investigated to assess the durability performance of this composite used for civil engineering applications. Specimens fabricated by hand lay-up process were exposed in an accelerated weathering chamber for 1500 h. Tensile and three-point bending tests were performed to evaluate the mechanical properties. Scanning electron microscope (SEM) was used to analyse the microstructures of the composites. In addition, the durability performance of flax/epoxy composite was compared with synthetic (glass and carbon) and hybrid fibre reinforced composites. The test results show that the tensile strength/modulus of the weathered composites decreased 29.9% and 34.9%, respectively. The flexural strength/modulus reduced 10.0% and 10.2%, respectively. SEM study confirmed the degradation in fibre/matrix interfacial bonding after exposure. Comparisons with other composites implies that flax fabric/epoxy composite has potential to be used for civil engineering applications when taking its structural and durability performance into account. Proper treatments to enhance its durability performance will make it more comparable to synthetic fibre reinforced composites when considering as construction building materials

Employment-based abstinence reinforcement following inpatient detoxification in HIV-positive opioid and/or cocaine-dependent patients.

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Dunn, Kelly E; Fingerhood, Michael; Wong, Conrad J; Svikis, Dace S; Nuzzo, Paul; Silverman, Kenneth

2014-02-01

Employment-based reinforcement interventions have been used to promote abstinence from drugs among chronically unemployed injection drug users. The current study used an employment-based reinforcement intervention to promote opioid and cocaine abstinence among opioid and/or cocaine-dependent, HIV-positive participants who had recently completed a brief inpatient detoxification. Participants (n = 46) were randomly assigned to an abstinence and work group that was required to provide negative urine samples in order to enter the workplace and to earn incentives for work (n = 16), a work-only group that was permitted to enter the workplace and to earn incentives independent of drug use (n = 15), and a no-voucher control group that did not receive any incentives for working (n = 15) over a 26-week period. The primary outcome was urinalysis-confirmed opioid, cocaine, and combined opioid/cocaine abstinence. Participants were 78% male and 89% African American. Results showed no significant between-groups differences in urinalysis-verified drug abstinence or HIV risk behaviors during the 6-month intervention. The work-only group had significantly greater workplace attendance, and worked more minutes per day when compared to the no-voucher group. Several features of the study design, including the lack of an induction period, setting the threshold for entering the workplace too high by requiring immediate abstinence from several drugs, and increasing the risk of relapse by providing a brief detoxification that was not supported by any continued pharmacological intervention, likely prevented the workplace from becoming established as a reinforcer that could be used to promote drug abstinence. However, increases in workplace attendance have important implications for adult training programs.

Habituation of reinforcer effectiveness

OpenAIRE

David R Lloyd; David R Lloyd; Douglas J Medina; Larry W Hawk; Whitney D Fosco; Jerry B Richards

2014-01-01

In this paper we propose an integrative model of habituation of reinforcer effectiveness (HRE) that links behavioral and neural based explanations of reinforcement. We argue that habituation of reinforcer effectiveness (HRE) is a fundamental property of reinforcing stimuli. Most reinforcement models implicitly suggest that the effectiveness of a reinforcer is stable across repeated presentations. In contrast, an HRE approach predicts decreased effectiveness due to repeated presentation. We ar...

Structural Behavior of Concrete Beams Reinforced with Basalt Fiber Reinforced Polymer (BFRP) Bars

Science.gov (United States)

Ovitigala, Thilan

The main challenge for civil engineers is to provide sustainable, environmentally friendly and financially feasible structures to the society. Finding new materials such as fiber reinforced polymer (FRP) material that can fulfill the above requirements is a must. FRP material was expensive and it was limited to niche markets such as space shuttles and air industry in the 1960s. Over the time, it became cheaper and spread to other industries such as sporting goods in the 1980-1990, and then towards the infrastructure industry. Design and construction guidelines are available for carbon fiber reinforced polymer (CFRP), aramid fiber reinforced polymer (AFRP) and glass fiber reinforced polymer (GFRP) and they are currently used in structural applications. Since FRP is linear elastic brittle material, design guidelines for the steel reinforcement are not valid for FRP materials. Corrosion of steel reinforcement affects the durability of the concrete structures. FRP reinforcement is identified as an alternative to steel reinforcement in corrosive environments. Although basalt fiber reinforced polymer (BFRP) has many advantages over other FRP materials, but limited studies have been done. These studies didn't include larger BFRP bar diameters that are mostly used in practice. Therefore, larger beam sizes with larger BFRP reinforcement bar diameters are needed to investigate the flexural and shear behavior of BFRP reinforced concrete beams. Also, shear behavior of BFRP reinforced concrete beams was not yet studied. Experimental testing of mechanical properties and bond strength of BFRP bars and flexural and shear behavior of BFRP reinforced concrete beams are needed to include BFRP reinforcement bars in the design codes. This study mainly focuses on the use of BFRP bars as internal reinforcement. The test results of the mechanical properties of BFRP reinforcement bars, the bond strength of BFRP reinforcement bars, and the flexural and shear behavior of concrete beams

Adapting without reinforcement.

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Kheifets, Aaron; Gallistel, C Randy

2012-11-01

Our data rule out a broad class of behavioral models in which behavioral change is guided by differential reinforcement. To demonstrate this, we showed that the number of reinforcers missed before the subject shifted its behavior was not sufficient to drive behavioral change. What's more, many subjects shifted their behavior to a more optimal strategy even when they had not yet missed a single reinforcer. Naturally, differential reinforcement cannot be said to drive a process that shifts to accommodate to new conditions so adeptly that it doesn't miss a single reinforcer: it would have no input on which to base this shift.

Statistical Analysis of Compressive and Flexural Test Results on the Sustainable Adobe Reinforced with Steel Wire Mesh

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Jokhio, Gul A.; Syed Mohsin, Sharifah M.; Gul, Yasmeen

2018-04-01

It has been established that Adobe provides, in addition to being sustainable and economic, a better indoor air quality without spending extensive amounts of energy as opposed to the modern synthetic materials. The material, however, suffers from weak structural behaviour when subjected to adverse loading conditions. A wide range of mechanical properties has been reported in literature owing to lack of research and standardization. The present paper presents the statistical analysis of the results that were obtained through compressive and flexural tests on Adobe samples. Adobe specimens with and without wire mesh reinforcement were tested and the results were reported. The statistical analysis of these results presents an interesting read. It has been found that the compressive strength of adobe increases by about 43% after adding a single layer of wire mesh reinforcement. This increase is statistically significant. The flexural response of Adobe has also shown improvement with the addition of wire mesh reinforcement, however, the statistical significance of the same cannot be established.

Adding Spice to the Porridge: The development of a synthetic cannabinoid market in an English prison.

Science.gov (United States)

Ralphs, Rob; Williams, Lisa; Askew, Rebecca; Norton, Anna

2017-02-01

In 2014, the annual report of the Her Majesty's Chief Inspector of Prisons (HMIP) for England and Wales raised concerns regarding New Psychoactive Substance (NPS) use in custody, specifically the consumption of synthetic cannabinoids. To date, however, the use of these substances in prison populations, and the markets that have emerged to facilitate it, have been under-researched. Our research was conducted in an English adult male prison using multi-method techniques. These included: in-depth interviews and focus groups with prison staff and prisoners; observations of prisoner-led focus groups, workshops and restorative justice circles involving discussion of synthetic cannabinoid use and markets; and analysis of routinely collected prison data measuring drug seizures, incidents of violence and incidents of self-harm. The findings highlight: (1) the scale and nature of synthetic cannabinoid markets in a custodial setting and the motivations for establishing them; (2) the nature and motivations for synthetic cannabinoids use in prison; and (3) the impact synthetic cannabinoid markets in this setting have upon prisoners, the prison system and the wider criminal justice system. The policy implications of the stated motivations for use and reported problems are discussed in relation to both prison and community settings, and the recently implemented Psychoactive Substance Act (2016). The paper concludes that the rise in synthetic cannabinoid use in custody and the size of the drug market are posing significant challenges to the management of offenders; including healthcare, appropriate detection techniques, license recall and sanctions for both use and supply. We argue that the primary motivation for consumption in this setting is the avoidance of drug use detection, and that this is likely to supersede other motivations for consumption in the future. We propose a revision of the use of mandatory drug tests (MDTs) both in prisons and in the management of offenders in

Fatty acid amide hydrolase inhibition heightens anandamide signaling without producing reinforcing effects in primates

Science.gov (United States)

Justinova, Zuzana; Mangieri, Regina A.; Bortolato, Marco; Chefer, Svetlana I.; Mukhin, Alexey G.; Clapper, Jason R.; King, Alvin R.; Redhi, Godfrey H.; Yasar, Sevil; Piomelli, Daniele; Goldberg, Steven R.

2008-01-01

Background CB1 cannabinoid receptors in the brain are known to participate in the regulation of reward-based behaviors, however, the contribution of each of the endocannabinoid transmitters, anandamide and 2-arachidonoylglycerol (2-AG), to these behaviors remains undefined. To address this question, we assessed the effects of URB597, a selective anandamide deactivation inhibitor, as a reinforcer of drug-seeking and drug-taking behavior in squirrel monkeys. Methods We investigated the reinforcing effects of the fatty acid amide hydrolase (FAAH) inhibitor URB597 in monkeys trained to intravenously self-administer Δ9-tetrahydrocannabinol (THC), anandamide or cocaine, and quantified brain endocannabinoid levels using liquid chromatography/mass spectrometry. We measured brain FAAH activity using an ex vivo enzyme assay. Results URB597 (0.3 mg/kg, intravenous) blocked FAAH activity and increased anandamide levels throughout the monkey brain. This effect was accompanied by a marked compensatory decrease in 2-AG levels. Monkeys did not self-administer URB597 and the drug did not promote reinstatement of extinguished drug-seeking behavior previously maintained by THC, anandamide, or cocaine. Pretreatment with URB597 did not modify self-administration of THC or cocaine even though, as expected, it significantly potentiated anandamide self-administration. Conclusions In the monkey brain, the FAAH inhibitor URB597 increases anandamide levels while causing a compensatory down-regulation in 2-AG levels. These effects are accompanied by a striking lack of reinforcing properties, which distinguishes URB597 from direct-acting cannabinoid agonists such as THC. Our results reveal an unexpected functional heterogeneity within the endocannabinoid signaling system, and suggest that FAAH inhibitors might be used therapeutically without risk of abuse or triggering of relapse to drug abuse. PMID:18814866

Red Blood Cell Membrane-Cloaked Nanoparticles For Drug Delivery

Science.gov (United States)

Carpenter, Cody Westcott

Herein we describe the development of the Red Blood Cell coated nanoparticle, RBC-NP. Purified natural erythrocyte membrane is used to coat drug-loaded poly(lacticco-glycolic acid) (PLGA). Synthetic PLGA co-polymer is biocompatible and biodegradable and has already received US FDA approval for drug-delivery and diagnostics. This work looks specifically at the retention of immunosuppressive proteins on RBC-NPs, right-sidedness of natural RBC membranes interfacing with synthetic polymer nanoparticles, sustained and retarded drug release of RBC-NPs as well as further surface modification of RBC-NPs for increased targeting of model cancer cell lines.

Investigations of timing during the schedule and reinforcement intervals with wheel-running reinforcement.

Science.gov (United States)

Belke, Terry W; Christie-Fougere, Melissa M

2006-11-01

Across two experiments, a peak procedure was used to assess the timing of the onset and offset of an opportunity to run as a reinforcer. The first experiment investigated the effect of reinforcer duration on temporal discrimination of the onset of the reinforcement interval. Three male Wistar rats were exposed to fixed-interval (FI) 30-s schedules of wheel-running reinforcement and the duration of the opportunity to run was varied across values of 15, 30, and 60s. Each session consisted of 50 reinforcers and 10 probe trials. Results showed that as reinforcer duration increased, the percentage of postreinforcement pauses longer than the 30-s schedule interval increased. On probe trials, peak response rates occurred near the time of reinforcer delivery and peak times varied with reinforcer duration. In a second experiment, seven female Long-Evans rats were exposed to FI 30-s schedules leading to 30-s opportunities to run. Timing of the onset and offset of the reinforcement period was assessed by probe trials during the schedule interval and during the reinforcement interval in separate conditions. The results provided evidence of timing of the onset, but not the offset of the wheel-running reinforcement period. Further research is required to assess if timing occurs during a wheel-running reinforcement period.

Smoking synthetic marijuana leads to self-mutilation requiring bilateral amputations.

Science.gov (United States)

Meijer, Karim A; Russo, Russell R; Adhvaryu, Dhaval V

2014-04-01

Synthetic cannabinoids have become a worldwide epidemic because they provide a sometimes legal, easily accessible, and presumably safe alternative to marijuana. Recently published reports have linked acute psychosis, myocardial infarctions, convulsions, self-harm, and even terrorist organizations to these designer substances. This case report outlines the first reported case of Black Diamond, a synthetic cannabis, leading to a self-inflicted burn to the bilateral upper extremities requiring a transradial amputation of the right arm and a toe transfer procedure of the left hand after loss of all digits. The patient presented to the emergency department with self-inflicted fourth-degree burns to the bilateral hands and forearms with second-degree burns of the face, for a total body surface area of 14.5%. The patient was found by firefighters with his hands aflame on his kitchen stove. With no previous medical or psychiatric history and collateral information to confirm the patient's mental status prior to use of Black Diamond, the patient's acute psychotic episode was attributed to Black Diamond. After multiple procedures and a lengthy recovery, the patient completed his post-graduate education and entered the professional world. As orthopedic surgeons, we should be involved in educating the public on the harm of these designer drugs, including self-mutilation. The popularity of synthetic drugs in the United States will continue to present a major challenge to all health care providers. Orthopedists are on the front lines of this epidemic because these drugs push patients into risky, traumatic behavior. Copyright 2014, SLACK Incorporated.

Defining the Construct of Synthetic Androgen Intoxication: An Application of General Brain Arousal.

Science.gov (United States)

Hildebrandt, Tom; Heywood, Ashley; Wesley, Daniel; Schulz, Kurt

2018-01-01

Synthetic androgens (i. e., anabolic-androgenic steroids) are the primary component to the majority of problematic appearance and performance enhancing drug (APED) use. Despite evidence that these substances are associated with increased risk for aggression, violence, body image disturbances, and polypharmacy and can develop a pattern of chronic use consistent with drug dependence, there are no formal definitions of androgen intoxication. Consequently, the purpose of this paper is to establish a testable theory of androgen intoxication. We present evidence and theorize that synthetic androgen intoxication can be defined by a pattern of poor self-regulation characterized by increased propensity for a range of behaviors (e.g., aggression, sex, drug seeking, exercise, etc.) via androgen mediated effects on general brain arousal. This theory posits that androgens reduce threshold for emotional reactivity, motor response, and alertness to sensory stimuli and disrupt inhibitory control over the behaviors associated with synthetic androgen use. These changes result from alteration to basic neurocircuitry that amplifies limbic activation and reduces top-down cortical control. The implications for this definition are to inform APED specific hypotheses about the behavioral and psychological effects of APED use and provide a basis for establishing clinical, legal, and public health guidelines to address the use and misuse of these substances.

Defining the Construct of Synthetic Androgen Intoxication: An Application of General Brain Arousal

Directory of Open Access Journals (Sweden)

Tom Hildebrandt

2018-03-01

Full Text Available Synthetic androgens (i. e., anabolic-androgenic steroids are the primary component to the majority of problematic appearance and performance enhancing drug (APED use. Despite evidence that these substances are associated with increased risk for aggression, violence, body image disturbances, and polypharmacy and can develop a pattern of chronic use consistent with drug dependence, there are no formal definitions of androgen intoxication. Consequently, the purpose of this paper is to establish a testable theory of androgen intoxication. We present evidence and theorize that synthetic androgen intoxication can be defined by a pattern of poor self-regulation characterized by increased propensity for a range of behaviors (e.g., aggression, sex, drug seeking, exercise, etc. via androgen mediated effects on general brain arousal. This theory posits that androgens reduce threshold for emotional reactivity, motor response, and alertness to sensory stimuli and disrupt inhibitory control over the behaviors associated with synthetic androgen use. These changes result from alteration to basic neurocircuitry that amplifies limbic activation and reduces top-down cortical control. The implications for this definition are to inform APED specific hypotheses about the behavioral and psychological effects of APED use and provide a basis for establishing clinical, legal, and public health guidelines to address the use and misuse of these substances.

Drug and Alcohol Use -- A Significant Risk Factor for HIV

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Clinical toxicology of newer recreational drugs.

Science.gov (United States)

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

Enhancing corrosion resistance of reinforced concrete structures with hybrid fiber reinforced concrete

International Nuclear Information System (INIS)

Blunt, J.; Jen, G.; Ostertag, C.P.

2015-01-01

Highlights: • Reinforced concrete beams were subjected to cyclic flexural loading. • Hybrid fiber reinforced composites were effective in reducing corrosion rates. • Crack resistance due to fibers increased corrosion resistance of steel rebar. • Galvanic corrosion measurements underestimated corrosion rates. • Polarization resistance measurements predicted mass loss more accurately. - Abstract: Service loads well below the yield strength of steel reinforcing bars lead to cracking of reinforced concrete. This paper investigates whether the crack resistance of Hybrid Fiber Reinforced Concrete (HyFRC) reduces the corrosion rate of steel reinforcing bars in concrete after cyclic flexural loading. The reinforcing bars were extracted to examine their surface for corrosion and compare microcell and macrocell corrosion mass loss estimates against direct gravimetric measurements. A delay in corrosion initiation and lower active corrosion rates were observed in the HyFRC beam specimens when compared to reinforced specimens containing plain concrete matrices cycled at the same flexural load

Natural - synthetic - artificial!

DEFF Research Database (Denmark)

Nielsen, Peter E

2010-01-01

The terms "natural," "synthetic" and "artificial" are discussed in relation to synthetic and artificial chromosomes and genomes, synthetic and artificial cells and artificial life.......The terms "natural," "synthetic" and "artificial" are discussed in relation to synthetic and artificial chromosomes and genomes, synthetic and artificial cells and artificial life....

Examination of the effects of varenicline, bupropion, lorcaserin, or naltrexone on responding for conditioned reinforcement in nicotine-exposed rats.

Science.gov (United States)

Guy, Elizabeth G; Fisher, Daniel C; Higgins, Guy A; Fletcher, Paul J

2014-12-01

Smoking tobacco remains one of the leading causes of preventable deaths in North America. Nicotine reinforces smoking behavior, in part, by enhancing the reinforcing properties of reward-related stimuli, or conditioned stimuli (CSs), associated with tobacco intake. To investigate how pharmaceutical interventions may affect this property of nicotine, we examined the effect of four US Food and Drug Administration (FDA) approved drugs on the ability of nicotine to enhance operant responding for a CS as a conditioned reinforcer. Thirsty rats were exposed to 13 Pavlovian sessions where a CS was paired with water delivery. Nicotine (0.4 mg/kg) injections were administered before each Pavlovian session. Then, in separate groups of rats, the effects of varenicline (1 mg/kg), bupropion (10 and 30 mg/kg), lorcaserin (0.6 mg/kg), and naltrexone (2 mg/kg), and their interaction with nicotine on responding for conditioned reinforcement were examined. Varenicline and lorcaserin each reduced nicotine-enhanced responding for conditioned reinforcement, whereas naltrexone had a modest effect of reducing response enhancements by nicotine. In contrast, bupropion enhanced the effect of nicotine on this measure. The results of these studies may inform how pharmaceutical interventions can affect smoking cessation attempts and relapse through diverse mechanisms, either substituting for, or interacting with, the reinforcement-enhancing properties of nicotine.

Synthetic marijuana "K2" induced ITP.

Science.gov (United States)

Öztürk, Erman; Oral, Alihan; Özdemir, Melek; Bambul, Nail

2015-01-01

Immune thrombocytopenia (ITP) is a heterogeneous disease which can be primary or secondary due to other conditions such as drugs. CB2 receptors (CB2R) also have a role in the ITP pathogenesis as CB2 receptor gene (CNR2) polymorphisms are associated with chronic immune thrombocytopenia and autoimmune diseases. K2 is synthetic marijuana which acts on cannabinoid receptors that are found on immune cells and thrombocytes. Here, we present a case who presented with ITP secondary to K2 usage and was successfully treated with 1 mg/kg prednisolone. This is the first ITP case in the literature due to K2. It is important in the era of the new drugs development of the CB2R mimetics.

Employment-Based Abstinence Reinforcement as a Maintenance Intervention for the Treatment of Cocaine Dependence: A Randomized Controlled Trial

Science.gov (United States)

DeFulio, Anthony; Donlin, Wendy D.; Wong, Conrad J.; Silverman, Kenneth

2009-01-01

Context: Due to the chronic nature of cocaine dependence, long-term maintenance treatments may be required to sustain abstinence. Abstinence reinforcement is among the most effective means of initiating cocaine abstinence. Practical and effective means of maintaining abstinence reinforcement programs over time are needed. Objective: Determine whether employment-based abstinence reinforcement can be an effective long-term maintenance intervention for cocaine dependence. Design: Participants (N=128) were enrolled in a 6-month job skills training and abstinence initiation program. Participants who initiated abstinence, attended regularly, and developed needed job skills during the first six months were hired as operators in a data entry business and randomly assigned to an employment only (Control, n = 24) or abstinence-contingent employment (n = 27) group. Setting: A nonprofit data entry business. Participants: Unemployed welfare recipients who persistently used cocaine while enrolled in methadone treatment in Baltimore. Intervention: Abstinence-contingent employment participants received one year of employment-based contingency management, in which access to employment was contingent on provision drug-free urine samples under routine and then random drug testing. If a participant provided drug-positive urine or failed to provide a mandatory sample, then that participant received a temporary reduction in pay and could not work until urinalysis confirmed recent abstinence. Main Outcome Measure: Cocaine-negative urine samples at monthly assessments across one year of employment. Results: During the one-year of employment, abstinence-contingent employment participants provided significantly more cocaine-negative urine samples than employment only participants (79.3% and 50.7%, respectively; p = 0.004, OR = 3.73, 95% CI = 1.60 – 8.69). Conclusions: Employment-based abstinence reinforcement that includes random drug testing is effective as a long-term maintenance

Synthetic risks, risk potency, and carcinogen regulation.

Science.gov (United States)

Viscusi, W K; Hakes, J K

1998-01-01

This article analyzes a comprehensive sample of over 350 chemicals tested for carcinogenicity to assess the determinants of the probability of regulation. Controlling for differences in the risk potency and noncancer risks, synthetic chemicals have a significantly higher probability of regulation overall: this is due to the greater likelihood of U.S. Food and Drug Administration (FDA) regulation. Measures of risk potency increase the probability of regulation by the U.S. Environmental Protection Agency (EPA), have a somewhat weaker positive effect on regulation by the U.S. Occupational Safety and Health Administration (OSHA), and decrease the likelihood of regulation by the FDA. The overall regulatory pattern is one in which the FDA targets synthetic chemicals and chemicals that pose relatively minor cancer risk. The EPA particularly performed more sensibly than many critics have suggested.

Prospects for applying synthetic biology to toxicology

DEFF Research Database (Denmark)

Behrendorff, James Bruce Yarnton H; Gillam, Elizabeth M.J.

