WorldWideScience

Sample records for involving mass drug

  1. Drug involvement in fatal overdoses

    Directory of Open Access Journals (Sweden)

    Christopher J. Ruhm

    2017-12-01

    Full Text Available Death certificate data from the Multiple Cause of Death (MCOD files were analyzed to better understand the drug categories most responsible for the increase in fatal overdoses occurring between 1999 and 2014. Statistical adjustment methods were used to account for the understatement in reported drug involvement occurring because death certificates frequently do not specify which drugs were involved in the deaths. The frequency of combination drug use introduced additional uncertainty and so a distinction was made between any versus exclusive drug involvement. Many results were sensitive to the starting and ending years chosen for examination. Opioid analgesics played a major role in the increased drug deaths for analysis windows starting in 1999 but other drugs, particularly heroin, became more significant for recent time periods. Combination drug use was important for all time periods and needs to be accounted for when designing policies to slow or reverse the increase in overdose deaths.

  2. Design for Mass User Involvement

    DEFF Research Database (Denmark)

    Vianello, Giovanna; Tan, Adrian

    as it creates a closer relationship to customers as well as creating the best possibilities for reducing impact of products on our natural environment. This new way of organizing the development process in collaboration with users holds many opportunities, but also challenges for companies and researchers. We...... formalism for the future in 2030 that is suited for a high tech, global manufacturing company. The design formalism involves the user throughout the design process and involves the company in the entire lifecycle of its products. It is believed that this approach will give companies a competitive advantage...

  3. 14 CFR 61.15 - Offenses involving alcohol or drugs.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Offenses involving alcohol or drugs. 61.15... involving alcohol or drugs. (a) A conviction for the violation of any Federal or State statute relating to... vehicle while intoxicated by alcohol or a drug, while impaired by alcohol or a drug, or while under the...

  4. Mass Spectrometry Imaging of Drugs of Abuse in Hair.

    Science.gov (United States)

    Flinders, Bryn; Cuypers, Eva; Porta, Tiffany; Varesio, Emmanuel; Hopfgartner, Gérard; Heeren, Ron M A

    2017-01-01

    Hair testing is a powerful tool routinely used for the detection of drugs of abuse. The analysis of hair is highly advantageous as it can provide prolonged drug detectability versus that in biological fluids and chronological information about drug intake based on the average growth of hair. However, current methodology requires large amounts of hair samples and involves complex time-consuming sample preparation followed by gas or liquid chromatography coupled with mass spectrometry. Mass spectrometry imaging is increasingly being used for the analysis of single hair samples, as it provides more accurate and visual chronological information in single hair samples.Here, two methods for the preparation of single hair samples for mass spectrometry imaging are presented.The first uses an in-house built cutting apparatus to prepare longitudinal sections, the second is a method for embedding and cryo-sectioning hair samples in order to prepare cross-sections all along the hair sample.

  5. Involving Corporations in Dispensing During Mass Prophylaxis

    Science.gov (United States)

    2007-03-01

    raise concerns that there will be resistance among those who feel the importance of their daily work exceeds the importance of devoting time for...under investigational processes. The current guidance states, “You will have to administer amoxicillin under an Investigational New Drug (IND

  6. 14 CFR 65.12 - Offenses involving alcohol or drugs.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Offenses involving alcohol or drugs. 65.12... alcohol or drugs. (a) A conviction for the violation of any Federal or state statute relating to the... narcotic drugs, marihuana, or depressant or stimulant drugs or substances is grounds for— (1) Denial of an...

  7. 14 CFR 63.12 - Offenses involving alcohol or drugs.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Offenses involving alcohol or drugs. 63.12... alcohol or drugs. (a) A conviction for the violation of any Federal or state statute relating to the... narcotic drugs, marihuana, or depressant or stimulant drugs or substances is grounds for— (1) Denial of an...

  8. Drug involvement of fatally injured drivers

    Science.gov (United States)

    2010-11-01

    While data focusing on the danger of driving under the influence : of alcohol is readily available and often cited, less is : known or discussed about drivers under the influence of : other drugs. The Fatality Analysis Reporting System (FARS), : a ce...

  9. Mass drug administration: the importance of synchrony.

    Science.gov (United States)

    Gao, Daozhou; Lietman, Thomas M; Dong, Chao-Ping; Porco, Travis C

    2017-06-01

    Mass drug administration, a strategy in which all individuals in a population are subject to treatment without individual diagnosis, has been recommended by the World Health Organization for controlling and eliminating several neglected tropical diseases, including trachoma and soil-transmitted helminths. In this article, we derive effective reproduction numbers and average post-treatment disease prevalences of a simple susceptible-infectious-susceptible epidemic model with constant, impulsive synchronized and non-synchronized drug administration strategies. In the non-synchronized model, the individuals in the population are treated at most once per period and their treatment times are uniformly distributed. Mathematically, the set of pulses for the non-synchronized model has the cardinality of the continuum. We show that synchronized and constant strategies are, respectively, the most and least effective treatments in disease control. Elimination through synchronized treatment is always possible when adequate drug efficacy and coverage are fulfilled and sustained. For a strategy with multiple rounds of synchronized treatment per period, the average post-treatment prevalence is irrelevant what the time differences between treatments are, as long as there are the same number of treatments per period. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  10. Military Involvement in the War on Drugs, "Just Say No"

    National Research Council Canada - National Science Library

    Tappan, John

    1998-01-01

    .... Past and present interdiction efforts have failed, troops are not properly trained, resources are declining and above all, an end state in the War on Drugs is not defined. Therefore, the military should not be involved in the War on Drugs.

  11. Radiocarbon mass spectrometry for drug development

    International Nuclear Information System (INIS)

    Ulrich, Schulze-Konig Tim

    2011-01-01

    Full text: Radiocarbon has a huge potential as a tracer for metabolism studies in humans. By using Accelerator Mass Spectrometry (AMS) for its detection, a unique sensitivity is reached reducing required radiation doses to a negligible level. Until recently, a widespread use of AMS in biomedical research was impeded by the high complexity of the instrument, time-consuming sample preparation, and a limited availability of measurement capacity. Over the last few years, tremendous progress has been achieved in the reduction of size and complexity of AMS instruments. It allowed designing a compact AMS system, dubbed BioMICADAS to address the needs of biomedical users. For more than two years, this system is in successful operation at a commercial service provider for the pharmaceutical industry. A further drastic simplification of radiocarbon mass spectrometers seems possible and could establish a regular usage of this technology in drug development. However, to reach this goal a better integration of AMS into the workflow of bioanalytical laboratories will be necessary. For this purpose, CO 2 accepting ion sources may be a key, since they enable an almost automated sample preparation. The status of radiocarbon AMS in biomedical research and its perspective will be discussed

  12. Gang Membership and Drug Involvement: Untangling the Complex Relationship

    Science.gov (United States)

    Bjerregaard, Beth

    2010-01-01

    Previous research has consistently demonstrated a relationship between gang membership and involvement in illegal substances. In addition, researchers have noted that gang members are frequently more heavily involved in drug sales, which often lead to increases in violent behaviors. Most of this research, however, is either cross-sectional or…

  13. Injection Drug Users' Involvement In Drug Economy: Dynamics of Sociometric and Egocentric Social Networks.

    Science.gov (United States)

    Yang, Cui; Latkin, Carl; Muth, Stephen Q; Rudolph, Abby

    2013-07-01

    The purpose of this analysis was to examine the effect of social network cohesiveness on drug economy involvement, and to test whether this relationship is mediated by drug support network size in a sample of active injection drug users. Involvement in the drug economy was defined by self-report of participation in at least one of the following activities: selling drugs, holding drugs or money for drugs, providing street security for drug sellers, cutting/packaging/cooking drugs, selling or renting drug paraphernalia (e.g., pipes, tools, rigs), and injecting drugs in others' veins. The sample consists of 273 active injection drug users in Baltimore, Maryland who reported having injected drugs in the last 6 months and were recruited through either street outreach or by their network members. Egocentric drug support networks were assessed through a social network inventory at baseline. Sociometric networks were built upon the linkages by selected matching characteristics, and k-plex rank was used to characterize the level of cohesiveness of the individual to others in the social network. Although no direct effect was observed, structural equation modeling indicated k-plex rank was indirectly associated with drug economy involvement through drug support network size. These findings suggest the effects of large-scale sociometric networks on injectors' drug economy involvement may occur through their immediate egocentric networks. Future harm reduction programs for injection drug users (IDUs) should consider providing programs coupled with economic opportunities to those drug users within a cohesive network subgroup. Moreover, individuals with a high connectivity to others in their network may be optimal individuals to train for diffusing HIV prevention messages.

  14. Drug and Alcohol Involvement in Four Types of Fatal Crashes*

    Science.gov (United States)

    Romano, Eduardo; Voas, Robert B.

    2011-01-01

    Objective: The aim of this study was to explore the relationship of drunk and drugged driving to the occurrence of fatal crashes associated with speeding, failure to obey/yield, inattention, and seat belt nonuse. Method: We examined data for fatally injured drivers involved in single-vehicle crashes killed in states in which more than 79% of the drivers were tested for drugs other than alcohol and had a known result. Results: About 25% of the drivers tested positive for drugs, a figure almost double that estimated by the 2007 National Roadside Survey. Cannabinoids and stimulants each contributed to about 23% of the drug-positive results (6% among all fatally injured single-vehicle drivers). Stimulants more than cannabinoids were found to be associated with the four types of crashes under study. Some drugs showed a protective effect over the four crash types under study. Significant interactions between drugs and alcohol were observed. Stimulants contributed to the different types of fatal crashes irrespective of the levels of alcohol consumed by the drivers. Conclusions: This study provides further evidence of a link between drug consumption and fatal crashes. It also opens the door to some interesting and sometimes unexpected questions regarding the way drugs contribute to crashes, which we found varies depending on the type of crash considered, the class of drug, and the presence of alcohol. Research is also needed on drugs that could have a protective effect on the occurrence of fatal crashes. These findings could be highly relevant to the design of drug-related traffic laws and programs targeted at curbing drugged driving. PMID:21683038

  15. Lessons Learnt From the Implementation of Mass Drug ...

    African Journals Online (AJOL)

    A Mass Drug Administration (MDA) campaign for elimination and control of Schistosomiasis in all the eight. (8) districts of Lusaka Province and for Soil Transmitted. Helminths in Lusaka District was conducted in the period th st. 26 – 31 January 2015. This study explores lessons learnt from Implementation of mass drug ...

  16. Establishing Drug Resistance in Microorganisms by Mass Spectrometry

    Science.gov (United States)

    Demirev, Plamen A.; Hagan, Nathan S.; Antoine, Miquel D.; Lin, Jeffrey S.; Feldman, Andrew B.

    2013-08-01

    A rapid method to determine drug resistance in bacteria based on mass spectrometry is presented. In it, a mass spectrum of an intact microorganism grown in drug-containing stable isotope-labeled media is compared with a mass spectrum of the intact microorganism grown in non-labeled media without the drug present. Drug resistance is determined by predicting characteristic mass shifts of one or more microorganism biomarkers using bioinformatics algorithms. Observing such characteristic mass shifts indicates that the microorganism is viable even in the presence of the drug, thus incorporating the isotopic label into characteristic biomarker molecules. The performance of the method is illustrated on the example of intact E. coli, grown in control (unlabeled) and 13C-labeled media, and analyzed by MALDI TOF MS. Algorithms for data analysis are presented as well.

  17. Citizen involvement in future drug R&D

    DEFF Research Database (Denmark)

    Møldrup, Claus; Morgall, Janine Marie; Almarsdóttir, Anna Birna

    2000-01-01

    This article adopts a prospective approach in an attempt to explore the potential benefit of citizen involvement in decision making concerning future drug R&D. This is one of the first Delphi studies to fully utilize internet technology to collect and process data. The results show an increasing ...

  18. Diffusion of treatment in social networks and mass drug administration

    NARCIS (Netherlands)

    Chami, Goylette F.; Kontoleon, Andreas A.; Bulte, Erwin; Fenwick, Alan; Kabatereine, Narcis B.; Tukahebwa, Edridah M.; Dunne, David W.

    2017-01-01

    Information, behaviors, and technologies spread when people interact. Understanding these interactions is critical for achieving the greatest diffusion of public interventions. Yet, little is known about the performance of starting points (seed nodes) for diffusion. We track routine mass drug

  19. Emergency department staff preparedness for mass casualty events involving children.

    Science.gov (United States)

    Rassin, Michal; Avraham, Miri; Nasi-Bashari, Anat; Idelman, Sigalit; Peretz, Yaniv; Morag, Shani; Silner, Dina; Weiss, Gali

    2007-01-01

    In recent years, the World Health Organization in general, and Israel in particular, have dealt with mass casualty events (MCEs) resulting from terrorism. Children are the casualties in many of these events-a reality that forces hospitals to prepare to deal with such a scenario. A literature review designed to identify unique recommendations regarding pediatric MCEs highlights both a lack of existing training programs and uncertainty on the part of health care staff when dealing with these events. The purpose of the study was to examine the preparedness level of emergency department staff to deal with MCEs involving pediatric casualties. The study included 104 physicians and nurses working in, or responding to, the emergency department at a hospital in Israel. The study included a 41-item questionnaire examining perception, approaches, and staff knowledge regarding dealing with pediatric MCEs versus those involving adults. The reliability of all sections of the questionnaire ranged between Chronbach's alpha coefficient 0.6 alpha-0.94. The preparedness levels for MCEs involving children were found to be low. Study participants ranked the likelihood of a pediatric MCE lower than one involving adults, while ranking significantly higher (P = .000) their ability to cope mentally and the knowledge and skills required when treating adults involved in MCEs. While nurses ranked higher than physicians regarding their knowledge and skills in dealing with pediatric MCE casualties, the level of knowledge for MCEs involving children was low in all subjects. Staff agreement for the parent of an MCE victim to be present during treatment was medium-low. On the basis of these findings, additional research involving a larger number of individuals and hospitals is indicated to determine if these results are consistent throughout the region.

  20. Mechanisms of Prescription Drug Diversion Among Drug-Involved Club- and Street-Based Populations

    Science.gov (United States)

    Inciardi, James A.; Surratt, Hilary L.; Kurtz, Steven P.; Cicero, Theodore J.

    2010-01-01

    Objective Prescription drug diversion involves the unlawful channeling of regulated pharmaceuticals from legal sources to the illicit marketplace, and can occur along all points in the drug delivery process, from the original manufacturing site to the wholesale distributor, the physician's office, the retail pharmacy, or the patient. However, empirical data on diversion are limited. Method In an attempt to develop a better understanding of how specific drug-using populations are diverting prescription opioids and other medications, or obtaining controlled drugs that have already been diverted, qualitative interviews and focus group data were collected on four separate populations of prescription drug abusers in Miami, Florida—club drug users, street-based illicit drug users, methadone maintenance patients, and HIV positive individuals who abuse and/or divert drugs. Results Sources of abused prescription drugs cited by focus group participants were extremely diverse, including their physicians and pharmacists; parents and relatives; “doctor shopping”; leftover supplies following an illness or injury; personal visits to Mexico, South America and the Caribbean; prescriptions intended for the treatment of mental illness; direct sales on the street and in nightclubs; pharmacy and hospital theft; through friends or acquaintances; under-the-door apartment flyers advertising telephone numbers to call; and “stealing from grandma's medicine cabinet.” Conclusion While doctor shoppers, physicians and the Internet receive much of the attention regarding diversion, the data reported in this paper suggest that there are numerous active street markets involving patients, Medicaid recipients and pharmacies as well. In addition, there are other data which suggest that the contributions of residential burglaries, pharmacy robberies and thefts, and “sneak thefts” to the diversion problem may be understated. PMID:17305688

  1. Low prosocial attachment, involvement with drug-using peers, and adolescent drug use: a longitudinal examination of mediational mechanisms.

    Science.gov (United States)

    Henry, Kimberly L

    2008-06-01

    The process of disengagement from prosocial entities (e.g., family and school) and either simultaneous or subsequent engagement with antisocial entities (e.g., friends who use drugs) is a critical contributor to adolescent drug use and delinquency. This study provides a series of formal mediation tests to demonstrate the relationship between poor family attachment, poor school attachment, involvement with friends who use drugs, and a student's own use of drugs. Results indicate that poor family attachment exerts its effect on drug use through poor school attachment and involvement with friends who use drugs. In addition, poor school attachment exerts its effect on drug use through involvement with friends who use drugs. The results of this study corroborate theories that suggest disengagement from prosocial entities is associated with involvement with antisocial entities and eventual involvement in drug use. Implications for prevention strategies are discussed. 2008 APA

  2. Drugged Driving: Increased Traffic Risks Involving Licit and Illicit Substances

    Science.gov (United States)

    Pilkinton, Melinda W.; Robertson, Angela; McCluskey, D. Lee

    2013-01-01

    Driving under the influence of drugs poses risks for traffic safety. Most research attention has been focused on the most prevalent drugs of abuse, such as alcohol, illegal drugs, and prescription drugs with high abuse potential. The objectives of this study were to determine the types of drugs used by convicted DUI offenders on the day of their…

  3. Diffusion of treatment in social networks and mass drug administration

    OpenAIRE

    Chami, Goylette F.; Kontoleon, Andreas A.; Bulte, Erwin; Fenwick, Alan; Kabatereine, Narcis B.; Tukahebwa, Edridah M.; Dunne, David W.

    2017-01-01

    Information, behaviors, and technologies spread when people interact. Understanding these interactions is critical for achieving the greatest diffusion of public interventions. Yet, little is known about the performance of starting points (seed nodes) for diffusion. We track routine mass drug administration-the large-scale distribution of deworming drugs-in Uganda. We observe friendship networks, socioeconomic factors, and treatment delivery outcomes for 16,357 individuals in 3491 households ...

  4. Injection drug users’ involvement in drug dealing in the downtown eastside of Vancouver: Social organization and systemic violence

    Science.gov (United States)

    Small, Will; Maher, Lisa; Lawlor, Jeff; Wood, Evan; Shannon, Kate; Kerr, Thomas

    2014-01-01

    Background Illicit drug markets are a key component of the risk environment surrounding injection drug use. However, relatively few studies have explored how injection drug users’ (IDUs) involvement in drug dealing shapes their experiences of drug market-related harm. This exploratory qualitative study aims to understand IDUs’ dealing activities and roles, as well as the perceived benefits and risks related to participation in illicit drug markets, including experiences of drug market violence. Methods Ten IDUs with extensive involvement in drug dealing activities were recruited from the Vancouver Injection Drug User Study (VIDUS) and participated in semi-structured qualitative interviews, which elicited discussion of experiences dealing drugs, perceived benefits and hazards related to dealing, and understandings of drug market violence. Results Participant's involvement in drug market activities included corporate sales, freelance or independent sales, and opportunistic sales termed “middling” as well as drug market-related hustles entailing selling bogus drugs and robbing dealers. Participants primarily dealt drugs to support their own illicit drug use, and we found that arrest and criminal justice involvement, hazards stemming from drug debts, and drug market-related violence were key risks related to dealing activities. Conclusion The challenges of managing personal consumption while selling drugs exacerbates the hazards associated with drug dealing. Efforts to address drug dealing among IDUs should consider both drug dependency and the material conditions that propel drug users towards dealing activities. Interventions should explore the potential of combining enhanced drug treatment programs with low threshold employment and alternative income generation opportunities. PMID:23664788

  5. Multi drug resistant tuberculosis presenting as anterior mediastinal mass

    Directory of Open Access Journals (Sweden)

    Parmarth Chandane

    2016-01-01

    Full Text Available Enlargement of the mediastinal lymphatic glands is a common presentation of intrathoracic tuberculosis (TB in children. However, usually, the mediastinal TB nodes enlarge to 2.8 ± 1.0 cm. In this report, we describe a case of anterior mediastinal lymphnode TB seen as huge mass (7 cm on computed tomography (CT thorax without respiratory or food pipe compromise despite anterior mediastinum being an enclosed space. CT guided biopsy of the mass cultured Mycobacterium TB complex which was resistant to isoniazide, rifampicin, streptomycin ofloxacin, moxifloxacin, and pyrazinamide. Hence, we report primary multi drug resistant TB presenting as anterior mediastinal mass as a rare case report.

  6. Prescriptions involving analgesic drugs at a secondary health facility ...

    African Journals Online (AJOL)

    Paracetamol was the most commonly prescribed analgesic drug accounting for 55.7% of all analgesic drugs prescribed while Dipyrone was the most commonly prescribed parenteral analgesic drug. Dipyrone accounted for 19% of total Analgesic drug prescriptions but 93% of analgesics administered by intramuscular route ...

  7. 1 Impact of praziquantel mass drug administration campaign on ...

    African Journals Online (AJOL)

    Abstract: As part of the Tanzania National Schistosomiasis Control Programme, Bahi district in central Tanzania, received two annual rounds of praziquantel mass drug administration (MDA) to control urinary schistosomiasis in schoolchildren. The objectives of this study were to assess the impact of the two rounds of MDA ...

  8. Lessons Learnt From the Implementation of Mass Drug ...

    African Journals Online (AJOL)

    Lessons Learnt From the Implementation of Mass Drug Administration for Schistosomiasis and Soil- Transmitted Helminths in Lusaka Province, Zambia. ... Alternatively, you can download the PDF file directly to your computer, from where it can be opened using a PDF reader. To download the PDF, click the Download link ...

  9. US Food and Drug Administration Perspectives on Clinical Mass Spectrometry.

    Science.gov (United States)

    Lathrop, Julia Tait; Jeffery, Douglas A; Shea, Yvonne R; Scholl, Peter F; Chan, Maria M

    2016-01-01

    Mass spectrometry-based in vitro diagnostic devices that measure proteins and peptides are underutilized in clinical practice, and none has been cleared or approved by the Food and Drug Administration (FDA) for marketing or for use in clinical trials. One way to increase their utilization is through enhanced interactions between the FDA and the clinical mass spectrometry community to improve the validation and regulatory review of these devices. As a reference point from which to develop these interactions, this article surveys the FDA's regulation of mass spectrometry-based devices, explains how the FDA uses guidance documents and standards in the review process, and describes the FDA's previous outreach to stakeholders. Here we also discuss how further communication and collaboration with the clinical mass spectrometry communities can identify opportunities for the FDA to provide help in the development of mass spectrometry-based devices and enhance their entry into the clinic. © 2015 American Association for Clinical Chemistry.

  10. DILEMMAS OF COMMUNITY-DIRECTED MASS DRUG ADMINISTRATION FOR LYMPHATIC FILARIASIS CONTROL

    DEFF Research Database (Denmark)

    Kisoka, William; Mushi, Declare; Meyrowitsch, Dan W.

    2017-01-01

    There has in recent years been a growing interest in the social significance of global health policy and associated interventions. This paper is concerned with neglected tropical disease control, which prescribes annual mass drug administration to interrupt transmission of, among others, lymphatic...... filariasis. In Tanzania, this intervention is conducted through community-directed distribution, which aims to improve drug uptake by promoting community participation and local ownership in the intervention. However, the average uptake of drugs often remains too low to achieve the intended interruption...... of transmission. The qualitative research presented here followed the implementation of mass drug administration in Lindi and Morogoro Regions, Tanzania, in 2011 to understand the different forms of involvement in the campaign and the experiences of stakeholders of their part in community-directed distribution...

  11. Therapeutic drug monitoring of immunosuppressant drugs by high-performance liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Taylor, Paul J

    2004-04-01

    The currently expanding range of immunosuppressant agents has placed new challenges on therapeutic drug-monitoring (TDM) services. Many of these drugs require the measurement of concentrations with subsequent dosage adjustment to maximize efficacy while minimizing toxicity. HPLC-mass spectrometry (HPLC-MS) is a relatively new technique for drug quantification and thus TDM of immunosuppressant drugs. Although mass spectrometry relies on producing, differentiating, and detecting ions in the gas phase, the development of the atmospheric pressure ionization interface (electrospray and chemical ionization) has enabled the direct coupling of solution introduction of compounds, via HPLC, to the mass analyzer. The impetus for using HPLC-MS for immunosuppressant measurement has come from the highly potent low-dose immunosuppressant drugs tacrolimus and sirolimus, which have low nanogram per milliliter circulating concentrations. A number of strategies have been reported for sample preparation and ways to automate these processes with solid-phase extraction and 2-dimensional chromatography. The disadvantages of HPLC-MS are initial cost of equipment and availability of suitably skilled scientific staff. The advantages of HPLC-mass spectrometry are high sensitivity, specificity, small sample requirements, minimal sample preparation, rapid throughput, and simultaneous measurement. Further, scientists have the ability to develop methods to measure new immunosuppressant drugs by HPLC-MS before commercial assays become available. With potential applications increasing in immunosuppressive drug monitoring, it can be envisaged that HPLC-MS may become standard equipment in TDM laboratories of the future.

  12. 46 CFR 4.05-12 - Alcohol or drug use by individuals directly involved in casualties.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Alcohol or drug use by individuals directly involved in... § 4.05-12 Alcohol or drug use by individuals directly involved in casualties. (a) For each marine... evidence of alcohol or drug use by individuals directly involved in the casualty. (b) The marine employer...

  13. 49 CFR 225.17 - Doubtful cases; alcohol or drug involvement.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Doubtful cases; alcohol or drug involvement. 225..., AND INVESTIGATIONS § 225.17 Doubtful cases; alcohol or drug involvement. (a) The reporting officer of... the possible involvement of alcohol or drug use or impairment in such accident or incident. If the...

  14. Drug Involvement among Alcoholic Men: Relationships to Psychopathology and Adaptation.

    Science.gov (United States)

    Gonzalez, Fernando; And Others

    Though significant evidence suggests that drug-using alcoholics (DUA) are more damaged psychologically, socially, and medically than non-drug-using alcoholics (NDUA), current research on adults offers no clear explanation for the differences. This study examined the psychological and demographic differences between (other) drug-using and…

  15. Cardiac involvement in primary systemic vasculitis and potential drug therapies to reduce cardiovascular risk.

    Science.gov (United States)

    Misra, Durga Prasanna; Shenoy, Sajjan N

    2017-01-01

    Cardiac involvement is common in primary systemic vasculitides and may be due to direct effect of the disease on the heart or due to therapy. We shall review involvement of the heart in the various forms of primary systemic vasculitis. Among anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), eosinophilic granulomatosis with polyangiitis most commonly involves the heart. Involvement of the heart confers poorer prognosis in AAV, which is also complicated by increased risk of cardiovascular events. Kawasaki's disease (KD) is the most common form of medium-vessel vasculitis to affect the heart, with coronary artery aneurysms being the most common manifestation. These predispose patients with KD to develop premature ischemic heart disease. Takayasu's arteritis is the most common large-vessel vasculitis to involve the heart and can result in aortic incompetence, myocarditis, or coronary heart disease. Involvement of the heart in Behcet's disease is usually in the form of intracardiac mass lesions, thrombosis, or endomyocardial fibrosis. Drugs used in the treatment of systemic vasculitis influence the risk of developing cardiovascular events. Corticosteroid therapy has been shown to increase the risk of myocardial infarction, whereas methotrexate, azathioprine, mycophenolate mofetil, rituximab, and anti-tumor necrosis alpha agents favorably modulate the risk of cardiovascular events, predominantly by dampening systemic inflammation. Awareness of cardiac involvement in vasculitis and accelerated cardiovascular risk in these patients should help clinicians to maximize the modulation of modifiable risk factors for heart disease in these individuals.

  16. 32 CFR 147.10 - Guideline H-Drug involvement.

    Science.gov (United States)

    2010-07-01

    ... Controlled Substances Act of 1970, as amended (e.g., marijuana or cannabis, depressants, narcotics... use of a drug or use of a legal drug in a manner that deviates from approved medical direction. (b..., sale, or distribution; (3) Diagnosis by a credentialed medical professional (e.g., physician, clinical...

  17. Examining a Causal Model of Early Drug Involvement Among Inner City Junior High School Youths.

    Science.gov (United States)

    Dembo, Richard; And Others

    Reflecting the need to construct more inclusive, socially and culturally relevant conceptions of drug use than currently exist, the determinants of drug involvement among inner-city youths within the context of a causal model were investigated. The drug involvement of the Black and Puerto Rican junior high school girls and boys was hypothesized to…

  18. 46 CFR 185.210 - Alcohol or drug use by individuals directly involved in casualties.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Alcohol or drug use by individuals directly involved in... whether there is any evidence of alcohol or drug use by individuals directly involved in the casualty. (b... evidence of drug or alcohol use, or evidence of intoxication, has been obtained; and (2) Specifies the...

  19. 46 CFR 122.210 - Alcohol or drug use by individuals directly involved in casualties.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Alcohol or drug use by individuals directly involved in... PASSENGERS OPERATIONS Marine Casualties and Voyage Records § 122.210 Alcohol or drug use by individuals... alcohol or drug use by individuals directly involved in the casualty. (b) The owner, agent, master, or...

  20. Diffusion of treatment in social networks and mass drug administration.

    Science.gov (United States)

    Chami, Goylette F; Kontoleon, Andreas A; Bulte, Erwin; Fenwick, Alan; Kabatereine, Narcis B; Tukahebwa, Edridah M; Dunne, David W

    2017-12-05

    Information, behaviors, and technologies spread when people interact. Understanding these interactions is critical for achieving the greatest diffusion of public interventions. Yet, little is known about the performance of starting points (seed nodes) for diffusion. We track routine mass drug administration-the large-scale distribution of deworming drugs-in Uganda. We observe friendship networks, socioeconomic factors, and treatment delivery outcomes for 16,357 individuals in 3491 households of 17 rural villages. Each village has two community medicine distributors (CMDs), who are the seed nodes and responsible for administering treatments. Here, we show that CMDs with tightly knit (clustered) friendship connections achieve the greatest reach and speed of treatment coverage. Importantly, we demonstrate that clustering predicts diffusion through social networks when spreading relies on contact with seed nodes while centrality is unrelated to diffusion. Clustering should be considered when selecting seed nodes for large-scale treatment campaigns.

  1. prescriptions involving analgesic drugs at a secondary health facility

    African Journals Online (AJOL)

    INTRODUCTION. Analgesics are broadly divided into two classes, that is, Opioid and non-opioid drugs. Opioids are generally reserved for relieve of severe pain and are usually provided under supervision and strict control because of tendency to dependence and abuse1. On the other hand non-opioid analgesics are freely.

  2. Intracellular thiols: involvement in drug metabolism and radiation response

    International Nuclear Information System (INIS)

    Astor, M.

    1983-01-01

    Nitro compunds are activated by coupled enzyme reactions to oxygen reactive intermediates leading to the formation of peroxide, under aerobic conditions, and to the depletion of thiols, under anaerobic conditions. Some nitro compounds as substrates for glutathione-S-transferase, show peroxide production without prior thiol removal. Other drugs reacting spontaneouly with glutathione also produce peroxide. Glutathione plays an important role in the metabolism of the nitrocompounds either by directly reacting with them or their reduced intermediates such as the nitroso, nitro and hydroxyl radical. In the case of misonidazole, protection against their cytotoxic effects can be achieved by the addition of exogenous thiols such as glutathione or cysteamine. Results indicate that oxygen and peroxide electrodes provide convenient means for measuring the products of metabolic activation of nitro compounds. Mechanisms are proposed whereby protein, nonprotein and glutathione thiols can interact with drug radicals or with DNA radicals. 60 references, 14 figures, 5 tables

  3. DEWORMING DELUSIONS? MASS DRUG ADMINISTRATION IN EAST AFRICAN SCHOOLS.

    Science.gov (United States)

    Allen, Tim; Parker, Melissa

    2016-09-01

    Recent debates about deworming school-aged children in East Africa have been described as the 'Worm Wars'. The stakes are high. Deworming has become one of the top priorities in the fight against infectious diseases. Staff at the World Health Organization, the Gates Foundation and the World Bank (among other institutions) have endorsed the approach, and school-based treatments are a key component of large-scale mass drug administration programmes. Drawing on field research in Uganda and Tanzania, and engaging with both biological and social evidence, this article shows that assertions about the effects of school-based deworming are over-optimistic. The results of a much-cited study on deworming Kenyan school children, which has been used to promote the intervention, are flawed, and a systematic review of randomized controlled trials demonstrates that deworming is unlikely to improve overall public health. Also, confusions arise by applying the term deworming to a variety of very different helminth infections and to different treatment regimes, while local-level research in schools reveals that drug coverage usually falls below target levels. In most places where data exist, infection levels remain disappointingly high. Without indefinite free deworming, any declines in endemicity are likely to be reversed. Moreover, there are social problems arising from mass drug administration that have generally been ignored. Notably, there are serious ethical and practical issues arising from the widespread practice of giving tablets to children without actively consulting parents. There is no doubt that curative therapy for children infected with debilitating parasitic infections is appropriate, but overly positive evaluations of indiscriminate deworming are counter-productive.

  4. Human soil-transmitted helminths: implications of mass drug administration.

    Science.gov (United States)

    Vercruysse, Jozef; Levecke, Bruno; Prichard, Roger

    2012-12-01

    With the London Declaration on neglected tropical disease (NTD), we are entering a new era of combating NTDs. However, the worldwide prospects of increased mass drug administration (MDA) treatments warrant caution on the development of anthelmintic resistance. In this review, we discuss the practical implications of MDA programs on the development of anthelmintic resistance in human soil-transmitted helminths (STH). There is poor evidence of anthelmintic resistance in human STH. Moreover, there is presumptive evidence that the refugia in MDA programs to control human STH is currently large, suggesting that the development of anthelmintic resistance in STH will be slow or may not occur. It remains unclear whether the current MDA strategy to control STH will sufficiently delay or prevent the development of anthelmintic resistance. First, differences in efficacy across and within STH species, and seasonal transmission of STH have not yet been considered. Second, any surveillance system to monitor drug efficacy is lacking. Finally, there is still no agreed strategy on how to deal with anthelmintic resistance once it emerges. Although anthelmintic resistance in human STH is currently of limited concern, various actions should be put in place for its delay and monitoring, and strategies should be developed in case anthelmintic resistance occurs.

  5. The influence of peer affiliation and student activities on adolescent drug involvement.

    Science.gov (United States)

    Jenkins, J E

    1996-01-01

    This study examined the importance of students' academic performance level and extracurricular activities as predictors of drug involvement relative to peer influence. Social development theory provided the theoretical rational for the study. Data were obtained from 2,229 randomly selected students in the eighth, tenth, and twelfth grades from seventeen school districts in northeastern Ohio. At all three grade levels, involvement in extracurricular activities and academic level were significantly correlated with students' gateway and hard drug use. Consistent with prior research, the strongest correlate of gateway and hard drug use across all grade levels was affiliation with drug-using friends. Having a job after school was marginally related to self-reported gateway drug use at grade level ten. Multiple regression analysis revealed that extracurricular involvement and academic performance level make small, but unique contributions to the prediction of adolescents' gateway drug use beyond affiliation with drug-using peers at all three grade levels. The findings of this study suggest that students' academic performance and extracurricular involvements are significantly related to adolescent gateway and hard drug use, but have less predictive significance relative to peer relationships.

  6. Does Recent Physical and Sexual Victimization Affect Further Substance Use for Adult Drug-Involved Offenders?

    Science.gov (United States)

    Zweig, Janine M.; Yahner, Jennifer; Rossman, Shelli B.

    2012-01-01

    This study examined whether physical and sexual victimization experiences were related to further substance use for a sample of drug-involved adult offenders and whether this increase could be attributed to depression experienced after the victimization occurred. A total of 674 men and 284 women from the longitudinal Multisite Adult Drug Court…

  7. Biomembrane models and drug-biomembrane interaction studies: Involvement in drug design and development

    OpenAIRE

    Pignatello, R.; Musumeci, T.; Basile, L.; Carbone, C.; Puglisi, G.

    2011-01-01

    Contact with many different biological membranes goes along the destiny of a drug after its systemic administration. From the circulating macrophage cells to the vessel endothelium, to more complex absorption barriers, the interaction of a biomolecule with these membranes largely affects its rate and time of biodistribution in the body and at the target sites. Therefore, investigating the phenomena occurring on the cell membranes, as well as their different interaction with drugs in the physi...

  8. Benefits of mass customized products: moderating role of product involvement and fashion innovativeness

    Directory of Open Access Journals (Sweden)

    Minjung Park

    2018-02-01

    Full Text Available The objective of this study was to explore impacts and benefits of mass customized products on emotional product attachment, favorable attitudes toward a mass customization program, and the ongoing effect on loyalty intentions. This study further investigated how benefits, attachment, attitudes, and loyalty intentions differed as a function of involvement and fashion innovativeness. 290 female online shoppers in South Korea participated in an online survey. Results of this study revealed that perceived benefits positively influenced emotional product attachment and attitudes toward a mass customization program. In addition, attachment positively influenced attitudes, which in turn affected loyalty intentions. This study also found that benefits, attachment, attitudes, and loyalty intentions were all higher in highly involved consumers (high fashion innovators than those in less involved consumers (low fashion innovators. This study concludes with theoretical and practical implications for mass customization programs.

  9. Benefits of mass customized products: moderating role of product involvement and fashion innovativeness.

    Science.gov (United States)

    Park, Minjung; Yoo, Jungmin

    2018-02-01

    The objective of this study was to explore impacts and benefits of mass customized products on emotional product attachment, favorable attitudes toward a mass customization program, and the ongoing effect on loyalty intentions. This study further investigated how benefits, attachment, attitudes, and loyalty intentions differed as a function of involvement and fashion innovativeness. 290 female online shoppers in South Korea participated in an online survey. Results of this study revealed that perceived benefits positively influenced emotional product attachment and attitudes toward a mass customization program. In addition, attachment positively influenced attitudes, which in turn affected loyalty intentions. This study also found that benefits, attachment, attitudes, and loyalty intentions were all higher in highly involved consumers (high fashion innovators) than those in less involved consumers (low fashion innovators). This study concludes with theoretical and practical implications for mass customization programs.

  10. Conduct Disorder Symptoms and Illicit Drug Use in Juvenile Justice Involved Youth: The Reciprocal Relationship Between Positive Illicit Drug-Use Attitudes and Illicit Drug Use.

    Science.gov (United States)

    Kolp, Haley M; Hershberger, Alexandra R; Sanders, Jasmyn; Um, Miji; Aalsma, Matthew; Cyders, Melissa A

    2017-11-29

    Conduct disorder (CD) symptoms cooccur at high rates with illicit drug use in juvenile justice involved youth, which results in poorer outcomes; however, research has not identified where best to intervene in this relationship, limiting the identification of modifiable risk factors to reduce negative effects of CD symptoms. Two mediation models were examined to investigate the potential for CD symptoms to influence a reciprocal relationship between illicit drug use and positive drug attitudes, controlling for age, gender, and race. Data were examined for 245 juvenile justice involved youth (mean age = 15.46, SD = 1.30, range 12-18, 64.9% Black, 80.4% male) who completed court-ordered psychological assessments. Findings indicate: (1) Positive attitudes toward illicit drug use significantly mediated the relationship between CD symptoms and illicit drug use (β = 0.16, CI 0.09-0.27; test for indirect effect z = 4.17, p drug use significantly mediated the relationship between CD symptoms and positive attitudes toward illicit drug use (β = 0.20, CI 0.12-0.32; test for indirect effect z = 4.87, p drug use both indirectly, through more positive attitudes toward illicit drug use, and directly, which further strengthens positive attitudes toward illicit drug use.

  11. Social and Structural Barriers to Housing Among Street-Involved Youth Who Use Illicit Drugs

    OpenAIRE

    Krüsi, Andrea; Fast, Danya; Small, Will; Wood, Evan; Kerr, Thomas

    2010-01-01

    In Canada, approximately 150,000 youth live on the street. Street-involvement and homelessness have been associated with various health risks, including increased substance use, blood-borne infections, and sexually transmitted diseases. We undertook a qualitative study to better understand the social and structural barriers street-involved youth who use illicit drugs encounter when seeking housing. We conducted 38 semi-structured interviews with street-involved youth in Vancouver, Canada from...

  12. Biomembrane models and drug-biomembrane interaction studies: Involvement in drug design and development

    Science.gov (United States)

    Pignatello, R.; Musumeci, T.; Basile, L.; Carbone, C.; Puglisi, G.

    2011-01-01

    Contact with many different biological membranes goes along the destiny of a drug after its systemic administration. From the circulating macrophage cells to the vessel endothelium, to more complex absorption barriers, the interaction of a biomolecule with these membranes largely affects its rate and time of biodistribution in the body and at the target sites. Therefore, investigating the phenomena occurring on the cell membranes, as well as their different interaction with drugs in the physiological or pathological conditions, is important to exploit the molecular basis of many diseases and to identify new potential therapeutic strategies. Of course, the complexity of the structure and functions of biological and cell membranes, has pushed researchers toward the proposition and validation of simpler two- and three-dimensional membrane models, whose utility and drawbacks will be discussed. This review also describes the analytical methods used to look at the interactions among bioactive compounds with biological membrane models, with a particular accent on the calorimetric techniques. These studies can be considered as a powerful tool for medicinal chemistry and pharmaceutical technology, in the steps of designing new drugs and optimizing the activity and safety profile of compounds already used in the therapy. PMID:21430952

  13. Biomembrane models and drug-biomembrane interaction studies: Involvement in drug design and development.

    Science.gov (United States)

    Pignatello, R; Musumeci, T; Basile, L; Carbone, C; Puglisi, G

    2011-01-01

    Contact with many different biological membranes goes along the destiny of a drug after its systemic administration. From the circulating macrophage cells to the vessel endothelium, to more complex absorption barriers, the interaction of a biomolecule with these membranes largely affects its rate and time of biodistribution in the body and at the target sites. Therefore, investigating the phenomena occurring on the cell membranes, as well as their different interaction with drugs in the physiological or pathological conditions, is important to exploit the molecular basis of many diseases and to identify new potential therapeutic strategies. Of course, the complexity of the structure and functions of biological and cell membranes, has pushed researchers toward the proposition and validation of simpler two- and three-dimensional membrane models, whose utility and drawbacks will be discussed. This review also describes the analytical methods used to look at the interactions among bioactive compounds with biological membrane models, with a particular accent on the calorimetric techniques. These studies can be considered as a powerful tool for medicinal chemistry and pharmaceutical technology, in the steps of designing new drugs and optimizing the activity and safety profile of compounds already used in the therapy.

  14. Biomembrane models and drug-biomembrane interaction studies: Involvement in drug design and development

    Directory of Open Access Journals (Sweden)

    R Pignatello

    2011-01-01

    Full Text Available Contact with many different biological membranes goes along the destiny of a drug after its systemic administration. From the circulating macrophage cells to the vessel endothelium, to more complex absorption barriers, the interaction of a biomolecule with these membranes largely affects its rate and time of biodistribution in the body and at the target sites. Therefore, investigating the phenomena occurring on the cell membranes, as well as their different interaction with drugs in the physiological or pathological conditions, is important to exploit the molecular basis of many diseases and to identify new potential therapeutic strategies. Of course, the complexity of the structure and functions of biological and cell membranes, has pushed researchers toward the proposition and validation of simpler two- and three-dimensional membrane models, whose utility and drawbacks will be discussed. This review also describes the analytical methods used to look at the interactions among bioactive compounds with biological membrane models, with a particular accent on the calorimetric techniques. These studies can be considered as a powerful tool for medicinal chemistry and pharmaceutical technology, in the steps of designing new drugs and optimizing the activity and safety profile of compounds already used in the therapy.

  15. Use of mass-media and active involvement in a national dental health campaign in Scotland

    DEFF Research Database (Denmark)

    Schou, L

    1987-01-01

    This paper describes the evaluation of a Dental Health Mass-Media Campaign directed at 5-7-yr-old children and their mothers. It aimed at increasing knowledge and awareness of dental health by making use of three different components: inserts in women's magazines; television commercial; material...... that future national health education campaigns combine the mass-media approach to increase health awareness with active involvement activities to stimulate behavioural changes....

  16. Elevated risk of incarceration among street-involved youth who initiate drug dealing

    Directory of Open Access Journals (Sweden)

    Carly Hoy

    2016-11-01

    Full Text Available Abstract Background Street-involved youth are known to be an economically vulnerable population that commonly resorts to risky activities such as drug dealing to generate income. While incarceration is common among people who use illicit drugs and associated with increased economic vulnerability, interventions among this population remain inadequate. Although previous research has documented the role of incarceration in further entrenching youth in both the criminal justice system and street life, less is known whether recent incarceration predicts initiating drug dealing among vulnerable youth. This study examines the relationship between incarceration and drug dealing initiation among street-involved youth. Methods Between September 2005 and November 2014, data were collected through the At-Risk Youth Study, a cohort of street-involved youth who use illicit drugs, in Vancouver, Canada. An extended Cox model with time-dependent variables was used to examine the relationship between recent incarceration and initiation into drug dealing, controlling for relevant confounders. Results Among 1172 youth enrolled, only 194 (16.6% were drug dealing naïve at baseline and completed at least one additional study visit to facilitate the assessment of drug dealing initiation. Among this sample, 56 (29% subsequently initiated drug dealing. In final multivariable Cox regression analysis, recent incarceration was significantly associated with initiating drug dealing (adjusted hazard ratio = 2.31; 95% confidence interval (CI 1.21–4.42, after adjusting for potential confounders. Measures of recent incarceration lagged to the prior study follow-up were not found to predict initiation of drug dealing (hazard ratio = 1.50; 95% CI 0.66–3.42. Conclusions These findings suggest that among this study sample, incarceration does not appear to significantly propel youth to initiate drug dealing. However, the initiation of drug dealing among youth coincides

  17. Mass spectrometry innovations in drug discovery and development.

    Science.gov (United States)

    Papac, D I; Shahrokh, Z

    2001-02-01

    This review highlights the many roles mass spectrometry plays in the discovery and development of new therapeutics by both the pharmaceutical and the biotechnology industries. Innovations in mass spectrometer source design, improvements to mass accuracy, and implementation of computer-controlled automation have accelerated the purification and characterization of compounds derived from combinatorial libraries, as well as the throughput of pharmacokinetics studies. The use of accelerator mass spectrometry, chemical reaction interface-mass spectrometry and continuous flow-isotope ratio mass spectrometry are promising alternatives for conducting mass balance studies in man. To meet the technical challenges of proteomics, discovery groups in biotechnology companies have led the way to development of instruments with greater sensitivity and mass accuracy (e.g., MALDI-TOF, ESI-Q-TOF, Ion Trap), the miniaturization of separation techniques and ion sources (e.g., capillary HPLC and nanospray), and the utilization of bioinformatics. Affinity-based methods coupled to mass spectrometry are allowing rapid and selective identification of both synthetic and biological molecules. With decreasing instrument cost and size and increasing reliability, mass spectrometers are penetrating both the manufacturing and the quality control arenas. The next generation of technologies to simplify the investigation of the complex fate of novel pharmaceutical entities in vitro and in vivo will be chip-based approaches coupled with mass spectrometry.

  18. Employment and risk of injection drug use initiation among street involved youth in Canadian setting.

    Science.gov (United States)

    Richardson, Lindsey; DeBeck, Kora; Feng, Cindy; Kerr, Thomas; Wood, Evan

    2014-09-01

    Youth unemployment has been associated with labour market and health disparities. However, employment as a determinant of high-risk health behaviour among marginalized young people has not been well described. We sought to assess a potential relationship between employment status and initiation of intravenous drug use among a prospective cohort of street-involved youth. We followed injecting naïve youth in the At-Risk Youth Study, a cohort of street-involved youth aged 14-26 in Vancouver, Canada, and employed Cox regression analyses to examine whether employment was associated with injection initiation. Among 422 injecting naïve youth recruited between September 2005 and November 2011, 77 participants transitioned from non-injection to injection drug use, for an incidence density of 10.3 (95% confidence interval [CI]: 8.0-12.6) per 100 person years. Results demonstrating that employment was inversely associated with injection initiation (adjusted hazard ratio: 0.53; 95% CI: 0.33-0.85) were robust to adjustment for a range of potential confounders. A lack of employment among street-involved youth was associated with the initiation of injection drug use, a practice that predisposes individuals to serious long-term health consequences. Future research should examine if reducing barriers to labour market involvement among street-involved youth prevents transitions into high-risk drug use. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Mass Media, Alcohol and Drugs: A New Trend.

    Science.gov (United States)

    Breed, Warren; De Foe, James R.

    1980-01-01

    Several television situational comedies are reviewed which presented marihuana use in a humorous and harmless way. Speculation is that continuation of this trend would have an impact on public attitudes toward drug use. (Author)

  20. Modeling of drug release from matrix systems involving moving boundaries: approximate analytical solutions.

    Science.gov (United States)

    Lee, Ping I

    2011-10-10

    The purpose of this review is to provide an overview of approximate analytical solutions to the general moving boundary diffusion problems encountered during the release of a dispersed drug from matrix systems. Starting from the theoretical basis of the Higuchi equation and its subsequent improvement and refinement, available approximate analytical solutions for the more complicated cases involving heterogeneous matrix, boundary layer effect, finite release medium, surface erosion, and finite dissolution rate are also discussed. Among various modeling approaches, the pseudo-steady state assumption employed in deriving the Higuchi equation and related approximate analytical solutions appears to yield reasonably accurate results in describing the early stage release of a dispersed drug from matrices of different geometries whenever the initial drug loading (A) is much larger than the drug solubility (C(s)) in the matrix (or A≫C(s)). However, when the drug loading is not in great excess of the drug solubility (i.e. low A/C(s) values) or when the drug loading approaches the drug solubility (A→C(s)) which occurs often with drugs of high aqueous solubility, approximate analytical solutions based on the pseudo-steady state assumption tend to fail, with the Higuchi equation for planar geometry exhibiting a 11.38% error as compared with the exact solution. In contrast, approximate analytical solutions to this problem without making the pseudo-steady state assumption, based on either the double-integration refinement of the heat balance integral method or the direct simplification of available exact analytical solutions, show close agreement with the exact solutions in different geometries, particularly in the case of low A/C(s) values or drug loading approaching the drug solubility (A→C(s)). However, the double-integration heat balance integral approach is generally more useful in obtaining approximate analytical solutions especially when exact solutions are not

  1. Semiautomated radioimmunoassay for mass screening of drugs of abuse

    International Nuclear Information System (INIS)

    Sulkowski, T.S.; Lathrop, G.D.; Merritt, J.H.; Landez, J.H.; Noe, E.R.

    1975-01-01

    A rapid, semiautomated radioimmunoassay system for detection of morphine, barbiturates, and amphetamines is described. The assays are applicable to large drug abuse screening programs. The heart of the system is the automatic pipetting station which can accomplish 600 pipetting operations per hour. The method uses 15 to 30 μl for the amphetamine and combined morphine/barbiturate assays. A number of other drugs were tested for interference with the assays and the results are discussed

  2. Determination of different recreational drugs in sweat by headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME GC/MS): Application to drugged drivers.

    Science.gov (United States)

    Gentili, Stefano; Mortali, Claudia; Mastrobattista, Luisa; Berretta, Paolo; Zaami, Simona

    2016-09-10

    A procedure based on headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography/mass spectrometry (GC/MS) has been developed for the determination of most commonly used drugs of abuse in sweat of drivers stopped during roadside controls. DrugWipe 5A sweat screening device was used to collect sweat by a specific pad rubbed gently over forehead skin surface. The procedure involved an acid hydrolysis, a HS-SPME extraction for drugs of abuse but Δ(9)-tetrahydrocannabinol, which was directly extracted in alkaline medium HS-SPME conditions, a GC separation of analytes by a capillary column and MS detection by electron impact ionisation. The method was linear from the limit of quantification (LOQ) to 50ng drug per pad (r(2)≥0.99), with an intra- and inter-assay precision and accuracy always less than 15% and an analytical recovery between 95.1% and 102.8%, depending on the considered analyte. Using the validated method, sweat from 60 apparently intoxicated drivers were found positive to one or more drugs of abuse, showing sweat patches testing as a viable economic and simple alternative to conventional (blood and/or urine) and non conventional (oral fluid) testing of drugs of abuse in drugged drivers. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. The Correlates and Consequences of Drug Involvement among Youths Entering a Juvenile Justice Diversion Program

    Science.gov (United States)

    Dembo, Richard; Wareham, Jennifer; Poythress, Norman; Cook, Brittany; Schmeidler, James

    2006-01-01

    We report the results of the relationship of lifetime and past year drug involvement to psychosocial functioning among youths entering a Juvenile Arbitration Program (a diversion program) in the 13th Judicial Circuit, who enrolled in a Center for Substance Abuse Treatment funded study. The project is a clinical trial evaluating an innovative…

  4. [Gender centrality in the process of identity construction of women involved in drug trafficking].

    Science.gov (United States)

    Barcinski, Mariana

    2009-01-01

    The present article aims to discuss the specificities of crimes perpetrated by women, especially the female participation in drug trafficking in Rio de Janeiro, Brazil. In addition to that, it intends to distinguish female from male criminality. The study is based on reflections made through interviews conducted with eight women presenting a history of involvement in drug trafficking in the slums of Rio de Janeiro. Through a systemic discursive approach(1), the analysis investigates the micro and macro elements involved in the process of the construction of the participants' identity. Results show that women's motivations to enter, remain and drop drug trafficking are in great part determined by gender, which along with color and class shapes the roles performed and the places occupied by men and women in society.

  5. Increase in Drug Overdose Deaths Involving Fentanyl-Rhode Island, January 2012-March 2014.

    Science.gov (United States)

    Mercado, Melissa C; Sumner, Steven A; Spelke, M Bridget; Bohm, Michele K; Sugerman, David E; Stanley, Christina

    2018-03-01

    This study identified sociodemographic, substance use, and multiple opioid prescriber and dispenser risk factors among drug overdose decedents in Rhode Island, in response to an increase in overdose deaths (ODs) involving fentanyl. This cross-sectional investigation comprised all ODs reviewed by Rhode Island's Office of the State Medical Examiners (OSME) during January 2012 to March 2014. Data for 536 decedents were abstracted from OSME's charts, death certificates, toxicology reports, and Prescription Monitoring Program (PMP) databases. Decedents whose cause of death involved illicit fentanyl (N = 69) were compared with decedents whose causes of death did not involve fentanyl (other drug decedents; N = 467). Illicit-fentanyl decedents were younger than other drug decedents (P = 0.005). While more other-drug decedents than illicit fentanyl decedents had postmortem toxicological evidence of consuming heroin (31.9% vs 19.8%, P < 0.001) and various pharmaceutical substances (P = 0.002-0.027), third party reports indicated more recent heroin use among illicit fentanyl decedents (62.3% vs 45.6%, P = 0.002). Approximately 35% of decedents filled an opioid prescription within 90 days of death; of these, one-third had a mean daily dosage greater than 100 morphine milligram equivalents (MME/day). Most decedents' opioid prescriptions were filled at one to two dispensers (83.9%) and written by one to two prescribers (75.8%). Notably, 29.2% of illicit fentanyl and 10.5% of other drug decedents filled prescriptions for buprenorphine, which is used to treat opioid use disorders. Illicit-fentanyl deaths frequently involved other illicit drugs (e.g., cocaine, heroin). The proportion of all decedents acquiring greater than 100 MME/day prescription dosages written and/or filled by few prescribers and dispensers is concerning. To protect patients, prescribers and dispensers should review PMP records and substance abuse history prior to providing opioids.

  6. Testing a causal model of environmental influences on the early drug involvement of inner city junior high school youths.

    Science.gov (United States)

    Dembo, R; Farrow, D; Schmeidler, J; Burgos, W

    1979-01-01

    The present study examines a causal model explaining inner city youths' drug involvement using environmental variables which previously have been investigated singly or in various combinations and shown to influence drug use: the availability of drugs in the neighborhood and at school, a view of the neighborhood as tough, the esteem given to drug using, gang-involved persons by peers, friends' substance use, and participation in drug/street culture spare-time activities. The results show friends' use of alcohol and marijuana and participation in drug/street culture out-of-school activities have strong direct effects on personal drug involvement for the Black and Puerto Rican junior high school males and females who were studied; further, friends' use of alcohol and marijuana and the status peers give to drug using, gang-involved persons have respectable indirect effects on drug involvement for the four groups. In addition to these common features, a number of differences in the factors relating to drug involvement are found in the four groups. Implications of the results for alternative methods of drug abuse prevention and treatment are discussed, as is the necessity of utilizing an environmental, sociocultural view of drug use to adequately explain youth drug taking.

  7. Fragmentation of toxicologically relevant drugs in positive-ion liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Niessen, W M A

    2011-01-01

    The identification of drugs and related compounds by LC-MS-MS is an important analytical challenge in several application areas, including clinical and forensic toxicology, doping control analysis, and environmental analysis. Although target-compound based analytical strategies are most frequently applied, at some point the information content of the MS-MS spectra becomes relevant. In this article, the positive-ion MS-MS spectra of a wide variety of drugs and related substances are discussed. Starting point was an MS-MS mass spectral library of toxicologically relevant compounds, available on the internet. The positive-ion MS-MS spectra of ∼570 compounds were interpreted by chemical and therapeutic class, thus involving a wide variety of drug compound classes, such benzodiazepines, beta-blockers, angiotensin-converting enzyme inhibitors, phenothiazines, dihydropyridine calcium channel blockers, diuretics, local anesthetics, vasodilators, as well as various subclasses of anti-diabetic, antidepressant, analgesic, and antihistaminic drugs. In addition, the scientific literature was searched for available MS-MS data of these compound classes and the interpretation thereof. The results of this elaborate study are presented in this article. For each individual compound class, the emphasis is on class-specific fragmentation, as discussing fragmentation of all individual compounds would take far too much space. The recognition of class-specific fragmentation may be quite informative in determining the compound class of a specific unknown, which may further help in the identification. In addition, knowledge on (class-specific) fragmentation may further help in the optimization of the selectivity in targeted analytical approaches of compounds of one particular class. Copyright © 2011 Wiley Periodicals, Inc.

  8. The adverse effects of albendazole and praziquantel in mass drug ...

    African Journals Online (AJOL)

    and headache. This shows that more pupils from Mwea, (albendazole and praziquantel) than from Ndia (albendazole alone) experienced minor side effects. These results show that both drugs have temporary, minor side effects, which can be managed by trained schoolteachers by ensuring that the school children do not ...

  9. Factors influencing drug uptake during mass drug administration for control of lymphatic filariasis in rural and urban Tanzania.

    Directory of Open Access Journals (Sweden)

    William J Kisoka

    Full Text Available BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF is based on annual mass drug administration (MDA with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission interruption within reasonable time. The present study aimed to identify predictors and barriers to individual drug uptake during MDA implementation by the National LF Elimination Programme in Tanzania. METHODS: A questionnaire based cross sectional household survey was carried out in two rural and two urban districts in Lindi and Morogoro regions shortly after the 2011 MDA. 3279 adults (≥15 years were interviewed about personal characteristics, socio-economic status, MDA drug uptake among themselves and their children, reasons for taking/not taking drugs, and participation in previous MDA activities for LF control. FINDINGS: The overall drug uptake rate was 55.1% (range of 44.5-75.6% between districts. There was no overall major difference between children (54.8% and adults (55.2% or between females (54.9% and males (55.8%, but the role of these and other predictors varied to some extent between study sites. Major overall predictors of drug uptake among the interviewed adults were increasing age and history of previous drug uptake. Being absent from home during drug distribution was the main reason for not taking the drugs (50.2% followed by clinical contraindications to treatment (10.8%, missing household visits of drug distributors (10.6%, and households not being informed about the distribution (9.0%. CONCLUSION: Drug uptake relied more on easily modifiable provider-related factors than on individual perceptions and practices in the target population. Limited investments in appropriate timing, dissemination of accurate timing information to recipients and motivation of drug distributors to visit all households (repeatedly when residents are absent are likely

  10. Mass spectrometric analysis of illicit drugs in wastewater and surface water.

    Science.gov (United States)

    Castiglioni, Sara; Zuccato, Ettore; Chiabrando, Chiara; Fanelli, Roberto; Bagnati, Renzo

    2008-01-01

    Residues of illicit drugs have been recently found in urban wastewater and surface water. Their levels reflect the amount of drugs collectively excreted by consumers and can therefore be used to estimate drug abuse. An overview of the most widely used illicit drugs and of the analytical methods used for their detection in wastewater and surface water is presented here. Solid-phase extraction and high performance liquid chromatography-tandem mass spectrometry are the techniques that have been used for these investigations. Instrumental conditions and fragmentation patterns of illicit drugs and their metabolites are described. (c) 2008 Wiley Periodicals, Inc.

  11. Use of mass-media and active involvement in a national dental health campaign in Scotland

    DEFF Research Database (Denmark)

    Schou, L

    1987-01-01

    This paper describes the evaluation of a Dental Health Mass-Media Campaign directed at 5-7-yr-old children and their mothers. It aimed at increasing knowledge and awareness of dental health by making use of three different components: inserts in women's magazines; television commercial; material......, distinguished from the other two components by demanding an active involvement of the participants, had the largest impact. The television commercial, merely demanding a passive involvement of the participants, was less well remembered, and the magazine insert had the lowest recollection. It is suggested...

  12. Ethics of research involving mandatory drug testing of high school athletes in Oregon.

    Science.gov (United States)

    Shamoo, Adil E; Moreno, Jonathan D

    2004-01-01

    There is consensus that children have questionable decisional capacity and, therefore, in general a parent or a guardian must give permission to enroll a child in a research study. Moreover, freedom from duress and coercion, the cardinal rule in research involving adults, is even more important for children. This principle is embodied prominently in the Nuremberg Code (1947) and is embodied in various federal human research protection regulations. In a program named "SATURN" (Student Athletic Testing Using Random Notification), each school in the Oregon public-school system may implement a mandatory drug-testing program for high school student athletes. A prospective study to identify drug use among student-athletes, SATURN is designed both to evaluate the influence of random drug testing and to validate the survey data through identification of individuals who do not report drug use. The enrollment of students in the drug-testing study is a requirement for playing a school sport. In addition to the coercive nature of this study design, there were ethically questionable practices in recruitment, informed consent, and confidentiality. This article concerns the question of whether research can be conducted with high school students in conjunction with a mandatory drug-testing program, while adhering to prevailing ethical standards regarding human-subjects research and specifically the participation of children in research.

  13. CAPILLARY ZONE ELECTROPHORESIS IONSPRAY MASS-SPECTROMETRY OF A SYNTHETIC DRUG PROTEIN CONJUGATE MIXTURE

    NARCIS (Netherlands)

    KOSTIAINEN, R; FRANSSEN, EJF; BRUINS, AP

    1993-01-01

    Low-molecular-mass proteins, such as lysozyme, may be suitable carriers to target drugs to the kidney. Naproxen, an anti-inflammatory drug, has been conjugated with lysozyme via a covalent amide bond formed between the carboxylic acid function of naproxen and the amino group of one of the lysines in

  14. Relationships between Illicit Drug Use and Body Mass Index among Adolescents

    Science.gov (United States)

    Blackstone, Sarah R.; Herrmann, Lynn K.

    2016-01-01

    Prior research has established associations between body mass index (BMI) and use of alcohol, tobacco, and marijuana. However, little research has been done investigating the relationship between other common illicit drugs and BMI trends. The present study investigated whether adolescents who reported using illicit drugs showed differences in BMI…

  15. The effects of involvement and ad type on attitudes toward direct-to-consumer advertising of prescription drugs.

    Science.gov (United States)

    Limbu, Yam; Torres, Ivonne M

    2009-01-01

    This article examines consumers' attitudes toward Direct-to-Consumer (DTC) advertising of prescription drugs that are influenced by the use different types of DTC ads and product involvement. Our findings suggest that product involvement and the type of DTC ad are significant predictors of consumers' attitudinal responses toward DTC advertising. High involvement consumers have more favorable attitudes toward the drug's price, DTC ad and brand name, and a higher intention to ask a doctor about the advertised drug than low involvement consumers. In contrast to Informational and Reminder DTC ads, Persuasive ads have more favorable effects on consumers' reactions to DTC prescription drug advertising.

  16. Alcohol involvement in opioid pain reliever and benzodiazepine drug abuse-related emergency department visits and drug-related deaths - United States, 2010.

    Science.gov (United States)

    Jones, Christopher M; Paulozzi, Leonard J; Mack, Karin A

    2014-10-10

    The abuse of prescription drugs has led to a significant increase in emergency department (ED) visits and drug-related deaths over the past decade. Opioid pain relievers (OPRs) and benzodiazepines are the prescription drugs most commonly involved in these events. Excessive alcohol consumption also accounts for a significant health burden and is common among groups that report high rates of prescription drug abuse. When taken with OPRs or benzodiazepines, alcohol increases central nervous system depression and the risk for overdose. Data describing alcohol involvement in OPR or benzodiazepine abuse are limited. To quantify alcohol involvement in OPR and benzodiazepine abuse and drug-related deaths and to inform prevention efforts, the Food and Drug Administration (FDA) and CDC analyzed 2010 data for drug abuse-related ED visits in the United States and drug-related deaths that involved OPRs and alcohol or benzodiazepines and alcohol in 13 states. The analyses showed alcohol was involved in 18.5% of OPR and 27.2% of benzodiazepine drug abuse-related ED visits and 22.1% of OPR and 21.4% of benzodiazepine drug-related deaths. These findings indicate that alcohol plays a significant role in OPR and benzodiazepine abuse. Interventions to reduce the abuse of alcohol and these drugs alone and in combination are needed.

  17. Test Sample for the Spatially Resolved Quantification of Illicit Drugs on Fingerprints Using Imaging Mass Spectrometry

    NARCIS (Netherlands)

    Muramoto, S.; Forbes, T.P.; van Asten, A.C.; Gillen, G.

    2015-01-01

    A novel test sample for the spatially resolved quantification of illicit drugs on the surface of a fingerprint using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and desorption electrospray ionization mass spectrometry (DESI-MS) was demonstrated. Calibration curves relating the signal

  18. Exploring patient and family involvement in the lifecycle of an orphan drug: a scoping review.

    Science.gov (United States)

    Young, Andrea; Menon, Devidas; Street, Jackie; Al-Hertani, Walla; Stafinski, Tania

    2017-12-22

    Patients and their families have become more active in healthcare systems and research. The value of patient involvement is particularly relevant in the area of rare diseases, where patients face delayed diagnoses and limited access to effective therapies due to the high level of uncertainty in market approval and reimbursement decisions. It has been suggested that patient involvement may help to reduce some of these uncertainties. This review explored existing and proposed roles for patients, families, and patient organizations at each stage of the lifecycle of therapies for rare diseases (i.e., orphan drug lifecycle). A scoping review was conducted using methods outlined by Arksey and O'Malley. To validate the findings from the literature and identify any additional opportunities that were missed, a consultative webinar was conducted with members of the Patient and Caregiver Liaison Group of a Canadian research network. Existing and proposed opportunities for involving patients, families, and patient organizations were reported throughout the orphan drug lifecycle and fell into 12 themes: research outside of clinical trials; clinical trials; patient reported outcomes measures; patient registries and biorepositories; education; advocacy and awareness; conferences and workshops; patient care and support; patient organization development; regulatory decision-making; and reimbursement decision-making. Existing opportunities were not described in sufficient detail to allow for the level of involvement to be assessed. Additionally, no information on the impact of involvement within specific opportunities was found. Based on feedback from patients and families, documentation of existing opportunities within Canada is poor. Opportunities for patient, family, and patient organization involvement exist throughout the orphan drug lifecycle. However, based on the information found, it is not possible to determine which opportunities would be most effective at each stage.

  19. Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study.