2017-01-01

The 30 years since the inception of Chemical Research in Toxicology, game-changing advances in chemical and molecular biology, the fundamental disciplines underpinning molecular toxicology, have been made. While these have led to important advances in the study of mechanisms by which chemicals...... damage cells and systems, there has been less focus on applying these advances to prediction, detection, and mitigation of toxicity. Over the last ∼15 years, synthetic biology, the repurposing of biological "parts" in systems engineered for useful ends, has been explored in other areas of the biomedical...... and life sciences, for such applications as detecting metabolites, drug discovery and delivery, investigating disease mechanisms, improving medical treatment, and producing useful chemicals. These examples provide models for the application of synthetic biology to toxicology, which, for the most part, has...

Theoretical and numerical analysis of reinforced concrete beams with confinement reinforcement

Directory of Open Access Journals (Sweden)

R. G. Delalibera

Full Text Available This paper discusses the use of confinement in over-reinforced concrete beams. This reinforcement consists of square stirrups, placed in the compression zone of the beam cross-section, in order to improve its ductility. A parametric numerical study is initially performed, using a finite element computational program that considers the material nonlinearities and the confinement effect. To investigate the influence of the transverse reinforcing ratio on the beam ductility, an experimental program was also conducted. Four over-reinforced beams were tested; three beam specimens with additional transverse reinforcement to confine the beams, and one without it. All specimens were fabricated with a concrete designed for a compressive strength of 25 MPa. The experimental results show that the post-peak ductility factor is proportional to the confining reinforcement ratio, however the same is not observed for the pre-peak ductility factor, which varied randomly with changes in the confining reinforcement ratio. It was also observed from the experiments that the confinement effect tends to be smaller close to the beam neutral axis.

Detection and cellular localisation of the synthetic soluble macromolecular drug carrier pHPMA

Energy Technology Data Exchange (ETDEWEB)

Kissel, Maria; Peschke, Peter; Strunz, Anke M.; Kuehnlein, Rainer; Debus, Juergen [Department of Radiation Oncology, E0505, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Subr, Vladimir; Ulbrich, Karel [Institute of Macromolecular Chemistry, Prague (Czech Republic); Friedrich, Eckhard [Division of Biology, University of Koblenz-Landau, Landau (Germany)

2002-08-01

Synthetic macromolecules such as copolymers of N-(2-hydroxypropyl)methacrylamide (pHPMA) are potential carriers for the delivery of drugs owing to their ability to passively accumulate in solid tumours [enhanced permeation and retention (EPR) effect]. To gain further knowledge about the biodistribution and the cellular localisation, poly(HPMA) was prepared for labelling by introducing biotin molecules. Biotinylated pHPMA (5 mol%) was intravenously injected into tumour-bearing rats and the accumulation of biotin-pHPMA was visualised using a streptavidin-alkaline phosphatase technique at day 7 post injection. In spite of the high solubility of pHPMA copolymers and the lack of attachment to cell structures, the biotinylated polymer could be easily detected in tissues fixed in 10% paraformaldehyde-phosphate buffer at 4 C for 48 h. While biotin-pHPMA could be detected intracytoplasmically in liver and spleen, a predominantly interstitial localisation was observed within the anaplastic prostate carcinoma (Dunning R3327-AT1). How biotin as a label influences the biodistribution of poly(HPMA) was assessed by scintigraphy, autoradiography and histology comparing homopolymer poly(HPMA) with biotin-pHPMA. The organ distribution patterns of the two polymers correlated well, except with respect to kidney. It is assumed that the accumulation of biotin-pHPMA in the distal tubuli is due to a biotin transporter in the brush border membrane. The technique presented is useful for a more comprehensive understanding of the biodistribution of soluble macromolecules. (orig.)

Detection and cellular localisation of the synthetic soluble macromolecular drug carrier pHPMA

International Nuclear Information System (INIS)

Kissel, Maria; Peschke, Peter; Strunz, Anke M.; Kuehnlein, Rainer; Debus, Juergen; Subr, Vladimir; Ulbrich, Karel; Friedrich, Eckhard

2002-01-01

Synthetic macromolecules such as copolymers of N-(2-hydroxypropyl)methacrylamide (pHPMA) are potential carriers for the delivery of drugs owing to their ability to passively accumulate in solid tumours [enhanced permeation and retention (EPR) effect]. To gain further knowledge about the biodistribution and the cellular localisation, poly(HPMA) was prepared for labelling by introducing biotin molecules. Biotinylated pHPMA (5 mol%) was intravenously injected into tumour-bearing rats and the accumulation of biotin-pHPMA was visualised using a streptavidin-alkaline phosphatase technique at day 7 post injection. In spite of the high solubility of pHPMA copolymers and the lack of attachment to cell structures, the biotinylated polymer could be easily detected in tissues fixed in 10% paraformaldehyde-phosphate buffer at 4 C for 48 h. While biotin-pHPMA could be detected intracytoplasmically in liver and spleen, a predominantly interstitial localisation was observed within the anaplastic prostate carcinoma (Dunning R3327-AT1). How biotin as a label influences the biodistribution of poly(HPMA) was assessed by scintigraphy, autoradiography and histology comparing homopolymer poly(HPMA) with biotin-pHPMA. The organ distribution patterns of the two polymers correlated well, except with respect to kidney. It is assumed that the accumulation of biotin-pHPMA in the distal tubuli is due to a biotin transporter in the brush border membrane. The technique presented is useful for a more comprehensive understanding of the biodistribution of soluble macromolecules. (orig.)

Antagonistic effects on mechanical properties of microfibrillar composites with dual reinforcement: explanation by FEA model of soft interface

Czech Academy of Sciences Publication Activity Database

Kelnar, Ivan; Kratochvíl, Jaroslav; Kaprálková, Ludmila; Zhigunov, Alexander; Padovec, Z.; Růžička, M.; Nevoralová, Martina

2017-01-01

Roč. 134, č. 20 (2017), s. 1-9, č. článku 44712. ISSN 0021-8995 R&D Projects: GA ČR(CZ) GA13-15255S Institutional support: RVO:61389013 Keywords : finite element analysis * interface * microfibrillar composites Subject RIV: JI - Composite Materials OBOR OECD: Composites (including laminates, reinforced plastics, cermets, combined natural and synthetic fibre fabrics Impact factor: 1.860, year: 2016

Rapid and sensitive detection of synthetic cannabinoids AMB-FUBINACA and α-PVP using surface enhanced Raman scattering (SERS)

Science.gov (United States)

Islam, Syed K.; Cheng, Yin Pak; Birke, Ronald L.; Green, Omar; Kubic, Thomas; Lombardi, John R.

2018-04-01

The application of surface enhanced Raman scattering (SERS) has been reported as a fast and sensitive analytical method in the trace detection of the two most commonly known synthetic cannabinoids AMB-FUBINACA and alpha-pyrrolidinovalerophenone (α-PVP). FUBINACA and α-PVP are two of the most dangerous synthetic cannabinoids which have been reported to cause numerous deaths in the United States. While instruments such as GC-MS, LC-MS have been traditionally recognized as analytical tools for the detection of these synthetic drugs, SERS has been recently gaining ground in the analysis of these synthetic drugs due to its sensitivity in trace analysis and its effectiveness as a rapid method of detection. This present study shows the limit of detection of a concentration as low as picomolar for AMB-FUBINACA while for α-PVP, the limit of detection is in nanomolar concentration using SERS.

Sex differences in the vulnerability to drug abuse: a review of preclinical studies.

Science.gov (United States)

Roth, Megan E; Cosgrove, Kelly P; Carroll, Marilyn E

2004-10-01

Clinical and preclinical findings indicate that males and females differ on several aspects of drug reinforcement. Females are more vulnerable than males during transition periods of drug use that are characteristic of drug addiction and relapse. Females are also more sensitive than males to the reinforcing effects of stimulants. It has been suggested that ovarian hormones contribute to the mechanisms of action underlying these sex differences. This review examines the preclinical literature on sex differences and ovarian hormonal influences on drug self-administration in animals. It summarizes the findings on the effects of these variables during different phases of drug addiction. Possible differences in the mechanisms of action of drugs of abuse due to interactions with sex differences or ovarian hormonal factors are considered. The animal literature on sex differences in drug abuse treatment effectiveness is also discussed.

New Drugs of Abuse and Withdrawal Syndromes.

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Andrabi, Sara; Greene, Spencer; Moukaddam, Nidal; Moukkadam, Nidal; Li, Benjamin

2015-11-01

New drugs of abuse continue to emerge, including synthetic cannabinoids, synthetic cathinones, and hallucinogens. It is important to recognize their individual psychopharmacologic properties, symptoms of intoxication, and symptoms of withdrawal. Providers must be vigilant of acute medical or psychiatric complications that may arise from use of these substances. Treatment of the patient also includes recognition of any substance use disorders as well as comorbid psychiatric disorders. Although pharmacologic treatments for substance use disorder (of the drugs included in this article) are limited, there are a variety of psychotherapeutic modalities that may be of some benefit. Published by Elsevier Inc.

Enhancement of a visual reinforcer by D-amphetamine and nicotine in adult rats: relation to habituation and food restriction.

Science.gov (United States)

Wright, Jennifer M; Ren, Suelynn; Constantin, Annie; Clarke, Paul B S

2018-03-01

Nicotine and D-amphetamine can strengthen reinforcing effects of unconditioned visual stimuli. We investigated whether these reinforcement-enhancing effects reflect a slowing of stimulus habituation and depend on food restriction. Adult male rats pressed an active lever to illuminate a cue light during daily 60-min sessions. Depending on the experiment, rats were challenged with fixed or varying doses of D-amphetamine (0.25-2 mg/kg IP) and nicotine (0.025-0.2 mg/kg SC) or with the tobacco constituent norharman (0.03-10 μg/kg IV). Experiment 1 tested for possible reinforcement-enhancing effects of D-amphetamine and norharman. Experiment 2 investigated whether nicotine and amphetamine inhibited the spontaneous within-session decline in lever pressing. Experiment 3 assessed the effects of food restriction. Amphetamine (0.25-1 mg/kg) and nicotine (0.1 mg/kg) increased active lever pressing specifically (two- to threefold increase). The highest doses of nicotine and amphetamine also affected inactive lever responding (increase and decrease, respectively). With the visual reinforcer omitted, responding was largely extinguished. Neither drug appeared to slow habituation, as assessed by the within-session decline in lever pressing, and reinforcement-enhancing effects still occurred if the drugs were given after this decline had occurred. Food restriction enhanced the reinforcement-enhancing effect of amphetamine but not that of nicotine. Responding remained goal-directed after several weeks of testing. Low doses of D-amphetamine and nicotine produced reinforcement enhancement even in free-feeding subjects, independent of the spontaneous within-session decline in responding. Reinforcement enhancement by amphetamine, but not nicotine, was enhanced by concurrent subchronic food restriction.

Axial Compression Tests on Corroded Reinforced Concrete Columns Consolidated with Fibre Reinforced Polymers

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Bin Ding

2017-06-01

Full Text Available Reinforced concrete structure featured by strong bearing capacity, high rigidity, good integrity, good fire resistance, and extensive applicability occupies a mainstream position in contemporary architecture. However, with the development of social economy, people need higher requirements on architectural structure; durability, especially, has been extensively researched. Because of the higher requirement on building material, ordinary reinforced concrete structure has not been able to satisfy the demand. As a result, some new materials and structures have emerged, for example, fibre reinforced polymers. Compared to steel reinforcement, fibre reinforced polymers have many advantages, such as high tensile strength, good durability, good shock absorption, low weight, and simple construction. The application of fibre reinforced polymers in architectural structure can effectively improve the durability of the concrete structure and lower the maintenance, reinforcement, and construction costs in severe environments. Based on the concepts of steel tube concrete, fibre reinforced composite material confined concrete, and fibre reinforced composite material tubed concrete, this study proposes a novel composite structure, i.e., fibre reinforced composite material and steel tube concrete composite structure. The structure was developed by pasting fibre around steel tube concrete and restraining core concrete using fibre reinforced composite material and steel tubes. The bearing capacity and ultimate deformation capacity of the structure was tested using column axial compression test.

Drugs + HIV, Learn the Link

Medline Plus

Full Text Available ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) ...

Synthetic cannabinoid and marijuana exposures reported to poison centers.

Science.gov (United States)

Forrester, M B; Kleinschmidt, K; Schwarz, E; Young, A

2012-10-01

Synthetic cannabinoids have recently gained popularity as a recreational drug because they are believed to result in a marijuana-like high. This investigation compared synthetic cannabinoids and marijuana exposures reported to a large statewide poison center system. Synthetic cannabinoid and marijuana exposures reported to Texas poison centers during 2010 were identified. The distribution of exposures to the two agents with respect to various demographic and clinical factors were compared by calculating the rate ratio (RR) of the synthetic cannabinoid and marijuana percentages for each subgroup and 95% confidence interval (CI). The proportion of synthetic cannabinoid and marijuana exposures, respectively, were 87.3% and 46.5% via inhalation (RR 1.88, 95% CI 1.38-2.61), 74.9% and 65.7% in male (RR 1.14, 95% CI 0.87-1.51), 40.2% and 56.6% age ≤ 19 years (RR 0.71, 95% CI 0.52-0.98), 79.2% and 58.6% occurring at a residence (RR 1.35, 95% CI 1.02-1.82), 8.4% and 16.2% managed on-site (RR 0.52. 95% CI 0.28-1.00), and 59.3% and 41.4% with serious medical outcomes (RR 1.43, 95% CI 1.03-2.05). Compared to marijuana, synthetic cannabinoid exposures were more likely to be used through inhalation, to involve adults, to be used at a residence, and to result in serious outcomes.

Animal models of drug addiction.

Science.gov (United States)

García Pardo, María Pilar; Roger Sánchez, Concepción; De la Rubia Ortí, José Enrique; Aguilar Calpe, María Asunción

2017-09-29

The development of animal models of drug reward and addiction is an essential factor for progress in understanding the biological basis of this disorder and for the identification of new therapeutic targets. Depending on the component of reward to be studied, one type of animal model or another may be used. There are models of reinforcement based on the primary hedonic effect produced by the consumption of the addictive substance, such as the self-administration (SA) and intracranial self-stimulation (ICSS) paradigms, and there are models based on the component of reward related to associative learning and cognitive ability to make predictions about obtaining reward in the future, such as the conditioned place preference (CPP) paradigm. In recent years these models have incorporated methodological modifications to study extinction, reinstatement and reconsolidation processes, or to model specific aspects of addictive behavior such as motivation to consume drugs, compulsive consumption or drug seeking under punishment situations. There are also models that link different reinforcement components or model voluntary motivation to consume (two-bottle choice, or drinking in the dark tests). In short, innovations in these models allow progress in scientific knowledge regarding the different aspects that lead individuals to consume a drug and develop compulsive consumption, providing a target for future treatments of addiction.

Biomaterials for drug delivery patches.

Science.gov (United States)

Santos, Lúcia F; Correia, Ilídio J; Silva, A Sofia; Mano, João F

2018-06-15

The limited efficiency of conventional drugs has been instigated the development of new and more effective drug delivery systems (DDS). Transdermal DDS, are associated with numerous advantages such its painless application and less frequent replacement and greater flexibility of dosing, features that triggered the research and development of such devices. Such systems have been produced using either biopolymer; or synthetic polymers. Although the first ones are safer, biocompatible and present a controlled degradation by human enzymes or water, the second ones are the most currently available in the market due to their greater mechanical resistance and flexibility, and non-degradation over time. This review highlights the most recent advances (mainly in the last five years) of patches aimed for transdermal drug delivery, focusing on the different materials (natural, synthetic and blends) and latest designs for the development of such devices, emphasizing also their combination with drug carriers that enable enhanced drug solubility and a more controlled release of the drug over the time. The benefits and limitations of different patches formulations are considered with reference to their appliance to transdermal drug delivery. Furthermore, a record of the currently available patches on the market is given, featuring their most relevant characteristics. Finally, a list of most recent/ongoing clinical trials regarding the use of patches for skin disorders is detailed and critical insights on the current state of patches for transdermal drug delivery are also provided. Copyright © 2018. Published by Elsevier B.V.

Haloperidol differentially affects reinforcement and motivational processes in rats running an alley for intravenous heroin.

Science.gov (United States)

McFarland, K; Ettenberg, A

1995-12-01

The role of drug-paired environmental stimuli in opiate self-administration was investigated by exposing animals to discrete cues that were predictive of the availability or unavailability of heroin reinforcement. Rats were trained to traverse a straight arm runway for a reinforcement consisting of a single 0.1 mg/kg intravenous infusion of heroin delivered upon entrance to the goal box. On each trial, one of two discriminative olfactory stimuli (orange and almond) was used: one which signaled the availability of heroin in the goal box (S+), and one which signaled its absence (S-). The effect of dopamine (DA) receptor antagonism on reinforcement and motivational processes was investigated by pretreating subjects with 0.0, 0.15 or 0.30 mg/kg of the DA receptor antagonist drug, haloperidol. Haloperidol had no effect on operant runway performance (i.e. goal time) in any condition. However, 24 h later, on the first post-treatment trial, those haloperidol animals that received heroin in the goal box on the previous trial (i.e. the S+ condition) ran reliably more slowly than subjects that received vehicle on the previous S+ trial. These results suggest that haloperidol does not affect the motivational properties of stimuli which predict the availability of heroin, while it does diminish the reinforcing effects of actually receiving heroin.

Effect of ionizing radiation on polypropylene composites reinforced with coconut fibers

Energy Technology Data Exchange (ETDEWEB)

Miranda, Leila F.; Pereira, Nilson C.; Faldini, Sonia B.; Masson, Terezinha J.; Silveira, Luiz H., E-mail: lfmiranda@sti.com.b [Universidade Presbiteriana Mackenzie, Sao Paulo, SP (Brazil). Escola de Engenharia. Curso de Engenharia de Materiais; Silva, Leonardo G. de Andrade e, E-mail: lgasilva@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2009-07-01

The use of the polymeric composite materials has been increasing but these materials have environmental problems related to the discard. To reduce the discard deleterious effect, coconuts, sisal, as well as sugar cane pulp natural based fiber have been studied to replace the synthetic ones. These fibers embedded in a polymeric matrix plays a similar role as the synthetic ones, in terms of mechanical and thermal properties. The natural fibers are environmentally friendly, easy to recycle and biodegradable. The aim of this work is the study of ionizing radiation effects on the properties of recycled polypropylene composites, reinforced with 10%, 15% and 20% of the coconut fibers, using as coupling agent a substance based on maleic anhydride (MAPP) graphitized polypropylene. The samples were molded by injection, irradiated and submitted to thermal and mechanical tests. The mechanical properties (hardness, impact strength and tensile strength), temperature of thermal distortion (HDT) and Vicat softening temperature of the non irradiated and irradiated composites were determined. The irradiation doses were of 30, 50 and 100kGy in a gamma cell. Regarding the thermal and mechanical properties of non-irradiated samples, the incorporation of coconut fibers to polypropylene resulted in a decrease of impact strength, tensile strength and Vicat softening temperature as well as in an increase in hardness and HDT. This result indicates that the coconut fibers do not act like a reinforcement agent but as biodegradable filler. In the irradiated samples, it was observed a decrease in the impact strength, tensile strength, HDT, and thermal distortion temperature and an increase in the hardness and tensile strength. The Vicat softening temperature shows no change. (author)

Effect of ionizing radiation on polypropylene composites reinforced with coconut fibers

International Nuclear Information System (INIS)

Miranda, Leila F.; Pereira, Nilson C.; Faldini, Sonia B.; Masson, Terezinha J.; Silveira, Luiz H.

2009-01-01

The use of the polymeric composite materials has been increasing but these materials have environmental problems related to the discard. To reduce the discard deleterious effect, coconuts, sisal, as well as sugar cane pulp natural based fiber have been studied to replace the synthetic ones. These fibers embedded in a polymeric matrix plays a similar role as the synthetic ones, in terms of mechanical and thermal properties. The natural fibers are environmentally friendly, easy to recycle and biodegradable. The aim of this work is the study of ionizing radiation effects on the properties of recycled polypropylene composites, reinforced with 10%, 15% and 20% of the coconut fibers, using as coupling agent a substance based on maleic anhydride (MAPP) graphitized polypropylene. The samples were molded by injection, irradiated and submitted to thermal and mechanical tests. The mechanical properties (hardness, impact strength and tensile strength), temperature of thermal distortion (HDT) and Vicat softening temperature of the non irradiated and irradiated composites were determined. The irradiation doses were of 30, 50 and 100kGy in a gamma cell. Regarding the thermal and mechanical properties of non-irradiated samples, the incorporation of coconut fibers to polypropylene resulted in a decrease of impact strength, tensile strength and Vicat softening temperature as well as in an increase in hardness and HDT. This result indicates that the coconut fibers do not act like a reinforcement agent but as biodegradable filler. In the irradiated samples, it was observed a decrease in the impact strength, tensile strength, HDT, and thermal distortion temperature and an increase in the hardness and tensile strength. The Vicat softening temperature shows no change. (author)

Synthetic Effect of Vivid Shark Skin and Polymer Additive on Drag Reduction Reinforcement

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Huawei Chen

2014-06-01

Full Text Available Natural shark skin has a well-demonstrated drag reduction function, which is mainly owing to its microscopic structure and mucus on the body surface. In order to improve drag reduction, it is necessary to integrate microscopic drag reduction structure and drag reduction agent. In this study, two hybrid approaches to synthetically combine vivid shark skin and polymer additive, namely, long-chain grafting and controllable polymer diffusion, were proposed and attempted to mimic such hierarchical topography of shark skin without waste of polymer additive. Grafting mechanism and optimization of diffusion port were investigated to improve the efficiency of the polymer additive. Superior drag reduction effects were validated, and the combined effect was also clarified through comparison between drag reduction experiments.

Human Drug Discrimination: Elucidating the Neuropharmacology of Commonly Abused Illicit Drugs.

Science.gov (United States)

Bolin, B Levi; Alcorn, Joseph L; Reynolds, Anna R; Lile, Joshua A; Stoops, William W; Rush, Craig R

2016-06-07

Drug-discrimination procedures empirically evaluate the control that internal drug states have over behavior. They provide a highly selective method to investigate the neuropharmacological underpinnings of the interoceptive effects of drugs in vivo. As a result, drug discrimination has been one of the most widely used assays in the field of behavioral pharmacology. Drug-discrimination procedures have been adapted for use with humans and are conceptually similar to preclinical drug-discrimination techniques in that a behavior is differentially reinforced contingent on the presence or absence of a specific interoceptive drug stimulus. This chapter provides a basic overview of human drug-discrimination procedures and reviews the extant literature concerning the use of these procedures to elucidate the underlying neuropharmacological mechanisms of commonly abused illicit drugs (i.e., stimulants, opioids, and cannabis) in humans. This chapter is not intended to review every available study that used drug-discrimination procedures in humans. Instead, when possible, exemplary studies that used a stimulant, opioid, or Δ 9 -tetrahydrocannabinol (the primary psychoactive constituent of cannabis) to assess the discriminative-stimulus effects of drugs in humans are reviewed for illustrative purposes. We conclude by commenting on the current state and future of human drug-discrimination research.

A Novel Drug-Mouse Phenotypic Similarity Method Detects Molecular Determinants of Drug Effects.

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Jeanette Prinz

2016-09-01

Full Text Available The molecular mechanisms that translate drug treatment into beneficial and unwanted effects are largely unknown. We present here a novel approach to detect gene-drug and gene-side effect associations based on the phenotypic similarity of drugs and single gene perturbations in mice that account for the polypharmacological property of drugs. We scored the phenotypic similarity of human side effect profiles of 1,667 small molecules and biologicals to profiles of phenotypic traits of 5,384 mouse genes. The benchmarking with known relationships revealed a strong enrichment of physical and indirect drug-target connections, causative drug target-side effect links as well as gene-drug links involved in pharmacogenetic associations among phenotypically similar gene-drug pairs. The validation by in vitro assays and the experimental verification of an unknown connection between oxandrolone and prokineticin receptor 2 reinforces the ability of this method to provide new molecular insights underlying drug treatment. Thus, this approach may aid in the proposal of novel and personalized treatments.

Flexural strength using Steel Plate, Carbon Fiber Reinforced Polymer (CFRP) and Glass Fiber Reinforced Polymer (GFRP) on reinforced concrete beam in building technology

Science.gov (United States)

Tarigan, Johannes; Patra, Fadel Muhammad; Sitorus, Torang

2018-03-01

Reinforced concrete structures are very commonly used in buildings because they are cheaper than the steel structures. But in reality, many concrete structures are damaged, so there are several ways to overcome this problem, by providing reinforcement with Fiber Reinforced Polymer (FRP) and reinforcement with steel plates. Each type of reinforcements has its advantages and disadvantages. In this study, researchers discuss the comparison between flexural strength of reinforced concrete beam using steel plates and Fiber Reinforced Polymer (FRP). In this case, the researchers use Carbon Fiber Reinforced Polymer (CFRP) and Glass Fiber Reinforced Polymer (GFRP) as external reinforcements. The dimension of the beams is 15 x 25 cm with the length of 320 cm. Based on the analytical results, the strength of the beam with CFRP is 1.991 times its initial, GFRP is 1.877 times while with the steel plate is 1.646 times. Based on test results, the strength of the beam with CFRP is 1.444 times its initial, GFRP is 1.333 times while the steel plate is 1.167 times. Based on these test results, the authors conclude that beam with CFRP is the best choice for external reinforcement in building technology than the others.

Building synthetic sterols computationally – unlocking the secrets of evolution?

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Tomasz eRog

2015-08-01

Full Text Available Cholesterol is vital in regulating the physical properties of animal cell membranes. While it remains unclear what renders cholesterol so unique, it is known that other sterols are less capable in modulating membrane properties, and there are membrane proteins whose function is dependent on cholesterol. Practical applications of cholesterol include e.g. its use in liposomes in drug delivery and cosmetics, cholesterol-based detergents in membrane protein crystallography, and its fluorescent analogs in studies of cholesterol transport in cells and tissues. Clearly, in spite of their difficult synthesis, producing the synthetic analogs of cholesterol is of great commercial and scientific interest. In this article, we discuss how synthetic sterols nonexistent in nature can be used to elucidate the roles of cholesterol's structural elements. To this end, we discuss recent atomistic molecular dynamics simulation studies that have predicted new synthetic sterols with properties comparable to those of cholesterol. We also discuss more recent experimental studies that have vindicated these predictions. The paper highlights the strength of computational simulations in making predictions for synthetic biology, thereby guiding experiments.

Plant synthetic biology.

Science.gov (United States)

Liu, Wusheng; Stewart, C Neal

2015-05-01

Plant synthetic biology is an emerging field that combines engineering principles with plant biology toward the design and production of new devices. This emerging field should play an important role in future agriculture for traditional crop improvement, but also in enabling novel bioproduction in plants. In this review we discuss the design cycles of synthetic biology as well as key engineering principles, genetic parts, and computational tools that can be utilized in plant synthetic biology. Some pioneering examples are offered as a demonstration of how synthetic biology can be used to modify plants for specific purposes. These include synthetic sensors, synthetic metabolic pathways, and synthetic genomes. We also speculate about the future of synthetic biology of plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reinforcing effects of methamphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder-the Spontaneously Hypertensive Rat

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Ryu Jong

2010-12-01

Full Text Available Abstract Substrains of the Spontaneously Hypertensive rat (SHR, a putative animal model of Attention-Deficit/Hyperactivity Disorder (ADHD, have demonstrated increased sensitivity to many drugs of abuse, including psychostimulants. Therefore, it was suggested that studies in SHR may help elucidate ADHD and comorbidity with substance use disorder (SUD. However, the drug intake profile of the SHR in the most relevant animal model of drug addiction, the self-administration (SA test, and its response on the conditioned place preference (CPP paradigm are not yet determined. In the present study, we employed SA and CPP tests to investigate the reinforcing effects of the psychostimulant methamphetamine in an SHR substrain obtained from Charles River, Japan (SHR/NCrlCrlj. Concurrent tests were also performed in Wistar rats, the strain representing "normal" heterogeneous population. To address if the presence of ADHD behaviors further increases sensitivity to the rewarding effect of methamphetamine during adolescence, a critical period for the onset of drug abuse, CPP tests were especially conducted in adolescent Wistar and SHR/NCrlCrlj. We found that the SHR/NCrlCrlj also acquired methamphetamine SA and CPP, indicating reinforcing effects of methamphetamine in this ADHD animal model. However, we did not observe increased responsiveness of the SHR/NCrlCrlj to methamphetamine in both SA and CPP assays. This indicates that the reinforcing effects of methamphetamine may be similar in strains and that the SHR/NCrlCrlj may not adequately model ADHD and increased sensitivity to methamphetamine.

Impact of Drug Metabolism/Pharmacokinetics and Their Relevance upon Taxus-based Drug Development.

Science.gov (United States)

Hao, Da-Cheng; Ge, Guang-Bo; Wang, Ping; Yang, Ling

2018-05-22

Drug metabolism and pharmacokinetic (DMPK) studies of Taxus natural products, their semi-synthetic derivatives and analogs are indispensable in the optimization of lead compounds and clinical therapy. These studies can lead to development of new drug entities with improved absorption, distribution, metabolism, excretion and toxicity (ADME/T) profiles. To date, there have been no comprehensive reviews of the DMPK features of Taxus derived medicinal compounds.Natural and semi-synthetic taxanes may cause and could be affected by drug-drug interaction (DDI). Hence ADME/T studies of various taxane-containing formulations are important; to date these studies indicate that the role of cytochrome p450s and drug transporters is more prominent than phase II drug metabolizing enzymes. Mechanisms of taxane DMPK mediated by nuclear receptors, microRNAs, and single nucleotide polymorphisms are being revealed. Herein we review the latest knowledge on these topics, as well as the gaps in knowledge of the DMPK issues of Taxus compounds. DDIs significantly impact the PK/pharmacodynamics performance of taxanes and co-administered chemicals, which may inspire researchers to develop novel formula. While the ADME/T profiles of some taxanes are well defined, DMPK studies should be extended to more Taxus compounds, species, and Taxus -involved formulations, which would be streamlined by versatile omics platforms and computational analyses. Further biopharmaceutical investigations will be beneficial tothe translation of bench findings to the clinical applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Sortase A: an ideal target for anti-virulence drug development.

Science.gov (United States)

Cascioferro, Stella; Totsika, Makrina; Schillaci, Domenico

2014-12-01

Sortase A is a membrane enzyme responsible for the anchoring of surface-exposed proteins to the cell wall envelope of Gram-positive bacteria. As a well-studied member of the sortase subfamily catalysing the cell wall anchoring of important virulence factors to the surface of staphylococci, enterococci and streptococci, sortase A plays a critical role in Gram-positive bacterial pathogenesis. It is thus considered a promising target for the development of new anti-infective drugs that aim to interfere with important Gram-positive virulence mechanisms, such as adhesion to host tissues, evasion of host defences, and biofilm formation. The additional properties of sortase A as an enzyme that is not required for Gram-positive bacterial growth or viability and is conveniently located on the cell membrane making it more accessible to inhibitor targeting, constitute additional reasons reinforcing the view that sortase A is an ideal target for anti-virulence drug development. Many inhibitors of sortase A have been identified to date using high-throughput or in silico screening of compound libraries (synthetic or natural), and while many have proved useful tools for probing the action model of the enzyme, several are also promising candidates for the development into potent inhibitors. This review is focused on the most promising sortase A inhibitor compounds that are currently in development as leads towards a new class of anti-infective drugs that are urgently needed to help combat the alarming increase in antimicrobial resistance. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hypocretin/orexin regulation of dopamine signaling: implications for reward and reinforcement mechanisms

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Rodrigo eEspaña

2012-08-01

Full Text Available The hypocretins/orexins are comprised of two neuroexcitatory peptides that are synthesized exclusively within a circumscribed region of the lateral hypothalamus. These peptides project widely throughout the brain and interact with a variety of regions involved in the regulation of arousal-related processes including those associated with motivated behavior. The current review focuses on emerging evidence indicating that the hypocretins influence reward and reinforcement processing via actions on the mesolimbic dopamine system. We discuss contemporary perspectives of hypocretin regulation of mesolimbic dopamine signaling in both drug free and drug states, as well as hypocretin regulation of behavioral responses to drugs of abuse, particularly as it relates to cocaine.

Hypocretin/orexin regulation of dopamine signaling: implications for reward and reinforcement mechanisms

Science.gov (United States)

Calipari, Erin S.; España, Rodrigo A.

2012-01-01

The hypocretins/orexins are comprised of two neuroexcitatory peptides that are synthesized exclusively within a circumscribed region of the lateral hypothalamus. These peptides project widely throughout the brain and interact with a variety of regions involved in the regulation of arousal-related processes including those associated with motivated behavior. The current review focuses on emerging evidence indicating that the hypocretins influence reward and reinforcement processing via actions on the mesolimbic dopamine system. We discuss contemporary perspectives of hypocretin regulation of mesolimbic dopamine signaling in both drug free and drug states, as well as hypocretin regulation of behavioral responses to drugs of abuse, particularly as it relates to cocaine. PMID:22933994

Suicide attempt with a mix of synthetic cannabinoids and synthetic cathinones: Case report of non-fatal intoxication with AB-CHMINACA, AB-FUBINACA, alpha-PHP, alpha-PVP and 4-CMC.

Science.gov (United States)

Klavž, Janez; Gorenjak, Maksimiljan; Marinšek, Martin

2016-08-01

We report on a case of intoxication with a mix of new psychoactive substances. A 38-year-old male was brought to the emergency department (ED) following the ingestion of an unknown drug in a suicide attempt. During the transport, he became progressively more somnolent and unresponsive to painful stimuli. Urine and stomach content were collected on admission to be screened for drugs of abuse and medicinal drugs. After admission, the patient's next of kin presented five small grip seal plastic bags containing different powders/crystals, and they were sent for analysis along with urine and stomach content to the toxicology laboratory. An easy and rapid sample preparation technique was applied for the extraction of urine and stomach content. Samples were extracted with liquid-liquid extraction (LLE) technique and analysed using gas chromatography-mass spectrometry (GC-MS). A small amount of powder material from the bags was diluted in methanol and injected directly into the GC-MS instrument. Obtained spectra (EI) were evaluated against SWGDRUG library. Five different designer drugs were identified in the powder material, including synthetic cannabinoids (AB-CHMINACA, AB-FUBINACA) and synthetic cathinones (alpha-PHP, alpha-PVP and 4-CMC). With the exception of 4-CMC, all of these substances were also detected in the stomach content along with the prescription drugs. This is the first time that a positive identification of these five drugs has been made by a clinical laboratory in Slovenia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Progress in synthetic biology of pinocembrin].

Science.gov (United States)

Guo, Lei; Kong, Jianqiang

2015-04-01

Pinocembrin, belonging to flavanons, was isolated from various plants. Pinocembrin has a variety of pharmacological activities, such as neuroprotective effect, antimicrobial activity, and antioxidant efficacy. Pinocembrin was approved as class I drugs to its phase II clinical trial by CFDA in 2009, mainly used for the treatment of ischemic stroke. As a promising compound, the manufacturing technologies of pinocembrin, including chemical synthesis, extraction from plant and synthetic biology, have attracted many attentions. Compared with the first two technologies, synthetic biology has many advantages, such as environment-friendly and low-cost. Construction of biosynthetic pathway in microorganism offers promising results for large scale pinocembrin production by fermentation after taking lots of effective strategies. This article reviews some of recent strategies in microorganisms to improve the yield, with focus on the selection of appropriate the key enzyme sources, the supply of precursors and cofactors by microorganisms, the choice of substance and the level of the key enzyme expression.

Myocardial infarction associated with use of the synthetic cannabinoid K2.

Science.gov (United States)

Mir, Arshid; Obafemi, Adebisi; Young, Amy; Kane, Colin

2011-12-01

Designer drugs have been problematic over the years. Products such as K2 and Spice, which contain synthetic cannabinoids, are marketed as incense and are widely available on the Internet and at various specialty shops. The effects are reported as cannabis-like after smoking them. In addition, use of these synthetic cannabinoids will not appear on a routine urine toxicology screen. Recently, K2 became a popular alternative to marijuana among youths. Health implications of these designer drugs are not completely understood. Little has been reported about the harmful effects of K2. We report here the first (to our knowledge) cases of myocardial infarction (MI) after smoking K2. Three patients presented separately to the emergency department complaining of chest pain within days after the use of K2. Acute MI was diagnosed in each case on the basis of electrocardiogram changes and elevated troponin levels. Coronary angiography was performed, and the results were normal for the first 2 patients. The incidence of ST-elevation MI is low among teenagers, and association with drug use should be suspected. Public education and awareness need to be heightened about the possible health implications of K2.

Hydrogel nanoparticles in drug delivery.

Science.gov (United States)

Hamidi, Mehrdad; Azadi, Amir; Rafiei, Pedram

2008-12-14

Hydrogel nanoparticles have gained considerable attention in recent years as one of the most promising nanoparticulate drug delivery systems owing to their unique potentials via combining the characteristics of a hydrogel system (e.g., hydrophilicity and extremely high water content) with a nanoparticle (e.g., very small size). Several polymeric hydrogel nanoparticulate systems have been prepared and characterized in recent years, based on both natural and synthetic polymers, each with its own advantages and drawbacks. Among the natural polymers, chitosan and alginate have been studied extensively for preparation of hydrogel nanoparticles and from synthetic group, hydrogel nanoparticles based on poly (vinyl alcohol), poly (ethylene oxide), poly (ethyleneimine), poly (vinyl pyrrolidone), and poly-N-isopropylacrylamide have been reported with different characteristics and features with respect to drug delivery. Regardless of the type of polymer used, the release mechanism of the loaded agent from hydrogel nanoparticles is complex, while resulting from three main vectors, i.e., drug diffusion, hydrogel matrix swelling, and chemical reactivity of the drug/matrix. Several crosslinking methods have been used in the way to form the hydrogel matix structures, which can be classified in two major groups of chemically- and physically-induced crosslinking.

Investigation of crack paths in natural fibre-reinforced composites

Directory of Open Access Journals (Sweden)

S. Keck

2015-10-01

Full Text Available Nowadays, fibre-reinforced composite materials are widely used in many fields, e.g. automotive and aerospace. Natural fibres such as flax and hemp provide good density specific mechanical properties. Additionally, the embodied production energy in natural fibres is much smaller than in synthetic ones. Within this paper the fracture mechanical behaviour of flax fibre-reinforced composites is discussed. Especially, this paper focuses on the determination and investigation of crack paths in compact tension specimens with three different fibre directions under a static as well as fatigue load. Differences and similarities in the obtained crack paths under different loading conditions are presented. Due to the pronounced orthotropic behaviour of those materials the crack path is not only governed by the stress state, but practically determined by the fibre direction and fibre volume fraction. Therefore, the well-known stress intensity factor solutions for the standard specimens are not applicable. It is necessary to carry out extensive numerical simulations to evaluate the stress intensity factor evolution along the growing crack in order to be able to determine fatigue crack growth rate curves. Those numerical crack growth simulations are performed with the three-dimensional crack simulation program ADAPCRACK3D to gain energy release rates and in addition stress intensity factors

Comparación entre redes de fibras sintéticas y redes de fibras de cáñamo para el refuerzo de muros de albañileria = Comparison between synthetic fiber networks and hemp fiber networks for the reinforcement of masonry walls

Directory of Open Access Journals (Sweden)

Alessandra Vilardi

2016-12-01

Full Text Available La existencia de una gran cantidad de edificios antiguos ha movilizado la investigación para estudiar nuevos sistemas de refuerzo a aquellas construcciones que sean dañadas por decadencia fisiológica o por terremoto. El presente documento demuestra la eficacia de un sistema de refuerzo innovador para los muros de mampostería, constituyentes los elementos estructurales de los edificios históricos. Se hace una comparación entre unas redes bidireccionales de fibras sintéticas tradicionales y las de fibras naturales, ambas pegadas a las dos fachadas del muro con matriz de mortero. El resultado muestra la aplicación de las fibras de cáñamo como refuerzo sísmico y una mayor compatibilidad de estas con el material que caracterizan los edificios antiguos. Abstract The existence of a large number of old buildings has mobilized research to study new systems of reinforcement to those buildings that are damaged by physiological decay or earthquake. This document demonstrates the effectiveness of an innovative reinforcement system for masonry walls, which are the structural elements of historic buildings. A comparison is made between bidirectional networks of traditional synthetic fibers and those of natural fibers, both glued to the two facades of the wall with mortar matrix. The result shows the application of hemp fibers as seismic reinforcement and a greater compatibility of these with the material that characterize the old buildings.

In situ biomolecule production by bacteria; a synthetic biology approach to medicine.

Science.gov (United States)

Flores Bueso, Yensi; Lehouritis, Panos; Tangney, Mark

2018-04-10

The ability to modify existing microbiota at different sites presents enormous potential for local or indirect management of various diseases. Because bacteria can be maintained for lengthy periods in various regions of the body, they represent a platform with enormous potential for targeted production of biomolecules, which offer tremendous promise for therapeutic and diagnostic approaches for various diseases. While biological medicines are currently limited in the clinic to patient administration of exogenously produced biomolecules from engineered cells, in situ production of biomolecules presents enormous scope in medicine and beyond. The slow pace and high expense of traditional research approaches has particularly hampered the development of biological medicines. It may be argued that bacterial-based medicine has been "waiting" for the advent of enabling technology. We propose that this technology is Synthetic Biology, and that the wait is over. Synthetic Biology facilitates a systematic approach to programming living entities and/or their products, using an approach to Research and Development (R&D) that facilitates rapid, cheap, accessible, yet sophisticated product development. Full engagement with the Synthetic Biology approach to R&D can unlock the potential for bacteria as medicines for cancer and other indications. In this review, we describe how by employing Synthetic Biology, designer bugs can be used as drugs, drug-production factories or diagnostic devices, using oncology as an exemplar for the concept of in situ biomolecule production in medicine. Copyright © 2018 Elsevier B.V. All rights reserved.

Assessing appetitive, aversive, and negative ethanol-mediated reinforcement through an immature rat model.

Science.gov (United States)

Pautassi, Ricardo M; Nizhnikov, Michael E; Spear, Norman E

2009-06-01

The motivational effects of drugs play a key role during the transition from casual use to abuse and dependence. Ethanol reinforcement has been successfully studied through Pavlovian and operant conditioning in adult rats and mice genetically selected for their ready acceptance of ethanol. Another model for studying ethanol reinforcement is the immature (preweanling) rat, which consumes ethanol and exhibits the capacity to process tactile, odor and taste cues and transfer information between different sensorial modalities. This review describes the motivational effects of ethanol in preweanling, heterogeneous non-selected rats. Preweanlings exhibit ethanol-mediated conditioned taste avoidance and conditioned place aversion. Ethanol's appetitive effects, however, are evident when using first- and second-order conditioning and operant procedures. Ethanol also devalues the motivational representation of aversive stimuli, suggesting early negative reinforcement. It seems that preweanlings are highly sensitive not only to the aversive motivational effects of ethanol but also to its positive and negative (anti-anxiety) reinforcement potential. The review underscores the advantages of using a developing rat to evaluate alcohol's motivational effects.

Synthetic biology and global health in the age of intellectual property

NARCIS (Netherlands)

Belt, van den H.

2014-01-01

Although synthetic biology (SB) conjures up a future cornucopia of new medicines and other health applications, the antimalarial drug artemisinin is still one of the few concrete illustrations to substantiate this promise. As SB’s favorite poster child, it is atypical because it exemplifies a rather

Experimental analysis of reinforced concrete beams strengthened in bending with carbon fiber reinforced polymer

Directory of Open Access Journals (Sweden)

M. M. VIEIRA

Full Text Available The use of carbon fiber reinforced polymer (CFRP has been widely used for the reinforcement of concrete structures due to its practicality and versatility in application, low weight, high tensile strength and corrosion resistance. Some construction companies use CFRP in flexural strengthening of reinforced concrete beams, but without anchor systems. Therefore, the aim of this study is analyze, through an experimental program, the structural behavior of reinforced concrete beams flexural strengthened by CFRP without anchor fibers, varying steel reinforcement and the amount of carbon fibers reinforcement layers. Thus, two groups of reinforced concrete beams were produced with the same geometric feature but with different steel reinforcement. Each group had five beams: one that is not reinforced with CFRP (reference and other reinforced with two, three, four and five layers of carbon fibers. Beams were designed using a computational routine developed in MAPLE software and subsequently tested in 4-point points flexural test up to collapse. Experimental tests have confirmed the effectiveness of the reinforcement, ratifying that beams collapse at higher loads and lower deformation as the amount of fibers in the reinforcing layers increased. However, the increase in the number of layers did not provide a significant increase in the performance of strengthened beams, indicating that it was not possible to take full advantage of strengthening applied due to the occurrence of premature failure mode in the strengthened beams for pullout of the cover that could have been avoided through the use of a suitable anchoring system for CFRP.

Reinforcement Schedules in a Verbal Reinforcement Combination and Renection-Impulsivity

OpenAIRE

TAMASE, Koji; UEDA, Masako

1986-01-01

It was predicted that higher proportion of the negative reinforcement "Wrong" than that of the positive reinforcement "Right" in a reinforcement combination will produce higher proportion of the correct response and this trend will be greater in reflective children than in impulsive children. From 140 kindergarten children 30 reflective and 30 impulsive children were selected and they were given a two-hole marble-dropping task. The best performance in the ratio of correct responses was obtain...

Model prodrugs for the intestinal peptide transporter. a synthetic approach for coupling of hydroxy-containing compounds to dieptides

DEFF Research Database (Denmark)

Friedrichsen, G; Nielsen, Carsten Uhd; Steffansen, Bente

2001-01-01

The human peptide transporter, hPepT1, situated in the small intestine, may be exploited to increase absorption of drugs or model drugs by attaching them to a dipeptide, which is recognised by hPepT1. A synthetic protocol for this kind of model prodrugs was developed, in which model drugs...

Sustainable drugs and global health care

Directory of Open Access Journals (Sweden)

Geoffrey A. Cordell

2009-01-01

Full Text Available Each day, Earth's finite resources are being depleted for energy, for material goods, for transportation, for housing, and for drugs. As we evolve scientifically and technologically, and as the population of the world rapidly approaches 7 billion and beyond, among the many issues with which we are faced is the continued availability of drugs for future global health care. Medicinal agents are primarily derived from two sources, synthetic and natural, or in some cases, as semi-synthetic compounds, a mixture of the two. For the developed world, efforts have been initiated to make drug production "greener", with milder reagents, shorter reaction times, and more efficient processing, thereby using less energy, and reactions which are more atom efficient, and generate fewer by-products. However, most of the world's population uses plants, in either crude or extract form, for their primary health care. There is relatively little discussion as yet, about the long term effects of the current, non-sustainable harvesting methods for medicinal plants from the wild, which are depleting these critical resources without concurrent initiatives to commercialize their cultivation. To meet future public health care needs, a paradigm shift is required in order to adopt new approaches using contemporary technology which will result in drugs being regarded as a sustainable commodity, irrespective of their source. In this presentation, several approaches to enhancing and sustaining the availability of drugs, both synthetic and natural, will be discussed, including the use of vegetables as chemical reagents, and the deployment of integrated strategies involving information systems, biotechnology, nanotechnology, and detection techniques for the development of medicinal plants with enhanced levels of bioactive agents.