    Science.gov (United States)

    Brady, Oliver J; Slater, Hannah C; Pemberton-Ross, Peter; Wenger, Edward; Maude, Richard J; Ghani, Azra C; Penny, Melissa A; Gerardin, Jaline; White, Lisa J; Chitnis, Nakul; Aguas, Ricardo; Hay, Simon I; Smith, David L; Stuckey, Erin M; Okiro, Emelda A; Smith, Thomas A; Okell, Lucy C

    2017-07-01

    Mass drug administration for elimination of Plasmodium falciparum malaria is recommended by WHO in some settings. We used consensus modelling to understand how to optimise the effects of mass drug administration in areas with low malaria transmission. We collaborated with researchers doing field trials to establish a standard intervention scenario and standard transmission setting, and we input these parameters into four previously published models. We then varied the number of rounds of mass drug administration, coverage, duration, timing, importation of infection, and pre-administration transmission levels. The outcome of interest was the percentage reduction in annual mean prevalence of P falciparum parasite rate as measured by PCR in the third year after the final round of mass drug administration. The models predicted differing magnitude of the effects of mass drug administration, but consensus answers were reached for several factors. Mass drug administration was predicted to reduce transmission over a longer timescale than accounted for by the prophylactic effect alone. Percentage reduction in transmission was predicted to be higher and last longer at lower baseline transmission levels. Reduction in transmission resulting from mass drug administration was predicted to be temporary, and in the absence of scale-up of other interventions, such as vector control, transmission would return to pre-administration levels. The proportion of the population treated in a year was a key determinant of simulated effectiveness, irrespective of whether people are treated through high coverage in a single round or new individuals are reached by implementation of several rounds. Mass drug administration was predicted to be more effective if continued over 2 years rather than 1 year, and if done at the time of year when transmission is lowest. Mass drug administration has the potential to reduce transmission for a limited time, but is not an effective replacement for existing

  20. Mass Drug Administration for Scabies Control in a Population with Endemic Disease.

    Science.gov (United States)

    Romani, Lucia; Whitfeld, Margot J; Koroivueta, Josefa; Kama, Mike; Wand, Handan; Tikoduadua, Lisi; Tuicakau, Meciusela; Koroi, Aminiasi; Andrews, Ross; Kaldor, John M; Steer, Andrew C

    2015-12-10

    Scabies is an underrecognized cause of illness in many developing countries. It is associated with impetigo, which can lead to serious systemic complications. We conducted a trial of mass drug administration for scabies control in Fiji. We randomly assigned three island communities to one of three different interventions for scabies control: standard care involving the administration of permethrin to affected persons and their contacts (standard-care group), mass administration of permethrin (permethrin group), or mass administration of ivermectin (ivermectin group). The primary outcome was the change in the prevalence of scabies and of impetigo from baseline to 12 months. A total of 2051 participants were enrolled; 803 were in the standard-care group, 532 in the permethrin group, and 716 in the ivermectin group. From baseline to 12 months, the prevalence of scabies declined significantly in all groups, with the greatest reduction seen in the ivermectin group. The prevalence declined from 36.6% to 18.8% in the standard-care group (relative reduction in prevalence, 49%; 95% confidence interval [CI], 37 to 60), from 41.7% to 15.8% in the permethrin group (relative reduction, 62%; 95% CI, 49 to 75), and from 32.1% to 1.9% in the ivermectin group (relative reduction, 94%; 95% CI, 83 to 100). The prevalence of impetigo also declined in all groups, with the greatest reduction seen in the ivermectin group. The prevalence declined from 21.4% to 14.6% in the standard-care group (relative reduction, 32%; 95% CI, 14 to 50), from 24.6% to 11.4% in the permethrin group (relative reduction, 54%; 95% CI, 35 to 73), and from 24.6% to 8.0% in the ivermectin group (relative reduction, 67%; 95% CI, 52 to 83). Adverse events were mild and were reported more frequently in the ivermectin group than in the permethrin group (15.6% vs. 6.8%). Mass drug administration, particularly the administration of ivermectin, was efficacious for the control of scabies and impetigo. (Funded by the

  1. Alcohol- and Drug-Involved Driving in the United States: Methodology for the 2007 National Roadside Survey

    Science.gov (United States)

    Lacey, John H.; Kelley-Baker, Tara; Voas, Robert B.; Romano, Eduardo; Furr-Holden, C. Debra; Torres, Pedro; Berning, Amy

    2011-01-01

    This article describes the methodology used in the 2007 U.S. National Roadside Survey to estimate the prevalence of alcohol- and drug-impaired driving and alcohol- and drug-involved driving. This study involved randomly stopping drivers at 300 locations across the 48 continental U.S. states at sites selected through a stratified random sampling…

  2. Factors influencing drug uptake during mass drug administration for control of lymphatic filariasis in rural and urban Tanzania

    DEFF Research Database (Denmark)

    Kisoka, William J.; Simonsen, Paul Erik; Malecela, Mwelecele N.

    2014-01-01

    BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission...... control. FINDINGS: The overall drug uptake rate was 55.1% (range of 44.5-75.6% between districts). There was no overall major difference between children (54.8%) and adults (55.2%) or between females (54.9%) and males (55.8%), but the role of these and other predictors varied to some extent between study...

  3. Nonmedical prescription opioids and pathways of drug involvement in the US: Generational differences.

    Science.gov (United States)

    Wall, Melanie; Cheslack-Postava, Keely; Hu, Mei-Chen; Feng, Tianshu; Griesler, Pamela; Kandel, Denise B

    2018-01-01

    This study sought to specify (1) the position of nonmedical prescription opioids (NMPO) in drug initiation sequences among Millennials (1979-96), Generation X (1964-79), and Baby Boomers (1949-64) and (2) gender and racial/ethnic differences in sequences among Millennials. Data are from the 2013-2014 National Surveys on Drug Use and Health (n = 73,026). We identified statistically significant drug initiation sequences involving alcohol/cigarettes, marijuana, NMPO, cocaine, and heroin using a novel method distinguishing significant sequences from patterns expected only due to correlations induced by common liability among drugs. Alcohol/cigarettes followed by marijuana was the most common sequence. NMPO or cocaine use after marijuana, and heroin use after NMPO or cocaine, differed by generation. Among successively younger generations, NMPO after marijuana and heroin after NMPO increased. Millennials were more likely to initiate NMPO than cocaine after marijuana; Generation X and Baby Boomers were less likely (odds ratios = 1.4;0.3;0.2). Millennials were more likely than Generation X and Baby Boomers to use heroin after NMPO (hazards ratios = 7.1;3.4;2.5). In each generation, heroin users were far more likely to start heroin after both NMPO and cocaine than either alone. Sequences were similar by gender. Fewer paths were significant among African-Americans. NMPOs play a more prominent role in drug initiation sequences among Millennials than prior generations. Among Millennials, NMPO use is more likely than cocaine to follow marijuana use. In all generations, transition to heroin from NMPO significantly occurs only when both NMPO and cocaine have been used. Delineation of drug sequences suggests optimal points in development for prevention and treatment efforts. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Canadian policy makers' views on pharmaceutical reimbursement contracts involving confidential discounts from drug manufacturers.

    Science.gov (United States)

    Morgan, Steven G; Thomson, Paige A; Daw, Jamie R; Friesen, Melissa K

    2013-10-01

    Pharmaceutical policy makers are increasingly negotiating reimbursement contracts that include confidential price terms that may be affected by drug utilization volumes, patterns, or outcomes. Though such contracts may offer a variety of benefits, including the ability to tie payment to the actual performance of a product, they may also create potential policy challenges. Through telephone interviews about this type of contract, we studied the views of officials in nine of ten Canadian provinces. Use of reimbursement contracts involving confidential discounts is new in Canada and ideas about power and equity emerged as cross-cutting themes in our interviews. Though confidential rebates can lower prices and thereby increase coverage of new medicines, several policy makers felt they had little power in the decision to negotiate rebates. Study participants explained that the recent rise in the use of rebates had been driven by manufacturers' pricing tactics and precedent set by other jurisdictions. Several policy makers expressed concerns that confidential rebates could result in inter-jurisdictional inequities in drug pricing and coverage. Policy makers also noted un-insured and under-insured patients must pay inflated "list prices" even if rebates are negotiated by drug plans. The establishment of policies for disciplined negotiations, inter-jurisdictional cooperation, and provision of drug coverage for all citizens are potential solutions to the challenges created by this new pharmaceutical pricing paradigm. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  5. Drugs and other chemicals involved in fatal poisoning in England and Wales during 2000 – 2011.

    Science.gov (United States)

    Handley, S A; Flanagan, R J

    2014-01-01

    Fatal poisoning data can reveal trends in the poisons encountered, which can help guide prescribing practices and product safety and other legislation, and more recently has helped to monitor the use of emerging drugs of abuse ( ‘ legal highs ’ ). We searched Mortality Statistics – Injury and poisoning, Series DH4 (2000 – 2005), Mortality Statistics – Deaths registered in England and Wales, Series DR (2006 – 2011), and the Office for National Statistics drug poisoning database for information on fatal poisoning during 2000 – 2011. We also searched the Pubmed database for ‘ fatal ’ and ‘ poisoning ’ and ‘ England ’ and ‘ Wales ’ : this search yielded seven papers that gave relevant information on deaths reported during 2000 – 2011 that were not superseded by later publications. DEATHS FROM POISONING: The annual number of deaths from poisoning fell from 2000 (3092) to 2010 (2749), before increasing to 3341 in 2011. This increase was due in part to a change in the ICD coding relating to alcohol poisoning, suggesting that such deaths had been under-recorded previously. Although fatalities from dextropropoxyphene declined (287 in 2004 and 18 in 2011) following the withdrawal of co-proxamol (paracetamol [acetaminophen] and dextropropoxyphene [propoxyphene] mixture) during 2005 – 2007, deaths involving codeine and most notably tramadol (836 deaths during 2000 – 2011) increased. Deaths from paracetamol poisoning either alone, or with alcohol reached 89 in 2011, the lowest annual figure since 1974. However, in reality there has been no marked downward trend since 1999 despite reductions in pack size, continued publicity as to the dangers of paracetamol overdose, and improved liver failure treatment, including transplantation. The annual number of deaths from antidepressants remained relatively stable (median: 397, range: 335 – 469). Although the number of deaths from dosulepin [dothiepin] decreased (186 in 2000 and 49 in 2011), the

  6. [Agency and victimization in the trajectory of women involved in drug trafficking in Rio de Janeiro].

    Science.gov (United States)

    Barcinski, Mariana

    2009-01-01

    The goal of the present article is to discuss the traditional victimization of women who get involved in criminal activities, focusing on agency and personal initiative as the main motivators. Through the discursive analysis of qualitative interviews with five women with a history in drug trafficking in Rio de Janeiro we sought to capture the dilemmas that characterize the ways in which these women justify their participation in a traditional male activity. At a micro level, the analysis focuses on the rhetoric efficacy of the different positions assumed by the participants(1). At a macro level, the analysis investigates how the participants appropriate different discourses about womanhood in order to give sense to their personal histories(2). The results show that the participants oscillate between appealing to external causes for justifying their choice (such as the lack of options characterizing the trajectory of marginalized populations and the personal involvement with criminal partners) and assuming responsibility for having been involved in drug trafficking. In this case, they often mention the power and respect they used to experience as traffickers as the main motivator for their criminal trajectory.

  7. Social and structural barriers to housing among street-involved youth who use illicit drugs.

    Science.gov (United States)

    Krüsi, Andrea; Fast, Danya; Small, Will; Wood, Evan; Kerr, Thomas

    2010-05-01

    In Canada, approximately 150,000 youth live on the street. Street-involvement and homelessness have been associated with various health risks, including increased substance use, blood-borne infections and sexually transmitted diseases. We undertook a qualitative study to better understand the social and structural barriers street-involved youth who use illicit drugs encounter when seeking housing. We conducted 38 semi-structured interviews with street-involved youth in Vancouver, Canada from May to October 2008. Interviewees were recruited from the At-risk Youth Study (ARYS) cohort, which follows youth aged 14 to 26 who have experience with illicit drug use. All interviews were thematically analyzed, with particular emphasis on participants' perspectives regarding their housing situation and their experiences seeking housing. Many street-involved youth reported feeling unsupported in their efforts to find housing. For the majority of youth, existing abstinence-focused shelters did not constitute a viable option and, as a result, many felt excluded from these facilities. Many youth identified inflexible shelter rules and a lack of privacy as outweighing the benefits of sleeping indoors. Single-room occupancy hotels (SROs) were reported to be the only affordable housing options, as many landlords would not rent to youth on welfare. Many youth reported resisting moving to SROs as they viewed them as unsafe and as giving up hope for a return to mainstream society. The findings of the present study shed light on the social and structural barriers street-involved youth face in attaining housing and challenge the popular view of youth homelessness constituting a lifestyle choice. Our findings point to the need for housing strategies that include safe, low threshold, harm reduction focused housing options for youth who engage in illicit substance use.

  8. Lifetime victimization and psychological distress: cluster profiles of out of treatment drug-involved women.

    Science.gov (United States)

    Golder, Seana; Logan, T K

    2010-01-01

    K-means clustering techniques were used to identify four cluster profiles characterized by unique patterns of victimization and psychological distress and further differentiated by distinct patterns of risk and protection across multiple life domains among a sample of 149 crack-using women. Results of this study suggest that important differences exist in patterns of victimization and psychological distress among drug-involved women. Identification of this variation can be used to tailor intervention strategies to the particular needs of different subgroups within the population of crack-using women.

  9. Effects of Radiation and Dietary Iron on Expression of Genes and Proteins Involved in Drug Metabolism

    Science.gov (United States)

    Faust, K. M.; Wotring, V. E.

    2014-01-01

    Liver function, especially the rate of metabolic enzyme activities, determines the concentration of circulating drugs and the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand any effects of spaceflight on the enzymes of the liver. Dietary factors and exposure to radiation are aspects of spaceflight that are potential oxidative stressors and both can be modeled in ground experiments. In this experiment, we examined the effects of high dietary iron and low dose gamma radiation (individually and combined) on the gene expression of enzymes involved in drug metabolism, redox homeostasis, and DNA repair. METHODS All procedures were approved by the JSC Animal Care and Use Committee. Male Sprague-Dawley rats were divided into 4 groups (n=8); control, high Fe diet (650 mg iron/kg), radiation (fractionated 3 Gy exposure from a Cs- 137 source) and combined high Fe diet + radiation exposure. Animals were euthanized 24h after the last treatment of radiation; livers were removed immediately and flash -frozen in liquid nitrogen. Expression of genes thought to be involved in redox homeostasis, drug metabolism and DNA damage repair was measured by RT-qPCR. Where possible, protein expression of the same genes was measured by western blotting. All data are expressed as % change in expression normalized to reference gene expression; comparisons were then made of each treatment group to the sham exposed/ normal diet control group. Data was considered significant at pprotein

  10. Exploring family and community involvement to protect Thai youths from alcohol and illegal drug abuse.

    Science.gov (United States)

    Wongtongkam, Nualnong; Ward, Paul Russell; Day, Andrew; Winefield, Anthony Harold

    2015-01-01

    Youth substance abuse is widely recognized as a major public health issue in Thailand. This study explores family and community risk and protective factors relevant to alcohol and illegal drug misuse in 1,778 Thai teenagers. Strong family attachment and a family history of antisocial behaviors were strongly associated with nearly all forms of substance abuse, with adjusted odds ratios ranging from 5.05 to 8.45. Community disorganization was strongly associated with self-reported substance use, although involvement in prosocial activities acted as a protective factor. The findings suggest that interventions that promote family cohesion and encourage community involvement may have considerable benefits in reducing substance abuse in Thai adolescents.

  11. A Randomized Trial of Probation Case Management for Drug-Involved Women Offenders

    Science.gov (United States)

    Guydish, Joseph; Chan, Monica; Bostrom, Alan; Jessup, Martha; Davis, Thomas; Marsh, Cheryl

    2008-01-01

    This paper reports findings from a clinical trial of a probation case management (PCM) intervention for drug-involved women offenders. Participants were randomly assigned to either PCM (n=92) or standard probation (n=91), and followed for 12 months using measures of substance abuse, psychiatric symptoms, social support and service utilization. Arrest data were collected from administrative datasets. The sample (N=183) included mostly African American (57%) and White (20%) women, with a mean age of 34.7 (SD = 9.2) and mean education of 11.6 years (SD = 2.1). Cocaine and heroin were the most frequently reported drugs of abuse, 86% reported prior history of incarceration, and 74% had children. Women assigned to both PCM and standard probation showed change over time in the direction of clinical improvement on 7 of 10 outcomes measured. However, changes observed for the PCM group were no different than those observed for the standard probation group. Higher levels of case management, drug abuse treatment, and probationary supervision may be required to achieve improved outcomes in this population. PMID:21464888

  12. Development of a metrics dashboard for monitoring involvement in the 340B Drug Pricing Program.

    Science.gov (United States)

    Karralli, Rusol; Tipton, Joyce; Dumitru, Doina; Scholz, Lisa; Masilamani, Santhi

    2015-09-01

    An electronic tool to support hospital organizations in monitoring and addressing financial and compliance challenges related to participation in the 340B Drug Pricing Program is described. In recent years there has been heightened congressional and regulatory scrutiny of the federal 340B program, which provides discounted drug prices on Medicaid-covered drugs to safety net hospitals and other 340B-eligible healthcare organizations, or "covered entities." Historically, the 340B program has lacked a metrics-driven reporting framework to help covered entities capture the value of 340B program involvement, community benefits provided to underserved populations, and costs associated with compliance with 340B eligibility requirements. As part of an initiative by a large health system to optimize its 340B program utilization and regulatory compliance efforts, a team of pharmacists led the development of an electronic dashboard tool to help monitor 340B program activities at the system's 340B-eligible facilities. After soliciting input from an array of internal and external 340B program stakeholders, the team designed the dashboard and associated data-entry tools to facilitate the capture and analysis of 340B program-related data in four domains: cost savings and revenue, program maintenance costs, community benefits, and compliance. A large health system enhanced its ability to evaluate and monitor 340B program-related activities through the use of a dashboard tool capturing key metrics on cost savings achieved, maintenance costs, and other aspects of program involvement. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  13. Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration

    DEFF Research Database (Denmark)

    Chu, Brian K.; Deming, Michael; Biritwum, Nana-Kwadwo

    2013-01-01

    Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached...

  14. Prospects for the control of neglected tropical diseases by mass drug administration

    NARCIS (Netherlands)

    Smits, Henk L.

    2009-01-01

    The prospects for the control of neglected tropical diseases, including soil-transmitted helminthiasis, shistosomiasis, lymphatic filariasis, onchocerciasis and trachoma, through mass drug administration, are exemplified by the elimination of the trachoma as a public-health problem in Morocco. In

  15. Modeling the Impact and Costs of Semiannual Mass Drug Administration for Accelerated Elimination of Lymphatic Filariasis

    NARCIS (Netherlands)

    W.A. Stolk (Wilma); Q.A. ten Bosch (Quirine); S.J. de Vlas (Sake); P.U. Fischer (Peter); G.J. Weil (Gary); A.S. Goldman (Ann)

    2013-01-01

    textabstractThe Global Program to Eliminate Lymphatic Filariasis (LF) has a target date of 2020. This program is progressing well in many countries. However, progress has been slow in some countries, and others have not yet started their mass drug administration (MDA) programs. Acceleration is

  16. Screening of drugs and toxic compounds with liquid chromatography-linear ion trap tandem mass spectrometry.

    Science.gov (United States)

    Sauvage, François-Ludovic; Saint-Marcoux, Franck; Duretz, Bénédicte; Deporte, Didier; Lachatre, Gérard; Marquet, Pierre

    2006-09-01

    In clinical and forensic toxicology, general unknown screening is used to detect and identify exogenous compounds. In this study, we aimed to develop a comprehensive general unknown screening method based on liquid chromatography coupled with a hybrid triple-quadrupole linear ion trap mass spectrometer. After solid-phase extraction, separation was performed using gradient reversed-phase chromatography. The mass spectrometer was operated in the information-dependent acquisition mode, switching between a survey scan acquired in the Enhanced Mass Spectrometry mode with dynamic subtraction of background noise and a dependent scan obtained in the enhanced product ion scan mode. The complete cycle time was 1.36 s. A library of 1000 enhanced product ion-tandem mass spectrometry spectra in positive mode and 250 in negative mode, generated using 3 alternated collision tensions during each scan, was created by injecting pure solutions of drugs and toxic compounds. Comparison with HPLC-diode array detection and gas chromatography-mass spectrometry for the analysis of 36 clinical samples showed that linear ion trap tandem mass spectrometry could identify most of the compounds (94% of the total). Some compounds were detected only by 1 of the other 2 techniques. Specific clinical cases highlighted the advantages and limitations of the method. A unique combination of new operating modes provided by hybrid triple-quadrupole linear ion trap mass spectrometers and new software features allowed development of a comprehensive and efficient method for the general unknown screening of drugs and toxic compounds in blood or urine.

  17. Age at drinking onset, alcohol dependence, and their relation to drug use and dependence, driving under the influence of drugs, and motor-vehicle crash involvement because of drugs.

    Science.gov (United States)

    Hingson, Ralph W; Heeren, Timothy; Edwards, Erika M

    2008-03-01

    We explored among people who ever consumed alcohol whether early age at drinking onset and alcohol dependence predicted drug use and dependence. We also examined among drinkers who have used drugs whether they also predict driving under the influence of drugs and motor-vehicle crash involvement because of drugs. A U.S. national sample of 42,867 persons age 18 and older was surveyed in 1991-1992 (response rate = 90%). Logistic regression examined these potential associations among 27,616 respondents who ever drank alcohol, controlling for numerous demographic and personal characteristics. Among "ever" drinkers, 22% used drugs, 10% had driven under the influence of drugs, and nearly 1% was in a motor-vehicle crash because of drug use, the equivalent of 1 million people. The younger the age of respondents when they first began drinking and whether they ever experienced alcohol dependence were independently associated with greater odds of ever using drugs and experiencing drug dependence. Among persons who consumed alcohol and drugs, having ever experienced drug dependence was the strongest predictor of driving under the influence of drugs and motor-vehicle crash involvement because of drug use. After controlling for drug dependence and age at first drug use, having experienced alcohol dependence was also independently associated with both outcomes. Efforts to prevent drug-related crashes should include drug use prevention and treatment, as well as prevention of early alcohol use and treatment of alcohol dependence.

  18. Racialized Mass Incarceration and the War on Drugs: A Critical Race Theory Appraisal.

    Science.gov (United States)

    Fornili, Katherine Smith

    The purpose of this column is to summarize important aspects of the racialized War on Drugs, including (a) the school-to-prison pipeline, (b) the for-profit prison system ("prison industrial complex"), (c) racialized mass incarceration, and (d) the disproportionately negative impact of the War on Drugs on families and communities of color. Analysis of critical race theory (CRT), the study of the relationships between race, racism, and power, will provide a cohesive framework for examining these four aspects. CRT maintains that American laws, including antidiscrimination laws, are structured to maintain White privilege (Alexander, 2010; Capers, 2014; Delgado & Stefancic, 2017; Nyika & Murray-Orr, 2017). Proponents of CRT are committed to progressive race consciousness and view CRT as a mechanism for analyzing and addressing racial inequity (Capers, 2014). We cannot incarcerate our way out of the drug epidemic. The War on Drugs is a war on individuals who experience a treatable medical condition and on the communities in which they reside. It should more properly be called "The War on Our Own People." The failed War on Drugs and the current administration's efforts to revive and strengthen it provide examples of how the dominant society allows, and perhaps even actively promotes, the destruction of minority communities. Addictions nurses object to the conditions that perpetuate the War on Drugs and racialized mass incarceration. We view it our ethical responsibility to advocate for social justice and healthy sociopolitical environments for all members of society, regardless of race, class, or creed.

  19. Mass Spectrometry in Clinical Laboratory: Applications in Therapeutic Drug Monitoring and Toxicology.

    Science.gov (United States)

    Garg, Uttam; Zhang, Yan Victoria

    2016-01-01

    Mass spectrometry (MS) has been used in research and specialized clinical laboratories for decades as a very powerful technology to identify and quantify compounds. In recent years, application of MS in routine clinical laboratories has increased significantly. This is mainly due to the ability of MS to provide very specific identification, high sensitivity, and simultaneous analysis of multiple analytes (>100). The coupling of tandem mass spectrometry with gas chromatography (GC) or liquid chromatography (LC) has enabled the rapid expansion of this technology. While applications of MS are used in many clinical areas, therapeutic drug monitoring, drugs of abuse, and clinical toxicology are still the primary focuses of the field. It is not uncommon to see mass spectrometry being used in routine clinical practices for those applications.

  20. Antiretroviral Drug Interactions: Overview of Interactions Involving New and Investigational Agents and the Role of Therapeutic Drug Monitoring for Management

    Directory of Open Access Journals (Sweden)

    R. Chris Rathbun

    2011-10-01

    Full Text Available Antiretrovirals are prone to drug-drug and drug-food interactions that can result in subtherapeutic or supratherapeutic concentrations. Interactions between antiretrovirals and medications for other diseases are common due to shared metabolism through cytochrome P450 (CYP450 and uridine diphosphate glucuronosyltransferase (UGT enzymes and transport by membrane proteins (e.g., p-glycoprotein, organic anion-transporting polypeptide. The clinical significance of antiretroviral drug interactions is reviewed, with a focus on new and investigational agents. An overview of the mechanistic basis for drug interactions and the effect of individual antiretrovirals on CYP450 and UGT isoforms are provided. Interactions between antiretrovirals and medications for other co-morbidities are summarized. The role of therapeutic drug monitoring in the detection and management of antiretroviral drug interactions is also briefly discussed.

  1. Collaborative Behavioral Management for Drug-Involved Parolees: Rationale and Design of the Step'n Out Study

    Science.gov (United States)

    Friedmann, Peter D.; Katz, Elizabeth C.; Rhodes, Anne G.; Taxman, Faye S.; O'Connell, Daniel J.; Frisman, Linda K.; Burdon, William M.; Fletcher, Bennett W.; Litt, Mark D.; Clarke, Jennifer; Martin, Steven S.

    2008-01-01

    This article describes the rationale, study design, and implementation for the Step'n Out study of the Criminal Justice Drug Abuse Treatment Studies. Step'n Out tests the relative effectiveness of collaborative behavioral management of drug-involved parolees. Collaborative behavioral management integrates the roles of parole officers and treatment…

  2. [Drug use and involvement in risky driving styles in a sample of university students. The uniHcos project].

    Science.gov (United States)

    Jiménez-Mejías, Eladio; Medina-García, Miguel Ángel; Martínez-Ruiz, Virginia; Pulido-Manzanero, José; Fernández-Villa, Tania

    2015-09-01

    Drug and alcohol use are known to increase the risk of traffic accidents, especially among youth. However, the association between habitual drug use and the adoption of risky driving behavior is not well known. The aim of this study was to identify and quantify the association between habitual drug use and involvement in risky driving practices overall and by gender among university students. A cross sectional study was conducted. The study population was composed of 559 car drivers younger than 31 years who completed an online questionnaire during the 2011-2012 academic year. Among other factors, the questionnaire assessed the following items: habitual drug consumption (20 or more days) during the last year and involvement in other risky driving practices during the last month. A total of 27.7% of students reported they had used drugs regularly during the last year. Drug use was associated with a higher frequency of involvement in risky driving practices. In men, the factors most strongly associated with drug consumption were speeding, driving under influence of alcohol, and feeling drowsy while driving. In women, drug consumption was mainly associated with smoking while driving, drunk driving, and driving without rest. The results of our study support the hypothesis that habitual drug use is associated with an increased frequency of risky driving behavior. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  3. Increases and decreases in drug use attributed to housing status among street-involved youth in a Canadian setting.

    Science.gov (United States)

    Cheng, Tessa; Wood, Evan; Nguyen, Paul; Kerr, Thomas; DeBeck, Kora

    2014-04-10

    Among a cohort of drug-using street-involved youth, we sought to identify the prevalence of reporting increases and decreases in illicit drug use due to their current housing status and to identify factors associated with reporting these changes. This longitudinal study was based on data collected between June 2008 and May 2012 from a prospective cohort of street-involved youth aged 14-26 in Vancouver, Canada. At semi-annual study follow-up visits, youth were asked if their drug use was affected by their housing status. Using generalized estimating equations, we identified factors associated with perceived increases and decreases in drug use attributed to housing status. Among our sample of 536 participants at baseline, 164 (31%) youth reported increasing their drug use due to their housing situation and 71 (13%) reported decreasing their drug use. In multivariate analysis, factors that were positively associated with perceived increases in drug use attributed to housing status included the following: being homeless, engaging in sex work and drug dealing. Regular employment was negatively associated with increasing drug use due to housing status. Among those who reported decreasing their drug use, only homelessness was significant in bivariate analysis. Perceived changes in drug use due to housing status were relatively common in this setting and were associated with being homeless and, among those who increased their drug use, engaging in risky income generation activities. These findings suggest that structural factors, particularly housing and economic opportunities, may be crucial interventions for reducing or limiting drug use among street-involved youth.

  4. Quantitative analysis of abused drugs in physiological fluids by gas chromatography/chemical ionization mass spectrometry

    International Nuclear Information System (INIS)

    Foltz, R.L.

    1978-01-01

    Methods have been developed for quantitative analysis of commonly abused drugs in physiological fluids using gas chromatography/chemical ionization mass spectrometry. The methods are being evaluated in volunteer analytical and toxicological laboratories, and analytical manuals describing the methods are being prepared. The specific drug and metabolites included in this program are: Δ 9 -tetrahydrocannabinol, methadone, phencyclidine, methaqualone, morphine, amphetamine, methamphetamine, mescaline, 2,5-dimethoxy-4-methyl amphetamine, cocaine, benzoylecgonine, diazepam, and N-desmethyldiazepam. The current analytical methods utilize relatively conventional instrumentation and procedures, and are capable of measuring drug concentrations as low as 1 ng/ml. Various newer techniques such as sample clean-up by high performance liquid chromatography, separation by glass capillary chromatography, and ionization by negative ion chemical ionization are being investigated with respect to their potential for achieving higher sensitivity and specificity, as well as their ability to facilitate simultaneous analysis of more than one drug and metabolite. (Auth.)

  5. Drug-abusing fathers: patterns of pair bonding, reproduction, and paternal involvement.

    Science.gov (United States)

    McMahon, Thomas J; Winkel, Justin D; Suchman, Nancy E; Rounsaville, Bruce J

    2007-10-01

    Despite concerns about compromise of fathering as a public policy issue, very little is known about the status of drug-abusing men as parents. In this pilot study, 50 men enrolled in methadone maintenance treatment completed a structured research interview designed to generate basic information about patterns of pair bonding, reproduction, and paternal involvement. Descriptive analysis of these data highlighted a number of trends in the nature of fathering that, although at odds with popular stereotypes, were similar to trends noted in research conducted with other populations of disenfranchised men. Consistent with a developmental-ecological perspective on parenting, the findings suggest that historical and situational influences interact within this population to compromise socially responsible efforts to function as a parent. The results also raise questions about the extent to which public policy initiatives designed to promote more responsible fathering are reaching this population, and they highlight ways that the drug abuse treatment system might better support men interested in being a more effective parent.

  6. Authoritative parenting and issue involvement as indicators of ad recall: an empirical investigation of anti-drug ads for parents.

    Science.gov (United States)

    Quick, Brian L; Stephenson, Michael T

    2007-01-01

    This investigation explores the role of authoritative parenting and issue involvement in regard to the recall of parental anti-drug ads encouraging child monitoring. In addition, the study tested whether issue involvement mediates the association between authoritative parenting and recall of parental anti-drug television ads among parents (N = 185) with adolescents in Grades 6, 7, and 8. The results indicate that (a) authoritative parenting is positively associated with favorable attitudes toward monitoring children and issue involvement regarding adolescent drug use, (b) issue involvement is associated with ad recall, (c) issue involvement mediates the relationship between authoritative parenting and ad recall, (d) ad recall is not associated with favorable attitudes toward parental monitoring, and (e) favorable attitudes regarding parental monitoring are positively associated with intentions to engage in monitoring within the next 6 months.

  7. Structural Characterization of Anticancer Drug Paclitaxel and Its Metabolites Using Ion Mobility Mass Spectrometry and Tandem Mass Spectrometry

    Science.gov (United States)

    Lee, Hong Hee; Hong, Areum; Cho, Yunju; Kim, Sunghwan; Kim, Won Jong; Kim, Hugh I.

    2016-02-01

    Paclitaxel (PTX) is a popular anticancer drug used in the treatment of various types of cancers. PTX is metabolized in the human liver by cytochrome P450 to two structural isomers, 3'- p-hydroxypaclitaxel (3 p-OHP) and 6α-hydroxypaclitaxel (6α-OHP). Analyzing PTX and its two metabolites, 3 p-OHP and 6α-OHP, is crucial for understanding general pharmacokinetics, drug activity, and drug resistance. In this study, electrospray ionization ion mobility mass spectrometry (ESI-IM-MS) and collision induced dissociation (CID) are utilized for the identification and characterization of PTX and its metabolites. Ion mobility distributions of 3 p-OHP and 6α-OHP indicate that hydroxylation of PTX at different sites yields distinct gas phase structures. Addition of monovalent alkali metal and silver metal cations enhances the distinct dissociation patterns of these structural isomers. The differences observed in the CID patterns of metalated PTX and its two metabolites are investigated further by evaluating their gas-phase structures. Density functional theory calculations suggest that the observed structural changes and dissociation pathways are the result of the interactions between the metal cation and the hydroxyl substituents in PTX metabolites.

  8. The Impact of Residential and Nonresidential Drug Treatment on Recidivism among Drug-Involved Probationers: A Survival Analysis

    Science.gov (United States)

    Krebs, Christopher P.; Strom, Kevin J.; Koetse, Willem H.; Lattimore, Pamela K.

    2009-01-01

    A variety of approaches for addressing drug use and drug-related crime among the nearly 5 million offenders on community supervision in the United States has been tried and evaluated, but questions remain about which policies or programs are most effective. The authors use a large data set to assess the impact of residential and nonresidential…

  9. Fatalities involving illicit drug use in Pretoria, South Africa, for the ...

    African Journals Online (AJOL)

    The most frequently detected drug was heroin, the presence of which was confirmed in 35.2% of cases, followed by cocaine in. 19.9%. Alcohol in combination with an illicit drug or drugs was detected in 56 cases (36.4%). Conclusions. Results from this study indicate that illicit drugs were implicated in a considerable number ...

  10. Fatalities involving illicit drug use in Pretoria, South Africa, for the ...

    African Journals Online (AJOL)

    The most frequently detected drug was heroin, the presence of which was confirmed in 35.2% of cases, followed by cocaine in 19.9%. Alcohol in combination with an illicit drug or drugs was detected in 56 cases (36.4%). Conclusions. Results from this study indicate that illicit drugs were implicated in a considerable number ...

  11. Liquid chromatography with tandem mass spectrometry for the simultaneous identification and quantification of cardiovascular drugs applied to the detection of substandard and falsified drugs.

    Science.gov (United States)

    Bernard, Mélisande; Akrout, Wiem; Van Buu, Christelle Tran; Metz, Carole; Antignac, Marie; Yagoubi, Najet; Do, Bernard

    2015-02-01

    The counterfeiting of pharmaceuticals has been detected since about 1990 and has alarmingly continued to pick up steam. We have been recently involved in an evaluation program of some of the most commonly prescribed cardiovascular drugs in Africa, for analysing an important number of tablets or capsules obtained from different places in seven African countries. A reversed-phase high-performance liquid chromatography with tandem mass spectrometry method was developed and validated to simultaneously control the identity and the quantity of acenocoumarol, amlodipine, atenolol, captopril, furosemide, hydrochlorothiazide and simvastatin in tablets. Their separation was performed on a Kinetex® C(18) (100 mm × 2.1 mm inside diameter, 2.6 μm) column using a gradient elution of 20 mM ammonium formate buffer and acetonitrile (90:10 10:90 v/v) at a flow rate of 0.5 mL/min. The analytes were detected using electrospray ionisation tandem mass spectrometry in both positive and negative modes with multiple reaction monitoring. Tandem mass spectrometry fragmentation patterns of captopril, furosemide and acenocoumarol, up to now not detailed in the literature, were also studied to assist in the selection of the most relevant transitions towards the objectives. The developed method was validated as per International Conference on Harmonisation guidelines with respect to specificity, linearity, trueness, precision, limits of detection and quantification. It has been successfully applied to the control of oral forms of seven cardiovascular drugs collected in African countries. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Rapid screening of pharmaceutical drugs using thermal desorption – SALDI mass spectrometry

    International Nuclear Information System (INIS)

    Grechnikov, A A; Kubasov, A E; Borodkov, A S; Georgieva, V B; Nikiforov, S M; Simanovsky, Ya O; Alimpiev, S S

    2012-01-01

    A novel approach to the rapid screening of pharmaceutical drugs by surface assisted laser desorption-ionization (SALDI) mass spectrometry with the rotating ball interface coupled with temperature programmed thermal desorption has been developed. Analytes were thermally desorbed and deposited onto the surface of amorphous silicon substrate attached to the rotating ball. The ball was rotated and the deposited analytes were analyzed using SALDI. The effectiveness of coupling SALDI mass spectrometry with thermal desorption was evaluated by the direct and rapid analysis of tablets containing lidocaine, diphenhydramine and propranolol without any sample pretreatment. The overall duration of the screening procedure was 30÷40 sec. Real urine samples were studied for drug analysis. It is shown that with simple preparation steps, urine samples can be quantitatively analyzed using the proposed technique with the detection limits in the range of 0.2÷0.5 ng/ml.

  13. Economic evaluations of mass drug administration: The importance of economies of scale and scope.

    Science.gov (United States)

    Turner, Hugo C; Toor, Jaspreet; Hollingsworth, T Déirdre; Anderson, Roy M

    2017-11-08

    It is recognised that changing the current approaches for the control of the neglected tropical diseases will be needed to reach the World Health Organization's (WHO) 2020 goals. Consequently, it is important that economic evaluations of the alternative approaches are conducted. A vital component of such evaluations is the issue of how the intervention's costs should be incorporated. We discuss this issue - focusing on mass drug administration. We argue that the common approach of assuming an intervention's cost per treatment is constant, regardless of the number of individuals treated, is a misleading way to consider the delivery costs of mass drug administration due to the occurrence of economies/diseconomies of scale and scope. Greater care and consideration are required when the costs are incorporated into such analyses. Without this, these economic evaluations could potentially lead to incorrect policy recommendations. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  14. An overview of hydrogen deuterium exchange mass spectrometry (HDX-MS) in drug discovery.

    Science.gov (United States)

    Masson, Glenn R; Jenkins, Meredith L; Burke, John E

    2017-10-01

    Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a powerful methodology to study protein dynamics, protein folding, protein-protein interactions, and protein small molecule interactions. The development of novel methodologies and technical advancements in mass spectrometers has greatly expanded the accessibility and acceptance of this technique within both academia and industry. Areas covered: This review examines the theoretical basis of how amide exchange occurs, how different mass spectrometer approaches can be used for HDX-MS experiments, as well as the use of HDX-MS in drug development, specifically focusing on how HDX-MS is used to characterize bio-therapeutics, and its use in examining protein-protein and protein small molecule interactions. Expert opinion: HDX-MS has been widely accepted within the pharmaceutical industry for the characterization of bio-therapeutics as well as in the mapping of antibody drug epitopes. However, there is room for this technique to be more widely used in the drug discovery process. This is particularly true in the use of HDX-MS as a complement to other high-resolution structural approaches, as well as in the development of small molecule therapeutics that can target both active-site and allosteric binding sites.

  15. Rapid drug detection in oral samples by porous silicon assisted laser desorption/ionization mass spectrometry.

    Science.gov (United States)

    Lowe, Rachel D; Guild, Georgia E; Harpas, Peter; Kirkbride, Paul; Hoffmann, Peter; Voelcker, Nicolas H; Kobus, Hilton

    2009-11-01

    The demand for analysis of oral fluid for illicit drugs has arisen with the increased adoption of roadside testing, particularly in countries where changes in legislation allow random roadside testing of drivers for the presence of a palette of illicit drugs such as methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA) and Delta9-tetrahydrocannabinol (THC). Oral samples are currently tested for such drugs at the roadside using an immunoassay-based commercial test kit. Positive roadside tests are sent for confirmatory laboratory analysis, traditionally by means of gas chromatography/mass spectrometry (GC/MS). We present here an alternative rapid analysis technique, porous silicon assisted laser desorption/ionization time-of-flight mass spectrometry (pSi LDI-MS), for the high-throughput analysis of oral fluids. This technique alleviates the need for sample derivatization, requires only sub-microliter sample volumes and allows fast analysis (of the order of seconds). In this study, the application of the technique is demonstrated with real samples from actual roadside testing. The analysis of oral samples resulted in detection of MA and MDMA with no extraction and analysis of THC after ethyl acetate extraction. We propose that, subject to miniaturization of a suitable mass spectrometer, this technique is well suited to underpin the deployment of oral fluid testing in the clinic, workplace and on the roadside. Copyright 2009 John Wiley & Sons, Ltd.

  16. An introduction to drug testing: the expanding role of mass spectrometry.

    Science.gov (United States)

    Hammett-Stabler, Catherine; Cotten, Steven W

    2012-01-01

    Measurement of drugs and their metabolites in biological fluids is the foundation of both therapeutic drug monitoring (TDM) and toxicology. Though different in their application, each discipline depends upon accurate identification and quantification if the measurements are to be useful. Thousands of methods are described for drug analysis but until recently most have relied upon analytical tools, such as spectrophotometry and immunoassay, that suffer from lack of specificity and sensitivity. The introduction of methods based on mass spectrometry (MS), coupled to gas or liquid chromatography, has revolutionized these areas. The methods are proving to be robust, versatile, and economical. This chapter introduces the reader to the application of MS to TDM and toxicology, the steps that should be considered during implementation, and the processes that should be implemented to assure continued quality.

  17. Microdosing studies using accelerated mass spectrometry as exploratory investigational new drug trials.

    Science.gov (United States)

    Bae, Soo Kyung; Shon, Ji-Hong

    2011-11-01

    Innovative attempts have been made to overcome nonproductivity and high expenditure in the clinical stages of new drug development. Microdosing studies using subpharmacological doses provide early insight into the body's disposition toward candidate compounds, and are innovative exploratory trials that can promote productivity in drug development. Highly sensitive analytical technology is crucial in microdosing studies that employ qualitative and quantitative assays of target materials in humans. Accelerator mass spectrometry (AMS) has facilitated the adoption of a human microdosing study in the early phase of clinical drug development. Results derived from AMS microdosing studies using labeled compounds can provide various types of information for candidate selection, including pharmacokinetic characteristics and metabolic profiles of candidate compounds. The applicability of microdosing studies is currently expanding into absolute bioavailability and mass balance studies. Although it remains uncertain whether microdosing adequately predicts the pharmacokinetics of therapeutic doses, further development of microdosing studies using AMS may benefit the field of new drug development and could pose a new challenge to researchers. The use of advanced technology in candidate selection will contribute to improved productivity and competitiveness in pharmaceutical research and development. The introduction of microdosing studies using AMS in Korea will present a newly applicable method for innovative clinical trials and contribute to development potential in global competition.

  18. A mass spectrometric method to determine activities of enzymes involved in polyamine catabolism

    International Nuclear Information System (INIS)

    Moriya, Shunsuke; Iwasaki, Kaori; Samejima, Keijiro; Takao, Koichi; Kohda, Kohfuku; Hiramatsu, Kyoko; Kawakita, Masao

    2012-01-01

    Highlights: ► Compounds in polyamine catabolic pathway were determined by a column-free ESI-TOF MS. ► N 1 - and N 8 -acetylspermidine were determined by a column-free ESI-MS/MS. ► The method was applied to determine activities of APAO, SMO, and SSAT in the pathway. ► The assay method contained stable isotope-labeled natural substrates. ► It is applicable to biological samples containing natural substrate and product. - Abstract: An analytical method for the determination of three polyamines (putrescine, spermidine, and spermine) and five acetylpolyamines [N 1 -acetylspermidine (N 1 AcSpd), N 8 -acetylspermidine (N 8 AcSpd), N 1 -acetylspermine, N 1 ,N 8 -diacetylspermidine, and N 1 ,N 12 -diacetylspermine] involved in the polyamine catabolic pathway has been developed using a hybrid tandem mass spectrometer. Heptafluorobutyryl (HFB) derivatives of these compounds and respective internal standards labeled with stable isotopes were analyzed simultaneously by TOF MS, based on peak areas appearing at appropriate m/z values. The isomers, N 1 AcSpd and N 8 AcSpd were determined from their fragment ions, the acetylamidopropyl and acetylamidobutyl groups, respectively, using MS/MS with 13 C 2 -N 1 AcSpd and 13 C 2 -N 8 AcSpd which have the 13 C 2 -acetyl group as an internal standard. The TOF MS method was successfully applied to measure the activity of enzymes involved in polyamine catabolic pathways, namely N 1 -acetylpolyamine oxidase (APAO), spermine oxidase (SMO), and spermidine/spermine N 1 -acetyltransferase (SSAT). The following natural substrates and products labeled with stable isotopes considering the application to biological samples were identified; for APAO, [4,9,12- 15 N 3 ]-N 1 -acetylspermine and [1,4,8- 15 N 3 ]spermidine ( 15 N 3 -Spd), respectively; for SMO, [1,4,8,12- 15 N 4 ]spermine and 15 N 3 -Spd, respectively; and for SSAT, 15 N 3 -Spd and [1,4,8- 15 N 3 ]-N 1 -acetylspermidine, respectively.

  19. A mass spectrometric method to determine activities of enzymes involved in polyamine catabolism

    Energy Technology Data Exchange (ETDEWEB)

    Moriya, Shunsuke; Iwasaki, Kaori [Department of Molecular Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kami-kitazawa, Setagaya-ku, Tokyo 156-8506 (Japan); Samejima, Keijiro, E-mail: samejima-kj@igakuken.or.jp [Department of Molecular Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kami-kitazawa, Setagaya-ku, Tokyo 156-8506 (Japan); Takao, Koichi [Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295 (Japan); Kohda, Kohfuku [Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo, Tokyo 202-8585 (Japan); Hiramatsu, Kyoko; Kawakita, Masao [Department of Molecular Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kami-kitazawa, Setagaya-ku, Tokyo 156-8506 (Japan)

    2012-10-20

    Highlights: Black-Right-Pointing-Pointer Compounds in polyamine catabolic pathway were determined by a column-free ESI-TOF MS. Black-Right-Pointing-Pointer N{sup 1}- and N{sup 8}-acetylspermidine were determined by a column-free ESI-MS/MS. Black-Right-Pointing-Pointer The method was applied to determine activities of APAO, SMO, and SSAT in the pathway. Black-Right-Pointing-Pointer The assay method contained stable isotope-labeled natural substrates. Black-Right-Pointing-Pointer It is applicable to biological samples containing natural substrate and product. - Abstract: An analytical method for the determination of three polyamines (putrescine, spermidine, and spermine) and five acetylpolyamines [N{sup 1}-acetylspermidine (N{sup 1}AcSpd), N{sup 8}-acetylspermidine (N{sup 8}AcSpd), N{sup 1}-acetylspermine, N{sup 1},N{sup 8}-diacetylspermidine, and N{sup 1},N{sup 12}-diacetylspermine] involved in the polyamine catabolic pathway has been developed using a hybrid tandem mass spectrometer. Heptafluorobutyryl (HFB) derivatives of these compounds and respective internal standards labeled with stable isotopes were analyzed simultaneously by TOF MS, based on peak areas appearing at appropriate m/z values. The isomers, N{sup 1}AcSpd and N{sup 8}AcSpd were determined from their fragment ions, the acetylamidopropyl and acetylamidobutyl groups, respectively, using MS/MS with {sup 13}C{sub 2}-N{sup 1}AcSpd and {sup 13}C{sub 2}-N{sup 8}AcSpd which have the {sup 13}C{sub 2}-acetyl group as an internal standard. The TOF MS method was successfully applied to measure the activity of enzymes involved in polyamine catabolic pathways, namely N{sup 1}-acetylpolyamine oxidase (APAO), spermine oxidase (SMO), and spermidine/spermine N{sup 1}-acetyltransferase (SSAT). The following natural substrates and products labeled with stable isotopes considering the application to biological samples were identified; for APAO, [4,9,12-{sup 15}N{sub 3}]-N{sup 1}-acetylspermine and [1,4,8-{sup 15}N{sub 3

  20. Mass media and the prevention of drug problems: a psychological appraisal.

    Science.gov (United States)

    O'connor, J

    1990-01-01

    It is often assumed that the mass media are capable of exerting great influence over large sections of their audience. In fact, to achieve anything like mass persuasion, certain conditions need to be met. The mass media can be a powerful influence if directed at emergent trends or attitudes, or in reinforcing behaviour that is being shaped by other forces. Messages to stop, curtail, or engage in new behaviours which run counter to prevailing norms will be ineffective without instruction and access to the means for change within an integrated system approach. It is crucial that the target population is segmented to receive tailored messages to which each group will be optimally receptive. The 'stage of change' a drug user is in is likely to be of particular importance.

  1. Beyond recidivism: changes in health and social service involvement following exposure to drug treatment court.

    Science.gov (United States)

    Rezansoff, Stefanie N; Moniruzzaman, Akm; Clark, Elenore; Somers, Julian M

    2015-10-31

    The majority of Drug Treatment Court (DTC) research has examined the impact of DTCs on criminal recidivism. Comparatively little research has addressed the association between DTC participation and engagement with community-based health and social services. The present study investigated changes in participant involvement with outpatient healthcare and income assistance within a DTC cohort. We hypothesized that involvement with community-based (outpatient) health and social services would increase post-DTC participation, and that service levels would be higher among program graduates and offenders with histories of co-occurring mental and substance use disorders. Participants were 631 offenders at the DTC in Vancouver, Canada (DTCV). Administrative data representing hospital, outpatient medical care, and income assistance were examined one-year pre/post program to assess differences over time. Generalized estimating equations were used to investigate the association between changes in service use and program involvement. We also examined the relationship between level of service use and offender characteristics. Members of the cohort were disproportionately Aboriginal (33 %), had been sentenced 2.7 times in the 2 years preceding their index offence, and 50 % had been diagnosed with a non substance-related mental disorder in the five years preceding the index offence. The mean number of outpatient services post DTCV was 51, and the mean amount of social assistance paid was $5,897. Outpatient service use increased following exposure to DTCV (Adjusted Rate Ratio (ARR) = 1.45) and was significantly higher among women (ARR = 1.47), program graduation (ARR = 1.23), and those previously diagnosed with concurrent substance use and mental disorders (ARR = 4.92). Overall, hospital admissions did not increase post-program, although rates were significantly higher among women (ARR = 1.76) and those with concurrent disorders (ARR = 2.71). Income

  2. Presence of illegal drugs in drivers involved in fatal road traffic accidents in Spain

    OpenAIRE

    Del Río, M Carmen; Álvarez, Francisco Javier

    2000-01-01

    Producción Científica This study investigated the presence of illegal drugs in the blood of 285 fatally injured drivers in Spain. Illegal drugs were detected in 10.2% of all samples. Illicit drugs alone were detected in 2.5% and together with other substances in 7.7%. Cocaine was the most common drug detected. The mean number (9S.D.) of substances detected was 2.691.2: consisting of 46 illegal drugs, 14 alcohol cases and 16 medicines. Three concentration levels of the different su...

  3. The role of personal opinions and experiences in compliance with mass drug administration for lymphatic filariasis elimination in Kenya.

    Directory of Open Access Journals (Sweden)

    Doris W Njomo

    Full Text Available The main strategy adopted for Lymphatic Filariasis (LF elimination globally is annual mass drug administration (MDA for 4 to 6 rounds. At least 65% of the population at risk should be treated in each round for LF elimination to occur. In Kenya, MDA using diethylcarbamazine citrate (DEC and albendazole data shows declining compliance (proportion of eligible populations who receive and swallow the drugs levels (85%-62.8%. The present study's aim was to determine the role of personal opinions and experiences in compliance with MDA.This was a retrospective cross-sectional study conducted between January and September 2009 in two districts based on December 2008 MDA round. In each district, one location with high and one with low compliance was selected. Through systematic sampling, nine villages were selected and interviewer-based questionnaires administered to 965 household heads or adult representatives also systematically sampled. The qualitative data were generated from opinion leaders, LF patients with clinical signs and community drug distributors (CDDs all purposively selected and interviewed. Sixteen focus group discussions (FGDs were also conducted with single-sex adult and youth male and female groups. Chi square test was used to assess the statistical significance of differences in compliance with treatment based on the records reviewed. The house-to-house method of drug distribution influenced compliance. Over one-quarter (27% in low compared to 15% in high compliance villages disliked this method. Problems related to size, number and taste of the drugs were more common in low (16.4% than in high (14.4% compliance villages. Reasons for failure to take the drugs were associated with compliance (p0.05.Community sensitization on treatment, drugs used, their regimen and distribution method involving all leaders should be strengthened by the Programme Implementers. The communities need to be made aware of the potential side effects of the

  4. Drug Sales, Gender, and Risk: Notions of Risk From the Perspective of Gang-Involved Young Adults.

    Science.gov (United States)

    Moloney, Molly; Hunt, Geoffrey; Joe-Laidler, Karen

    2015-05-01

    We examine gender and meanings of risk in interviews (2007-2010) with gang-involved young men and women (n = 253) engaged in illicit drug sales in San Francisco, California. The in-depth interviews from this NIDA-funded study were coded using the software NVivo to identify patterns and themes. We examine their interpretations of the risks of drug-selling and their narratives about gender differences in these risks. We find distinct discourses regarding the role of femininities and masculinities and male and female bodies in shaping risk as well as the nexus between gender, family, and risk for female drug sellers.

  5. Targeted Multiresidue Analysis of Veterinary Drugs in Milk-Based Powders Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

    Science.gov (United States)

    Wittenberg, James B; Simon, Kelli A; Wong, Jon W

    2017-08-30

    An analytical method was developed and validated for the determination of 40 veterinary drugs in various milk-based powders. The method involves acetonitrile/water extraction, solid-phase filtration for lipid removal in fat-containing matrices, and analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The limits of quantitation (LOQ) ranged from 0.02 to 82 ng/g. Acceptable recoveries (70-120%, RSD powder. Similar results were obtained for whole milk powder, milk protein concentrate, whey protein concentrate, and whey protein isolate. This new method will allow for better monitoring of a wide range of veterinary drugs in milk-based powders.

  6. Are Outness and Community Involvement Risk or Protective Factors for Alcohol and Drug Abuse Among Sexual Minority Women?

    Science.gov (United States)

    Feinstein, Brian A; Dyar, Christina; London, Bonita

    2017-07-01

    Sexual minority women (SMW) are at increased risk for substance abuse compared to heterosexual women. Two psychosocial factors that have been implicated in SMW's substance abuse are outness and LGBT community involvement, but findings have been mixed as to whether these are risk or protective factors. One possible explanation is that they may have different consequences for subgroups of SMW (lesbians, bisexual women, and queer women). While being open about one's sexual orientation and involved in the community may be protective for lesbians, discrimination against bisexual women may lead these same factors to contribute to substance abuse for bisexual women. It is unclear how these associations will operate for queer women, given limited research on this subpopulation. The current study examined whether sexual identity moderated the associations between outness and community involvement with alcohol and drug abuse. We also examined whether perceived discrimination would help explain why these associations may be different for subgroups of SMW. A sample of 288 self-identified SMW (113 lesbians, 106 bisexual women, and 69 queer women) completed an online survey. Higher outness was associated with higher alcohol and drug abuse for bisexual women, but not for lesbians or queer women. Similarly, higher community involvement was associated with higher drug abuse for bisexual women, but not for lesbians or queer women. Among bisexual women, the association between community involvement and drug abuse was mediated by perceived discrimination. Further, the association between outness and drug abuse was mediated by both community involvement and perceived discrimination. Findings demonstrate that outness and community involvement function as risk factors for substance abuse for bisexual women, in part due to their associations with discrimination.

  7. Protection motivation theory and adolescent drug trafficking: relationship between health motivation and longitudinal risk involvement.

    Science.gov (United States)

    Wu, Ying; Stanton, Bonita F; Li, Xiaoming; Galbraith, Jennifer; Cole, Matthew L

    2005-03-01

    To assess health protection motivation as explained by the constructs of protection motivation theory (PMT) and its association with drug trafficking over 2 years. The sample included 817 African American youth (13-16 years old) participating in an adolescent risk-reduction program. We developed an instrument measuring the level of health protection motivation (LHPM) using factor analysis. Changes in LHPM over time were examined among drug traffickers, abstainers, initiators, and nonrisk youths. In sum, 151 participants reported selling and/or delivering drugs during the study period. The significant inverse correlation between drug-trafficking intention and health protection motivation was consistent with PMT. Changes in LHPM were strongly associated with the dynamics of behavior over 2 years. Adolescent drug trafficking can be predicted by an overall level of health protection motivation. PMT and related theories should be considered in the design of drug-trafficking prevention intervention.

  8. Mass administration of the antimalarial drug mefloquine to Guantánamo detainees: a critical analysis.

    Science.gov (United States)

    Nevin, Remington L

    2012-10-01

    Recently, evidence has emerged from an unusual form of mass drug administration practised among detainees held at US Naval Station Guantánamo Bay, Cuba ('Guantánamo'), ostensibly as a public health measure. Mefloquine, an antimalarial drug originally developed by the US military, whose use is associated with a range of severe neuropsychiatric adverse effects, was administered at treatment doses to detainees immediately upon their arrival at Guantánamo, prior to laboratory testing for malaria and irrespective of symptoms of disease. In this analysis, the history of mefloquine's development is reviewed and the indications for its administration at treatment doses are discussed. The stated rationale for the use of mefloquine among Guantánamo detainees is then evaluated in the context of accepted forms of population-based malaria control. It is concluded that there was no plausible public health indication for the use of mefloquine at Guantánamo and that based on prevailing standards of care, the clinical indications for its use are decidedly unclear. This analysis suggests the troubling possibility that the use of mefloquine at Guantánamo may have been motivated in part by knowledge of the drug's adverse effects, and points to a critical need for further investigation to resolve unanswered questions regarding the drug's potentially inappropriate use. Published 2012. This article is a US Government work and is in the public domain in the USA.

  9. 78 FR 17744 - Social Security Ruling, SSR 13-2p; Titles II and XVI: Evaluating Cases Involving Drug Addiction...

    Science.gov (United States)

    2013-03-22

    ...; Titles II and XVI: Evaluating Cases Involving Drug Addiction and Alcoholism (DAA); Correction AGENCY... c. i., third sentence, hyphenate ``nonmedical'' to read ``non-medical''. On page 11944, third column...., first sentence, hyphenate ``nonmedical'' to read ``non-medical''. On page 11944, footnote 22, replace...

  10. Understanding the Black Box of Gang Organization: Implications for Involvement in Violent Crime, Drug Sales, and Violent Victimization

    Science.gov (United States)

    Decker, Scott H.; Katz, Charles M.; Webb, Vincent J.

    2008-01-01

    This article examines the influence of gang organization on several behavioral measures. Using interview data from juvenile detention facilities in three Arizona sites, this article examines the relationship between gang organizational structure and involvement in violent crime, drug sales, victimization, and arrest. The gang literature suggests…

  11. Atmospheric pressure ionization-tandem mass spectrometry of the phenicol drug family.

    Science.gov (United States)

    Alechaga, Élida; Moyano, Encarnación; Galceran, M Teresa

    2013-11-01

    In this work, the mass spectrometry behaviour of the veterinary drug family of phenicols, including chloramphenicol (CAP) and its related compounds thiamphenicol (TAP), florfenicol (FF) and FF amine (FFA), was studied. Several atmospheric pressure ionization sources, electrospray (ESI), atmospheric pressure chemical ionization and atmospheric pressure photoionization were compared. In all atmospheric pressure ionization sources, CAP, TAP and FF were ionized in both positive and negative modes; while for the metabolite FFA, only positive ionization was possible. In general, in positive mode, [M + H](+) dominated the mass spectrum for FFA, while the other compounds, CAP, TAP and FF, with lower proton affinity showed intense adducts with species present in the mobile phase. In negative mode, ESI and atmospheric pressure photoionization showed the deprotonated molecule [M-H](-), while atmospheric pressure chemical ionization provided the radical molecular ion by electron capture. All these ions were characterized by tandem mass spectrometry using the combined information obtained by multistage mass spectrometry and high-resolution mass spectrometry in a quadrupole-Orbitrap instrument. In general, the fragmentation occurred via cyclization and losses or fragmentation of the N-(alkyl)acetamide group, and common fragmentation pathways were established for this family of compounds. A new chemical structure for the product ion at m/z 257 for CAP, on the basis of the MS(3) and MS(4) spectra is proposed. Thermally assisted ESI and selected reaction monitoring are proposed for the determination of these compounds by ultra high-performance liquid chromatography coupled to tandem mass spectrometry, achieving instrumental detection limits down to 0.1 pg. Copyright © 2013 John Wiley & Sons, Ltd.

  12. Multiple and substitute addictions involving prescription drugs misuse among 12th graders: gateway theory revisited with Market Basket Analysis.

    Science.gov (United States)

    Jayawardene, Wasantha Parakrama; YoussefAgha, Ahmed Hassan

    2014-01-01

    This study aimed to identify the sequential patterns of drug use initiation, which included prescription drugs misuse (PDM), among 12th-grade students in Indiana. The study also tested the suitability of the data mining method Market Basket Analysis (MBA) to detect common drug use initiation sequences in large-scale surveys. Data from 2007 to 2009 Annual Surveys of Alcohol, Tobacco, and Other Drug Use by Indiana Children and Adolescents were used for this study. A close-ended, self-administered questionnaire was used to ask adolescents about the use of 21 substance categories and the age of first use. "Support%" and "confidence%" statistics of Market Basket Analysis detected multiple and substitute addictions, respectively. The lifetime prevalence of using any addictive substance was 73.3%, and it has been decreasing during past few years. Although the lifetime prevalence of PDM was 19.2%, it has been increasing. Males and whites were more likely to use drugs and engage in multiple addictions. Market Basket Analysis identified common drug use initiation sequences that involved 11 drugs. High levels of support existed for associations among alcohol, cigarettes, and marijuana, whereas associations that included prescription drugs had medium levels of support. Market Basket Analysis is useful for the detection of common substance use initiation sequences in large-scale surveys. Before initiation of prescription drugs, physicians should consider the adolescents' risk of addiction. Prevention programs should address multiple addictions, substitute addictions, common sequences in drug use initiation, sex and racial differences in PDM, and normative beliefs of parents and adolescents in relation to PDM.

  13. [Drug abuse in adolescent offenders: analysis of the psychosocial variables involved].

    Science.gov (United States)

    Contreras Martínez, Lourdes; Molina Banqueri, Virginia; Cano Lozano, Ma Carmen

    2012-01-01

    Research shows that drugs and delinquency are frequently linked, the abuse of various types of substance being a widespread practice among young offenders. At the same time, some psychosocial characteristics are associated with both drug abuse and criminal/antisocial behavior. To help us explore the relationship between young offenders' drug abuse and certain psychosocial variables, we examined closed judicial files on young offenders from the Juvenile Justice Service in Jaen (Spain) corresponding to the period 2001 to 2010. From the contents of these judicial files we analyzed demographic variables such as gender and age, as well as psychosocial variables such as drug abuse, peer group, violent behavior, self-control, tolerance to frustration and attributional style. The results show that most of the young offenders use some type of drug, as well as revealing differential patterns of use according to gender. Also observed is a link between drug abuse and deviant peer group, violent behavior and the above-mentioned psychological variables. Finally, we found some differences in these psychological variables depending on the type of drug used.

  14. Liquid chromatography coupled with tandem mass spectrometry for the quantitative analysis of anticancer drugs in biological matrices

    NARCIS (Netherlands)

    Stokvis, Ellen

    2004-01-01

    In this thesis, the development and validation of liquid chromatography tandem mass spectrometric (LC-MS/MS) methods for the quantitative bioanalysis of anticancer drugs are described. The monitoring of these drugs in biological fluids and tissues is important during both pre-clinical and clinical

  15. Rurality and criminal history as predictors of HIV risk among drug-involved offenders.

    Science.gov (United States)

    Webster, J Matthew; Mateyoke-Scrivner, Allison; Staton, Michele; Leukefeld, Carl

    2007-01-01

    The current study examined rurality and criminality as predictors of the lifetime HIV risk behaviors of 661 male, drug-abusing state prisoners. HIV risk behaviors included the number of lifetime sex partners, the number of lifetime drug injections, the number of times had sex with an injection drug user, and the frequency with which a condom was used. Regression analyses showed that criminality was related to the number of lifetime injections, whereas rurality was related to fewer lifetime sex partners and less frequent condom use. A rurality by criminality interaction for sex with an injection drug user was found. Specifically, those from rural areas who had more extensive criminal histories reported relatively high numbers of sex partners who were IDUs. Results are discussed in the context of rural and criminal justice interventions for HIV risk behavior.

  16. Mechanism(s) involved in opioid drug abuse modulation of HAND.

    Science.gov (United States)

    Dutta, Raini; Roy, Sabita

    2012-07-01

    Drug abuse and HIV infection are interlinked. From the onset of the HIV/AIDS epidemic, the impact of illicit drug use on HIV disease progression has been a focus of many investigations. Both laboratory-based and epidemiological studies strongly indicate that drug abuse may exacerbate HIV disease progression and increase mortality and morbidity in these patients. Increase susceptibility to opportunistic infection has been implicated as one of the major causes for this detriment. Furthermore, opioids are known to elicit prevalence of neurodegenerative disorders in HIV-infected patients. Numerous authors have delineated various molecular as well as cellular mechanisms associated with neurological complications in these patients. This review gives an overview of these findings. Understanding the mechanisms will allow for the development of targeted therapies aimed at reducing the progression of neurocognitive decline in the drug abusing HIV infected individuals.

  17. Investigation of diazepam drug using thermal analyses, mass spectrometry and semi-empirical MO calculation

    Science.gov (United States)

    Zayed, M. A.; Fahmey, M. A.; Hawash, M. F.

    2005-03-01

    In the present work diazepam (Dz) drug was investigated using thermal analyses (TA) measurements (TG/DTG) in comparison with EI mass spectral (MS) fragmentation at 70 and 20 eV. Semi-empirical MO calculations, MNDO procedure, have been carried out on diazepam both as neutral molecule and the corresponding positively charged molecular ion. These include molecular geometry, bond order, charge distribution, heats of formation and ionization energy. Thermogravimetric and kinetic analysis, reveal a high response of the drug to the temperature variation with very fast rate. It is completely decomposed in the temperature range between 204 and 340 °C with average kinetic energy (KE) at 164.69 kJ mol -1. On the other hand, diazepam can easily fragmented at low energy after ionization by electron energy at 9.56 eV. The losses of CO gas molecules followed by chlorine gas from the entity of diazepam (both neutral and charged molecular ion) as the best selected pathway were observed in both mass spectra (MS) and thermal analyses (TA). MNDO calculation was applied to declare both TA and MS observations.

  18. Fast analysis of caffeine in beverages and drugs by paper spray tandem mass spectrometry.

    Science.gov (United States)

    Taverna, Domenico; Di Donna, Leonardo; Bartella, Lucia; Napoli, Anna; Sindona, Giovanni; Mazzotti, Fabio

    2016-05-01

    A simple and fast method based on paper spray mass spectrometry for the determination of caffeine in commercial beverages and drugs has been developed; the analyses were carried out in MRM mode, monitoring the transitions m/z 195 → m/z 138 for caffeine and m/z 198 → m/z 140 for the labeled internal standard. To verify the reliability of the proposed approach, a spiked sample (soda drink and paracetamol tablet) with a known amount of caffeine has been prepared and analyzed by PS-MS, providing accuracy values about 100 %; the LOQ and LOD values were calculated at 1.2 and 1.6 μg/mL, respectively. Both beverages and drugs were also analyzed with the classic analytical method based on LC-UV measurements, showing consistent results between the two approaches, thus confirming the reliability of the developed ambient MS determination. Graphical Abstract The assay of caffeine by paper mass spectrometry.

  19. Tracking problems and possible solutions in the quantitative determination of small molecule drugs and metabolites in biological fluids using liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Bakhtiar, Ray; Majumdar, Tapan K

    2007-01-01

    During the last decade, quantification of low molecular weight molecules using liquid chromatography-tandem mass spectrometry in biological fluids has become a common procedure in many preclinical and clinical laboratories. This overview highlights a number of issues involving "small molecule drugs", bioanalytical liquid chromatography-tandem mass spectrometry, which are frequently encountered during assay development. In addition, possible solutions to these issues are proposed with examples in some of the case studies. Topics such as chromatographic peak shape, carry-over, cross-talk, standard curve non-linearity, internal standard selection, matrix effect, and metabolite interference are presented. Since plasma is one of the most widely adopted biological fluid in drug discovery and development, the focus of this discussion will be limited to plasma analysis. This article is not intended to be a comprehensive overview and readers are encouraged to refer to the citations herein.

  20. Costs of Integrated Mass Drug Administration for Neglected Tropical Diseases in Haiti

    Science.gov (United States)

    Goldman, Ann S.; Brady, Molly A.; Direny, Abdel; Desir, Luccene; Oscard, Roland; Vely, Jean-Francois; Linehan, Mary; Baker, Margaret

    2011-01-01

    We conducted a cost analysis of Haiti's Ministry of Public Health and Population neglected tropical disease program, Projet des Maladies Tropicales Negligées and collected data for 9 of 55 communes participating in the May 2008–April 2009 mass drug administration (MDA). The Projet des Maladies Tropicales Negligées Program partnered with IMA World Health and Hôpital Ste. Croix to implement MDA for treatment of lymphatic filariasis and soil-transmitted helminthiasis by using once a year treatment with albendazole and diethylcarbamazine in a population of approximately 8 million persons. Methods included analyzing partner financial records and conducting retrospective surveys of personnel. In the nine communes, 633,261 persons were treated at a cost of U.S. $0.64 per person, which included the cost of donated drugs, and at a cost of U.S. $0.42 per person treated, when excluding donated drug costs. The MDA for lymphatic filariasis in Haiti began in 2000, with the treatment of 105,750 persons at a cost per person of U.S. $2.23. The decrease in cost per person treated is the result of cumulative implementation experience and economies of scale. PMID:22049035

  1. Current status of hyphenated mass spectrometry in studies of the metabolism of drugs of abuse, including doping agents.

    Science.gov (United States)

    Meyer, Markus R; Maurer, Hans H

    2012-01-01

    This paper reviews scientific contributions on the identification and/or quantification of metabolites of drugs of abuse in in vitro assays or various body samples using hyphenated mass spectrometry. Gas chromatography-mass spectrometry (GC-MS) as well as liquid chromatography-mass spectrometry (LC-MS) approaches are considered and discussed if they have been reported in the last five years and are relevant to clinical and forensic toxicology or doping control. Workup and artifact formation are discussed, and typical examples of studies of the metabolism of designer drugs, doping agents, herbal drugs, and synthetic cannabinoids are provided. Procedures for quantifying metabolites in body samples for pharmacokinetic studies or in enzyme incubations for enzyme kinetic studies are also reviewed. In conclusion, the reviewed papers showed that both GC-MS and LC-MS still have important roles to play in research into the metabolism of drugs of abuse, including doping agents.

  2. CONDITIONS THAT INCREASE DRUG MARKET INVOLVEMENT: THE INVITATIONAL EDGE AND THE CASE OF MEXICANS IN SOUTH TEXAS.

    Science.gov (United States)

    Valdez, Avelardo; Kaplan, Charles

    2007-01-01

    Research on drug trafficking has not been able to discern the exact nature of illegal drug markets and the relationship between their individual and group participants. This article delineates the role of Mexican immigrants and Mexican-American participants involved in the stratified drug market of South Texas. This article synthesizes ethnographic materials drawn from two previous National Institute on Drug Abuse (NIDA) studies in order identify the different types of drug distribution behaviors that occur within the groups, the differentiated roles of individuals, the organizational framework, and most significantly, the processes that link market participants to others outside of the drug market. This illegal behavior can be interpreted as an adaptive mechanism that is a direct response to the marginal economic status imposed by macro socio-economical background factors. As well, we conclude that the specific foreground factors of the opportunities offered by the context, culture, and proximity of the U.S./Mexico border and invitational edges explain this behavior. There are both parallels and particular differences between the South Texas case and the structuring and functioning of informal legal and illegal markets that are characteristic of other economically disadvantaged communities.

  3. Inductively coupled plasma mass spectrometry in the analysis of biological samples and pharmaceutical drugs

    Science.gov (United States)

    Ossipov, K.; Seregina, I. F.; Bolshov, M. A.

    2016-04-01

    Inductively coupled plasma mass spectrometry (ICP-MS) is widely used in the analysis of biological samples (whole blood, serum, blood plasma, urine, tissues, etc.) and pharmaceutical drugs. The shortcomings of this method related to spectral and non-spectral interferences are manifested in full measure in determination of the target analytes in these complex samples strongly differing in composition. The spectral interferences are caused by similarity of masses of the target component and sample matrix components. Non-spectral interferences are related to the influence of sample matrix components on the physicochemical processes taking place during formation and transportation of liquid sample aerosols into the plasma, on the value and spatial distribution of plasma temperature and on the transmission of the ion beam from the interface to mass spectrometer detector. The review is devoted to analysis of different mechanisms of appearance of non-spectral interferences and to ways for their minimization or elimination. Special attention is paid to the techniques of biological sample preparation, which largely determine the mechanisms of the influence of sample composition on the results of element determination. The ways of lowering non-spectral interferences by instrumental parameter tuning and application of internal standards are considered. The bibliography includes 189 references.

  4. General equations for determining species involved in solution equilibria and equilibrium constants from solution molecular mass measurements

    OpenAIRE

    Davidson, Matthew G.; Snaith, Ronald; Stalke, Dietmar; Wright, Dominic S.

    1993-01-01

    A simple way by which equilibrium species can be identified with reasonable certainty, and equilibrium constants and thermodynamic data can be thereby extracted, from variable-concentration cryoscopic molecular mass measurements in solution is reported. The method relies on the assumption that the individual molecular species involved in such solution equilibria exert independent and additive contributions to the depression in freezing point from that of the pure solvent. Given this assumptio...

  5. Adverse event management in mass drug administration for neglected tropical diseases.

    Science.gov (United States)

    Caplan, Arthur; Zink, Amanda

    2014-03-01

    The ethical challenges of reporting and managing adverse events (AEs) and serious AEs (SAEs) in the context of mass drug administration (MDA) for the treatment of neglected tropical diseases (NTDs) require reassessment of domestic and international policies on a global scale. Although the World Health Organization has set forth AE/SAE guidelines specifically for NTD MDA that incorporate suspected causality, and recommends that only SAEs get reported in this setting, most regulatory agencies continue to require the reporting of all SAEs exhibiting even a merely temporal relationship to activities associated with an MDA program. This greatly increases the potential for excess "noise" and undue risk aversion and is not only impractical but arguably unethical where huge proportions of populations are being treated for devastating diseases, and no good baseline exists against which to compare possible AE/SAE reports. Other population-specific variables that might change the way drug safety ought to be assessed include differing efficacy rates of a drug, background morbidity/mortality rates of the target disease in question, the growth rate of the incidence of disease, the availability of rescue or salvage therapies, and the willingness of local populations to take risks that other populations might not. The fact that NTDs are controllable and potentially eradicable with well-tolerated, effective, existing drugs might further alter our assessment of MDA safety and AE/SAE tolerability. At the same time, diffuseness of population, communication barriers, lack of resources, and other difficult surveillance challenges may present in NTD-affected settings. These limitations could impair the ability to monitor an MDA program's success, as well as hinder efforts to obtain informed consent or provide rescue therapy. Denying beneficial research interventions and MDA programs intended to benefit millions requires sound ethical justification based on more than the identification of

  6. [Involvement of microRNA in the induction of drug-metabolizing enzymes].

    Science.gov (United States)

    Shizu, Ryota; Numazawa, Satoshi; Yoshida, Takemi

    2012-01-01

    MicroRNAs (miRNAs) are small noncoding RNAs of about 20 nucleotides in length and participate in the post-transcriptional regulation of gene expression. Accumulating evidence indicates that miRNA binds to 3'-UTR of its target mRNAs and thereby destabilizes the transcripts or suppresses the translation. It is expected that miRNAs could have diverse functions and therefore play a role in the gene expression caused by the drug treatment, which have yet to be determined. Demonstration of the participation of specific miRNA in the drug-mediated gene expression would make it a biomarker for the toxicological assessment and help an understanding of molecular machinery of the drug-drug interaction. Under these backgrounds, we investigated the change of miRNAs in the liver of mice treated with phenobarbital, a typical inducer for drug-metabolizing enzymes, and demonstrate the participation of miRNAs in the phenobarbital-regulated gene expression. We investigated the relationship between phenobarbital-mediated changes in miRNA and mRNA by using Agilent miRNA microarray and DNA microarray, followed by real time RT-PCR. From these experiments, it was suggested that the phenobarbital-induced changes in cyp2c29 and mrp3 are regulated by miR-30a and miR-29b, respectively. In addition, we obtained evidence that indicates a phenobarbital-mediated decrease in miR-122, a highly abundant liver-specific miRNA, leads to the activation of the transcription factor CAR and thereby induces drug-metabolizing enzymes.

  7. Current use of high-resolution mass spectrometry in drug screening relevant to clinical and forensic toxicology and doping control.

    Science.gov (United States)

    Ojanperä, Ilkka; Kolmonen, Marjo; Pelander, Anna

    2012-05-01

    Clinical and forensic toxicology and doping control deal with hundreds or thousands of drugs that may cause poisoning or are abused, are illicit, or are prohibited in sports. Rapid and reliable screening for all these compounds of different chemical and pharmaceutical nature, preferably in a single analytical method, is a substantial effort for analytical toxicologists. Combined chromatography-mass spectrometry techniques with standardised reference libraries have been most commonly used for the purpose. In the last ten years, the focus has shifted from gas chromatography-mass spectrometry to liquid chromatography-mass spectrometry, because of progress in instrument technology and partly because of the polarity and low volatility of many new relevant substances. High-resolution mass spectrometry (HRMS), which enables accurate mass measurement at high resolving power, has recently evolved to the stage that is rapidly causing a shift from unit-resolution, quadrupole-dominated instrumentation. The main HRMS techniques today are time-of-flight mass spectrometry and Orbitrap Fourier-transform mass spectrometry. Both techniques enable a range of different drug-screening strategies that essentially rely on measuring a compound's or a fragment's mass with sufficiently high accuracy that its elemental composition can be determined directly. Accurate mass and isotopic pattern acts as a filter for confirming the identity of a compound or even identification of an unknown. High mass resolution is essential for improving confidence in accurate mass results in the analysis of complex biological samples. This review discusses recent applications of HRMS in analytical toxicology.

  8. A Multimodal Data Analysis Approach for Targeted Drug Discovery Involving Topological Data Analysis (TDA).

    Science.gov (United States)

    Alagappan, Muthuraman; Jiang, Dadi; Denko, Nicholas; Koong, Albert C

    In silico drug discovery refers to a combination of computational techniques that augment our ability to discover drug compounds from compound libraries. Many such techniques exist, including virtual high-throughput screening (vHTS), high-throughput screening (HTS), and mechanisms for data storage and querying. However, presently these tools are often used independent of one another. In this chapter, we describe a new multimodal in silico technique for the hit identification and lead generation phases of traditional drug discovery. Our technique leverages the benefits of three independent methods-virtual high-throughput screening, high-throughput screening, and structural fingerprint analysis-by using a fourth technique called topological data analysis (TDA). We describe how a compound library can be independently tested with vHTS, HTS, and fingerprint analysis, and how the results can be transformed into a topological data analysis network to identify compounds from a diverse group of structural families. This process of using TDA or similar clustering methods to identify drug leads is advantageous because it provides a mechanism for choosing structurally diverse compounds while maintaining the unique advantages of already established techniques such as vHTS and HTS.

  9. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

    Directory of Open Access Journals (Sweden)

    Herxheimer Andrew

    2002-03-01

    Full Text Available Abstract Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis.

  10. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

    Science.gov (United States)

    Croft, Ashley M; Herxheimer, Andrew

    2002-01-01

    Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis. PMID:11914150

  11. MDMA (Ecstacy): Useful Information for Health Professionals Involved in Drug Education Programs.

    Science.gov (United States)

    Elk, Carrie

    1996-01-01

    Provides a brief history of 3,4-ethylenedioxymethamphetamine (MDMA). Presents a summation of current findings and implications including MDMA in drug education. Examines typical dosage, effects, user profile, and therapeutic aspects. Calls for increased research to address the lack of formal scientific data regarding the nature and effects of…

  12. A Controlled Trial of Mass Drug Administration to Interrupt Transmission of Multi Drug Resistant Falciparum Malaria in Cambodian Villages.

    Science.gov (United States)

    Tripura, Rupam; Peto, Thomas J; Nguon, Chea; Davoeung, Chan; Mukaka, Mavuto; Sirithiranont, Pasathorn; Dhorda, Mehul; Promnarate, Cholrawee; Imwong, Mallika; von Seidlein, Lorenz; Duanguppama, Jureeporn; Patumrat, Krittaya; Rekol, Huy; Grobusch, Martin P; Day, Nicholas P J; White, Nicholas J; Dondorp, Arjen M

    2018-03-07

    The increase in multidrug resistant Plasmodium falciparum in Southeast Asia suggests a need for acceleration of malaria elimination. We evaluated the effectiveness and safety of mass drug administrations (MDA) to interrupt malaria transmission. Four malaria-endemic villages in western Cambodia were randomized to three rounds of MDA (a three-day course of dihydroartemisinin with piperaquine-phosphate), administered in either early or at the end of the study-period. Comprehensive malaria treatment records were collected during 2014-2017. Subclinical parasite prevalence was estimated by ultra-sensitive quantitative polymerase chain reaction (uPCR) quarterly over 12 months. MDA coverage with at least one complete round was 88% (1999/2268), ≥2-rounds 73% (1645/2268), and all 3-rounds 58% (1310/2268). P.falciparum incidence in intervention and control villages was similar over the 12 months prior to the study: 39/1000 person-years vs 45/1000 person-years (p=0.50). The primary outcome, P.falciparum incidence in the 12 months after MDA, was lower in intervention villages (1.5/1,000 person-years vs 37.1/1,000 person-years; incidence rate ratio 24.5, 95%CI 3.4-177; p=0.002). Following MDA in 2016, there were no clinical falciparum malaria cases over 12 months (0/2044 person-years) in all 4 villages. After an initial decrease of P.vivax prevalence in intervention villages, P.vivaxprevalence had returned to approximately half of the baseline prevalence by 12 months, and was no longer significantly lower than in control villages. No severe adverse events were attributed to treatment. MDAs with high coverage were safe, and associated with the absence of clinical P.falciparum cases for at least one year. Registered on clinicaltrials.gov (NCT01872702).

  13. Mass drug administration for trachoma: how long is not long enough?

    Directory of Open Access Journals (Sweden)

    Violeta Jimenez

    2015-03-01

    Full Text Available Blinding trachoma is targeted for elimination by 2020 using the SAFE strategy (Surgery, Antibiotics, Facial cleanliness, and Environmental improvements. Annual mass drug administration (MDA with azithromycin is a cornerstone of this strategy. If baseline prevalence of clinical signs of trachomatous inflammation - follicular among 1-9 year-olds (TF1-9 is ≥ 10% but 30%, 7 or more annual MDAs may be required to achieve the target. There are five years left before the 2020 deadline to eliminate blinding trachoma. Low endemic settings are poised to succeed in their elimination goals. However, newly-identified high prevalence districts warrant immediate inclusion in the global program. Intensified application of the SAFE strategy is needed in order to guarantee blinding trachoma elimination by 2020.

  14. Urban lymphatic filariasis in the city of Tanga, Tanzania, after seven rounds of mass drug administration

    DEFF Research Database (Denmark)

    Mwakitalu, Mbutolwe E.; Malecela, Mwele N.; Pedersen, Erling Møller

    2013-01-01

    Urban lymphatic filariasis (LF) has been listed among the challenges to the ongoing global efforts to eliminate LF. This is partly because the control strategies developed for rural areas - where most LF occurs - do not easily comply with human organization and behaviour in urban areas, and partly...... because the urban vectors thrive and proliferate in poorly planned urban settlements. This study investigated LF infection, disease and transmission in the medium-sized city of Tanga (approx. 300,000 inhabitants), Tanzania, after seven rounds of mass drug administration (MDA). Three representative sites...... of mosquito proofing measures including bed nets, environmental sanitation to prevent vector breeding) in order to reach successful LF control in the city. The high LF disease burden noted, despite the reduction in infection and transmission, moreover emphasizes the importance of allocating resources...

  15. Perspective on the Military Involvement in the War on Drugs - Is There a Better Way?

    National Research Council Canada - National Science Library

    Whitten, Daniel

    1999-01-01

    .... However, we seem determined on expanding military roles in the region. During the past two decades the administrations in power have continued to escalate the military's involvement in this fight...

  16. Cancer multidrug resistance: mechanisms involved and strategies for circumvention using a drug delivery system.

    Science.gov (United States)

    Kibria, Golam; Hatakeyama, Hiroto; Harashima, Hideyoshi

    2014-01-01

    Multidrug resistance (MDR), the principal mechanism by which many cancers develop resistance to chemotherapy, is one of the major obstacles to the successful clinical treatment of various types of cancer. Several key regulators are responsible for mediating MDR, a process that renders chemotherapeutic drugs ineffective in the internal organelles of target cells. A nanoparticulate drug delivery system (DDS) is a potentially promising tool for circumventing such MDR, which can be achieved by targeting tumor cells themselves or tumor endothelial cells that support the survival of MDR cancer cells. The present article discusses key factors that are responsible for MDR in cancer cells, with a specific focus on the application of DDS to overcome MDR via the use of chemotherapy or macromolecules.

  17. Correlates of Sex Trading among Drug-Involved Women in Committed Intimate Relationships: A Risk Profile.

    Science.gov (United States)

    Jiwatram-Negrón, Tina; El-Bassel, Nabila

    2015-01-01

    Despite a slight decline in new human immunodeficiency virus (HIV) infections in New York, marked increases and concentrated epidemics continue among subsets of the population, including women engaged in sex trading. We examined the prevalence and correlates of sex trading among 346 low-income, HIV-negative women in HIV-concordant intimate relationships. Women and their long-term main partners were recruited to participate in an HIV prevention intervention. Baseline data were used in this article. Of the 346 women in the study, 28% reported sex trading during the prior 90 days. Multivariate analyses showed increased relative risk of sex trading by lifetime experience of severe intimate partner violence (IPV), drug, and alcohol use, and marginal significance for mental health hospitalization, partner drug dependency, and homelessness. These findings suggest an urgent need for HIV prevention and intervention efforts targeted toward women in intimate relationships who trade sex for money or drugs, with an emphasis on IPV, mental health, history of incarceration, and substance abuse. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  18. Illicit Drug Analysis Using Two-Dimension Liquid Chromatography/Tandem Mass Spectrometry.

    Science.gov (United States)

    Mallet, Claude; Botch-Jones, Sabra

    2016-10-01

    For the identification of illicit drugs in forensic toxicological casework, analysis can be delayed and potentially compromised due to lengthy sample preparation techniques. For a complete forensic identification, a robust methodology is required and the current trend in forensic laboratories is the use of liquid chromatography coupled to mass spectrometry (LC/MS or LC/MS-MS). However, to achieve satisfactory results, extensive and time-consuming sample preparation protocols are required to reach sub-ng/mL levels. The concept of sequential 2D extraction was designed to capture the retention behavior of a target analyte in response to various extraction parameters. Therefore, optimized conditions can be selected to excise a region of interest during extraction. The utilization of multi-dimensional chromatography combined with a micro-extraction technique was evaluated to decrease sample preparation time while enhancing the separation integrity observed with current single-dimensional chromatography techniques. A wide range of illicit drugs were spiked in human urine and extracted using three extraction protocols for performance evaluation. The extraction process was performed using a reversed-phase solid phase extraction (SPE) in 1D, 2D-optimized, 2D-sequential and cumulative elution modes. The chosen 2D chromatography conditions that were used in this application were identified using a 6 × 6 automated methods development protocol (144 methods total). The extraction of urine samples containing target analytes was completed in less than 20 min. The analysis was performed using 200 µL of the final organic solvent (MeOH) extracts. The limit of detection for all drugs was measured at 100 pg/mL (ppt) from a 1 mL sample volume. Several analytes showed excellent signal at 10 pg/mL (ppt). © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Rapid, Secure Drug Testing Using Fingerprint Development and Paper Spray Mass Spectrometry.

    Science.gov (United States)

    Costa, Catia; Webb, Roger; Palitsin, Vladimir; Ismail, Mahado; de Puit, Marcel; Atkinson, Samuel; Bailey, Melanie J

    2017-11-01

    Paper spray mass spectrometry (PS-MS) is a technique that has recently emerged and has shown excellent analytical sensitivity to a number of drugs in blood. As an alternative to blood, fingerprints have been shown to provide a noninvasive and traceable sampling matrix. Our goal was to validate the use of fingerprint samples to detect cocaine use. Samples were collected on triangular pieces (168 mm 2 ) of washed Whatman Grade I chromatography paper. Following application of internal standard, spray solvent and a voltage were applied to the paper before mass spectrometry detection. A fingerprint visualization step was incorporated into the analysis procedure by addition of silver nitrate solution and exposing the sample to ultraviolet light. Limits of detection for cocaine, benzoylecgonine, and methylecgonine were 1, 2, and 31 ng/mL respectively, with relative standard deviations fingerprint samples yielded a 99% true-positive rate and a 2.5% false-positive rate, based on the detection of cocaine, benzoylecgonine, or methylecgonine with use of a single fingerprint. The method offers a qualitative and noninvasive screening test for cocaine use. The analysis method developed is rapid (4 min/sample) and requires no sample preparation. © 2017 American Association for Clinical Chemistry.

  20. Study of $\\tau$ decays involving kaons, spectral functions and determination of the strange quark mass

    CERN Document Server

    Barate, R.; Ghez, Philippe; Goy, C.; Lees, J.P.; Merle, E.; Minard, M.N.; Pietrzyk, B.; Alemany, R.; Casado, M.P.; Chmeissani, M.; Crespo, J.M.; Fernandez, E.; Fernandez-Bosman, M.; Garrido, L.; Grauges, E.; Juste, A.; Martinez, M.; Merino, G.; Miquel, R.; Mir, L.M.; Pacheco, A.; Park, I.C.; Riu, I.; Colaleo, A.; Creanza, D.; De Palma, M.; Gelao, G.; Iaselli, G.; Maggi, G.; Maggi, M.; Nuzzo, S.; Ranieri, A.; Raso, G.; Ruggieri, F.; Selvaggi, G.; Silvestris, L.; Tempesta, P.; Tricomi, A.; Zito, G.; Huang, X.; Lin, J.; Ouyang, Q.; Wang, T.; Xie, Y.; Xu, R.; Xue, S.; Zhang, J.; Zhang, L.; Zhao, W.; Abbaneo, D.; Becker, U.; Boix, G.; Cattaneo, M.; Ciulli, V.; Dissertori, G.; Drevermann, H.; Forty, R.W.; Frank, M.; Halley, A.W.; Hansen, J.B.; Harvey, John; Janot, P.; Jost, B.; Lehraus, I.; Leroy, O.; Mato, P.; Minten, A.; Moutoussi, A.; Ranjard, F.; Rolandi, Gigi; Rousseau, D.; Schlatter, D.; Schmitt, M.; Schneider, O.; Tejessy, W.; Teubert, F.; Tomalin, I.R.; Tournefier, E.; Wright, A.E.; Ajaltouni, Z.; Badaud, F.; Chazelle, G.; Deschamps, O.; Falvard, A.; Ferdi, C.; Gay, P.; Guicheney, C.; Henrard, P.; Jousset, J.; Michel, B.; Monteil, S.; Montret, J.C.; Pallin, D.; Perret, P.; Podlyski, F.; Hansen, J.D.; Hansen, J.R.; Hansen, P.H.; Nilsson, B.S.; Rensch, B.; Waananen, A.; Daskalakis, G.; Kyriakis, A.; Markou, C.; Simopoulou, E.; Siotis, I.; Vayaki, A.; Blondel, A.; Bonneaud, G.; Brient, J.C.; Rouge, A.; Rumpf, M.; Swynghedauw, M.; Verderi, M.; Videau, H.; Focardi, E.; Parrini, G.; Zachariadou, K.; Cavanaugh, R.; Corden, M.; Georgiopoulos, C.; Antonelli, A.; Bencivenni, G.; Bologna, G.; Bossi, F.; Campana, P.; Capon, G.; Cerutti, F.; Chiarella, V.; Laurelli, P.; Mannocchi, G.; Murtas, F.; Murtas, G.P.; Passalacqua, L.; Pepe-Altarelli, M.; Curtis, L.; Lynch, J.G.; Negus, P.; O'Shea, V.; Raine, C.; Teixeira-Dias, P.; Thompson, A.S.; Buchmuller, O.; Dhamotharan, S.; Geweniger, C.; Hanke, P.; Hansper, G.; Hepp, V.; Kluge, E.E.; Putzer, A.; Sommer, J.; Tittel, K.; Werner, S.; Wunsch, M.; Beuselinck, R.; Binnie, D.M.; Cameron, W.; Dornan, P.J.; Girone, M.; Goodsir, S.; Martin, E.B.; Marinelli, N.; Sedgbeer, J.K.; Spagnolo, P.; Thomson, Evelyn J.; Williams, M.D.; Ghete, V.M.; Girtler, P.; Kneringer, E.; Kuhn, D.; Rudolph, G.; Betteridge, A.P.; Bowdery, C.K.; Buck, P.G.; Colrain, P.; Crawford, G.; Finch, A.J.; Foster, F.; Hughes, G.; Jones, R.W.L.; Robertson, N.A.; Williams, M.I.; Giehl, I.; Hoffmann, C.; Jakobs, K.; Kleinknecht, K.; Quast, G.; Renk, B.; Rohne, E.; Sander, H.G.; van Gemmeren, P.; Wachsmuth, H.; Zeitnitz, C.; Aubert, J.J.; Benchouk, C.; Bonissent, A.; Carr, J.; Coyle, P.; Etienne, F.; Motsch, F.; Payre, P.; Talby, M.; Thulasidas, M.; Aleppo, M.; Antonelli, M.; Ragusa, F.; Berlich, R.; Buescher, Volker; Dietl, H.; Ganis, G.; Huttmann, K.; Lutjens, G.; Mannert, C.; Manner, W.; Moser, H.G.; Schael, S.; Settles, R.; Seywerd, H.; Stenzel, H.; Wiedenmann, W.; Wolf, G.; Azzurri, P.; Boucrot, J.; Callot, O.; Chen, S.; Cordier, A.; Davier, M.; Duflot, L.; Grivaz, J.F.; Heusse, P.; Hocker, Andreas; Jacholkowska, A.; Kim, D.W.; Le Diberder, F.; Lefrancois, J.; Lutz, A.M.; Schune, M.H.; Veillet, J.J.; Videau, I.; Zerwas, D.; Bagliesi, Giuseppe; Bettarini, S.; Boccali, T.; Bozzi, C.; Calderini, G.; Dell'Orso, R.; Ferrante, I.; Foa, L.; Giassi, A.; Gregorio, A.; Ligabue, F.; Lusiani, A.; Marrocchesi, P.S.; Messineo, A.; Palla, F.; Rizzo, G.; Sanguinetti, G.; Sciaba, A.; Sguazzoni, G.; Tenchini, R.; Vannini, C.; Venturi, A.; Verdini, P.G.; Blair, G.A.; Cowan, G.; Green, M.G.; Medcalf, T.; Strong, J.A.; von Wimmersperg-Toeller, J.H.; Botterill, D.R.; Clifft, R.W.; Edgecock, T.R.; Norton, P.R.; Thompson, J.C.; Bloch-Devaux, Brigitte; Colas, P.; Emery, S.; Kozanecki, W.; Lancon, E.; Lemaire, M.C.; Locci, E.; Perez, P.; Rander, J.; Renardy, J.F.; Roussarie, A.; Schuller, J.P.; Schwindling, J.; Trabelsi, A.; Vallage, B.; Black, S.N.; Dann, J.H.; Johnson, R.P.; Kim, H.Y.; Konstantinidis, N.; Litke, A.M.; McNeil, M.A.; Taylor, G.; Booth, C.N.; Cartwright, S.; Combley, F.; Kelly, M.S.; Lehto, M.; Thompson, L.F.; Affholderbach, K.; Boehrer, Armin; Brandt, S.; Grupen, C.; Prange, G.; Giannini, G.; Gobbo, B.; Rothberg, J.; Wasserbaech, S.; Armstrong, S.R.; Charles, E.; Elmer, P.; Ferguson, D.P.S.; Gao, Y.; Gonzalez, S.; Greening, T.C.; Hayes, O.J.; Hu, H.; Jin, S.; McNamara, P.A., III; Nachtman, J.M.; Nielsen, J.; Orejudos, W.; Pan, Y.B.; Saadi, Y.; Scott, I.J.; Walsh, J.; Wu, Sau Lan; Wu, X.; Zobernig, G.

    1999-01-01

    All ALEPH measurements of branching ratios of tau decays involving kaons are summarized including a combination of results obtained with K^0_S and K^0_L detection. The decay dynamics are studied, leading to the determination of contributions from vector K^*(892) and K^{*}(1410), and axial-vector K_1(1270) and K_1(1400) resonances. Agreement with isospin symmetry is observed among the different final states. Under the hypothesis of the conserved vector current, the spectral function for the K\\bar{K}\\pi mode is compared with the corresponding cross section for low energy e^+e^- annihilation, yielding an axial-vector fraction of (94^{+6}_{-8})% for this mode. The branching ratio for tau decay into all strange final states is determined to be B(\\tau^-\\to X^-(S=-1)\

  1. Natural compounds involved in adipose tissue mass control in in vitro studies

    Directory of Open Access Journals (Sweden)

    Katarzyna Kowalska

    2011-08-01

    Full Text Available The World Health Organization (WHO has recognized obesity as an epidemic of the 21st century. Obesity is pathological fat accumulation in the body influenced by many factors: metabolic, endocrine, genetic, environmental, psychological and behavioral. The quality and quantity of food intake to a considerable degree determine excessive fat accumulation in the body. The strategy in obesity prevention includes, among other things, a proper diet. It is widely known that a diet rich in fruits and vegetables reduces body weight. Adipocytes are not only cells serving as storage depots for “energy”, but are also specialized cells influenced by various hormones, cytokines and nutrients, which have pleiotropic effects on the body. Knowledge of adipocyte biology is crucial for our understanding of the pathophysiological basis of obesity and metabolic diseases, such as type 2 diabetes. Furthermore, rational manipulation of adipose physiology is a promising avenue for therapy of these conditions. Adipose tissue mass can be reduced through elimination of adipocytes by apoptosis, inhibition of adipogenesis and increased lipolysis in adipocytes. Natural products have a potential to induce apoptosis, inhibit adipogenesis and stimulate lipolysis in adipocytes. Various dietary bioactive compounds target different stages of the adipocyte life cycle and may be useful as natural therapeutic agents in obesity prevention.

  2. Mass

    International Nuclear Information System (INIS)

    Quigg, Chris

    2007-01-01

    In the classical physics we inherited from Isaac Newton, mass does not arise, it simply is. The mass of a classical object is the sum of the masses of its parts. Albert Einstein showed that the mass of a body is a measure of its energy content, inviting us to consider the origins of mass. The protons we accelerate at Fermilab are prime examples of Einsteinian matter: nearly all of their mass arises from stored energy. Missing mass led to the discovery of the noble gases, and a new form of missing mass leads us to the notion of dark matter. Starting with a brief guided tour of the meanings of mass, the colloquium will explore the multiple origins of mass. We will see how far we have come toward understanding mass, and survey the issues that guide our research today.

  3. Action of some drugs on enzymes involved in DNA-repair and semiconservative DNA-synthesis

    International Nuclear Information System (INIS)

    Wawra, E.; Klein, W.; Kocsis, F.; Weniger, P.

    1975-07-01

    Different antirheumatic and cytostatic drugs had been tested by measurement of the thymidine incorporation into DNA of spleen cells under conditions, under which either DNA-synthesis or repair after gamma- or UV-irradiation takes place. There are substances, which inhibit either only the semiconservative DNA-synthesis (vinblastine, isonicotinic acid hydracide) or only DNA-repair after gamma-irradiation (mixture of penicillin-G and procaine-penicillin-G) or both (cyclophosphamide, phenylbutazone, procarbazine, nalidixic acid). Vincristine shows no effect on the thymidine incorporation in DNA, but by density gradient centrifugation it has been found that it influences the ligase reaction. Two DNA polymerases had been isolated from spleen cells, one of the low molecular and one of the high molecular weight type. The influences of the described drugs on these enzymes and on a deoxyribonuclease I from beef pancreas have been tested in ''in vitro'' systems. In all cases, it has been found that there is no effect or only a very small one, compared with the action of well known inhibitors as e.g. ethidium bromide and p-chloromercuribenzoate, and this cannot be responsible for the suppressions found in DNA-repair and semiconservative DNA-synthesis. (author)

  4. Albumin is synthesized in epididymis and aggregates in a high molecular mass glycoprotein complex involved in sperm-egg fertilization.

    Directory of Open Access Journals (Sweden)

    Kélen Fabíola Arroteia

    Full Text Available The epididymis has an important role in the maturation of sperm for fertilization, but little is known about the epididymal molecules involved in sperm modifications during this process. We have previously described the expression pattern for an antigen in epididymal epithelial cells that reacts with the monoclonal antibody (mAb TRA 54. Immunohistochemical and immunoblotting analyses suggest that the epitope of the epididymal antigen probably involves a sugar moiety that is released into the epididymal lumen in an androgen-dependent manner and subsequently binds to luminal sperm. Using column chromatography, SDS-PAGE with in situ digestion and mass spectrometry, we have identified the protein recognized by mAb TRA 54 in mouse epididymal epithelial cells. The ∼65 kDa protein is part of a high molecular mass complex (∼260 kDa that is also present in the sperm acrosomal vesicle and is completely released after the acrosomal reaction. The amino acid sequence of the protein corresponded to that of albumin. Immunoprecipitates with anti-albumin antibody contained the antigen recognized by mAb TRA 54, indicating that the epididymal molecule recognized by mAb TRA 54 is albumin. RT-PCR detected albumin mRNA in the epididymis and fertilization assays in vitro showed that the glycoprotein complex containing albumin was involved in the ability of sperm to recognize and penetrate the egg zona pellucida. Together, these results indicate that epididymal-derived albumin participates in the formation of a high molecular mass glycoprotein complex that has an important role in egg fertilization.

  5. Albumin is synthesized in epididymis and aggregates in a high molecular mass glycoprotein complex involved in sperm-egg fertilization.

    Science.gov (United States)

    Arroteia, Kélen Fabíola; Barbieri, Mainara Ferreira; Souza, Gustavo Henrique Martins Ferreira; Tanaka, Hiromitsu; Eberlin, Marcos Nogueira; Hyslop, Stephen; Alvares, Lúcia Elvira; Pereira, Luís Antonio Violin Dias

    2014-01-01

    The epididymis has an important role in the maturation of sperm for fertilization, but little is known about the epididymal molecules involved in sperm modifications during this process. We have previously described the expression pattern for an antigen in epididymal epithelial cells that reacts with the monoclonal antibody (mAb) TRA 54. Immunohistochemical and immunoblotting analyses suggest that the epitope of the epididymal antigen probably involves a sugar moiety that is released into the epididymal lumen in an androgen-dependent manner and subsequently binds to luminal sperm. Using column chromatography, SDS-PAGE with in situ digestion and mass spectrometry, we have identified the protein recognized by mAb TRA 54 in mouse epididymal epithelial cells. The ∼65 kDa protein is part of a high molecular mass complex (∼260 kDa) that is also present in the sperm acrosomal vesicle and is completely released after the acrosomal reaction. The amino acid sequence of the protein corresponded to that of albumin. Immunoprecipitates with anti-albumin antibody contained the antigen recognized by mAb TRA 54, indicating that the epididymal molecule recognized by mAb TRA 54 is albumin. RT-PCR detected albumin mRNA in the epididymis and fertilization assays in vitro showed that the glycoprotein complex containing albumin was involved in the ability of sperm to recognize and penetrate the egg zona pellucida. Together, these results indicate that epididymal-derived albumin participates in the formation of a high molecular mass glycoprotein complex that has an important role in egg fertilization.

  6. In situ mass spectrometry imaging and ex vivo characterization of renal crystalline deposits induced in multiple preclinical drug toxicology studies.

    Directory of Open Access Journals (Sweden)

    Anna Nilsson

    Full Text Available Drug toxicity observed in animal studies during drug development accounts for the discontinuation of many drug candidates, with the kidney being a major site of tissue damage. Extensive investigations are often required to reveal the mechanisms underlying such toxicological events and in the case of crystalline deposits the chemical composition can be problematic to determine. In the present study, we have used mass spectrometry imaging combined with a set of advanced analytical techniques to characterize such crystalline deposits in situ. Two potential microsomal prostaglandin E synthase 1 inhibitors, with similar chemical structure, were administered to rats over a seven day period. This resulted in kidney damage with marked tubular degeneration/regeneration and crystal deposits within the tissue that was detected by histopathology. Results from direct tissue section analysis by matrix-assisted laser desorption ionization mass spectrometry imaging were combined with data obtained following manual crystal dissection analyzed by liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy. The chemical composition of the crystal deposits was successfully identified as a common metabolite, bisulphonamide, of the two drug candidates. In addition, an un-targeted analysis revealed molecular changes in the kidney that were specifically associated with the area of the tissue defined as pathologically damaged. In the presented study, we show the usefulness of combining mass spectrometry imaging with an array of powerful analytical tools to solve complex toxicological problems occurring during drug development.

  7. Improving Patient Involvement in the Drug Development Process: Case Study of Potential Applications from an Online Peer Support Network.

    Science.gov (United States)

    Anand, Amrutha; Brandwood, Helen Jane; Jameson Evans, Matt

    2017-11-01

    To date, social media has been used predominantly by the pharmaceutical industry to market products and to gather feedback and comments on products from consumers, a process termed social listening. However, social media has only been used cautiously in the drug development cycle, mainly because of regulations, restrictions on engagement with patients, or a lack of guidelines for social media use from regulatory bodies. Despite this cautious approach, there is a clear drive, from both the industry and consumers, for increased patient participation in various stages of the drug development process. The authors use the example of HealthUnlocked, one of the world's largest health networks, to illustrate the potential applications of online health communities as a means of increasing patient involvement at various stages of the drug development process. Having identified the willingness of the user population to be involved in research, numerous ways to engage users on the platform have been identified and explored. This commentary describes some of these approaches and reports how online health networks that encourage people to share their experiences in managing their health can, in turn, enable rapid patient engagement for clinical research within the constraints of industry regulation. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  8. Mycobacterium fluoroquinolone resistance protein B, a novel small GTPase, is involved in the regulation of DNA gyrase and drug resistance

    Science.gov (United States)

    Tao, Jun; Han, Jiao; Wu, Hanyu; Hu, Xinling; Deng, Jiaoyu; Fleming, Joy; Maxwell, Anthony; Bi, Lijun; Mi, Kaixia

    2013-01-01

    DNA gyrase plays a vital role in resolving DNA topological problems and is the target of antibiotics such as fluoroquinolones. Mycobacterium fluoroquinolone resistance protein A (MfpA) from Mycobacterium smegmatis is a newly identified DNA gyrase inhibitor that is believed to confer intrinsic resistance to fluoroquinolones. However, MfpA does not prevent drug-induced inhibition of DNA gyrase in vitro, implying the involvement of other as yet unknown factors. Here, we have identified a new factor, named Mycobacterium fluoroquinolone resistance protein B (MfpB), which is involved in the protection of DNA gyrase against drugs both in vivo and in vitro. Genetic results suggest that MfpB is necessary for MfpA protection of DNA gyrase against drugs in vivo; an mfpB knockout mutant showed greater susceptibility to ciprofloxacin than the wild-type, whereas a strain overexpressing MfpA and MfpB showed higher loss of susceptibility. Further biochemical characterization indicated that MfpB is a small GTPase and its GTP bound form interacts directly with MfpA and influences its interaction with DNA gyrase. Mutations in MfpB that decrease its GTPase activity disrupt its protective efficacy. Our studies suggest that MfpB, a small GTPase, is required for MfpA-conferred protection of DNA gyrase. PMID:23275532

  9. Early peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass

    Directory of Open Access Journals (Sweden)

    Vivas Yurena

    2011-12-01

    Full Text Available Abstract Background The progression towards type 2 diabetes depends on the allostatic response of pancreatic beta cells to synthesise and secrete enough insulin to compensate for insulin resistance. The endocrine pancreas is a plastic tissue able to expand or regress in response to the requirements imposed by physiological and pathophysiological states associated to insulin resistance such as pregnancy, obesity or ageing, but the mechanisms mediating beta cell mass expansion in these scenarios are not well defined. We have recently shown that ob/ob mice with genetic ablation of PPARγ2, a mouse model known as the POKO mouse failed to expand its beta cell mass. This phenotype contrasted with the appropriate expansion of the beta cell mass observed in their obese littermate ob/ob mice. Thus, comparison of these models islets particularly at early ages could provide some new insights on early PPARγ dependent transcriptional responses involved in the process of beta cell mass expansion Results Here we have investigated PPARγ dependent transcriptional responses occurring during the early stages of beta cell adaptation to insulin resistance in wild type, ob/ob, PPARγ2 KO and POKO mice. We have identified genes known to regulate both the rate of proliferation and the survival signals of beta cells. Moreover we have also identified new pathways induced in ob/ob islets that remained unchanged in POKO islets, suggesting an important role for PPARγ in maintenance/activation of mechanisms essential for the continued function of the beta cell. Conclusions Our data suggest that the expansion of beta cell mass observed in ob/ob islets is associated with the activation of an immune response that fails to occur in POKO islets. We have also indentified other PPARγ dependent differentially regulated pathways including cholesterol biosynthesis, apoptosis through TGF-β signaling and decreased oxidative phosphorylation.

  10. Improvements on enzymatic hydrolysis of human hair for illicit drug determination by gas chromatography/mass spectrometry.

    Science.gov (United States)

    Míguez-Framil, Martha; Moreda-Piñeiro, Antonio; Bermejo-Barrera, Pilar; López, Patricia; Tabernero, María Jesús; Bermejo, Ana María

    2007-11-15

    The use of ultrasound energy for accelerating the pronase E enzymatic hydrolysis of human hair for extracting illicit drugs has been novelty tested. The enzymatic extracts obtained after 30 min of sonication in an ultrasonic water bath were subjected to an optimized solid-phase extraction process, which involved a solution of 2.0% (v/v) acetic acid in methanol as eluting solution and concentration by N2 stream evaporation. A gas chromatography/mass spectrometry method was used to separate and determine cocaine, benzoylecgonine, codeine, morphine, and 6-monoacethylmorphine in 20 min. Variables affecting ultrasound-assisted pronase E hydrolysis such as hydrolysis temperature, hydrolysis time, enzyme concentration, catalyzer (1,4-dithiothreitol) concentration, ionic strength, pH, and ultrasound frequency were simultaneously evaluated by a Plackett-Burman design 2(8) PBD of resolution III. The most statistically significant variables were ionic strength and pH, which means that analyte extraction is mainly attributed to pronase E activity. The optimization or evaluation of all the factors has led to an accelerated pronase E hydrolysis of human hair, which can be completed in 30 min. Results have been found to be statistically similar to those obtained with conventional pronase E hydrolysis. The accelerated method was finally applied to several human hair samples from multidrug abusers.

  11. Effects of meal composition and meal timing on the expression of genes involved in hepatic drug metabolism in rats.

    Science.gov (United States)

    de Vries, E M; Oosterman, J E; Eggink, H M; de Goede, P; Sen, S; Foppen, E; Boudzovitch-Surovtseva, O; Boelen, A; Romijn, J A; laFleur, S E; Kalsbeek, A

    2017-01-01

    With chronotherapy, drug administration is synchronized with daily rhythms in drug clearance and pharmacokinetics. Daily rhythms in gene expression are centrally mastered by the suprachiasmatic nucleus of the hypothalamus as well as by tissue clocks containing similar molecular mechanisms in peripheral organs. The central timing system is sensitive to changes in the external environment such as those of the light-dark cycle, meal timing and meal composition. We investigated how changes in diet composition and meal timing would affect the daily hepatic expression rhythms of the nuclear receptors PXR and CAR and of enzymes involved in P450 mediated drug metabolism, as such changes could have consequences for the practice of chronotherapy. Rats were subjected to either a regular chow or a free choice high-fat-high-sugar (fcHFHS) diet. These diets were provided ad libitum, or restricted to either the light phase or the dark phase. In a second experiment, rats had access to chow either ad libitum or in 6 meals equally distributed over 24 hours. Pxr, Alas1 and Por displayed significant day-night rhythms under ad libitum chow fed conditions, which for Pxr was disrupted under fcHFHS diet conditions. Although no daily rhythms were detected in expression of CAR, Cyp2b2 and Cyp3a2, the fcHFHS diet did affect basal expression of these genes. In chow fed rats, dark phase feeding induced a diurnal rhythm in Cyp2b2 expression while light phase feeding induced a diurnal rhythm in Car expression and completely shifted the peak expression of Pxr, Car, Cyp2b2, Alas1 and Por. The 6-meals-a-day feeding only abolished the Pxr rhythm but not the rhythms of the other genes. We conclude that although nuclear receptors and enzymes involved in the regulation of hepatic drug metabolism are sensitive to meal composition, changes in meal timing are mainly effectuated via changes in the molecular clock.

  12. Hydrophilic Interaction Liquid Chromatography/Mass Spectrometry: An Attractive and Prospective Method for the Quantitative Bioanalysis in Drug Metabolism.

    Science.gov (United States)

    Li, Zheng; Han, Jie; Sun, Shi-an; Chen, Kai; Tang, Dao-quan

    2016-01-01

    During the development, dosage optimization and safety evaluation of a drug, rapid and precise monitoring of administered drug and/or its metabolites in biological samples including blood, plasma, serum, tissues and saliva are vital. As drug biotransformation produces more hydrophilic metabolites for the enhancement of drug elimination, which is often a challenge for traditional reversed-phase liquid chromatography (RPLC) separation. Because hydrophilic interaction liquid chromatography (HILIC) is capable of retaining polar compounds and readily compatible with mass spectrometry (MS), HILIC has been used as a complementary separation technique to RPLC for analysis of polar metabolites, especially polar drugs and their metabolites. This review covers core aspects of HILIC-MS/MS method and overall profile of its application in analysis of drug and/or its metabolites. The emphasis of this paper has been placed on the applications of HILIC-MS/MS method in quantitative bioanalysis of drugs alone or along with their metabolites in drug metabolism studies in recent years. As a fundamental and critical step of bioanalytical method, conventional sample preparation techniques of biological matrices for the HILIC-MS/MS analysis of drugs and/or their metabolites are also briefly featured.

  13. Glass bottle sampling solid phase microextraction gas chromatography mass spectrometry for breath analysis of drug metabolites.

    Science.gov (United States)

    Lu, Yan; Niu, Wenqi; Zou, Xue; Shen, Chengyin; Xia, Lei; Huang, Chaoqun; Wang, Hongzhi; Jiang, Haihe; Chu, Yannan

    2017-05-05

    Breath analysis is a non-invasive approach which may be applied to disease diagnosis and pharmacokinetic study. In the case of offline analysis, the exhaled gas needs to be collected and the sampling bag is often used as the storage vessel. However, the sampling bag usually releases some extra compounds, which may interfere with the result of the breath test. In this study, a novel breath sampling glass bottle was developed with a syringe needle sampling port for solid phase microextraction (SPME). Such a glass bottle scarcely liberates compounds and can be used to collect exhaled gas for ensuing analysis by gas chromatography-mass spectrometry (GC-MS). The glass bottle sampling SPME-GC-MS analysis was carried out to investigate the breath metabolites of myrtol, a multicompound drug normally used in the treatment of bronchitis and sinusitis. Four compounds, α-pinene, 2,3-dehydro-1,8-cineole, d-limonene and 1,8-cineole were found in the exhaled breath of all eight volunteers who had taken the myrtol. While for other ten subjects who had not used the myrtol, these compounds were undetectable. In the SPME-GC-MS analysis of the headspace of myrtol, three compounds were detected including α-pinene, d-limonene and 1,8-cineole. Comparing the results of breath and headspace analysis, it indicates that 2,3-dehydro-1,8-cineole in the breath is the metabolite of 1,8-cineole. It is the first time that this metabolite was identified in human breath. The study demonstrates that the glass bottle sampling SPME-GC-MS method is applicable to exhaled gas analysis including breath metabolites investigation of drugs like myrtol. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Modeling the impact and costs of semiannual mass drug administration for accelerated elimination of lymphatic filariasis.

    Directory of Open Access Journals (Sweden)

    Wilma A Stolk

    Full Text Available The Global Program to Eliminate Lymphatic Filariasis (LF has a target date of 2020. This program is progressing well in many countries. However, progress has been slow in some countries, and others have not yet started their mass drug administration (MDA programs. Acceleration is needed. We studied how increasing MDA frequency from once to twice per year would affect program duration and costs by using computer simulation modeling and cost projections. We used the LYMFASIM simulation model to estimate how many annual or semiannual MDA rounds would be required to eliminate LF for Indian and West African scenarios with varied pre-control endemicity and coverage levels. Results were used to estimate total program costs assuming a target population of 100,000 eligibles, a 3% discount rate, and not counting the costs of donated drugs. A sensitivity analysis was done to investigate the robustness of these results with varied assumptions for key parameters. Model predictions suggested that semiannual MDA will require the same number of MDA rounds to achieve LF elimination as annual MDA in most scenarios. Thus semiannual MDA programs should achieve this goal in half of the time required for annual programs. Due to efficiency gains, total program costs for semiannual MDA programs are projected to be lower than those for annual MDA programs in most scenarios. A sensitivity analysis showed that this conclusion is robust. Semiannual MDA is likely to shorten the time and lower the cost required for LF elimination in countries where it can be implemented. This strategy may improve prospects for global elimination of LF by the target year 2020.

  15. Stable isotope- and mass spectrometry-based metabolomics as tools in drug metabolism: a study expanding tempol pharmacology.

    Science.gov (United States)

    Li, Fei; Pang, Xiaoyan; Krausz, Kristopher W; Jiang, Changtao; Chen, Chi; Cook, John A; Krishna, Murali C; Mitchell, James B; Gonzalez, Frank J; Patterson, Andrew D

    2013-03-01

    The application of mass spectrometry-based metabolomics in the field of drug metabolism has yielded important insights not only into the metabolic routes of drugs but has provided unbiased, global perspectives of the endogenous metabolome that can be useful for identifying biomarkers associated with mechanism of action, efficacy, and toxicity. In this report, a stable isotope- and mass spectrometry-based metabolomics approach that captures both drug metabolism and changes in the endogenous metabolome in a single experiment is described. Here the antioxidant drug tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) was chosen because its mechanism of action is not completely understood and its metabolic fate has not been studied extensively. Furthermore, its small size (MW = 172.2) and chemical composition (C(9)H(18)NO(2)) make it challenging to distinguish from endogenous metabolites. In this study, mice were dosed with tempol or deuterated tempol (C(9)D(17)HNO(2)) and their urine was profiled using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Principal component analysis of the urinary metabolomics data generated a Y-shaped scatter plot containing drug metabolites (protonated and deuterated) that were clearly distinct from the endogenous metabolites. Ten tempol drug metabolites, including eight novel metabolites, were identified. Phase II metabolism was the major metabolic pathway of tempol in vivo, including glucuronidation and glucosidation. Urinary endogenous metabolites significantly elevated by tempol treatment included 2,8-dihydroxyquinoline (8.0-fold, P tempol treatment including pantothenic acid (1.3-fold, P < 0.05) and isobutrylcarnitine (5.3-fold, P < 0.01). This study underscores the power of a stable isotope- and mass spectrometry-based metabolomics in expanding the view of drug pharmacology.

  16. Ring Chromosome 17 Not Involving the Miller-Dieker Region: A Case with Drug-Resistant Epilepsy.

    Science.gov (United States)

    Coppola, Antonietta; Morrogh, Deborah; Farrell, Fiona; Balestrini, Simona; Hernandez-Hernandez, Laura; Krithika, S; Sander, Josemir W; Waters, Jonathan J; Sisodiya, Sanjay M

    2017-12-01

    Chromosomal abnormalities are often identified in people with neurodevelopmental disorders including intellectual disability, autism, and epilepsy. Ring chromosomes, which usually involve gene copy number loss, are formed by fusion of subtelomeric or telomeric chromosomal regions. Some ring chromosomes, including ring 14, 17, and 20, are strongly associated with seizure disorders. We report an individual with a ring chromosome 17, r(17)(p13.3q25.3), with a terminal 17q25.3 deletion and no short arm copy number loss, and with a phenotype characterized by intellectual disability and drug-resistant epilepsy, including a propensity for nonconvulsive status epilepticus.

  17. Violent and disruptive behavior among drug-involved prisoners: relationship with psychiatric symptoms.

    Science.gov (United States)

    Friedmann, Peter D; Melnick, Gerald; Jiang, Lan; Hamilton, Zachary

    2008-01-01

    This study examines the relationship between psychiatric symptoms and violent/disruptive behavior among 192 inmates who participated in prison-based substance abuse treatment. Participants came from two sites able to provide narrative reports of disciplinary actions in the Criminal Justice Drug Abuse Treatment Studies' Co-Occurring Disorders Screening Instrument study. In multivariate logistic models, a lifetime history of thought insertion/control ideation (OR, 11.6; 95% CI, 1.8-75.2), antisocial personality disorder (OR, 3.3; 95% CI, 1.2-8.9), and disciplinary action related to possession of controlled substances or contraband (OR, 4.9; 95% CI, 1.9-12.3) were associated with increased risk for violent or disruptive behavior while in prison, whereas lifetime phobic symptoms (OR, 0.2; 95% CI, 0.1-0.54) and high school graduation (OR, 0.4; 95% CI, 0.2-1.0) were associated with a decreased risk of violence and disruptive behavior in general. We conclude that, among inmates in substance abuse treatment, symptoms that increase risk for violence or disruptive behavior include thought control/insertion ideation and disciplinary infractions related to controlled substances, contraband, or failure to participate in assigned programs, as well a history of antisocial personality disorder.

  18. Orbitrap technology for comprehensive metabolite-based liquid chromatographic–high resolution-tandem mass spectrometric urine drug screening – Exemplified for cardiovascular drugs

    Energy Technology Data Exchange (ETDEWEB)

    Helfer, Andreas G.; Michely, Julian A.; Weber, Armin A.; Meyer, Markus R.; Maurer, Hans H., E-mail: hans.maurer@uks.eu

    2015-09-03

    LC–high resolution (HR)-MS well established in proteomics has become more and more important in bioanalysis of small molecules over the last few years. Its high selectivity and specificity provide best prerequisites for its use in broad screening approaches. Therefore, Orbitrap technology was tested for developing a general metabolite-based LC–HR-MS/MS screening approach for urinalysis of drugs necessary in clinical and forensic toxicology. After simple urine precipitation, the drugs and their metabolites were separated within 10 min and detected by a Q-Exactive mass spectrometer in full scan with positive/negative switching, and subsequent data dependent acquisition (DDA) mode. Identification criteria were the presence of accurate precursor ions, isotopic patterns, five most intense fragment ions, and comparison with full HR-MS/MS library spectra. The current library contains over 1900 parent drugs and 1200 metabolites. The method was validated for typical drug representatives and metabolites concerning recovery, matrix effects, process efficiency, and limits showed acceptable results. The applicability was tested first for cardiovascular drugs, which should be screened for in poisoning cases and for medication adherence of hypertension patients. The novel LC–HR-MS/MS method allowed fast, simple, and robust urine screening, particularly for cardiovascular drugs showing the usefulness of Orbitrap technology for drug testing. - Highlights: • First study on the application of Orbitrap technology for comprehensive drug screening in clinical and forensic toxicology. • Simple workup, sufficient separation, and powerful screening and identification using modern high resolution MS. • Validation of the assay according to guidelines for qualitative approaches. • Elucidation of the power of new data evaluation software in combination with a new reference drug and metabolite library. • Great relevance for science and practice in clinical and forensic

  19. Orbitrap technology for comprehensive metabolite-based liquid chromatographic–high resolution-tandem mass spectrometric urine drug screening – Exemplified for cardiovascular drugs

    International Nuclear Information System (INIS)

    Helfer, Andreas G.; Michely, Julian A.; Weber, Armin A.; Meyer, Markus R.; Maurer, Hans H.

    2015-01-01

    LC–high resolution (HR)-MS well established in proteomics has become more and more important in bioanalysis of small molecules over the last few years. Its high selectivity and specificity provide best prerequisites for its use in broad screening approaches. Therefore, Orbitrap technology was tested for developing a general metabolite-based LC–HR-MS/MS screening approach for urinalysis of drugs necessary in clinical and forensic toxicology. After simple urine precipitation, the drugs and their metabolites were separated within 10 min and detected by a Q-Exactive mass spectrometer in full scan with positive/negative switching, and subsequent data dependent acquisition (DDA) mode. Identification criteria were the presence of accurate precursor ions, isotopic patterns, five most intense fragment ions, and comparison with full HR-MS/MS library spectra. The current library contains over 1900 parent drugs and 1200 metabolites. The method was validated for typical drug representatives and metabolites concerning recovery, matrix effects, process efficiency, and limits showed acceptable results. The applicability was tested first for cardiovascular drugs, which should be screened for in poisoning cases and for medication adherence of hypertension patients. The novel LC–HR-MS/MS method allowed fast, simple, and robust urine screening, particularly for cardiovascular drugs showing the usefulness of Orbitrap technology for drug testing. - Highlights: • First study on the application of Orbitrap technology for comprehensive drug screening in clinical and forensic toxicology. • Simple workup, sufficient separation, and powerful screening and identification using modern high resolution MS. • Validation of the assay according to guidelines for qualitative approaches. • Elucidation of the power of new data evaluation software in combination with a new reference drug and metabolite library. • Great relevance for science and practice in clinical and forensic

  20. Comparison and validation of two mathematical models for the impact of mass drug administration on Ascaris lumbricoides and hookworm infection

    NARCIS (Netherlands)

    L.E. Coffeng (Luc); J. Truscott (James); S.H. Farrell (Sam H.); H.C. Turner (Hugo C.); R. Sarkar (Rajiv); G. Kang (Gagandeep); S.J. de Vlas (Sake); R.M. Anderson (Roy)

    2017-01-01

    textabstractThe predictions of two mathematical models of the transmission dynamics of Ascaris lumbricoides and hookworm infection and the impact of mass drug administration (MDA) are compared, using data from India. One model has an age structured partial differential equation (PDE) deterministic

  1. Differences between men and women in self-reported body mass index and its relation to drug use

    NARCIS (Netherlands)

    Vera-Villarroel, P.; Piqueras, J.A.; Kuhne, W.; Cuijpers, P.; van Straten, A.

    2014-01-01

    Background: Obesity is a public health problem of alarming proportions, including among the university population in Latin America. The purpose of this study was to determine the relation between the self-reported body mass index and the associated drug use and health-risk behaviors.Methods: We

  2. Generic solid phase extraction-liquid chromatography-tandem mass spectrometry method for fast determination of drugs in biological fluids

    NARCIS (Netherlands)

    Schellen, A.; Ooms, B.; Lagemaat, D. van de; Vreeken, R.; Dongen, W.D. van

    2003-01-01

    A generic method was developed for the fast determination of a wide range of drugs in serum or plasma. The methodology comprises generic solid-phase extraction, on-line coupled to gradient HPLC with tandem mass spectrometric detection (SPE-LC-MS/MS). The individual components of the SPE-LC-MS/MS

  3. Desorption electrospray ionisation mass spectrometry: A rapid screening tool for veterinary drug preparations and forensic samples from hormone crime investigations

    NARCIS (Netherlands)

    Nielen, M.W.F.; Hooijerink, H.; Claassen, F.C.; Engelen, M.C.; Beek, van T.A.

    2009-01-01

    Hormone and veterinary drug screening and forensics can benefit from the recent developments in desorption electrospray ionisation (DESI) mass spectrometry (MS). In this work the feasibility of DESI application has been studied. Using a linear ion trap or quadrupole time-of-flight (TOF) MS

  4. Mass spectrometry study of increased breakdown of an anticonvulsivant drug substance

    Science.gov (United States)

    Buret, D.; Breton, D.; Clair, P.; Lafosse, M.

    2006-06-01

    The French Military Health Service (SSA) developed a new pharmaceutic speciality as a treatment against neurotoxic organophosphate poisoning (NSP), as a substitute for existing therapeutics. The Armed Forces Central Pharmacy (PCA) is in charge of the development of therapeutic formulation and stability studies. This product includes three drug substances: atropine, pralidoxime and avizafone, an amine prodrug of diazepam, soluble in water. The PCA performed a stability study of this formulation according to the International Conference on Harmonization (ICH) recommendations: it was used to display interaction between the molecules and the plastic of the cartridge (the container turned yellow). Since no degradation product of atropine and pralidoxime was observed, a complementary evaluation of avizafone and its main known degradation products (diazepam, carbostyril and methylaminobenzochlorophenone [MACB]) was initiated. The results were used to determine the degradation products obtained under different conditions and the kind of mechanisms, which may occur as the formulation ages: adsorption or absorption by the bulk and/or increasing degradation products. The analytical methods developed here are a direct sample analysis by mass spectrometry (MS) using different ionization modes and liquid chromatography (LC) with UV detection to confirm the results obtain with MS.

  5. Cessation of mass drug administration for lymphatic filariasis in Zanzibar in 2006: was transmission interrupted?

    Directory of Open Access Journals (Sweden)

    Maria P Rebollo

    2015-03-01

    Full Text Available Lymphatic filariasis (LF is targeted for elimination through annual mass drug administration (MDA for 4-6 years. In 2006, Zanzibar stopped MDA against LF after five rounds of MDA revealed no microfilaraemic individuals during surveys at selected sentinel sites. We asked the question if LF transmission was truly interrupted in 2006 when MDA was stopped.In line with ongoing efforts to shrink the LF map, we performed the WHO recommended transmission assessment surveys (TAS in January 2012 to verify the absence of LF transmission on the main Zanzibar islands of Unguja and Pemba. Altogether, 3275 children were tested on both islands and 89 were found to be CFA positive; 70 in Pemba and 19 in Unguja. The distribution of schools with positive children was heterogeneous with pronounced spatial variation on both islands. Based on the calculated TAS cut-offs of 18 and 20 CFA positive children for Pemba and Unguja respectively, we demonstrated that transmission was still ongoing in Pemba where the cut-off was exceeded.Our findings indicated ongoing transmission of LF on Pemba in 2012. Moreover, we presented evidence from previous studies that LF transmission was also active on Unguja shortly after stopping MDA in 2006. Based on these observations the government of Zanzibar decided to resume MDA against LF on both islands in 2013.

  6. Cessation of mass drug administration for lymphatic filariasis in Zanzibar in 2006: was transmission interrupted?

    Science.gov (United States)

    Rebollo, Maria P; Mohammed, Khalfan A; Thomas, Brent; Ame, Shaali; Ali, Said Mohammed; Cano, Jorge; Escalada, Alba Gonzalez; Bockarie, Moses J

    2015-03-01

    Lymphatic filariasis (LF) is targeted for elimination through annual mass drug administration (MDA) for 4-6 years. In 2006, Zanzibar stopped MDA against LF after five rounds of MDA revealed no microfilaraemic individuals during surveys at selected sentinel sites. We asked the question if LF transmission was truly interrupted in 2006 when MDA was stopped. In line with ongoing efforts to shrink the LF map, we performed the WHO recommended transmission assessment surveys (TAS) in January 2012 to verify the absence of LF transmission on the main Zanzibar islands of Unguja and Pemba. Altogether, 3275 children were tested on both islands and 89 were found to be CFA positive; 70 in Pemba and 19 in Unguja. The distribution of schools with positive children was heterogeneous with pronounced spatial variation on both islands. Based on the calculated TAS cut-offs of 18 and 20 CFA positive children for Pemba and Unguja respectively, we demonstrated that transmission was still ongoing in Pemba where the cut-off was exceeded. Our findings indicated ongoing transmission of LF on Pemba in 2012. Moreover, we presented evidence from previous studies that LF transmission was also active on Unguja shortly after stopping MDA in 2006. Based on these observations the government of Zanzibar decided to resume MDA against LF on both islands in 2013.

  7. Fine mapping the spatial distribution and concentration of unlabeled drugs within tissue micro-compartments using imaging mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Anna Nilsson

    Full Text Available Readouts that define the physiological distributions of drugs in tissues are an unmet challenge and at best imprecise, but are needed in order to understand both the pharmacokinetic and pharmacodynamic properties associated with efficacy. Here we demonstrate that it is feasible to follow the in vivo transport of unlabeled drugs within specific organ and tissue compartments on a platform that applies MALDI imaging mass spectrometry to tissue sections characterized with high definition histology. We have tracked and quantified the distribution of an inhaled reference compound, tiotropium, within the lungs of dosed rats, using systematic point by point MS and MS/MS sampling at 200 microm intervals. By comparing drug ion distribution patterns in adjacent tissue sections, we observed that within 15 min following exposure, tiotropium parent MS ions (mass-to-charge; m/z 392.1 and fragmented daughter MS/MS ions (m/z 170.1 and 152.1 were dispersed in a concentration gradient (80 fmol-5 pmol away from the central airways into the lung parenchyma and pleura. These drug levels agreed well with amounts detected in lung compartments by chemical extraction. Moreover, the simultaneous global definition of molecular ion signatures localized within 2-D tissue space provides accurate assignment of ion identities within histological landmarks, providing context to dynamic biological processes occurring at sites of drug presence. Our results highlight an important emerging technology allowing specific high resolution identification of unlabeled drugs at sites of in vivo uptake and retention.

  8. Role of novel multidrug efflux pump involved in drug resistance in Klebsiella pneumoniae.

    Directory of Open Access Journals (Sweden)

    Vijaya Bharathi Srinivasan

    Full Text Available BACKGROUND: Multidrug resistant Klebsiella pneumoniae have caused major therapeutic problems worldwide due to the emergence of the extended-spectrum β-lactamase producing strains. Although there are >10 major facilitator super family (MFS efflux pumps annotated in the genome sequence of the K. pneumoniae bacillus, apparently less is known about their physiological relevance. PRINCIPAL FINDINGS: Insertional inactivation of kpnGH resulting in increased susceptibility to antibiotics such as azithromycin, ceftazidime, ciprofloxacin, ertapenem, erythromycin, gentamicin, imipenem, ticarcillin, norfloxacin, polymyxin-B, piperacillin, spectinomycin, tobramycin and streptomycin, including dyes and detergents such as ethidium bromide, acriflavine, deoxycholate, sodium dodecyl sulphate, and disinfectants benzalkonium chloride, chlorhexidine and triclosan signifies the wide substrate specificity of the transporter in K. pneumoniae. Growth inactivation and direct fluorimetric efflux assays provide evidence that kpnGH mediates antimicrobial resistance by active extrusion in K. pneumoniae. The kpnGH isogenic mutant displayed decreased tolerance to cell envelope stressors emphasizing its added role in K. pneumoniae physiology. CONCLUSIONS AND SIGNIFICANCE: The MFS efflux pump KpnGH involves in crucial physiological functions besides being an intrinsic resistance determinant in K. pneumoniae.