HPMA Copolymer-Drug Conjugates with Controlled Tumor-Specific Drug Release.

Science.gov (United States)

Chytil, Petr; Koziolová, Eva; Etrych, Tomáš; Ulbrich, Karel

2018-01-01

Over the past few decades, numerous polymer drug carrier systems are designed and synthesized, and their properties are evaluated. Many of these systems are based on water-soluble polymer carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, or multidrug resistance inhibitors, all covalently bound to a carrier by a biodegradable spacer that enables controlled release of the active molecule to achieve the desired pharmacological effect. Among others, the synthetic polymer carriers based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers are some of the most promising carriers for this purpose. This review focuses on advances in the development of HPMA copolymer carriers and their conjugates with anticancer drugs, with triggered drug activation in tumor tissue and especially in tumor cells. Specifically, this review highlights the improvements in polymer drug carrier design with respect to the structure of a spacer to influence controlled drug release and activation, and its impact on the drug pharmacokinetics, enhanced tumor uptake, cellular trafficking, and in vivo antitumor activity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Marijuana-based drugs: innovative therapeutics or designer drugs of abuse?

Science.gov (United States)

Seely, Kathryn A; Prather, Paul L; James, Laura P; Moran, Jeffery H

2011-02-01

The principal psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), activates CB1 cannabinoid receptors (CB1Rs). Unfortunately, pharmacological research into the design of effective THC analogs has been hampered by psychiatric side effects. THC-based drug design of a less academic nature, however, has led to the marketing of "synthetic marijuana," labeled as K2 or "Spice," among other terms, which elicits psychotropic actions via CB1R activation. Because of structural dissimilarity to THC, the active ingredients of K2/Spice preparations are widely unregulated. The K2/Spice "phenomenon" provides a context for considering whether marijuana-based drugs will truly provide innovative therapeutics or merely perpetuate drug abuse.

Effects of synthetic and natural toxicants on livestock.

Science.gov (United States)

Shull, L R; Cheeke, P R

1983-07-01

Synthetic and natural toxicants are constituents of soil, air, water and foodstuffs. Their impact on animal agriculture has resulted from acute and chronic intoxication and residues transferred into meat, dairy and poultry products. Recent advances in analytical chemistry and the sciences associated with toxicology have allowed better assessment of the hazard of toxicants on animals including man. Historically, natural toxicants (phytotoxins, mycotoxins and minerals) that are associated with many common feedstuffs accounted for toxicity episodes of epidemic proportions. Most synthetic chemicals (pesticides, nonpesticidal organic chemicals and drugs) have been introduced in increasing numbers since the 1940's. In the 1960's and '70's, recognition of the need to control their environmental distribution stimulated the introduction of numerous laws and regulations. In the last decade, several problematic synthetic chemicals have been banned, particularly those found to persist in the environment or those confirmed or suspected as carcinogens in humans. At the farm level, the development of various preventative management strategies has decreased the exposure of livestock to natural toxicants. In the future, the impact of natural toxicants on animal agriculture is expected to lessen as their existence, etiology and toxicology are determined. On the other hand, synthetic chemicals will continue to threaten animal health as greater numbers and quantities are released into the environment. These challenges should stimulate a greater involvement of animal scientists in toxicology.

Robust microcapsules with controlled permeability from silk fibroin reinforced with graphene oxide.

Science.gov (United States)

Ye, Chunhong; Combs, Zachary A; Calabrese, Rossella; Dai, Hongqi; Kaplan, David L; Tsukruk, Vladimir V

2014-12-29

Robust and stable microcapsules are assembled from poly-amino acid-modified silk fibroin reinforced with graphene oxide flakes using layer-by-layer (LbL) assembly, based on biocompatible natural protein and carbon nanosheets. The composite microcapsules are extremely stable in acidic (pH 2.0) and basic (pH 11.5) conditions, accompanied with pH-triggered permeability, which facilitates the controllable encapsulation and release of macromolecules. Furthermore, the graphene oxide incorporated into ultrathin LbL shells induces greatly reinforced mechanical properties, with an elastic modulus which is two orders of magnitude higher than the typical values of original silk LbL shells and shows a significant, three-fold reduction in pore size. Such strong nanocomposite microcapsules can provide solid protection of encapsulated cargo under harsh conditions, indicating a promising candidate with controllable loading/unloading for drug delivery, reinforcement, and bioengineering applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[From synthetic biology to synthetic humankind].

Science.gov (United States)

Nouvel, Pascal

2015-01-01

In this paper, we propose an historical survey of the expression "synthetic biology" in order to identify its main philosophical components. The result of the analysis is then used to investigate the meaning of the notion of "synthetic man". It is shown that both notions share a common philosophical background that can be summed up by the short but meaningful assertion: "biology is technology". The analysis allows us to distinguish two notions that are often confused in transhumanist literature: the notion of synthetic man and the notion of renewed man. The consequences of this crucial distinction are discussed. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Synthetic biology: Novel approaches for microbiology.

Science.gov (United States)

Padilla-Vaca, Felipe; Anaya-Velázquez, Fernando; Franco, Bernardo

2015-06-01

In the past twenty years, molecular genetics has created powerful tools for genetic manipulation of living organisms. Whole genome sequencing has provided necessary information to assess knowledge on gene function and protein networks. In addition, new tools permit to modify organisms to perform desired tasks. Gene function analysis is speed up by novel approaches that couple both high throughput data generation and mining. Synthetic biology is an emerging field that uses tools for generating novel gene networks, whole genome synthesis and engineering. New applications in biotechnological, pharmaceutical and biomedical research are envisioned for synthetic biology. In recent years these new strategies have opened up the possibilities to study gene and genome editing, creation of novel tools for functional studies in virus, parasites and pathogenic bacteria. There is also the possibility to re-design organisms to generate vaccine subunits or produce new pharmaceuticals to combat multi-drug resistant pathogens. In this review we provide our opinion on the applicability of synthetic biology strategies for functional studies of pathogenic organisms and some applications such as genome editing and gene network studies to further comprehend virulence factors and determinants in pathogenic organisms. We also discuss what we consider important ethical issues for this field of molecular biology, especially for potential misuse of the new technologies. Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.

Management of Reinforcement Corrosion

DEFF Research Database (Denmark)

Küter, André; Geiker, Mette Rica; Møller, Per

Reinforcement corrosion is the most important cause for deterioration of reinforced concrete structures, both with regard to costs and consequences. Thermodynamically consistent descriptions of corrosion mechanisms are expected to allow the development of innovative concepts for the management...... of reinforcement corrosion....

Drugs + HIV, Learn the Link

Medline Plus

Full Text Available ... Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine and E-Cigs Other Drugs Related Topics Addiction Science Adolescent ... Blog NIDA in the News NIDA Notes Podcasts E-Newsletters Public Education Projects Contact the Press Office ...

Albumin–Polymer–Drug Conjugates: Long Circulating, High Payload Drug Delivery Vehicles

DEFF Research Database (Denmark)

Smith, Anton Allen Abbotsford; Zuwala, Kaja; Pilgram, Oliver

2016-01-01

Albumin is an exquisite tool of nature used in biomedicine to achieve long blood residence time for drugs, but the payload it can carry is typically limited to one molecule per protein. In contrast, synthetic macromolecular prodrugs contain multiple copies of drugs per polymer chain but offer only...... a marginal increase in the circulation lifetime of the drugs. We combine the benefits of the two platforms and at the same time overcome their respective limitations. Specifically, we develop the synthesis of albumin–polymer–drug conjugates to obtain long circulating, high payload drug delivery vehicles....... In vivo data validate that albumin endows the conjugate with a blood residence time similar to that of the protein and well exceeding that of the polymer. Therapeutic activity of the conjugates is validated using prodrugs of panobinostat, an HIV latency reversal agent, in which case the conjugates matched...

[Application of operant conditioning techniques to forensic toxicology: experimental studies on alcohol and abusable drugs].

Science.gov (United States)

Hishida, S

1996-10-01

This paper describes some experiments that apply the operant conditioning techniques to forensic toxicological research. These techniques may be useful in investigating the mechanisms of action, toxic symptoms, legal competence and drug metabolism associated with substance abuse such as abuse of alcohol, psychotropic drugs, narcotics, stimulants, and organic solvents. 1) Genetic research on alcohol preference in rats. We applied operant conditioning to investigate alcohol preference in rats and constructed an apparatus for the measurement of discriminated operate responses for water or alcohol reinforcement in rat. This apparatus is a modified Skinner box with a one-lever two-liquid system. Fixed ratio-10 (FR-10) schedules of reinforcement are used to increase the work of the rat before it obtains the reinforcement. The voluntary choice of water or 10% ethanol by the rat can be assessed quantitatively by measuring the lever-pushing responses. It is an extremely useful method for measuring the real alcohol preference of rats. A rat was kept in a Skinner box overnight. The numbers of responses and reinforcement for water and ethanol and the volumes of the two liquids consumed were recorded. The ratio of ethanol reinforcement was defined as the number of ethanol reinforcement to the total number of ethanol and water reinforcement. The ratio of ethanol intake was defined as the volume of ethanol consumed to the volume of water and ethanol consumed. Ethanol consumption per g body weight was calculated from the volume of ethanol consumed by the rat. We used this apparatus to investigate alcohol preference of more than 300 Wistar Albino Rats, and divided them into a high alcohol preference (HAP) group and a low alcohol preference (LAP) group. Inbreeding between littermates was conducted in each of the HAP and LAP groups. The liver tissue of each offspring was obtained and the cytosol fraction was collected and subjected to isoelectric focusing using polyacrylamide gel

Synthetic cannabinoid JWH-018 and psychosis: an explorative study.

Science.gov (United States)

Every-Palmer, Susanna

2011-09-01

Aroma, Spice, K2 and Dream are examples of a class of new and increasingly popular recreational drugs. Ostensibly branded "herbal incense", they have been intentionally adulterated with synthetic cannabinoids such as JWH-018 in order to confer on them cannabimimetic psychoactive properties while circumventing drug legislation. JWH-018 is a potent cannabinoid receptor agonist. Little is known about its pharmacology and toxicology in humans. This is the first research considering the effects of JWH-018 on a psychiatric population and exploring the relationship between JWH-018 and psychotic symptoms. This paper presents the results of semi-structured interviews regarding the use and effects of JWH-018 in 15 patients with serious mental illness in a New Zealand forensic and rehabilitative service. All 15 subjects were familiar with a locally available JWH-018 containing product called "Aroma" and 86% reported having used it. They credited the product's potent psychoactivity, legality, ready availability and non-detection in drug testing as reasons for its popularity, with most reporting it had replaced cannabis as their drug of choice. Most patients had assumed the product was "natural" and "safe". Anxiety and psychotic symptoms were common after use, with 69% of users experiencing or exhibiting symptoms consistent with psychotic relapse after smoking JWH-018. Although psychological side effects were common, no one reported becoming physically unwell after using JWH-018. Three subjects described developing some tolerance to the product, but no one reported withdrawal symptoms. It seems likely that JWH-018 can precipitate psychosis in vulnerable individuals. People with risk factors for psychosis should be counseled against using synthetic cannabinoids. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effects of partial reinforcement and time between reinforced trials on terminal response rate in pigeon autoshaping.

Science.gov (United States)

Gottlieb, Daniel A

2006-03-01

Partial reinforcement often leads to asymptotically higher rates of responding and number of trials with a response than does continuous reinforcement in pigeon autoshaping. However, comparisons typically involve a partial reinforcement schedule that differs from the continuous reinforcement schedule in both time between reinforced trials and probability of reinforcement. Two experiments examined the relative contributions of these two manipulations to asymptotic response rate. Results suggest that the greater responding previously seen with partial reinforcement is primarily due to differential probability of reinforcement and not differential time between reinforced trials. Further, once established, differences in responding are resistant to a change in stimulus and contingency. Secondary response theories of autoshaped responding (theories that posit additional response-augmenting or response-attenuating mechanisms specific to partial or continuous reinforcement) cannot fully accommodate the current body of data. It is suggested that researchers who study pigeon autoshaping train animals on a common task prior to training them under different conditions.

Influence of transverse reinforcement on perforation resistance of reinforced concrete slabs under hard missile impact

International Nuclear Information System (INIS)

Orbovic, Nebojsa; Sagals, Genadijs; Blahoianu, Andrei

2015-01-01

This paper describes the work conducted by the Canadian Nuclear Safety Commission (CNSC) related to the influence of transverse reinforcement on perforation capacity of reinforced concrete (RC) slabs under “hard” missile impact (impact with negligible missile deformations). The paper presents the results of three tests on reinforced concrete slabs conducted at VTT Technical Research Centre (Finland), along with the numerical simulations as well as a discussion of the current code provisions related to impactive loading. Transverse reinforcement is widely used for improving the shear and punching strength of concrete structures. However, the effect of this reinforcement on the perforation resistance under localized missile impact is still unclear. The goal of this paper is to fill the gap in the current literature related to this topic. Based on similar tests designed by the authors with missile velocity below perforation velocity, it was expected that transverse reinforcement would improve the perforation resistance. Three slabs were tested under almost identical conditions with the only difference being the transverse reinforcement. One slab was designed without transverse reinforcement, the second one with the transverse reinforcement in form of conventional stirrups with hooks and the third one with the transverse reinforcement in form of T-headed bars. Although the transverse reinforcement reduced the overall damage of the slabs (the rear face scabbing), the conclusion from the tests is that the transverse reinforcement does not have important influence on perforation capacity of concrete slabs under rigid missile impact. The slab with T-headed bars presented a slight improvement compared to the baseline specimen without transverse reinforcement. The slab with conventional stirrups presented slightly lower perforation capacity (higher residual missile velocity) than the slab without transverse reinforcement. In conclusion, the performed tests show slightly

In Silico Synthesis of Synthetic Receptors: A Polymerization Algorithm.

Science.gov (United States)

Cowen, Todd; Busato, Mirko; Karim, Kal; Piletsky, Sergey A

2016-12-01

Molecularly imprinted polymer (MIP) synthetic receptors have proposed and applied applications in chemical extraction, sensors, assays, catalysis, targeted drug delivery, and direct inhibition of harmful chemicals and pathogens. However, they rely heavily on effective design for success. An algorithm has been written which mimics radical polymerization atomistically, accounting for chemical and spatial discrimination, hybridization, and geometric optimization. Synthetic ephedrine receptors were synthesized in silico to demonstrate the accuracy of the algorithm in reproducing polymers structures at the atomic level. Comparative analysis in the design of a synthetic ephedrine receptor demonstrates that the new method can effectively identify affinity trends and binding site selectivities where commonly used alternative methods cannot. This new method is believed to generate the most realistic models of MIPs thus produced. This suggests that the algorithm could be a powerful new tool in the design and analysis of various polymers, including MIPs, with significant implications in areas of biotechnology, biomimetics, and the materials sciences more generally. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Positron emission tomography molecular imaging of dopaminergic system in drug addiction.

Science.gov (United States)

Hou, Haifeng; Tian, Mei; Zhang, Hong

2012-05-01

Dopamine (DA) is involved in drug reinforcement, but its role in drug addiction remains unclear. Positron emission tomography (PET) is the first technology used for the direct measurement of components of the dopaminergic system in the living human brain. In this article, we reviewed the major findings of PET imaging studies on the involvement of DA in drug addiction, especially in heroin addiction. Furthermore, we summarized PET radiotracers that have been used to study the role of DA in drug addiction. To investigate presynaptic function in drug addiction, PET tracers have been developed to measure DA synthesis and transport. For the investigation of postsynaptic function, several radioligands targeting dopamine one (D1) receptor and dopamine two (D2) receptor are extensively used in PET imaging studies. Moreover, we also summarized the PET imaging findings of heroin addiction studies, including heroin-induced DA increases and the reinforcement, role of DA in the long-term effects of heroin abuse, DA and vulnerability to heroin abuse and the treatment implications. PET imaging studies have corroborated the role of DA in drug addiction and increase our understanding the mechanism of drug addiction. Copyright © 2012 Wiley Periodicals, Inc.

Beyond THC: the new generation of cannabinoid designer drugs

Directory of Open Access Journals (Sweden)

Liana eFattore

2011-09-01

Full Text Available Synthetic cannabinoids are functionally similar to delta9-tetrahydrocannabinol (THC, the psychoactive principle of cannabis, and bind to the same cannabinoid receptors in the brain and peripheral organs. From 2008, synthetic cannabinoids were detected in herbal smoking mixtures sold on websites and in head shops under the brand name of Spice Gold, Yucatan Fire, Aroma, and others. Although these products (also known as Spice drugs or legal highs do not contain tobacco or cannabis, when smoked they produce effects similar to THC. Intoxication, withdrawal, psychosis and death have been recently reported after consumption, posing difficult social, political and health challenges. More than 140 different Spice products have been identified to date. The ability to induce strong cannabis-like psychoactive effects, along with the fact that they are readily available on the Internet, still legal in many countries, marketed as natural safe substances, and undetectable by conventional drug screening tests, has rendered these drugs very popular and particularly appealing to young and drug-naïve individuals seeking new experiences. An escalating number of compounds with cannabinoid receptor activity are currently being found as ingredients of Spice, of which almost nothing is known in terms of pharmacology, toxicology and safety. Since legislation started to control the synthetic cannabinoids identified in these herbal mixtures, many new analogs have appeared on the market. New cannabimimetic compounds are likely to be synthesized in the near future to replace banned synthetic cannabinoids, leading to a dog chasing its tail situation. Spice smokers are exposed to drugs that are extremely variable in composition and potency, and are at risk of serious, if not lethal, outcomes. Social and health professionals should maintain a high degree of alertness for Spice use and its possible psychiatric effects in vulnerable people.

Finite element modelling of concrete beams reinforced with hybrid fiber reinforced bars

Science.gov (United States)

Smring, Santa binti; Salleh, Norhafizah; Hamid, NoorAzlina Abdul; Majid, Masni A.

2017-11-01

Concrete is a heterogeneous composite material made up of cement, sand, coarse aggregate and water mixed in a desired proportion to obtain the required strength. Plain concrete does not with stand tension as compared to compression. In order to compensate this drawback steel reinforcement are provided in concrete. Now a day, for improving the properties of concrete and also to take up tension combination of steel and glass fibre-reinforced polymer (GFRP) bars promises favourable strength, serviceability, and durability. To verify its promise and support design concrete structures with hybrid type of reinforcement, this study have investigated the load-deflection behaviour of concrete beams reinforced with hybrid GFRP and steel bars by using ATENA software. Fourteen beams, including six control beams reinforced with only steel or only GFRP bars, were analysed. The ratio and the ordinate of GFRP to steel were the main parameters investigated. The behaviour of these beams was investigated via the load-deflection characteristics, cracking behaviour and mode of failure. Hybrid GFRP-Steel reinforced concrete beam showed the improvement in both ultimate capacity and deflection concomitant to the steel reinforced concrete beam. On the other hand, finite element (FE) modelling which is ATENA were validated with previous experiment and promising the good result to be used for further analyses and development in the field of present study.

Metabolism and toxicological analysis of synthetic cannabinoids in biological fluids and tissues.

Science.gov (United States)

Presley, B C; Gurney, S M R; Scott, K S; Kacinko, S L; Logan, B K

2016-07-01

Synthetic cannabinoids, which began proliferating in the United States in 2009, have gone through numerous iterations of modification to their chemical structures. More recent generations of compounds have been associated with significant adverse outcomes following use, including cognitive and psychomotor impairment, seizures, psychosis, tissue injury and death. These effects increase the urgency for forensic and public health laboratories to develop methods for the detection and identification of novel substances, and apply these to the determination of their metabolism and disposition in biological samples. This comprehensive review describes the history of the appearance of the drugs in the United States, discusses the naming conventions emerging to designate new structures, and describes the most prominent new compounds linked to the adverse effects now associated with their use. We review in depth the metabolic pathways that have been elucidated for the major members of each of the prevalent synthetic cannabinoid drug subclasses, the enzyme systems responsible for their metabolism, and the use of in silico approaches to assist in predicting and identifying the metabolites of novel compounds and drug subclasses that will continue to appear. Finally, we review and critique analytical methods applied to the detection of the drugs and their metabolites, including immunoassay screening, and liquid chromatography mass spectrometry confirmatory techniques applied to urine, serum, whole blood, oral fluid, hair, and tissues. Copyright © 2016 Central Police University.

Synthetic biology in mammalian cells: Next generation research tools and therapeutics

Science.gov (United States)

Lienert, Florian; Lohmueller, Jason J; Garg, Abhishek; Silver, Pamela A

2014-01-01

Recent progress in DNA manipulation and gene circuit engineering has greatly improved our ability to programme and probe mammalian cell behaviour. These advances have led to a new generation of synthetic biology research tools and potential therapeutic applications. Programmable DNA-binding domains and RNA regulators are leading to unprecedented control of gene expression and elucidation of gene function. Rebuilding complex biological circuits such as T cell receptor signalling in isolation from their natural context has deepened our understanding of network motifs and signalling pathways. Synthetic biology is also leading to innovative therapeutic interventions based on cell-based therapies, protein drugs, vaccines and gene therapies. PMID:24434884

Synthesis of Aluminum Triacrylate as Reactive Filler in EPDM Reinforcement

Directory of Open Access Journals (Sweden)

Akram Shokrzadeh

2013-01-01

Full Text Available The organo-metal salt of aluminum triacrylate (ALTA with a general formula of (CH2=CHCOO3Al was  synthesized  as  a  reactive  fller  for  elastomers through a two-step synthetic procedure. Fourier transform-infrared spectroscopy (FTIR, DSC and DTA were employed for ALTA analysis and to study its cure characteristics. In this research, two composites based on ethylene propylene diene monomer rubber (EPDM with two types of reactive fllers of  modifed organoclay and ALTA were prepared by a laboratory two-roll mill. The types and different ratios of organoclay and ALTA on curing characteristics, mechanical properties such as tensile properties, hardness, and abrasion resistance were studied. The increase in fller content of both composites  led  to  the  incremental  increase  in  tensile strength, modulus, hardness, elongation-at-break and also the incremental increase in abrasion resistance of both composites. The improvement in reinforcing properties of ALTA in comparison with nanoclay is attributed to homopolymerization and graft copolymerization of ALTA at the same time during curing of the EPDM composites by peroxide. Making such additives may be taken as an effective action to achieve more durable and cheaper way to reinforce elastomers.

Structural characterization and mechanical properties of polypropylene reinforced natural fibers

Science.gov (United States)

Karim, M. A. A.; Zaman, I.; Rozlan, S. A. M.; Berhanuddin, N. I. C.; Manshoor, B.; Mustapha, M. S.; Khalid, A.; Chan, S. W.

2017-10-01

Recently the development of natural fiber composite instead of synthetics fiber has lead to eco-friendly product manufacturing to meet various applications in the field of automotive, construction and manufacturing. The use of natural fibers offer an alternative to the reinforcing fibers because of their good mechanical properties, low density, renewability, and biodegradability. In this present research, the effects of maleic anhydride polypropylene (MAPP) on the mechanical properties and material characterization behaviour of kenaf fiber and coir fiber reinforced polypropylene were investigated. Different fractions of composites with 10wt%, 20wt% and 30wt% fiber content were prepared by using brabender mixer at 190°C. The 3wt% MAPP was added during the mixing. The composites were subsequently molded with injection molding to prepare the test specimens. The mechanical properties of the samples were investigated according to ISO 527 to determine the tensile strength and modulus. These results were also confirmed by the SEM machine observations of fracture surface of composites and FTIR analysis of the chemical structure. As the results, the presence of MAPP helps increasing the mechanical properties of both fibers and 30wt% kenaf fiber with 3wt% MAPP gives the best result compare to others.