  9. Structural and functional study of YER067W, a new protein involved in yeast metabolism control and drug resistance.

    Directory of Open Access Journals (Sweden)

    Tatiana Domitrovic

    2010-06-01

    Full Text Available The genome of Saccharomyces cerevisiae is arguably the best studied eukaryotic genome, and yet, it contains approximately 1000 genes that are still relatively uncharacterized. As the majority of these ORFs have no homologs with characterized sequence or protein structure, traditional sequence-based approaches cannot be applied to deduce their biological function. Here, we characterize YER067W, a conserved gene of unknown function that is strongly induced in response to many stress conditions and repressed in drug resistant yeast strains. Gene expression patterns of YER067W and its paralog YIL057C suggest an involvement in energy metabolism. We show that yeast lacking YER067W display altered levels of reserve carbohydrates and a growth deficiency in media that requires aerobic metabolism. Impaired mitochondrial function and overall reduction of ergosterol content in the YER067W deleted strain explained the observed 2- and 4-fold increase in resistance to the drugs fluconazole and amphotericin B, respectively. Cell fractionation and immunofluorescence microscopy revealed that Yer067w is associated with cellular membranes despite the absence of a transmembrane domain in the protein. Finally, the 1.7 A resolution crystal structure of Yer067w shows an alpha-beta fold with low similarity to known structures and a putative functional site.YER067W's involvement with aerobic energetic metabolism suggests the assignment of the gene name RGI1, standing for respiratory growth induced 1. Altogether, the results shed light on a previously uncharacterized protein family and provide basis for further studies of its apparent role in energy metabolism control and drug resistance.

  10. Extent, quality and impact of patient and public involvement in antimicrobial drug development research: A systematic review.

    Science.gov (United States)

    Evans, David; Bird, Emma; Gibson, Andy; Grier, Sally; Chin, Teh Li; Stoddart, Margaret; MacGowan, Alasdair

    2018-02-01

    Patient and public involvement (PPI) is increasingly recognized as bringing a range of benefits to clinical and health services research. Recent systematic reviews have identified and synthesized many benefits (eg higher recruitment rates) and some costs (eg extra time need). Much of the literature focuses on PPI in long-term conditions rather than more acute health care in which the majority of microbiological research is undertaken. The aim was to identify the extent, quality and impact of PPI in antimicrobial drug development research. Objectives were to identify any relevant reporting of PPI in antimicrobial research; appraise the quality of reporting on PPI using recognized PPI reporting and critical appraisal tools; and extract and synthesize data on the impact of PPI. A systematic review was undertaken with a search strategy based on four word groups (PPI, patients, antimicrobial drug development and outcomes). Eight online databases were searched. English language publication, publication between 1996 and 2016 and studies describing PPI in antimicrobial drug development research. No studies were found through online searching that met the search strategy and inclusion criteria. One relevant protocol paper with a brief mention of PPI was identified through expert recommendation. Commentary papers recommending PPI were identified through website searching and expert opinion. Despite strong policy guidance encouraging PPI at the international and national levels, and anecdotal accounts of PPI taking place, evidence for the extent, quality and impact of PPI in antimicrobial drug development research has not yet appeared in the peer-reviewed literature. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

  11. Langerhans′ cell histiocytosis involving posterior elements of the dorsal spine: An unusual cause of extradural spinal mass in an adult

    Directory of Open Access Journals (Sweden)

    Devendra K Tyagi

    2011-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is a clonal proliferation of Langerhans cells occurring as an isolated lesion or as part of a systemic proliferation. It is commoner in children younger than 10 years of age with sparing of the posterior elements in more than 95% of cases. We describe a case of LCH in an adult female presenting with paraplegia. MRI revealed a well-defined extradural contrast enhancing mass at D2-D4 vertebral level involving the posterior elements of spine. D2-5 laminectomy with excision of lesion was performed which lead to marked improvement of patients neurological status. Histopathology was suggestive of eosinophilic granuloma. We describe the case, discuss its uniqueness and review the literature on this rare tumor presentation.

  12. Adverse Events Involving Radiation Oncology Medical Devices: Comprehensive Analysis of US Food and Drug Administration Data, 1991 to 2015

    Energy Technology Data Exchange (ETDEWEB)

    Connor, Michael J. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Department of Radiation Oncology, University of California Irvine School of Medicine, Irvine, California (United States); Marshall, Deborah C.; Moiseenko, Vitali; Moore, Kevin; Cervino, Laura; Atwood, Todd; Sanghvi, Parag; Mundt, Arno J.; Pawlicki, Todd [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Recht, Abram [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2017-01-01

    Purpose: Radiation oncology relies on rapidly evolving technology and highly complex processes. The US Food and Drug Administration collects reports of adverse events related to medical devices. We sought to characterize all events involving radiation oncology devices (RODs) from the US Food and Drug Administration's postmarket surveillance Manufacturer and User Facility Device Experience (MAUDE) database, comparing these with non–radiation oncology devices. Methods and Materials: MAUDE data on RODs from 1991 to 2015 were sorted into 4 product categories (external beam, brachytherapy, planning systems, and simulation systems) and 5 device problem categories (software, mechanical, electrical, user error, and dose delivery impact). Outcomes included whether the device was evaluated by the manufacturer, adverse event type, remedial action, problem code, device age, and time since 510(k) approval. Descriptive statistics were performed with linear regression of time-series data. Results for RODs were compared with those for other devices by the Pearson χ{sup 2} test for categorical data and 2-sample Kolmogorov-Smirnov test for distributions. Results: There were 4234 ROD and 4,985,698 other device adverse event reports. Adverse event reports increased over time, and events involving RODs peaked in 2011. Most ROD reports involved external beam therapy (50.8%), followed by brachytherapy (24.9%) and treatment planning systems (21.6%). The top problem types were software (30.4%), mechanical (20.9%), and user error (20.4%). RODs differed significantly from other devices in each outcome (P<.001). RODs were more likely to be evaluated by the manufacturer after an event (46.9% vs 33.0%) but less likely to be recalled (10.5% vs 37.9%) (P<.001). Device age and time since 510(k) approval were shorter among RODs (P<.001). Conclusions: Compared with other devices, RODs may experience adverse events sooner after manufacture and market approval. Close postmarket surveillance

  13. Restless Sleep and Variable Sleep Timing During Late Childhood Accelerate the Onset of Alcohol and Other Drug Involvement.

    Science.gov (United States)

    Hasler, Brant P; Kirisci, Levent; Clark, Duncan B

    2016-07-01

    Limited prospective data indicate that premorbid sleep disturbances elevate the risk for subsequent alcohol and other drug problems, yet the implications for subsequent substance involvement trajectories remain unclear. In the present analyses, we examined risk associations between sleep characteristics during late childhood and the onset of substance use and substance use disorders into adulthood. A sample of 707 children was recruited at ages 9-13 years and followed over seven additional visits through age 30 years. In 304 participants, fathers had a history of substance use disorder involving illicit drugs. Self-reported baseline sleep characteristics (restless sleep and variable sleep timing) were assessed at approximately ages 9-13 years. Assessment of alcohol, cannabis, and cocaine involvement occurred at follow-up visits. Cox proportional hazard models tested sleep characteristics as predictors of two substance-related outcomes (age at first use or diagnosis of disorder), as well as the onset of major depressive disorder. Restless sleep at baseline significantly predicted an earlier onset age for trying alcohol and cannabis and showed a trend toward predicting early onset of cannabis use disorder. Restless sleep also predicted an earlier onset of depression. Irregular sleep timing at baseline significantly predicted an earlier onset age for alcohol use disorder and showed trends toward predicting early onsets of disorders of cannabis and cocaine use. Disturbed sleep during late childhood appears to accelerate the onset of not only initial substance use but also the development of clinically defined substance use disorder. Sleep-focused preventative efforts during late childhood may reduce the incidence of mood and substance use disorders.

  14. Associations between Electronic Media Use and Involvement in Violence, Alcohol and Drug Use among United States High School Students

    Directory of Open Access Journals (Sweden)

    Denniston, Maxine

    2011-07-01

    Full Text Available Objective: We identified associations between time spent watching television and time spent playing video or computer games or using computers and involvement in interpersonal violence, alcohol and drug use in a nationally representative sample of United States high school students.Methods: We analyzed data from the 2007 national Youth Risk Behavior Survey. Exposure variables were time spent watching television and time spent playing computer or video games or using computers (hereafter denoted as “computer/video game use” on an average school day; outcome variables included multiple measures assessing involvement in violence and alcohol or drug use. Chi-square tests were used to identify statistically significant associations between each exposure variable and each of the outcome variables. We used logistic regression to obtain crude odds ratios for outcome variables with a significant chi-square p-value and to obtain adjusted odds ratios controlling for sex, race, and grade in school.Results: Overall, 35.4% (95% CI=33.1%-37.7% of students reported frequent television (TV use and 24.9% (95% CI=22.9%-27.0% reported frequent computer/video game use. A number of risk behaviors, including involvement in physical fights and initiation of alcohol use before age 13, were significantly associated with frequent TV use or frequent computer/video game use, even after controlling for sex, race/ethnicity and grade.Conclusion: Findings highlight the need for additional research to better understand the mechanisms by which electronic media exposure and health-risk behaviors are associated and for the development of strategies that seek to understand how the content and context (e.g., watching with peers, having computer in common area of media use influence risk behaviors among youth. [West J Emerg Med. 2011;12(3:310-315.

  15. Discovery and characterization of antibody variants using mass spectrometry-based comparative analysis for biosimilar candidates of monoclonal antibody drugs.

    Science.gov (United States)

    Li, Wenhua; Yang, Bin; Zhou, Dongmei; Xu, Jun; Ke, Zhi; Suen, Wen-Chen

    2016-07-01

    Liquid chromatography mass spectrometry (LC-MS) is the most commonly used technique for the characterization of antibody variants. MAb-X and mAb-Y are two approved IgG1 subtype monoclonal antibody drugs recombinantly produced in Chinese hamster ovary (CHO) cells. We report here that two unexpected and rare antibody variants have been discovered during cell culture process development of biosimilars for these two approved drugs through intact mass analysis. We then used comprehensive mass spectrometry-based comparative analysis including reduced light, heavy chains, and domain-specific mass as well as peptide mapping analysis to fully characterize the observed antibody variants. The "middle-up" mass comparative analysis demonstrated that the antibody variant from mAb-X biosimilar candidate was caused by mass variation of antibody crystalline fragment (Fc), whereas a different variant with mass variation in antibody antigen-binding fragment (Fab) from mAb-Y biosimilar candidate was identified. Endoproteinase Lys-C digested peptide mapping and tandem mass spectrometry analysis further revealed that a leucine to glutamine change in N-terminal 402 site of heavy chain was responsible for the generation of mAb-X antibody variant. Lys-C and trypsin coupled non-reduced and reduced peptide mapping comparative analysis showed that the formation of the light-heavy interchain trisulfide bond resulted in the mAb-Y antibody variant. These two cases confirmed that mass spectrometry-based comparative analysis plays a critical role for the characterization of monoclonal antibody variants, and biosimilar developers should start with a comprehensive structural assessment and comparative analysis to decrease the risk of the process development for biosimilars. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Novel culture technique involving an histone deacetylase inhibitor reduces the marginal islet mass to correct streptozotocin-induced diabetes.

    Science.gov (United States)

    Shin, Jun-Seop; Min, Byoung-Hoon; Lim, Jong-Yeon; Kim, Byoung-Keun; Han, Hyun-Ju; Yoon, Kun-Ho; Kim, Sang-Joon; Park, Chung-Gyu

    2011-01-01

    Islet transplantation is limited by the difficulties in isolating the pancreatic islets from the cadaveric donor and maintaining them in culture. To increase islet viability and function after isolation, here we present a novel culture technique involving an histone deacetylase inhibitor (HDACi) to rejuvenate the isolated islets. Pancreatic islets were isolated from Sprague-Dawley (SD) rats and one group (FIs; freshly isolated islets) was used after overnight culture and the other group (RIs; rejuvenated islet) was subjected to rejuvenation culture procedure, which is composed of three discrete steps including degranulation, chromatin remodeling, and regranulation. FIs and RIs were compared with regard to intracellular insulin content, glucose-stimulated insulin secretion (GSIS) capacity, gene expression profile, viability and apoptosis rate under oxidative stresses, and the engraftment efficacy in the xenogeneic islet transplantation models. RIs have been shown to have 1.9 ± 0.28- and 1.7 ± 0.31-fold greater intracellular insulin content and GSIS capacity, respectively, than FIs. HDACi increased overall histone acetylation levels, with inducing increased expression of many genes including insulin 1, insulin 2, GLUT2, and Ogg1. This enhanced islet capacity resulted in more resistance against oxidative stresses and increase of the engraftment efficacy shown by reduction of twofold marginal mass of islets in xenogeneic transplantation model. In conclusion, a novel rejuvenating culture technique using HDACi as chromatin remodeling agents improved the function and viability of the freshly isolated islets, contributing to the reduction of islet mass for the control of hyperglycemia in islet transplantation.

  17. Simultaneous identification of abused drugs, benzodiazepines, and new psychoactive substances in urine by liquid chromatography tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    Hei-Hwa Lee

    2016-03-01

    Full Text Available A literature search reveals no studies concerning simultaneous identification of commonly abused drugs, benzodiazepines, and new psychoactive substances in urine by liquid chromatography tandem mass spectrometry (LC–MS/MS. We developed and validated an LC–MS/MS method for simultaneous identification of multiple abused drugs, benzodiazepines, and new psychoactive substances in urine from suspected drug abusers. The instrument was operated in multiple-reaction monitoring using an electrospray ionization mode. Chromatograms were separated using an ACE5 C18 column on a gradient of acetonitrile. After liquid–liquid extraction, samples were passed through a 0.22-μm polyvinylidene difluoride filter before injection into the LC–MS/MS. The limits of quantitation ranged from 0.5 ng/mL to 31.3 ng/mL. The linearity ranged from 0.5 ng/mL to 200 ng/mL. The precision results were below 15.4% (intraday and 18.7% (interday. The intraday accuracy ranged from 85.9% to 121.0%; interday accuracy ranged from 66.1% to 128.7%. The proposed method was applied to 769 urine samples. The most common three drugs identified were ketamine, amphetamine, and opiates. The drug positive rate for one or more drugs was 79.6%. Our results demonstrate the suitability of the LC–MS/MS method for simultaneous identification of multiple abused drugs, benzodiazepines, and new psychoactive substances in urine.

  18. Determination of Four Anti-epileptic Drugs in Plasma Using Ultra Performance Liquid Chromatography with Mass Detection Technique.

    Science.gov (United States)

    Hassib, Sonia T; Hashem, Hanaa M A; Mahrouse, Marianne A; Mostafa, Eman A

    2018-04-10

    Status epilepticus (SE) is considered the second most frequent neurologic emergency. Its therapeutic management is performed using sequential anti-epileptic drug regimens. Diazepam (DIA), midazolam (MID), phenytoin (PHT) and phenobarbital (PB) are four drugs of different classes used sequentially in the management of SE. A sensitive, selective, accurate and precise method was developed and validated for simultaneous determination of the four anti-epileptic drugs in human plasma. Their separation and quantification were achieved using ultra performance liquid chromatography (UPLC) with mass detection using carbamazepine as internal standard (IS). For the first three drugs and IS, UPLC-MS/MS with electrospray ionization working in multiple reaction monitoring mode was used at the following transitions: m/z 285→193 for DIA, m/z 326→291 for MID, m/z 253→182 for PHT and m/z 237→194, 237→192 for IS. For the fourth drug (PB), molecular ion peak of PB [M+H] + at m/z 233 was used for its quantitation. The method was linear over concentration ranges of 5-500 ng/ml for DIA and MID and 0.25-20 μg/ml for PHT and PB, respectively. Bio-analytical validation of the developed method was carried out according to European Medicines Agency guidelines. The developed method can be applied for routine drug analysis, therapeutic drug monitoring and bioequivalence studies. This article is protected by copyright. All rights reserved.

  19. Spray-inlet microwave plasma torch ionization tandem mass spectrometry for the direct detection of drug samples in liquid solutions.

    Science.gov (United States)

    Miao, Meng; Zhao, Gaosheng; Wang, Yaliang; Xu, Li; Dong, Junguo; Cheng, Ping

    2017-12-30

    Drug abuse or dependence results in a series of social problems, including crime and traffic accidents. Spray-inlet microwave plasma torch tandem mass spectrometry (MPT-MS/MS) was developed and used for the direct detection of such drugs in liquid solutions. Drug sample solutions were directly sprayed into the flame of an MPT by a sampling pump and the ions produced by Penning ionization and ion-molecule reactions were guided into a quadrupole time-of-flight (QTOF) tandem mass spectrometer for mass analysis. The MPT was operated at 40 W and 2.45 GHz in a 700 mL/min argon flow both for the inner and middle plasma. Intact quasi-molecular and molecular ions of various drugs were successfully characterized by spray-inlet MPT-MS/MS. The analysis of one sample was finished within 30 s. Furthermore, the method exhibited excellent efficiency, precision and sensitivity, and the limits of detection and limits of quantification of the samples in methanol were in the range of 5.25-60.0 and 17.5-200 ng g -1 , respectively. Excellent linearities with coefficients of determination (R 2 ) of 0.9627-0.9980 were verified in the range 0.05-50 μg g -1 . Four different beverages purchased locally were also analyzed with spray-inlet MPT-MS/MS, and caffeine was directly determined in two of the beverages. By adding six standard drug samples to sport drinks (each drug was 1 μg g -1 ) and Chinese spirit (each drug was 0.1 μg g -1 ), all the drugs except for caffeine were detected successfully. This study indicates that spay-inlet MPT-MS/MS is an effective method for direct and rapid identification of drug solutions, and it has substantial potential for fast and sensitive drug residue detection. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Effects of meal composition and meal timing on the expression of genes involved in hepatic drug metabolism in rats.

    Directory of Open Access Journals (Sweden)

    E M de Vries

    Full Text Available With chronotherapy, drug administration is synchronized with daily rhythms in drug clearance and pharmacokinetics. Daily rhythms in gene expression are centrally mastered by the suprachiasmatic nucleus of the hypothalamus as well as by tissue clocks containing similar molecular mechanisms in peripheral organs. The central timing system is sensitive to changes in the external environment such as those of the light-dark cycle, meal timing and meal composition. We investigated how changes in diet composition and meal timing would affect the daily hepatic expression rhythms of the nuclear receptors PXR and CAR and of enzymes involved in P450 mediated drug metabolism, as such changes could have consequences for the practice of chronotherapy.Rats were subjected to either a regular chow or a free choice high-fat-high-sugar (fcHFHS diet. These diets were provided ad libitum, or restricted to either the light phase or the dark phase. In a second experiment, rats had access to chow either ad libitum or in 6 meals equally distributed over 24 hours.Pxr, Alas1 and Por displayed significant day-night rhythms under ad libitum chow fed conditions, which for Pxr was disrupted under fcHFHS diet conditions. Although no daily rhythms were detected in expression of CAR, Cyp2b2 and Cyp3a2, the fcHFHS diet did affect basal expression of these genes. In chow fed rats, dark phase feeding induced a diurnal rhythm in Cyp2b2 expression while light phase feeding induced a diurnal rhythm in Car expression and completely shifted the peak expression of Pxr, Car, Cyp2b2, Alas1 and Por. The 6-meals-a-day feeding only abolished the Pxr rhythm but not the rhythms of the other genes.We conclude that although nuclear receptors and enzymes involved in the regulation of hepatic drug metabolism are sensitive to meal composition, changes in meal timing are mainly effectuated via changes in the molecular clock.

  1. Impact of an Ivermectin Mass Drug Administration on Scabies Prevalence in a Remote Australian Aboriginal Community.

    Science.gov (United States)

    Kearns, Thérèse M; Speare, Richard; Cheng, Allen C; McCarthy, James; Carapetis, Jonathan R; Holt, Deborah C; Currie, Bart J; Page, Wendy; Shield, Jennifer; Gundjirryirr, Roslyn; Bundhala, Leanne; Mulholland, Eddie; Chatfield, Mark; Andrews, Ross M

    2015-10-01

    Scabies is endemic in many Aboriginal and Torres Strait Islander communities, with 69% of infants infected in the first year of life. We report the outcomes against scabies of two oral ivermectin mass drug administrations (MDAs) delivered 12 months apart in a remote Australian Aboriginal community. Utilizing a before and after study design, we measured scabies prevalence through population census with sequential MDAs at baseline and month 12. Surveys at months 6 and 18 determined disease acquisition and treatment failures. Scabies infestations were diagnosed clinically with additional laboratory investigations for crusted scabies. Non-pregnant participants weighing ≥15 kg were administered a single 200 μg/kg ivermectin dose, repeated after 2-3 weeks if scabies was diagnosed, others followed a standard alternative algorithm. We saw >1000 participants at each population census. Scabies prevalence fell from 4% at baseline to 1% at month 6. Prevalence rose to 9% at month 12 amongst the baseline cohort in association with an identified exposure to a presumptive crusted scabies case with a higher prevalence of 14% amongst new entries to the cohort. At month 18, scabies prevalence fell to 2%. Scabies acquisitions six months after each MDA were 1% and 2% whilst treatment failures were 6% and 5% respectively. Scabies prevalence reduced in the six months after each MDA with a low risk of acquisition (1-2%). However, in a setting where living conditions are conducive to high scabies transmissibility, exposure to presumptive crusted scabies and population mobility, a sustained reduction in prevalence was not achieved. Australian New Zealand Clinical Trial Register (ACTRN-12609000654257).

  2. Scabies community prevalence and mass drug administration in two Fijian villages.

    Science.gov (United States)

    Haar, Karin; Romani, Lucia; Filimone, Raikanikoda; Kishore, Kamal; Tuicakau, Meciusela; Koroivueta, Josefa; Kaldor, John M; Wand, Handan; Steer, Andrew; Whitfeld, Margot

    2014-06-01

    Scabies has been estimated to affect approximately 300 million people worldwide each year. Scabies rates are high and pose a significant public health problem in Fiji. Community-based comparison treatment trials have not been undertaken. We estimated scabies prevalence and compared the efficacy and tolerability of mass drug administration (MDA) of benzyl benzoate lotion (BB) or oral ivermectin (IVM) in two villages in Fiji. A prospective MDA trial was undertaken in two Fijian villages, comparing three daily applications of BB with single dose IVM or permethrin cream for those aged under two years. The therapies were offered to all community members regardless of the presence of scabies or its symptoms. The difference in prevalence was measured before and after the intervention and absolute risk reduction (ARR) and relative risk (RR) calculated. In the BB group, there were 572 eligible participants, of whom 435 (76%) enrolled and 201 (46%) returned for follow-up. In the IVM group, there were 667 eligible participants, of whom 325 (49%) enrolled and 126 (39%) returned. Scabies prevalence was lower after the intervention in both groups. It fell from 37.9 to 20.0% (ARR 18.0%; RR 0.52) in the BB group and from 23.7 to 9.5% (ARR 14.2%; RR 0.40) in the IVM group. Our study provides proof of principle that MDA for scabies can reduce scabies prevalence at the community level, and that there was no significant difference in this trial between BB and oral IVM. © 2013 The Authors. International Journal of Dermatology published by John Wiley & Sons Ltd on behalf of The International Society of Dermatology.

  3. Analysis of drugs of abuse in wastewater by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    van Nuijs, Alexander L N; Tarcomnicu, Isabela; Bervoets, Lieven; Blust, Ronny; Jorens, Philippe G; Neels, Hugo; Covaci, Adrian

    2009-10-01

    The simultaneous analysis of nine drugs of abuse (DOAs) and their metabolites (amphetamine, methamphetamine, methylenedioxymethamphetamine, methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, cocaine, benzoylecgonine, ecgonine methyl ester and 6-monoacetylmorphine) in wastewater based on hydrophilic interaction liquid chromatography (HILIC) coupled to tandem mass spectrometry (MS/MS) was optimised and validated. For each analyte, the deuterated analogue was used for quantification. The separation by HILIC showed good performance for all compounds, especially for the hydrophilic compounds, which elute early (amphetamine-like stimulants) or show no retention (ecgonine methyl ester) in reversed-phase liquid chromatography. Sample preparation based on solid-phase extraction was optimised by comparing Oasis HLB and Oasis MCX sorbents for various parameters such as sample pH, amount of sorbent bed and washing solvent. The method was validated for each compound by assessing the following parameters (following International Conference on Harmonisation guidelines): specificity, limit of quantification (LOQ), linearity, accuracy, precision, recovery and matrix effects. LOQs were 2 ng/L for 6-monoacetylmorphine, ecgonine methyl ester and amphetamine and 1 ng/L for the rest of the compounds, corresponding with the lowest point in the calibration curve. Except for 6-monoacetylmorphine, all compounds were detected from 1 to 819 ng/L in influent wastewater samples (n = 12) collected from 11 different wastewater treatment plants across Belgium. The presence of ecgonine methyl ester in wastewater could be demonstrated for the first time. In the future, the new HILIC-MS/MS method will be applied to assess the use of DOAs in Belgium using the "sewage epidemiology" approach.

  4. Optimising strategies for Plasmodium falciparum malaria elimination in Cambodia: primaquine, mass drug administration and artemisinin resistance.

    Directory of Open Access Journals (Sweden)

    Richard J Maude

    Full Text Available Malaria elimination requires a variety of approaches individually optimized for different transmission settings. A recent field study in an area of low seasonal transmission in South West Cambodia demonstrated dramatic reductions in malaria parasite prevalence following both mass drug administration (MDA and high treatment coverage of symptomatic patients with artemisinin-piperaquine plus primaquine. This study employed multiple combined strategies and it was unclear what contribution each made to the reductions in malaria.A mathematical model fitted to the trial results was used to assess the effects of the various components of these interventions, design optimal elimination strategies, and explore their interactions with artemisinin resistance, which has recently been discovered in Western Cambodia. The modelling indicated that most of the initial reduction of P. falciparum malaria resulted from MDA with artemisinin-piperaquine. The subsequent continued decline and near elimination resulted mainly from high coverage with artemisinin-piperaquine treatment. Both these strategies were more effective with the addition of primaquine. MDA with artemisinin combination therapy (ACT increased the proportion of artemisinin resistant infections, although much less than treatment of symptomatic cases with ACT, and this increase was slowed by adding primaquine. Artemisinin resistance reduced the effectiveness of interventions using ACT when the prevalence of resistance was very high. The main results were robust to assumptions about primaquine action, and immunity.The key messages of these modelling results for policy makers were: high coverage with ACT treatment can produce a long-term reduction in malaria whereas the impact of MDA is generally only short-term; primaquine enhances the effect of ACT in eliminating malaria and reduces the increase in proportion of artemisinin resistant infections; parasite prevalence is a better surveillance measure for

  5. Effects of the antioxidant drug tempol on renal oxygenation in mice with reduced renal mass

    Science.gov (United States)

    Lai, En Yin; Luo, Zaiming; Onozato, Maristela L.; Rudolph, Earl H.; Solis, Glenn; Jose, Pedro A.; Wellstein, Anton; Aslam, Shakil; Quinn, Mark T.; Griendling, Kathy; Le, Thu; Li, Ping; Palm, Fredrik; Welch, William J.

    2012-01-01

    We tested the hypothesis that reactive oxygen species (ROS) contributed to renal hypoxia in C57BL/6 mice with ⅚ surgical reduction of renal mass (RRM). ROS can activate the mitochondrial uncoupling protein 2 (UCP-2) and increase O2 usage. However, UCP-2 can be inactivated by glutathionylation. Mice were fed normal (NS)- or high-salt (HS) diets, and HS mice received the antioxidant drug tempol or vehicle for 3 mo. Since salt intake did not affect the tubular Na+ transport per O2 consumed (TNa/QO2), further studies were confined to HS mice. RRM mice had increased excretion of 8-isoprostane F2α and H2O2, renal expression of UCP-2 and renal O2 extraction, and reduced TNa/QO2 (sham: 20 ± 2 vs. RRM: 10 ± 1 μmol/μmol; P Tempol normalized all these parameters while further increasing compensatory renal growth and glomerular volume. RRM mice had preserved blood pressure, glomeruli, and patchy tubulointerstitial fibrosis. The patterns of protein expression in the renal cortex suggested that RRM kidneys had increased ROS from upregulated p22phox, NOX-2, and -4 and that ROS-dependent increases in UCP-2 led to hypoxia that activated transforming growth factor-β whereas erythroid-related factor 2 (Nrf-2), glutathione peroxidase-1, and glutathione-S-transferase mu-1 were upregulated independently of ROS. We conclude that RRM activated distinct processes: a ROS-dependent activation of UCP-2 leading to inefficient renal O2 usage and cortical hypoxia that was offset by Nrf-2-dependent glutathionylation. Thus hypoxia in RRM may be the outcome of NADPH oxidase-initiated ROS generation, leading to mitochondrial uncoupling counteracted by defense pathways coordinated by Nrf-2. PMID:22492941

  6. Efficacy of a group-based multimedia HIV prevention intervention for drug-involved women under community supervision: project WORTH.

    Science.gov (United States)

    El-Bassel, Nabila; Gilbert, Louisa; Goddard-Eckrich, Dawn; Chang, Mingway; Wu, Elwin; Hunt, Tim; Epperson, Matt; Shaw, Stacey A; Rowe, Jessica; Almonte, Maria; Witte, Susan

    2014-01-01

    This study is designed to address the need for evidence-based HIV/STI prevention approaches for drug-involved women under criminal justice community supervision. We tested the efficacy of a group-based traditional and multimedia HIV/STI prevention intervention (Project WORTH: Women on the Road to Health) among drug-involved women under community supervision. We randomized 306 women recruited from community supervision settings to receive either: (1) a four-session traditional group-based HIV/STI prevention intervention (traditional WORTH); (2) a four-session multimedia group-based HIV/STI prevention intervention that covered the same content as traditional WORTH but was delivered in a computerized format; or (3) a four-session group-based Wellness Promotion intervention that served as an attention control condition. The study examined whether the traditional or multimedia WORTH intervention was more efficacious in reducing risks when compared to Wellness Promotion; and whether multimedia WORTH was more efficacious in reducing risks when compared to traditional WORTH. Primary outcomes were assessed over the 12-month post-intervention period and included the number of unprotected sex acts, the proportion of protected sex acts, and consistent condom use. At baseline, 77% of participants reported unprotected vaginal or anal sex (n = 237) and 63% (n = 194) had multiple sex partners. Women assigned to traditional or multimedia WORTH were significantly more likely than women assigned to the control condition to report an increase in the proportion of protected sex acts (β = 0.10; 95% CI = 0.02-0.18) and a decrease in the number of unprotected sex acts (IRR = 0.72; 95% CI = 0.57-0.90). The promising effects of traditional and multimedia WORTH on increasing condom use and high participation rates suggest that WORTH may be scaled up to redress the concentrated epidemics of HIV/STIs among drug-involved women in the criminal justice system. Clinical

  7. [Use of time-of-flight mass spectrometry with ionization division fragments of californium-252 for studying the mechanisms of action of drugs on DNA and its components].

    Science.gov (United States)

    Sukhodub, L F; Grebenik, L I; Chivanov, V D

    1994-01-01

    Using soft-ionization mass spectrometry (252-Cf particle desorption mass spectrometry, PDMS) a minor adduct of anticancer drug prospidine and deoxyguanosine-5-phosphate (pdG) has been found. It has been shown experimentally that PDMS is very useful for study of biological mixtures as well as mechanisms of interactions between drugs and biomolecules.

  8. 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.

  9. A systematic review of factors that shape implementation of mass drug administration for lymphatic filariasis in sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Adam Silumbwe

    2017-05-01

    Full Text Available Abstract Background Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. Methods A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. Results The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Conclusion Mass drug administration for lymphatic filariasis elimination programmes should design their implementation

  10. A systematic review of factors that shape implementation of mass drug administration for lymphatic filariasis in sub-Saharan Africa.

    Science.gov (United States)

    Silumbwe, Adam; Zulu, Joseph Mumba; Halwindi, Hikabasa; Jacobs, Choolwe; Zgambo, Jessy; Dambe, Rosalia; Chola, Mumbi; Chongwe, Gershom; Michelo, Charles

    2017-05-22

    Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF) elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA) region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs) through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Mass drug administration for lymphatic filariasis elimination programmes should design their implementation strategies differently based on specific contextual factors to

  11. Femtosecond dynamics of a non-steroidal anti-inflammatory drug (piroxicam) in solution: The involvement of twisting motion

    Science.gov (United States)

    Gil, Michał; Douhal, Abderrazzak

    2008-06-01

    In this contribution, we report on fast and ultrafast dynamics of a non-steroidal anti-inflammatory drug, piroxicam (PX), in methyl acetate (MAC) and triacetin (TAC), two solvents of different viscosities. The enol form of PX undergoes a femtosecond (shorter than 100 fs) electronically excited state intramolecular proton-transfer reaction to produce keto tautomers. These structures exhibit an internal twisting motion to generate keto rotamers in ˜2-5 ps, a time being longer in TAC. The transient absorption/emission spectrum is very broad indicating that the potential-energy surface at the electronically excited state is very flat, and reflecting the involvement of several coordinates along which the wavepacket of the fs-produced structures evolve.

  12. Classical neurotransmitters and neuropeptides involved in major depression in a multi-neurotransmitter system: a focus on antidepressant drugs.

    Science.gov (United States)

    Werner, Felix-Martin; Coveñas, R

    2013-01-01

    We summarize the alterations of classical neurotransmitters and neuropeptides and the corresponding subreceptors involved in major depression. Neuronal circuits in the brainstem, hippocampus and hypothalamus are developed, since they can be used to derive a multimodal pharmacotherapy. In this sense, serotonin hypoactivity could occur through a strong presynaptic inhibition of glutaminergic neurons via the subtype 5 of metabotropic glutaminergic receptors, and noradrenaline hypoactivity could be due to an enhanced presynaptic inhibition of GABAergic neurons via GABAB receptors. In the hippocampus, dopamine hypoactivity leads to a decreased positive effect. In clinical trials, the antidepressant effect of drugs interfering with the mentioned subreceptors, for example the triple reuptake inhibitor amitifadine, is being investigated. Moreover, the alterations of neuropeptides, such as corticotropin-releasing hormone, neuropeptide Y and galanin are pointed out. The additional antidepressant effect of analogs, agonists and antagonists of the mentioned neuropeptides should be examined.

  13. A novel compact mass detection platform for the open access (OA) environment in drug discovery and early development.

    Science.gov (United States)

    Gao, Junling; Ceglia, Scott S; Jones, Michael D; Simeone, Jennifer; Antwerp, John Van; Zhang, Li-Kang; Ross, Charles W; Helmy, Roy

    2016-04-15

    A new 'compact mass detector' co-developed with an instrument manufacturer (Waters Corporation) as an interface for liquid chromatography (LC), specifically Ultra-high performance LC(®) (UPLC(®) or UHPLC) analysis was evaluated as a potential new Open Access (OA) LC-MS platform in the Drug Discovery and Early Development space. This new compact mass detector based platform was envisioned to provide increased reliability and speed while exhibiting significant cost, noise, and footprint reductions. The new detector was evaluated in batch mode (typically 1-3 samples per run) to monitor reactions and check purity, as well as in High Throughput Screening (HTS) mode to run 24, 48, and 96 well plates. The latter workflows focused on screening catalysis conditions, process optimization, and library work. The objective of this investigation was to assess the performance, reliability, and flexibility of the compact mass detector in the OA setting for a variety of applications. The compact mass detector results were compared to those obtained by current OA LC-MS systems, and the capabilities and benefits of the compact mass detector in the open access setting for chemists in the drug discovery and development space are demonstrated. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Involvement of cannabinoid CB1 receptors in drug addiction: effects of rimonabant on behavioral responses induced by cocaine.

    Science.gov (United States)

    Filip, Małgorzata; Gołda, Anna; Zaniewska, Magdalena; McCreary, Andrew C; Nowak, Ewa; Kolasiewicz, Wacław; Przegaliński, Edmund

    2006-01-01

    A lot of evidence indicate that endocannabinoids and cannabinoid CB(1) receptors are implicated in drug addiction. In the present study, we investigated the effect of the cannabinoid CB(1) receptor antagonist/partial agonist rimonabant on the cocaine-maintained reinforcement and relapse to cocaine seeking as well as on the cocaine challenge-induced hyperactivity in sensitized rats and on discriminative stimulus effects of cocaine in rats. We found that endocannabinoids were not involved in maintenance of cocaine reinforcement and its subjective effects since pharmacological blockade of cannabinoid CB(1) receptors altered neither self-administration nor discriminative stimulus effects of cocaine. On the other hand, withdrawal from repeated access or exposure to cocaine and then a reinstatement of cocaine-seeking behavior or a sensitized locomotor response to a single cocaine challenge, respectively, was potently reduced by pretreatment with rimonabant. The latter observations may show that repeated cocaine treatment and the drug withdrawal produce--apart from behavioral effects--also different neural consequences in the endocannabinoid systems in rats.

  15. Emergency Department Visits Involving Misuse and Abuse of the Antipsychotic Quetiapine: Results from the Drug Abuse Warning Network (DAWN

    Directory of Open Access Journals (Sweden)

    Margaret E. Mattson

    2015-01-01

    Full Text Available Case reports in medical literature suggest that the atypical antipsychotic quetiapine, a medication not previously considered to have abuse potential, is now being subject to misuse and abuse (MUA; ie, taken when not prescribed for them or used in a way other than instructed by their health professional. Here we present systematic, nationally representative data from the 2005 to 2011 Drug Abuse Warning Network (DAWN for prevalence of emergency department (ED visits among the U.S. general population involving quetiapine and related to MUA, suicide attempts, and adverse reactions. Nationally, quetiapine-related ED visits increased 90% between 2005 and 2011, from 35,581 ED visits to 67,497. DAWN data indicate that when used without medical supervision for recreational/self-medication purposes, quetiapine poses health risks for its users, especially among polydrug users and women. These findings suggest that the medical and public health communities should increase vigilance concerning this drug and its potential for MUA.

  16. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...

  17. Rapid screening for drugs of abuse in biological fluids by ultra high performance liquid chromatography/Orbitrap mass spectrometry.

    Science.gov (United States)

    Jagerdeo, Eshwar; Schaff, Jason E

    2016-08-01

    We present a UPLC(®)-High Resolution Mass Spectrometric method to simultaneously screen for nineteen benzodiazepines, twelve opiates, cocaine and three metabolites, and three "Z-drug" hypnotic sedatives in both blood and urine specimens. Sample processing consists of a high-speed, high-temperature enzymatic hydrolysis for urine samples followed by a rapid supported liquid extraction (SLE). The combination of ultra-high resolution chromatography with high resolution mass spectrometry allows all 38 analytes to be uniquely detected with a ten minute analytical run. Limits of detection for all target analytes are 3ng/mL or better, with only 0.3mL of specimen used for analysis. The combination of low sample volume with fast processing and analysis makes this method a suitable replacement for immunoassay screening of the targeted drug classes, while providing far superior specificity and better limits of detection than can routinely be obtained by immunoassay. Published by Elsevier B.V.

  18. Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine.

    Science.gov (United States)

    Maurer, Hans H; Sauer, Christoph; Theobald, Denis S

    2006-06-01

    This review summarizes the major metabolic pathways of the drugs of abuse, tetrahydrocannabinol, cocaine, heroin, morphine, and codeine, in humans including the involvement of isoenzymes. This knowledge may be important for predicting their possible interactions with other xenobiotics, understanding pharmaco-/toxicokinetic and pharmacogenetic variations, toxicological risk assessment, developing suitable toxicological analysis procedures, and finally for understanding certain pitfalls in drug testing. The detection times of these drugs and/or their metabolites in biological samples are summarized and the implications of the presented data on the possible interactions of drugs of abuse with other xenobiotics, ie, inhibition or induction of individual polymorphic and nonpolymorphic isoenzymes, discussed.

  19. Dilute-and-shoot coupled to nanoflow liquid chromatography high resolution mass spectrometry for the determination of drugs of abuse and sport drugs in human urine.

    Science.gov (United States)

    Alcántara-Durán, Jaime; Moreno-González, David; Beneito-Cambra, Miriam; García-Reyes, Juan F

    2018-05-15

    In this work, a sensitive nanoflow liquid chromatography high-resolution mass spectrometry screening method has been developed for the determination of multiclass drugs of abuse and sport drugs in human urine. 81 drugs belonging to different multiclass pharmaceuticals were targeted. The method is based on the use of a nanoLC column (75 µm × 150 mm, 3 µm particle size and 100 Å pore) with the nanospray emitter tip integrated so that dead volumes are significantly minimized. Data acquisition method included both full-scan and all ion fragmentation experiments using an Orbitrap analyser (Q-Exactive) operated in the positive ionization mode. To increase laboratory throughput, a dilute-and-shoot methodology has been tested and proposed, based solely on direct urine dilution without further sample workup. Matrix effects were evaluated, showing a negligible effect for all studied compounds when a dilution 1:50 was implemented. Despite this high-dilution factor, limits of quantification were still satisfactory, with values below 5 µg L -1 in most cases, being lower than their minimum required performance limits correspond established by the World Anti-Doping Agency. Therefore, the use of the dilute-and-shoot method with the enhanced sensitivity provided by nanoflow LC setup could be useful tool for the determination of studied compounds in drug testing, thus increasing laboratory performance, because a minimum sample treatment steps are required. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Strongyloides seroprevalence before and after an ivermectin mass drug administration in a remote Australian Aboriginal community.

    Directory of Open Access Journals (Sweden)

    Therese M Kearns

    2017-05-01

    Full Text Available Strongyloides seroprevalence is hyper-endemic in many Australian Aboriginal and Torres Strait Islander communities, ranging from 35-60%. We report the impact on Strongyloides seroprevalence after two oral ivermectin mass drug administrations (MDAs delivered 12 months apart in a remote Australian Aboriginal community.Utilizing a before and after study design, we measured Strongyloides seroprevalence through population census with sequential MDAs at baseline and month 12. Surveys at months 6 and 18 determined changes in serostatus. Serodiagnosis was undertaken by ELISA that used sonicated Strongyloides ratti antigen to detect anti-Strongyloides IgG. Non-pregnant participants weighing ≥15 kg were administered a single 200 μg/kg ivermectin dose, repeated after 10-42 days if Strongyloides and/or scabies was diagnosed; others followed a standard alternative algorithm. A questionnaire on clinical symptoms was administered to identify adverse events from treatment and self-reported symptoms associated with serostatus.We surveyed 1013 participants at the baseline population census and 1060 (n = 700 from baseline cohort and 360 new entrants at month 12. Strongyloides seroprevalence fell from 21% (175/818 at baseline to 5% at month 6. For participants from the baseline cohort this reduction was sustained at month 12 (34/618, 6%, falling to 2% at month 18 after the second MDA. For new entrants to the cohort at month 12, seroprevalence reduced from 25% (75/297 to 7% at month 18. Strongyloides positive seroconversions for the baseline cohort six months after each MDA were 2.5% (4/157 at month 6 and 1% at month 18, whilst failure to serorevert remained unchanged at 18%. At 12 months, eosinophilia was identified in 59% of baseline seropositive participants and 89% of seropositive new entrants, compared with 47%baseline seronegative participants and 51% seronegative new entrants. Seropositivity was not correlated with haemoglobin or any self-reported clinical

  1. Is mass drug administration against lymphatic filariasis required in urban settings? The experience in Kano, Nigeria.

    Science.gov (United States)

    Pam, Dung D; de Souza, Dziedzom K; D'Souza, Susan; Opoku, Millicent; Sanda, Safiya; Nazaradden, Ibrahim; Anagbogu, Ifeoma N; Okoronkwo, Chukwu; Davies, Emmanuel; Elhassan, Elisabeth; Molyneux, David H; Bockarie, Moses J; Koudou, Benjamin G

    2017-10-01

    The Global Programme to Eliminate Lymphatic Filariasis (GPELF), launched in 2000, has the target of eliminating the disease as a public health problem by the year 2020. The strategy adopted is mass drug administration (MDA) to all eligible individuals in endemic communities and the implementation of measures to reduce the morbidity of those suffering from chronic disease. Success has been recorded in many rural endemic communities in which elimination efforts have centered. However, implementation has been challenging in several urban African cities. The large cities of West Africa, exemplified in Nigeria in Kano are challenging for LF elimination program because reaching 65% therapeutic coverage during MDA is difficult. There is therefore a need to define a strategy which could complement MDA. Thus, in Kano State, Nigeria, while LF MDA had reached 33 of the 44 Local Government Areas (LGAs) there remained eleven 'urban' LGAs which had not been covered by MDA. Given the challenges of achieving at least 65% coverage during MDA implementation over several years in order to achieve elimination, it may be challenging to eliminate LF in such settings. In order to plan the LF control activities, this study was undertaken to confirm the LF infection prevalence in the human and mosquito populations in three urban LGAs. The prevalence of circulating filarial antigen (CFA) of Wuchereria bancrofti was assessed by an immuno-chromatography test (ICT) in 981 people in three urban LGAs of Kano state, Nigeria. Mosquitoes were collected over a period of 4 months from May to August 2015 using exit traps, gravid traps and pyrethrum knock-down spray sheet collections (PSC) in different households. A proportion of mosquitoes were analyzed for W. bancrofti, using dissection, loop-mediated isothermal amplification (LAMP) assay and conventional polymerase chain reaction (PCR). The results showed that none of the 981 subjects (constituted of West Africa may not be of significant importance

  2. Maintaining effective mass drug administration for lymphatic filariasis through in-process monitoring in Sierra Leone

    Directory of Open Access Journals (Sweden)

    Hodges Mary H

    2012-10-01

    Full Text Available Abstract Background Since 2007 Sierra Leone has conducted mass drug administration (MDA for the elimination of lymphatic filariasis (LF implemented by unpaid community health volunteers (CHVs. Other health campaigns such as Mother and Child Health Weeks (MCHW pay for services to be implemented at community level and these persons are then known as community health workers (CHWs. In 2010, the LF MDA in the 12 districts of the Southern, Northern and Eastern Provinces un-expectantly coincided with universal distribution of Long Lasting Insecticide Treated Nets (LLITNs during the MCHW. In-process monitoring of LF MDA was performed to ensure effective coverage was attained in hard to reach sites (HTR in both urban and rural locations where vulnerable populations reside. Methods Independent monitors interviewed individuals eligible for LF MDA and tallied those who recalled having taken ivermectin and albendazole, calculated program coverage and reported results daily by phone. Monitoring of coverage in HTR sites in the 4 most rapidly urbanizing towns was performed after 4 weeks of LF MDA and again after 8 weeks throughout all 12 districts. End process monitoring was performed in randomly selected HTR sites not previously sampled throughout all 12 districts and compared to coverage calculated from the pre-MDA census and reported treatments. Results Only one town had reached effective program coverage (≥80% after 4 weeks following which CHWs were recruited for LF MDA in all district headquarter towns. After 8 weeks only 4 of 12 districts had reached effective coverage so LF MDA was extended for a further month in all districts. By 12 weeks effective program coverage had been reached in all districts except Port Loko and there was no significant difference between those interviewed in communities versus households or by sex. Effective epidemiological coverage (≥65% was reported in all districts and overall was significantly higher in males versus

  3. Liquid Microjunction Surface Sampling Probe Electrospray Mass Spectrometry for Detection of Drugs and Metabolites in Thin Tissue Sections

    Energy Technology Data Exchange (ETDEWEB)

    Van Berkel, Gary J [ORNL; Kertesz, Vilmos [ORNL; Koeplinger, Kenneth A. [Merck Research Laboratories; Vavek, Marissa [Merck Research Laboratories; Kong, Ah-Ng Tony [Rutgers University

    2008-01-01

    A self-aspirating, liquid micro-junction surface sampling probe/electrospray emitter mass spectrometry system was demonstrated for use in the direct analysis of spotted and dosed drugs and their metabolites in thin tissue sections. Proof-of-principle sampling and analysis directly from tissue without the need for sample preparation was demonstrated first by raster scanning a region on a section of rat liver onto which reserpine was spotted. The mass spectral signal from selected reaction monitoring was used to develop a chemical image of the spotted drug on the tissue. The probe was also used to selectively spot sample areas of sagittal whole mouse body tissue sections that had been dosed orally (90 mg/kg) with R,S-sulforaphane 3 hrs prior to sacrifice. Sulforaphane and its glutathione and N-acetyl cysteine conjugates were monitored with selected reaction monitoring and detected in the stomach and various other tissues from the dosed mouse. No signal for these species was observed in the tissue from a control mouse. The same dosed tissue section was used to illustrate the possibility of obtaining a line scan across the whole body section. In total these results illustrate the potential for rapid screening of the distribution of drugs and metabolites in tissue sections with the micro-liquid junction surface sampling probe/electrospray mass spectrometry approach.

  4. Bioanalysis and metabolite identification of anticancer drugs in mass balance studies

    NARCIS (Netherlands)

    Dubbelman, A.C.

    2012-01-01

    Anticancer drugs are valuable assets in the treatment of cancer. However, before a new drug is admitted to the market and available for patients, it has to survive a lengthy path of pre-clinical and clinical studies to demonstrate its efficacy and safety. Critical information required to understand

  5. Improved forensic hair evidence for drugs of abuse by mass spectrometry

    NARCIS (Netherlands)

    Duvivier, W.F.

    2016-01-01

    Forensic hair analysis can be used as alternative evidence next to body fluids, and to obtain retrospective timeline information of an individual’s drug exposure. Chapter 1 describes the general concepts of drug incorporation into hair, external contamination, and the current

  6. Improved forensic hair evidence for drugs of abuse by mass spectrometry

    NARCIS (Netherlands)

    Duvivier, W.F.

    2016-01-01

    Forensic hair analysis can be used as alternative evidence next to body fluids, and to obtain retrospective timeline information of an individual’s drug exposure. Chapter 1 describes the general concepts of drug incorporation into hair, external contamination, and the current

  7. Community perceptions of targeted anti-malarial mass drug administrations in two provinces in Vietnam: a quantitative survey.

    Science.gov (United States)

    Nguyen, Thuy-Nhien; Thu, Pham N Huong; Hung, Ngo Trong; Son, Do Hung; Tien, Nguyen Thanh; Van Dung, Nguyen; Quang, Huynh Hong; Seidlein, Lorenz von; Cheah, Phaik Yeong; Dondorp, Arjen M; Day, Nicholas P J; White, Nicholas J; Hien, Tran Tinh

    2017-01-06

    As part of a targeted malaria elimination project, mass drug administrations (MDAs) were conducted in Vietnam. The impact of MDAs on malaria transmission depends largely on the efficacy of the anti-malarial drug regimen, the malaria epidemiology in the site and the population coverage. To explore why some people participate in MDAs and others do not, a quantitative survey of the villagers' perceptions was undertaken in Vietnam. In 2013/2014 MDAs were conducted in a village in Binh Phuoc province and a village in Ninh Thuan province. Within three months of the drug administration, 59 respondents in a village in Binh Phuoc and 79 respondents in a village in Ninh Thuan were randomly selected and interviewed. Comprehension of the purpose of the intervention was of paramount importance for participation in the intervention. Respondents aware that the intervention aims to protect against malaria were significantly more likely to participate than respondents who were unaware of the MDA's purpose. Secondly, how and by whom villagers were informed was critical for participation. There was a strong association between sensitization by an informant such as a member of the local health team with participation in the intervention. The study suggests several approaches to increase participation in mass drug administration campaigns. Training trustworthy informants to sensitize the study population is critical to maximize village participation in this setting. To achieve high coverage the entire community must understand and agree with the intervention.

  8. Controversies in knowledge translation for community-based drug treatment: the need to the end policies of the war on drugs and mass incarceration of drug offenders to achieve health equity.

    Science.gov (United States)

    Wallace, Barbara C

    2012-12-01

    The purpose of this article was to discuss significant challenges to the achievement of urban health, specifically acknowledging numerous controversies in knowledge translation for community-based drug treatment that prevent the achievement of health equity. Seven specific controversies are analyzed in this article. The results of the analysis are recommendations for moving toward the resolution of each controversy. Among the most important recommendations is a call to end the policies of the war on drugs and mass incarceration of drug offenders-as policies reflecting how politics and the misuse of power may derail knowledge translation. The article provides justification for evidence-based policy that supports community-based drug treatment as a public health approach consistent with the goals of health equity, ethical practice, and effective knowledge translation.

  9. A multi-residue method for 17 anticoccidial drugs and ractopamine in animal tissues by liquid chromatography-tandem mass spectrometry and time-of-flight mass spectrometry.

    Science.gov (United States)

    Matus, Johanna L; Boison, Joe O

    2016-05-01

    A new and sensitive multi-residue liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-quadrupole time-of-flight-mass spectrometry (LC-QToF-MS) method was developed and validated for the determination and confirmation of residues of 17 anticoccidials, plus free ractopamine in poultry muscle and liver, and bovine muscle, liver, and kidney tissues. The 17 anticoccidials are lasalocid, halofuginone, narasin, monensin, semduramicin, ethopabate, robenidine, buquinolate, toltrazuril as its sulfone metabolite, maduramicin, salinomycin, diclazuril, amprolium, decoquinate, dinitolmide, clopidol, and the nicarbazin metabolite DNC (N,N1-bis(4-nitrophenyl)urea). The analytes were extracted and cleaned up within a 3-hour period by simply extracting the analytes into a solvent mixture with salts followed by centrifugation, dilution, and filtration. The validated method was used in a pilot study for the analysis of 173 samples that included quail liver, bovine kidney, liver, muscle, and horse muscle. The predominant residues found in this study were monensin, ractopamine, and lasalocid. The results of this pilot study showed that this new method is applicable to real samples, and is fit for use in a regulatory testing programme. © 2016 Her Majesty the Queen in Right of Canada. Drug Testing and Analysis. © 2016 John Wiley & Sons, Ltd. © 2016 Her Majesty the Queen in Right of Canada. Drug Testing and Analysis. © 2016 John Wiley & Sons, Ltd.

  10. Quantitative analysis of drug distribution by ambient mass spectrometry imaging method with signal extinction normalization strategy and inkjet-printing technology.

    Science.gov (United States)

    Luo, Zhigang; He, Jingjing; He, Jiuming; Huang, Lan; Song, Xiaowei; Li, Xin; Abliz, Zeper

    2018-03-01

    Quantitative mass spectrometry imaging (MSI) is a robust approach that provides both quantitative and spatial information for drug candidates' research. However, because of complicated signal suppression and interference, acquiring accurate quantitative information from MSI data remains a challenge, especially for whole-body tissue sample. Ambient MSI techniques using spray-based ionization appear to be ideal for pharmaceutical quantitative MSI analysis. However, it is more challenging, as it involves almost no sample preparation and is more susceptible to ion suppression/enhancement. Herein, based on our developed air flow-assisted desorption electrospray ionization (AFADESI)-MSI technology, an ambient quantitative MSI method was introduced by integrating inkjet-printing technology with normalization of the signal extinction coefficient (SEC) using the target compound itself. The method utilized a single calibration curve to quantify multiple tissue types. Basic blue 7 and an antitumor drug candidate (S-(+)-deoxytylophorinidine, CAT) were chosen to initially validate the feasibility and reliability of the quantitative MSI method. Rat tissue sections (heart, kidney, and brain) administered with CAT was then analyzed. The quantitative MSI analysis results were cross-validated by LC-MS/MS analysis data of the same tissues. The consistency suggests that the approach is able to fast obtain the quantitative MSI data without introducing interference into the in-situ environment of the tissue sample, and is potential to provide a high-throughput, economical and reliable approach for drug discovery and development. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Capillary Electrophoresis Hyphenated with Mass Spectrometry for Determination of Inflammatory Bowel Disease Drugs in Clinical Urine Samples

    Directory of Open Access Journals (Sweden)

    Katarína Maráková

    2017-11-01

    Full Text Available Azathioprine is the main thiopurine drug used in the treatment of immune-based inflammations of gastrointestinal tract. For the purpose of therapy control and optimization, effective and reliable analytical methods for a rapid drug monitoring in biological fluids are essential. Here, we developed a separation method based on the capillary electrophoresis (CE hyphenated with tandem mass spectrometry (MS/MS for the simultaneous determination of azathioprine and its selected metabolites (6-thioguanine, 6-mercaptopurine, and 6-methylmercaptopurine as well as other co-medicated drugs (mesalazine, prednisone, and allopurinol. The optimized CE-MS/MS conditions provided a very efficient and stable system for the separation and sensitive detection of these drugs in human urine matrices. The developed method was successfully applied for the assay of the targeted drugs and their selected metabolites in urine samples collected from patients suffering from inflammatory bowel disease (IBD and receiving azathioprine therapy. The developed CE-MS/MS method, due to its reliability, short analysis time, production of complex clinical profiles, and favorable performance parameters, evaluated according to FDA guidelines for bioanalytical method validation, is proposed for routine clinical laboratories to optimize thiopurine therapy, estimate enzymatic activity, and control patient compliance with medication and co-medication.

  12. Drug use and other risk factors related to lower body mass index among HIV-infected individuals.

    Science.gov (United States)

    Quach, Lien A; Wanke, Christine A; Schmid, Christopher H; Gorbach, Sherwood L; Mwamburi, D Mkaya; Mayer, Kenneth H; Spiegelman, Donna; Tang, Alice M

    2008-05-01

    Malnutrition is associated with morbidity and mortality in HIV-infected individuals. Little research has been conducted to identify the roles that clinical, illicit drug use and socioeconomic characteristics play in the nutritional status of HIV-infected patients. This cross-sectional analysis included 562 HIV-infected participants enrolled in the Nutrition for Healthy Living study conducted in Boston, MA and Providence, RI. The relationship between body mass index (BMI) and several covariates (type of drug use, demographic, and clinical characteristics) were examined using linear regression. Overall, drug users had a lower BMI than non-drug users. The BMI of cocaine users was 1.4 kg/m(2) less than that of patients who did not use any drugs, after adjusting for other covariates (p=0.02). The BMI of participants who were over the age of 55 years was 2.0 kg/m(2) less than that of patients under the age of 35, and BMI increased by 0.3 kg/m(2) with each 100 cells/mm(3) increase in CD4 count. HAART use, adherence to HAART, energy intake, AIDS status, hepatitis B and hepatitis C co-infections, cigarette smoking and depression were not associated with BMI in the final model. In conclusion, BMI was lower in drug users than non-drug users, and was lowest in cocaine users. BMI was also directly associated with CD4 count and inversely related to age more than 55 years old. HIV-infected cocaine users may be at higher risk of developing malnutrition, suggesting the need for anticipatory nutritional support.

  13. Instruments for radiation measurement in life sciences (4). 7. Application of accelerator mass spectrometry for drug development. Human mass balance studies at discovery stage

    International Nuclear Information System (INIS)

    Miyaoka, Teiji

    2005-01-01

    Following the recent trend of Position Paper issued from European Agency for the Evaluation of Medicinal Products on the non-clinical safety studies to support clinical trials with a single micro dose, human mass balance studies at discovery stages were made with special interest in using AMS (accelerator mass spectrometry) with a small amount of hot (radioisotope-labeled) drug. This method was found to be effective for the purpose of screening in the clinical study for pharmaceutical development. To show an example of the test, 5, 50, 500μg/body of C14-ARA (α1A adrenoreceptor antagonist, 50 nCi or 1.85 kBq/body/dose) were given (cross over) to several persons to be inspected and C14-quantity in the blood plasma or urine was determined with AMS until after 168 hours or so. The results of the present experiment demonstrate that human mass balance study at discovery stages is possible with ultra high sensitive measuring systems such as AMS and PET (positron emission tomography). (S. Ohno)

  14. Is mass drug administration against lymphatic filariasis required in urban settings? The experience in Kano, Nigeria.

    Directory of Open Access Journals (Sweden)

    Dung D Pam

    2017-10-01

    Full Text Available The Global Programme to Eliminate Lymphatic Filariasis (GPELF, launched in 2000, has the target of eliminating the disease as a public health problem by the year 2020. The strategy adopted is mass drug administration (MDA to all eligible individuals in endemic communities and the implementation of measures to reduce the morbidity of those suffering from chronic disease. Success has been recorded in many rural endemic communities in which elimination efforts have centered. However, implementation has been challenging in several urban African cities. The large cities of West Africa, exemplified in Nigeria in Kano are challenging for LF elimination program because reaching 65% therapeutic coverage during MDA is difficult. There is therefore a need to define a strategy which could complement MDA. Thus, in Kano State, Nigeria, while LF MDA had reached 33 of the 44 Local Government Areas (LGAs there remained eleven 'urban' LGAs which had not been covered by MDA. Given the challenges of achieving at least 65% coverage during MDA implementation over several years in order to achieve elimination, it may be challenging to eliminate LF in such settings. In order to plan the LF control activities, this study was undertaken to confirm the LF infection prevalence in the human and mosquito populations in three urban LGAs.The prevalence of circulating filarial antigen (CFA of Wuchereria bancrofti was assessed by an immuno-chromatography test (ICT in 981 people in three urban LGAs of Kano state, Nigeria. Mosquitoes were collected over a period of 4 months from May to August 2015 using exit traps, gravid traps and pyrethrum knock-down spray sheet collections (PSC in different households. A proportion of mosquitoes were analyzed for W. bancrofti, using dissection, loop-mediated isothermal amplification (LAMP assay and conventional polymerase chain reaction (PCR.The results showed that none of the 981 subjects (constituted of <21% of children 5-10 years old tested

  15. Effects of meal composition and meal timing on the expression of genes involved in hepatic drug metabolism in rats

    NARCIS (Netherlands)

    de Vries, E M; Oosterman, Johanneke E; Eggink, Hannah M; de Goede, P; Sen, Satish; Foppen, E; Boudzovitch-Surovtseva, Olga; Boelen, A.; Romijn, Johannes A; La Fleur, S.E.; Kalsbeek, A

    2017-01-01

    INTRODUCTION: With chronotherapy, drug administration is synchronized with daily rhythms in drug clearance and pharmacokinetics. Daily rhythms in gene expression are centrally mastered by the suprachiasmatic nucleus of the hypothalamus as well as by tissue clocks containing similar molecular

  16. Effects of meal composition and meal timing on the expression of genes involved in hepatic drug metabolism in rats

    NARCIS (Netherlands)

    de Vries, E. M.; Oosterman, J. E.; Eggink, H. M.; de Goede, P.; Sen, S.; Foppen, E.; Boudzovitch-Surovtseva, O.; Boelen, A.; Romijn, J. A.; laFleur, S. E.; Kalsbeek, A.

    2017-01-01

    With chronotherapy, drug administration is synchronized with daily rhythms in drug clearance and pharmacokinetics. Daily rhythms in gene expression are centrally mastered by the suprachiasmatic nucleus of the hypothalamus as well as by tissue clocks containing similar molecular mechanisms in

  17. Drug facilitated sexual assault: detection and stability of benzodiazepines in spiked drinks using gas chromatography-mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Lata Gautam

    Full Text Available Benzodiazepines are detected in a significant number of drug facilitated sexual assaults (DFSA. Whilst blood and urine from the victim are routinely analysed, due to the delay in reporting DFSA cases and the short half lives of most of these drugs in blood and urine, drug detection in such samples is problematic. Consideration of the drinks involved and analysis for drugs may start to address this. Here we have reconstructed the 'spiking' of three benzodiazepines (diazepam, flunitrazepam and temazepam into five drinks, an alcopop (flavoured alcoholic drink, a beer, a white wine, a spirit, and a fruit based non-alcoholic drink (J2O chosen as representative of those drinks commonly used by women in 16-24 year old age group. Using a validated GC-MS method for the simultaneous detection of these drugs in the drinks we have studied the storage stability of the benzodiazepines under two different storage conditions, uncontrolled room temperature and refrigerator (4°C over a 25 day period. All drugs could be detected in all beverages over this time period. Diazepam was found to be stable in all of the beverages, except the J2O, under both storage conditions. Flunitrazepam and temazepam were found not to be stable but were detectable (97% loss of temazepam and 39% loss of flunitrazepam from J2O. The recommendations from this study are that there should be a policy change and that drinks thought to be involved in DFSA cases should be collected and analysed wherever possible to support other evidence types.

  18. Drug Facilitated Sexual Assault: Detection and Stability of Benzodiazepines in Spiked Drinks Using Gas Chromatography-Mass Spectrometry

    Science.gov (United States)

    Gautam, Lata; Sharratt, Sarah D.; Cole, Michael D.

    2014-01-01

    Benzodiazepines are detected in a significant number of drug facilitated sexual assaults (DFSA). Whilst blood and urine from the victim are routinely analysed, due to the delay in reporting DFSA cases and the short half lives of most of these drugs in blood and urine, drug detection in such samples is problematic. Consideration of the drinks involved and analysis for drugs may start to address this. Here we have reconstructed the ‘spiking’ of three benzodiazepines (diazepam, flunitrazepam and temazepam) into five drinks, an alcopop (flavoured alcoholic drink), a beer, a white wine, a spirit, and a fruit based non-alcoholic drink (J2O) chosen as representative of those drinks commonly used by women in 16–24 year old age group. Using a validated GC-MS method for the simultaneous detection of these drugs in the drinks we have studied the storage stability of the benzodiazepines under two different storage conditions, uncontrolled room temperature and refrigerator (4°C) over a 25 day period. All drugs could be detected in all beverages over this time period. Diazepam was found to be stable in all of the beverages, except the J2O, under both storage conditions. Flunitrazepam and temazepam were found not to be stable but were detectable (97% loss of temazepam and 39% loss of flunitrazepam from J2O). The recommendations from this study are that there should be a policy change and that drinks thought to be involved in DFSA cases should be collected and analysed wherever possible to support other evidence types. PMID:24586489

  19. Investigation of the immunogenicity of a protein drug using equilibrium dialysis and liquid chromatography tandem mass spectrometry detection.

    Science.gov (United States)

    Ji, Qin C; Rodila, Ramona; Morgan, Sherry J; Humerickhouse, Rod A; El-Shourbagy, Tawakol A

    2005-09-01

    Biotherapeutics such as protein and peptide drugs have attracted significant attention in the medical community and pharmaceutical industry in recent years. Immunogenicity is one of the major concerns in the development and application of biotherapeutics. Although great efforts have been put forth in reducing immunogenicity, monitoring the free ("active") drug concentration and the antibody formation is critical for preclinical and clinical studies. Currently, it is still a challenging task to have a standardized test method monitoring immunogenicity when biotherapeutic compounds such as proteins and peptides are administrated. Combined with liquid chromatography/tandem mass spectrometry detection, the equilibrium dialysis technique that is conventionally used for measuring the free and bound concentration of small organic molecules was extended to the application of measuring the free and bound concentrations of a protein drug with a relative molecular mass over 10,000 from plasma samples containing antibody. This novel approach could also be used for accurately measuring the antibody concentration when a reference standard of the antibody is available.

  20. Mass spectrometry-guided optimization and characterization of a biologically active transferrin-lysozyme model drug conjugate.

    Science.gov (United States)

    Nguyen, Son N; Bobst, Cedric E; Kaltashov, Igor A

    2013-05-06

    Transferrin is a promising drug carrier that has the potential to deliver metals, small organic molecules and therapeutic proteins to cancer cells and/or across physiological barriers (such as the blood-brain barrier). Despite this promise, very few transferrin-based therapeutics have been developed and reached clinical trials. This modest success record can be explained by the complexity and heterogeneity of protein conjugation products, which also pose great challenges to their analytical characterization. In this work, we use lysozyme conjugated to transferrin as a model therapeutic that targets the central nervous system (where its bacteriostatic properties may be exploited to control infection) and develop analytical protocols based on electrospray ionization mass spectrometry to characterize its structure and interactions with therapeutic targets and physiological partners critical for its successful delivery. Mass spectrometry has already become an indispensable tool facilitating all stages of the protein drug development process, and this work demonstrates the enormous potential of this technique in facilitating the development of a range of therapeutically effective protein-drug conjugates.

  1. Troubled families and individualised solutions: an institutional discourse analysis of alcohol and drug treatment practices involving affected others.

    Science.gov (United States)

    Selbekk, Anne Schanche; Sagvaag, Hildegunn

    2016-09-01

    Research shows that members of the families with patients suffering from alcohol and other drug-related issues (AOD) experience stress and strain. An important question is, what options do AOD treatment have for them when it comes to support? To answer this, we interviewed directors and clinicians from three AOD treatment institutions in Norway. The study revealed that family-oriented practices are gaining ground as a 'going concern'. However, the relative position of family-orientation in the services, is constrained and shaped by three other going concerns related to: (i) discourse on health and illness, emphasising that addiction is an individual medical and psychological phenomenon, rather than a relational one; (ii) discourse on rights and involvement, emphasising the autonomy of the individual patient and their right to define the format of their own treatment; and (iii) discourse on management, emphasising the relationship between cost and benefit, where family-oriented practices are defined as not being cost-effective. All three discourses are connected to underpin the weight placed on individualised practices. Thus, the findings point to a paradox: there is a growing focus on the needs of children and affected family members, while the possibility of performing integrated work on families is limited. © 2016 Foundation for the Sociology of Health & Illness.

  2. Mechanisms of photosensitization by drugs: Involvement of tyrosines in the photomodification of proteins mediated by tiaprofenic acid in vitro.

    Science.gov (United States)

    Miranda, M A; Castell, J V; Sarabia, Z; Hernández, D; Puertes, I; Morera, I M; Gómez-Lechón, M J

    1997-10-01

    The photosensitizing potential of drugs must be related to their photoreactivity towards the target biomolecules. In this context, a representative photosensitizing drug (tiaprofenic acid) was co-irradiated with a model protein, bovine serum albumin (BSA). This led to a significant degree of protein crosslinking and to the formation of trace amounts of drug-BSA photoadducts. Amino acid analysis of the hydrolysed (HC1) protein showed that His and Tyr undergo a dramatic decrease (approx. 90%) as a consequence of drug-mediated photodynamic processes. When the drug was irradiated in the presence of the pure amino acids, extensive phototransformation of the latter was observed. Other photosensitizing drugs gave rise to similar processes when irradiated in the presence of BSA or the isolated amino acids. In conclusion, histidine and tyrosine appear to be key sites for the photosensitized damage to proteins. Photodegradation of the isolated amino acids in vitro may be an indicator of the photosensitizing potential of drugs.

  3. A STUDY ON ADVERSE DRUG REACTIONS INVOLVING CENTRAL NERVOUS SYSTEM, ITS SEVERITY AND CAUSALITY ASSESSMENT IN PEDIATRIC PATIENTS ADMITTED TO A TERTIARY CARE HOSPITAL

    Directory of Open Access Journals (Sweden)

    Arati

    2015-09-01

    Full Text Available A retrospective study was conducted in Department of pediatrics SCB Medical College and SVPPGIP for a period of 2 years i.e. September 2012 to August 2014 . All the patients from birth to 14 years admitted to the pediatric ward in this study were under ADR surveillance. Patients admitted to our hospital with adverse drug reaction o r patients developing adverse drug reaction in our hospital were studied; only those cases where the central nervous system was involved were taken in our study. The cases were compiled and the causality of offending drugs was found using WHO - UMC causality assessment score. The severity of drug reaction in every case was determined by using HARTWIG’s severity scoring scale. Total 350 Adverse reactions were reported in this period with prevalence rate of 2.04% i.e. 20 out of 1000 children faced ADR due to dr ugs, with annual incidence rate of 0.9% and 1.14% over two years. Out of total 350 cases dermatological system was most commonly involved i.e. 207 cases (59.14%. This is followed by involvement of central nervous system 46 number of cases (13.14%. The GI system was involved in 34 cases i.e. (9.71%. Life threatening reactions like anaphylaxis, angioedema and shock like immediate life threatening ADRs were reported in 16 cases. Our study group was the patient in whom the ADR involved the CNS. Out of 46 suc h cases, there were 25 female and 21 male. Various reaction due to drug were encephalopathy , eps, febrile seizure, tremor, head reeling, ototoxicity, persistant cry, pseudotumor cerebri, psychosis, seizure, status epilepticus, toxic amblyopia, tremor, atax ia etc. The most common CNS manifestation was Extra pyramidal side effects (EPS involving 21% of cases. The most common Drug causing CNS manifestation was ATT (HRZE causing blindness, Eps, psychosis , toxic amblyopia blindness etc.

  4. The differentiation of fibre- and drug type Cannabis seedlings by gas chromatography/mass spectrometry and chemometric tools.

    Science.gov (United States)

    Broséus, Julian; Anglada, Frédéric; Esseiva, Pierre

    2010-07-15

    Cannabis cultivation in order to produce drugs is forbidden in Switzerland. Thus, law enforcement authorities regularly ask forensic laboratories to determinate cannabis plant's chemotype from seized material in order to ascertain that the plantation is legal or not. As required by the EU official analysis protocol the THC rate of cannabis is measured from the flowers at maturity. When laboratories are confronted to seedlings, they have to lead the plant to maturity, meaning a time consuming and costly procedure. This study investigated the discrimination of fibre type from drug type Cannabis seedlings by analysing the compounds found in their leaves and using chemometrics tools. 11 legal varieties allowed by the Swiss Federal Office for Agriculture and 13 illegal ones were greenhouse grown and analysed using a gas chromatograph interfaced with a mass spectrometer. Compounds that show high discrimination capabilities in the seedlings have been identified and a support vector machines (SVMs) analysis was used to classify the cannabis samples. The overall set of samples shows a classification rate above 99% with false positive rates less than 2%. This model allows then discrimination between fibre and drug type Cannabis at an early stage of growth. Therefore it is not necessary to wait plants' maturity to quantify their amount of THC in order to determine their chemotype. This procedure could be used for the control of legal (fibre type) and illegal (drug type) Cannabis production. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  5. Direct detection of illicit drugs from biological fluids by desorption/ionization mass spectrometry with nanoporous silicon microparticles.

    Science.gov (United States)

    Guinan, T M; Kirkbride, P; Della Vedova, C B; Kershaw, S G; Kobus, H; Voelcker, N H

    2015-12-07

    Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) is a high throughput analytical technique capable of detecting low molecular weight analytes, including illicit drugs, and with potential applications in forensic toxicology as well as athlete and workplace testing, particularly for biological fluids (oral fluids, urine and blood). However, successful detection of illicit drugs using SALDI-MS often requires extraction steps to reduce the inherent complexity of biological fluids. Here, we demonstrate an all-in-one extraction and analytical system consisting of hydrophobically functionalized porous silicon microparticles (pSi-MPs) for affinity SALDI-MS of prescription and illicit drugs. This novel approach allows for the analysis of drugs from multiple biological fluids without sample preparation protocols. The effect of pSi-MP size, pore diameter, pore depth and functionalization on analytical performance is investigated. pSi-MPs were optimized for the rapid and high sensitivity detection of methadone, cocaine and 3,4-methylenedioxymethamphetamine (MDMA). This optimized system allowed extraction and detection of methadone from spiked saliva and clinical urine samples. Furthermore, by detecting oxycodone in additional clinical saliva and plasma samples, we were able to demonstrate the versatility of the pSi-MP SALDI-MS technique.

  6. Generic solid phase extraction-liquid chromatography-tandem mass spectrometry method for fast determination of drugs in biological fluids.

    Science.gov (United States)

    Schellen, Anniek; Ooms, Bert; van de Lagemaat, Dick; Vreeken, Rob; van Dongen, William D

    2003-05-25

    A generic method was developed for the fast determination of a wide range of drugs in serum or plasma. The methodology comprises generic solid-phase extraction, on-line coupled to gradient HPLC with tandem mass spectrometric detection (SPE-LC-MS/MS). The individual components of the SPE-LC-MS/MS system were optimized in an integrated approach to maximize the application range and minimize the method development time. The optimized generic SPE-LC-MS/MS protocol was evaluated for 11 drugs with different physicochemical properties. Good quantification for 10 out of 11 of the pharmaceuticals in serum or plasma could be readily achieved. The quantitative assays gave recoveries better than 95%, lower quantification limits of 0.2-2.0 ng/ml, acceptable precision and accuracy and good linearity over 2-4 orders of magnitude. Carry-over was determined to be in the range of 0.02-0.10%, without optimization.

  7. Profiling Nonrecipients of Mass Drug Administration for Schistosomiasis and Hookworm Infections : A Comprehensive Analysis of Praziquantel and Albendazole Coverage in Community-Directed Treatment in Uganda

    NARCIS (Netherlands)

    Chami, Goylette F.; Kontoleon, Andreas A.; Bulte, Erwin|info:eu-repo/dai/nl/141315245; Fenwick, Alan; Kabatereine, Narcis B.; Tukahebwa, Edridah M.; Dunne, David W.

    2016-01-01

    Background. Repeated mass drug administration (MDA) with preventive chemotherapies is the mainstay of morbidity control for schistosomiasis and soil-transmitted helminths, yet the World Health Organization recently reported that less than one-third of individuals who required preventive

  8. Mass Spectrometry to Determine Intracellular Concentrations of Antiretroviral Drugs: From chemistry to clinical application

    NARCIS (Netherlands)

    J.J.A. van Kampen (Jeroen)

    2009-01-01

    textabstractAround 1995 – 1996, treatment options for patients infected with the human immunodefiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS) 1, 2, improved dramatically. Therapy with a combination of several classes of antiretroviral drugs resulted in a

  9. Acetoxy drug : Protein transacetylase of buffalo liver - Characterization and mass spectrometry of the acetylated protein product

    NARCIS (Netherlands)

    Kohli, E.; Gaspari, M.; Raj, H.G.; Parmar, V.S.; Sharma, S.K.; Greef, J. van der; Kumari, R.; Gupta, G.; Seema; Khurana, P.; Tyagi, Y.K.; Watterson, A.C.; Olsen, C.E.

    2004-01-01

    The purification and characterization of the buffalo liver microsomal transacetylase (TAase) catalyzing the transfer of acetyl groups from a model acetoxy drug: 7,8-diacetoxy-4-methylcoumarin (DAMC) to GST3-3 has been described here. The enzyme was routinely assayed using DAMC and cytosolic GST as

  10. Drug-Induced Thrombophilic or Prothrombotic States: An Underestimated Clinical Problem That Involves Both Legal and Illegal Compounds.

    Science.gov (United States)

    Girolami, A; Cosi, E; Tasinato, V; Santarossa, C; Ferrari, S; Girolami, B

    2017-10-01

    Vascular thrombosis, both arterial and venous, is a condition associated with significant morbidity and mortality. There are multiple risk factors for thrombosis, both congenital and acquired, and in the majority of cases, these risk factors are not modifiable. Over the past 2 decades, multiple drugs (both illegal and legal) have been associated with increased risk of thrombosis. However, due to limited scientific literature regarding the prothrombotic tendencies of these drugs, there is a concomitant limited understanding of the pathophysiology of drug-induced thrombosis. As drugs are one of the few modifiable risk factors for thrombosis, further study and dissemination of knowledge regarding drug-associated and drug-induced thrombosis are essential and have the potential to lead to decreased future incidence of thrombosis. The mechanisms at the basis of the thrombophilic activity of these drugs are variable and sometimes still ill recognized. Increased levels of clotting factors, reduction in coagulation natural inhibitors, decreased fibrinolysis, activated clotting factors, increased blood viscosity, endothelial damage, and increased platelet number and activation are the most frequent causes. Arterial steal or coronary arteries no flow has also been implicated. In some cases due to the intake of several drugs, more than one mechanism is present in a given patient. The purpose of the present review is to analyze all the drugs demonstrated to be potentially thrombotic. It is hoped that a prudent use or nonuse of these drugs might result in a reduction of thrombosis-associated diseases.

  11. Community members' perceptions of mass drug administration for control of lymphatic filariasis in rural rural and urban Tanzania

    DEFF Research Database (Denmark)

    Kisoka, William J.; Tersbøl, Britt Pinkowski; Meyrowitsch, Dan Wolf

    2016-01-01

    public health care is often deeply troubled and fails to meet the basic health needs of impoverished populations. This presents particular challenges for the implementation of mass drug administration (MDA), which currently is the principal means of control and eventual elimination. Several MDA...... and marginalization by the health care system and political authorities. However, the results suggest that if the communities are brought on board with genuine respect for their integrity and informed self-determination, there is scope for major improvements in community support for MDA-based control activities....

  12. Reassessment of areas with persistent Lymphatic Filariasis nine years after cessation of mass drug administration in Sri Lanka.

    Science.gov (United States)

    Rao, Ramakrishna U; Samarasekera, Sandhya D; Nagodavithana, Kumara C; Dassanayaka, Tharanga D M; Punchihewa, Manjula W; Ranasinghe, Udaya S B; Weil, Gary J

    2017-10-01

    Sri Lanka was one of the first countries to initiate a lymphatic filariasis (LF) elimination program based on WHO guidelines. The Anti-Filariasis Campaign provided 5 annual rounds of mass drug administration (MDA) with diethylcarbamazine plus albendazole in all 8 endemic districts from 2002-2006. Microfilaremia (Mf) prevalences have been consistently Sri Lanka with efficient transmission by Culex. Test and treat or other programs targeting adult males plus bed net promotion may be more effective than MDA for clearing remaining hotspots of transmission in Sri Lanka.

  13. Long-lasting insecticidal nets are synergistic with mass drug administration for interruption of lymphatic filariasis transmission in Nigeria.

    Directory of Open Access Journals (Sweden)

    Abel Eigege

    Full Text Available In central Nigeria Anopheles mosquitoes transmit malaria and lymphatic filariasis (LF. The strategy used for interrupting LF transmission in this area is annual mass drug administration (MDA with albendazole and ivermectin, but after 8 years of MDA, entomological evaluations in sentinel villages showed continued low-grade mosquito infection rates of 0.32%. After long-lasting insecticidal net (LLIN distribution by the national malaria program in late 2010, however, we were no longer able to detect infected vectors over a 24-month period. This is evidence that LLINs are synergistic with MDA in interrupting LF transmission.

  14. A series of forensic toxicology and drug seizure cases involving illicit fentanyl alone and in combination with heroin, cocaine or heroin and cocaine.

    Science.gov (United States)

    Marinetti, Laureen J; Ehlers, Brooke J

    2014-10-01

    The Montgomery County Coroner's Office Toxicology Section and the Miami Valley Regional Crime Lab (MVRCL) Drug Chemistry Section have been receiving case work in drug seizures, death cases and human performance cases involving products marketed as heroin or as illicit fentanyl. Upon analysis by the Drug Chemistry Section, these products were found to contain various drug(s) including illicit fentanyl only, illicit fentanyl and heroin, illicit fentanyl and cocaine and illicit fentanyl, heroin and cocaine. Both the Chemistry and Toxicology Sections began seeing these combinations starting in late October 2013. The percentage of the combinations encountered by the MVRCL as well as the physical appearance of the product, and the results of presumptive screening tests will be discussed. The demographics of the users and the results of toxicology and autopsy findings on the decedents will also be discussed. According to regional drug task force undercover agents, there is evidence that some of the products are being sold as illicit fentanyl and not just as a heroin product. Also, there is no evidence to support that the fentanyl source is being diverted from pharmaceutical grade fentanyl. The chemistry section currently has over 109 confirmed cases, and the toxicology section currently has 81 confirmed drug deaths, 8 driving under the influence of drugs and 1 suicidal hanging. Both sections are continuing to see these cases at the present time. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Role of cytochrome P450-mediated metabolism and involvement of reactive metabolite formations on antiepileptic drug-induced liver injuries.

    Science.gov (United States)

    Sasaki, Eita; Yokoi, Tsuyoshi

    2018-01-01

    Several drugs have been withdrawn from the market or restricted to avoid unexpected adverse outcomes. Drug-induced liver injury (DILI) is a serious issue for drug development. Among DILIs, idiosyncratic DILIs have been a serious problem in drug development and clinical uses. Idiosyncratic DILI is most often unrelated to pharmacological effects or the dosing amount of a drug. The number of drugs that cause idiosyncratic DILI continue to grow in part because no practical preclinical tests have emerged that can identify drug candidates with the potential for developing idiosyncratic DILIs. Nevertheless, the implications of drug metabolism-related factors and immune-related factors on idiosyncratic DILIs has not been fully clarified because this toxicity can not be reproduced in animals. Therefore, accumulated evidence for the mechanisms of the idiosyncratic toxicity has been limited to only in vitro studies. This review describes current knowledge of the effects of cytochrome P450 (CYP)-mediated metabolism and its detoxification abilities based on studies of idiosyncratic DILI animal models developed recently. This review also focused on antiepileptic drugs, phenytoin (diphenyl hydantoin, DPH) and carbamazepine (CBZ), which have rarely caused severe adverse reactions, such as fulminant hepatitis, and have been recognized as sources of idiosyncratic DILI. The studies of animal models of idiosyncratic DILIs have produced new knowledge of chronic administration, CYP inductions/inhibitions, glutathione contents, and immune-related factors for the initiation of idiosyncratic DILIs. Considering changes in the drug metabolic profile and detoxification abilities, idiosyncratic DILIs caused by antiepileptic drugs will lead to understanding the mechanisms of these DILIs.

  16. Lessons from implementing mass drug administration for soil transmitted helminths among pre-school aged children during school based deworming program at the Kenyan coast

    Directory of Open Access Journals (Sweden)

    Rosemary M. Musuva

    2017-06-01

    Full Text Available Abstract Background The 2012 London declaration which committed to “sustaining, expanding and extending drug access programmes to ensure the necessary supply of drugs and other interventions to help control soil-transmitted helminths (STH by 2020” has seen many countries in Africa roll out mass drug administration (MDA especially among school age children. In Kenya, however, during the National school-based deworming exercise, pre-school aged children (PSAC have to access treatment at primary schools as the pre-school teachers are not trained to carry out deworming. With studies being conducted on the effectiveness of MDAs, the experiences of key education stakeholders which could improve the programme by giving best practices, and challenges experienced have not been documented. Methods This was a cross-sectional qualitative study using Focus group discussions (FGDs and Key informant interviews (KIIs. It was conducted in 4 sub-counties with high STH prevalence at the Kenyan coast (Matuga, Malindi, Lunga Lunga and Msambweni to understand best practices for implementing MDA among PSAC.FGDs categorized by gender were conducted among local community members, whereas KIIs involved pre-school teachers, primary school teachers, community health extension workers (CHEWs and opinion leaders. Participants were purposefully selected with the saturation model determining the number of interviews and focus groups. Voice data collected was transcribed verbatim then coded and analyzed using ATLAS.Ti version 6. Results Majority of the primary school teachers and CHEWs reported that they were satisfied with the method of mobilization used and the training tools. This was however not echoed by the pre-school teachers, parents and chiefs who complained of being left out of the process. Best practices mentioned included timely drug delivery, support from pre-school teachers, and management of side effects. Overcrowding during the drug administration day

  17. Organs-on-Chips in Drug Development: The Importance of Involving Stakeholders in Early Health Technology Assessment

    NARCIS (Netherlands)

    Middelkamp, Heleen H.T.; van der Meer, Andries Dirk; Hummel, J. Marjan; Stamatialis, Dimitrios; Mummery, Christine Lindsay; Passier, Petrus Christianus Johannes Josephus; IJzerman, Maarten Joost

    2016-01-01

    Organs-on-chips are three-dimensional, microfluidic cell culture systems that simulate the function of tissues and organ subunits. Organ-on-chip systems are expected to contribute to drug candidate screening and the reduction of animal tests in preclinical drug development and may increase

  18. A comparison of two mathematical models of the impact of mass drug administration on the transmission and control of schistosomiasis.

    Science.gov (United States)

    Truscott, J E; Gurarie, D; Alsallaq, R; Toor, J; Yoon, N; Farrell, S H; Turner, H C; Phillips, A E; Aurelio, H O; Ferro, J; King, C H; Anderson, R M

    2017-03-01

    The predictions of two mathematical models describing the transmission dynamics of schistosome infection and the impact of mass drug administration are compared. The models differ in their description of the dynamics of the parasites within the host population and in their representation of the stages of the parasite lifecycle outside of the host. Key parameters are estimated from data collected in northern Mozambique from 2011 to 2015. This type of data set is valuable for model validation as treatment prior to the study was minimal. Predictions from both models are compared with each other and with epidemiological observations. Both models have difficulty matching both the intensity and prevalence of disease in the datasets and are only partially successful at predicting the impact of treatment. The models also differ from each other in their predictions, both quantitatively and qualitatively, of the long-term impact of 10 years' school-based mass drug administration. We trace the dynamical differences back to basic assumptions about worm aggregation, force of infection and the dynamics of the parasite in the snail population in the two models and suggest data which could discriminate between them. We also discuss limitations with the datasets used and ways in which data collection could be improved. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Determination of pesticides and veterinary drug residues in food by liquid chromatography-mass spectrometry: A review.

    Science.gov (United States)

    Masiá, Ana; Suarez-Varela, Maria Morales; Llopis-Gonzalez, Agustin; Picó, Yolanda

    2016-09-14

    Monitoring of pesticides and veterinary drug residues is required to enforce legislation and guarantee food safety. Liquid chromatography-mass spectrometry (LC-MS) is the prevailing technique for assessing both types of residues because LC offers a versatile and universal separation mechanism suitable for non-gas chromatography (GC) amenable and the majority of GC-amenable compounds. This characteristic becomes more relevant when LC is coupled to MS because the high sensitivity and specificity of the detector allows to apply generic sample preparation procedures, which simultaneously extract a wide variety of residues with different physico-chemical properties. Determination of metabolites and degradation products, non-target suspected screening of an increasing number of residues, and even unknowns identification are also becoming inherent LC-MS advantages thanks to the latest advances. For routine analysis and, in particular, for official surveillance purposes in food control, analytical methods properly validated following strict guidelines are needed. After a brief introduction and an outline of the legislation applicable around the world, aspects such as improvement of specificity of high-throughput methods, resolution and mass accuracy of identification strategies and quantitative accuracy are critically reviewed in this article. In them, extraction, separation and determination are emphasized. The main objective is to offer an assessment of the state of the art and identify research needs and future trends in determining pesticide and veterinary drug residues in food by LC-MS. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Emergency Department Visits for Drug-Related Suicide Attempts Involving Antidepressants by Adolescents and Young Adults: 2004 to 2008. The DAWN Report

    Science.gov (United States)

    Substance Abuse and Mental Health Services Administration, 2011

    2011-01-01

    In 2008, adolescents made 23,124 visits to the emergency department (ED) for drug-related suicide attempts, and young adults made 38,036 such visits; of these visits, 23.0 percent (5,312 visits) among adolescents and 17.6 percent (6,700 visits) among young adults involved antidepressants. Among ED visits for suicide attempts involving…

  1. Direct coupling of electromembrane extraction to mass spectrometry - Advancing the probe functionality toward measurements of zwitterionic drug metabolites.

    Science.gov (United States)

    Rye, Torstein Kige; Fuchs, David; Pedersen-Bjergaard, Stig; Petersen, Nickolaj Jacob

    2017-08-29

    A triple-flow electromembrane extraction (EME) probe was developed and coupled directly to electrospray-ionization mass spectrometry (ESI-MS). Metabolic reaction mixtures (pH 7.4) containing drug substances and related metabolites were continuously drawn (20 μL/min) into the EME probe in one flow channel, and mixed inside the probe with 7.5 μL min -1 of 1 M formic acid as make-up flow from a second flow channel. Following this acidification, the drug substances and their related metabolites were continuously extracted by EME at 400 V, across a supported liquid membrane (SLM) comprising 2-nitrophenyl octyl ether (and for some experiments containing 30% triphenyl phosphate (TPP)), and into 20 μL min -1 of formic acid as acceptor phase, which was introduced through a third flow channel. The acceptor phase was pumped directly to the MS system, and the ion intensity of extracted analytes was followed continuously as function of time. The triple-flow EME probe was used for co-extraction of positively charged parent drugs and their zwitterionic drug metabolites (hydroxyzine and its carboxylic acid metabolite cetirizine; and vortioxetine and its carboxylic acid metabolite Lu AA34443). While the zwitterionic metabolites could not be extracted at pH 7.4, it was shown that by acidifying the sample solution the zwitterionic metabolites could be extracted effectively. Various extraction parameters like make-up flow, extraction voltage and SLM composition were optimized for simultaneous extraction of parent drugs and metabolites. It was found that TPP added to the SLM improved extraction efficiencies of certain drug metabolites. Finally the optimized and characterized triple-flow EME probe was used for online studying the in-vitro metabolism of hydroxyzine and vortioxetine by rat liver microsomes. Due to the automated pre-extraction acidification of the rat liver microsomal solutions, it was possible to continuously monitor formation of the zwitterionic drug

  2. Intellectual abilities and motivation toward substance abuse treatment in drug-involved offenders: a pilot study in the Belgian criminal justice system.

    Science.gov (United States)

    Vandevelde, Stijn; Broekaert, Eric; Schuyten, Gilberte; Van Hove, Geert

    2005-06-01

    A sample of Belgian drug-involved inmates (N=116) completed the European Addiction Severity Index, the Raven Standard Progressive Matrices (SPM), and the Circumstances, Motivation, and Readiness Scales. The pilot results demonstrate that nearly 50% of the participating drug-involved offenders display low intellectual abilities (SPM score definitely below average). Legal difficulties, drug abuse, and psychological problems are identified as the most severe problem areas for the total group. The participants display low to moderately low scores regarding motivation, readiness, and external reasons to stay in or leave treatment. No to very limited correlations between motivational attributes and other variables such as the length of the prison sentence and the number of violent crimes are found. Participants with high intellectual abilities are less motivated to enter substance abuse treatment compared to their counterparts with average and low intellectual abilities. Implications for treatment are discussed.

  3. Identification and measurement of illicit drugs and their metabolites in urban wastewater by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Castiglioni, Sara; Zuccato, Ettore; Crisci, Elisabetta; Chiabrando, Chiara; Fanelli, Roberto; Bagnati, Renzo

    2006-12-15

    Residues of illicit drugs and their metabolites that are excreted by humans may flow into and through wastewater treatment plants. The aim of this study was to develop a method for the determination of cocaine, amphetamines, morphine, cannabinoids, methadone, and some of their metabolites in wastewater. Composite 24-h samples from urban treatment plants were enriched with deuterated internal standards before solid-phase extraction. High-pressure liquid chromatography tandem mass spectrometry with multiple reaction monitoring was used for quantitation. Recoveries were generally higher than 80%, and limits of quantifications were in the low nanograms-per-liter range for untreated and treated wastewater. The overall variability of the method was lower than 10% for untreated and 5% for treated wastewater. The method was applied to wastewater samples coming from two treatment plants in Italy and Switzerland. Quantification ranges were found to be 0.2-1 microg/L for cocaine and its metabolite benzoylecgonine, 80-200 ng/L for morphine, 10 ng/L for 6-acetylmorphine, 60-90 ng/L for 11-nor-9-carboxy-Delta9-tetrahydrocannabinol, 10-90 ng/L for methadone and its main metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, and lower than 20 ng/L for amphetamines. As previously reported for cocaine, this method could be useful to estimate and monitor drug consumption in the population in real time, helping social scientists and authorities to combat drug abuse.

  4. Associations of Body Mass Index with Sexual Risk-Taking and Injection Drug Use among US High School Students

    Directory of Open Access Journals (Sweden)

    Richard Lowry

    2014-01-01

    Full Text Available The purpose of this study was to determine if body mass index (BMI is associated with behaviors that may increase risk for HIV and other sexually transmitted diseases (STDs among US high school students. We analyzed nationally representative data from the 2005–2011 national Youth Risk Behavior Surveys (YRBS to examine associations of BMI categories with sexual risk behaviors and injection drug use among sexually active high school students, using sex-stratified logistic regression models. Controlling for race/ethnicity and grade, among female and male students, both underweight (BMI < 5th percentile and obesity (BMI ≥ 95th percentile were associated with decreased odds of being currently sexually active (i.e., having had sexual intercourse during the past 3 months. However, among sexually active female students, obese females were more likely than normal weight females to have had 4 or more sex partners (odds ratio, OR = 1.59, not used a condom at last sexual intercourse (OR = 1.30, and injected illegal drugs (OR = 1.98. Among sexually active male students, overweight (85th percentile ≤ BMI < 95th percentile was associated with not using a condom at last sexual intercourse (OR = 1.19 and obesity was associated with injection drug use (OR = 1.42. Among sexually active students, overweight and obesity may be indicators of increased risk for HIV and other STDs.

  5. Determination of pesticides and veterinary drug residues in food by liquid chromatography-mass spectrometry: A review

    Energy Technology Data Exchange (ETDEWEB)

    Masiá, Ana [Food and Environmental Safety Research Group, Department of Preventive Medicine and Public Health, Food Science, Toxicology and Legal Medicine, University of Valencia, Valencia (Spain); Research Center on Desertification (CIDE, UV-CSIC-GV), Carretera Moncada-Náquera, Moncada (Spain); Suarez-Varela, Maria Morales; Llopis-Gonzalez, Agustin [Unit of Public Health, Hygiene and Environmental Health, Department of Preventive Medicine and Public Health, Food Science, Toxicology and Legal Medicine, University of Valencia, Valencia (Spain); CIBER Epidemiología y Salud Pública (CIBERESP), Madrid (Spain); Center for Advanced Research in Public Health (CSISP-FISABIO), Valencia (Spain); Picó, Yolanda, E-mail: Yolanda.Pico@uv.es [Food and Environmental Safety Research Group, Department of Preventive Medicine and Public Health, Food Science, Toxicology and Legal Medicine, University of Valencia, Valencia (Spain); Research Center on Desertification (CIDE, UV-CSIC-GV), Carretera Moncada-Náquera, Moncada (Spain); CIBER Epidemiología y Salud Pública (CIBERESP), Madrid (Spain)

    2016-09-14

    Monitoring of pesticides and veterinary drug residues is required to enforce legislation and guarantee food safety. Liquid chromatography-mass spectrometry (LC-MS) is the prevailing technique for assessing both types of residues because LC offers a versatile and universal separation mechanism suitable for non-gas chromatography (GC) amenable and the majority of GC-amenable compounds. This characteristic becomes more relevant when LC is coupled to MS because the high sensitivity and specificity of the detector allows to apply generic sample preparation procedures, which simultaneously extract a wide variety of residues with different physico-chemical properties. Determination of metabolites and degradation products, non-target suspected screening of an increasing number of residues, and even unknowns identification are also becoming inherent LC-MS advantages thanks to the latest advances. For routine analysis and, in particular, for official surveillance purposes in food control, analytical methods properly validated following strict guidelines are needed. After a brief introduction and an outline of the legislation applicable around the world, aspects such as improvement of specificity of high-throughput methods, resolution and mass accuracy of identification strategies and quantitative accuracy are critically reviewed in this article. In them, extraction, separation and determination are emphasized. The main objective is to offer an assessment of the state of the art and identify research needs and future trends in determining pesticide and veterinary drug residues in food by LC-MS. - Highlights: • An overview of status and future trends in this field. • Analytical method's compliance with guidelines to ensure reliability. • QuEChERS platform is a referent to extract both, pesticides and veterinary drugs in food. • The progress that liquid chromatography has shown in recent years is revised. • Determination of target, non-target and unknowns is

  6. Determination of pesticides and veterinary drug residues in food by liquid chromatography-mass spectrometry: A review

    International Nuclear Information System (INIS)

    Masiá, Ana; Suarez-Varela, Maria Morales; Llopis-Gonzalez, Agustin; Picó, Yolanda

    2016-01-01

    Monitoring of pesticides and veterinary drug residues is required to enforce legislation and guarantee food safety. Liquid chromatography-mass spectrometry (LC-MS) is the prevailing technique for assessing both types of residues because LC offers a versatile and universal separation mechanism suitable for non-gas chromatography (GC) amenable and the majority of GC-amenable compounds. This characteristic becomes more relevant when LC is coupled to MS because the high sensitivity and specificity of the detector allows to apply generic sample preparation procedures, which simultaneously extract a wide variety of residues with different physico-chemical properties. Determination of metabolites and degradation products, non-target suspected screening of an increasing number of residues, and even unknowns identification are also becoming inherent LC-MS advantages thanks to the latest advances. For routine analysis and, in particular, for official surveillance purposes in food control, analytical methods properly validated following strict guidelines are needed. After a brief introduction and an outline of the legislation applicable around the world, aspects such as improvement of specificity of high-throughput methods, resolution and mass accuracy of identification strategies and quantitative accuracy are critically reviewed in this article. In them, extraction, separation and determination are emphasized. The main objective is to offer an assessment of the state of the art and identify research needs and future trends in determining pesticide and veterinary drug residues in food by LC-MS. - Highlights: • An overview of status and future trends in this field. • Analytical method's compliance with guidelines to ensure reliability. • QuEChERS platform is a referent to extract both, pesticides and veterinary drugs in food. • The progress that liquid chromatography has shown in recent years is revised. • Determination of target, non-target and unknowns is

  7. Determination of drugs in surface water and wastewater samples by liquid chromatography-mass spectrometry: Methods and preliminary results including toxicity studies with Vibrio fischeri

    Science.gov (United States)

    Farre, M.; Ferrer, I.; Ginebreda, A.; Figueras, M.; Olivella, L.; Tirapu, L.; Vilanova, M.; Barcelo, D.

    2001-01-01

    In the present work a combined analytical method involving toxicity and liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was developed for the determination of pharmaceutical compounds in water samples. The drugs investigated were the analgesics: ibuprofen, ketoprofen, naproxen, and diclofenac, the decomposition product of the acetyl salicylic acid: salicylic acid and one lipid lowering agent, gemfibrozil. The selected compounds are acidic substances, very polar and all of them are analgesic compounds that can be purchased without medical prescription. The developed protocol consisted, first of all, on the use Microtox?? and ToxAlert??100 toxicity tests with Vibrio fischeri for the different pharmaceutical drugs. The 50% effective concentration (EC50) values and the toxicity units (TU) were determined for every compound using both systems. Sample enrichment of water samples was achieved by solid-phase extraction procedure (SPE), using the Merck LiChrolut?? EN cartridges followed by LC-ESI-MS. Average recoveries loading 1 l of samples with pH=2 varied from 69 to 91% and the detection limits in the range of 15-56 ng/l. The developed method was applied to real samples from wastewater and surface-river waters of Catalonia (north-east of Spain). One batch of samples was analyzed in parallel also by High Resolution Gas Chromatography coupled with Mass Spectrometry (HRGC-MS) and the results have been compared with the LC-ESI-MS method developed in this work. ?? 2001 Elsevier Science B.V. All rights reserved.

  8. Mass spectrometry imaging of illicit drugs in latent fingerprints by matrix-free and matrix-assisted desorption/ionization techniques.

    Science.gov (United States)

    Skriba, Anton; Havlicek, Vladimir

    2018-02-01

    Compared with classical matrix-assisted laser-desorption ionization mass spectrometry (MALDI), the matrix free-based strategies generate a cleaner background, without significant noise or interference coming from an applied matrix, which is beneficial for the analysis of small molecules, such as drugs of abuse. In this work, we probed the detection efficiency of methamphetamine, heroin and cocaine in nanostructure-assisted laser desorption-ionization (NALDI) and desorption electrospray ionization and compared the sensitivity of these two matrix-free tools with a standard MALDI mass spectrometry experiment. In a typical mass spectrometry imaging (MSI) setup, papillary line latent fingerprints were recorded as a mixture a common skin fatty acid or interfering cosmetics with a drug. In a separate experiment, all drugs (1 µL of 1 μM standard solution) were detected by all three ionization techniques on a target. In the case of cocaine and heroin, NALDI mass spectrometry was the most sensitive and revealed signals even from 0.1 μM solution. The drug/drug contaminant (fatty acid or cosmetics) MSI approach could be used by law enforcement personnel to confirm drug abusers of having come into contact with the suspected drug by use of fingerprint scans at time of apprehension which can aid in reducing the work of lab officials.

  9. Conflict of interest reporting by authors involved in promotion of off-label drug use: an analysis of journal disclosures.

    Directory of Open Access Journals (Sweden)

    Aaron S Kesselheim

    Full Text Available Litigation documents reveal that pharmaceutical companies have paid physicians to promote off-label uses of their products through a number of different avenues. It is unknown whether physicians and scientists who have such conflicts of interest adequately disclose such relationships in the scientific publications they author.We collected whistleblower complaints alleging illegal off-label marketing from the US Department of Justice and other publicly available sources (date range: 1996-2010. We identified physicians and scientists described in the complaints as having financial relationships with defendant manufacturers, then searched Medline for articles they authored in the subsequent three years. We assessed disclosures made in articles related to the off-label use in question, determined the frequency of adequate disclosure statements, and analyzed characteristics of the authors (specialty, author position and articles (type, connection to off-label use, journal impact factor, citation count/year. We identified 39 conflicted individuals in whistleblower complaints. They published 404 articles related to the drugs at issue in the whistleblower complaints, only 62 (15% of which contained an adequate disclosure statement. Most articles had no disclosure (43% or did not mention the pharmaceutical company (40%. Adequate disclosure rates varied significantly by article type, with commentaries less likely to have adequate disclosure compared to articles reporting original studies or trials (adjusted odds ratio [OR] = 0.10, 95%CI = 0.02-0.67, p = 0.02. Over half of the authors (22/39, 56% made no adequate disclosures in their articles. However, four of six authors with ≥ 25 articles disclosed in about one-third of articles (range: 10/36-8/25 [28%-32%].One in seven authors identified in whistleblower complaints as involved in off-label marketing activities adequately disclosed their conflict of interest in subsequent journal publications. This is

  10. Conflict of interest reporting by authors involved in promotion of off-label drug use: an analysis of journal disclosures.

    Science.gov (United States)

    Kesselheim, Aaron S; Wang, Bo; Studdert, David M; Avorn, Jerry

    2012-01-01

    Litigation documents reveal that pharmaceutical companies have paid physicians to promote off-label uses of their products through a number of different avenues. It is unknown whether physicians and scientists who have such conflicts of interest adequately disclose such relationships in the scientific publications they author. We collected whistleblower complaints alleging illegal off-label marketing from the US Department of Justice and other publicly available sources (date range: 1996-2010). We identified physicians and scientists described in the complaints as having financial relationships with defendant manufacturers, then searched Medline for articles they authored in the subsequent three years. We assessed disclosures made in articles related to the off-label use in question, determined the frequency of adequate disclosure statements, and analyzed characteristics of the authors (specialty, author position) and articles (type, connection to off-label use, journal impact factor, citation count/year). We identified 39 conflicted individuals in whistleblower complaints. They published 404 articles related to the drugs at issue in the whistleblower complaints, only 62 (15%) of which contained an adequate disclosure statement. Most articles had no disclosure (43%) or did not mention the pharmaceutical company (40%). Adequate disclosure rates varied significantly by article type, with commentaries less likely to have adequate disclosure compared to articles reporting original studies or trials (adjusted odds ratio [OR] = 0.10, 95%CI = 0.02-0.67, p = 0.02). Over half of the authors (22/39, 56%) made no adequate disclosures in their articles. However, four of six authors with ≥ 25 articles disclosed in about one-third of articles (range: 10/36-8/25 [28%-32%]). One in seven authors identified in whistleblower complaints as involved in off-label marketing activities adequately disclosed their conflict of interest in subsequent journal publications. This is a much

  11. Conflict of Interest Reporting by Authors Involved in Promotion of Off-Label Drug Use: An Analysis of Journal Disclosures

    Science.gov (United States)

    Kesselheim, Aaron S.; Wang, Bo; Studdert, David M.; Avorn, Jerry

    2012-01-01

    Background Litigation documents reveal that pharmaceutical companies have paid physicians to promote off-label uses of their products through a number of different avenues. It is unknown whether physicians and scientists who have such conflicts of interest adequately disclose such relationships in the scientific publications they author. Methods and Findings We collected whistleblower complaints alleging illegal off-label marketing from the US Department of Justice and other publicly available sources (date range: 1996–2010). We identified physicians and scientists described in the complaints as having financial relationships with defendant manufacturers, then searched Medline for articles they authored in the subsequent three years. We assessed disclosures made in articles related to the off-label use in question, determined the frequency of adequate disclosure statements, and analyzed characteristics of the authors (specialty, author position) and articles (type, connection to off-label use, journal impact factor, citation count/year). We identified 39 conflicted individuals in whistleblower complaints. They published 404 articles related to the drugs at issue in the whistleblower complaints, only 62 (15%) of which contained an adequate disclosure statement. Most articles had no disclosure (43%) or did not mention the pharmaceutical company (40%). Adequate disclosure rates varied significantly by article type, with commentaries less likely to have adequate disclosure compared to articles reporting original studies or trials (adjusted odds ratio [OR] = 0.10, 95%CI = 0.02–0.67, p = 0.02). Over half of the authors (22/39, 56%) made no adequate disclosures in their articles. However, four of six authors with ≥25 articles disclosed in about one-third of articles (range: 10/36–8/25 [28%–32%]). Conclusions One in seven authors identified in whistleblower complaints as involved in off-label marketing activities adequately disclosed their conflict of

  12. [Involvement of endogenous tachykinins in the development of jejunal mucosa injury induced by on-steroidal anti-inflammatory drugs].

    Science.gov (United States)

    Sendur, Paweł; Ceranowicz, Piotr; Sendur, Ryszard; Cieszkowski, Jakub; Warzecha, Zygmunt; Dembiński, Artur

    2013-01-01

    Previous studies have shown that tachykinins, the largest family of neuropeptides, affect the development of mucosal damage in the stomach and colon. The aim of the study was to assess the influence of tachykinins receptors antagonists on the development of the mucosa injury in the proximal and distal jejunum. Mucosal damage was induced by administration of non-steroidal anti inflammatory drugs (NSAIDs), indomethacin, celecoxib or combination of indomethacin plus celecoxib given intragastrically. NK-1 receptor antagonist (SR 140333), NK-2 receptor antagonist (SR 48968) and NK-3 receptor antagonist (SR 142801) were administered intraperitoneally twice, 30 min before treatment with NSAID and again 24 h later, 30 min before the end of the experiment. Administration of indomethacin, a relatively selective inhibitor for cyclooxygenase-1 (COX-1), induced mucosal lesions in the jejunum. Lesions area in the distal jejunum was 8-fold bigger than in the proximal jejunum. This effect was associated with a significant reduction in mucosal blood flow and an increase in mucosal concentration of pro-inflammatory interleukin-1beta (IL-1beta). Celecoxib, selective inhibitor for COX-2 failed to induce mucosal lesions and did not affect the mucosal blood flow and IL-1beta concentration in the proximal and distal jejunum. In rats treated with a combination of indomethacin plus celecoxib, ulcers reached maximal area. This effect was associated with the highest concentration of mucosal IL-1beta and maximal reduction in mucosal blood flow. Administration of NK-1 receptor antagonist, SR 140333 reduced jejunal damage induced by indomethacin given alone or in combination with celecoxib. This effect was associated with significant reduction in mucosal concentration of IL-1beta. Effect of SR 140333 on mucosal blood flow was statistically insignificant. Neither NK-2 nor NK-3 receptor inhibitor affected mucosal blood flow, IL-1beta concentration area of NSAIDs-induced mucosal damage in the

  13. Sampling and mass spectrometry approaches for the detection of drugs and foreign contaminants in breath for homeland security applications

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Audrey Noreen [Michigan State Univ., East Lansing, MI (United States)

    2009-01-01

    Homeland security relies heavily on analytical chemistry to identify suspicious materials and persons. Traditionally this role has focused on attribution, determining the type and origin of an explosive, for example. But as technology advances, analytical chemistry can and will play an important role in the prevention and preemption of terrorist attacks. More sensitive and selective detection techniques can allow suspicious materials and persons to be identified even before a final destructive product is made. The work presented herein focuses on the use of commercial and novel detection techniques for application to the prevention of terrorist activities. Although drugs are not commonly thought of when discussing terrorism, narcoterrorism has become a significant threat in the 21st century. The role of the drug trade in the funding of terrorist groups is prevalent; thus, reducing the trafficking of illegal drugs can play a role in the prevention of terrorism by cutting off much needed funding. To do so, sensitive, specific, and robust analytical equipment is needed to quickly identify a suspected drug sample no matter what matrix it is in. Single Particle Aerosol Mass Spectrometry (SPAMS) is a novel technique that has previously been applied to biological and chemical detection. The current work applies SPAMS to drug analysis, identifying the active ingredients in single component, multi-component, and multi-tablet drug samples in a relatively non-destructive manner. In order to do so, a sampling apparatus was created to allow particle generation from drug tablets with on-line introduction to the SPAMS instrument. Rules trees were developed to automate the identification of drug samples on a single particle basis. A novel analytical scheme was also developed to identify suspect individuals based on chemical signatures in human breath. Human breath was sampled using an RTube{trademark} and the trace volatile organic compounds (VOCs) were preconcentrated using solid

  14. Adenovirus-vectored drug-vaccine duo as a potential driver for conferring mass protection against infectious diseases.

    Science.gov (United States)

    Zhang, Jianfeng; Tarbet, E Bart; Toro, Haroldo; Tang, De-chu C

    2011-11-01

    The disease-fighting power of vaccines has been a public health bonanza credited with the worldwide reduction of mortality and morbidity. The goal to further amplify its power by boosting vaccine coverage requires the development of a new generation of rapid-response vaccines that can be mass produced at low costs and mass administered by nonmedical personnel. The new vaccines also have to be endowed with a higher safety margin than that of conventional vaccines. The nonreplicating adenovirus-vectored vaccine holds promise in boosting vaccine coverage because the vector can be rapidly manufactured in serum-free suspension cells in response to a surge in demand, and noninvasively administered by nasal spray into human subjects in compliance with evolutionary medicine. In contrast to parenteral injection, noninvasive mucosal vaccination minimizes systemic inflammation. Moreover, pre-existing adenovirus immunity does not interfere appreciably with the potency of an adenovirus-vectored nasal vaccine. Nasal administration of adenovirus vectors encoding pathogen antigens is not only fear-free and painless, but also confers rapid and sustained protection against mucosal pathogens as a drug-vaccine duo since adenovirus particles alone without transgene expression can induce an anti-influenza state in the airway. In addition to human vaccination, animals can also be mass immunized by this class of vectored vaccines.

  15. Accuracy of Coverage Survey Recall following an Integrated Mass Drug Administration for Lymphatic Filariasis, Schistosomiasis, and Soil-Transmitted Helminthiasis.

    Directory of Open Access Journals (Sweden)

    Philip J Budge

    2016-01-01

    Full Text Available Achieving target coverage levels for mass drug administration (MDA is essential to elimination and control efforts for several neglected tropical diseases (NTD. To ensure program goals are met, coverage reported by drug distributors may be validated through household coverage surveys that rely on respondent recall. This is the first study to assess accuracy in such surveys.Recall accuracy was tested in a series of coverage surveys conducted at 1, 6, and 12 months after an integrated MDA in Togo during which three drugs (albendazole, ivermectin, and praziquantel were distributed. Drug distribution was observed during the MDA to ensure accurate recording of persons treated during the MDA. Information was obtained for 506, 1131, and 947 persons surveyed at 1, 6, and 12 months, respectively. Coverage (defined as the percentage of persons taking at least one of the MDA medications within these groups was respectively 88.3%, 87.4%, and 80.0%, according to the treatment registers; it was 87.9%, 91.4% and 89.4%, according to survey responses. Concordance between respondents and registers on swallowing at least one pill was >95% at 1 month and >86% at 12 months; the lower concordance at 12 months was more likely due to difficulty matching survey respondents with the year-old treatment register rather than inaccurate responses. Respondents generally distinguished between pills similar in appearance; concordance for recall of which pills were taken was over 80% in each survey.In this population, coverage surveys provided remarkably consistent coverage estimates for up to one year following an integrated MDA. It is not clear if similar consistency will be seen in other settings, however, these data suggest that in some settings coverage surveys might be conducted as much as one year following an MDA without compromising results. This might enable integration of post-MDA coverage measurement into large, multipurpose, periodic surveys, thereby conserving

  16. From dust to dust: ethical and practical issues involved in the location, exhumation, and identification of bodies from mass graves.

    Science.gov (United States)

    Williams, Erin D; Crews, John D

    2003-06-01

    There are many potential purposes served by the investigation of human remains: criminal fact-finding, archaeological exploration, forensic research, and others. This paper focuses on the identification of remains from mass graves to find missing persons. The primary goal of such efforts is to honor the memory of the dead by bringing closure to living family members, thus supporting the human rights of both the living and the deceased. Cultures, customs, political, and interpersonal specifics will vary, but that singular goal should remain the central guiding principle. This article presents ethical and practical issues resulting from efforts to locate, exhume, and identify the remains of mass fatalities.

  17. Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

    NARCIS (Netherlands)

    Hinney, A.; Kesselmeier, M.; Jall, S.; Volckmar, A.-L.; Föcker, M.; Antel, J.; Heid, I. M.; Winkler, T. W.; Grant, S. F. A.; Guo, Y.; Bergen, A. W.; Kaye, W.; Berrettini, W.; Hakonarson, H.; Herpertz-Dahlmann, B.; de Zwaan, M.; Herzog, W.; Ehrlich, S.; Zipfel, S.; Egberts, K. M.; Adan, R.; Brandys, M.; van Elburg, A.; Boraska Perica, V.; Franklin, C. S.; Tschöp, M. H.; Zeggini, E.; Bulik, C. M.; Collier, D.; Scherag, A.; Müller, T. D.; Hebebrand, J.; Perica, Vesna Boraska; Franklin, Christopher S.; Floyd, James A. B.; Thornton, Laura M.; Huckins, Laura M.; Southam, Lorraine; Rayner, N. William; Tachmazidou, Ioanna; Klump, Kelly L.; Treasure, Janet; Lewis, Cathryn M.; Schmidt, Ulrike; Tozzi, Federica; Iezebrink, Kirsty; Hebebrand, Johannes; Gorwood, Philip; Adan, Roger A. H.; Kas, Martien J. H.; Favaro, Angela; Santonastaso, Paolo; Fernández-Aranda, Fernando; Gratacos, Monica; Rybakowski, Filip; Dmitrzak-Weglarz, Monika; Kaprio, Jaakko; Keski-Rahkonen, Anna; Raevuori-Helkamaa, Anu; van Furth, Eric F.; Slof-Op't Landt, Margarita C. T.; Hudson, James I.; Reichborn-Kjennerud, Ted; Knudsen, Gun Peggy S.; Monteleone, Palmiero; Kaplan, Allan S.; Karwautz, Andreas; Hakonarson, Hakon; Berrettini, Wade H.; Guo, Yiran; Li, Dong; Schork, Nicholas J.; Komaki, Gen; Ando, Tetsuya; Inoko, Hidetoshi; Esko, Tõnu; Fischer, Krista; Männik, Katrin; Metspalu, Andres; Baker, Jessica H.; Cone, Roger D.; Dackor, Jennifer; DeSocio, Janiece E.; Hilliard, Christopher E.; O'Toole, Julie K.; Pantel, Jacques; Szatkiewicz, Jin P.; Taico, Chrysecolla; Zerwas, Stephanie; Trace, Sara E.; Davis, Oliver S. P.; Helder, Sietske; Bühren, Katharina; Burghardt, Roland; de Zwaan, Martina; Egberts, Karin; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Imgart, Hartmut; Scherag, André; Scherag, Susann; Zipfel, Stephan; Boni, Claudette; Ramoz, Nicolas; Versini, Audrey; Brandys, Marek K.; Danner, Unna N.; de Kove, Carolien; Hendriks, Judith; Koeleman, Bobby P. C.; Ophoff, Roel A.; Strengman, Eric; van Elburg, Annemarie A.; Bruson, Alice; Clementi, Maurizio; Degortes, Daniela; Forzan, Monica; Tenconi, Elena; Docampo, Elisa; Escaramí, Geòrgia; Jiménez-Murcia, Susana; Lissowska, Jolanta; Rajewski, Andrzej; Szeszenia-Dabrowska, Neonila; Slopien, Agnieszka; Hauser, Joanna; Karhunen, Leila; Meulenbelt, Ingrid; Slagboom, P. Eline; Tortorella, Alfonso; Maj, Mario; Dedoussis, George; Dikeos, Dimitris; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Tsitsika, Artemis; Papezova, Hana; Slachtova, Lenka; Martaskova, Debora; Kennedy, James L.; Levitan, Robert D.; Yilmaz, Zeynep; Huemer, Julia; Koubek, Doris; Merl, Elisabeth; Wagner, Gudrun; Lichtenstein, Paul; Breen, Gerome; Cohen-Woods, Sarah; Farmer, Anne; McGuffin, Peter; Cichon, Sven; Giegling, Ina; Herms, Stefan; Rujescu, Dan; Schreiber, Stefan; Wichmann, H.-Erich; Dina, Christian; Sladek, Rob; Gambaro, Giovanni; Soranzo, Nicole; Julia, Antonio; Marsal, Sara; Rabionet, Raquel; Gaborieau, Valerie; Dick, Danielle M.; Palotie, Aarno; Ripatti, Samuli; Widén, Elisabeth; Andreassen, Ole A.; Espeseth, Thomas; Lundervold, Astri; Reinvang, Ivar; Steen, Vidar M.; Hellard, Stephanie Le; Mattingsdal, Morten; Ntalla, Ioanna; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Navratilova, Marie; Gallinger, Steven; Pinto, Dalila; Scherer, Stephen W.; Aschauer, Harald; Carlberg, Laura; Schosser, Alexandra; Alfredsson, Lars; Ding, Bo; Klareskog, Lars; Padyukov, Leonid; Finan, Chris; Kalsi, Gursharan; Roberts, Marion; Logan, Darren W.; Peltonen, Leena; Ritchie, Graham R. S.; Barrett, Jeff C.; Estivill, Xavier; Hinney, Anke; Sullivan, Patrick F.; Collier, David A.; Zeggini, Eleftheria; Bulik, Cynthia M.; Anderson, Carl A.; Barrett, Jeffrey C.; McGinnis, Ralph; Sambrook, Jennifer; Stephens, Jonathan; Ouwehand, Willem H.; McArdle, Wendy L.; Ring, Susan M.; Strachan, David P.; Alexander, Graeme; Conlon, Peter J.; Dominiczak, Anna; Duncanson, Audrey; Hill, Adrian; Langford, Cordelia; Lord, Graham; Maxwell, Alexander P.; Morgan, Linda; Sandford, Richard N.; Sheerin, Neil; Vannberg, Frederik O.; Blackburn, Hannah; Chen, Wei-Min; Edkins, Sarah; Gillman, Mathew; Gray, Emma; Hunt, Sarah E.; Nengut-Gumuscu, Suna; Potter, Simon; Rich, Stephen S.; Simpkin, Douglas; Whittaker, Pamela; de Bakker, P.; Bültmann, U.; Geleijnse, M.; Harst, P. V.; Koppelman, G.; Rosmalen, J. G.; van Rossum, L.; Smidt, H.; Swertz, M. A.; Stolk, R. P.; Alizadeh, B.; de Boer, R.; Boezen, H. M.; Bruinenberg, M.; Franke, L.; van der Harst, P.; Hillege, H.; van der Klauw, M.; Navis, G.; Ormel, J.; Postma, D.; Rosmalen, J.; Slaets, J.; Snieder, H.; Stolk, R.; Wolffenbuttel, B.; Wijmenga, C.; Berg, J.; Blackwood, D.; Campbell, H.; Cavanagh, J.; Connell, J.; Connor, M.; Cunningham-Burley, S.; Deary, I.; Dominiczak, A.; Ellis, P.; FitzPatrick, B.; Ford, I.; Gertz, R.; Grau, A.; Haddow, G.; Jackson, C.; Kerr, S.; Lindsay, R.; McGilchrist, M.; McIntyre, D.; Morris, A.; Morton, R.; Muir, W.; Murray, G.; Palmer, C.; Pell, J.; Philp, A.; Porteous, D.; Porteous, M.; Procter, R.; Ralston, S.; Reid, D.; Sinnott, R.; Smith, B.; Clair, D. S.; Sullivan, F.; Sweetland, M.; Ure, J.; Watt, G.; Wolf, R.; Wright, A.; Berndt, S. I.; Gustafsson, S.; Mägi, R.; Ganna, A.; Wheeler, E.; Feitosa, M. F.; Justice, A. E.; Monda, K. L.; Croteau-Chonka, D. C.; Day, F. R.; Esko, T.; Fall, T.; Ferreira, T.; Gentilini, D.; Jackson, A. U.; Luan, J.; Randall, J. C.; Vedantam, S.; Willer, C. J.; Wood, A. R.; Workalemahu, T.; Hu, Y. J.; Lee, S. H.; Liang, L.; Lin, D. Y.; Min, J. L.; Neale, B. M.; Thorleifsson, G.; Yang, J.; Albrecht, E.; Amin, N.; Bragg-Gresham, J. L.; Cadby, G.; den Heijer, M.; Eklund, N.; Fischer, K.; Goel, A.; Hottenga, J. J.; Huffman, J. E.; Jarick, I.; Johansson, A.; Johnson, T.; Kanoni, S.; Kleber, M. E.; König, I. R.; Kristiansson, K.; Kutalik, Z.; Lamina, C.; Lecoeur, C.; Li, G.; Mangino, M.; McArdle, W. L.; Medina-Gomez, C.; Müller-Nurasyid, M.; Ngwa, J. S.; Nolte, I. M.; Paternoster, L.; Pechlivanis, S.; Perola, M.; Peters, M. J.; Preuss, M.; Rose, L. M.; Shi, J.; Shungin, D.; Smith, A. V.; Strawbridge, R. J.; Surakka, I.; Teumer, A.; Trip, M. D.; Tyrer, J.; van Vliet-Ostaptchouk, J. V.; Vandenput, L.; Waite, L. L.; Zhao, J. H.; Absher, D.; Asselbergs, F. W.; Atalay, M.; Attwood, A. P.; Balmforth, A. J.; Basart, H.; Beilby, J.; Bonnycastle, L. L.; Brambilla, P.; Chasman, D. I.; Chines, P. S.; Collins, F. S.; Connell, J. M.; Cookson, W.; de Faire, U.; de Vegt, F.; dei, M.; Dimitriou, M.; Edkins, S.; Estrada, K.; Evans, D. M.; Farrall, M.; Ferrario, M. M.; Ferrières, J.; Frau, F.; Gejman, P. V.; Grallert, H.; Grönberg, H.; Gudnason, V.; Hall, A. S.; Hall, P.; Hartikainen, A. L.; Hayward, C.; Heard-Costa, N. L.; Heath, A. C.; Homuth, G.; Hu, F. B.; Hunt, S. E.; Hyppönen, E.; Iribarren, C.; Jacobs, K. B.; Jansson, J. O.; Jula, A.; Kähönen, M.; Kathiresan, S.; Kee, F.; Khaw, K. T.; Kivimaki, M.; Koenig, W.; Kraja, A. T.; Kumari, M.; Kuulasmaa, K.; Kuusisto, J.; Laitinen, J. H.; Lakka, T. A.; Langenberg, C.; Launer, L. J.; Lind, L.; Lindström, J.; Liu, J.; Liuzzi, A.; Lokki, M. L.; Lorentzon, M.; Madden, P. A.; Magnusson, P. K.; Manunta, P.; Marek, D.; März, W.; Mateo Leach, I.; McKnight, B.; Medland, S. E.; Mihailov, E.; Milani, L.; Montgomery, G. W.; Mooser, V.; Mühleisen, T. W.; Munroe, P. B.; Musk, A. W.; Narisu, N.; Nicholson, G.; Nohr, E. A.; Ong, K. K.; Oostra, B. A.; Palmer, C. N.; Palotie, A.; Peden, J. F.; Pedersen, N.; Peters, A.; Polasek, O.; Pouta, A.; Pramstaller, P. P.; Prokopenko, I.; Pütter, C.; Radhakrishnan, A.; Raitakari, O.; Rendon, A.; Rivadeneira, F.; Rudan, I.; Saaristo, T. E.; Sambrook, J. G.; Sanders, A. R.; Sanna, S.; Saramies, J.; Schipf, S.; Schreiber, S.; Schunkert, H.; Shin, S. Y.; Signorini, S.; Sinisalo, J.; Skrobek, B.; Soranzo, N.; Stancakova, A.; Stark, K.; Stephens, J. C.; Stirrups, K.; Stumvoll, M.; Swift, A. J.; Theodoraki, E. V.; Thorand, B.; Tregouet, D. A.; Tremoli, E.; van der Klauw, M. M.; van Meurs, J. B.; Vermeulen, S. H.; Viikari, J.; Virtamo, J.; Vitart, V.; Waeber, G.; Wang, Z.; Widen, E.; Wild, S. H.; Willemsen, G.; Winkelmann, B. R.; Witteman, J. C.; Wolffenbuttel, B. H.; Wong, A.; Wright, A. F.; Zillikens, M.; Amouyel, P.; Boehm, B. O.; Boerwinkle, E.; Boomsma, D. I.; Caulfield, M. J.; Chanock, S. J.; Cupples, L.; Cusi, D.; Dedoussis, G. V.; Erdmann, J.; Eriksson, J. G.; Franks, P. W.; Froguel, P.; Gieger, C.; Gyllensten, U.; Hamsten, A.; Harris, T. B.; Hengstenberg, C.; Hicks, A. A.; Hingorani, A.; Hofman, A.; Hovingh, K. G.; Hveem, K.; Illig, T.; Jarvelin, M. R.; Jöckel, K. H.; Keinanen-Kiukaanniemi, S. M.; Kiemeney, L. A.; Kuh, D.; Laakso, M.; Lehtimäki, T.; Levinson, D. F.; Martin, N. G.; Metspalu, A.; Morris, A. D.; Nieminen, M. S.; Njølstad, I.; Ohlsson, C.; Oldehinkel, A. J.; Ouwehand, W. H.; Palmer, L. J.; Penninx, B.; Power, C.; Province, M. A.; Psaty, B. M.; Qi, L.; Rauramaa, R.; Ridker, P. M.; Ripatti, S.; Salomaa, V.; Samani, N. J.; Sørensen, T. I.; Spector, T. D.; Stefansson, K.; Tönjes, A.; Tuomilehto, J.; Uitterlinden, A. G.; Uusitupa, M.; Vollenweider, P.; Wallaschofski, H.; Wareham, N. J.; Watkins, H.; Wichmann, H.-; Wilson, J. F.; Abecasis, G. R.; Assimes, T. L.; Barroso, I.; Boehnke, M.; Borecki, I. B.; Deloukas, P.; Fox, C. S.; Frayling, T.; Groop, L. C.; Haritunian, T.; Hunter, D.; Kaplan, R. C.; Karpe, F.; Moffatt, M.; Mohlke, K. L.; O'Connell, J. R.; Pawitan, Y.; Schadt, E. E.; Schlessinger, D.; Steinthorsdottir, V.; Strachan, D. P.; Thorsteinsdottir, U.; van Duijn, C. M.; Visscher, P. M.; Di Blasio, A. M.; Hirschhorn, J. N.; Lindgren, C. M.; Morris, A. P.; Meyre, D.; McCarthy, M. I.; Speliotes, E. K.; North, K. E.; Loos, R. J.; Adair, L. S.; Ang, W.; van Beijsterveldt, T.; Bergen, N.; Benke, K.; Berry, D. J.; Bradfield, J. P.; Charoen, P.; Coin, L.; Cooper, C.; Cousminer, D. L.; Das, S.; Davis, O. S.; Elliott, P.; Estivill, X.; Feenstra, B.; Flexeder, C.; Freathy, R. M.; Gaillard, R.; Geller, F.; Gillman, M.; Grant, S. F.; Groen-Blokhuis, M.; Goh, L. K.; Guxens, M.; Hattersley, A. T.; Haworth, C. M.; Hadley, D.; Heinrich, J.; Hocher, B.; Holloway, J. W.; Holst, C.; Horikoshi, M.; Huikari, V.; Hypponen, E.; Iñiguez, C.; Jaddoe, V. W.; Kaakinen, M.; Kilpeläinen, T. O.; Kirin, M.; Kowgier, M.; Lakka, H. M.; Lange, L. A.; Lawlor, D. A.; Lewin, A.; Lindgren, C.; Lindi, V.; Maggi, R.; Marsh, J.; Melbye, M.; Middeldorp, C.; Millwood, I.; Mook-Kanamori, D. O.; Murray, J. C.; Nivard, M.; Ntalla, I.; Oken, E.; O'Reilly, P. F.; Panoutsopoulou, K.; Pararajasingham, J.; Pearson, E. R.; Pennell, C. E.; Price, T. S.; Raitakari, O. T.; Rodriguez, A.; Salem, R. M.; Saw, S. M.; Sebert, S.; Siitonen, N.; Simell, O.; Sovio, U.; Pourcain, B. S.; Sunyer, J.; Taal, H. R.; teo, Y. Y.; Thiering, E.; Tiesler, C.; Timpson, N. J.; Valcárcel, B.; Warrington, N. M.; White, S.; Widén, E.; Yaghootkar, H.; Elks, C. E.; Perry, J. R.; Sulem, P.; Franceschini, N.; He, C.; Lunetta, K. L.; Visser, J. A.; Byrne, E. M.; Gudbjartsson, D. F.; Koller, D. L.; Lin, P.; Marongiu, M.; McArdle, P. F.; Stolk, L.; van Wingerden, S. H.; Corre, T.; Ingelsson, E.; Smith, E. N.; Ulivi, S.; Warrington, M.; Zgaga, L.; Alavere, H.; Aspelund, T.; Bandinelli, S.; Berenson, G. S.; Bergmann, S.; Blackburn, H.; Buring, J. E.; Busonero, F.; Chen, W.; Cornelis, M. C.; Couper, D.; Coviello, A. D.; D'Adamo, P.; de Geus, E. J.; Döring, A.; Davey Smith, G.; Easton, D. F.; Eiriksdottir, G.; Emilsson, V.; Eriksson, J.; Ferrucci, L.; Folsom, A. R.; Foroud, T.; Garcia, M.; Gasparini, P.; Hankinson, S. E.; Ferreli, L.; Hernandez, D. G.; Järvelin, M. R.; Johnson, A. D.; Karasik, D.; Kiel, D. P.; Kolcic, I.; Kraft, P.; Laven, J. S.; Li, S.; Levy, D.; Murray, S. S.; Nalls, M. A.; Navarro, P.; Nelis, M.; Ness, A. R.; Northstone, K.; Peacock, M.; Paré, G.; Parker, A. N.; Pedersen, N. L.; Peltonen, L.; Pharoah, P.; Plump, A. S.; Porcu, E.; Rafnar, T.; Rice, J. P.; Ring, S. M.; Sala, C.; Schork, N. J.; Scuteri, A.; Segrè, A. V.; Shuldiner, A. R.; Srinivasan, S. R.; Tammesoo, M. L.; Tikkanen, E.; Toniolo, D.; Tsui, K.; Tryggvadottir, L.; Uda, M.; van Dam, R. M.; Waterworth, D. M.; Weedon, M. N.; Wichmann, H. E.; Young, L.; Zhai, G.; Zhuang, W. V.; Bierut, L. J.; Boyd, H. A.; Crisponi, L.; Demerath, E. W.; Econs, M. J.; Hunter, D. J.; Streeten, E. A.; Murabito, J. M.; Murray, A.; Brandt, Harry; Crawford, Steve; Crow, Scott; Fichter, Manfred M.; Halmi, Katherine A.; Johnson, Craig; Via, Maria La; Mitchell, James; Strober, Michael; Rotondo, Alessandro; Woodside, D. Blake; Keel, Pamela; Lilenfeld, Lisa; Plotnicov, Kathy; Bergen, Andrew W.; Berrettini, Wade; Kaye, Walter; Magistretti, Pierre

    2017-01-01

    The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity.