Optimisation of mechanical properties of bamboo fibre reinforced-PLA biocomposites

Science.gov (United States)

Nurnadia M., J.; Fazita, M. R. Nurul; Abdul Khalil H. P., S.; Mohamad Haafiz M., K.

2017-12-01

The majority of the raw materials that have been widely used in industries are petroleum-based. Growing environmental awareness, the depletion of fossil fuels, and climate change are the key drivers to seek more ecologically friendly materials, such as natural fibres to replace synthetic fibres in polymeric composite. Among the natural fibres available, bamboo fibre has relatively high strength. Poly (lactic) acid (PLA), one of the well-known biopolymers, has been used as a matrix in order to produce totally biodegradable biocomposites. In this study, bamboo fibres were compounded with PLA by a twin screw extruder. The bamboo fibre reinforced PLA composites were then manufactured via the compression moulding method. The influences of screw speed and die temperature during extrusion on the mechanical properties, the tensile and flexural of the biocomposites, were studied. The effects of fibre content and fibre length were also investigated. Taguchi experimental design approach was adopted to determine the optimum set of conditions to achieve the "best" mechanical properties of the composites. Tensile and flexural properties were characterised based on the D638-10 and D790-10 standards, respectively. It was observed that the fibre aspect ratio and fibre content significantly affected the mechanical performance of bamboo fibres reinforced PLA composites.

Glutamatergic substrates of drug addiction and alcoholism1

Science.gov (United States)

Gass, Justin T.; Foster Olive, M.

2008-01-01

The past two decades have witnessed a dramatic accumulation of evidence indicating that the excitatory amino acid glutamate plays an important role in drug addiction and alcoholism. The purpose of this review is to summarize findings on glutamatergic substrates of addiction, surveying data from both human and animal studies. The effects of various drugs of abuse on glutamatergic neurotransmission are discussed, as are the effects of pharmacological or genetic manipulation of various components of glutamate transmission on drug reinforcement, conditioned reward, extinction, and relapse-like behavior. In addition, glutamatergic agents that are currently in use or are undergoing testing in clinical trials for the treatment of addiction are discussed, including acamprosate, N-acetylcysteine, modafinil, topiramate, lamotrigine, gabapentin and mematine. All drugs of abuse appear to modulate glutamatergic transmission, albeit by different mechanisms, and this modulation of glutamate transmission is believed to result in long-lasting neuroplastic changes in the brain that may contribute to the perseveration of drug-seeking behavior and drug-associated memories. In general, attenuation of glutamatergic transmission reduces drug reward, reinforcement, and relapse-like behavior. On the other hand, potentiation of glutamatergic transmission appears to facilitate the extinction of drug-seeking behavior. However, attempts at identifying genetic polymorphisms in components of glutamate transmission in humans have yielded only a limited number of candidate genes that may serve as risk factors for the development of addiction. Nonetheless, manipulation of glutamatergic neurotransmission appears to be a promising avenue of research in developing improved therapeutic agents for the treatment of drug addiction and alcoholism. PMID:17706608

Clinical Effects of Synthetic Cannabinoid Receptor Agonists Compared with Marijuana in Emergency Department Patients with Acute Drug Overdose.

Science.gov (United States)

Zaurova, Milana; Hoffman, Robert S; Vlahov, David; Manini, Alex F

2016-12-01

Synthetic cannabinoid receptor agonists (SCRAs) are heterogeneous compounds originally intended as probes of the endogenous cannabinoid system or as potential therapeutic agents. We assessed the clinical toxicity associated with recent SCRA use in a large cohort of drug overdose patients. This subgroup analysis of a large (n = 3739) drug overdose cohort study involved consecutive ED patients at two urban teaching hospitals collected between 2009 and 2013. Clinical characteristics of patients with the exposure to SCRAs (SRCA subgroup) were compared with those from patients who smoked traditional cannabinoids (marijuana subgroup). Data included demographics, exposure details, vital signs, mental status, and basic chemistries gathered as part of routine clinical care. Study outcomes included altered mental status and cardiotoxicity. Eighty-seven patients reported exposure to any cannabinoid, of whom 17 reported SCRAs (17 cases, 70 controls, mean age 38.9 years, 77 % males, 31 % Hispanic). There were no significant differences between SRCA and marijuana with respect to demographics (age, gender, and race/ethnicity), exposure history (suicidality, misuse, and intent), vital signs, or serum chemistries. Mental status varied between SRCA and marijuana, with agitation significantly more likely in SCRA subgroup (OR = 3.8, CI = 1.2-11.9). Cardiotoxicity was more pronounced in the SCRA subgroup with dysrhythmia significantly more likely (OR = 9.2, CI = 1.0-108). In the first clinical study comparing the adverse effects of SCRA overdose vs. marijuana controls in an ED population, we found that SCRA overdoses had significantly pronounced neurotoxicity and cardiotoxicity compared with marijuana.

Preparation and characterization of corn reinforced polymer sheet of fibers; Obtencao e caracterizacao de polimero reforcado com fibras da folha de milho

Energy Technology Data Exchange (ETDEWEB)

Moreira, Tatiana Martinez; Seo, Emilia Satoshi Miyamaru, E-mail: tatianaltda@hotmail.com, E-mail: esmiyseo@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2016-10-15

There is a global trend in seeking plant fibers to replace the synthetic fibers to obtain reinforced composites aimed at the use of renewable resources. In this context, this paper aims to develop the process of preparing maize leaf fibers, characterizing them and adapting them for applications in the construction industry and develop a reinforced polymer composite with these fibers. Corn leaves were dried in environmental temperature, treated by mercerizing, then neutralized with acid solution and washed in running water. The characterization of the corn leaf fibers was carried out by X-ray diffraction, X-ray fluorescence, scanning electron microscopy, specific surface area, thermogravimetry and specific mass. The mercerizing treatment was effective, because the maize fibers have characteristics similar to synthetic fibers, leading to a possibility of new technological uses. The polymeric composite material was developed by extrusion processes and injection and tested for tensile testing, differential scanning calorimetry and scanning electron microscopy, thus reused an organic waste that would be disposed of by inserting it in a technological process, contributing to the research and development of new polymeric materials as well as to reduce waste discarded as scrap. (author)

Negative mood reverses devaluation of goal-directed drug-seeking favouring an incentive learning account of drug dependence.

Science.gov (United States)

Hogarth, Lee; He, Zhimin; Chase, Henry W; Wills, Andy J; Troisi, Joseph; Leventhal, Adam M; Mathew, Amanda R; Hitsman, Brian

2015-09-01

Two theories explain how negative mood primes smoking behaviour. The stimulus-response (S-R) account argues that in the negative mood state, smoking is experienced as more reinforcing, establishing a direct (automatic) association between the negative mood state and smoking behaviour. By contrast, the incentive learning account argues that in the negative mood state smoking is expected to be more reinforcing, which integrates with instrumental knowledge of the response required to produce that outcome. One differential prediction is that whereas the incentive learning account anticipates that negative mood induction could augment a novel tobacco-seeking response in an extinction test, the S-R account could not explain this effect because the extinction test prevents S-R learning by omitting experience of the reinforcer. To test this, overnight-deprived daily smokers (n = 44) acquired two instrumental responses for tobacco and chocolate points, respectively, before smoking to satiety. Half then received negative mood induction to raise the expected value of tobacco, opposing satiety, whilst the remainder received positive mood induction. Finally, a choice between tobacco and chocolate was measured in extinction to test whether negative mood could augment tobacco choice, opposing satiety, in the absence of direct experience of tobacco reinforcement. Negative mood induction not only abolished the devaluation of tobacco choice, but participants with a significant increase in negative mood increased their tobacco choice in extinction, despite satiety. These findings suggest that negative mood augments drug-seeking by raising the expected value of the drug through incentive learning, rather than through automatic S-R control.

Improving the performance of solventogenic clostridia by reinforcing the biotin synthetic pathway.

Science.gov (United States)

Yang, Yunpeng; Lang, Nannan; Yang, Gaohua; Yang, Sheng; Jiang, Weihong; Gu, Yang

2016-05-01

An efficient production process is important for industrial microorganisms. The cellular efficiency of solventogenic clostridia, a group of anaerobes capable of producing a wealth of bulk chemicals and biofuels, must be improved for competitive commercialization. Here, using Clostridium acetobutylicum, a species of solventogenic clostridia, we revealed that the insufficient biosynthesis of biotin, a pivotal coenzyme for many important biological processes, is a major limiting bottleneck in this anaerobe's performance. To address this problem, we strengthened the biotin synthesis of C. acetobutylicum by overexpressing four relevant genes involved in biotin transport and biosynthesis. This strategy led to faster growth and improved the titer and productivity of acetone, butanol and ethanol (ABE solvents) of C. acetobutylicum in both biotin-containing and biotin-free media. Expressionally modulating these four genes by modifying the ribosome binding site further promoted cellular performance, achieving ABE solvent titer and productivity as high as 21.9g/L and 0.30g/L/h, respectively, in biotin-free medium; these values exceeded those of the wild-type strain by over 30%. More importantly, biotin synthesis reinforcement also conferred improved ability of C. acetobutylicum to use hexose and pentose sugars, further demonstrating the potential of this metabolic-engineering strategy in solventogenic clostridia. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Methylphenidate does not influence smoking-reinforced responding or attentional performance in adult smokers with and without attention deficit hyperactivity disorder (ADHD).

Science.gov (United States)

Kollins, Scott H; Schoenfelder, Erin; English, Joseph S; McClernon, F Joseph; Dew, Rachel E; Lane, Scott D

2013-10-01

Individuals with Attention Deficit Hyperactivity Disorder (ADHD) smoke cigarettes at rates higher than the general population and questions have been raised about how stimulant drugs-the frontline pharmacological treatment for ADHD-influence smoking risk and behavior in those with ADHD. In the present study adult regular smokers with (n = 16) and without (n = 17) ADHD participated in 3 experimental sessions in which they completed a Progressive Ratio (PR) task to measure the relative reinforcing effects of cigarette smoking and money after oral administration of placebo and 2 active doses of methylphenidate (10 mg and 40 mg). We also measured attention and inhibitory control via a Continuous Performance Test (CPT). Methylphenidate had no effect on smoking-reinforced responding, attention, or inhibitory control in either group. Attention and inhibitory control were associated with smoking-reinforced responding, but unsystematically and only in the non-ADHD group. Several design features, such as the value of the monetary response option, the PR schedule, and the potential effects of smoking on attention and inhibitory control, could have contributed to the negative findings and are discussed as such. Although inconsistent with some previous human laboratory studies of stimulant drugs and smoking, results are consistent with recent trials of stimulant drugs as adjuncts for smoking cessation in adult smokers with ADHD. In general, methylphenidate at mild and moderate doses did not influence the relative reinforcing effects of cigarette smoking in adults with and without ADHD. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Methods for producing reinforced carbon nanotubes

Science.gov (United States)

Ren, Zhifen [Newton, MA; Wen, Jian Guo [Newton, MA; Lao, Jing Y [Chestnut Hill, MA; Li, Wenzhi [Brookline, MA

2008-10-28

Methods for producing reinforced carbon nanotubes having a plurality of microparticulate carbide or oxide materials formed substantially on the surface of such reinforced carbon nanotubes composite materials are disclosed. In particular, the present invention provides reinforced carbon nanotubes (CNTs) having a plurality of boron carbide nanolumps formed substantially on a surface of the reinforced CNTs that provide a reinforcing effect on CNTs, enabling their use as effective reinforcing fillers for matrix materials to give high-strength composites. The present invention also provides methods for producing such carbide reinforced CNTs.

Synthetic biology devices and circuits for RNA-based 'smart vaccines': a propositional review.

Science.gov (United States)

Andries, Oliwia; Kitada, Tasuku; Bodner, Katie; Sanders, Niek N; Weiss, Ron

2015-02-01

Nucleic acid vaccines have been gaining attention as an alternative to the standard attenuated pathogen or protein based vaccine. However, an unrealized advantage of using such DNA or RNA based vaccination modalities is the ability to program within these nucleic acids regulatory devices that would provide an immunologist with the power to control the production of antigens and adjuvants in a desirable manner by administering small molecule drugs as chemical triggers. Advances in synthetic biology have resulted in the creation of highly predictable and modular genetic parts and devices that can be composed into synthetic gene circuits with complex behaviors. With the recent advent of modified RNA gene delivery methods and developments in the RNA replicon platform, we foresee a future in which mammalian synthetic biologists will create genetic circuits encoded exclusively on RNA. Here, we review the current repertoire of devices used in RNA synthetic biology and propose how programmable 'smart vaccines' will revolutionize the field of RNA vaccination.

Cell Wall Remodeling by a Synthetic Analog Reveals Metabolic Adaptation in Vancomycin Resistant Enterococci.

Science.gov (United States)

Pidgeon, Sean E; Pires, Marcos M

2017-07-21

Drug-resistant bacterial infections threaten to overburden our healthcare system and disrupt modern medicine. A large class of potent antibiotics, including vancomycin, operate by interfering with bacterial cell wall biosynthesis. Vancomycin-resistant enterococci (VRE) evade the blockage of cell wall biosynthesis by altering cell wall precursors, rendering them drug insensitive. Herein, we reveal the phenotypic plasticity and cell wall remodeling of VRE in response to vancomycin in live bacterial cells via a metabolic probe. A synthetic cell wall analog was designed and constructed to monitor cell wall structural alterations. Our results demonstrate that the biosynthetic pathway for vancomycin-resistant precursors can be hijacked by synthetic analogs to track the kinetics of phenotype induction. In addition, we leveraged this probe to interrogate the response of VRE cells to vancomycin analogs and a series of cell wall-targeted antibiotics. Finally, we describe a proof-of-principle strategy to visually inspect drug resistance induction. Based on our findings, we anticipate that our metabolic probe will play an important role in further elucidating the interplay among the enzymes involved in the VRE biosynthetic rewiring.

FORMULATION DEVELOPMENT OF MUCOADHESIVE MICROCAPSULES OF METFORMIN HYDROCHLORIDE USING NATURAL AND SYNTHETIC POLYMERS AND IN VITRO CHARACTERIZATION

OpenAIRE

Yellanki Shiva Kumar; Deb Sambit kumar; Goranti Sharada; Nerella Naveen kumar

2010-01-01

The objective of this work was to develop optimized and systematically evaluate performances of mucoadhesive microcapsules of antihyperglycemic agent drug Metformin. Alginate microcapsules coated with mucoadhesive natural or synthetic polymers were prepared by Orifice-Ionic Gelation technique utilizing calcium chloride as a cross linking agent. The effect of type (natural or synthetic) and concentration of coating polymers and concentration of alginate on formulation was investigated. Prepare...

Use of Preclinical Drug vs. Food Choice Procedures to Evaluate Candidate Medications for Cocaine Addiction.

Science.gov (United States)

Banks, Matthew L; Hutsell, Blake A; Schwienteck, Kathryn L; Negus, S Stevens

2015-06-01

Drug addiction is a disease that manifests as an inappropriate allocation of behavior towards the procurement and use of the abused substance and away from other behaviors that produce more adaptive reinforcers (e.g. exercise, work, family and social relationships). The goal of treating drug addiction is not only to decrease drug-maintained behaviors, but also to promote a reallocation of behavior towards alternative, nondrug reinforcers. Experimental procedures that offer concurrent access to both a drug reinforcer and an alternative, nondrug reinforcer provide a research tool for assessment of medication effects on drug choice and behavioral allocation. Choice procedures are currently the standard in human laboratory research on medications development. Preclinical choice procedures have been utilized in biomedical research since the early 1940's, and during the last 10-15 years, their use for evaluation of medications to treat drug addiction has increased. We propose here that parallel use of choice procedures in preclinical and clinical studies will facilitate translational research on development of medications to treat cocaine addiction. In support of this proposition, a review of the literature suggests strong concordance between preclinical effectiveness of candidate medications to modify cocaine choice in nonhuman primates and rodents and clinical effectiveness of these medications to modify either cocaine choice in human laboratory studies or metrics of cocaine abuse in patients with cocaine use disorder. The strongest evidence for medication effectiveness in preclinical choice studies has been obtained with maintenance on the monoamine releaser d -amphetamine, a candidate agonist medication for cocaine use analogous to use of methadone to treat heroin abuse or nicotine formulations to treat tobacco dependence.

Sex differences in selecting between food and cocaine reinforcement are mediated by estrogen.

Science.gov (United States)

Kerstetter, Kerry A; Ballis, Maya A; Duffin-Lutgen, Stevie; Carr, Amanda E; Behrens, Alexandra M; Kippin, Tod E

2012-11-01

Cocaine-dependent women, relative to their male counterparts, report shorter cocaine-free periods and report transiting faster from first use to entering treatment for addiction. Similarly, preclinical studies indicate that female rats, particularly those in the estrus phase of their reproductive cycle, show increased operant responding for cocaine under a wide variety of schedules. Making maladaptive choices is a component of drug dependence, and concurrent reinforcement schedules that examine cocaine choice offers an animal model of the conditions of human drug use; therefore, the examination of sex differences in decision-making may be critical to understanding why women display a more severe profile of cocaine addiction than men. Accordingly, we assessed sex and estrous cycle differences in choice between food (45 mg grain pellets) and intravenous cocaine (0.4 or 1.0 mg/kg per infusion) reinforcement in male, female (freely cycling), and ovariectomized (OVX) females treated with either estrogen benzoate (EB; 5 μg per day) or vehicle. At both cocaine doses, intact female rats choose cocaine over food significantly more than male rats. However, the estrous cycle did not impact the level of cocaine choice in intact females. Nevertheless, OVX females treated with vehicle exhibited a substantially lower cocaine choice compared with those receiving daily EB or to intact females. These results demonstrate that intact females have a greater preference for cocaine over food compared with males. Furthermore, this higher preference is estrogen-dependent, but does not vary across the female reproductive cycle, suggesting that ovarian hormones regulate cocaine choice. The present findings indicate that there is a biological predisposition for females to forgo food reinforcement to obtain cocaine reinforcement, which may substantially contribute to women experiencing a more severe profile of cocaine addiction than men.

Oral controlled release drug delivery system and Characterization of oral tablets; A review

Directory of Open Access Journals (Sweden)

Muhammad Zaman

2016-01-01

Full Text Available Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets. 

Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex

Science.gov (United States)

Goldstein, Rita Z.; Volkow, Nora D.

2005-01-01

Objective Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. Method An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. Results The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to track, update, and modulate the salience of a reinforcer as a function of context and expectation and the ability to control and inhibit prepotent responses. Conclusions These results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervaluing of alternative reinforcers, and deficits in inhibitory control for drug responses. These changes in addiction, which the authors call I-RISA (impaired response inhibition and salience attribution), expand the traditional concepts of drug dependence that emphasize limbic-regulated responses to pleasure and reward. PMID:12359667

Initial validation of two opiate craving questionnaires the obsessive compulsive drug use scale and the desires for drug questionnaire.

Science.gov (United States)

Franken, Ingmar H A; Hendriksa, Vincent M; van den Brink, Wim

2002-01-01

In the present study, the factor structure, internal consistency, and the concurrent validity of two heroin craving questionnaires are examined. The Desires for Drug Questionnaire (DDQ) measures three factors: desire and intention, negative reinforcement, and control. The Obsessive Compulsive Drug Use Scale (OCDUS) also measures three factors: thoughts about heroin and interference, desire and control, and resistance to thoughts and intention. Subjects were 102 Dutch patients who were currently in treatment for drug dependency. All proposed scales have good reliability and concurrent validity. Implementation of these instruments in both clinical and research field is advocated.

Carbon Fiber Reinforced Polymer Grids for Shear and End Zone Reinforcement in Bridge Beams

Science.gov (United States)

2018-01-01

Corrosion of reinforcing steel reduces life spans of bridges throughout the United States; therefore, using non-corroding carbon fiber reinforced polymer (CFRP) reinforcement is seen as a way to increase service life. The use of CFRP as the flexural ...

Physical capture and release of drug molecules, water and cations by a smectite clay

DEFF Research Database (Denmark)

Carvalho dos Santos, Éverton

-fluorohectorite (LiFh, Li1.2(Mg4.8Li1.2)Si8O20F4), a synthetic clay mineral from the smectite family, have been experimentally analyzed. By means of X-rays powder diffraction (XRD), using both an in-house instrument and synchrotron radiation, UV-Vis spectroscopy, Thermogravimetric Analysis coupled to an Infrared......-analysis and inelastic neutron scattering data we established that the drug presence into the interlayer space of Fh is weakening the water-clay interactions. Furthermore, CIPRO’s release from Fh in synthetic gastric acid juice (SGA) as a function of time and temperature was also carefully followed. Our studies showed...... and toxicological tests, we demonstrated that the effectiveness and toxicity of pure CIPRO is unaffected in the clay-drug complex. To conclude, the high drug adsorption capacity as well as the slow and gradual release from CIPRO when intercalated in Fh adds this synthetic smectite to the list of promising drug...

Analytical toxicology of emerging drugs of abuse--an update.

Science.gov (United States)

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.

Towards the Development of Synthetic Antibiotics: Designs Inspired by Natural Antimicrobial Peptides.

Science.gov (United States)

Azmi, Fazren; Skwarczynski, Mariusz; Toth, Istvan

2016-01-01

Virtually every living organism produces gene-encoded antimicrobial peptides (AMPs) that provide an immediate defence against pathogen invasion. Many AMPs have been isolated and used as antibiotics that are effective against multidrug-resistant bacteria. Although encouraging, AMPs have such poor drug-like properties that their application for clinical use is restricted. In turn, this has diverted research to the development of synthetic molecules that retain the therapeutic efficacy of AMPs but are endowed with greater biological stability and safety profiles. Most of the synthetic molecules, either based on a peptidic or non-peptidic scaffold, have been designed to mimic the amphiphilic properties of native AMPs, which are widely believed to be the key determinant of their antibacterial activity. In this review, the structural, chemical and biophysical features that govern the biological activities of various synthetic designs are discussed extensively. Recent innovative approaches from the literature that exhibit novel concepts towards the development of new synthetic antibacterial agents, including the engineered delivery platform incorporated with AMP mimetics, are also emphasised.

75 FR 67019 - Presidential Determination on Major Illicit Drug Transit or Major Illicit Drug Producing...

Science.gov (United States)

2010-11-01

... and synthetic drugs including marijuana, MDMA, and methamphetamine are produced in Canada and... base, and crack cocaine, primarily from Bolivia; and marijuana. The United States recognizes Brazil's... high- potency marijuana that is trafficked to the United States. The frequent mixing of methamphetamine...

Stability of Synthetic Cathinones in Urine.