  18. Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

    NARCIS (Netherlands)

    Hinney, A; Kesselmeier, M; Jall, S; Volckmar, A-L; Föcker, M; Antel, J; Heid, I M; Winkler, T W; Grant, S F A; Guo, Y; Bergen, A W; Kaye, W; Berrettini, W; Hakonarson, H; Herpertz-Dahlmann, B; de Zwaan, M; Herzog, W; Ehrlich, S; Zipfel, S; Egberts, K M; Adan, R; Brandys, M; van Elburg, A; Boraska Perica, V; Franklin, C S; Tschöp, M H; Zeggini, E; Bulik, C M; Collier, D; Scherag, A; Müller, T D; Hebebrand, J; Hottenga, J.J.; Willemsen, Gonneke; Boomsma, D.I.; van Beijsterveldt, C.E.M.; Middeldorp, C.M.; de Geus, Eco

    The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity.

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

    Science.gov (United States)

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

    2017-07-01

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

  20. Prevalence of Active and Latent Yaws in the Solomon Islands 18 Months after Azithromycin Mass Drug Administration for Trachoma.

    Science.gov (United States)

    Marks, Michael; Sokana, Oliver; Nachamkin, Eli; Puiahi, Elliot; Kilua, Georgina; Pillay, Allan; Bottomley, Christian; Solomon, Anthony W; Mabey, David C

    2016-08-01

    Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination. This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1-14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA) and the non-treponemal Rapid Plasma Reagin (RPR) test. A total of 1,284 children were enrolled in the study. Amongst children aged 5-14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6-47.7%). The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1-8.7%), and this did not differ significantly from our initial post-mass drug administration (MDA) follow-up survey (4.3% versus 3.5%, p = 0.43) but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p threshold, and strategies to improve coverage at all stages of yaws eradication efforts should be investigated.

  1. KRAS G12C Drug Development: Discrimination between Switch II Pocket Configurations Using Hydrogen/Deuterium-Exchange Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Jia; Harrison, Rane A.; Li, Lianbo; Zeng, Mei; Gondi, Sudershan; Scott, David; Gray, Nathanael S.; Engen, John R.; Westover, Kenneth D. (NEU); (DFCI); (UTSMC); (Harvard-Med)

    2017-09-01

    KRAS G12C, the most common RAS mutation found in non-small-cell lung cancer, has been the subject of multiple recent covalent small-molecule inhibitor campaigns including efforts directed at the guanine nucleotide pocket and separate work focused on an inducible pocket adjacent to the switch motifs. Multiple conformations of switch II have been observed, suggesting that switch II pocket (SIIP) binders may be capable of engaging a range of KRAS conformations. Here we report the use of hydrogen/deuterium-exchange mass spectrometry (HDX MS) to discriminate between conformations of switch II induced by two chemical classes of SIIP binders. We investigated the structural basis for differences in HDX MS using X-ray crystallography and discovered a new SIIP configuration in response to binding of a quinazoline chemotype. These results have implications for structure-guided drug design targeting the RAS SIIP.

  2. Simultaneous determination of antiretroviral drugs in human hair with liquid chromatography-electrospray ionization-tandem mass spectrometry.

    Science.gov (United States)

    Wu, Yan; Yang, Jin; Duan, Cailing; Chu, Liuxi; Chen, Shenghuo; Qiao, Shan; Li, Xiaoming; Deng, Huihua

    2018-04-15

    The determination of the concentrations of antiretroviral drugs in hair is believed to be an important means for the assessment of the long-term adherence to highly active antiretroviral therapy. At present, the combination of tenofovir, lamivudine and nevirapine is widely used in China. However, there was no research reporting simultaneous determination of the three drugs in hair. The present study aimed to develop a sensitive method for simultaneous determination of the three drugs in 2-mg and 10-mg natural hair (Method 1 and Method 2). Hair samples were incubated in methanol at 37 °C for 16 h after being rinsed with methanol twice. The analysis was performed on high performance liquid chromatography tandem mass spectrometry with electronic spray ionization in positive mode and multiple reactions monitoring. Method 1 and Method 2 showed the limits of detection at 160 and 30 pg/mg for tenofovir, at 5 and 6 pg/mg for lamivudine and at 15 and 3 pg/mg for nevirapine. The two methods showed good linearity with the square of correlation coefficient >0.99 at the ranges of 416-5000 and 77-5000 pg/mg for tenofovir, 12-5000 and 15-5000 pg/mg for lamivudine and 39-50,000 and 6-50,000 pg/mg for nevirapine. They gave intra-day and inter-day coefficient of variation <15% and the recoveries ranging from 80.6 to 122.3% and from 83.1 to 114.4%. Method 2 showed LOD and LOQ better than Method 1 for tenofovir and nevirapine and matched Method 1 for lamivudine, but there was high consistency between them in the determination of the three drugs in hair. The population analysis with Method 2 revealed that the concentrations in hair were decreased with the distance of hair segment away from the scalp for the three antiretroviral drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Modelling control of Schistosoma haematobium infection: predictions of the long-term impact of mass drug administration in Africa.

    Science.gov (United States)

    Gurarie, David; Yoon, Nara; Li, Emily; Ndeffo-Mbah, Martial; Durham, David; Phillips, Anna E; Aurelio, H Osvaldo; Ferro, Josefo; Galvani, Alison P; King, Charles H

    2015-10-22

    Effective control of schistosomiasis remains a challenging problem for endemic areas of the world. Given knowledge of the biology of transmission and past experience with mass drug administration (MDA) programs, it is important to critically evaluate the likelihood that MDA programs will achieve substantial reductions in Schistosoma prevalence. In implementing the World Health Organization Roadmap for Neglected Tropical Diseases it would useful for policymaking to model projections of the status of Schistosoma control in MDA-treated areas in the next 5-10 years. Calibrated mathematical models were used to project the effects of different frequency and coverage of MDA for schistosomiasis haematobia control in present-day endemic communities, taking into account uncertainties of parasite biology and input data. The modeling approach in this analysis was the Stratified Worm Burden model developed in our earlier works, calibrated using data from longitudinal S. haematobium control trials in Kenya. Model-based simulations of MDA control in typical low-risk and higher-risk communities indicated that infection prevalence can be substantially reduced within 10 years only when there is a high degree of community participation (>70 %) with at least annual MDA. Significant risk for re-emergence of infection remains if MDA is suspended. In a stable (stationary) ecosystem, Schistosoma reproduction and transmission are sufficiently robust that the process of human infection continues, even under pressure from aggressive MDA. MDA alone is unlikely to interrupt transmission, and once mass treatment is suspended, the prevalence of human infection is likely to rebound to pre-control levels over a period of 25-30 years. MDA success in achieving very low levels of infection prevalence is highly dependent on treatment coverage and frequency within the local human population, and requires that both adults and children be included in drug delivery coverage. Ultimately, supplemental

  4. Model mass spectrometric study of competitive interactions of antimicrobial bisquaternary ammonium drugs and aspirin with membrane phospholipids

    Directory of Open Access Journals (Sweden)

    Vekey K.

    2013-03-01

    Full Text Available The aim of the study is to reveal molecular mechanisms of possible activity modulation of antimicrobial bis-quaternary ammonium compounds (BQAC and aspirin (ASP through noncovalent competitive complexation under their combined introduction into the model systems with membrane phospholipids. Methods. Binary and triple systems containing either decamethoxinum or ethonium, or thionium and aspirin, as well as dipalmitoyl-phosphatidylcholine (DPPC have been investigated by electrospray ionization mass spectrometry. Results. Basing on the analysis of associates recorded in the mass spectra, the types of nonocovalent complexes formed in the systems studied were determined and the supposed role of the complexation in the BQAC and ASP activity modulation was discussed. The formation of associates of BQAC dications with ASP anion is considered as one of the possible ways of deactivation of ionic forms of the medications. The formation of stable complexes of BQAC with DPPC and ASP with DPPC in binary systems as well as the complexes distribution in triple-components systems BQAC:ASP:DPPC point to the existence of competition between drugs of these two types for the binding to DPPC. Conclusions. The results obtained point to the competitive complexation in the model molecular systems containing the BQAC, aspirin and membrane phospholipids. The observed phenomenon testifies to the possibility of modulating the activity of bisquaternary antimicrobial agents and aspirin under their combined usage, due to the competition between the drugs for binding to the target membrane phospholipid molecules and also due to the formation of stable noncovalent complexes between BQAC and ASP.

  5. Mass drug administration and the sustainable control of schistosomiasis: Community health workers are vital for global elimination efforts.

    Science.gov (United States)

    Inobaya, Marianette T; Chau, Thao N; Ng, Shu-Kay; MacDougall, Colin; Olveda, Remigio M; Tallo, Veronica L; Landicho, Jhoys M; Malacad, Carol M; Aligato, Mila F; Guevarra, Jerric R; Ross, Allen G

    2018-01-01

    Schistosomiasis control is centred on preventive chemotherapy through mass drug administration (MDA). However, endemic countries continue to struggle to attain target coverage rates and patient compliance. In the Philippines, barangay health workers (BHWs) play a vital role in the coordination of MDA, acting as advocates, implementers, and educators. The aim of this study was to determine whether BHW knowledge and attitudes towards schistosomiasis and MDA is sufficient and correlated with resident knowledge and drug compliance. A cross-sectional survey was conducted in 2015 among 2186 residents and 224 BHWs in the province of Northern Samar, the Philippines using a structured survey questionnaire. BHWs showed good familiarity on how schistosomiasis is acquired and diagnosed. Nevertheless, both BHWs and residents had poor awareness of the signs and symptoms of schistosomiasis, disease prevention, and treatment options. There was no correlation between the knowledge scores of the BHWs and the residents (r=0.080, p=0.722). Kruskal-Wallis analysis revealed significant differences in BHW knowledge scores between the low (3.29, 95% confidence interval 3.16-3.36), moderate (3.61, 95% confidence interval 3.49-3.69), and high (4.05, 95% confidence interval 3.77-4.13) compliance village groups (p=0.002), with the high compliance areas having the highest mean knowledge scores. This study highlights the importance of community health workers in obtaining the World Health Organization drug coverage rate of 75% and improving compliance with MDA in the community. Investing in the education of community health workers with appropriate disease-specific training is crucial if disease elimination is ultimately to be achieved. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  6. RUMOURS, RIOTS AND THE REJECTION OF MASS DRUG ADMINISTRATION FOR THE TREATMENT OF SCHISTOSOMIASIS IN MOROGORO, TANZANIA.

    Science.gov (United States)

    Hastings, Julie

    2016-09-01

    In 2008 in Morogoro region, Tanzania, mass drug administration (MDA) to school-aged children to treat two neglected tropical diseases (NTDs) - urinary schistosomiasis and soil-transmitted helminths - was suspended by the Ministry of Health and Social Welfare after riots broke out in schools where drugs were being administered. This article discusses why this biomedical intervention was so vehemently rejected, including an eyewitness account. As the protest spread to the village where I was conducting fieldwork, villagers accused me of bringing medicine into the village with which to 'poison' the children and it was necessary for me to leave immediately under the protection of the Tanzanian police. The article examines the considerable differences between biomedical and local understandings of one of these diseases, urinary schistosomiasis. Such a disjuncture was fuelled further by the apparent rapidity of rolling out MDA and subsequent failures in communication between programme staff and local people. Rumours of child fatalities as well as children's fainting episodes and illnesses following treatment brought about considerable conjecture both locally and nationally that the drugs had been either faulty, counterfeit, hitherto untested on humans or part of a covert sterilization campaign. The compelling arguments by advocates of MDA for the treatment of NTDs rest on the assumption that people suffering from these diseases will be willing to swallow the medicine. However, as this article documents, this is not always the case. For treatment of NTDs to be successful it is not enough for programmes to focus on economic and biomedical aspects of treatment, rolling out 'one size fits all' programmes in resource-poor settings. It is imperative to develop a biosocial approach: to consider the local social, biological, historical, economic and political contexts in which these programmes are taking place and in which the intended recipients of treatment live their lives

  7. Detection of singly- and doubly-charged quaternary ammonium drugs in equine urine by liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Ho, Emmie N M; Kwok, W H; Wong, April S Y; Wan, Terence S M

    2012-01-13

    Quaternary ammonium drugs (QADs) are anticholinergic agents some of which are known to have been abused or misused in equine sports. A recent review of literature shows that the screening methods reported thus far for QADs mainly cover singly-charged QADs. Doubly-charged QADs are extremely polar substances which are difficult to be extracted and poorly retained on reversed-phase columns. It would be ideal if a comprehensive method can be developed which can detect both singly- and doubly-charged QADs. This paper describes an efficient liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the simultaneous detection and confirmation of 38 singly- and doubly-charged QADs at sub-parts-per-billion (ppb) to low-ppb levels in equine urine after solid-phase extraction. Quaternary ammonium drugs were extracted from equine urine by solid-phase extraction (SPE) using an ISOLUTE(®) CBA SPE column and analysed by LC/MS/MS in the positive electrospray ionisation mode. Separation of the 38 QADs was achieved on a polar group embedded C18 LC column with a mixture of aqueous ammonium formate (pH 3.0, 10 mM) and acetonitrile as the mobile phase. Detection and confirmation of the 38 QADs at sub-ppb to low-ppb levels in equine urine could be achieved within 16 min using selected reaction monitoring (SRM). Matrix interference of the target transitions at the expected retention times was not observed. Other method validation data, including precision and recovery, were acceptable. The method was successfully applied to the analyses of drug-administration samples. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Highly sensitive capillary electrophoresis-mass spectrometry for rapid screening and accurate quantitation of drugs of abuse in urine.

    Science.gov (United States)

    Kohler, Isabelle; Schappler, Julie; Rudaz, Serge

    2013-05-30

    The combination of capillary electrophoresis (CE) and mass spectrometry (MS) is particularly well adapted to bioanalysis due to its high separation efficiency, selectivity, and sensitivity; its short analytical time; and its low solvent and sample consumption. For clinical and forensic toxicology, a two-step analysis is usually performed: first, a screening step for compound identification, and second, confirmation and/or accurate quantitation in cases of presumed positive results. In this study, a fast and sensitive CE-MS workflow was developed for the screening and quantitation of drugs of abuse in urine samples. A CE with a time-of-flight MS (CE-TOF/MS) screening method was developed using a simple urine dilution and on-line sample preconcentration with pH-mediated stacking. The sample stacking allowed for a high loading capacity (20.5% of the capillary length), leading to limits of detection as low as 2 ng mL(-1) for drugs of abuse. Compound quantitation of positive samples was performed by CE-MS/MS with a triple quadrupole MS equipped with an adapted triple-tube sprayer and an electrospray ionization (ESI) source. The CE-ESI-MS/MS method was validated for two model compounds, cocaine (COC) and methadone (MTD), according to the Guidance of the Food and Drug Administration. The quantitative performance was evaluated for selectivity, response function, the lower limit of quantitation, trueness, precision, and accuracy. COC and MTD detection in urine samples was determined to be accurate over the range of 10-1000 ng mL(-1) and 21-1000 ng mL(-1), respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Prevalence of trachoma in the Kayes region of Mali eight years after stopping mass drug administration.

    Science.gov (United States)

    Traoré, Lamine; Dembele, Benoit; Keita, Modibo; Reid, Steven D; Dembéle, Mahamadou; Mariko, Bréhima; Coulibaly, Famolo; Goldman, Whitney; Traoré, Dramane; Coulibaly, Daouda; Guindo, Boubacar; Amon, Joseph J; Knieriemen, Marily; Zhang, Yaobi

    2018-02-01

    In 2009, three years after stopping mass treatment with azithromycin, a trachoma impact survey in four health districts in the Kayes region of Mali found a prevalence of trachomatous inflammation-follicular (TF) among children aged 1 to 9 years of >5% and a trachomatous trichiasis (TT) prevalence within the general population (≥1-year-old) of <1%. As a result, the government's national trachoma program expanded trichiasis surgery and related activities required to achieve trachoma elimination. In 2015, to assess progress towards elimination, a follow-up impact survey was conducted in the Kayes, Kéniéba, Nioro and Yélimané health districts. The survey used district level two-stage cluster random sampling methodology with 20 clusters of 30 households in each evaluation unit. Subjects were eligible for examination if they were ≥1 year. TF and TT cases were identified and confirmed by experienced ophthalmologists. In total 14,159 people were enumerated and 11,620 (82%) were examined. TF prevalence (95% confidence interval (CI)) was 0.5% (0.3-1%) in Kayes, 0.8% (0.4-1.7%) in Kéniéba, 0.2% (0-0.9%) in Nioro and 0.3% (0.1-1%) in Yélimané. TT prevalence (95% CI) was 0.04% (0-0.25%) in Kayes, 0.29% (0.11-0.6%) in Kéniéba, 0.04% (0-0.25%) in Nioro and 0.07% (0-0.27%) in Yélimané. Eight years after stopping MDA and intensifying trichiasis surgery outreach campaigns, all four districts reached the TF elimination threshold of <5% and three of four districts reached the TT elimination threshold of <0.1%.

  10. Multidimensional family therapy HIV/STD risk-reduction intervention: an integrative family-based model for drug-involved juvenile offenders.

    Science.gov (United States)

    Marvel, Francoise; Rowe, Cynthia L; Colon-Perez, Lissette; DiClemente, Ralph J; Liddle, Howard A

    2009-03-01

    Drug and juvenile justice involved youths show remarkably high rates of human immunodeficiency virus (HIV)/sexually transmitted disease (STD) risk behaviors. However, existing interventions aimed at reducing adolescent HIV risk behavior have rarely targeted these vulnerable young adolescents, and many approaches focus on individual-level change without attention to family or contextual influences. We describe a new, family-based HIV/ STD prevention model that embeds HIV/STD focused multifamily groups within an adolescent drug abuse and delinquency evidence-based treatment, Multidimensional Family Therapy (MDFT). The approach has been evaluated in a multisite randomized clinical trial with juvenile justice involved youths in the National Institute on Drug Abuse Criminal Justice Drug Abuse Treatment Studies (www.cjdats.org). Preliminary baseline to 6-month outcomes are promising. We describe research on family risk and protective factors for adolescent problem behaviors, and offer a rationale for family-based approaches to reduce HIV/STD risk in this population. We describe the development and implementation of the Multidimensional Family Therapy HIV/STD risk-reduction intervention (MDFT-HIV/ STD) in terms of using multifamily groups and their integration in standard MDFT and also offers a clinical vignette. The potential significance of this empirically based intervention development work is high; MDFT-HIV/STD is the first model to address largely unmet HIV/STD prevention and sexual health needs of substance abusing juvenile offenders within the context of a family-oriented evidence-based intervention.

  11. Involvement of the Pleiotropic Drug Resistance Response, Protein Kinase C Signaling, and Altered Zinc Homeostasis in Resistance of Saccharomyces cerevisiae to Diclofenac ▿

    Science.gov (United States)

    van Leeuwen, Jolanda S.; Vermeulen, Nico P. E.; Vos, J. Chris

    2011-01-01

    Diclofenac is a widely used analgesic drug that can cause serious adverse drug reactions. We used Saccharomyces cerevisiae as a model eukaryote with which to elucidate the molecular mechanisms of diclofenac toxicity and resistance. Although most yeast cells died during the initial diclofenac treatment, some survived and started growing again. Microarray analysis of the adapted cells identified three major processes involved in diclofenac detoxification and tolerance. In particular, pleiotropic drug resistance (PDR) genes and genes under the control of Rlm1p, a transcription factor in the protein kinase C (PKC) pathway, were upregulated in diclofenac-adapted cells. We tested if these processes or pathways were directly involved in diclofenac toxicity or resistance. Of the pleiotropic drug resistance gene products, the multidrug transporter Pdr5p was crucially important for diclofenac tolerance. Furthermore, deletion of components of the cell wall stress-responsive PKC pathway increased diclofenac toxicity, whereas incubation of cells with the cell wall stressor calcofluor white before the addition of diclofenac decreased its toxicity. Also, diclofenac induced flocculation, which might trigger the cell wall alterations. Genes involved in ribosome biogenesis and rRNA processing were downregulated, as were zinc-responsive genes. Paradoxically, deletion of the zinc-responsive transcription factor Zap1p or addition of the zinc chelator 1,10-phenanthroline significantly increased diclofenac toxicity, establishing a regulatory role for zinc in diclofenac resistance. In conclusion, we have identified three new pathways involved in diclofenac tolerance in yeast, namely, Pdr5p as the main contributor to the PDR response, cell wall signaling via the PKC pathway, and zinc homeostasis, regulated by Zap1p. PMID:21724882

  12. Prevalence of Active and Latent Yaws in the Solomon Islands 18 Months after Azithromycin Mass Drug Administration for Trachoma.

    Directory of Open Access Journals (Sweden)

    Michael Marks

    2016-08-01

    Full Text Available Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination.This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1-14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA and the non-treponemal Rapid Plasma Reagin (RPR test.A total of 1,284 children were enrolled in the study. Amongst children aged 5-14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6-47.7%. The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1-8.7%, and this did not differ significantly from our initial post-mass drug administration (MDA follow-up survey (4.3% versus 3.5%, p = 0.43 but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p <0.0001. Village-level MDA coverage was strongly associated with dual-seropositivity (p = 0.005. Amongst children aged 1-4 years, 16 had a positive TPPA (3.5%, 95% CI 1.6-7.1%. This did not differ significantly from the seroprevalence in this age group that had

  13. Human cytosolic glutathione-S-transferases: quantitative analysis of expression, comparative analysis of structures and inhibition strategies of isozymes involved in drug resistance.

    Science.gov (United States)

    Mohana, Krishnamoorthy; Achary, Anant

    2017-08-01

    Glutathione-S-transferase (GST) inhibition is a strategy to overcome drug resistance. Several isoforms of human GSTs are present and they are expressed in almost all the organs. Specific expression levels of GSTs in various organs are collected from the human transcriptome data and analysis of the organ-specific expression of GST isoforms is carried out. The variations in the level of expressions of GST isoforms are statistically significant. The GST expression differs in diseased conditions as reported by many investigators and some of the isoforms of GSTs are disease markers or drug targets. Structure analysis of various isoforms is carried out and literature mining has been performed to identify the differences in the active sites of the GSTs. The xenobiotic binding H site is classified into H1, H2, and H3 and the differences in the amino acid composition, the hydrophobicity and other structural features of H site of GSTs are discussed. The existing inhibition strategies are compared. The advent of rational drug design, mechanism-based inhibition strategies, availability of high-throughput screening, target specific, and selective inhibition of GST isoforms involved in drug resistance could be achieved for the reversal of drug resistance and aid in the treatment of diseases.

  14. Atmospheric identification of active ingredients in over-the-counter pharmaceuticals and drugs of abuse by atmospheric pressure glow discharge mass spectrometry (APGD-MS).

    Science.gov (United States)

    Brewer, Tim M; Verkouteren, Jennifer R

    2011-09-15

    Atmospheric pressure glow discharge mass spectrometry was used to characterize the active ingredients in pharmaceutical over-the-counter (OTC) drug formulations (Tylenol Allergy, Alka-Seltzer Plus Nighttime, Sudafed, Aleve and Mucinex DM) and drugs of abuse (crack cocaine, methamphetamine, MDMA (ecstasy) and hydrocodone). Material was desorbed and directly ionized under atmospheric conditions by allowing the substance to come in direct contact with the plasma followed by mass spectrometric detection. With this technique, controlled substances and OTC medications were readily distinguished from one another. Characteristic mass spectra were identified for the active ingredients in the OTC and drugs of abuse. Importantly, all drug compounds studied here, both OTC and illicit, demonstrated signals for either molecular ions or protonated molecules as well as fragmentation patterns that are readily identified in the National Institute of Standards and Technology (NIST) electron ionization (EI) mass spectral library. It is believed that this technique holds promise for forensic and law enforcement communities for real-time atmospheric analysis of drugs with database-searchable spectra of controlled substances. Published in 2011 by John Wiley & Sons, Ltd.

  15. Analysis of drugs of forensic interest with capillary zone electrophoresis/time-of-flight mass spectrometry based on the use of non-volatile buffers.

    Science.gov (United States)

    Gottardo, Rossella; Mikšík, Ivan; Aturki, Zeineb; Sorio, Daniela; Seri, Catia; Fanali, Salvatore; Tagliaro, Franco

    2012-02-01

    The present work is aimed at investigating the influence of the background electrolyte composition and concentration on the separation efficiency and resolution and mass spectrometric detection of illicit drugs in a capillary zone electrophoresis-electrospray ionization-time of flight mass spectrometry (CZE-ESI-TOF MS) system. The effect of phosphate, borate and Tris buffers on the separation and mass spectrometry response of a mixture of 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, methadone, cocaine, morphine, codeine and 6-monoacetylmorphine was studied, in comparison with a reference ammonium formate separation buffer. Inorganic non-volatile borate and Tris buffers proved hardly suitable for capillary electrophoresis-mass spectrometry (CE-MS) analysis, but quite unexpectedly ammonium phosphate buffers showed good separation and ionization performances for all the analytes tested. Applications of this method to real samples of hair from drug addicts are also provided. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Multi-residue determination of 115 veterinary drugs and pharmaceutical residues in milk powder, butter, fish tissue and eggs using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Dasenaki, Marilena E; Thomaidis, Nikolaos S

    2015-06-23

    A simple and sensitive multi-residue method for the determination of 115 veterinary drugs and pharmaceuticals, belonging in more than 20 different classes, in butter, milk powder, egg and fish tissue has been developed. The method involves a simple generic solid-liquid extraction step (solvent extraction, SE) with 0.1% formic acid in aqueous solution of EDTA 0.1% (w/v)-acetonitrile (ACN)-methanol (MeOH) (1:1:1, v/v) with additional ultrasonic-assisted extraction. Precipitation of lipids and proteins was promoted by subjecting the extracts at very low temperature (-23°C) for 12h. Further cleanup with hexane ensures fat removal from the matrix. Analysis was performed by liquid chromatography coupled with electrospray ionization and tandem mass spectrometry (LC-ESI-MS/MS). Two separate runs were performed for positive and negative ionization in multiple reaction monitoring mode (MRM). Particular attention was devoted to extraction optimization: different sample-to-extracting volume ratios, different concentrations of formic acid in the extraction solvent and different ultrasonic extraction temperatures were tested in butter, egg and milk powder samples. The method was also applied in fish tissue samples. It was validated, on the basis of international guidelines, for all four matrices. Quantitative analysis was performed by means of standard addition calibration. For over 80% of the analytes, the recoveries were between 50% and 120% in all matrices studied, with RSD values in the range of 1-18%. Limits of detection (LODs) and quantification (LOQs) ranged from 0.008 μg kg(-1) (oxfendazole in butter) to 3.15 μg kg(-1) (hydrochlorthiazide in egg). The evaluated method provides reliable screening, quantification, and identification of 115 veterinary drug and pharmaceutical residues in foods of animal origin and has been successfully applied in real samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21

    Directory of Open Access Journals (Sweden)

    Kemin Yan

    2018-03-01

    Full Text Available Objective: Ileal transposition (IT surgery has been reported to improve glucose and lipid metabolism, and fibroblast growth factor 21 (FGF21 is a powerful metabolic regulator. In the present study, we aimed to investigate the effects of IT surgery on metabolism and its possible relationship with the FGF21 signaling pathway in diabetic Goto-Kakizaki (GK rats.Methods: Ten-week-old male GK rats were subjected to IT surgery with translocation of a 10 cm ileal segment to the proximal jejunum (IT group or sham surgery without the ileum transposition (Sham-IT group. Rats in the no surgery group did not receive any surgical intervention. Six weeks later, body weight, fat mass, fasting blood glucose (FBG, and serum levels of FGF21 and leptin were measured. The expression of the FGF21 signaling pathway and white adipose tissue (WAT browning-related genes in the WAT and liver were evaluated by real-time reverse transcription polymerase chain reaction (RT-qPCR and western blot.Results: IT surgery significantly decreased the body weights and FBG levels and increased the insulin sensitivity of GK rats. The total WAT mass of the IT rats showed a 41.5% reduction compared with the Sham-IT rats, and serum levels of FGF21 and leptin of the IT rats decreased by 26.3 and 61.7%, respectively (all P < 0.05. The mRNA levels of fibroblast growth factor receptor 1 (FGFR1 and its co-receptor β klotho (KLB in the perirenal WAT (pWAT of the IT rats were 1.4- and 2.4-fold that of the Sham-IT rats, respectively, and the FGFR1 protein levels were 1.7-fold of the Sham-IT rats (all P < 0.05. In accordance with the pWAT, the protein levels of FGFR1 and KLB in the epididymal WAT (eWAT of the IT rats notably increased to 3.0- and 3.9-fold of the Sham-IT rats (P < 0.05. Furthermore, uncoupling protein 1 (UCP1 protein levels in the eWAT and pWAT of the IT rats also increased to 2.2- and 2.3-fold of the Sham-IT rats (P < 0.05. However, the protein levels of FGFR1 and KLB in the

  18. Involvement of CUL4A in Regulation of Multidrug Resistance to P-gp Substrate Drugs in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yunshan Wang

    2013-12-01

    Full Text Available CUL4A encodes a core component of a cullin-based E3 ubiquitin ligase complex that regulates many critical processes such as cell cycle progression, DNA replication, DNA repair and chromatin remodeling by targeting a variety of proteins for ubiquitination and degradation. In the research described in this report we aimed to clarify whether CUL4A participates in multiple drug resistance (MDR in breast cancer cells. We first transfected vectors carrying CUL4A and specific shCUL4A into breast cancer cells and corresponding Adr cells respectively. Using reverse transcription polymerase chain reactions and western blots, we found that overexpression of CUL4A in MCF7 and MDA-MB-468 cells up-regulated MDR1/P-gp expression on both the transcription and protein levels, which conferred multidrug resistance to P-gp substrate drugs, as determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assays. On the other hand, silencing CUL4A in MCF7/Adr and MDA-MB-468/Adr cells led to the opposite effect. Moreover, ERK1/2 in CUL4A-overexpressing cells was highly activated and after treatment with PD98059, an ERK1/2-specific inhibitor, CUL4A-induced expression of MDR1/P-gp was decreased significantly. Lastly, immunohistochemistry in breast cancer tissues showed that P-gp expression had a positive correlation with the expression of CUL4A and ERK1/2. Thus, these results implied that CUL4A and ERK1/2 participated in multi-drug resistance in breast cancer through regulation of MDR1/P-gp expression.

  19. Resection of tumors of the third ventricle involving the hypothalamus: effects on body mass index using a dedicated surgical approach.

    Science.gov (United States)

    Mortini, Pietro; Gagliardi, Filippo; Bailo, Michele; Boari, Nicola; Castellano, Antonella; Falini, Andrea; Losa, Marco

    2017-07-01

    Resection of large lesions growing into the third ventricle is considered nowadays still a demanding surgery, due to the high risk of severe endocrine and neurological complications. Some neurosurgical approaches were considered in the past the procedures of choice to access the third ventricle, however they were burden by endocrine and neurological consequences, like memory loss and epilepsy. We report here the endocrine and functional results in a series of patients operated with a recently developed approach specifically tailored for the resection of large lesions growing into the third ventricle. Authors conducted a retrospective analysis on 10 patients, operated between 2011 and 2012, for the resection of large tumors growing into the third ventricle. Total resection was achieved in all patients. No perioperative deaths were recorded and all patients were alive after the follow-up. One year after surgery 8/10 patients had an excellent outcome with a Karnofsky Performance Status of 100 and a Glasgow Outcome score of 5, with 8 patients experiencing an improvement of the Body Mass Index. Modern neurosurgery allows a safe and effective treatment of large lesions growing into the third ventricle with a postoperative good functional status.

  20. Sequential modelling of the effects of mass drug treatments on anopheline-mediated lymphatic filariasis infection in Papua New Guinea.

    Directory of Open Access Journals (Sweden)

    Brajendra K Singh

    Full Text Available Lymphatic filariasis (LF has been targeted by the WHO for global eradication leading to the implementation of large scale intervention programs based on annual mass drug administrations (MDA worldwide. Recent work has indicated that locality-specific bio-ecological complexities affecting parasite transmission may complicate the prediction of LF extinction endpoints, casting uncertainty on the achievement of this initiative. One source of difficulty is the limited quantity and quality of data used to parameterize models of parasite transmission, implying the important need to update initially-derived parameter values. Sequential analysis of longitudinal data following annual MDAs will also be important to gaining new understanding of the persistence dynamics of LF. Here, we apply a Bayesian statistical-dynamical modelling framework that enables assimilation of information in human infection data recorded from communities in Papua New Guinea that underwent annual MDAs, into our previously developed model of parasite transmission, in order to examine these questions in LF ecology and control.Biological parameters underlying transmission obtained by fitting the model to longitudinal data remained stable throughout the study period. This enabled us to reliably reconstruct the observed baseline data in each community. Endpoint estimates also showed little variation. However, the updating procedure showed a shift towards higher and less variable values for worm kill but not for any other drug-related parameters. An intriguing finding is that the stability in key biological parameters could be disrupted by a significant reduction in the vector biting rate prevailing in a locality.Temporal invariance of biological parameters in the face of intervention perturbations indicates a robust adaptation of LF transmission to local ecological conditions. The results imply that understanding the mechanisms that underlie locally adapted transmission dynamics will

  1. Multi-residue method for the detection of veterinary drugs in distillers grains by liquid chromatography-Orbitrap high resolution mass spectrometry.

    Science.gov (United States)

    Kaklamanos, George; Vincent, Ursula; von Holst, Christoph

    2013-12-27

    Distillers Grain (DG) is an important by-product of ethanol production. The ethanol production process uses only the starch portion of the plant and all the remaining nutrients, protein, fat, minerals, and vitamins remain in DGs, a valuable feed material for livestock. The use of antimicrobial drugs is helpful to limit harmful bacterial growth during the early part of the fermentation process. This can lead to the possible presence of contaminants in the by-products that are used in the food and feed industries, resulting in a major concern for the development of bacterial resistance in both humans and animals. To facilitate the detection of antimicrobial and other commonly used veterinary drugs in DGs, a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed targeting a wide range of 12 chemical classes of anti-bacterial substances and drugs, such as ionophore and non-ionophore authorized coccidiostats, banned coccidiostats, macrolides, tetracyclines, nitroimidazoles, amphenicols, quinolones, sulphonamides, tranquilizers, non-steroidal anti-inflammatory drugs and benzimidazoles. Following a simple and fast extraction step with a mixture of organic solvents, the extract was directly injected into the LC coupled to an Orbitrap mass analyzer. The identification of residues is based on accurate mass measurement. The high mass resolution of 50,000 full width at half maximum (FWHM) and corresponding narrow mass windows permitted a very selective and sensitive detection of the analytes in such a complex matrix. A single-laboratory validation procedure was carried out evaluating selectivity, sensitivity, linearity, precision and accuracy. The method showed satisfactory analytical performance for precision and trueness, and allowed the determination of the compounds at low concentration. The proposed multi-method demonstrated that liquid chromatography coupled to an Orbitrap mass spectrometer is a promising analytical technique, suitable for

  2. [Update of a database on plants involved in the composition of 825 drugs: Pharmaplantes-Kénitra 98].

    Science.gov (United States)

    Choulli, M K; Quyou, A; Ait Aguil, F; Rmouch, H

    1999-01-01

    The main objective of this work lies in the setting up of a database on plants used in medicines which is aimed at pharmacological development of plant resources in Morocco. We have, as a first step, made an inventory of different plant species involved in medicine making in Morocco. This survey dealt with 825 miscellaneous pharmaceutical products and reveals the use of 445 different plant species in medicine making. For each plant species, we have also noted the parts of the plant which are used in the pharmaceutical industry. Furthermore, we have taken an interest in plant extracts involved in this medicine making. The results show that in all these medicines contain 46 extracts of a vegetal nature. At the top of the list, menthol is used in the manufacture of 110 pharmaceutical products. Finally, an analysis per pharmaco-therapeutic family reveals the impact of the involvement of these plants on each of these families. In fact, it turns out that 204 plant species play a part in medicines classified in the family of gastro-entero-hepatology whereas only one plant is involved in anti-inflammatory medicines.

  3. Prescription drug monitoring program data tracking of opioid addiction treatment outcomes in integrated dual diagnosis care involving injectable naltrexone.

    Science.gov (United States)

    Sajid, Ayesha; Whiteman, Aaron; Bell, Richard L; Greene, Marion S; Engleman, Eric A; Chambers, R Andrew

    2016-10-01

    Fourfold increases in opioid prescribing and dispensations over 2 decades in the U.S. has paralleled increases in opioid addictions and overdoses, requiring new preventative, diagnostic, and treatment strategies. This study examines Prescription Drug Monitoring Program (PDMP) tracking as a novel measure of opioid addiction treatment outcomes in a university-affiliated integrated mental health-addiction treatment clinic. Repeated measure parametrics examined PDMP and urine drug screening (UDS) data before and after first injection for all patients (N = 68) who received at least one long-acting naltrexone injection (380 mg/IM) according to diagnostic groupings of having either (i) alcohol (control); (ii) opioid; or (iii) combined alcohol and opioid use disorders. There were no group differences post-injection in treatment days, injections delivered, or treatment service encounters. UDS and PDMP measures of opioid exposures were greater in opioid compared to alcohol-only patients. Post-first injection, UDS's positive for opioids declined (p prescriptions (p prescriptions to those patients. (Am J Addict 2016;25:557-564). © 2016 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc. on behalf of The American Academy of Addiction Psychiatry (AAAP).

  4. The combined fixed-dose antituberculous drugs alter some reproductive functions with oxidative stress involvement in wistar rats

    Directory of Open Access Journals (Sweden)

    O. Awodele, B.Pharm M.Sc MPH PhD D.Sc FPCPharm FASI

    Full Text Available The reproductive toxicity of combined fixed-dose first-line antituberculosis (CFDAT regimen was assessed in rats. Thirty-two (32 Wistar rats weighing 168.1 ± 8.0 g were divided into four groups of eight rats per group. Two groups of male and female rats were administered oral distilled water (1.6 ml and CFDAT drugs containing rifampicin, isoniazid, pyrazinamide and ethambutol (RIPE, 92.5 mg/m2 per body surface area respectively for forty-five days. Serum follicle stimulating hormone, luteinizing and testosterone were reduced significantly (p  0.05 levels in the treated females. In addition, RIPE reduced (p < 0.05 total proteins levels and increased (p < 0.05, 53% catalase levels in male but not female animals. Superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, reduced glutathione levels as well as lipid peroxidation were unaltered in all rats respectively. Histopathological studies revealed congested peritesticular vessels and no changes in the ovary when compared with control. Overall, our results demonstrate reproductive toxicity potentials of RIPE in the rat, thus, suggesting that these reproductive parameters be monitored during antituberculous chemotherapy. Keywords: Fixed dose combined antituberculous drugs, Sub-chronic study, Reproductive toxicity, Rats

  5. (Un)targeted scanning of locks of hair for drugs of abuse by direct analysis in real time-high-resolution mass spectrometry

    NARCIS (Netherlands)

    Duvivier, W.F.; Rutten, van Marc; Beek, van T.A.; Nielen, M.W.F.

    2016-01-01

    Forensic hair evidence can be used to obtain retrospective timelines of drug use by analysis of hair segments. However, this is a laborious and time-consuming process, and mass spectrometric (MS) imaging techniques, which show great potential for single-hair targeted analysis, are less useful due to

  6. Mathematical modelling of lymphatic filariasis elimination programmes in India: Required duration of mass drug administration and post-treatment level of infection indicators

    NARCIS (Netherlands)

    Jambulingam, P. (Purushothaman); S.V. Subramanian; S.J. de Vlas (Sake); Vinubala, C. (Chellasamy); W.A. Stolk (Wilma)

    2016-01-01

    textabstractBackground: India has made great progress towards the elimination of lymphatic filariasis. By 2015, most endemic districts had completed at least five annual rounds of mass drug administration (MDA). The next challenge is to determine when MDA can be stopped. We performed a simulation

  7. Paper Spray and Extraction Spray Mass Spectrometry for the Direct and Simultaneous Quantification of Eight Drugs of Abuse in Whole Blood

    NARCIS (Netherlands)

    Espy, R.D.; Teunissen, S.F.; Manicke, N.E.; Ren, Y.; Ouyang, Z.; van Asten, A.; Cooks, R.G.

    2014-01-01

    Determination of eight drugs of abuse in blood has been performed using paper spray or extraction spray mass spectrometry in under 2 min with minimal sample preparation. A method has been optimized for quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA),

  8. Performance of the linear ion trap Orbitrap mass analyzer for qualitative and quantitative analysis of drugs of abuse and relevant metabolites in sewage water

    NARCIS (Netherlands)

    Bijlsma, L.; Emke, E.; Hernández, F.; de Voogt, P.

    2013-01-01

    This work illustrates the potential of liquid chromatography coupled to a hybrid linear ion trap Fourier Transform Orbitrap mass spectrometer for the simultaneous identification and quantification of 24 drugs of abuse and relevant metabolites in sewage water. The developed methodology consisted of

  9. Effect of repeated mass drug administration with praziquantel and track and treat of taeniosis cases on the prevalence of taeniosis in Taenia solium endemic rural communities of Tanzania

    DEFF Research Database (Denmark)

    Braae, Uffe Christian; Magnussen, Pascal; Ndawi, Benedict

    2017-01-01

    This study evaluated the effect of mass drug administration (MDA) with praziquantel administered to school-aged children (SAC) combined with ‘track and treat’ of taeniosis cases in the general population on the copro-antigen (Ag) prevalence of taeniosis. The study was conducted in 14 villages...

  10. Profiling Nonrecipients of Mass Drug Administration for Schistosomiasis and Hookworm Infections: A Comprehensive Analysis of Praziquantel and Albendazole Coverage in Community-Directed Treatment in Uganda

    NARCIS (Netherlands)

    Chami, G.; Kontoleon, Andreas A.; Bulte, E.H.; Fenwick, Alan

    2016-01-01

    Background. Repeated mass drug administration (MDA) with preventive chemotherapies is the mainstay of morbidity control for schistosomiasis and soil-transmitted helminths, yet the World Health Organization recently reported that less than one-third of individuals who required preventive

  11. Community-directed mass drug administration is undermined by status seeking in friendship networks and inadequate trust in health advice networks

    NARCIS (Netherlands)

    Chami, Goylette F.; Kontoleon, Andreas A.; Bulte, Erwin; Fenwick, Alan; Kabatereine, Narcis B.; Tukahebwa, Edridah M.; Dunne, David W.

    2017-01-01

    Over 1.9 billion individuals require preventive chemotherapy through mass drug administration (MDA). Community-directed MDA relies on volunteer community medicine distributors (CMDs) and their achievement of high coverage and compliance. Yet, it is unknown if village social networks influence

  12. Community-directed mass drug administration is undermined by status seeking in friendship networks and inadequate trust in health advice networks

    NARCIS (Netherlands)

    Chami, Goylette F.; Kontoleon, Andreas A.; Bulte, Erwin; Fenwick, Alan; Kabatereine, Narcis B.; Tukahebwa, Edridah M.; Dunne, David W.

    2017-01-01

    Over 1.9 billion individuals require preventive chemotherapy through mass drug administration (MDA). Community-directed MDA relies on volunteer community medicine distributors (CMDs) and their achievement of high coverage and compliance. Yet, it is unknown if village social networks influence

  13. A mathematical model for long-term effect of diethylcarbamazine-albendazole mass drug administration on lymphatic filariasis

    Science.gov (United States)

    Tasman, H.; Supali, T.; Supriatna, A. K.; Nuraini, N.; Soewono, E.

    2015-03-01

    In this paper we discuss a mathematical model for the transmission of lymphatic filariasis disease. The human population is divided into susceptible, latent, acute and chronic subpopulations. Treatment is carried out within the scheme of mass drug administration (MDA) by giving the diethylcarbamazine (DEC) and albendazole (ALB) to all individuals. In the model, we assume that the treatments have direct killing effect to microfilariae, increase of immune-mediated effect. The treated individuals are assumed to remain susceptible to the disease. This is due to the fact that the treatment is only partially effective against macrofilaria. Simulations of the model reveals that DEC-ALB treatment does give significant reduction of acute and chronic compartments at the end of the treatment period and slow down the growth after the treatment before eventually tend to the endemic state. It showed that repeated treatment during MDA is effective to decrease the transmission. This suggests that terminating MDA program after a long period of its application may still effective in controlling the disease.

  14. Therapeutic drug monitoring of everolimus using the dried blood spot method in combination with liquid chromatography-mass spectrometry.

    Science.gov (United States)

    van der Heijden, J; de Beer, Y; Hoogtanders, K; Christiaans, M; de Jong, G J; Neef, C; Stolk, L

    2009-11-01

    An assay of everolimus based on finger prick sampling and consecutive application as a blood spot on sampling paper has been developed. We explored several methods [K. Hoogtanders, J. van der Heijden, M. Christiaans, P. Edelbroek, J. van Hooff, L. Stolk, J. Pharm. Biomed. Anal. 44 (2006) 658-664; A. Allanson, M. Cotton, J. Tettey, et al., J. Pharm. Biomed. Anal. 44 (2007) 963-969] and developed a new method, namely the impregnation of sampling paper with a solution of plasma-protein, formic acid and ammonium acetate, in combination with the extraction of the blood spot by filter filtration. This kind of sample preparation provides new possibilities for blood spot sampling especially if analytes are adsorbed to the paper. The dried blood spot was analysed using the HPLC-electrospray-tandem mass spectrometry method, with 32-desmethoxyrapamycin as the internal standard. The working range of our study was 2-30 microg/l. Within this range, intra-and inter-assay variability for precision and accuracy was spot samples proved stable for 3 days at 60 degrees C and for 32 days at 4 degrees C. Everolimus concentrations of one stable out-patient were compared after both blood spot sampling and conventional venous sampling on various occasions. Results indicate that this new method is promising for therapeutic drug monitoring in stable renal transplant patients.

  15. Common Peak Approach Using Mass Spectrometry Data Sets for Predicting the Effects of Anticancer Drugs on Breast Cancer

    Directory of Open Access Journals (Sweden)

    Masaru Ushijima

    2007-01-01

    Full Text Available We propose a method for biomarker discovery from mass spectrometry data, improving the common peak approach developed by Fushiki et al. (BMC Bioinformatics, 7:358, 2006. The common peak method is a simple way to select the sensible peaks that are shared with many subjects among all detected peaks by combining a standard spectrum alignment and kernel density estimates. The key idea of our proposed method is to apply the common peak approach to each class label separately. Hence, the proposed method gains more informative peaks for predicting class labels, while minor peaks associated with specifi c subjects are deleted correctly. We used a SELDI-TOF MS data set from laser microdissected cancer tissues for predicting the treatment effects of neoadjuvant therapy using an anticancer drug on breast cancer patients. The AdaBoost algorithm is adopted for pattern recognition, based on the set of candidate peaks selected by the proposed method. The analysis gives good performance in the sense of test errors for classifying the class labels for a given feature vector of selected peak values.

  16. Coverage and Compliance of Mass Drug Administration in Lymphatic Filariasis: A Comparative Analysis in a District of West Bengal, India

    Directory of Open Access Journals (Sweden)

    Tanmay Kanti Panja

    2012-01-01

    Full Text Available Background: Despite several rounds of Mass Drug Administration (MDA as an elimination strategy of Lymphatic Filariasis (LF from India, still the coverage is far behind the required level of 85%.Objectives: The present study was carried out with the objectives to assess the coverage and compliance of MDA and their possible determinants. Methods: A cross-sectional community based study was conducted in Paschim Midnapur district of West Bengal, India for consecutive two years following MDA. Study participants were chosen by 30-cluster sampling technique. Data was collected by using pre-tested semi-structured proforma to assess the coverage and compliance of MDA along with possible determinants for non-attaining the expected coverage. Results: In the year 2009, coverage, compliance, coverage compliance gap (CCG and effective coverage was seen to be 84.1%, 70.5%, 29.5% and 59.3% respectively. In 2010, the results further deteriorated to 78.5%, 66.9%, 33.3% and 57% respectively. The poor coverage and compliance were attributed to improper training of service providers and lack of community awareness regarding MDA.Conclusion: The study emphasized supervised consumption, retraining of service providers before MDA activities, strengthening behaviour change communication strategy for community awareness. Advocacy by the program managers and policy makers towards prioritization of MDA program will make the story of filaria elimination a success.

  17. Fragmentation Pathways of Trifluoroacetyl Derivatives of Methamphetamine, Amphetamine, and Methylenedioxyphenyl alkylamine Designer Drugs by Gas Chromatography/Mass Spectrometry

    International Nuclear Information System (INIS)

    Kumazawa, T.; Xiao-Pen, L.; Sato, K.

    2011-01-01

    Methamphetamine (MA), amphetamine (AM), and the methylenedioxyphenyl alkylamine designer drugs, such as 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy ethylamphetamine (MDEA), N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), 3,4-methylenedioxyamphetamine (MDA), and 3,4-(methylenedioxyphenyl)-2-butanamine (BDB), are widely abused as psychedelics. In this paper, these compounds were derivatized with trifluoroacetic (TFA) anhydride and analyzed by gas chromatography/mass spectrometry using electron ionization in positive mode. Gas chromatographic separation for TFA derivatives of all compounds was successfully resolved using an Equity-5 fused silica capillary column with a poly (5% diphenyl-95% dimethylsiloxane) stationary phase. Base peaks or prominent peaks of MA, AM, MDMA, MDEA, MBDB, MDA, and BDB appeared at m/z 154, 140, 154, 168, 168, 135, and 135, respectively. These occurred due to a-cleavage from the amide nitrogen, splitting into the TFA imine species and benzyl or methylenedioxybenzyl cations. Further prominent fragment ions at m/z 118 for MA and AM, m/z 162 for MDMA, MDEA, and MDA, and m/z 176 for MBDB and BDB were produced by cleavage of the phenylpropane or methylenedioxy propane hydrocarbon radical cation via a hydrogen rearrangement. These fragmentation pathways for the TFA derivatives of all the compounds are summarized and illustrated in this paper.

  18. Identification of impurities in methotrexate drug substances using high-performance liquid chromatography coupled with a photodiode array detector and Fourier transform ion cyclotron resonance mass spectrometry.

    Science.gov (United States)

    Wu, Cai-Sheng; Tong, Yuan-Feng; Wang, Peng-Yuan; Wang, Dong-Mei; Wu, Song; Zhang, Jin-Lan

    2013-05-15

    Methotrexate (MTX) is an antineoplastic therapeutic medicine that acts as an antimetabolite of folic acid. In this study we identified the impurities in MTX drug substances produced by different manufacturers and in different batches using high-performance liquid chromatography coupled with a photodiode array detector and Fourier transform ion cyclotron resonance mass spectrometry (HPLC-PDA/FTICR-MS). MTX and its impurities were separated on a Restek Pinnacle II C18 column (250 × 4.6 mm, 5 µm) with a gradient elution system composed of 0.2% formic acid and acetonitrile at a flow rate of 1.0 mL/min. Ultraviolet (UV) detection was set at 305 nm. Mass detection was carried out using FTICR-MS with full-scan mass analysis at a resolving power of 100 000 coupled with multiple-stage mass analysis using a parent list of compounds. Fifteen impurities were detected in MTX drug substances, and their structures were predicted from using HPLC-PDA/FTICR-MS data, including their UV spectra, high-resolution mass spectrometry (HRMS), fragmentation patterns, and MS(n) spectra. Ten of the impurities detected in the MTX drug substances are reported for the first time. There was a high abundance of esterified impurities in some batches of MTX drug substances, over the identification threshold of International Conference on Harmonization (ICH) guidelines, which requires particular attention. This paper describes a HPLC-PDA/FTICR-MS method to profile and identify impurities in MTX drug substances. The results suggest that HPLC-PDA/FTICR-MS is a valuable analytical technique for the rapid identification of impurities. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Mediating effects of bullying involvement on the relationship of body mass index with social phobia, depression, suicidality, and self-esteem and sex differences in adolescents in Taiwan.

    Science.gov (United States)

    Yen, Cheng-Fang; Liu, Tai-Ling; Ko, Chih-Hung; Wu, Yu-Yu; Cheng, Chung-Ping

    2014-03-01

    The aims of this study were to examine the mediating effect of bullying involvement on the relationships between body mass index (BMI) and mental health problems, including social phobia, depression, suicidality, and low self-esteem among adolescents in Taiwan. The moderation effect of sex on the mediating role of bullying involvement was also examined. Five thousand two hundred and fifty-two students of high schools completed the questionnaires. Victimization and perpetration of passive and active bullying were assessed using the Chinese version of the School Bullying Experience Questionnaire. BMI was calculated from self-reported weight and height measurements. The Social Phobia Inventory, the Mandarin Chinese version of the Center for Epidemiological Studies-Depression Scale, the suicidality-related questionnaire from the epidemiological version of the Kiddie-Schedule for Affective Disorders and Schizophrenia, and the Rosenberg Self-Esteem Scale were applied to assess social phobia, depression, suicidality, and low self-esteem, respectively. The mediating effect of bullying involvement on the associations between increased BMI and mental health problems was examined by the Sobel test. The moderation effect of sex on the mediating role of bullying involvement was tested by the multiple-group structural equation model. Victimization of passive and active bullying and perpetration of passive bullying, but not perpetration of active bullying, had a mediating effect on the relationships between increased BMI and all four mental health problems. Sex did not have a significant moderation effect on the mediating role of bullying involvement. Bullying involvement should be a target of prevention and intervention in developing a strategy to improve mental health among adolescents with increased BMI. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Understanding the structure, dynamics, and mass transport properties of self assembling peptide hydrogels for injectable, drug delivery applications

    Science.gov (United States)

    Branco, Monica Cristina

    hydrogels as a function of peptide sequence and concentration. Changes in nanoscale dynamics and structure inherently lead to substantial differences in bulk properties, such as the elastic modulus and network mesh size. Learning how the material properties of the gels influence the transport rate of therapeutics through the hydrogel is essential to the development of delivery vehicles. The remainder of the thesis focuses on correlating the mesh sizes of MAX1 and MAX8 gels to the diffusion and mass transport properties of model dextran and protein probes. Here, work is centered on how peptide charge and concentration, as well as probe structure, in particular hydrodynamic diameter and charge, dictate the temporal release of model probes from the peptide hydrogels. Experiments include self diffusion studies and bulk release experiments with model dextrans and proteins from gels before and after syringe delivery. Overall, this thesis will demonstrate the importance of understanding material properties from the nanoscale up to the macroscale for application based design. With this approach, better and specific development of self-assembling peptide materials can be achieved, allowing for the rational engineering of peptide sequences to form hydrogels appropriate for specific drug delivery applications.

  1. Neighborhood characteristics and sexual intimate partner violence against women among low-income, drug-involved New York City residents: results from the IMPACT Studies.

    Science.gov (United States)

    Frye, Victoria; Blaney, Shannon; Cerdá, Magdalena; Vlahov, David; Galea, Sandro; Ompad, Danielle C

    2014-07-01

    We assessed relations among neighborhood characteristics and sexual intimate partner violence against women (SIPVAW), among low-income, drug-involved, women (n = 360) and men (n = 670) in New York City between 2005 and 2009. Six percent of women (n = 22) and 5% of men (n = 33) reported experiencing and perpetrating SIPVAW in the past year with a main partner. In adjusted mixed models among women, neighborhood ethnic heterogeneity was significantly negatively associated with SIPVAW victimization. In adjusted logistic models among men, neighborhood collective efficacy was significantly positively associated with SIPVAW perpetration. Novel theoretical frameworks are needed to guide research on neighborhoods and partner violence. © The Author(s) 2014.

  2. Can the dopaminergic-related effects of general anesthetics be linked to mechanisms involved in drug abuse and addiction?

    Science.gov (United States)

    Melo, A; Tavares, I; Sousa, N; Pêgo, J M

    2015-08-01

    General anesthetics (GA) are well known for the ability to induce a state of reversible loss of consciousness and unresponsiveness to painful stimuli. However, evidence from animal models and clinical studies show that GA exposure may induce behavioral changes beyond acute effects. Most research and concerns are focused on changes in cognition and memory. We will look at effects of GA on behavior that is mediated by the dopaminergic system. Pharmacological resemblance of GA with drugs of abuse, and the complexity and importance of dopaminergic systems in both reward seeking and addictive illnesses make us believe that it deserves an overview about what is already known and what matters to us as healthcare workers and specifically as anesthesiologists. A review of available evidence strongly suggests that there may be a link between the effects of GA on the brain and substance abuse, partly explained by their influence on the dopaminergic system. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  3. Hypothesizing Music Intervention Enhances Brain Functional Connectivity Involving Dopaminergic Recruitment: Common Neuro-correlates to Abusable Drugs.

    Science.gov (United States)

    Blum, Kenneth; Simpatico, Thomas; Febo, Marcelo; Rodriquez, Chris; Dushaj, Kristina; Li, Mona; Braverman, Eric R; Demetrovics, Zsolt; Oscar-Berman, Marlene; Badgaiyan, Rajendra D

    2017-07-01

    The goal of this review is to explore the clinical significance of music listening on neuroplasticity and dopaminergic activation by understanding the role of music therapy in addictive behavior treatment. fMRI data has shown that music listening intensely modifies mesolimbic structural changes responsible for reward processing (e.g., nucleus accumbens [NAc]) and may control the emotional stimuli's effect on autonomic and physiological responses (e.g., hypothalamus). Music listening has been proven to induce the endorphinergic response blocked by naloxone, a common opioid antagonist. NAc opioid transmission is linked to the ventral tegmental area (VTA) dopamine release. There are remarkable commonalities between listening to music and the effect of drugs on mesolimbic dopaminergic activation. It has been found that musical training before the age of 7 results in changes in white-matter connectivity, protecting carriers with low dopaminergic function (DRD2A1 allele, etc.) from poor decision-making, reward dependence, and impulsivity. In this article, we briefly review a few studies on the neurochemical effects of music and propose that these findings are relevant to the positive clinical findings observed in the literature. We hypothesize that music intervention enhances brain white matter plasticity through dopaminergic recruitment and that more research is needed to explore the efficacy of these therapies.

  4. Cell signaling pathways involved in drug-mediated fetal hemoglobin induction: Strategies to treat sickle cell disease.

    Science.gov (United States)

    Pace, Betty S; Liu, Li; Li, Biaoru; Makala, Levi H

    2015-08-01

    The developmental regulation of globin gene expression has shaped research efforts to establish therapeutic modalities for individuals affected with sickle cell disease and β-thalassemia. Fetal hemoglobin has been shown to block sickle hemoglobin S polymerization to improve symptoms of sickle cell disease; moreover, fetal hemoglobin functions to replace inadequate hemoglobin A synthesis in β-thalassemia thus serving as an effective therapeutic target. In the perinatal period, fetal hemoglobin is synthesized at high levels followed by a decline to adult levels by one year of age. It is known that naturally occurring mutations in the γ-globin gene promoters and distant cis-acting transcription factors produce persistent fetal hemoglobin synthesis after birth to ameliorate clinical symptoms. Major repressor proteins that silence γ-globin during development have been targeted for gene therapy in β-hemoglobinopathies patients. In parallel effort, several classes of pharmacological agents that induce fetal hemoglobin expression through molecular and cell signaling mechanisms have been identified. Herein, we reviewed the progress made in the discovery of signaling molecules targeted by pharmacologic agents that enhance γ-globin expression and have the potential for future drug development to treat the β-hemoglobinopathies. © 2015 by the Society for Experimental Biology and Medicine.

  5. Utility of imaging mass spectrometry (IMS) by matrix-assisted laser desorption ionization (MALDI) on an ion trap mass spectrometer in the analysis of drugs and metabolites in biological tissues.

    Science.gov (United States)

    Drexler, Dieter M; Garrett, Timothy J; Cantone, Joseph L; Diters, Richard W; Mitroka, James G; Prieto Conaway, Maria C; Adams, Stephen P; Yost, Richard A; Sanders, Mark

    2007-01-01

    The properties and potential liabilities of drug candidate are investigated in detailed ADME assays and in toxicity studies, where findings are placed in context of exposure to dosed drug and metabolites. The complex nature of biological samples may necessitate work-up procedures prior to high performance liquid chromatography-mass spectrometric (HPLC-MS) analysis of endogenous or xenobiotic compounds. This concept can readily be applied to biological fluids such as blood or urine, but in localized samples such as organs and tissues potentially important spatial, thus anatomical, information is lost during sample preparation as the result of homogenization and extraction procedures. However, the localization of test article or spatial identification of metabolites may be critical to the understanding of the mechanism of target-organ toxicity and its relevance to clinical safety. Tissue imaging mass spectrometry (IMS) by matrix-assisted laser desorption ionization (MALDI) and ion trap mass spectrometry (MS) with higher order mass spectrometric scanning functions was utilized for localization of dosed drug or metabolite in tissue. Laser capture microscopy (LCM) was used to obtain related samples from tissue for analyses by standard MALDI-MS and HPLC-MS. In a toxicology study, rats were administered with a high dosage of a prodrug for 2 weeks. Birefringent microcrystalline material (10-25 microm) was observed in histopathologic formalin-fixed tissue samples. Direct analysis by IMS provided the identity of material in the microcrystals as circulating active drug while maintaining spatial orientation. Complementary data from visual cross-polarized light microscopy as well as standard MALDI-MS and HPLC-MS experiments on LCM samples validated the qualitative results obtained by IMS. Furthermore, the HPLC-MS analysis on the LCM samples afforded a semi-quantitative assessment of the crystalline material in the tissue samples. IMS by MALDI ion trap MS proved sensitive

  6. The use of ion mobility spectrometry and gas chromatography/mass spectrometry for the detection of illicit drugs on clandestine records

    Science.gov (United States)

    Donnelly, Brian; Jourdan, Thomas; Fetterolf, Dean D.; Beasley, James O., II

    1995-01-01

    Illicit drug distribution has over the past decade grown tremendously from simple 'drug pushing' where drugs were distributed from poorly organized individuals to today's well organized and well financed drug cartels. This change to a more 'corporate-like' atmosphere has resulted in a greater use of record keeping to monitor the profits generated. The use of record keeping by drug distributors is not restricted to high level drug smugglers but is used at all levels within the distribution network. Dealers at all levels including street dealers are generally 'fronted', given on consignment quantities of drugs that they in turn sell to customers, thereby requiring the need for records to keep track of drug sales versus liabilities. These records because of their illicit nature are often encrypted to hide the fact that they are indeed records of drug transactions. The creation of a handwritten notation concerning a drug transaction is normally brought on because of a purchase or sale. In a sale, this is commonly accomplished through a consignment, or the designation of a quantity to a customer to whom that amount has been 'fronted'. Because this activity generates a debt, it follows that an accounting for payments made, as well as new transactions completed, is only logical. One of the most common means of representing these is through an 'accounting flow', in which payments are subtracted from a running balance while new sales are added to it. The examination of illicit drug records has been the key to the prosecution of numerous federal, state, and local drug cases for a number of years. The Document Section of the FBI Laboratory, through its Racketeering Records Analysis Unit (RRAU), has been involved in such analytical efforts since 1983. Detailed analytical research brought about an evolution in the systematic approach utilized in the RRAU since that time. The close proximity of the drugs to the records often results in trace drug evidence being transferred to

  7. Biomarkers that Discriminate Multiple Myeloma Patients with or without Skeletal Involvement Detected Using SELDI-TOF Mass Spectrometry and Statistical and Machine Learning Tools

    Directory of Open Access Journals (Sweden)

    Sudeepa Bhattacharyya

    2006-01-01

    Full Text Available Multiple Myeloma (MM is a severely debilitating neoplastic disease of B cell origin, with the primary source of morbidity and mortality associated with unrestrained bone destruction. Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS was used to screen for potential biomarkers indicative of skeletal involvement in patients with MM. Serum samples from 48 MM patients, 24 with more than three bone lesions and 24 with no evidence of bone lesions were fractionated and analyzed in duplicate using copper ion loaded immobilized metal affinity SELDI chip arrays. The spectra obtained were compiled, normalized, and mass peaks with mass-to-charge ratios (m/z between 2000 and 20,000 Da identified. Peak information from all fractions was combined together and analyzed using univariate statistics, as well as a linear, partial least squares discriminant analysis (PLS-DA, and a non-linear, random forest (RF, classification algorithm. The PLS-DA model resulted in prediction accuracy between 96–100%, while the RF model was able to achieve a specificity and sensitivity of 87.5% each. Both models as well as multiple comparison adjusted univariate analysis identified a set of four peaks that were the most discriminating between the two groups of patients and hold promise as potential biomarkers for future diagnostic and/or therapeutic purposes.

  8. Use of a charge reducing agent to enable intact mass analysis of cysteine-linked antibody-drug-conjugates by native mass spectrometry

    Directory of Open Access Journals (Sweden)

    Kamila J. Pacholarz

    2016-06-01

    Full Text Available Antibody-drug-conjugates (ADC are a growing class of anticancer biopharmaceuticals. Conjugation of cysteine linked ADCs, requires initial reduction of mAb inter-chain disulfide bonds, as the drugs are attached via thiol chemistry. This results in the active mAb moiety being transformed from a covalently linked tetramer to non-covalently linked complexes, which hinders precise determination of drug load with LC–MS. Here, we show how the addition of the charge reducing agent triethylammonium acetate (TEAA preserves the intact mAb structure, is well suited to the study of cysteine linked conjugates and facilitates easy drug load determination by direct infusion native MS.

  9. Comparison of the quantitative performance of a Q-Exactive high-resolution mass spectrometer with that of a triple quadrupole tandem mass spectrometer for the analysis of illicit drugs in wastewater.

    Science.gov (United States)

    Fedorova, Ganna; Randak, Tomas; Lindberg, Richard H; Grabic, Roman

    2013-08-15

    Analysis of drugs in wastewater is gaining more interest, as new approaches to estimate drug consumption from the amount of drug residues in wastewater have been proposed. The aim of this study was to compare the quantitative performance of high-resolution mass spectrometry with that of triple quadrupole mass spectrometry. A Q-Exactive mass spectrometer was operated in full scan (HRFS) (70 000 FWHM) and product scan (HRPS) (17 500 FWHM) modes. The first and third quadrupoles of the QqQ MS/MS instrument were operated at 0.7 FWHM. A mass-extracted window of 5 ppm around the theoretical m/z of each analyte was used to construct chromatograms. An HESI-II ion source was used for the ionization of target compounds. In-line-SPE-LC configuration was used for the extraction and separation of target analytes. All three methods showed good linearity and repeatability. High-resolution detection of product ions exhibited better sensitivity and selectivity for some compounds. For most of the tested compounds, LOQs ranged from 0.46 to 20 ng L(-1) . Good agreement between measured and nominal concentrations was observed for most of the compounds at different levels of fortification. Both MS/MS methods showed good selectivity, while HRFS gave some false positive results. The Q-Exactive mass spectrometer proved to be suitable for trace detection and quantification of most of the tested drugs in wastewater, with performance comparable to that of the commonly used MS/MS triple quadrupole, but with better selectivity. Copyright © 2013 John Wiley & Sons, Ltd.

  10. High-resolution twin-ion metabolite extraction (HiTIME) mass spectrometry: nontargeted detection of unknown drug metabolites by isotope labeling, liquid chromatography mass spectrometry, and automated high-performance computing.

    Science.gov (United States)

    Leeming, Michael G; Isaac, Andrew P; Pope, Bernard J; Cranswick, Noel; Wright, Christine E; Ziogas, James; O'Hair, Richard A J; Donald, William A

    2015-04-21

    The metabolic fate of a compound can often determine the success of a new drug lead. Thus, significant effort is directed toward identifying the metabolites formed from a given molecule. Here, an automated and nontargeted procedure is introduced for detecting drug metabolites without authentic metabolite standards via the use of stable isotope labeling, liquid chromatography mass spectrometry (LC/MS), and high-performance computing. LC/MS of blood plasma extracts from rats that were administered a 1:1 mixture of acetaminophen (APAP) and (13)C6-APAP resulted in mass spectra that contained "twin" ions for drug metabolites that were not detected in control spectra (i.e., no APAP administered). Because of the development of a program (high-resolution twin-ion metabolite extraction; HiTIME) that can identify twin-ions in high-resolution mass spectra without centroiding (i.e., reduction of mass spectral peaks to single data points), 9 doublets corresponding to APAP metabolites were identified. This is nearly twice that obtained by use of existing programs that make use of centroiding to reduce computational cost under these conditions with a quadrupole time-of-flight mass spectrometer. By a manual search for all reported APAP metabolite ions, no additional twin-ion signals were assigned. These data indicate that all the major metabolites of APAP and multiple low-abundance metabolites (e.g., acetaminophen hydroxy- and methoxysulfate) that are rarely reported were detected. This methodology can be used to detect drug metabolites without prior knowledge of their identity. HiTIME is freely available from https://github.com/bjpop/HiTIME .

  11. Comparison and validation of two mathematical models for the impact of mass drug administration on Ascaris lumbricoides and hookworm infection.

    Science.gov (United States)

    Coffeng, Luc E; Truscott, James E; Farrell, Sam H; Turner, Hugo C; Sarkar, Rajiv; Kang, Gagandeep; de Vlas, Sake J; Anderson, Roy M

    2017-03-01

    The predictions of two mathematical models of the transmission dynamics of Ascaris lumbricoides and hookworm infection and the impact of mass drug administration (MDA) are compared, using data from India. One model has an age structured partial differential equation (PDE) deterministic framework for the distribution of parasite numbers per host and sexual mating. The second model is an individual-based stochastic model. Baseline data acquired prior to treatment are used to estimate key transmission parameters, and forward projections are made, given the known MDA population coverage. Predictions are compared with observed post-treatment epidemiological patterns. The two models could equally well predict the short-term impact of deworming on A. lumbricoides and hookworm infection levels, despite being fitted to different subsets and/or summary statistics of the data. As such, the outcomes give confidence in their use as aids to policy formulation for the use of PCT to control A. lumbricoides and hookworm infection. The models further largely agree in a qualitative sense on the added benefit of semi-annual vs. annual deworming and targeting of the entire population vs. only children, as well as the potential for interruption of transmission. Further, this study also illustrates that long-term predictions are sensitive to modelling assumptions about which age groups contribute most to transmission, which depends on human demography and age-patterns in exposure and contribution to the environmental reservoir of infection, the latter being notoriously difficult to empirically quantify. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. The importance of patient compliance in repeated rounds of mass drug administration (MDA) for the elimination of intestinal helminth transmission.

    Science.gov (United States)

    Farrell, Sam H; Truscott, James E; Anderson, Roy M

    2017-06-12

    Systematic non-compliance to chemotherapeutic treatment among a portion of the eligible population is thought to be a major obstacle to the elimination of helminth infections by mass drug administration (MDA). MDA for helminths is repeated at defined intervals such as yearly or every 2 years, as a consequence of the inability of the human host to develop fully protective immunity to reinfection. As such, how an individual complies to these repeated rounds of MDA can have a significant impact on parasite transmission. The importance of this factor is poorly understood at present. Few epidemiological studies have examined longitudinal trends in compliance in the many communities in areas of endemic helminth infection that are undergoing MDA. Reducing systematic non-compliance will obviously increase the number of individuals treated, but it may also alter the dynamics of parasite transmission. Here we develop an individual-based stochastic model of helminth transmission and MDA treatment to investigate how different patterns of compliance influence the impact of MDA for two groups of helminths, the soil transmitted nematode infections and the schistosome parasites. We study the effect of several alternative treatment and compliance patterns on the dynamics of transmission. We find that the impact of different compliance patterns, ranging from random treatment at each round of chemotherapy to systematic non-compliance by a proportion of the population, is very dependent on both transmission intensity in a defined setting and the type of infection that the treatment is targeted at. Systematic non-compliance has a greater impact on the potential for elimination of Schistosoma mansoni transmission by intensive MDA, than it does on Ascaris lumbricoides. We discuss the implications of our findings for the prioritisation of resources in MDA programmes and for monitoring and evaluation programme design. The key message generated by the analyses is that great care must be

  13. Mass drug administration of azithromycin for trachoma reduces the prevalence of genital Chlamydia trachomatis infection in the Solomon Islands.

    Science.gov (United States)

    Marks, M; Bottomley, C; Tome, H; Pitakaka, R; Butcher, R; Sokana, O; Kako, H; Solomon, A W; Mabey, D C

    2016-06-01

    Chlamydia trachomatis is the most common bacterial sexually transmitted infection and is frequently asymptomatic; ocular C. trachomatis strains cause trachoma. Mass drug administration (MDA) of azithromycin for trachoma might also reduce the prevalence of genital C. trachomatis. In a survey conducted in the Solomon Islands in 2014, prior to MDA, the prevalence of genital C. trachomatis was 20.3% (95% CI 15.9% to 25.4%). We conducted a survey to establish the impact of MDA with azithromycin on genital C. trachomatis. Women attending three community outpatient clinics, predominantly for antenatal care, 10 months after MDA with azithromycin given for trachoma elimination, were enrolled in this survey. Self-taken high vaginal swabs were for C. trachomatis and Neisseria gonorrhoeae using the BD Probetec strand displacement assay. 298 women were enrolled. C. trachomatis infection was diagnosed in 43 women (14.4%, 95% CI 10.6% to 18.9%) and N. gonorrhoeae in 9 (3%, 95% CI 1.4% to 5.7%). The age-adjusted OR for C. trachomatis infection was consistent with a significant decrease in the prevalence of C. trachomatis following MDA (OR 0.58, 95% CI 0.37 to 0.94, p=0.027). There was no change in the prevalence of N. gonorrhoeae between following MDA (OR 0.51, 95% CI 0.22 to 1.22, p=0.13). This study demonstrated a 40% reduction in the age-adjusted prevalence of genital C. trachomatis infection following azithromycin MDA for trachoma elimination. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  14. Quantification of rifapentine, a potent antituberculosis drug, from dried blood spot samples using liquid chromatographic-tandem mass spectrometric analysis.

    Science.gov (United States)

    Parsons, Teresa L; Marzinke, Mark A; Hoang, Thuy; Bliven-Sizemore, Erin; Weiner, Marc; Mac Kenzie, William R; Dorman, Susan E; Dooley, Kelly E

    2014-11-01

    The quantification of antituberculosis drug concentrations in multinational trials currently requires the collection of modest blood volumes, centrifugation, aliquoting of plasma, freezing, and keeping samples frozen during shipping. We prospectively enrolled healthy individuals into the Tuberculosis Trials Consortium Study 29B, a phase I dose escalation study of rifapentine, a rifamycin under evaluation in tuberculosis treatment trials. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying rifapentine in whole blood on dried blood spots (DBS) to facilitate pharmacokinetic/pharmacodynamic analyses in clinical trials. Paired plasma and whole-blood samples were collected by venipuncture, and whole blood was spotted on Whatman protein saver 903 cards. The methods were optimized for plasma and then validated for DBS. The analytical measuring range for quantification of rifapentine and its metabolite was 50 to 80,000 ng/ml in whole-blood DBS. The analyte was stable on the cards for 11 weeks with a desiccant at room temperature and protected from light. The method concordance for paired plasma and whole-blood DBS samples was determined after correcting for participant hematocrit or population-based estimates of bias from Bland-Altman plots. The application of either correction factor resulted in acceptable correlation between plasma and whole-blood DBS (Passing-Bablok regression corrected for hematocrit; y = 0.98x + 356). Concentrations of rifapentine may be determined from whole-blood DBS collected via venipuncture after normalization in order to account for the dilutional effects of red blood cells. Additional studies are focused on the application of this methodology to capillary blood collected by finger stick. The simplicity of processing, storage, shipping, and low blood volume makes whole-blood DBS attractive for rifapentine pharmacokinetic evaluations, especially in international and pediatric trials. Copyright © 2014

  15. Detection and identification of drugs and toxicants in human body fluids by liquid chromatography-tandem mass spectrometry under data-dependent acquisition control and automated database search.

    Science.gov (United States)

    Oberacher, Herbert; Schubert, Birthe; Libiseller, Kathrin; Schweissgut, Anna

    2013-04-03

    Systematic toxicological analysis (STA) is aimed at detecting and identifying all substances of toxicological relevance (i.e. drugs, drugs of abuse, poisons and/or their metabolites) in biological material. Particularly, gas chromatography-mass spectrometry (GC/MS) represents a competent and commonly applied screening and confirmation tool. Herein, we present an untargeted liquid chromatography-tandem mass spectrometry (LC/MS/MS) assay aimed to complement existing GC/MS screening for the detection and identification of drugs in blood, plasma and urine samples. Solid-phase extraction was accomplished on mixed-mode cartridges. LC was based on gradient elution in a miniaturized C18 column. High resolution electrospray ionization-MS/MS in positive ion mode with data-dependent acquisition control was used to generate tandem mass spectral information that enabled compound identification via automated library search in the "Wiley Registry of Tandem Mass Spectral Data, MSforID". Fitness of the developed LC/MS/MS method for application in STA in terms of selectivity, detection capability and reliability of identification (sensitivity/specificity) was demonstrated with blank samples, certified reference materials, proficiency test samples, and authentic casework samples. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. [Stopping with the criminality: a way out of youths involved in traffic of drugs in slums in the city of Rio de Janeiro].

    Science.gov (United States)

    Meirelles, Zilah Vieira; Minayo Gomez, Carlos

    2009-01-01

    This article deals with the lives of young egress of drug traffic in the slums of the city of Rio de Janeiro. Its main objective is to examine the circumstances and the specific conditions that drive young people to abandon this illegal work activity. The method used to collect data was the topical life story in order to find out how 30 youths, from seven slums, had got involved until their departure from the 'movement'. Data shows that youths, entering trafficking, had an expectation of empowerment. With time, this attitude will wane, as they realize they are living with situations of betrayal, punishment and fear. The process for getting out occurs when the youth begins to question this type of work and sees other ways of life, more consistent with their aspirations. The facts conclude that when getting an early involvement in organized crime it leaves them physically and emotionally exhausted, as selling drugs is an ongoing confrontation through constant episodes of armed conflicts and arms dealing.

  17. Identification of Genes Upregulated by the Transcription Factor Bcr1 That Are Involved in Impermeability, Impenetrability, and Drug Resistance of Candida albicans a/α Biofilms

    Science.gov (United States)

    Srikantha, Thyagarajan; Daniels, Karla J.; Pujol, Claude; Kim, Elena

    2013-01-01

    Candida albicans forms two types of biofilm, depending upon the configuration of the mating type locus. Although architecturally similar, a/α biofilms are impermeable, impenetrable, and drug resistant, whereas a/a and α/α biofilms lack these traits. The difference appears to be the result of an alternative matrix. Overexpression in a/a cells of BCR1, a master regulator of the a/α matrix, conferred impermeability, impenetrability, and drug resistance to a/a biofilms. Deletion of BCR1 in a/α cells resulted in the loss of these a/α-specific biofilm traits. Using BCR1 overexpression in a/a cells, we screened 107 genes of interest and identified 8 that were upregulated by Bcr1. When each was overexpressed in a/a biofilms, the three a/α traits were partially conferred, and when each was deleted in a/α cells, the traits were partially lost. Five of the eight genes have been implicated in iron homeostasis, and six encode proteins that are either in the wall or plasma membrane or secreted. All six possess sites for O-linked and N-linked glycosylation that, like glycosylphosphatidylinositol (GPI) anchors, can cross-link to the wall and matrix, suggesting that they may exert a structural role in conferring impermeability, impenetrability, and drug resistance, in addition to their physiological functions. The fact that in a screen of 107 genes, all 8 of the Bcr1-upregulated genes identified play a role in impermeability, impenetrability, and drug resistance suggests that the formation of the a/α matrix is highly complex and involves a larger number of genes than the initial ones identified here. PMID:23563485

  18. High-throughput analysis of drugs in biological fluids by desorption electrospray ionization mass spectrometry coupled with thin liquid membrane extraction

    DEFF Research Database (Denmark)

    Rosting, Cecilie; Pedersen-Bjergaard, Stig; Hansen, Steen Honore'

    2013-01-01

    Biological fluids such as urine, saliva and whole blood were analyzed for contents of drugs by a new combination of desorption electrospray ionization mass spectrometry (DESI-MS) and thin liquid membrane extraction (TLME). Analytes from the sample were extracted into a thin liquid membrane...... into the method, methadone was detected in urine in full-scan mode with an LOD of 4 ng mL(-1), while amitriptyline, nortriptyline and pethidine showed LODs of 17 ng mL(-1). Quantification was possible for several basic drugs using one common internal standard, providing relative accuracies in the range of 10...

  19. Evaluation of a High Resolving Power Time-of-Flight Mass Spectrometer for Drug Analysis in Terms of Resolving Power and Acquisition Rate

    Science.gov (United States)

    Pelander, Anna; Decker, Petra; Baessmann, Carsten; Ojanperä, Ilkka

    2011-02-01

    Liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) is applied increasingly to various fields of small molecule analysis. The moderate resolving power (RP) of standard TOFMS instruments poses a risk of false negative results when complex biological matrices are to be analyzed. In this study, the performance of a high resolving power TOFMS instrument (maXis by Bruker Daltonik, Bremen, Germany) was evaluated for drug analysis. By flow injection analysis of critical drug mixtures, including a total of 17 compounds with nominal masses of 212-415 Da and with mass differences of 8.8-23.5 mDa, RP varied from 34,400 to 51,900 (FWHM). The effect of acquisition rate on RP, mass accuracy, and isotopic pattern fit was studied by applying 1, 2, 5, 10, and 20 Hz acquisition rates in a 16 min gradient elution LC separation. All three variables were independent of the acquisition rate, with an average mass accuracy and isotopic pattern fit factor (mSigma) of 0.33 ppm and 5.9, respectively. The average relative standard deviation of RP was 1.8%, showing high repeatability. The performance was tested further with authentic urine extracts containing a co-eluting compound pair with a nominal mass of 296 Da and an 11.2 mDa mass difference. The authentic sample components were readily resolved and correctly identified by the automated data analysis. The average RP, mass accuracy, and isotopic pattern fit were 36,600, 0.9 ppm, and 7.3 mSigma, respectively.

  20. Matrix effect in the analysis of drugs of abuse from urine with desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS) and desorption electrospray ionization-mass spectrometry (DESI-MS)

    International Nuclear Information System (INIS)

    Suni, Niina M.; Lindfors, Pia; Laine, Olli; Ostman, Pekka; Ojanperae, Ilkka; Kotiaho, Tapio; Kauppila, Tiina J.; Kostiainen, Risto

    2011-01-01

    Highlights: → DAPPI-MS and DESI-MSI in the analysis of drugs of abuse from urine. → DAPPI-MS has better urine matrix tolerance over DESI-MS. → Urine matrix can affect the ionization mechanism in DAPPI. → DAPPI-MS/MS can be used for screening of drugs from urine after sample pretreatment. - Abstract: We have studied the matrix effect within direct analysis of benzodiazepines and opioids from urine with desorption electrospray ionization-mass spectrometry (DESI-MS) and desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS). The urine matrix was found to affect the ionization mechanism of the opioids in DAPPI-MS favoring proton transfer over charge exchange reaction. The sensitivity for the drugs in solvent matrix was at the same level with DESI-MS and DAPPI-MS (LODs 0.05-6 μg mL -1 ) but the decrease in sensitivity due to the urine matrix was higher with DESI (typically 20-160-fold) than with DAPPI (typically 2-15-fold) indicating better matrix tolerance of DAPPI over DESI. Also in MS/MS mode, DAPPI provided better sensitivity than DESI for the drugs in urine. The feasibility of DAPPI-MS/MS was then studied in screening the same drugs from five authentic, forensic post mortem urine samples. A reference measurement with gas chromatography-mass spectrometry (GC-MS) (including pretreatment) revealed 16 findings from the samples, whereas with DAPPI-MS/MS after sample pretreatment, 15 findings were made. Sample pretreatment was found necessary, since only eight findings were made from the same samples untreated.

  1. Matrix effect in the analysis of drugs of abuse from urine with desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS) and desorption electrospray ionization-mass spectrometry (DESI-MS)

    Energy Technology Data Exchange (ETDEWEB)

    Suni, Niina M.; Lindfors, Pia; Laine, Olli [Division of Pharmaceutical Chemistry, University of Helsinki, P.O. Box 56, Helsinki FI-00014 (Finland); Ostman, Pekka; Ojanperae, Ilkka [Hjelt Institute, Department of Forensic Medicine, University of Helsinki, P.O. Box 40, Helsinki FI-00014 (Finland); Kotiaho, Tapio [Division of Pharmaceutical Chemistry, University of Helsinki, P.O. Box 56, Helsinki FI-00014 (Finland); Laboratory of Analytical Chemistry, Department of Chemistry, University of Helsinki, P.O. Box 55, Helsinki FI-00014 (Finland); Kauppila, Tiina J. [Division of Pharmaceutical Chemistry, University of Helsinki, P.O. Box 56, Helsinki FI-00014 (Finland); Kostiainen, Risto, E-mail: risto.kostiainen@helsinki.fi [Division of Pharmaceutical Chemistry, University of Helsinki, P.O. Box 56, Helsinki FI-00014 (Finland)

    2011-08-05

    Highlights: {yields} DAPPI-MS and DESI-MSI in the analysis of drugs of abuse from urine. {yields} DAPPI-MS has better urine matrix tolerance over DESI-MS. {yields} Urine matrix can affect the ionization mechanism in DAPPI. {yields} DAPPI-MS/MS can be used for screening of drugs from urine after sample pretreatment. - Abstract: We have studied the matrix effect within direct analysis of benzodiazepines and opioids from urine with desorption electrospray ionization-mass spectrometry (DESI-MS) and desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS). The urine matrix was found to affect the ionization mechanism of the opioids in DAPPI-MS favoring proton transfer over charge exchange reaction. The sensitivity for the drugs in solvent matrix was at the same level with DESI-MS and DAPPI-MS (LODs 0.05-6 {mu}g mL{sup -1}) but the decrease in sensitivity due to the urine matrix was higher with DESI (typically 20-160-fold) than with DAPPI (typically 2-15-fold) indicating better matrix tolerance of DAPPI over DESI. Also in MS/MS mode, DAPPI provided better sensitivity than DESI for the drugs in urine. The feasibility of DAPPI-MS/MS was then studied in screening the same drugs from five authentic, forensic post mortem urine samples. A reference measurement with gas chromatography-mass spectrometry (GC-MS) (including pretreatment) revealed 16 findings from the samples, whereas with DAPPI-MS/MS after sample pretreatment, 15 findings were made. Sample pretreatment was found necessary, since only eight findings were made from the same samples untreated.

  2. Fluoroscopically guided transforaminal epidural steroid injections at a quaternary-care teaching institution: effect of trainee involvement and patient body mass index on fluoroscopy time and patient dose

    International Nuclear Information System (INIS)

    Tiegs-Heiden, C.A.; Murthy, N.S.; Geske, J.R.; Diehn, F.E.; Schueler, B.A.; Wald, J.T.; Kaufmann, T.J.; Lehman, V.T.; Carr, C.M.; Amrami, K.K.; Morris, J.M.; Thielen, K.R.; Maus, T.P.

    2016-01-01

    Aim: To investigate whether there are differences in fluoroscopy time and patient dose for fluoroscopically guided lumbar transforaminal epidural steroid injections (TFESIs) performed by staff radiologists versus with trainees and to evaluate the effect of patient body mass index (BMI) on fluoroscopy time and patient dose, including their interactions with other variables. Materials and methods: Single-level lumbar TFESIs (n=1844) between 1 January 2011 and 31 December 2013 were reviewed. Fluoroscopy time, reference point air kerma (K a,r ), and kerma area product (KAP) were recorded. BMI and trainee involvement were examined as predictors of fluoroscopy time, K a,r , and KAP in models adjusted for age and gender in multivariable linear models. Stratified models of BMI groups by trainee presence were performed. Results: Increased age was the only significant predictor of increased fluoroscopy time (p<0.0001). K a,r and KAP were significantly higher in patients with a higher BMI (p<0.0001 and p=0.0009). When stratified by BMI, longer fluoroscopy time predicted increased K a,r and KAP in all groups (p<0.0001). Trainee involvement was not a statistically significant predictor of fluoroscopy time or K a,r in any BMI category. KAP was lower with trainees in the overweight group (p=0.0009) and higher in male patients for all BMI categories (p<0.02). Conclusion: Trainee involvement did not result in increased fluoroscopy time or patient dose. BMI did not affect fluoroscopy time; however, overweight and obese patients received significantly higher K a,r and KAP. Male patients received a higher KAP in all BMI categories. Limiting fluoroscopy time and good collimation practices should be reinforced in these patients. - Highlights: • Trainee involvement did not contribute to increased fluoroscopy time or dose. • BMI did not affect fluoroscopy time. • Overweight and obese patients received significantly higher Ka,r and KAP.

  3. Rapid screening of abused drugs by direct analysis in real time (DART) coupled to time-of-flight mass spectrometry (TOF-MS) combined with ion mobility spectrometry (IMS).

    Science.gov (United States)

    Lian, Ru; Wu, Zhongping; Lv, Xiaobao; Rao, Yulan; Li, Haiyang; Li, Jinghua; Wang, Rong; Ni, Chunfang; Zhang, Yurong

    2017-10-01

    Increasing in cases involving drugs of abuse leads to heavy burden for law enforcement agencies, exacerbating demand for rapid screening technique. In this study, atmospheric pressure ionization technologies including direct analysis in real time (DART) ion source coupled to a time-of-flight mass spectrometer (DART-TOF-MS)as well asdopant-assisted positive photoionization ion mobility spectrometry (DAPP-IMS) without radioactivity were utilized together as the powerful analytical tool for the rapid screening and identification of 53 abused drugs.The limits of detection (LOD) were 0.05-2μg/mL when using DART-TOF-MS and 0.02-2μg when using DAPP-IMS which could satisfy the actual requirement in forensic science laboratory. The advantages of this method included fast response, high-throughput potential, high specificity, and minimal sample preparation. A screening library of reduced mobility (K 0 ), accurate mass of informative precursor ion ([M+H] + ) and fragment ions was established respectively by employing a bench-top DAPP-IMS and TOF-MS in-source collision induced dissociation (CID) mode. Then the standardized screening procedure was developed with criteria for the confirmation of positive result. A total of 50 seized drug samples provided by local forensic laboratory we reanalyzed to testify the utility of the method. This study suggests that a method combing DART-TOF-MS and DAPP-IMS is promising for the rapid screening and identification of abused drugs with minimal sample preparation and absence of chromatography. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments.

    Science.gov (United States)

    Watanabe, Takao; Kusuhara, Hiroyuki; Watanabe, Tomoko; Debori, Yasuyuki; Maeda, Kazuya; Kondo, Tsunenori; Nakayama, Hideki; Horita, Shigeru; Ogilvie, Brian W; Parkinson, Andrew; Hu, Zhuohan; Sugiyama, Yuichi

    2011-06-01

    The present study investigated prediction of the overall renal tubular secretion and hepatic clearances of anionic drugs based on in vitro transport studies. The saturable uptake of eight drugs, most of which were OAT3 substrates (rosuvastatin, pravastatin, pitavastatin, valsartan, olmesartan, trichlormethiazide, p-aminohippurate, and benzylpenicillin) by freshly prepared human kidney slices underestimated the overall intrinsic clearance of the tubular secretion; therefore, a scaling factor of 10 was required for in vitro-in vivo extrapolation. We examined the effect of gemfibrozil and its metabolites, gemfibrozil glucuronide and the carboxylic metabolite, gemfibrozil M3, on pravastatin uptake by human kidney slices. The inhibition study using human kidney slices suggests that OAT3 plays a predominant role in the renal uptake of pravastatin. Comparison of unbound concentrations and K(i) values (1.5, 9.1, and 4.0 μM, for gemfibrozil, gemfibrozil glucuronide, and gemfibrozil M3, respectively) suggests that the mechanism of the interaction is due mainly to inhibition by gemfibrozil and gemfibrozil glucuronide. Furthermore, extrapolation of saturable uptake by cryopreserved human hepatocytes predicts clearance comparable with the observed hepatic clearance although fluvastatin and rosuvastatin required a scaling factor of 11 and 6.9, respectively. This study suggests that in vitro uptake assays using human kidney slices and hepatocytes provide a good prediction of the overall tubular secretion and hepatic clearances of anionic drugs and renal drug-drug interactions. It is also recommended that in vitro-in vivo extrapolation be performed in animals to obtain more reliable prediction.

  5. Community-directed mass drug administration is undermined by status seeking in friendship networks and inadequate trust in health advice networks

    OpenAIRE

    Chami, Goylette F.; Kontoleon, Andreas A.; Bulte, Erwin; Fenwick, Alan; Kabatereine, Narcis B.; Tukahebwa, Edridah M.; Dunne, David W.

    2017-01-01

    Over 1.9 billion individuals require preventive chemotherapy through mass drug administration (MDA). Community-directed MDA relies on volunteer community medicine distributors (CMDs) and their achievement of high coverage and compliance. Yet, it is unknown if village social networks influence effective MDA implementation by CMDs. In Mayuge District, Uganda, census-style surveys were conducted for 16,357 individuals from 3,491 households in 17 villages. Praziquantel, albendazole, and ivermecti...

  6. Application and evaluation of a high-resolution mass spectrometry screening method for veterinary drug residues in incurred fish and imported aquaculture samples.

    Science.gov (United States)

    Turnipseed, Sherri B; Storey, Joseph M; Wu, I-Lin; Gieseker, Charles M; Hasbrouck, Nicholas R; Crosby, Tina C; Andersen, Wendy C; Lanier, Shanae; Casey, Christine R; Burger, Robert; Madson, Mark R

    2018-02-14

    The ability to detect chemical contaminants, including veterinary drug residues in animal products such as fish, is an important example of food safety analysis. In this paper, a liquid chromatography high-resolution mass spectrometry (LC-HRMS) screening method using a quadrupole-Orbitrap instrument was applied to the analysis of veterinary drug residues in incurred tissues from aquacultured channel catfish, rainbow trout, and Atlantic salmon and imported aquacultured products including European eel, yellow croaker, and tilapia. Compared to traditional MS methods, the use of HRMS with nontargeted data acquisition and exact mass measurement capability greatly increased the scope of compounds that could be monitored simultaneously. The fish samples were prepared for analysis using a simple efficient procedure that consisted of an acidic acetonitrile extraction followed by solid phase extraction cleanup. Two different HRMS acquisition programs were used to analyze the fish extracts. This method detected and identified veterinary drugs including quinolones, fluoroquinolones, avermectins, dyes, and aminopenicillins at residue levels in fish that had been dosed with those compounds. A metabolite of amoxicillin, amoxicillin diketone, was also found at high levels in catfish, trout, and salmon. The method was also used to characterize drug residues in imported fish. In addition to confirming findings of fluoroquinolone and sulfonamide residues that were found by traditional targeted MS methods, several new compounds including 2-amino mebendazole in eel and ofloxacin in croaker were detected and identified. Graphical Abstract Aquacultured samples are analyzed with a high-resolution mass spectrometry screening method to detect and identify unusual veterinary drug residues including ofloxacin in an imported fish.

  7. The past matters: estimating intrinsic hookworm transmission intensity in areas with past mass drug administration to control lymphatic filariasis.

    Science.gov (United States)

    Werkman, Marleen; Truscott, James E; Toor, Jaspreet; Wright, James E; Anderson, Roy M

    2017-05-23

    Current WHO guidelines for soil-transmitted helminth (STH) control focus on mass drug administration (MDA) targeting preschool-aged (pre-SAC) and school-aged children (SAC), with the goal of eliminating STH as a public health problem amongst children. Recently, attention and funding has turned towards the question whether MDA alone can result in the interruption of transmission for STH. The lymphatic filariasis (LF) elimination programme, have been successful in reaching whole communities. There is the possibility of building upon the infrastructure created for these LF-programmes to enhance the control of STH. Using hookworm as an example, we explore what further MDA coverage might be required to induce interruption of transmission for hookworm in the wake of a successful LF programme. Analyses based on the model of STH transmission and MDA impact predict the effects of previous LF control by MDA over five years, on a defined baseline prevalence of STH in an area with a defined transmission intensity (the basic reproductive number R 0 ). If the LF MDA programme achieved a high coverage (70, 70 and 60% for pre-SAC, SAC and adults, respectively) we expect that in communities with a hookworm prevalence of 15%, after 5 years of LF control, the intrinsic R 0 value in that setting is 2.47. By contrast, if lower LF coverages were achieved (40, 40 and 30% for pre-SAC, SAC and adults, respectively), with the same prevalence of 15% at baseline (after 5 years of LF MDA), the intrinsic hookworm R 0 value is predicted to be 1.67. The intrinsic R 0 value has a large effect on the expected successes of follow-up STH programmes post LF MDA. Consequently, the outcomes of identical programmes may differ between these communities. To design the optimal MDA intervention to eliminate STH infections, it is vital to have information on historical MDA programmes and baseline prevalence to estimate the intrinsic transmission intensity for the defined setting (R 0 ). The baseline

  8. The role of gender relations in uptake of mass drug administration for lymphatic filariasis in Alor District, Indonesia.

    Science.gov (United States)

    Krentel, Alison; Wellings, Kaye

    2018-03-12

    The Global Programme to Eliminate Lymphatic Filariasis has set 2020 as a target to eliminate lymphatic filariasis (LF) as a public health problem through mass drug administration (MDA) to all eligible people living in endemic areas. To obtain a better understanding of compliance with LF treatment, a qualitative study using 43 in-depth interviews was carried out in Alor District, Indonesia to explore factors that motivate uptake of LF treatment, including the social and behavioural differences between compliant and non-compliant individuals. In this paper, we report on the findings specific to the role of family and gender relations and how they affect compliance. The sample comprised 21 men and 22 women; 24 complied with treatment while 19 did not. Gender relations emerged as a key theme in access, uptake and compliance with MDA. The view that the husband, as head of household, had the power, control, and in some cases the responsibility to influence whether his wife took the medication was common among both men and women. Gender also affected priorities for health care provision in the household as well as overall decision making regarding health in the household. Four models of responsibility for health decision making emerged: (i) responsibility resting primarily with the husband; (ii) responsibility resting primarily with the wife; (iii) responsibility shared equally by both husband and wife; and (iv) responsibility autonomously assumed by each individual for his or her own self, regardless of the course of action of the other spouse. (i) Gender relations and social hierarchy influence compliance with LF treatment because they inherently affect decisions taken within the household regarding health; (ii) health care interventions need to take account of the complexity of gender roles; (iii) the fact that women's power tends to be implicit and not overtly recognised in the household or the community has important implications for health care interventions; (iv

  9. The impact of repeated rounds of mass drug administration with diethylcarbamazine plus albendazole on bancroftian filariasis in Papua New Guinea.

    Directory of Open Access Journals (Sweden)

    Gary J Weil

    Full Text Available This study employed various monitoring methods to assess the impact of repeated rounds of mass drug administration (MDA on bancroftian filariasis in Papua New Guinea, which has the largest filariasis problem in the Pacific region.Residents of rural villages near Madang were studied prior to and one year after each of three rounds of MDA with diethylcarbamazine plus albendazole administered per World Health Organization (WHO guidelines. The mean MDA compliance rate was 72.9%. Three rounds of MDA decreased microfilaremia rates (Mf, 1 ml night blood by filter from 18.6% pre-MDA to 1.3% after the third MDA (a 94% decrease. Mf clearance rates in infected persons were 71%, 90.7%, and 98.1% after 1, 2, and 3 rounds of MDA. Rates of filarial antigenemia assessed by card test (a marker for adult worm infection decreased from 47.5% to 17.1% (a 64% decrease after 3 rounds of MDA. The filarial antibody rate (IgG(4 antibodies to Bm14, an indicator of filarial infection status and/or exposure to mosquito-borne infective larvae decreased from 59.3% to 25.1% (a 54.6% decrease. Mf, antigen, and antibody rates decreased more rapidly in children <11 years of age (by 100%, 84.2%, and 76.8%, respectively relative to older individuals, perhaps reflecting their lighter infections and shorter durations of exposure/infection prior to MDA. Incidence rates for microfilaremia, filarial antigenemia, and antifilarial antibodies also decreased significantly after MDA. Filarial DNA rates in Anopheles punctulatus mosquitoes that had recently taken a blood meal decreased from 15.1% to 1.0% (a 92.3% decrease.MDA had dramatic effects on all filariasis parameters in the study area and also reduced incidence rates. Follow-up studies will be needed to determine whether residual infection rates in residents of these villages are sufficient to support sustained transmission by the An. punctulatus vector. Lymphatic filariasis elimination should be feasible in Papua New Guinea if MDA can

  10. Lymphatic filariasis in Papua New Guinea: distribution at district level and impact of mass drug administration, 1980 to 2011

    Science.gov (United States)

    2013-01-01

    Background Lymphatic filariasis (LF) caused by Wuchereria bancrofti is present at high prevalence in some parts of Papua New Guinea. However, there has been no rigorous data-based representative assessment of nationwide prevalence of LF. The LF programme has been daunted by the scope of the problem, and progress on mass drug administration (MDA) has been slow and lacking in resources. Methods A systematic literature review identified LF surveys in Papua New Guinea between 1980 and 2011. Results were extracted by location, time period and test used (blood slide, immunochromatographic test (ICT) or Og4C3 ELISA) and combined by district. Three criteria schemes based on the Global Programme to Eliminate Lymphatic Filariasis guidelines, with modifications, were developed to classify and prioritize districts by prevalence level. Results of repeated surveys in the same sites were used to investigate the impact of MDA on LF prevalence over the time period. Results There were 312 distinct survey sites identified in 80 of the 89 districts over the 31-year period. The overall LF prevalence in the sites tested was estimated at 18.5 to 27.5% by blood slide for microfilariae (Mf), 10.1% to 12.9% by ICT and 45.4% to 48.8% by Og4C3. Biases in site selection towards areas with LF, and change in type of assay used, affected the prevalence estimates, but overall decline in prevalence over the time period was observed. Depending on the criteria used, 34 to 36 districts (population 2.7 to 2.9 million) were classed as high endemic (≥5% prevalence), 15 to 25 districts (1.7 to 1.9 million) as low endemic (Papua New Guinea enables better estimation of the national burden, identifies gaps in knowledge, quantifies and locates the population at risk, and can be used to predict the likely impact of MDA and/or vector control. Better targeting of districts by level of prevalence will strengthen the control programme, facilitate monitoring of the disease trend and increase the likelihood of

  11. Wide-Scope Screening Method for Multiclass Veterinary Drug Residues in Fish, Shrimp, and Eel Using Liquid Chromatography-Quadrupole High-Resolution Mass Spectrometry.

    Science.gov (United States)

    Turnipseed, Sherri B; Storey, Joseph M; Lohne, Jack J; Andersen, Wendy C; Burger, Robert; Johnson, Aaron S; Madson, Mark R

    2017-08-30

    A screening method for veterinary drug residues in fish, shrimp, and eel using LC with a high-resolution MS instrument has been developed and validated. The method was optimized for over 70 test compounds representing a variety of veterinary drug classes. Tissues were extracted by vortex mixing with acetonitrile acidified with 2% acetic acid and 0.2% p-toluenesulfonic acid. A centrifuged portion of the extract was passed through a novel solid phase extraction cartridge designed to remove interfering matrix components from tissue extracts. The eluent was then evaporated and reconstituted for analysis. Data were collected with a quadrupole-Orbitrap high-resolution mass spectrometer using both nontargeted and targeted acquisition methods. Residues were detected on the basis of the exact mass of the precursor and a product ion along with isotope pattern and retention time matching. Semiquantitative data analysis compared MS 1 signal to a one-point extracted matrix standard at a target testing level. The test compounds were detected and identified in salmon, tilapia, catfish, shrimp, and eel extracts fortified at the target testing levels. Fish dosed with selected analytes and aquaculture samples previously found to contain residues were also analyzed. The screening method can be expanded to monitor for an additional >260 veterinary drugs on the basis of exact mass measurements and retention times.

  12. Aggressive Angioimmunoblastic T Cell Lymphomas (AITL) with Soft Tissue Extranodal Mass Varied Histopathological Patterns with Peripheral Blood, Bone Marrow, and Splenic Involvement and Review of Literature.

    Science.gov (United States)

    Mukherjee, Tanushri; Dutta, Rajat; Pramanik, S

    2018-03-01

    Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T cell non-Hodgkin lymphoma with an aggressive fatal course and it has varied clinical presentation with an uncommon presentation when they present as soft tissue masses or when there is spill in the peripheral blood or there are composite lymphomas that are rare presentations. Common presentations include lymphadenopathy, fever and systemic symptoms, hemolytic anemias, skin rashes, and rheumatoid arthritis. The classical histopathology is absence of follicles in lymph nodes with presence of high endothelial venules and the tumor cells of small to medium-sized lymphocytes with pale cytoplasm mixed with reactive T cells. On immunohistochemistry, the cells are positive for CD3, CD4, CD10, BCL2, and CXCL13. In this observational study, the clinicopathologic presentation and the immunohistochemical profile of five cases who initially presented with a soft tissue mass which is an extremely rare presentation of this rare type of non-Hodgkin lymphoma that was diagnosed at our center with peripheral blood and bone marrow involvement and the clinicopathologic presentation, immunohistochemical profile, and response to treatment on follow-up are correlated with the literature review. One case had a fulminant and aggressive course and was fatal within 2 months of diagnosis. The rest of the four cases are on regular chemotherapy and follow-up. Our five cases had presented with soft tissue masses, two in the axillary regio,n two in the hand, and one in the scapular region with an extranodal presentation, and there was associated lymphadenopathy which developed subsequently with classic histomorphology and immunohistochemical findings. The age range was 46-54 years and all five cases were males. Three cases were with anemia (hemoglobin range 6.5-8.0 mg/dl) and all five cases were having peripheral blood plasmacytosis. Histopathology was classic with paracortical involvement with polymorphous population of cells with

  13. Multiple Reaction Monitoring Mode Based Liquid Chromatography-Mass Spectrometry Method for Simultaneous Quantification of Brassinolide and Other Plant Hormones Involved in Abiotic Stresses

    Directory of Open Access Journals (Sweden)

    Deepak M. Kasote

    2016-01-01

    Full Text Available Plant hormones are the key regulators of adaptive stress response. Abiotic stresses such as drought and salt are known to affect the growth and productivity of plants. It is well known that the levels of plant hormones such as zeatin (ZA, abscisic acid (ABA, salicylic acid (SA, jasmonic acid (JA, and brassinolide (BR fluctuate upon abiotic stress exposure. At present, there is not any single suitable liquid chromatography-mass spectrometry (LC-MS method for simultaneous analysis of BR and other plant hormones involved in abiotic stresses. In the present study, we developed a simple, sensitive, and rapid method for simultaneous analysis of five major plant hormones, ZA, ABA, JA, SA, and BR, which are directly or indirectly involved in drought and salt stresses. The optimized extraction procedure was simple and easy to use for simultaneous measurement of these plant hormones in Arabidopsis thaliana. The developed method is highly reproducible and can be adapted for simultaneous measurement of changes in plant hormones (ZA, ABA, JA, SA, and BR in response to abiotic stresses in plants like A. thaliana and tomato.

  14. Multiple Reaction Monitoring Mode Based Liquid Chromatography-Mass Spectrometry Method for Simultaneous Quantification of Brassinolide and Other Plant Hormones Involved in Abiotic Stresses.

    Science.gov (United States)

    Kasote, Deepak M; Ghosh, Ritesh; Chung, Jun Young; Kim, Jonggeun; Bae, Inhwan; Bae, Hanhong

    2016-01-01

    Plant hormones are the key regulators of adaptive stress response. Abiotic stresses such as drought and salt are known to affect the growth and productivity of plants. It is well known that the levels of plant hormones such as zeatin (ZA), abscisic acid (ABA), salicylic acid (SA), jasmonic acid (JA), and brassinolide (BR) fluctuate upon abiotic stress exposure. At present, there is not any single suitable liquid chromatography-mass spectrometry (LC-MS) method for simultaneous analysis of BR and other plant hormones involved in abiotic stresses. In the present study, we developed a simple, sensitive, and rapid method for simultaneous analysis of five major plant hormones, ZA, ABA, JA, SA, and BR, which are directly or indirectly involved in drought and salt stresses. The optimized extraction procedure was simple and easy to use for simultaneous measurement of these plant hormones in Arabidopsis thaliana. The developed method is highly reproducible and can be adapted for simultaneous measurement of changes in plant hormones (ZA, ABA, JA, SA, and BR) in response to abiotic stresses in plants like A. thaliana and tomato.

  15. Qualitative and quantitative temporal analysis of licit and illicit drugs in wastewater in Australia using liquid chromatography coupled to mass spectrometry.

    Science.gov (United States)

    Bade, Richard; White, Jason M; Gerber, Cobus

    2018-01-01

    The combination of qualitative and quantitative bimonthly analysis of pharmaceuticals and illicit drugs using liquid chromatography coupled to mass spectrometry is presented. A liquid chromatography-quadrupole time of flight instrument equipped with Sequential Window Acquisition of all THeoretical fragment-ion spectra (SWATH) was used to qualitatively screen 346 compounds in influent wastewater from two wastewater treatment plants in South Australia over a 14-month period. A total of 100 compounds were confirmed and/or detected using this strategy, with 61 confirmed in all samples including antidepressants (amitriptyline, dothiepin, doxepin), antipsychotics (amisulpride, clozapine), illicit drugs (cocaine, methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA)), and known drug adulterants (lidocaine and tetramisole). A subset of these compounds was also included in a quantitative method, analyzed on a liquid chromatography-triple quadrupole mass spectrometer. The use of illicit stimulants (methamphetamine) showed a clear decrease, levels of opioid analgesics (morphine and methadone) remained relatively stable, while the use of new psychoactive substances (methylenedioxypyrovalerone (MDPV) and Alpha PVP) varied with no visible trend. This work demonstrates the value that high-frequency sampling combined with quantitative and qualitative analysis can deliver. Graphical abstract Temporal analysis of licit and illicit drugs in South Australia.

  16. Mass Spectrometric Characterization of Circulating Covalent Protein Adducts Derived from a Drug Acyl Glucuronide Metabolite: Multiple Albumin Adductions in Diclofenac Patients

    Science.gov (United States)

    Hammond, Thomas G.; Meng, Xiaoli; Jenkins, Rosalind E.; Maggs, James L.; Castelazo, Anahi Santoyo; Regan, Sophie L.; Bennett, Stuart N. L.; Earnshaw, Caroline J.; Aithal, Guruprasad P.; Pande, Ira; Kenna, J. Gerry; Stachulski, Andrew V.; Park, B. Kevin

    2014-01-01

    Covalent protein modifications by electrophilic acyl glucuronide (AG) metabolites are hypothetical causes of hypersensitivity reactions associated with certain carboxylate drugs. The complex rearrangements and reactivities of drug AG have been defined in great detail, and protein adducts of carboxylate drugs, such as diclofenac, have been found in liver and plasma of experimental animals and humans. However, in the absence of definitive molecular characterization, and specifically, identification of signature glycation conjugates retaining the glucuronyl and carboxyl residues, it cannot be assumed any of these adducts is derived uniquely or even fractionally from AG metabolites. We have therefore undertaken targeted mass spectrometric analyses of human serum albumin (HSA) isolated from diclofenac patients to characterize drug-derived structures and, thereby, for the first time, have deconstructed conclusively the pathways of adduct formation from a drug AG and its isomeric rearrangement products in vivo. These analyses were informed by a thorough understanding of the reactions of HSA with diclofenac AG in vitro. HSA from six patients without drug-related hypersensitivities had either a single drug-derived adduct or one of five combinations of 2–8 adducts from among seven diclofenac N-acylations and three AG glycations on seven of the protein’s 59 lysines. Only acylations were found in every patient. We present evidence that HSA modifications by diclofenac in vivo are complicated and variable, that at least a fraction of these modifications are derived from the drug’s AG metabolite, and that albumin adduction is not inevitably a causation of hypersensitivity to carboxylate drugs or a coincidental association. PMID:24902585

  17. Sampling of illicit drugs for quantitative analysis--part II. Study of particle size and its influence on mass reduction.

    Science.gov (United States)

    Bovens, M; Csesztregi, T; Franc, A; Nagy, J; Dujourdy, L

    2014-01-01

    The basic goal in sampling for the quantitative analysis of illicit drugs is to maintain the average concentration of the drug in the material from its original seized state (the primary sample) all the way through to the analytical sample, where the effect of particle size is most critical. The size of the largest particles of different authentic illicit drug materials, in their original state and after homogenisation, using manual or mechanical procedures, was measured using a microscope with a camera attachment. The comminution methods employed included pestle and mortar (manual) and various ball and knife mills (mechanical). The drugs investigated were amphetamine, heroin, cocaine and herbal cannabis. It was shown that comminution of illicit drug materials using these techniques reduces the nominal particle size from approximately 600 μm down to between 200 and 300 μm. It was demonstrated that the choice of 1 g increments for the primary samples of powdered drugs and cannabis resin, which were used in the heterogeneity part of our study (Part I) was correct for the routine quantitative analysis of illicit seized drugs. For herbal cannabis we found that the appropriate increment size was larger. Based on the results of this study we can generally state that: An analytical sample weight of between 20 and 35 mg of an illicit powdered drug, with an assumed purity of 5% or higher, would be considered appropriate and would generate an RSDsampling in the same region as the RSDanalysis for a typical quantitative method of analysis for the most common, powdered, illicit drugs. For herbal cannabis, with an assumed purity of 1% THC (tetrahydrocannabinol) or higher, an analytical sample weight of approximately 200 mg would be appropriate. In Part III we will pull together our homogeneity studies and particle size investigations and use them to devise sampling plans and sample preparations suitable for the quantitative instrumental analysis of the most common illicit

  18. A drug fatality involving Kratom.

    Science.gov (United States)

    Neerman, Michael F; Frost, Randall E; Deking, Janine

    2013-01-01

    A 17-year-old white man who showed no obvious signs of trauma was found unresponsive in bed and was pronounced dead at the scene. The decedent had a documented history of heroin abuse and chronic back pain and reportedly self-medicated with Kratom (mitragynine). The autopsy was remarkable only for pulmonary congestion and edema and a distended bladder, both of which are consistent with, though not diagnostic of, opiate use. A laboratory work-up revealed therapeutic levels of over-the-counter cold medications and benzodiazepines. However, of interest was a level of mitragynine at 0.60 mg/L. Given the facts of the case, the Medical Examiner certified the cause of death as "possible Kratom toxicity" and the manner of death was classified as "accident." © 2012 American Academy of Forensic Sciences.

  19. Screening in veterinary drug analysis and sports doping control based on full-scan, accurate-mass spectrometry

    NARCIS (Netherlands)

    Peters, R.J.B.; Stolker, A.A.M.; Mol, J.G.J.; Lommen, A.; Lyris, E.; Angelis, Y.S.; Vonaparti, A.; Stamou, M.; Georgakopoulos, C.G.; Nielen, M.W.F.

    2010-01-01

    A common trend in food contaminants and sports doping control is towards a limited number of targeted, full-scan, accurate-mass spectrometry (MS) methods based on time-of-flight (TOF) or Fourier-transform orbital trap (Orbitrap) mass analyzers. Retrospective analysis of the full-scan datasets of

  20. An examination of outlaw motorcycle gangs and their involvement in the illicit drug market and the effectiveness of anti-association legislative responses.

    Science.gov (United States)

    Goldsworthy, Terry; McGillivray, Laura

    2017-03-01

    In 2013 the Queensland Government introduced criminal association and mandatory sentencing laws for members of outlaw motorcycle gangs (OMCGs). Forms of "criminal association" or "anti-bikie" laws have been introduced in several Australian jurisdictions, and recent High Court decisions upholding their constitutionality will ensure that they remain part of our justice landscape. Generally, the aims of these laws are to declare a specific organisation as "criminal" and impose various legal orders and offences that thwart the consorting of members and address organised crime, such as unexplained wealth regimes. There have been significant criticisms of these styles of association laws both here and internationally. The aim of this research is to show the extent of involvement of OMCGs in the drug trade and associated organised crime activity, and whether anti-association laws are an effective response to this type of organised criminal activity. This paper relied on six years of data outlining the criminal activity of OMCGs from the Queensland Police Service (QPS) obtained under the legislative framework of The Queensland Right to Information Act (RTI) 2009. Information obtained from the Queensland Commission into Organised Crime (2015) and Queensland Taskforce into organised crime legislation (2015) was also used. The data suggest that the role of OMCGs in the drug market has been overstated and is not as dominant as has been portrayed by government agencies and the popular media. Generally, OMCGs account for less than one percent of organised crime type activity. This is also true for drug type offences where OMCGs are responsible for less than one percent of offences. The findings show that the Queensland example has highlighted the ineffectiveness of the criminal association laws and the mandatory sentencing provisions in that they have had little impact on drug market activity and little success in the courts. The analysis presented here is twofold: an

  1. Contamination Profiles and Mass Loadings of Macrolide Antibiotics and Illicit Drugs from a Small Urban Wastewater Treatment Plant

    Science.gov (United States)

    Information is limited regarding sources, distribution, environmental behavior, and fate of prescribed and illicit drugs. Wastewater treatment plant (WWTP) effluents can be one of the sources of pharmaceutical and personal care products (PPCP) into streams, rivers and lakes. The ...

  2. Drug-facilitated sexual assault (DFSA) involving 4-methylethcathinone (4-MEC), 3,4-Methylenedioxypyrovalerone (MDPV) and doxylamine highlighted by hair analysis.

    Science.gov (United States)

    Larabi, Islam Amine; Martin, Marie; Etting, Isabelle; Penot, Pauline; Fabresse, Nicolas; Alvarez, Jean Claude

    2018-03-10

    Recently, the emergence of new psychoactive substances (NPS) has led to their wide use among clubbers and men who have sex with men (MSM) for their stimulant effects. However, their use in drug facilitated sexual assault (DFSA) has rarely been described. Herein we report a case of a 44 years-old man who was assaulted after a party. Due to late reporting of the offense, only hair (black) was sampled 15 days later and a segmental analysis was achieved to look for most DFSA agents and NPS. Twenty mg of each segment (A:0-1cm, B:1-3cm and C:3-5cm) were incubated in phosphate buffer pH 5.0. After alkaline liquid extraction and chromatographic separation on 1.9 μm Hypersil GOLD PFP column, compounds were detected by a TSQ Vantage mass spectrometer with electrospray ionization in positive mode with MRM acquisition. 4-methylethcathinone (4-MEC), methylenedioxypyrovalerone (MDPV) and doxylamine were found in proximal segment at very low concentrations (3, 5 and 9 pg/mg, respectively) which is in agreement with a single exposure in the previous month corresponding to the alleged facts. These substances were not detected in segments B and C showing a lack of repetitive exposure before the alleged event. Thus, the results do not contradict the patient's claim of being assaulted. Doxylamine has already been encountered in such cases but no publications referring to 4-MEC or MDPV use have ever been documented. Our case reports the unusual administration of cathinones to achieve a sexual assault and stresses the interest of seeking for designer drugs when dealing with DFSA cases. This article is protected by copyright. All rights reserved.

  3. The use of liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring of antibiotics in cancer patients.

    Science.gov (United States)

    El-Najjar, Nahed; Jantsch, Jonathan; Gessner, André

    2017-08-28

    Cancer remains a leading cause of mortality and morbidity worldwide. In addition to organ failure, the most frequent reasons for admission of cancer patients to intensive care units (ICU) are: infections and sepsis. As critically ill, the complexity of the health situation of cancer patients renders the standard antimicrobial regimen more complex and even inadequate which results in increased mortality rates. This is due to pathophysiological changes in the volume of distribution, increased clearance, as well as to organ dysfunction. While in the former cases a decrease in drug efficacy is observed, the hallmark of the latter one is overdosing leading to increased toxicity at the expense of efficacy. Furthermore, an additional risk factor is the potential drug-drug interaction between antibiotics and antineoplastic agents. Therefore, therapeutic drug monitoring (TDM) is a necessity to improve the clinical outcome of antimicrobial therapy in cancer patients. To be applied in routine analysis the method used for TDM should be cheap, fast and highly accurate/sensitive. Furthermore, as ICU patients are treated with a cocktail of antibiotics the method has to cover the simultaneous analysis of antibiotics used as a first/second line of treatment. The aim of the current review is to briefly survey the pitfalls in the current antimicrobial therapy and the central role of TDM in dose adjustment and drug-drug interaction's evaluation. A major section is dedicated to summarize the currently published analytical methods and to shed light on the difficulties and potential problems that can be encountered during method development.

  4. Profiling of drug binding proteins by monolithic affinity chromatography in combination with liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Zhang, Xuepei; Wang, Tongdan; Zhang, Hanzhi; Han, Bing; Wang, Lishun; Kang, Jingwu

    2014-09-12

    A new approach for proteome-wide profiling drug binding proteins by using monolithic capillary affinity chromatography in combination with HPLC-MS/MS is reported. Two immunosuppresive drugs, namely FK506 and cyclosporin A, were utilized as the experimental models for proof-of-concept. The monolithic capillary affinity columns were prepared through a single-step copolymerization of the drug derivatives with glycidyl methacrylate and ethylene dimethacrylate. The capillary chromatography with the affinity monolithic column facilitates the purification of the drug binding proteins from the cell lysate. By combining the capillary affinity column purification and the shot-gun proteomic analysis, totally 33 FK506- and 32 CsA-binding proteins including all the literature reported target proteins of these two drugs were identified. Among them, two proteins, namely voltage-dependent anion-selective channel protein 1 and serine/threonine-protein phosphatase PGAM5 were verified by using the recombinant proteins. The result supports that the monolithic capillary affinity chromatography is likely to become a valuable tool for profiling of binding proteins of small molecular drugs as well as bioactive compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. [Determination of 49 drugs and 5 metabolites in drinking water samples using ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry].

    Science.gov (United States)

    Wang, Shuo; Zhang, Xiangming; Zhang, Jing; Shao, Bing; Li, Shuming

    2015-07-01

    A method for the determination of 54 drugs in drinking water samples was developed by using ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI MS/MS). The target drugs in drinking water samples were enriched and cleaned-up by HLB solid-phase extraction (SPE) cartridges and then eluted with 5 mL methanol. The elute was collected, concentrated under a gentle stream of nitrogen gas, diluted with 0.4 mL 0.1% formic acid solution, and analyzed by UPLC-ESI MS/MS. The separation of the 54 drugs was performed on an ACQUITY UPLC™ BEH C18 column using mobile phases of 0.1% formic acid and methanol by gradient elution. The multiple reaction monitoring (MRM) mode was employed in mass spectrometry acquisition. The matrix-matched external standard calibration was used for quantitation. The results showed that the average recoveries of the drugs in ground water, tap water and surface water were 58.7%-104.4%, 53.1%-109.5%, and 50.7%-118.8%, respectively, and the corresponding relative standard deviations (RSD, n=6) were 0.3%-12.8%, 1.0%-15.5%, and 0.4%-19.3%, respectively. The method quantification limits (MQL) for target compounds were in the range of 0.002-5.000 ng/L. The developed method was applied to analyze the water samples from Beijing. The results showed that 26 drugs were detected in ground water samples.

  6. Capillary column switching restricted-access media-liquid chromatography-electrospray ionization-tandem mass spectrometry system for simultaneous and direct analysis of drugs in biofluids.

    Science.gov (United States)

    Santos-Neto, Alvaro J; Markides, Karin E; Sjöberg, Per J R; Bergquist, Jonas; Lancas, Fernando M

    2007-08-15

    Capillary online restricted-access media-liquid chromatography-electrospray ionization-tandem mass spectrometry (RAM-LC-ESI-MS/MS) for direct analysis of drugs and metabolites spiked in biological fluids was developed. Using a column switching setup it was possible to perform effective sample preparation and analysis of raw biological fluids (plasma and urine) without matrix effects in the electrospray mass spectrometric detection step. The peak focusing efficiency of the extraction column was more effective in backflush compared to foreflush mode. The system was able to concentrate diminished samples of polar drugs and their metabolites reaching quantifiable results as low as 1 ng/mL utilizing a sample volume of only 333 nL of biofluids. New column hardware was developed to circumvent clogging problems experienced with plasma injections. The glass fiber filter frit, which is commonly used, was replaced with a short piece of 20 microm i.d. fused silica capillary. The extraction columns were able to handle up to 60 injections and showed a high loading capacity, making the saturation of the MS detector the limiting factor on the linear dynamic range. The simultaneous separation and detection of 10 drugs and metabolites was obtained in 8 min of analysis, including the online sample preparation and enrichment step.

  7. Fluoroscopically guided transforaminal epidural steroid injections at a quaternary-care teaching institution: effect of trainee involvement and patient body mass index on fluoroscopy time and patient dose.

    Science.gov (United States)

    Tiegs-Heiden, C A; Murthy, N S; Geske, J R; Diehn, F E; Schueler, B A; Wald, J T; Kaufmann, T J; Lehman, V T; Carr, C M; Amrami, K K; Morris, J M; Thielen, K R; Maus, T P

    2016-01-01

    To investigate whether there are differences in fluoroscopy time and patient dose for fluoroscopically guided lumbar transforaminal epidural steroid injections (TFESIs) performed by staff radiologists versus with trainees and to evaluate the effect of patient body mass index (BMI) on fluoroscopy time and patient dose, including their interactions with other variables. Single-level lumbar TFESIs (n=1844) between 1 January 2011 and 31 December 2013 were reviewed. Fluoroscopy time, reference point air kerma (Ka,r), and kerma area product (KAP) were recorded. BMI and trainee involvement were examined as predictors of fluoroscopy time, Ka,r, and KAP in models adjusted for age and gender in multivariable linear models. Stratified models of BMI groups by trainee presence were performed. Increased age was the only significant predictor of increased fluoroscopy time (pfluoroscopy time predicted increased Ka,r and KAP in all groups (pfluoroscopy time or Ka,r in any BMI category. KAP was lower with trainees in the overweight group (p=0.0009) and higher in male patients for all BMI categories (pfluoroscopy time or patient dose. BMI did not affect fluoroscopy time; however, overweight and obese patients received significantly higher Ka,r and KAP. Male patients received a higher KAP in all BMI categories. Limiting fluoroscopy time and good collimation practices should be reinforced in these patients. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  8. The Necessity of OCT-4 and CDX2 for Early Development and Gene Expression Involved in Differentiation of Inner Cell Mass and Trophectoderm Lineages in Bovine Embryos.

    Science.gov (United States)

    Sakurai, Nobuyuki; Takahashi, Kazuki; Emura, Natsuko; Fujii, Takashi; Hirayama, Hiroki; Kageyama, Soichi; Hashizume, Tsutomu; Sawai, Ken

    2016-10-01

    The functions of POU class 5 transcription factor 1 (Oct-4) and caudal-type homeobox 2 (Cdx2) in the differentiation of the murine inner cell mass (ICM) and trophectoderm (TE) have been described in detail. However, little is known about the roles of OCT-4 and CDX2 in preimplantation bovine embryos. To elucidate their functions during early development in bovine embryos, we performed OCT-4 and CDX2 downregulation using RNA interference. We injected OCT-4- or CDX2-specific short interfering RNAs (siRNAs) into bovine zygotes. The rate of blastocyst development of OCT-4-downregulated embryos was lower compared with uninjected or control siRNA-injected embryos. Gene expression analysis revealed decreased CDX2 and fibroblast growth factor 4 expression in OCT-4-downregulated embryos. CDX2-downregulated embryos developed to the blastocyst stage; however, in most cases, blastocoel formation was delayed. Gene expression analysis revealed decreased GATA3 expression and elevated NANOG expression in CDX2-downregulated embryos. In conclusion, OCT-4 and CDX2 are essential for early development and gene expression involved in differentiation of ICM and TE lineages in bovine embryos.

  9. Analytical detection of explosives and illicit, prescribed and designer drugs using proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS)

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Bishu; Petersson, Fredrik; Juerschik, Simone [Institut fuer Ionenphysik und Angewandte Physik, Universitaet Innsbruck, Technikerstr. 25, 6020 Innsbruck (Austria); Sulzer, Philipp; Jordan, Alfons [IONICON Analytik GmbH, Eduard-Bodem-Gasse 3, 6020 Innsbruck (Austria); Maerk, Tilmann D. [Institut fuer Ionenphysik und Angewandte Physik, Universitaet Innsbruck, Technikerstr. 25, 6020 Innsbruck (Austria); IONICON Analytik GmbH, Eduard-Bodem-Gasse 3, 6020 Innsbruck (Austria); Watts, Peter; Mayhew, Chris A. [School of Physics and Astronomy, University of Birmingham, Edgbaston, Birmingham B15 4TT (United Kingdom)

    2011-07-01

    This work demonstrates the extremely favorable features of Proton Transfer Reaction Time-of-flight Mass Spectrometry (PTR-TOF-MS) for the detection and identification of solid explosives, chemical warfare agent simulants and illicit, prescribed and designer drugs in real time. Here, we report the use of PTR-TOF, for the detection of explosives (e.g., trinitrotoluene, trinitrobenzene) and illicit, prescribed and designer drugs (e.g., ecstasy, morphine, heroin, ethcathinone, 2C-D). For all substances, the protonated parent ion (as we used H{sub 3}O{sup +} as a reagent ion) could be detected, providing a high level of confidence in their identification since the high mass resolution allows compounds having the same nominal mass to be separated. We varied the E/N from 90 to 220 T{sub d} (1 T{sub d}=10{sup -17} Vcm{sup -1}). This allowed us to study fragmentation pathways as a function of E/N (reduced electric field). For a few compounds rather unusual E/N dependencies were also discovered.

  10. Comprehensive qualitative and quantitative determination of pesticides and veterinary drugs in honey using liquid chromatography-Orbitrap high resolution mass spectrometry.

    Science.gov (United States)

    Gómez-Pérez, María Luz; Plaza-Bolaños, Patricia; Romero-González, Roberto; Martínez-Vidal, José Luis; Garrido-Frenich, Antonia

    2012-07-27

    A database has been created for the simultaneous analysis of more than 350 pesticides and veterinary drugs (including antibiotics) using ultra-high performance liquid chromatography coupled to high resolution Orbitrap mass spectrometry (UHPLC-Orbitrap-MS). This is a comprehensive exact mass database built using the Exactive-Orbitrap analyzer. The developed database includes exact masses of the target ions and retention time data, and allows the automatic search of the included compounds. Generic chromatographic and MS conditions have been applied. The presented database is suitable for qualitative analysis, and it was also evaluated for quantitative purposes in routine analysis, after the optimization and validation of a generic extraction method in honey samples. Adequate recovery and precision values for most of the studied analytes were obtained and the limits of detection (LOD) ranged from 1 to 50 μg kg(-1). For pesticides, LODs were always lower than the MRLs established by European Union in honey, except for a few compounds. This method was applied to the analysis of 26 real honey samples and some pesticides (azoxystrobin, coumaphos, dimethoate and thiacloprid) were detected in 4 samples. Azoxystrobin and coumaphos were determined in two different samples (organic honey) at 1.5 μg kg(-1) and 5.1 μg kg(-1). Veterinary drugs were not detected in the analyzed samples. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. The Cedar Project: resilience in the face of HIV vulnerability within a cohort study involving young Indigenous people who use drugs in three Canadian cities.

    Science.gov (United States)

    Pearce, Margo E; Jongbloed, Kate A; Richardson, Chris G; Henderson, Earl W; Pooyak, Sherri D; Oviedo-Joekes, Eugenia; Christian, Wunuxtsin M; Schechter, Martin T; Spittal, Patricia M

    2015-10-29

    Indigenous scholars have long argued that it is critical for researchers to identify factors related to cultural connectedness that may protect against HIV and hepatitis C infection and buffer the effects of historical and lifetime trauma among young Indigenous peoples. To our knowledge, no previous epidemiological studies have explored the effect of historical and lifetime traumas, cultural connectedness, and risk factors on resilience among young, urban Indigenous people who use drugs. This study explored risk and protective factors associated with resilience among participants of the Cedar Project, a cohort study involving young Indigenous peoples who use illicit drugs in three cities in British Columbia, Canada. We utilized the Connor-Davidson Resilience Scale to measure resilience, the Childhood Trauma Questionnaire to measure childhood maltreatment, and the Symptom-Checklist 90-Revised to measure psychological distress among study participants. Multivariate linear mixed effects models (LME) estimated the effect of study variables on mean change in resilience scores between 2011-2012. Among 191 participants, 92 % had experienced any form of childhood maltreatment, 48 % had a parent who attended residential school, and 71 % had been in foster care. The overall mean resilience score was 62.04, with no differences between the young men and women (p = 0.871). Adjusted factors associated with higher mean resilience scores included having grown up in a family that often/always lived by traditional culture (B = 7.70, p = 0.004) and had often/always spoken their traditional language at home (B = 10.52, p people in this study have faced multiple complex challenges to their strength. However, cultural foundations continue to function as buffers that protect young Indigenous people from severe health outcomes, including vulnerability to HIV and HCV infection.

  12. Direct coupling of electromembrane extraction to mass spectrometry – Advancing the probe functionality toward measurements of zwitterionic drug metabolites

    DEFF Research Database (Denmark)

    Kige Rye, Torstein; Fuchs, David; Pedersen-Bjergaard, Stig

    2017-01-01

    -nitrophenyl octyl ether (and for some experiments containing 30% triphenyl phosphate (TPP)), and into 20 μL min-1 of formic acid as acceptor phase, which was introduced through a third flow channel. The acceptor phase was pumped directly to the MS system, and the ion intensity of extracted analytes...... of parent drugs and metabolites. It was found that TPP added to the SLM improved extraction efficiencies of certain drug metabolites. Finally the optimized and characterized triple-flow EME probe was used for online studying the in-vitro metabolism of hydroxyzine and vortioxetine by rat liver microsomes....... Due to the automated pre-extraction acidification of the rat liver microsomal solutions, it was possible to continuously monitor formation of the zwitterionic drug metabolites. As the triple-flow EME probe allowed modification of the pH of the sample without changing the pH in the bulk sample...

  13. Black Youths and Illegal Drugs.

    Science.gov (United States)

    Joseph, Janice; Pearson, Patricia G.

    2002-01-01

    Examines the effect of drugs on black youths, discussing different types of drug involvement, reasons for drug involvement, extent and nature of involvement, drugs and crime, drugs and health issues, drug control strategies, and prevention. Policy implications include prioritizing drug prevention among black youths, providing alternatives to drug…

  14. A method to detect metal-drug complexes and their interactions with pathogenic bacteria via graphene nanosheet assist laser desorption/ionization mass spectrometry and biosensors.