Science.gov (United States)

Glicksberg, Lindsay; Kerrigan, Sarah

2018-03-01

In this report, we evaluate the concentration, pH, temperature and analyte-dependent effects on cathinone stability in preserved human urine. A total of 22 synthetic cathinones were evaluated at 100 ng/mL and 1,000 ng/mL in pH 4 and pH 8 urine over 6 months. Specimens were stored at -20°C, 4°C, 20°C and 32°C. The stability of synthetic cathinones was highly dependent on urine pH and storage temperature. Cathinones were considerably more stable in acidic urine (pH 4) at low temperature. In alkaline urine (pH 8) at 32°C, significant losses (>20%) were observed within hours for the majority of drugs. In contrast, all drugs were stable in frozen and refrigerated urine at pH 4 for the duration of the study. These results highlight the importance of sample storage and the potential for pre-analytical changes in concentration during routine shipping and handling of specimens. Significant structural influence was also observed. Cathinones bearing a tertiary amine (pyrrolidine group) were significantly more stable than their secondary amine counterparts. The methylenedioxy group also exerted a significant stabilizing effect on both the tertiary and secondary amines. In the absence of the methylenedioxy group, no significant differences in stability were observed between the unsubstituted and ring substituted secondary amines. Half-lives at ambient temperature in pH 8 urine ranged from 9 h (3-fluoromethcathinone) to 4.3 months (methylenedioxypyrovalerone and 3,4-methylenedioxy-α-pyrrolidinobutiophenone), demonstrating the importance of analyte dependence, and the dual stabilizing effect of both the pyrollidine and methylenedioxy groups. Biological evidence may be subjected to a variety of environmental conditions prior to, and during transport to the forensic laboratory. These findings demonstrate the inherent instability of certain cathinone species in biological evidence under some conditions. Moreover, this study highlights the need for quantitative drug findings in

Synthetic cannabinoids found in "spice" products alter body temperature and cardiovascular parameters in conscious male rats.

Science.gov (United States)

Schindler, Charles W; Gramling, Benjamin R; Justinova, Zuzana; Thorndike, Eric B; Baumann, Michael H

2017-10-01

The misuse of synthetic cannabinoids is a persistent public health concern. Because these drugs target the same cannabinoid receptors as the active ingredient of marijuana, Δ 9 -tetrahydrocannabinol (THC), we compared the effects of synthetic cannabinoids and THC on body temperature and cardiovascular parameters. Biotelemetry transmitters for the measurement of body temperature or blood pressure (BP) were surgically implanted into separate groups of male rats. THC and the synthetic cannabinoids CP55,940, JWH-018, AM2201 and XLR-11 were injected s.c., and rats were placed into isolation cubicles for 3h. THC and synthetic cannabinoids produced dose-related decreases in body temperature that were most prominent in the final 2h of the session. The rank order of potency was CP55,940>AM2201=JWH-018>THC=XLR-11. The cannabinoid inverse agonist rimonabant antagonized the hypothermic effect of all compounds. Synthetic cannabinoids elevated BP in comparison to vehicle treatment during the first h of the session, while heart rate was unaffected. The rank order of potency for BP increases was similar to that seen for hypothermia. Hypertensive effects of CP55,940 and JWH-018 were not antagonized by rimonabant or the neutral antagonist AM4113. However, the BP responses to both drugs were antagonized by pretreatment with either the ganglionic blocker hexamethonium or the α 1 adrenergic antagonist prazosin. Our results show that synthetic cannabinoids produce hypothermia in rats by a mechanism involving cannabinoid receptors, while they increase BP by a mechanism independent of these sites. The hypertensive effect appears to involve central sympathetic outflow. Published by Elsevier B.V.

Combining noncontingent reinforcement and differential reinforcement schedules as treatment for aberrant behavior.

OpenAIRE

Marcus, B A; Vollmer, T R

1996-01-01

Research has shown that noncontingent reinforcement (NCR) can be an effective behavior-reduction procedure when based on a functional analysis. The effects of NCR may be a result of elimination of the contingency between aberrant behavior and reinforcing consequences (extinction) or frequent and free access to reinforcers that may reduce the participant's motivation to engage in aberrant behaviors or mands. If motivation is momentarily reduced, behavior such as mands may not be sensitive to p...

An Effectiveness Trial of Contingency Management in a Felony Preadjudication Drug Court

Science.gov (United States)

Marlowe, Douglas B; Festinger, David S; Dugosh, Karen L; Arabia, Patricia L; Kirby, Kimberly C

2008-01-01

This study evaluated a contingency management (CM) program in a drug court. Gift certificates for compliance were delivered at 4- to 6-week intervals (total value  =  $390.00). Participants in one condition earned gift certificates that escalated by $5.00 increments. Participants in a second condition began earning higher magnitude gift certificates, and the density of reinforcement was gradually decreased. No main effects of CM were detected, which appears to be attributable to a ceiling effect from the intensive contingencies already delivered in the drug court and the low density of reinforcement. Preplanned interaction analyses suggested that participants with more serious criminal backgrounds might have performed better in the CM conditions. This suggests that CM programs may be best suited for more incorrigible drug offenders. PMID:19192860

Degradation of Waterfront Reinforced Concrete Structures

African Journals Online (AJOL)

Key words: Degradation, reinforced concrete, Dar es Salaam port. Abstract—One of the ... especially corrosion of the reinforcement. ... Corrosion of steel reinforcement contributes .... cracks along the line of reinforcement bars and most of the ...

76 FR 55616 - Schedules of Controlled Substances: Temporary Placement of Three Synthetic Cathinones Into...

Science.gov (United States)

2011-09-08

..., and methamphetamine, are central nervous system (CNS) stimulants. The three synthetic cathinones... Forensic Laboratory Information System (NFLIS), a national repository of drug evidence analysis from..., palpitations, muscular tension in the jaw and limbs, headache, agitation, anxiety, tremor, and fever or...

Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions.

Science.gov (United States)

Eberle, Alex N; Rout, Bhimsen; Qi, Mei Bigliardi; Bigliardi, Paul L

2017-01-01

Peptides play decisive roles in the skin, ranging from host defense responses to various forms of neuroendocrine regulation of cell and organelle function. Synthetic peptides conjugated to radionuclides or photosensitizers may serve to identify and treat skin tumors and their metastatic forms in other organs of the body. In the introductory part of this review, the role and interplay of the different peptides in the skin are briefly summarized, including their potential application for the management of frequently occurring skin cancers. Special emphasis is given to different targeting options for the treatment of melanoma and melanotic lesions. Radionuclide Targeting: α-Melanocyte-stimulating hormone (α-MSH) is the most prominent peptide for targeting of melanoma tumors via the G protein-coupled melanocortin-1 receptor that is (over-)expressed by melanoma cells and melanocytes. More than 100 different linear and cyclic analogs of α-MSH containing chelators for 111In, 67/68Ga, 64Cu, 90Y, 212Pb, 99mTc, 188Re were synthesized and examined with experimental animals and in a few clinical studies. Linear Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH2 (NAP-amide) and Re-cyclized Cys- Cys-Glu-His-D-Phe-Arg-Trp-Cys-Arg-Pro-Val-NH2 (Re[Arg11]CCMSH) containing different chelators at the N- or C-terminus served as lead compounds for peptide drugs with further optimized characteristics. Alternatively, melanoma may be targeted with radiopeptides that bind to melanin granules occurring extracellularly in these tumors. Photosensitizer targeting: A more recent approach is the application of photosensitizers attached to the MSH molecule for targeted photodynamic therapy using LED or coherent laser light that specifically activates the photosensitizer. Experimental studies have demonstrated the feasibility of this approach as a more gentle and convenient alternative compared to radionuclides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Confinement of Reinforced-Concrete Columns with Non-Code Compliant Confining Reinforcement plus Supplemental Pen-Binder

Directory of Open Access Journals (Sweden)

Anang Kristianto

2012-11-01

Full Text Available One of the important requirements for earthquake resistant building related to confinement is the use of seismic hooks in the hoop or confining reinforcement of reinforced-concrete column elements. However, installation of a confining reinforcement with a 135-degree hook is not easy. Therefore, in practice, many construction workers apply a confining reinforcement with a 90-degreehook (non-code compliant. Based on research and records of recent earthquakes in Indonesia, the use of a non-code compliant confining reinforcement for concrete columns produces structures with poor seismic performance. This paper presents a study that introduces an additional element that is expected to improve the effectiveness of concrete columns confined with a non-code compliant confining reinforcement. The additional element, named a pen-binder, is used to keep the non-code compliant confining reinforcement in place. The effectiveness of this element under pure axial concentric loading was investigatedcomprehensively.The specimens tested in this study were 18 concrete columns,with a cross-section of 170 mm x 170 mm and a height of 480 mm. The main test variables were the material type of the pen-binder, the angle of the hook, and the confining reinforcement configuration.The test results indicate that adding pen-binders can effectively improve the strength and ductility of the column specimens confined with a non-code compliant confining reinforcement

Hazardous drugs: new challenges, new opportunities

Directory of Open Access Journals (Sweden)

Silvia Valero García

2016-03-01

Full Text Available Occupational exposure to hazardous drugs can cause harmful effects on health professionals and several protective measures must be taken. Nevertheless, classification of hazardous drugs is not the same in all the published repertoires and the terminology is still confusing: hazardous drugs, biohazardous drugs or risky drugs are terms improperly described and can define very different drugs with a very different hazard profiles. In Spain, there is not an updated official list of hazardous drugs, and healthcare professionals must consider and follow other published lists. In our opinion, it is mandatory to do a consensus among these professionals, administration and labor union organizations in order to clarify some conflictive questions not only in healthcare settings but in investigational and academic scenarios too. These multidisciplinary groups should be involved also in teaching new and non-experienced personnel and in the knowledge reinforcement for the experienced ones

Influence of reinforcement's corrosion into hyperstatic reinforced concrete beams: a probabilistic failure scenarios analysis

Directory of Open Access Journals (Sweden)

G. P. PELLIZZER

Full Text Available AbstractThis work aims to study the mechanical effects of reinforcement's corrosion in hyperstatic reinforced concrete beams. The focus is the probabilistic determination of individual failure scenarios change as well as global failure change along time. The limit state functions assumed describe analytically bending and shear resistance of reinforced concrete rectangular cross sections as a function of steel and concrete resistance and section dimensions. It was incorporated empirical laws that penalize the steel yield stress and the reinforcement's area along time in addition to Fick's law, which models the chloride penetration into concrete pores. The reliability theory was applied based on Monte Carlo simulation method, which assesses each individual probability of failure. The probability of global structural failure was determined based in the concept of failure tree. The results of a hyperstatic reinforced concrete beam showed that reinforcements corrosion make change into the failure scenarios modes. Therefore, unimportant failure modes in design phase become important after corrosion start.

CYP3A4 Mediates Oxidative Metabolism of the Synthetic Cannabinoid AKB-48.

Science.gov (United States)

Holm, Niels Bjerre; Nielsen, Line Marie; Linnet, Kristian

2015-09-01

Synthetic cannabinoid designer drugs have emerged as drugs of abuse during the last decade, and acute intoxication cases are documented in the scientific literature. Synthetic cannabinoids are extensively metabolized, but our knowledge of the involved enzymes is limited. Here, we investigated the metabolism of N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48), a compound identified in herbal blends from 2012 and onwards. We screened for metabolite formation using a panel of nine recombinant cytochrome P450 (CYP) enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, and 3A4) and compared the formed metabolites to human liver microsomal (HLM) incubations with specific inhibitors against CYP2D6, 2C19, and 3A4, respectively. The data reported here demonstrate CYP3A4 to be the major CYP enzyme responsible for the oxidative metabolism of AKB-48, preferentially performing the oxidation on the adamantyl moiety. Genetic polymorphisms are likely not important with regard to toxicity given the major involvement of CYP3A4. Adverse drug-drug interactions (DDIs) could potentially occur in cases with co-intake of strong CYP3A4 inhibitors, e.g., HIV antivirals and azole antifungal agents.

Influence of Natural, Synthetic Polymers and Fillers on sustained release matrix tablets of Pregabalin

OpenAIRE

Vijaya Durga. K; Ashok Kumar. P; Suresh V Kulkarni

2013-01-01

The objective of the present study was to develop sustained release matrix tablets of Pregabalin for the treatment of neuropathic pain and epilepsy. The tablets were prepared by wet granulation and formulated using drug with Hydrophilic, hydrophobic, synthetic, natural polymers and 4 different fillers were used. The effect of Polymer concentration, combination and fillers on drug release rate was analyzed for the formulations F-1 to F-17. The tablets were subjected to physicochemical studies,...

Biodegradable polyesters reinforced with triclosan loaded polylactide micro/nanofibers: Properties, release and biocompatibility

Directory of Open Access Journals (Sweden)

L. J. del Valle

2012-04-01

Full Text Available Mechanical properties and drug release behavior were studied for three biodegradable polyester matrices (polycaprolactone, poly(nonamethylene azelate and the copolymer derived from 1,9-nonanediol and an equimolar mixture of azelaic and pimelic acids reinforced with polylactide (PLA fibers. Electrospinning was used to produce suitable mats constituted by fibers of different diameters (i.e. from micro- to nanoscale and a homogeneous dispersion of a representative hydrophobic drug (i.e. triclosan. Fabrics were prepared by a molding process, which allowed cold crystallization of PLA micro/nanofibers and hot crystallization of the polyester matrices. The orientation of PLA molecules during electrospinning favored the crystallization process, which was slightly enhanced when the diameter decreased. Incorporation of PLA micro/nanofibers led to a significant increase in the elastic modulus and tensile strength, and in general to a decrease in the strain at break. The brittle fracture was clearer when high molecular weight samples with high plastic deformation were employed. Large differences in the release behavior were detected depending on the loading process, fiber diameter size and hydrophobicity of the polyester matrix. The release of samples with the drug only loaded into the reinforcing fibers was initially fast and then became slow and sustained, resulting in longer lasting antimicrobial activity. Biocompatibility of all samples studied was demonstrated by adhesion and proliferation assays using HEp-2 cell cultures.

Preparation and evaluation of a novel anticancer drug delivery carrier for 5-Fluorouracil using synthetic bola-amphiphile based on lysine as polar heads

Energy Technology Data Exchange (ETDEWEB)

Hu, Beibei [School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (China); Yuan, Yue, E-mail: hiyueyuan@163.com [School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (China); Yan, Yun [College of Chemistry and Molecular Engineering, Peking University, 202 Chenfu Road, Beijing 100871 (China); Zhou, Xiaoping [School of Pharmacy, Jilin University, 1266 Fujin Road, Changchun 130021 (China); Li, Yue; Kan, Qiming [School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (China); Li, Sanming, E-mail: li_sanming@sina.com [School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (China)

2017-06-01

A novel bolaamphiphile surfactant N,N′-(dodecane-1, 12-diyl) bis (2,6-diaminohexanamide) (DADL) was designed and synthesized using L-lysine and 1,12-diaminododecane as the hydrophilic and hydrophobic part, respectively. After separation and purification, the structure of the synthetic bolaamphiphile surfactant was verified by FTIR, MS and {sup 1}H NMR. The synthetic bolaamphiphile was able to self-assemble to form vesicles. After formulation screening, vesicles loaded with 5-Fluorouracil (5-Fu) were prepared with Tween 60 and DADL by sonication and were examined by dynamic light scattering and transmission electron microscopy. Micro-FTIR was applied to investigate the conformation of the bola molecules within the vesicle membrane. The release profile of the vesicles showed a pH-sensitive and sustained release. No significant toxicity was observed in an in vitro cell viability assay. The antitumor efficacy of the 5-Fu-loaded vesicles on H{sub 22} tumor-bearing mice was remarkably high due to the EPR effects. These results show that our novel bolaamphiphile derived from lysine has excellent potential as a pH-sensitive drug carrier. - Highlights: • A novel bolaamphiphile molecule with lysine as hydrophilic part was synthesized. • The synthesized bolaamphiphile could self-assemble to form nano-sized vesicles. • The vesicles were pH-sensitive and have tumor-targeting potential.

Dendrimers bind antioxidant polyphenols and cisplatin drug.

Directory of Open Access Journals (Sweden)

Amine Abderrezak

Full Text Available Synthetic polymers of a specific shape and size play major role in drug delivery systems. Dendrimers are unique synthetic macromolecules of nanometer dimensions with a highly branched structure and globular shape with potential applications in gene and drug delivery. We examine the interaction of several dendrimers of different compositions mPEG-PAMAM (G3, mPEG-PAMAM (G4 and PAMAM (G4 with hydrophilic and hydrophobic drugs cisplatin, resveratrol, genistein and curcumin at physiological conditions. FTIR and UV-visible spectroscopic methods as well as molecular modeling were used to analyse drug binding mode, the binding constant and the effects of drug complexation on dendrimer stability and conformation. Structural analysis showed that cisplatin binds dendrimers in hydrophilic mode via Pt cation and polymer terminal NH(2 groups, while curcumin, genistein and resveratrol are located mainly in the cavities binding through both hydrophobic and hydrophilic contacts. The overall binding constants of durg-dendrimers are ranging from 10(2 M(-1 to 10(3 M(-1. The affinity of dendrimer binding was PAMAM-G4>mPEG-PAMAM-G4>mPEG-PAMAM-G3, while the order of drug-polymer stability was curcumin>cisplatin>genistein>resveratrol. Molecular modeling showed larger stability for genisten-PAMAM-G4 (ΔG = -4.75 kcal/mol than curcumin-PAMAM-G4 ((ΔG = -4.53 kcal/mol and resveratrol-PAMAM-G4 ((ΔG = -4.39 kcal/mol. Dendrimers might act as carriers to transport hydrophobic and hydrophilic drugs.

Designing synthetic biology.

Science.gov (United States)

Agapakis, Christina M

2014-03-21

Synthetic biology is frequently defined as the application of engineering design principles to biology. Such principles are intended to streamline the practice of biological engineering, to shorten the time required to design, build, and test synthetic gene networks. This streamlining of iterative design cycles can facilitate the future construction of biological systems for a range of applications in the production of fuels, foods, materials, and medicines. The promise of these potential applications as well as the emphasis on design has prompted critical reflection on synthetic biology from design theorists and practicing designers from many fields, who can bring valuable perspectives to the discipline. While interdisciplinary connections between biologists and engineers have built synthetic biology via the science and the technology of biology, interdisciplinary collaboration with artists, designers, and social theorists can provide insight on the connections between technology and society. Such collaborations can open up new avenues and new principles for research and design, as well as shed new light on the challenging context-dependence-both biological and social-that face living technologies at many scales. This review is inspired by the session titled "Design and Synthetic Biology: Connecting People and Technology" at Synthetic Biology 6.0 and covers a range of literature on design practice in synthetic biology and beyond. Critical engagement with how design is used to shape the discipline opens up new possibilities for how we might design the future of synthetic biology.

What to Do If Your Adult Friend or Loved One Has a Problem with Drugs

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

What to Do If You Have a Problem with Drugs: For Teens and Young Adults

Science.gov (United States)

... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Finite element modeling of reinforced concrete beams with a hybrid combination of steel and aramid reinforcement

International Nuclear Information System (INIS)

Hawileh, R.A.

2015-01-01

Highlights: • Modeling of concrete beams reinforced steel and FRP bars. • Developed finite element models achieved good results. • The models are validated via comparison with experimental results. • Parametric studies are performed. - Abstract: Corrosion of steel bars has an adverse effect on the life-span of reinforced concrete (RC) members and is usually associated with crack development in RC beams. Fiber reinforced polymer (FRP) bars have been recently used to reinforce concrete members in flexure due to their high tensile strength and superior corrosion resistance properties. However, FRP materials are brittle in nature, thus RC beams reinforced with such materials would exhibit a less ductile behavior when compared to similar members reinforced with conventional steel reinforcement. Recently, researchers investigated the performance of concrete beams reinforced with a hybrid combination of steel and Aramid Fiber Reinforced Polymer (AFRP) reinforcement to maintain a reasonable level of ductility in such members. The function of the AFRP bars is to increase the load-carrying capacity, while the function of the steel bars is to ensure ductility of the flexural member upon yielding in tension. This paper presents a three-dimensional (3D) finite element (FE) model that predicted the load versus mid-span deflection response of tested RC beams conducted by other researchers with a hybrid combination of steel and AFRP bars. The developed FE models account for the constituent material nonlinearities and bond–slip behavior between the reinforcing bars and adjacent concrete surfaces. It was concluded that the developed models can accurately capture the behavior and predicts the load-carrying capacity of such RC members. In addition, a parametric study is conducted using the validated models to investigate the effect of AFRP bar size, FRP material type, bond–slip action, and concrete compressive strength on the performance of concrete beams when reinforced

Health monitoring of precast bridge deck panels reinforced with glass fiber reinforced polymer (GFRP) bars.

Science.gov (United States)

2012-03-01

The present research project investigates monitoring concrete precast panels for bridge decks that are reinforced with Glass Fiber Reinforced Polymer (GFRP) bars. Due to the lack of long term research on concrete members reinforced with GFRP bars, lo...

Caregiver preference for reinforcement-based interventions for problem behavior maintained by positive reinforcement.

Science.gov (United States)

Gabor, Anne M; Fritz, Jennifer N; Roath, Christopher T; Rothe, Brittany R; Gourley, Denise A

2016-06-01

Social validity of behavioral interventions typically is assessed with indirect methods or by determining preferences of the individuals who receive treatment, and direct observation of caregiver preference rarely is described. In this study, preferences of 5 caregivers were determined via a concurrent-chains procedure. Caregivers were neurotypical, and children had been diagnosed with developmental disabilities and engaged in problem behavior maintained by positive reinforcement. Caregivers were taught to implement noncontingent reinforcement (NCR), differential reinforcement of alternative behavior (DRA), and differential reinforcement of other behavior (DRO), and the caregivers selected interventions to implement during sessions with the child after they had demonstrated proficiency in implementing the interventions. Three caregivers preferred DRA, 1 caregiver preferred differential reinforcement procedures, and 1 caregiver did not exhibit a preference. Direct observation of implementation in concurrent-chains procedures may allow the identification of interventions that are implemented with sufficient integrity and preferred by caregivers. © 2016 Society for the Experimental Analysis of Behavior.

Recent advances in fluorination techniques and their anticipated impact on drug metabolism and toxicity.

Science.gov (United States)

Murphy, Cormac D; Sandford, Graham

2015-04-01

Fluorine's unique physicochemical properties make it a key element for incorporation into pharmacologically active compounds. Its presence in a drug can alter a number of characteristics that affect ADME-Tox, which has prompted efforts at improving synthetic fluorination procedures. This review describes the influence of fluorine on attributes such as potency, lipophilicity, metabolic stability and bioavailablility and how the effects observed are related to the physicochemical characteristics of the element. Examples of more recently used larger scale synthetic methods for introduction of fluorine into drug leads are detailed and the potential for using biological systems for fluorinated drug production is discussed. The synthetic procedures for carbon-fluorine bond formation largely still rely on decades-old technology for the manufacturing scale and new reagents and methods are required to meet the demands for the preparation of structurally more complex drugs. The improvement of in vitro and computational methods should make fluorinated drug design more efficient and place less emphasis on approaches such as fluorine scanning and animal studies. The introduction of new fluorinated drugs, and in particular those that have novel fluorinated functional groups, should be accompanied by rigorous environmental assessment to determine the nature of transformation products that may cause ecological damage.

Drug discovery: Fighting evolution with chemical synthesis

Science.gov (United States)

Yan, Ming; Baran, Phil S.

2016-05-01

A synthetic strategy has been developed that provides easy access to structurally diverse analogues of naturally occurring antibiotics, providing a fresh means of attack in the war against drug-resistant bacteria. See Article p.338

Effects of reinforcer magnitude on responding under differential-reinforcement-of-low-rate schedules of rats and pigeons.

Science.gov (United States)

Doughty, Adam H; Richards, Jerry B

2002-07-01

Experiment I investigated the effects of reinforcer magnitude on differential-reinforcement-of-low-rate (DRL) schedule performance in three phases. In Phase 1, two groups of rats (n = 6 and 5) responded under a DRI. 72-s schedule with reinforcer magnitudes of either 30 or 300 microl of water. After acquisition, the water amounts were reversed for each rat. In Phase 2, the effects of the same reinforcer magnitudes on DRL 18-s schedule performance were examined across conditions. In Phase 3, each rat responded unider a DR1. 18-s schedule in which the water amotnts alternated between 30 and 300 microl daily. Throughout each phase of Experiment 1, the larger reinforcer magnitude resulted in higher response rates and lower reinforcement rates. The peak of the interresponse-time distributions was at a lower value tinder the larger reinforcer magnitude. In Experiment 2, 3 pigeons responded under a DRL 20-s schedule in which reinforcer magnitude (1-s or 6-s access to grain) varied iron session to session. Higher response rates and lower reinforcement rates occurred tinder the longer hopper duration. These results demonstrate that larger reinforcer magnitudes engender less efficient DRL schedule performance in both rats and pigeons, and when reinforcer magnitude was held constant between sessions or was varied daily. The present results are consistent with previous research demonstrating a decrease in efficiency as a function of increased reinforcer magnituide tinder procedures that require a period of time without a specified response. These findings also support the claim that DRI. schedule performance is not governed solely by a timing process.

The usage of carbon fiber reinforcement polymer and glass fiber reinforcement polymer for retrofit technology building

Science.gov (United States)

Tarigan, Johannes; Meka, Randi; Nursyamsi

2018-03-01

Fiber Reinforcement Polymer has been used as a material technology since the 1970s in Europe. Fiber Reinforcement Polymer can reinforce the structure externally, and used in many types of buildings like beams, columns, and slabs. It has high tensile strength. Fiber Reinforcement Polymer also has high rigidity and strength. The profile of Fiber Reinforcement Polymer is thin and light, installation is simple to conduct. One of Fiber Reinforcement Polymer material is Carbon Fiber Reinforcement Polymer and Glass Fiber Reinforcement Polymer. These materials is tested when it is installed on concrete cylinders, to obtain the comparison of compressive strength CFRP and GFRP. The dimension of concrete is diameter of 15 cm and height of 30 cm. It is amounted to 15 and divided into three groups. The test is performed until it collapsed to obtain maximum load. The results of research using CFRP and GFRP have shown the significant enhancement in compressive strength. CFRP can increase the compressive strength of 26.89%, and GFRP of 14.89%. For the comparison of two materials, CFRP is more strengthening than GFRP regarding increasing compressive strength. The usage of CFRP and GFRP can increase the loading capacity.

Biological Evidence for Paradoxical Improvement of Psychiatric Disorder Symptoms by Addictive Drugs.

Science.gov (United States)

Müller, Christian P; Kornhuber, Johannes

2017-06-01

Addiction biology has focused on the mechanisms of the positive and negative reinforcing actions of addictive drugs but neglected potential benefits. Two new studies provide the first insights into a neurobiology of psychoactive drug instrumentalization. This may help us design better models for addiction neuroscience and opens a new dimension for the development of personalized pharmacotherapy of drug addiction. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vibrated and self-compacting fibre reinforced concrete: experimental investigation on the fibre orientation

Science.gov (United States)

Conforti, A.; Plizzari, G. A.; Zerbino, R.

2017-09-01

In addition to the fibre type and content, the residual properties of fibre reinforced concrete are influenced by fibre orientation. Consequently, the performance fibre reinforced concrete can be affected by its fresh properties (workability, flowing capacity) and by casting and compaction processes adopted. This paper focuses on the study of the orientation of steel or macro-synthetic fibres in two materials characterized by very different fresh properties: vibrated and self-compacting concrete. Four rectangular slabs 1800 mm long, 925 mm wide and 100 mm high were produced changing concrete and fibre type. From each slab, eighteen small prisms (550 mm long) were firstly cut either orthogonal or parallel to casting direction and, secondly, notched and tested in bending according to EN 14651. Experimental results showed that the toughness properties of a thin slab significantly varies both in vibrated and self-compacting concrete, even if in case of self-compacting concrete this variation resulted higher. Steel fibres led to greater variability of results compared to polymer one, underlining a different fibre orientation. A discussion on the relative residual capacity measured on the prisms sawn from the slabs and the parameters obtained from standard specimens is performed.

Reinforced concrete tomography

International Nuclear Information System (INIS)

Mariscotti, M.A.J.; Morixe, M.; Tarela, P.A.; Thieberger, P.

1997-01-01

In this paper we describe the technique of reinforced concrete tomography, its historical background, recent technological developments and main applications. Gamma radiation sensitive plates are imprinted with radiation going through the concrete sample under study, and then processed to reveal the presence of reinforcement and defects in the material density. The three dimensional reconstruction, or tomography, of the reinforcement out of a single gammagraphy is an original development alternative to conventional methods. Re-bar diameters and positions may be determined with an accuracy of ± 1 mm 0.5-1 cm, respectively. The non-destructive character of this technique makes it particularly attractive in cases of inhabited buildings and diagnoses of balconies. (author) [es

Reward-based hypertension control by a synthetic brain-dopamine interface.

Science.gov (United States)

Rössger, Katrin; Charpin-El Hamri, Ghislaine; Fussenegger, Martin

2013-11-05

Synthetic biology has significantly advanced the design of synthetic trigger-controlled devices that can reprogram mammalian cells to interface with complex metabolic activities. In the brain, the neurotransmitter dopamine coordinates communication with target neurons via a set of dopamine receptors that control behavior associated with reward-driven learning. This dopamine transmission has recently been suggested to increase central sympathetic outflow, resulting in plasma dopamine levels that correlate with corresponding brain activities. By functionally rewiring the human dopamine receptor D1 (DRD1) via the second messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing cAMP response element-binding protein 1(CREB1)-specific cAMP-responsive operator modules, we have designed a synthetic dopamine-sensitive transcription controller that reversibly fine-tunes specific target gene expression at physiologically relevant brain-derived plasma dopamine levels. Following implantation of circuit-transgenic human cell lines insulated by semipermeable immunoprotective microcontainers into mice, the designer device interfaced with dopamine-specific brain activities and produced a systemic expression response when the animal's reward system was stimulated by food, sexual arousal, or addictive drugs. Reward-triggered brain activities were able to remotely program peripheral therapeutic implants to produce sufficient amounts of the atrial natriuretic peptide, which reduced the blood pressure of hypertensive mice to the normal physiologic range. Seamless control of therapeutic transgenes by subconscious behavior may provide opportunities for treatment strategies of the future.

Antimicrobial activity of new porphyrins of synthetic and natural origin

Science.gov (United States)

Gyulkhandanyan, Grigor V.; Ghazaryan, Robert K.; Paronyan, Marina H.; Ulikhanyan, Ghukas I.; Gyulkhandanyan, Aram G.; Sahakyan, Lida A.

2012-03-01

Antimicrobial photodynamic inactivation has been successfully used against Gram (+) microorganisms, but most of the photosensitizers (PSs) on Gram (-) bacteria acts weakly. PSs are the natural or synthetic origin dyes, mainly porphyrins. We have synthesized more than 100 new cationic porphyrins and metalloporphyrins with different functional groups (hydroxyethyl, butyl, allyl, methallyl) and metals (cobalt, iron, copper, zinc, silver and other); from the nettle have also been purified pheophytin (a+b) and pheophytin (a) and have synthesized their Ag-and Zn-metalloporphyrins. It was found that in the dark (cytotoxic) mode, the most highly efficiency against microorganisms showed Agmetalloporphyrins of both types of porphyrins (synthetic and natural). Metalloporphyrin of natural origin Ag-pheophytin (a + b) is a strong antibacterial agent and causes 100% death as the Gram (+) microorganisms (St. aureus and MRSA) and the Gram (-) microorganisms (E.coli and Salmonella). It is established that for the destruction of Gram (+) and Gram (-) microorganisms in photodynamic mode cationic water-soluble synthetic metalloporphyrins, especially Zn-TBut4PyP, many times more effective than pheophytins. In vivo conditions on mice established that the best therapeutic activity against various strains of the microorganism St. aureus has the synthetic metalloporphyrin Ag-TBut4PyP. It is significantly more efficient than known drug "Chlorophyllipt" (2.5-3 times) and leads the survival rate of animals up to 50-60%.

Reinforced long saphenous vein bypass graft for infrainguinal reconstruction procedures: case series and literature review.

LENUS (Irish Health Repository)

Hynes, Niamh

2006-03-01

Poor rehabilitation rates and the high-cost of managing postamputation patients justify an aggressive revascularization policy in critical lower limb ischemia. Endovascular therapy is our first choice for limb salvage in these patients. However there are patients for whom endovascular therapy is not feasible. When bypass is necessary, autologous vein is a superior conduit to synthetic material. However, varicosities usually contraindicate autologous vein bypass because of the risk of aneurysm formation, rupture and increased intimal hyperplasia compared with nonvaricose venous grafts. We report the use of varicosed long saphenous vein (LSV) with external Dacron support in infrainguinal bypass procedures for limb salvage, where endovascular therapy was not feasible. The external Dacron tube was not brought close to the distal anastomotic area itself. With a mean follow-up of 18 months, duplex ultrasonography and computed tomography angiography showed no evidence of stenosis of the reinforced vein segments or aneurysmal degeneration of the residual vein. External reinforcement with Dacron prosthesis allows the use of autogenous greater saphenous veins with varicose dilatation without compromising graft patency and limb salvage.

The study of mechanical properties of pineapple leaf fibre reinforced tapioca based bioplastic resin composite

Directory of Open Access Journals (Sweden)

Mathivanan D.

2016-01-01

Full Text Available Natural fibre reinforced composite has brought the material engineering to a high new level of research. Natural fibres are compatible with matrices like polypropylene and can be used as reinforcement material to reduce the composition of plastic in a material. Natural fibres such as kenaf, pineapple leaf, and coir already found its importance in reducing the dependence of petroleum based products. However the biodegradability of the product at the end of the intended lifespan is still questionable. This has led many researches to look for a suitable replacement for synthetic fibres and achieve better adhesion between fibre and matrix. In this study, fiber and matrix which are hydrophilic in nature was used and the mixture was extruded and hot compressed to acquire better mechanical properties. The specimens were fabricated and tested according to ASTM D638. The 30% composition illustrates the best average modulus value among other composition and from this result it can be concluded that the increase of PALF fibre in TBR composite increases the modulus strength of the composite.

Mechanical properties and fire retardancy of bidirectional reinforced composite based on biodegradable starch resin and basalt fibres

Directory of Open Access Journals (Sweden)

2008-11-01

Full Text Available Environmental problems caused by extensive use of polymeric materials arise mainly due to lack of landfill space and depletion of finite natural resources of fossil raw materials, such as petroleum or natural gas. The substitution of synthetic petroleum-based resins with natural biodegradable resins appears to be one appropriate measure to remedy the above-mentioned situation. This study presents the development of a composite that uses environmentally degradable starch-based resin as matrix and basalt fibre plain fabric as reinforcement. Prepreg sheets were manufactured by means of a modified doctor blade system and a hot power press. The sheets were used to manufacture bidirectional-reinforced specimens with fibre volume contents ranging from 33 to 61%. Specimens were tested for tensile and flexural strength, and exhibited values of up to 373 and 122 MPa, respectively. Through application of silane coupling agents to the reinforcement fibres, the flexural composite properties were subsequently improved by as much as 38%. Finally, in order to enhance the fire retardancy and hence the applicability of the composite, fire retardants were applied to the resin, and their effectiveness was tested by means of flame rating (according to UL 94 and thermogravimetric analysis (TGA, respectively.

Drug-drug interactions and adverse drug reactions in polypharmacy among older adults: an integrative review 1

Science.gov (United States)

Rodrigues, Maria Cristina Soares; de Oliveira, Cesar

2016-01-01

ABSTRACT Objective: to identify and summarize studies examining both drug-drug interactions (DDI) and adverse drug reactions (ADR) in older adults polymedicated. Methods: an integrative review of studies published from January 2008 to December 2013, according to inclusion and exclusion criteria, in MEDLINE and EMBASE electronic databases were performed. Results: forty-seven full-text studies including 14,624,492 older adults (≥ 60 years) were analyzed: 24 (51.1%) concerning ADR, 14 (29.8%) DDI, and 9 studies (19.1%) investigating both DDI and ADR. We found a variety of methodological designs. The reviewed studies reinforced that polypharmacy is a multifactorial process, and predictors and inappropriate prescribing are associated with negative health outcomes, as increasing the frequency and types of ADRs and DDIs involving different drug classes, moreover, some studies show the most successful interventions to optimize prescribing. Conclusions: DDI and ADR among older adults continue to be a significant issue in the worldwide. The findings from the studies included in this integrative review, added to the previous reviews, can contribute to the improvement of advanced practices in geriatric nursing, to promote the safety of older patients in polypharmacy. However, more research is needed to elucidate gaps. PMID:27598380

Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project

OpenAIRE

Sliva, Anna; Yang, Huanming; Boeke, Jef D.; Mathews, Debra J. H.

2015-01-01

First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) Project is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with...

Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.

Science.gov (United States)

Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

2013-09-01

This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.

Effects of muscimol, amphetamine, and DAMGO injected into the nucleus accumbens shell on food-reinforced lever pressing by undeprived rats.

Science.gov (United States)

Stratford, Thomas R; Wirtshafter, David

2012-05-01

Previous studies have shown that large increases in food intake in nondeprived animals can be induced by injections of both the GABA(A) agonist muscimol and the μ-opioid agonist DAMGO into the nucleus accumbens shell (AcbSh), while injections of the catecholamine agonist amphetamine have little effect. In the current study we examined whether injections of these drugs are able to increase food-reinforced lever pressing in nondeprived rats. Twelve subjects were trained to lever press on a continuous reinforcement schedule while food deprived and were then tested after being placed back on ad libitum feeding. Under these conditions, responding was markedly increased by injections of either muscimol or DAMGO, although the onset of the effects of the latter drug was delayed by 30-40 min. In contrast, amphetamine injections failed to increase reinforced lever pressing, although they did enhance responding on a non-reinforced lever, presumably reflecting alterations in behavioral activation. These results demonstrate that stimulation of GABA(A) and μ-opioid receptors within the AcbSh is able to promote not only food intake, but also food-directed operant behavior. In contrast, stimulation of AcbSh dopamine receptors may enhance behavioral arousal, but does not appear to specifically potentiate behaviors directed toward food procurement. Copyright © 2012 Elsevier Inc. All rights reserved.

Prediction of reinforcement corrosion using corrosion induced cracks width in corroded reinforced concrete beams

International Nuclear Information System (INIS)

Khan, Inamullah; François, Raoul; Castel, Arnaud

2014-01-01

This paper studies the evolution of reinforcement corrosion in comparison to corrosion crack width in a highly corroded reinforced concrete beam. Cracking and corrosion maps of the beam were drawn and steel reinforcement was recovered from the beam to observe the corrosion pattern and to measure the loss of mass of steel reinforcement. Maximum steel cross-section loss of the main reinforcement and average steel cross-section loss between stirrups were plotted against the crack width. The experimental results were compared with existing models proposed by Rodriguez et al., Vidal et al. and Zhang et al. Time prediction models for a given opening threshold are also compared to experimental results. Steel cross-section loss for stirrups was also measured and was plotted against the crack width. It was observed that steel cross-section loss in the stirrups had no relationship with the crack width of longitudinal corrosion cracks. -- Highlights: •Relationship between crack and corrosion of reinforcement was investigated. •Corrosion results of natural process and then corresponds to in-situ conditions. •Comparison with time predicting model is provided. •Prediction of load-bearing capacity from crack pattern was studied

Cytochrome P450-mediated metabolism of the synthetic cannabinoids UR-144 and XLR-11

DEFF Research Database (Denmark)

Nielsen, Line Marie; Holm, Niels Bjerre; Olsen, Lars

2016-01-01

In recent years, synthetic cannabinoids have emerged in the illicit drug market, in particular via the Internet, leading to abuse of these drugs. There is currently limited knowledge about the specific enzymes involved in the metabolism of these drugs. In this study, we investigated the cytochrome...... of UR-144 and XLR-11, while inhibition of the other CYP enzymes in HLM had only minor effects. Thus, CYP3A4 is the major contributor to the CYP mediated metabolism of UR-144 and XLR-11 with minor contributions from CYP1A2. Users of UR-144 and XLR-11 are thus subject to the influence of potential drug-drug...... interactions, if they are concomitantly medicated with CYP3A4 inducers (e.g. some antiepileptics) or inhibitors (e.g. some antifungal drugs). Copyright © 2015 John Wiley & Sons, Ltd....

Synthetic oleanane triterpenoids: multifunctional drugs with a broad range of applications for prevention and treatment of chronic disease.

Science.gov (United States)

Liby, Karen T; Sporn, Michael B

2012-10-01

We review the rationale for the use of synthetic oleanane triterpenoids (SOs) for prevention and treatment of disease, as well as extensive biological data on this topic resulting from both cell culture and in vivo studies. Emphasis is placed on understanding mechanisms of action. SOs are noncytotoxic drugs with an excellent safety profile. Several hundred SOs have now been synthesized and in vitro have been shown to: 1) suppress inflammation and oxidative stress and therefore be cytoprotective, especially at low nanomolar doses, 2) induce differentiation, and 3) block cell proliferation and induce apoptosis at higher micromolar doses. Animal data on the use of SOs in neurodegenerative diseases and in diseases of the eye, lung, cardiovascular system, liver, gastrointestinal tract, and kidney, as well as in cancer and in metabolic and inflammatory/autoimmune disorders, are reviewed. The importance of the cytoprotective Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1/nuclear factor (erythroid-derived 2)-like 2/antioxidant response element (Keap1/Nrf2/ARE) pathway as a mechanism of action is explained, but interactions with peroxisome proliferator-activated receptor γ (PARPγ), inhibitor of nuclear factor-κB kinase complex (IKK), janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT), human epidermal growth factor receptor 2 (HER2)/ErbB2/neu, phosphatase and tensin homolog (PTEN), the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway, mammalian target of rapamycin (mTOR), and the thiol proteome are also described. In these interactions, Michael addition of SOs to reactive cysteine residues in specific molecular targets triggers biological activity. Ultimately, SOs are multifunctional drugs that regulate the activity of entire networks. Recent progress in the earliest clinical trials with 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) methyl ester (bardoxolone methyl) is also

Characterization of Thermal Stability of Synthetic and Semi-Synthetic Engine Oils

Directory of Open Access Journals (Sweden)

Anand Kumar Tripathi

2015-03-01

Full Text Available Engine oils undergo oxidative degradation and wears out during service. Hence it is important to characterize ageing of engine oils at different simulated conditions to evaluate the performance of existing oils and also design new formulations. This work focuses on characterizing the thermo-oxidative degradation of synthetic and semi-synthetic engine oils aged at 120, 149 and 200 °C. Apparent activation energy of decomposition of aged oils evaluated using the isoconversional Kissinger-Akahira-Sunose technique was used as a thermal stability marker. The temporal variation of stability at different ageing temperatures was corroborated with kinematic viscosity, oxidation, sulfation and nitration indices, total base number, antiwear additive content and molecular structure of the organic species present in the oils. At the lowest temperature employed, synthetic oil underwent higher rate of oxidation, while semi-synthetic oil was stable for longer time periods. At higher temperatures, the initial rate of change of average apparent activation energy of synthetic oil correlated well with a similar variation in oxidation number. A mixture of long chain linear, branched, and cyclic hydrocarbons were observed when semi-synthetic oil was degraded at higher temperatures.

AKI associated with synthetic cannabinoids: a case series.

Science.gov (United States)

Bhanushali, Gautam Kantilal; Jain, Gaurav; Fatima, Huma; Leisch, Leah J; Thornley-Brown, Denyse

2013-04-01

SPICE, or K2, encompasses preparations of synthetic cannabinoids marketed as incense products, bath additives, and air fresheners and used for recreational purposes. These preparations are usually smoked for their cannabis-like effects and do not appear on routine urine toxicology screens. We report four cases of oliguric AKI associated with SPICE use in previously healthy men. All showed improvement in renal function without need for renal replacement therapy. Renal biopsy, performed in three of the patients, revealed acute tubular necrosis. The close temporal and geographic associations between the clinical presentation and the development of AKI strongly suggest an association between these SPICE preparations and AKI. Further investigations are required to identify the potential nephrotoxic agent(s). Nephrotoxicity from designer drugs should be included in the differential diagnosis of AKI, especially in young adults with negative urine drug screens.

The Reinforcing Event (RE) Menu

Science.gov (United States)

Addison, Roger M.; Homme, Lloyd E.

1973-01-01

A motivational system, the Contingency Management System, uses contracts in which some amount of defined task behavior is demanded for some interval of reinforcing event. The Reinforcing Event Menu, a list of high probability reinforcing behaviors, is used in the system as a prompting device for the learner and as an aid for the administrator in…

Steel fiber reinforced concrete

International Nuclear Information System (INIS)

Baloch, S.U.

2005-01-01

Steel-Fiber Reinforced Concrete is constructed by adding short fibers of small cross-sectional size .to the fresh concrete. These fibers reinforce the concrete in all directions, as they are randomly oriented. The improved mechanical properties of concrete include ductility, impact-resistance, compressive, tensile and flexural strength and abrasion-resistance. These uniqlte properties of the fiber- reinforcement can be exploited to great advantage in concrete structural members containing both conventional bar-reinforcement and steel fibers. The improvements in mechanical properties of cementitious materials resulting from steel-fiber reinforcement depend on the type, geometry, volume fraction and material-properties of fibers, the matrix mix proportions and the fiber-matrix interfacial bond characteristics. Effects of steel fibers on the mechanical properties of concrete have been investigated in this paper through a comprehensive testing-programme, by varying the fiber volume fraction and the aspect-ratio (Lid) of fibers. Significant improvements are observed in compressive, tensile, flexural strength and impact-resistance of concrete, accompanied by marked improvement in ductility. optimum fiber-volume fraction and aspect-ratio of steel fibers is identified. Test results are analyzed in details and relevant conclusions drawn. The research is finally concluded with future research needs. (author)

Corrosion of reinforcement bars in steel ibre reinforced concrete structures

DEFF Research Database (Denmark)

Solgaard, Anders Ole Stubbe

and the influence of steel fibres on initiation and propagation of cracks in concrete. Moreover, the impact of fibres on corrosion-induced cover cracking was covered. The impact of steel fibres on propagation of reinforcement corrosion was investigated through studies of their impact on the electrical resistivity...... of concrete, which is known to affect the corrosion process of embedded reinforcement. The work concerning the impact of steel fibres on initiation and propagation of cracks was linked to corrosion initiation and propagation of embedded reinforcement bars via additional studies. Cracks in the concrete cover...... are known to alter the ingress rate of depassivating substances and thereby influence the corrosion process. The Ph.D. study covered numerical as well as experimental studies. Electrochemically passive steel fibres are electrically isolating thus not changing the electrical resistivity of concrete, whereas...

DRUGS – “WAY” OF LIFE

Directory of Open Access Journals (Sweden)

Anna Nowacka

2010-12-01

Full Text Available This article refers to the phenomenon of an increasing number of people abusing drugs in the 20th century. In addition to the natural types of narcotics there are many other semi-synthetic and fully synthetic substances made available to the market by chemical and pharmaceutical industries. The use of narcotics and psychoactive substances usually causes adverse and often irreversible health effects. In Department of Laboratory Diagnostics of the Institute of Occupational Medicine and Environmental Health in Sosnowiec tests for presence of drugs are among routinely conducted analyses. The presence of drugs has been revealed in 898 cases between the years 2004 and 2008. On top of the list of the most frequently detected narcotics were: amphetamine, cannabis, opiates, methamphetamine and cocaine. At the same time the most popular psychoactive substances are atropine, scopolamine and psilocybin. Additionally, the laboratory analyses indicated in many cases the presence of derivatives of benzodiazepines, trycyclic antidepressants and alcohol. Regional Centre of Acute Intoxication in Sosnowiec, Poland, hospitalized 78 patients due to overdose of drugs, narcotics or psychoactive substances as a result of experimenting with such substances. Half of the hospitalized cases patients have tried to commit suicide; one of the attempts has led to death. According to patients’ history their problems with reaching out for the use of psychoactive substances and narcotics were mainly caused by socio-psychological disorders.

Algorithms for Reinforcement Learning

CERN Document Server

Szepesvari, Csaba

2010-01-01

Reinforcement learning is a learning paradigm concerned with learning to control a system so as to maximize a numerical performance measure that expresses a long-term objective. What distinguishes reinforcement learning from supervised learning is that only partial feedback is given to the learner about the learner's predictions. Further, the predictions may have long term effects through influencing the future state of the controlled system. Thus, time plays a special role. The goal in reinforcement learning is to develop efficient learning algorithms, as well as to understand the algorithms'

Three fatalities associated with the synthetic cannabinoids 5F-ADB, 5F-PB-22, and AB-CHMINACA.

Science.gov (United States)

Angerer, V; Jacobi, S; Franz, F; Auwärter, V; Pietsch, J

2017-12-01

The use of synthetic cannabinoids (SC) has been widespread in certain groups of drug users for many years. In the scientific literature many intoxication cases and a number of fatalities after the use of synthetic cannabinoids were reported. In this paper three death cases are described with involvement of the synthetic cannabinoids 5F-PB-22, AB-CHMINACA, and 5F-ADB. The three cases occurred in the eastern region of Germany, which is known as a region of high methamphetamine abuse. All decedents were male, between 25 and 41 years old, and had a known history of drug use. Femoral blood concentrations of the synthetic cannabinoids were measured using a validated LC-MS/MS method. The concentration of 5F-PB-22 in the first case was 0.37ng/mL, the concentration of AB-CHMINACA in the second case was approximately 4.1ng/mL (extrapolated) and the 5F-ADB concentration in the third case was 0.38ng/mL. Compared to other published cases the concentrations in the here presented cases seem to be in the lower range. However, taking into account the scene of death, the results of the forensic autopsy and the full toxicological analysis, the deaths can be explained as a direct consequence of consumption of synthetic cannabinoids, although in case one and two relevant amounts of ethanol were found, and in case three trimipramine and olanzapine were present in non-toxic concentrations. It has to be noted that concentrations of synthetic cannabinoids in femoral blood cannot directly be judged as toxic or lethal due to the possibility of postmortem redistribution and the development of tolerance after frequent use. Therefore, all available information has to be considered carefully before stating SC use as the cause of death. Copyright © 2017 Elsevier B.V. All rights reserved.

Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project.

Science.gov (United States)

Sliva, Anna; Yang, Huanming; Boeke, Jef D; Mathews, Debra J H

2015-08-01

First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) PROJECT is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with this field of research and operate under a common set of principles. In this commentary, we survey the current ethics and regulatory landscape of synthetic biology and present the Sc2.0 Statement of Ethics and Governance to which all members of the project adhere. This statement focuses on four aspects of the Sc2.0 PROJECT: societal benefit, intellectual property, safety, and self-governance. We propose that such project-level agreements are an important, valuable, and flexible model of self-regulation for similar global, large-scale synthetic biology projects in order to maximize the benefits and minimize potential harms. Copyright © 2015 by the Genetics Society of America.

Drug Trafficking as a Lethal Regional Threat in Central America

Science.gov (United States)

2011-12-16

and Bolivia. 28 Panama It produces marijuana and serves as a critical transit country for all drugs coming from South America to the United...Colombian drug cartels. Paraguay This is a marijuana producing country. Its production probably never leaves South America; it is believed to supply...broad diversification of their products. The Mexican DTOs went through great efforts to establish laboratories for the cheap synthetic drugs in Mexico

Highly tough and transparent layered composites of nanocellulose and synthetic silicate

Science.gov (United States)

Wu, Chun-Nan; Yang, Quanling; Takeuchi, Miyuki; Saito, Tsuguyuki; Isogai, Akira

2013-12-01

A highly tough and transparent film material was prepared from synthetic saponite (SPN) nanoplatelets of low aspect ratios and nanofibrillar cellulose. The nanofibrillar cellulose was chemically modified by topological surface oxidation using 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO) as a catalyst. Both synthetic SPN nanoplatelets and TEMPO-oxidized cellulose nanofibrils (TOCNs) have abundant negative charges in high densities on their surfaces and are dispersed in water at the individual nanoelement level. Layered nanocomposite structures of the SPN nanoplatelets and TOCNs were formed through a simple cast-drying process of the mixed aqueous dispersions. The TOCN/SPN composites with 0-50% w/w SPN content were optically transparent. Mechanical properties of the TOCN/SPN composites varied depending on the SPN content. The composite with 10% w/w SPN content (5.6% volume fraction) exhibited characteristic mechanical properties: Young's modulus of 14 GPa, tensile strength of 420 MPa, and strain-to-failure of 10%. The work of fracture of the composites increased from 4 to 30 MJ m-3 - or by more than 700% - as the SPN content was increased from 0 to 10% w/w. This surprising improvement in toughness was interpreted based on a model for fracture of polymer composites reinforced with low-aspect-ratio platelets.A highly tough and transparent film material was prepared from synthetic saponite (SPN) nanoplatelets of low aspect ratios and nanofibrillar cellulose. The nanofibrillar cellulose was chemically modified by topological surface oxidation using 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO) as a catalyst. Both synthetic SPN nanoplatelets and TEMPO-oxidized cellulose nanofibrils (TOCNs) have abundant negative charges in high densities on their surfaces and are dispersed in water at the individual nanoelement level. Layered nanocomposite structures of the SPN nanoplatelets and TOCNs were formed through a simple cast-drying process of the mixed aqueous dispersions. The

[Caffeine: a nutrient, a drug or a drug of abuse].

Science.gov (United States)

Pardo Lozano, Ricardo; Alvarez García, Yolanda; Barral Tafalla, Diego; Farré Albaladejo, Magí

2007-01-01

Coffee, tea, chocolate and caffeinated drinks are the main sources of caffeine, which is consumed in almost all ages and socioeconomic levels. Caffeine acts as a non-selective adenosine receptor antagonist in the central nervous system. Its main effects are as psychostimulant, acting in addition on the respiratory, muscular and cardiovascular systems. Basically, caffeine is metabolized by the hepatic cytochrome P-450 1A2 enzymes (CYP1A2). Several drugs can interact with its metabolism. The observed interindividual differences of its effects can be explained by variations in its metabolism. The main therapeutic use of caffeine is bronchodilator in respiratory diseases. Other possible uses are under investigation. Acute or chronic consumption of caffeine can induce several adverse effects, including intoxication that can be lethal. Finally, caffeine can be considered a drug of abuse. It has positive reinforcing actions, produces tolerance, and a withdrawal syndrome after stopping its consumption. Caffeine can cause different mental disorders such as dependence, which is not included in the DSM-IV-R, withdrawal syndrome and intoxication. Depending on its use, caffeine can be considered a nutrient, a drug or a drug of abuse.

Spice/K2 drugs--more than innocent substitutes for marijuana.

Science.gov (United States)

Zawilska, Jolanta B; Wojcieszak, Jakub

2014-03-01

Smokeable herbal mixtures containing synthetic agonists of cannabinoid receptors, known under brand names such as Spice, K2 and Kronic, represent a relatively new type of designer psychoactive drugs that has recently emerged on the recreational drug market. Although the Spice packages are labelled 'not for human consumption' or 'for aromatherapy only' and declared to be purely herbal, these herbal mixtures produce cannabis-like effects after smoking. This review surveys the current state of knowledge regarding the pharmacological properties of synthetic cannabimimetics and the prevalence and pattern of their use. Special emphasis is given to the negative consequences of using these products, including, among others, hallucinations, psychoses with delusions, seizures, cardiovascular symptoms and acute kidney injury.

Continuous Reinforced Concrete Beams

DEFF Research Database (Denmark)

Hoang, Cao Linh; Nielsen, Mogens Peter

1996-01-01

This report deals with stress and stiffness estimates of continuous reinforced concrete beams with different stiffnesses for negative and positive moments e.g. corresponding to different reinforcement areas in top and bottom. Such conditions are often met in practice.The moment distribution...

Modelling reinforcement corrosion in concrete

DEFF Research Database (Denmark)

Michel, Alexander; Geiker, Mette Rica; Stang, Henrik

2012-01-01

A physio-chemical model for the simulation of reinforcement corrosion in concrete struc-tures was developed. The model allows for simulation of initiation and subsequent propaga-tion of reinforcement corrosion. Corrosion is assumed to be initiated once a defined critical chloride threshold......, a numerical example is pre-sented, that illustrates the formation of corrosion cells as well as propagation of corrosion in a reinforced concrete structure....

The Reinforcement Learning Competition 2014

OpenAIRE

Dimitrakakis, Christos; Li, Guangliang; Tziortziotis, Nikoalos

2014-01-01

Reinforcement learning is one of the most general problems in artificial intelligence. It has been used to model problems in automated experiment design, control, economics, game playing, scheduling and telecommunications. The aim of the reinforcement learning competition is to encourage the development of very general learning agents for arbitrary reinforcement learning problems and to provide a test-bed for the unbiased evaluation of algorithms.

First Characterization of AKB-48 Metabolism, a Novel Synthetic Cannabinoid, Using Human Hepatocytes and High-Resolution Mass Spectrometry

OpenAIRE

Gandhi, Adarsh S.; Zhu, Mingshe; Pang, Shaokun; Wohlfarth, Ariane; Scheidweiler, Karl B.; Liu, Hua-fen; Huestis, Marilyn A.

2013-01-01

Since the federal authorities scheduled the first synthetic cannabinoids, JWH-018 and JWH-073, new synthetic cannabinoids were robustly marketed. N-(1-Adamantyl)-1-pentylindazole-3-carboxamide (AKB-48), also known as APINACA, was recently observed in Japanese herbal smoking blends. The National Forensic Laboratory Information System registered 443 reports of AKB-48 cases in the USA from March 2010 to January 2013. In May 2013, the Drug Enforcement Administration listed AKB-48 as a Schedule I ...

Origins of food reinforcement in infants12345

Science.gov (United States)

Kong, Kai Ling; Feda, Denise M; Eiden, Rina D; Epstein, Leonard H

2015-01-01

Background: Rapid weight gain in infancy is associated with a higher risk of obesity in children and adults. A high relative reinforcing value of food is cross-sectionally related to obesity; lean children find nonfood alternatives more reinforcing than do overweight/obese children. However, to our knowledge, there is no research on how and when food reinforcement develops. Objective: This study was designed to assess whether the reinforcing value of food and nonfood alternatives could be tested in 9- to 18-mo-old infants and whether the reinforcing value of food and nonfood alternatives is differentially related to infant weight status. Design: Reinforcing values were assessed by using absolute progressive ratio schedules of reinforcement, with presentation of food and nonfood alternatives counterbalanced in 2 separate studies. Two nonfood reinforcers [Baby Einstein–Baby MacDonald shows (study 1, n = 27) or bubbles (study 2, n = 30)] were tested against the baby’s favorite food. Food reinforcing ratio (FRR) was quantified by measuring the reinforcing value of food (Food Pmax) in proportion to the total reinforcing value of food and a nonfood alternative (DVD Pmax or BUB Pmax). Results: Greater weight-for-length z score was associated with a greater FRR of a favorite food in study 1 (FRR-DVD) (r = 0.60, P positively associated with FRR-DVD (r = 0.57, P = 0.009) and FRR-BUB (r = 0.37, P = 0.047). Conclusions: Our newly developed paradigm, which tested 2 different nonfood alternatives, demonstrated that lean infants find nonfood alternatives more reinforcing than do overweight/obese infants. This observation suggests that strengthening the alternative reinforcers may have a protective effect against childhood obesity. This research was registered at clinicaltrials.gov as NCT02229552. PMID:25733636

The psychological and neurochemical mechanisms of drug memory reconsolidation: implications for the treatment of addiction.

Science.gov (United States)

Milton, Amy L; Everitt, Barry J

2010-06-01

Memory reconsolidation is the process by which memories, destabilised at retrieval, require restabilisation to persist in the brain. It has been demonstrated that even old, well-established memories require reconsolidation following retrieval; therefore, memory reconsolidation could potentially be exploited to disrupt, or even erase, aberrant memories that underlie psychiatric disorders, thereby providing a novel therapeutic target. Drug addiction is one such disorder; it is both chronic and relapsing, and one prominent risk factor for a relapse episode is the presentation of environmental cues that have previously been associated with drugs of abuse. This 'cue-induced relapse' can be accounted for in psychological terms by reinforcing memories of the pavlovian association between the cue and the drug, which can thus influence behaviour through at least three psychologically and neurobiologically dissociable mechanisms: conditioned reinforcement, conditioned approach and conditioned motivation. As each of these psychological processes could contribute to the resumption of drug-seeking following abstinence, it is important to develop treatments that can reduce drug-seeking re-established via influences on each or all of these pavlovian processes, in order to minimise the risk of a subsequent relapse. Investigation of the memory reconsolidation mechanisms of the memories underlying conditioned reinforcement, conditioned approach and conditioned motivation indicate that they depend upon different neurochemical systems, including the glutamatergic and adrenergic systems within limbic corticostriatal circuitry. We also discuss here the subsequent translation to the clinic of this preclinical work.

Impact of Sex and Gonadal Hormones on Cocaine and Food Reinforcement Paradigms

OpenAIRE

Kerstetter, Kerry A.; Kippin, Tod E.

2011-01-01

Men and women express sexually dimorphic patterns of cocaine abuse, such that women progress faster from initially trying cocaine to becoming dependent upon the drug and display a greater incidence of relapse. Sex differences in response to cocaine are also seen in the laboratory in both humans and animal models. In this review, animal models of cocaine abuse that have reported sex differences in appetitive reinforcement are discussed. In both human and animal studies, sex differences in the ...

Effects of RO 15-1788 on a running response rewarded on continuous or partial reinforcement schedules.

Science.gov (United States)

Hawkins, M; Sinden, J; Martin, I; Gray, J A

1988-01-01

Two experiments were run in which rats were rewarded with food for running in a straight alley at one trial a day, followed by extinction of the running response. During acquisition of the response, reward was delivered either on a continuous reinforcement (CRF) or on a quasirandom 50% partial reinforcement (PRF) schedule. The groups given PRF were more resistant to extinction than those given CRF, the well-known partial reinforcement extinction effect. In Experiment 1 different groups of rats were injected during acquisition only with 1, 5 or 10 mg/kg of the benzodiazepine antagonist, RO 15-1788, or with placebo. In Experiment 2, 5 mg/kg RO 15-1788 or placebo were administered in a full cross-over design during acquisition, extinction or both. At the end of Experiment 2 only [3H]-flunitrazepam binding was measured in either the presence or absence of added gamma-aminobutyrate (GABA) in homogenates of hippocampi dissected from the animals that had received behavioural training. The drug affected running speeds during both acquisition and extinction in different ways depending upon the schedule of reinforcement (CRF or PRF) and also gave rise to enhanced GABA stimulation of [3H]-flunitrazepam binding. The results are discussed in relation to the hypothesis that the neurochemical pathways by which reinforcement schedules modify behaviour include a step influenced by benzodiazepine receptors.

Editorial: in silico drug design and medicinal chemistry).

Science.gov (United States)

Singla, Rajeev K

2015-01-01

Medicinal chemistry is not limited to molecules, their structures and design but also highly cohesive to pharmacological activities. The potency of a molecule varies by its structure. Hence structural activity relationship is the sub-branch which deals with the estimation of ability of a molecule in depicting any pharmacological activity. In silico drug design is a novel technique which is employed in designing a molecule by using computer aided software’s and bringing a superior and potent molecule. In recent years, in silico drug design has been merged with medicinal chemistry especially by the techniques like ligand based strategy to isolate the required structures. By such strategic techniques, there are high chances of delivering high throughput screening which involves of screening large number of molecules in a very less time. Involvement of such techniques would be a boon for development of new drug entity as it can aid in development of newer, safe, effective and potent drug molecules. Hence, the present issue is aimed to emphasize the cohesion between in silico drug design and it significance in medicinal chemistry. The articles which would be published will mainly focus on the role of in silico drug design techniques in the development of molecules to target various disease and disorders. Molecules can from natural/ synthetic/semi synthetic origin. Articles will be a treasure box consisting of employment of computational methods for unprecedented molecules. The issue will be sure an endorsement for international readership and researchers.

Peer influences on drug self-administration: an econometric analysis in socially housed rats.

Science.gov (United States)

Peitz, Geoffrey W; Strickland, Justin C; Pitts, Elizabeth G; Foley, Mark; Tonidandel, Scott; Smith, Mark A

2013-04-01

Social-learning theories of substance use propose that members of peer groups influence the drug use of other members by selectively modeling, reinforcing, and punishing either abstinence-related or drug-related behaviors. The objective of the present study was to examine the social influences on cocaine self-administration in isolated and socially housed rats, under conditions where the socially housed rats were tested simultaneously with their partner in the same chamber. To this end, male rats were obtained at weaning and housed in isolated or pair-housed conditions for 6 weeks. Rats were then implanted with intravenous catheters and cocaine self-administration was examined in custom-built operant conditioning chambers that allowed two rats to be tested simultaneously. For some socially housed subjects, both rats had simultaneous access to cocaine; for others, only one rat of the pair had access to cocaine. An econometric analysis was applied to the data, and the reinforcing strength of cocaine was measured by examining consumption (i.e. quantity demanded) and elasticity of demand as a function of price, which was manipulated by varying the dose and ratio requirements on a fixed ratio schedule of reinforcement. Cocaine consumption decreased as a function of price in all groups. Elasticity of demand did not vary across groups, but consumption was significantly lower in socially housed rats paired with a rat without access to cocaine. These data suggest that the presence of an abstaining peer decreases the reinforcing strength of cocaine, thus supporting the development of social interventions in drug abuse prevention and treatment programs.

Use of diffusion-ordered NMR spectroscopy and HPLC-UV-SPE-NMR to identify undeclared synthetic drugs in medicines illegally sold as phytotherapies.

Science.gov (United States)

Silva, Lorena M A; Filho, Elenilson G A; Thomasi, Sérgio S; Silva, Bianca F; Ferreira, Antonio G; Venâncio, Tiago

2013-09-01

The informal (and/or illegal) e-commerce of pharmaceutical formulations causes problems that governmental health agencies find hard to control, one of which concerns formulas sold as natural products. The purpose of this work was to explore the advantages and limitations of DOSY and HPLC-UV-SPE-NMR. These techniques were used to identify the components of a formula illegally marketed in Brazil as an herbal medicine possessing anti-inflammatory and analgesic properties. DOSY was able to detect the major components present at higher concentrations. Complete characterization was achieved using HPLC-UV-SPE-NMR, and 1D and 2D NMR analyses enabled the identification of known synthetic drugs. These were ranitidine and a mixture of orphenadrine citrate, piroxicam, and dexamethasone, which are co-formulated in a remedy called Rheumazim that is used to relieve severe pain, but it is prohibited in Brazil because of a lack of sufficient pharmacokinetic and pharmacodynamic information. Copyright © 2013 John Wiley & Sons, Ltd.

Geographic Variability and Anti-Staphylococcal Activity of the Chrysophaentins and Their Synthetic Fragments

Directory of Open Access Journals (Sweden)

Jared T. Hammill

2012-05-01

Full Text Available Drug-resistant Staphylococcus aureus is a continuing public health concern, both in the hospital and community settings. Antibacterial compounds that possess novel structural scaffolds and are effective against multiple S. aureus strains, including current drug-resistant ones, are needed. Previously, we have described the chrysophaentins, a family of bisdiarylbutene macrocycles from the chrysophyte alga Chrysophaeum taylori that inhibit the growth of S. aureus and methicillin-resistant S. aureus (MRSA. In this study we have analyzed the geographic variability of chrysophaentin production in C. taylori located at different sites on the island of St. John, U.S. Virgin Islands, and identified two new linear chrysophaentin analogs, E2 and E3. In addition, we have expanded the structure activity relationship through synthesis of fragments comprising conserved portions of the chrysophaentins, and determined the antimicrobial activity of natural chrysophaentins and their synthetic analogs against five diverse S. aureus strains. We find that the chrysophaentins show similar activity against all S. aureus strains, regardless of their drug sensitivity profiles. The synthetic chrysophaentin fragments indeed mimic the natural compounds in their spectrum of antibacterial activity, and therefore represent logical starting points for future medicinal chemistry studies of the natural products and their analogs.

Effect of hybrid fiber reinforcement on the cracking process in fiber reinforced cementitious composites

DEFF Research Database (Denmark)

Pereira, Eduardo B.; Fischer, Gregor; Barros, Joaquim A.O.

2012-01-01

The simultaneous use of different types of fibers as reinforcement in cementitious matrix composites is typically motivated by the underlying principle of a multi-scale nature of the cracking processes in fiber reinforced cementitious composites. It has been hypothesized that while undergoing...... tensile deformations in the composite, the fibers with different geometrical and mechanical properties restrain the propagation and further development of cracking at different scales from the micro- to the macro-scale. The optimized design of the fiber reinforcing systems requires the objective...... materials is carried out by assessing directly their tensile stress-crack opening behavior. The efficiency of hybrid fiber reinforcements and the multi-scale nature of cracking processes are discussed based on the experimental results obtained, as well as the micro-mechanisms underlying the contribution...

Synthetic environments

Science.gov (United States)

Lukes, George E.; Cain, Joel M.

1996-02-01

The Advanced Distributed Simulation (ADS) Synthetic Environments Program seeks to create robust virtual worlds from operational terrain and environmental data sources of sufficient fidelity and currency to interact with the real world. While some applications can be met by direct exploitation of standard digital terrain data, more demanding applications -- particularly those support operations 'close to the ground' -- are well-served by emerging capabilities for 'value-adding' by the user working with controlled imagery. For users to rigorously refine and exploit controlled imagery within functionally different workstations they must have a shared framework to allow interoperability within and between these environments in terms of passing image and object coordinates and other information using a variety of validated sensor models. The Synthetic Environments Program is now being expanded to address rapid construction of virtual worlds with research initiatives in digital mapping, softcopy workstations, and cartographic image understanding. The Synthetic Environments Program is also participating in a joint initiative for a sensor model applications programer's interface (API) to ensure that a common controlled imagery exploitation framework is available to all researchers, developers and users. This presentation provides an introduction to ADS and the associated requirements for synthetic environments to support synthetic theaters of war. It provides a technical rationale for exploring applications of image understanding technology to automated cartography in support of ADS and related programs benefitting from automated analysis of mapping, earth resources and reconnaissance imagery. And it provides an overview and status of the joint initiative for a sensor model API.

ROLE OF NATURAL POLYMERS IN SUSTAINED RELEASE DRUG DELIVERY SYSTEM: APPLICATIONS AND RECENT APPROACHES

OpenAIRE

Prakash Pawan; Porwal Mayur; Saxena Ashwin

2011-01-01