    Science.gov (United States)

    Abdelhamid, Hani Nasser; Wu, Hui-Fen

    2012-11-02

    A new method was proposed to probe the interactions between transition metals of Fe(II), Fe(III), Cu(II) with a non steroidal anti-inflammatory drug (NSAID), flufenamic acid (FF) using graphene as a matrix for Graphene assisted laser desorption ionization mass spectrometry (GALDI-MS). Metal-drug complexation was confirmed via UV absorption spectroscopy, fluorescence spectroscopy, pH meter, and change in solution conductivity. The optimal molar ratios for these complexation interactions are stoichiometry 1:2 in both Cu(II) and Fe(II) complexes, and 1:3 in Fe(III) complexes at physiological pH (7.4). Metal complexation of the drug could enhance fluorescence for 20 fold which is due to the charge transfer reaction or increase rigidity of the drug. The main interaction between graphene and flufenamic acid is the П-П interaction which allows us to probe the metal-drug complexation. The GALDI-MS could sensitively detect the drug at m/z 281.0 Da (protonated molecule) with detection limit 2.5 pmol (1.0 μM) and complexation at m/z 661.0, 654.0 and 933.0 Da corresponding to [Cu(II)(FF)(2)(H(2)O)(2)+H](+), [Fe(II)(FF)(2)(H(2)O)(2)+H](+) and [Fe(III) (FF)(3)(H(2)O)(2)+H](+), respectively (with limit of detection (LOD) 2.0 pmol (10.0 μM). Matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) spectra show change in the protein profile of intact pathogenic bacteria (Pseudomonas aeroginosa, Staphylococcus aureus). The change in the ionization ability (mainly proton affinity) of pathogenic bacteria may be due to the interactions between the bacteria with the drug (or its complexes). Shielding carboxylic group by metals and increase the hydrophilicity could enhance the biocompatibility of complexes toward the pathogenic bacteria which can be used as biosensors with high sensitivity and lowest detectable concentrations are in the range of 3.3×10(3)-3.9×10(4) cfu mL(-1) with large linear dynamic range. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. A method to detect metal–drug complexes and their interactions with pathogenic bacteria via graphene nanosheet assist laser desorption/ionization mass spectrometry and biosensors

    International Nuclear Information System (INIS)

    Abdelhamid, Hani Nasser; Wu, Hui-Fen

    2012-01-01

    Highlights: ► Probe transition metals-complexes based on noncovalent functionalized graphene for MALDI-MS. ► Study interaction of transition metals complexes with pathogenic bacteria. ► Propose a new biosensor for two pathogenic bacteria. - Abstract: A new method was proposed to probe the interactions between transition metals of Fe(II), Fe(III), Cu(II) with a non steroidal anti-inflammatory drug (NSAID), flufenamic acid (FF) using graphene as a matrix for Graphene assisted laser desorption ionization mass spectrometry (GALDI-MS). Metal–drug complexation was confirmed via UV absorption spectroscopy, fluorescence spectroscopy, pH meter, and change in solution conductivity. The optimal molar ratios for these complexation interactions are stoichiometry 1:2 in both Cu(II) and Fe(II) complexes, and 1:3 in Fe(III) complexes at physiological pH (7.4). Metal complexation of the drug could enhance fluorescence for 20 fold which is due to the charge transfer reaction or increase rigidity of the drug. The main interaction between graphene and flufenamic acid is the Π–Π interaction which allows us to probe the metal–drug complexation. The GALDI-MS could sensitively detect the drug at m/z 281.0 Da (protonated molecule) with detection limit 2.5 pmol (1.0 μM) and complexation at m/z 661.0, 654.0 and 933.0 Da corresponding to [Cu(II)(FF) 2 (H 2 O) 2 + H] + , [Fe(II)(FF) 2 (H 2 O) 2 + H] + and [Fe(III) (FF) 3 (H 2 O) 2 + H] + , respectively (with limit of detection (LOD) 2.0 pmol (10.0 μM). Matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) spectra show change in the protein profile of intact pathogenic bacteria (Pseudomonas aeroginosa, Staphylococcus aureus). The change in the ionization ability (mainly proton affinity) of pathogenic bacteria may be due to the interactions between the bacteria with the drug (or its complexes). Shielding carboxylic group by metals and increase the hydrophilicity could enhance the biocompatibility of complexes

  16. HIV-1 A1 Subtype Epidemic in Italy Originated from Africa and Eastern Europe and Shows a High Frequency of Transmission Chains Involving Intravenous Drug Users.

    Directory of Open Access Journals (Sweden)

    Alessia Lai

    Full Text Available Subtype A accounts for only 12% of HIV-1 infections worldwide but predominates in Russia and Former Soviet Union countries of Eastern Europe. After an early propagation via heterosexual contacts, this variant spread explosively among intravenous drug users. A distinct A1 variant predominates in Greece and Albania, which penetrated directly from Africa. Clade A1 accounts for 12.5% of non-B subtypes in Italy, being the most frequent after F1 subtype.Aim of this study was to investigate the circulation of A1 subtype in Italy and trace its origin and diffusion through phylogenetic and phylodynamic approaches.The phylogenetic analysis of 113 A1 pol sequences included in the Italian ARCA database, indicated that 71 patients (62.8% clustered within 5 clades. A higher probability to be detected in clusters was found for patients from Eastern Europe and Italy (88.9% and 60.4%, respectively compared to those from Africa (20% (p < .001. Higher proportions of clustering sequences were found in intravenous drug users with respect to heterosexuals (85.7% vs. 59.3%, p = .056 and in women with respect to men (81.4% vs. 53.2%, p < .006. Subtype A1 dated phylogeny indicated an East African origin around 1961. Phylogeographical reconstruction highlighted 3 significant groups. One involved East European and some Italian variants, the second encompassed some Italian and African strains, the latter included the majority of viruses carried by African and Italian subjects and all viral sequences from Albania and Greece.Subtype A1 originated in Central Africa and spread among East European countries in 1982. It entered Italy through three introduction events: directly from East Africa, from Albania and Greece, and from the area encompassing Moldavia and Ukraine. As in previously documented A1 epidemics of East European countries, HIV-1 A1 subtype spread in Italy in part through intravenous drug users. However, Eastern European women contributed to the penetration of

  17. Community-directed mass drug administration is undermined by status seeking in friendship networks and inadequate trust in health advice networks.

    Science.gov (United States)

    Chami, Goylette F; Kontoleon, Andreas A; Bulte, Erwin; Fenwick, Alan; Kabatereine, Narcis B; Tukahebwa, Edridah M; Dunne, David W

    2017-06-01

    Over 1.9 billion individuals require preventive chemotherapy through mass drug administration (MDA). Community-directed MDA relies on volunteer community medicine distributors (CMDs) and their achievement of high coverage and compliance. Yet, it is unknown if village social networks influence effective MDA implementation by CMDs. In Mayuge District, Uganda, census-style surveys were conducted for 16,357 individuals from 3,491 households in 17 villages. Praziquantel, albendazole, and ivermectin were administered for one month in community-directed MDA to treat Schistosoma mansoni, hookworm, and lymphatic filariasis. Self-reported treatment outcomes, socioeconomic characteristics, friendship networks, and health advice networks were collected. We investigated systematically missed coverage and noncompliance. Coverage was defined as an eligible person being offered at least one drug by CMDs; compliance included ingesting at least one of the offered drugs. These outcomes were analyzed as a two-stage process using a Heckman selection model. To further assess if MDA through CMDs was working as intended, we examined the probability of accurate drug administration of 1) praziquantel, 2) both albendazole and ivermectin, and 3) all drugs. This analysis was conducted using bivariate Probit regression. Four indicators from each social network were examined: degree, betweenness centrality, closeness centrality, and the presence of a direct connection to CMDs. All models accounted for nested household and village standard errors. CMDs were more likely to offer medicines, and to accurately administer the drugs as trained by the national control programme, to individuals with high friendship degree (many connections) and high friendship closeness centrality (households that were only a short number of steps away from all other households in the network). Though high (88.59%), additional compliance was associated with directly trusting CMDs for health advice. Effective treatment

  18. C18-attached membrane funnel-based spray ionization mass spectrometry for quantification of anti-diabetic drug from human plasma.

    Science.gov (United States)

    Li, Wan; Chen, Xiangfeng; Wong, Y-L Elaine; Hung, Y-L Winnie; Wang, Ze; Deng, Liulin; Dominic Chan, T-W

    2016-08-24

    In this work, sorbent-attached membrane funnel-based spray ionization mass spectrometry was explored for quantitative analysis of anti-diabetic drugs spiked in human plasma. C18-attached membrane funnel was fabricated for in situ extraction and clean-up to alleviate matrix suppression effect in the ionization process. Repaglinide was used as a target analyte of anti-diabetic drugs. Under optimal working conditions, good linearity (R(2) > 0.99) was obtained in the concentration range of 1-100 ng mL(-1). The method detection limit of target drugs spiked in the human plasma was around 0.30 ng mL(-1). Through the application of an isotope-labeled internal standard, the signal fluctuation caused by residual background matrices was largely alleviated and the precision of measurement (RSD) was below 15%. The recovery of repaglinide for 5, 25, and 100 ng mL(-1) of spiked human plasma matrixes ranged from 87% to 112%. The developed method was successfully applied to determine repaglinide in plasma volunteers who orally received a dose of drug association. Our results demonstrated that membrane funnel-based spray is a simple and sensitive method for rapid screening analysis of complex biological samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Gold nanoparticles bridging infra-red spectroscopy and laser desorption/ionization mass spectrometry for direct analysis of over-the-counter drug and botanical medicines.

    Science.gov (United States)

    Chau, Siu-Leung; Tang, Ho-Wai; Ng, Kwan-Ming

    2016-05-05

    With a coating of gold nanoparticles (AuNPs), over-the-counter (OTC) drugs and Chinese herbal medicine granules in KBr pellets could be analyzed by Fourier Transform Infra-red (FT-IR) spectroscopy and Surface-assisted Laser Desorption/Ionization mass spectrometry (SALDI-MS). FT-IR spectroscopy allows fast detection of major active ingredient (e.g., acetaminophen) in OTC drugs in KBr pellets. Upon coating a thin layer of AuNPs on the KBr pellet, minor active ingredients (e.g., noscapine and loratadine) in OTC drugs, which were not revealed by FT-IR, could be detected unambiguously using AuNPs-assisted LDI-MS. Moreover, phytochemical markers of Coptidis Rhizoma (i.e. berberine, palmatine and coptisine) could be quantified in the concentrated Chinese medicine (CCM) granules by the SALDI-MS using standard addition method. The quantitative results matched with those determined by high-performance liquid chromatography with ultraviolet detection. Being strongly absorbing in UV yet transparent to IR, AuNPs successfully bridged FT-IR and SALDI-MS for direct analysis of active ingredients in the same solid sample. FT-IR allowed the fast analysis of major active ingredient in drugs, while SALDI-MS allowed the detection of minor active ingredient in the presence of excipient, and also quantitation of phytochemicals in herbal granules. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Development and characterization of a small electromembrane extraction probe coupled with mass spectrometry for real-time and online monitoring of in vitro drug metabolism

    DEFF Research Database (Denmark)

    Dugstad, Helene Bonkerud; Petersen, Nickolaj J.; Jensen, Henrik

    2014-01-01

    A small and very simple electromembrane extraction probe (EME-probe) was developed and coupled directly to electrospray ionization mass spectrometry (ESI-MS), and this system was used to monitor in real time in vitro metabolism by rat liver microsomes of drug substances from a small reaction...... (incubation) chamber (37 °C). The drug-related substances were continuously extracted from the 1.0 mL metabolic reaction mixture and into the EME-probe by an electrical potential of 2.5 V. The extraction probe consisted of a 1-mm long and 350-μm ID thin supported liquid membrane (SLM) of 2-nitrophenyl octyl...... ether. The drugs and formed metabolites where extracted through the SLM and directly into a 3 μL min(-1) flow of 60 mM HCOOH inside the probe serving as the acceptor solution. The acceptor solution was directed into the ESI-MS-system, and the MS continuously monitored the drug-related substances...

  1. A method for studies on interactions between a gold-based drug and plasma proteins based on capillary electrophoresis with inductively coupled plasma mass spectrometry detection

    DEFF Research Database (Denmark)

    Nguyen, Tam T T N; Østergaard, Jesper; Gammelgaard, Bente

    2015-01-01

    An analytical method based on capillary electrophoresis (CE) and inductively coupled plasma mass spectrometry (ICP-MS) detection was developed for studies on the interaction of gold-containing drugs and plasma proteins using auranofin as example. A detection limit of 18 ng/mL of auranofin...... corresponding to 5.2 ng/mL Au and a precision of 1.5 % were obtained. Kinetic studies of the interaction between auranofin and protein were performed by incubation in aqueous solutions as well as 20 % human plasma at 37 °C. The reaction of auranofin with human serum albumin (HSA) and plasma proceeded fast; 50...... was the major auranofin-interacting protein in plasma. The CE-ICP-MS method is proposed as a novel approach for kinetic studies of the interactions between gold-based drugs and plasma proteins. Graphical Abstract Development of a CE-ICP-MS based method allows for studies on interaction of the gold containing...

  2. Rapid wide-scope screening of drugs of abuse, prescription drugs with potential for abuse and their metabolites in influent and effluent urban wastewater by ultrahigh pressure liquid chromatography-quadrupole-time-of-flight-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, Felix, E-mail: felix.hernandez@qfa.uji.es [Research Institute for Pesticides and Water, University Jaume I, Avda. Sos Baynat s/n, E-12071 Castellon (Spain); Bijlsma, Lubertus, E-mail: bijlsma@guest.uji.es [Research Institute for Pesticides and Water, University Jaume I, Avda. Sos Baynat s/n, E-12071 Castellon (Spain); Sancho, Juan V.; Diaz, Ramon; Ibanez, Maria [Research Institute for Pesticides and Water, University Jaume I, Avda. Sos Baynat s/n, E-12071 Castellon (Spain)

    2011-01-17

    This work illustrates the potential of hybrid quadrupole-time-of-flight mass spectrometry (QTOF MS) coupled to ultrahigh pressure liquid chromatography (UHPLC) to investigate the presence of drugs of abuse in wastewater. After solid-phase extraction with Oasis MCX cartridges, seventy-six illicit drugs, prescription drugs with potential for abuse, and metabolites were investigated in the samples by TOF MS using electrospray interface under positive ionization mode, with MS data acquired over an m/z range of 50-1000 Da. For 11 compounds, reference standards were available, and experimental data (e.g., retention time and fragmentation data) could be obtained, facilitating a more confident identification. The use of a QTOF instrument enabled the simultaneous application of two acquisition functions with different collision energies: a low energy (LE) function, where none or poor fragmentation took place, and a high energy (HE) function, where fragmentation in the collision cell was promoted. This approach, known as MS{sup E}, enabled the simultaneous acquisition of full-spectrum accurate mass data of both protonated molecules and fragment ions in a single injection, providing relevant information that facilitates the rapid detection and reliable identification of these emerging contaminants in the sample matrices analyzed. In addition, isomeric compounds, like the opiates, morphine and norcodeine, could be discriminated by their specific fragments observed in HE TOF MS spectra, without the need of reference standards. UHPLC-QTOF MS was proven to be a powerful and efficient technique for rapid wide-scope screening and identification of many relevant drugs in complex matrices, such as influent and effluent urban wastewater.

  3. Rapid wide-scope screening of drugs of abuse, prescription drugs with potential for abuse and their metabolites in influent and effluent urban wastewater by ultrahigh pressure liquid chromatography-quadrupole-time-of-flight-mass spectrometry

    International Nuclear Information System (INIS)

    Hernandez, Felix; Bijlsma, Lubertus; Sancho, Juan V.; Diaz, Ramon; Ibanez, Maria

    2011-01-01

    This work illustrates the potential of hybrid quadrupole-time-of-flight mass spectrometry (QTOF MS) coupled to ultrahigh pressure liquid chromatography (UHPLC) to investigate the presence of drugs of abuse in wastewater. After solid-phase extraction with Oasis MCX cartridges, seventy-six illicit drugs, prescription drugs with potential for abuse, and metabolites were investigated in the samples by TOF MS using electrospray interface under positive ionization mode, with MS data acquired over an m/z range of 50-1000 Da. For 11 compounds, reference standards were available, and experimental data (e.g., retention time and fragmentation data) could be obtained, facilitating a more confident identification. The use of a QTOF instrument enabled the simultaneous application of two acquisition functions with different collision energies: a low energy (LE) function, where none or poor fragmentation took place, and a high energy (HE) function, where fragmentation in the collision cell was promoted. This approach, known as MS E , enabled the simultaneous acquisition of full-spectrum accurate mass data of both protonated molecules and fragment ions in a single injection, providing relevant information that facilitates the rapid detection and reliable identification of these emerging contaminants in the sample matrices analyzed. In addition, isomeric compounds, like the opiates, morphine and norcodeine, could be discriminated by their specific fragments observed in HE TOF MS spectra, without the need of reference standards. UHPLC-QTOF MS was proven to be a powerful and efficient technique for rapid wide-scope screening and identification of many relevant drugs in complex matrices, such as influent and effluent urban wastewater.

  4. Mass drug administration and the sustainable control of schistosomiasis: Community health workers are vital for global elimination efforts

    Directory of Open Access Journals (Sweden)

    Marianette T. Inobaya

    2018-01-01

    Conclusions: This study highlights the importance of community health workers in obtaining the World Health Organization drug coverage rate of 75% and improving compliance with MDA in the community. Investing in the education of community health workers with appropriate disease-specific training is crucial if disease elimination is ultimately to be achieved.

  5. On-chip electromembrane extraction for monitoring drug metabolism in real time by electrospray ionization mass spectrometry

    DEFF Research Database (Denmark)

    Petersen, Nickolaj J.; Pedersen, Jacob Sønderby; Poulsen, Nicklas Nørgård

    2012-01-01

    the in vitro metabolism of amitriptyline in real time. There was no need to stop the metabolisms by protein precipitation as in conventional metabolic studies, since the EME selectively extracted the drug and metabolites from the reaction solution comprised of rat liver microsomes in buffer. Compositional...

  6. Liquid chromatography-high resolution-tandem mass spectrometry using Orbitrap technology for comprehensive screening to detect drugs and their metabolites in blood plasma.

    Science.gov (United States)

    Helfer, Andreas G; Michely, Julian A; Weber, Armin A; Meyer, Markus R; Maurer, Hans H

    2017-05-01

    Orbitrap technology was successfully applied for broad metabolite-based LC-high resolution (HR)-MS screening of drugs in clinical and forensic toxicology. This paper aims to elucidate whether this technology can also be used for a corresponding blood plasma screening after simple precipitation without or with consecutive on-line extraction using turbulent flow chromatography (TurboFlow). The analytes were separated within 10 min and detected by a Q-Exactive mass spectrometer in full scan mode after positive/negative switching. In one single run, a target screening for about 700 relevant compounds was developed in parallel with data-dependent acquisition for unknowns. A compound was positively identified when the corresponding accurate mass precursor ion and the five most intense fragment ions were detected and the MS/MS spectrum fits well with the corresponding full HR-MS/MS reference library currently containing over 2000 parent drugs and 2500 metabolites. All over all run times were 17 min for precipitation and 21 min for TurboFlow after precipitation. Method validation was successfully performed for representative drugs and metabolites concerning recovery, matrix effect, process efficiency, and limits of detection and identification. Process efficiency data ranged for most analytes from 3 to 138% with coefficients of variation (CV) ≤ 20% for precipitation and from 1 to 156% with CV ≤ 20% for TurboFlow. Applicability studies showed that the developed method provided fast, simple, and robust screening and identification of a broad range of drugs within therapeutic ranges. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Quality by Design–Applied Liquid Chromatography-Tandem Mass Spectrometry Determination of Enzalutamide Anti-Prostate Cancer Therapy Drug in Spiked Plasma Samples

    Directory of Open Access Journals (Sweden)

    ASK Sankar

    2017-08-01

    Full Text Available This research article presents the Quality by Design (QbD–finalised conditions for a method that uses liquid chromatography-tandem mass spectrometry for the determination of concentration of enzalutamide (ENZ, an atypical anticancer drug, in a drug formulation and in spiked plasma samples. Critical process attributes (CPA considered to be the influential parameters in separation, identification, and quantification processes by ultrahigh-performance liquid chromatography-electrospray ionisation-tandem mass spectrometry (UHPLC-ESI-MS/MS were organic content, buffer strength, pH modifier, flow rate, spray voltage, sheath gas, and auxiliary gas that alter critical analytical attributes, such as retention time (R1 and area (R2. These factors were evaluated first in a factorial design (Taguchi orthogonal array design and then extensively in a central composite design (CCD to zero-in on the mobile phase for the quantification of ENZ standard drug and along with its internal standard (ENZIS in spiked plasma samples and in formulation. Pareto chart from initial factorial design (Taguchi orthogonal array design model suggested which of the CPA factors should be given the weightage, that is, to be exhaustively analysed in the CCD and response surface analysis. The elaborated parameters proposed by World Health Organization were studied by method validation, ie, selectivity, linearity, accuracy, precision repeatability system-suitability tests, method robustness/ruggedness, sensitivity, and stability. The strategy followed gives an insight on the development of a robust QbD-compliant quantitative UHPLC-ESI-MS/MS method for ENZ drug containing plasma samples (spiked.

  8. Magnetic micro-solid-phase extraction based on magnetite-MCM-41 with gas chromatography-mass spectrometry for the determination of antidepressant drugs in biological fluids.

    Science.gov (United States)

    Kamaruzaman, Sazlinda; Sanagi, Mohd Marsin; Yahaya, Noorfatimah; Wan Ibrahim, Wan Aini; Endud, Salasiah; Wan Ibrahim, Wan Nazihah

    2017-11-01

    A new facile magnetic micro-solid-phase extraction coupled to gas chromatography and mass spectrometry detection was developed for the extraction and determination of selected antidepressant drugs in biological fluids using magnetite-MCM-41 as adsorbent. The synthesized sorbent was characterized by several spectroscopic techniques. The maximum extraction efficiency for extraction of 500 μg/L antidepressant drugs from aqueous solution was obtained with 15 mg of magnetite-MCM-41 at pH 12. The analyte was desorbed using 100 μL of acetonitrile prior to gas chromatography determination. This method was rapid in which the adsorption procedure was completed in 60 s. Under the optimized conditions using 15 mL of antidepressant drugs sample, the calibration curve showed good linearity in the range of 0.05-500 μg/L (r 2  = 0.996-0.999). Good limits of detection (0.008-0.010 μg/L) were obtained for the analytes with good relative standard deviations of drugs. This method was successfully applied to the determination of amitriptyline and chlorpromazine in plasma and urine samples. The recoveries of spiked plasma and urine samples were in the range of 86.1-115.4%. Results indicate that magnetite micro-solid-phase extraction with gas chromatography and mass spectrometry is a convenient, fast, and economical method for the extraction and determination of amitriptyline and chlorpromazine in biological samples. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Effect of repeated mass drug administration with praziquantel and track and treat of taeniosis cases on the prevalence of taeniosis in Taenia solium endemic rural communities of Tanzania

    DEFF Research Database (Denmark)

    Braae, Uffe Christian; Magnussen, Pascal; Ndawi, Benedict

    This study evaluated the effect of mass drug administration (MDA) with praziquantel administered to school-aged children (SAC) combined with ‘track and treat’ of taeniosis cases on the prevalence of taeniosis. The study was conducted in 14 villages in Mbozi and Mbeya district, Tanzania. SAC...... received MDA with praziquantel in 2012 (both districts) and in 2013 (Mbozi only). Three cross-sectional population-based surveys were performed in 2012 (R0), 2013 (R1), and 2014 (R2). In each survey approximately 3,000 participants of all ages were tested using copro-antigen-ELISA. The prevalence...

  10. Gas chromatography-electron ionization mass spectrometry and liquid chromatography-electrospray tandem mass spectrometry for determination of impurities in the anti-cancer drug isophosphoramide mustard

    Science.gov (United States)

    Cole, Richard B.; Chou, Chau-Wen; Boué, Stephen M.; Leblanc, Blaise W.; Rodgers, Andrew H.; Struck, Robert F.; Morgan, Lee Roy

    2004-02-01

    Isophosphoramide mustard (IPM) is known to have substantial anti-cancer activities in various animal models. Liquid chromatography-electrospray mass spectrometry (LC-ES-MS) and LC-ES-MS/MS methodologies have been developed and applied to the analysis of synthesized preparations of IPM. Our studies reveal that the principal impurity in IPM is N-(2-chloroethyl)-N'-ethylphosphorodiamidic acid (MC-IPM) formed by dehydrochlorination of IPM with subsequent hydrogenation during synthesis. This impurity is present at levels in the range of 2-5% depending upon synthesis conditions. In addition, a second IPM derivative has been characterized by LC-ES-MS/MS and has been shown to be the product of a reaction of IPM with the dilute perchloric acid mobile phase used for liquid chromatography separations. The LC-ES-MS/MS method has been successfully employed to detect IPM spiked into a blood plasma sample. This work establishes that LC-ES-MS/MS is a viable tool for the detailed characterization of IPM and related products.

  11. Performance of the linear ion trap Orbitrap mass analyzer for qualitative and quantitative analysis of drugs of abuse and relevant metabolites in sewage water.

    Science.gov (United States)

    Bijlsma, Lubertus; Emke, Erik; Hernández, Félix; de Voogt, Pim

    2013-03-20

    This work illustrates the potential of liquid chromatography coupled to a hybrid linear ion trap Fourier Transform Orbitrap mass spectrometer for the simultaneous identification and quantification of 24 drugs of abuse and relevant metabolites in sewage water. The developed methodology consisted of automatic solid-phase extraction using Oasis HLB cartridges, chromatographic separation of the targeted drugs, full-scan accurate mass data acquisition under positive electrospray ionization mode over an m/z range of 50-600Da at a resolution of 30,000 FWHM and simultaneous MS(n) measurements to obtain information of fragment ions generated in the linear ion trap. Accurate mass of the protonated molecule, together with at least one nominal mass product ion and retention time allowed the confident identification of the compounds detected in these complex matrices. In addition to the highly reliable qualitative analysis, Orbitrap analyzer also proved to have satisfactory potential for quantification at sub-ppb analyte levels, a possibility that has been very little explored in the literature until now. The limits of quantification ranged from 4 to 68ngL(-1) in influent sewage water, and from 2 to 35ngL(-1) in effluent, with the exception of MDA, morphine and THC that presented higher values as a consequence of the high ionization suppression in this type of samples. Satisfactory recoveries (70-120%) and precision (abuse could be identified and quantified, mainly MDMA, benzoylecgonine, codeine, oxazepam and temazepam. Orbitrap also showed potential for retrospective investigation of ketamine metabolites in the samples without the need of additional analysis. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Association of depression with body mass index classification, metabolic disease, and lifestyle: A web-based survey involving 11,876 Japanese people.

    Science.gov (United States)

    Hidese, Shinsuke; Asano, Shinya; Saito, Kenji; Sasayama, Daimei; Kunugi, Hiroshi

    2018-02-10

    Body mass index (BMI) and lifestyle-related physical illnesses have been implicated in the pathology of depression. We aimed to investigate the association of depression wih BMI classification (i.e., underweight, normal, overweight, and obese), metabolic disease, and lifestyle using a web-based survey in a large cohort. Participants were 1000 individuals who have had depression (mean age: 41.4 ± 12.3 years, 501 men) and 10,876 population-based controls (45.1 ± 13.6 years, 5691 men). The six-item Kessler scale (K6) test was used as a psychological distress scale. Compared to in the controls, obesity and hyperlipidemia were more common and frequency of a snack or night meal consumption was higher, whereas frequencies of breakfast consumption and vigorous and moderate physical activities were lower in the patients. K6 test scores were higher for underweight or obese people compared to normal or overweight people. A logistic regression analysis showed that the K6 test cut-off score was positively associated with being underweight, hyperlipidemia, and the frequency of a snack or night meal consumption, whereas it was negatively associated with the frequency of breakfast consumption in the patients. Logistic regression analyses showed that self-reported depression was positively associated with metabolic diseases and the frequency of a snack or night meal consumption, whereas it was negatively associated with the frequency of breakfast consumption. The observed associations of depression with BMI classification, metabolic disease, and lifestyle suggest that lifestyle and related physical conditions are involved in at least a portion of depressive disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Detecting drug-target binding in cells using fluorescence-activated cell sorting coupled with mass spectrometry analysis

    Science.gov (United States)

    Wilson, Kris; Webster, Scott P.; Iredale, John P.; Zheng, Xiaozhong; Homer, Natalie Z.; Pham, Nhan T.; Auer, Manfred; Mole, Damian J.

    2018-01-01

    The assessment of drug-target engagement for determining the efficacy of a compound inside cells remains challenging, particularly for difficult target proteins. Existing techniques are more suited to soluble protein targets. Difficult target proteins include those with challenging in vitro solubility, stability or purification properties that preclude target isolation. Here, we report a novel technique that measures intracellular compound-target complex formation, as well as cellular permeability, specificity and cytotoxicity-the toxicity-affinity-permeability-selectivity (TAPS) technique. The TAPS assay is exemplified here using human kynurenine 3-monooxygenase (KMO), a challenging intracellular membrane protein target of significant current interest. TAPS confirmed target binding of known KMO inhibitors inside cells. We conclude that the TAPS assay can be used to facilitate intracellular hit validation on most, if not all intracellular drug targets.

  14. Quantification of 31 illicit and medicinal drugs and metabolites in whole blood by fully automated solid-phase extraction and ultra-performance liquid chromatography-tandem mass spectrometry

    DEFF Research Database (Denmark)

    Bjørk, Marie Kjærgaard; Simonsen, Kirsten Wiese; Andersen, David Wederkinck

    2013-01-01

    An efficient method for analyzing illegal and medicinal drugs in whole blood using fully automated sample preparation and short ultra-high-performance liquid chromatography–tandem mass spectrometry (MS/MS) run time is presented. A selection of 31 drugs, including amphetamines, cocaine, opioids...

  15. The differentiation of fibre- and drug type Cannabis seedlings by gas chromatography/mass spectrometry and chemometric tools

    OpenAIRE

    Broséus, J.; Anglada, F.; Esseiva, P.

    2010-01-01

    Cannabis cultivation in order to produce drugs is forbidden in Switzerland. Thus, law enforcement authorities regularly ask forensic laboratories to determinate cannabis plant's chemotype from seized material in order to ascertain that the plantation is legal or not. As required by the EU official analysis protocol the THC rate of cannabis is measured from the flowers at maturity. When laboratories are confronted to seedlings, they have to lead the plant to maturity, meaning a time consumi...

  16. C18-attached membrane funnel-based spray ionization mass spectrometry for quantification of anti-diabetic drug from human plasma

    International Nuclear Information System (INIS)

    Li, Wan; Chen, Xiangfeng; Wong, Y.-L. Elaine; Hung, Y.-L. Winnie; Wang, Ze; Deng, Liulin; Dominic Chan, T.-W.

    2016-01-01

    In this work, sorbent-attached membrane funnel-based spray ionization mass spectrometry was explored for quantitative analysis of anti-diabetic drugs spiked in human plasma. C 18 -attached membrane funnel was fabricated for in situ extraction and clean-up to alleviate matrix suppression effect in the ionization process. Repaglinide was used as a target analyte of anti-diabetic drugs. Under optimal working conditions, good linearity (R 2  > 0.99) was obtained in the concentration range of 1–100 ng mL −1 . The method detection limit of target drugs spiked in the human plasma was around 0.30 ng mL −1 . Through the application of an isotope-labeled internal standard, the signal fluctuation caused by residual background matrices was largely alleviated and the precision of measurement (RSD) was below 15%. The recovery of repaglinide for 5, 25, and 100 ng mL −1 of spiked human plasma matrixes ranged from 87% to 112%. The developed method was successfully applied to determine repaglinide in plasma volunteers who orally received a dose of drug association. Our results demonstrated that membrane funnel-based spray is a simple and sensitive method for rapid screening analysis of complex biological samples. - Highlights: • Sorbent attached membrane funnel based spray platform was used for drug determination in human plasma. • The matrix suppression effect of human plasma was largely eliminated. • The method was applied to determine repaglinide in plasma volunteers. • Membrane funnel-based spray is promising for analysis of biological samples.

  17. A brief, trauma-informed intervention increases safety behavior and reduces HIV risk for drug-involved women who trade sex

    Directory of Open Access Journals (Sweden)

    Michele R. Decker

    2017-08-01

    Full Text Available Abstract Background Female sex workers (FSWs are an important population for HIV acquisition and transmission. Their risks are shaped by behavioral, sexual network, and structural level factors. Violence is pervasive and associated with HIV risk behavior and infection, yet interventions to address the dual epidemics of violence and HIV among FSWs are limited. Methods We used participatory methods to develop a brief, trauma-informed intervention, INSPIRE (Integrating Safety Promotion with HIV Risk Reduction, to improve safety and reduce HIV risk for FSWs. A quasi-experimental, single group pretest-posttest study evaluated intervention feasibility, acceptability and efficacy among FSWs in Baltimore, MD, most of whom were drug-involved (baseline n = 60; follow-up n = 39 [65%]; non-differential by demographics or outcomes. Qualitative data collected at follow-up contextualizes findings. Results Based on community partnership and FSW input, emergent goals included violence-related support, connection with services, and buffering against structural forces that blame FSWs for violence. Qualitative and quantitative results demonstrate feasibility and acceptability. At follow-up, improvements were seen in avoidance of client condom negotiation (p = 0.04, and frequency of sex trade under the influence of drugs or alcohol (p = 0.04. Women’s safety behavior increased (p < 0.001. Participants improved knowledge and use of sexual violence support (p < 0.01 and use of intimate partner violence support (p < 0.01. By follow-up, most respondents (68.4% knew at least one program to obtain assistance reporting violence to police. Over the short follow-up period, client violence increased. In reflecting on intervention acceptability, participants emphasized the value of a safe and supportive space to discuss violence. Discussion This brief, trauma-informed intervention was feasible and highly acceptable to FSWs. It prompted safety behavior, mitigated

  18. Simultaneous high-throughput determination of interaction kinetics for drugs and cyclodextrins by high performance affinity chromatography with mass spectrometry detection.

    Science.gov (United States)

    Wang, Caifen; Wang, Xiaobo; Xu, Xiaonan; Liu, Botao; Xu, Xu; Sun, Lixin; Li, Haiyan; Zhang, Jiwen

    2016-02-25

    The individual determination of the apparent dissociation rate constant (kd,app) using high performance affinity chromatography (HPAC) is a tedious process requiring numerous separate tests and massive data fitting, unable to provide the apparent association rate constant (ka) and equilibrium binding constant (Ka). In this study, a HPAC with mass spectrometry detection (HPAC-MS/MS) was employed to determine the drug-cyclodextrin (CD) interaction kinetics with low sample loading quantity (drugs determined in one injection. The kd,app measured by HPAC-MS/MS approach were 0.89 ± 0.07, 4.34 ± 0.01, 1.48 ± 0.01 and 7.77 ± 0.04 s(-1) for ketoprofen, trimethoprim, indapamide and acetaminophen, with kd,app for acetaminophen consistent with that from the HPAC method with UV detector in our previous studies. For twenty drugs with diverse structures and chemical properties, good correlationship was found between kd,app measured by single compound analysis method and high-throughput HPAC-MS/MS approach, with the correlation coefficient of 0.987 and the significance F less than 0.001. Comprehensive quantification of ka,app, kd,app and Ka values was further performed based on the measurement of kd,app by peak profiling method and Ka by the peak fitting method. And the investigation of the drug-CD interaction kinetics under different conditions indicated that the column temperature and mobile phase composition significantly affected the determination of ka,app, kd,app and Ka while also dependent on the acidity and basicity of drugs. In summary, the high-throughput HPAC-MS/MS approach has been demonstrated high efficiency in determination of the drug-CD primary interaction kinetic parameter, especially, kd,app, being proven as a novel tool in screening the right CD for the solubilization of the right drug. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. The Cedar Project: Negative health outcomes associated with involvement in the child welfare system among young Indigenous people who use injection and non-injection drugs in two Canadian cities.

    Science.gov (United States)

    Clarkson, Adam F; Christian, Wayne M; Pearce, Margo E; Jongbloed, Kate A; Caron, Nadine R; Teegee, Mary P; Moniruzzaman, Akm; Schechter, Martin T; Spittal, Patricia M

    2015-05-07

    Indigenous leaders and child and family advocates are deeply concerned about the health impacts of the child welfare system, including HIV vulnerability. The objectives of this study were to describe the prevalence of having been apprehended into the child welfare system and associated HIV vulnerabilities among young Indigenous people who use drugs. The Cedar Project is a cohort of young Indigenous people ages 14-30 years who use illicit drugs in Vancouver and Prince George, British Columbia. Multivariable logistic regression modeling determined associations between a history of involvement in the child welfare system and vulnerability to HIV infection. Of 605 participants, 65% had been taken from their biological parents. Median age of first apprehension was 4 years old. Having been sexually abused, having a parent who attended residential school and being HIV-positive were all independently associated with having been involved in the child welfare system. Participants who had been involved in the child welfare system were also more likely to have been homeless, paid for sex, diagnosed and hospitalized with mental illness, self-harmed, thought about suicide, and attempted suicide. Among participants who used injection drugs, those who had been involved in child welfare were more likely to have shared needles and overdosed. This study has found compelling evidence that young Indigenous people who use drugs in two cities in BC are experiencing several distressing health outcomes associated with child welfare involvement, including HIV infection. Jurisdictional reforms and trauma-informed programs that use culture as intervention are urgently needed.

  20. Polar organic chemical integrative sampling and liquid chromatography- electrospray/ion-trap mass spectrometry for assessing selected prescription and illicit drugs in treated sewage effluents

    Science.gov (United States)

    Jones-Lepp, T. L.; Alvarez, D.A.; Petty, J.D.; Huckins, J.N.

    2004-01-01

    The purpose of the research presented in this paper was twofold: (1) to demonstrate the coupling of two state-of-the-art techniques: a time-weighted polar organic chemical integrative sampler (POCIS) and microliquid chromatography–electrospray/ion-trap mass spectrometry and (2) to assess the ability of these methodologies to detect six drugs (azithromycin, fluoxetine, omeprazole, levothyroxine, methamphetamine, methylenedioxymethamphetamine [MDMA]) in a real-world environment, e.g., waste water effluent. In the effluent from three wastewater treatment plants (WWTPs), azithromycin was detected at concentrations ranging from 15 to 66 ng/L, which is equivalent to a total annual release of 1 to 4 kg into receiving waters. Detected and confirmed in the effluent from two WWTPs were two illicit drugs, methamphetamine and MDMA, at 2 and 0.5 ng/L, respectively. Although the ecotoxicologic significance of drugs in environmental matrices, particularly water, has not been closely examined, it can only be surmised that these substances have the potential to adversely affect biota that are continuously exposed to them even at very low levels. The potential for chronic effects on human health is also unknown but of increasing concern because of the multiuse character of water, particularly in densely populated, arid areas.

  1. An evaluation of coverage and compliance of mass drug administration 2006 for elimination of lymphatic filariasis in endemic areas of Gujarat

    Directory of Open Access Journals (Sweden)

    Kumar Pradeep

    2008-01-01

    Full Text Available Background: Mass drug administration (MDA means once-in-a-year administration of diethyl carbamazine (DEC tablet to all people (excluding children under 2 years, pregnant women and severely ill persons in identified endemic areas. It aims at cessation of transmission of lymphatic filariasis. Objective: What has been the coverage and compliance of MDA in Gujarat during the campaign in December 2006? Study Design: Cross-sectional population based house-to-house visit. Setting: Urban and rural areas in Gujarat identified as endemic for filariasis where MDA 2006 was undertaken. Study Variables: Exploratory - Rural and urban districts; Outcome - coverage, compliance, actual coverage, side effects. Analysis: Percentage and proportions. Results: Twenty-six clusters, each comprising 32 households from six endemic districts, yielded an eligible population of 4164. The coverage rate was 85.2% with variation across different areas. The compliance with drug ingestion was 89% with a gap of 11% to be targeted by intensive IEC. The effective coverage (75.8% was much below the target (85%. Side effects of DEC were minimum, transient and drug-specific. Overall coverage was marginally better in rural areas. The causes of poor coverage and compliance have been discussed and relevant suggestions have been made.

  2. Ultra high performance liquid chromatography-electrospray ionization-tandem mass spectrometry screening method for direct analysis of designer drugs, "spice" and stimulants in oral fluid.

    Science.gov (United States)

    Strano-Rossi, Sabina; Anzillotti, Luca; Castrignanò, Erika; Romolo, Francesco Saverio; Chiarotti, Marcello

    2012-10-05

    An ultra high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) screening method for the direct analysis in oral fluid (OF) of 24 drugs, including new synthetic cannabinoids and so-called "smart" designer drugs, in a single chromatographic run was set up. Benzylpiperazine, methylone, 5,6-methylenedioxy-2-aminoindane (MDAI), fenproporex, 4-fluoroamphetamine (4-FA), 4-methyl-N-ethylcathinone (4-MEC), 4-methylamphetamine (4-MA), methylbenzodioxolylbutanamine (MBDB), mephedrone, methylthioamphetamine (MTA), methylenedioxypyrovalerone (MDPV), mefenorex, nabilone, furfenorex, clobenzorex, JWH-200, AM 694, JWH-250, JWH-073, JWH-018, JWH-019, JWH-122, HU 210 and CP 47497 were determined in a chromatographic run of 9 min only with no sample pre-treatment, after addition of ISs and dilution in mobile phase A. This method is designed to be applied to 250 μL of OF sample, anyway is suitable to be used on smaller volumes (till 100 μL). LODs vary from 1ng/mL to 20 ng/mL. No interfering peaks were observed due to similar analytes, common therapeutic drugs or endogenous compounds. Matrix effect, although present especially for mephedrone, is acceptable, allowing the detection of the compounds at the LODs described. The developed method was applied on 400 real OF samples from on-site tests performed by police officers. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Software-aided approach to investigate peptide structure and metabolic susceptibility of amide bonds in peptide drugs based on high resolution mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Tatiana Radchenko

    Full Text Available Interest in using peptide molecules as therapeutic agents due to high selectivity and efficacy is increasing within the pharmaceutical industry. However, most peptide-derived drugs cannot be administered orally because of low bioavailability and instability in the gastrointestinal tract due to protease activity. Therefore, structural modifications peptides are required to improve their stability. For this purpose, several in-silico software tools have been developed such as PeptideCutter or PoPS, which aim to predict peptide cleavage sites for different proteases. Moreover, several databases exist where this information is collected and stored from public sources such as MEROPS and ExPASy ENZYME databases. These tools can help design a peptide drug with increased stability against proteolysis, though they are limited to natural amino acids or cannot process cyclic peptides, for example. We worked to develop a new methodology to analyze peptide structure and amide bond metabolic stability based on the peptide structure (linear/cyclic, natural/unnatural amino acids. This approach used liquid chromatography / high resolution, mass spectrometry to obtain the analytical data from in vitro incubations. We collected experimental data for a set (linear/cyclic, natural/unnatural amino acids of fourteen peptide drugs and four substrate peptides incubated with different proteolytic media: trypsin, chymotrypsin, pepsin, pancreatic elastase, dipeptidyl peptidase-4 and neprilysin. Mass spectrometry data was analyzed to find metabolites and determine their structures, then all the results were stored in a chemically aware manner, which allows us to compute the peptide bond susceptibility by using a frequency analysis of the metabolic-liable bonds. In total 132 metabolites were found from the various in vitro conditions tested resulting in 77 distinct cleavage sites. The most frequent observed cleavage sites agreed with those reported in the literature. The

  4. Software-aided approach to investigate peptide structure and metabolic susceptibility of amide bonds in peptide drugs based on high resolution mass spectrometry

    Science.gov (United States)

    Fontaine, Fabien; Morettoni, Luca; Zamora, Ismael

    2017-01-01

    Interest in using peptide molecules as therapeutic agents due to high selectivity and efficacy is increasing within the pharmaceutical industry. However, most peptide-derived drugs cannot be administered orally because of low bioavailability and instability in the gastrointestinal tract due to protease activity. Therefore, structural modifications peptides are required to improve their stability. For this purpose, several in-silico software tools have been developed such as PeptideCutter or PoPS, which aim to predict peptide cleavage sites for different proteases. Moreover, several databases exist where this information is collected and stored from public sources such as MEROPS and ExPASy ENZYME databases. These tools can help design a peptide drug with increased stability against proteolysis, though they are limited to natural amino acids or cannot process cyclic peptides, for example. We worked to develop a new methodology to analyze peptide structure and amide bond metabolic stability based on the peptide structure (linear/cyclic, natural/unnatural amino acids). This approach used liquid chromatography / high resolution, mass spectrometry to obtain the analytical data from in vitro incubations. We collected experimental data for a set (linear/cyclic, natural/unnatural amino acids) of fourteen peptide drugs and four substrate peptides incubated with different proteolytic media: trypsin, chymotrypsin, pepsin, pancreatic elastase, dipeptidyl peptidase-4 and neprilysin. Mass spectrometry data was analyzed to find metabolites and determine their structures, then all the results were stored in a chemically aware manner, which allows us to compute the peptide bond susceptibility by using a frequency analysis of the metabolic-liable bonds. In total 132 metabolites were found from the various in vitro conditions tested resulting in 77 distinct cleavage sites. The most frequent observed cleavage sites agreed with those reported in the literature. The main advantages of

  5. Quantification of imatinib in human serum: validation of a high-performance liquid chromatography-mass spectrometry method for therapeutic drug monitoring and pharmacokinetic assays

    Directory of Open Access Journals (Sweden)

    Rezende VM

    2013-08-01

    Full Text Available Vinicius Marcondes Rezende,1 Ariane Rivellis,1 Mafalda Megumi Yoshinaga Novaes,1 Dalton de Alencar Fisher Chamone,2 Israel Bendit1,21Laboratory of Tumor Biology, 2Department of Hematology, School of Medicine, University of São Paulo, São Paulo, BrazilBackground: Imatinib mesylate has been a breakthrough treatment for chronic myeloid leukemia. It has become the ideal tyrosine kinase inhibitor and the standard treatment for chronic-phase leukemia. Striking results have recently been reported, but intolerance to imatinib and noncompliance with treatment remain to be solved. Molecular monitoring by quantitative real-time polymerase chain reaction is the gold standard for monitoring patients, and imatinib blood levels have also become an important tool for monitoring.Methods: A fast and cheap method was developed and validated using high-performance liquid chromatography-mass spectrometry for quantification of imatinib in human serum and tamsulosin as the internal standard. Remarkable advantages of the method includes use of serum instead of plasma, less time spent on processing and analysis, simpler procedures, and requiring reduced amounts of biological material, solvents, and reagents. Stability of the analyte was also studied. This research also intended to drive the validation scheme in clinical centers. The method was validated according to the requirements of the US Food and Drug Administration and Brazilian National Health Surveillance Agency within the range of 0.500–10.0 µg/mL with a limit of detection of 0.155 µg/mL. Stability data for the analyte are also presented.Conclusion: Given that the validated method has proved to be linear, accurate, precise, and robust, it is suitable for pharmacokinetic assays, such as bioavailability and bioequivalence, and is being successfully applied in routine therapeutic drug monitoring in the hospital service.Keywords: imatinib, high-performance liquid chromatography-mass spectrometry, therapeutic

  6. Rapid, simple, and highly sensitive analysis of drugs in biological samples using thin-layer chromatography coupled with matrix-assisted laser desorption/ionization mass spectrometry.

    Science.gov (United States)

    Kuwayama, Kenji; Tsujikawa, Kenji; Miyaguchi, Hajime; Kanamori, Tatsuyuki; Iwata, Yuko T; Inoue, Hiroyuki

    2012-01-01

    Rapid and precise identification of toxic substances is necessary for urgent diagnosis and treatment of poisoning cases and for establishing the cause of death in postmortem examinations. However, identification of compounds in biological samples using gas chromatography and liquid chromatography coupled with mass spectrometry entails time-consuming and labor-intensive sample preparations. In this study, we examined a simple preparation and highly sensitive analysis of drugs in biological samples such as urine, plasma, and organs using thin-layer chromatography coupled with matrix-assisted laser desorption/ionization mass spectrometry (TLC/MALDI/MS). When the urine containing 3,4-methylenedioxymethamphetamine (MDMA) without sample dilution was spotted on a thin-layer chromatography (TLC) plate and was analyzed by TLC/MALDI/MS, the detection limit of the MDMA spot was 0.05 ng/spot. The value was the same as that in aqueous solution spotted on a stainless steel plate. All the 11 psychotropic compounds tested (MDMA, 4-hydroxy-3-methoxymethamphetamine, 3,4-methylenedioxyamphetamine, methamphetamine, p-hydroxymethamphetamine, amphetamine, ketamine, caffeine, chlorpromazine, triazolam, and morphine) on a TLC plate were detected at levels of 0.05-5 ng, and the type (layer thickness and fluorescence) of TLC plate did not affect detection sensitivity. In addition, when rat liver homogenate obtained after MDMA administration (10 mg/kg) was spotted on a TLC plate, MDMA and its main metabolites were identified using TLC/MALDI/MS, and the spots on a TLC plate were visualized by MALDI/imaging MS. The total analytical time from spotting of intact biological samples to the output of analytical results was within 30 min. TLC/MALDI/MS enabled rapid, simple, and highly sensitive analysis of drugs from intact biological samples and crude extracts. Accordingly, this method could be applied to rapid drug screening and precise identification of toxic substances in poisoning cases and

  7. The acceptability of mass administrations of anti-malarial drugs as part of targeted malaria elimination in villages along the Thai–Myanmar border

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    Ladda Kajeechiwa

    2016-09-01

    Full Text Available Abstract Background A targeted malaria elimination project, including mass drug administrations (MDA of dihydroartemisinin/piperaquine plus a single low dose primaquine is underway in villages along the Thailand Myanmar border. The intervention has multiple components but the success of the project will depend on the participation of the entire communities. Quantitative surveys were conducted to study reasons for participation or non-participation in the campaign with the aim to identify factors associated with the acceptance and participation in the mass drug administrations. Methods The household heads in four study villages in which MDAs had taken place previously were interviewed between January 2014 and July 2015. Results 174/378 respondents (46 % completed three rounds of three drug doses each, 313/378 (83 % took at least three consecutive doses and 56/378 (15 % did not participate at all in the MDA. The respondents from the two villages (KNH and TPN were much more likely to participate in the MDA than respondents from the other two villages (HKT and TOT. The more compliant villages KNH and TPN had both an appearance of cohesive communities with similar demographic and ethnic backgrounds. By contrast the villages with low participation were unique. One village was fragmented following years of armed conflict and many respondents gave little inclination to cooperate with outsiders. The other village with low MDA coverage was characterised by a high percentage of short-term residents with little interest in community interventions. A universal reason for non-participation in the MDA applicable to all villages was an inadequate understanding of the intervention. Conclusions It is unlikely that community engagement can unite fragmented communities in participating in an intervention, which benefits the community. Understanding the purpose and the reasons underlying the intervention is an important pre-condition for participation. In the

  8. Analytics of nonpeptidic erythropoietin mimetic agents in sports drug testing employing high-resolution/high-accuracy liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Vogel, Matthias; Dib, Josef; Tretzel, Laura; Piper, Thomas; Thomas, Andreas; Schänzer, Wilhelm; Thevis, Mario

    2016-09-01

    Since its release as anti-anemic drug, recombinant erythropoietin (rEPO) gradually entered the illicit way to sports competitions as endurance-enhancing drug. Novel modifications biopharmaceutically introduced into the rEPO molecule in the form of carbohydrate or polyethylene glycol moieties made robust and sensitive test methods vital to doping controls in order to provide the necessary tools enabling the conviction of dishonest athletes. Modern protein analysis by means of gel electrophoretic separation and western blotting represents the status quo in rEPO anti-doping analysis. However, new therapeutically promising erythropoietin receptor activating compounds have been developed that exhibit cytokine hormone-mimicking properties but lack any protein structure. Progression to evade parenteral application and substitute for rEPO by low molecular mass and orally available compounds is still one of the major objectives in pharmaceutical research. In this approach, four promising in-house synthesized nonpeptidic erythropoietin mimetic agents, namely compound 129, compound 163, A1B10C1, and A5B10C4 were thoroughly evaluated by employing high-resolution/high-accuracy liquid chromatography tandem mass spectrometry experiments. Characteristic product ions were determined supporting the identification of these drugs and putative metabolites as well as related compounds in future doping controls. Test methods employing direct urine injection and receptor affinity purification strategies were assessed, which demonstrated that EPO receptor purification is of limited utility for nonpeptidic EPOR agonists while direct urine injection allowed for comprehensive method characterization. Thereby, achieved limits of detection were 1 ng/mL for compounds 129/163 and 5 ng/mL for A1B10C1/A5B10C4.

  9. Simultaneous determination of ten antiepileptic drugs in human plasma by liquid chromatography and tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in therapeutic drug monitoring.

    Science.gov (United States)

    Yin, Lei; Wang, Tingting; Shi, Meiyun; Zhang, Ying; Zhao, Xiaojun; Yang, Yan; Gu, Jingkai

    2016-03-01

    A simple, rapid, and high-throughput liquid chromatography with tandem mass spectrometry method for the simultaneous quantitation of ten antiepileptic drugs in human plasma has been developed and validated. The method required only 10 μL of plasma. After simple protein precipitation using acetonitrile, the analytes and internal standard diphenhydramine were separated on a Zorbax SB-C18 column (50 × 4.6 mm, 2.7 μm) using acetonitrile/water as the mobile phase at a flow rate of 0.9 mL/min. The total run time was 6 min for each sample. The validation results of specificity, matrix effects, recovery, linearity, precision, and accuracy were satisfactory. The lower limit of quantification was 0.04 μg/mL for carbamazepine, 0.02 μg/mL for lamotrigine, 0.01 μg/mL for oxcarbazepine, 0.4 μg/mL for 10-hydroxycarbazepine, 0.1 μg/mL for carbamazepine-10,11-epoxide, 0.15 μg/mL for levetiracetam, 0.06 μg/mL for phenytoin, 0.3 μg/mL for valproic acid, 0.03 μg/mL for topiramate, and 0.15 μg/mL for phenobarbital. The intraday precision and interday precision were less than 7.6%, with the accuracy ranging between -8.1 and 7.9%. The method was successfully applied to therapeutic drug monitoring of 1237 patients with epilepsy after administration of standard antiepileptic drugs. The method has been proved to meet the high-throughput requirements in therapeutic drug monitoring. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Simultaneous determination of a hydrophobic drug candidate and its metabolite in human plasma with salting-out assisted liquid/liquid extraction using a mass spectrometry friendly salt.

    Science.gov (United States)

    Wu, Huaiqin; Zhang, Jun; Norem, Katherine; El-Shourbagy, Tawakol A

    2008-12-01

    In previously reported applications of salting-out assisted liquid/liquid extraction (SALLE) with acetonitrile, only inorganic salts were evaluated and implemented as the salting-out reagents. A potential concern of the method for the subsequent LC-MS analysis of biological samples was that a portion of the added salt (typically of high concentration) might be extracted and affect the chromatography separation and ionization of chromatography effluents in a mass spectrometer. Here we report, for the first time, the use of a mass spectrometry friendly organic salt, ammonium acetate, as a salting-out reagent in SALLE with acetonitrile for the simultaneous quantitation of an Abbott investigational new drug ABT-869 and its hydrophilic metabolite in human plasma. The performance of SALLE with ammonium acetate was compared with that of a previously reported method with a conventional liquid/liquid extraction technique using a set of pooled incurred samples. The % differences of the measured concentrations for 24 samples from these two methods were found to be within acceptance criteria, demonstrating SALLE with ammonium acetate as a reliable sample preparation technique. The SALLE method is simple, fast (25 min/plate), easy for automation, free of drying down step, and environmentally friendly. SALLE with mass spectrometry friendly salts has been applied to regulated sample analysis of both hydrophilic and hydrophobic compounds. It is envisioned that SALLE with acetonitrile and ammonium acetate be a universal method for high throughput automated sample preparation for bioanalytical chemistry.

  11. Combining Fragment-Ion and Neutral-Loss Matching during Mass Spectral Library Searching: A New General Purpose Algorithm Applicable to Illicit Drug Identification.

    Science.gov (United States)

    Moorthy, Arun S; Wallace, William E; Kearsley, Anthony J; Tchekhovskoi, Dmitrii V; Stein, Stephen E

    2017-12-19

    A mass spectral library search algorithm that identifies compounds that differ from library compounds by a single "inert" structural component is described. This algorithm, the Hybrid Similarity Search, generates a similarity score based on matching both fragment ions and neutral losses. It employs the parameter DeltaMass, defined as the mass difference between query and library compounds, to shift neutral loss peaks in the library spectrum to match corresponding neutral loss peaks in the query spectrum. When the spectra being compared differ by a single structural feature, these matching neutral loss peaks should contain that structural feature. This method extends the scope of the library to include spectra of "nearest-neighbor" compounds that differ from library compounds by a single chemical moiety. Additionally, determination of the structural origin of the shifted peaks can aid in the determination of the chemical structure and fragmentation mechanism of the query compound. A variety of examples are presented, including the identification of designer drugs and chemical derivatives not present in the library.

  12. Moisture and drug solid-state monitoring during a continuous drying process using empirical and mass balance models

    DEFF Research Database (Denmark)

    Fonteyne, Margot; Gildemyn, Delphine; Peeters, Elisabeth

    2014-01-01

    of Process Analytical Technology (PAT) tools (Raman and NIR spectroscopy) and a mass balance approach. The six-segmented fluid bed drying system being part of a fully continuous from-powder-to-tablet production line (ConsiGma™-25) was used for this study. A theophylline:lactose:PVP (30:67.5:2.5) blend......, the different size fractions of the dried granules obtained during different experiments (fines, yield and oversized granules) were compared separately, revealing differences in both solid state of theophylline and moisture content between the different granule size fractions. © 2014 Elsevier B.V. All rights...... reserved...

  13. Determination of drugs in plasma samples by disposable pipette extraction with C18-BSA phase and liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Pinto, Mônia Ap Lemos; de Souza, Israel D; Queiroz, Maria Eugênia C

    2017-05-30

    This work describes restricted access material (RAM) constituted of porous octadecylsilane particles with the outer surface covered with bovine serum albumin (C18-BSA) as a stationary phase to extract drugs from plasma samples by disposable pipette extraction (DPX) for further analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The C18-BSA phase simultaneously excluded macromolecules by chemical diffusion barrier (BSA network) and enrichment of the interior phase (C18) with drug traces by sorption. The hydrophilic barrier of the C18-BSA allows small molecules (drugs) to permeate through the hydrophobic part (C18), while at the same time it excludes the macromolecules by chemical diffusion barrier (BSA network). Optimization of the DPX variables (sorption equilibration time, exclusion of endogenous compounds, and elution step) improved the sensitivity and selectivity of the method, which presented a linear range from the lower limit of quantification (0.5-20.0ngmL -1 ) to the upper limit of quantification (32.5-10,500ngmL -1 ), inter- and intra-assay precision with coefficients of variation (CV) lower than 15%, and relative standard error (RSE) of the accuracy ranging from -12% to 11%. The developed method was successfully used to determine five antipsychotics (olanzapine, quetiapine, clozapine, haloperidol, and chlorpromazine) in combination with seven antidepressants (mirtazapine, paroxetine, citalopram, sertraline, imipramine, clomipramine, and fluoxetine), two anticonvulsants (carbamazepine and lamotrigine), and two anxiolytics (diazepam and clonazepam) in plasma samples from schizophrenic patients for therapeutic drug monitoring. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Real Time Extraction Kinetics of Electro Membrane Extraction Verified by Comparing Drug Metabolism Profiles Obtained from a Flow-Flow Electro Membrane Extraction-Mass Spectrometry System with LC-MS

    DEFF Research Database (Denmark)

    Fuchs, David; Jensen, Henrik; Pedersen-Bjergaard, Stig

    2015-01-01

    A simple to construct and operate, "dip-in" electromembrane extraction (EME) probe directly coupled to electrospray ionization-mass spectrometry (ESI-MS) for rapid extraction and real time analysis of various analytes was developed. The setup demonstrated that EME-MS can be used as a viable...... alternative to conventional protein precipitation followed by liquid chromatography-mass spectrometry (LC-MS) for studying drug metabolism. Comparison of EME-MS with LC-MS for drug metabolism analysis demonstrated for the first time that real time extraction of analytes by EME is possible. Metabolism kinetics...... were investigated for three different drugs: amitriptyline, promethazine, and methadone. By comparing the EME-MS extraction profiles of the drug substances and formed drug metabolites with the metabolism profiles obtained by conventional protein precipitation followed by LC-MS good correlation...

  15. Rapid Conformational Analysis of Protein Drugs in Formulation by Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS)

    DEFF Research Database (Denmark)

    Esmail Nazari, Zeinab; van de Weert, Marco; Bou-Assaf, George

    2016-01-01

    Hydrogen Deuterium Exchange coupled to Mass Spectrometry (HDX-MS) has become an established method for analysis of protein higher-order structure. Here, we use HDX-MS methodology based on manual Solid-Phase Extraction (SPE) to allow fast and simplified conformational analysis of proteins under...... pharmaceutically relevant formulation conditions. Of significant practical utility, the methodology allows global HDX-MS analyses to be performed without refrigeration or external cooling of the setup. In Mode 1, we used DMSO-containing solvents for SPE, allowing the HDX-MS analysis to be performed at acceptable...... in formulation, using an internal HDX reference peptide (P7I) to control for any sample-to-sample variations in back exchange. Advantages of the methodology include low sample use, optimized excipient removal using multiple solvents, and fast data acquisition. Our results indicate that the SPE-HDX-MS system can...

  16. Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry.

    Science.gov (United States)

    Vu, Hoan; Pedro, Liliana; Mak, Tin; McCormick, Brendan; Rowley, Jessica; Liu, Miaomiao; Di Capua, Angela; Williams-Noonan, Billy; Pham, Ngoc B; Pouwer, Rebecca; Nguyen, Bao; Andrews, Katherine T; Skinner-Adams, Tina; Kim, Jessica; Hol, Wim G J; Hui, Raymond; Crowther, Gregory J; Van Voorhis, Wesley C; Quinn, Ronald J

    2018-03-03

    Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain.

  17. Increasing throughput and information content for in vitro drug metabolism experiments using ultra-performance liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer.

    Science.gov (United States)

    Castro-Perez, Jose; Plumb, Robert; Granger, Jennifer H; Beattie, Iain; Joncour, Karine; Wright, Andrew

    2005-01-01

    The field of drug metabolism has been revolutionized by liquid chromatography/mass spectrometry (LC/MS) applications with new technologies such as triple quadrupoles, ion traps and time-of-flight (ToF) instrumentation. Over the years, these developments have often relied on the improvements to the mass spectrometer hardware and software, which has allowed users to benefit from lower levels of detection and ease-of-use. One area in which the development pace has been slower is in high-performance liquid chromatography (HPLC). In the case of metabolite identification, where there are many challenges due to the complex nature of the biological matrices and the diversity of the metabolites produced, there is a need to obtain the most accurate data possible. Reactive or toxic metabolites need to be detected and identified as early as possible in the drug discovery process, in order to reduce the very costly attrition of compounds in late-phase development. High-resolution, exact mass measurement plays a very important role in metabolite identification because it allows the elimination of false positives and the determination of non-trivial metabolites in a much faster throughput environment than any other standard current methodology available to this field. By improving the chromatographic resolution, increased peak capacity can be achieved with a reduction in the number of co-eluting species leading to superior separations. The overall enhancement in the chromatographic resolution and peak capacity is transferred into a net reduction in ion suppression leading to an improvement in the MS sensitivity. To investigate this, a number of in vitro samples were analyzed using an ultra-performance liquid chromatography (UPLC) system, with columns packed with porous 1.7 mum particles, coupled to a hybrid quadrupole time-of-flight (ToF) mass spectrometer. This technique showed very clear examples for fundamental gains in sensitivity, chromatographic resolution and speed of

  18. Drug Release Analysis and Optimization for Drug-Eluting Stents

    Directory of Open Access Journals (Sweden)

    Hongxia Li

    2013-01-01

    Full Text Available The drug release analysis and optimization for drug-eluting stents in the arterial wall are studied, which involves mechanics, fluid dynamics, and mass transfer processes and design optimization. The Finite Element Method (FEM is used to analyze the process of drug release in the vessels for drug-eluting stents (DES. Kriging surrogate model is used to build an approximate function relationship between the drug distribution and the coating parameters, replacing the expensive FEM reanalysis of drug release for DES in the optimization process. The diffusion coefficients and the coating thickness are selected as design variables. An adaptive optimization approach based on kriging surrogate model is proposed to optimize the lifetime of the drug in artery wall. The adaptive process is implemented by an infilling sampling criterion named Expected Improvement (EI, which is used to balance local and global search and tends to find the global optimal design. The effect of coating diffusivity and thickness on the drug release process for a typical DES is analyzed by means of FEM. An implementation of the optimization method for the drug release is then discussed. The results demonstrate that the optimized design can efficiently improve the efficacy of drug deposition and penetration into the arterial walls.

  19. Characterization of the designer drug deschloroketamine (2-methylamino-2-phenylcyclohexanone) by gas chromatography/mass spectrometry, liquid chromatography/high-resolution mass spectrometry, multistage mass spectrometry, and nuclear magnetic resonance.

    Science.gov (United States)

    Frison, Giampietro; Zamengo, Luca; Zancanaro, Flavio; Tisato, Francesco; Traldi, Pietro

    2016-01-15

    Clinical and forensic toxicology laboratories are challenged every day by the analytical aspects of the new psychoactive substances phenomenon. In this study we describe the analytical characterization of a new ketamine derivative, deschloroketamine (2-methylamino-2-phenylcyclohexanone), contained in seized powders. The analytical techniques employed include gas chromatography/mass spectrometry (GC/MS), liquid chromatography/electrospray ionization coupled with Orbitrap high-resolution/MS (LC/ESI-HRMS), multistage MS (ESI-MS(n)), and NMR. The LC/ESI-HRMS analyses consisted of accurate mass measurements of MH(+) ions in full-scan mode; comparison of experimental and calculated MH(+) isotopic patterns; and examination of the isotopic fine structure (IFS) of the M + 1, M + 2, M + 3 isotopic peaks relative to the monoisotopic M + 0 peak. The collision-induced product ions of the MH(+) ions were studied by both HRMS and MS(n). (1)H and (13)C NMR measurements were carried out to confirm the chemical structure of the analyte. The EI mass spectra obtained by GC/MS analysis showed the presence of molecular ions at m/z 203, and main fragment ions at m/z 175, 174, 160, 147, 146, and 132. The application of LC/ESI-HRMS allowed us to obtain: the accurate mass of deschloroketamine MH(+) ions with a mass accuracy of 1.47 ppm; fully superimposable experimental and calculated MH(+) isotopic patterns, with a relative isotopic abundance value of 3.69 %; and the IFS of the M + 1, M + 2, M + 3 isotopic peaks completely in accordance with theoretical values. Examination of the product ions of MH(+), as well as the study of both (1)H and (13)C NMR spectra, enabled the full characterization of the molecular structure of deschloroketamine. The combination of the employed analytical techniques allowed the characterization of the seized psychoactive substance, in spite of the lack of a reference standard. Deschloroketamine is a ketamine analogue considered to be

  20. The Added Value of Water, Sanitation, and Hygiene Interventions to Mass Drug Administration for Reducing the Prevalence of Trachoma: A Systematic Review Examining

    Directory of Open Access Journals (Sweden)

    Anyess Travers

    2013-01-01

    Full Text Available Trachoma is the leading cause of infectious blindness worldwide. The SAFE strategy, the World Health Organization-recommended method to eliminate blinding trachoma, combines developments in water, sanitation, surgery, and antibiotic treatment. Current literature does not focus on the comprehensive effect these components have on one another. The present systematic review analyzes the added benefit of water, sanitation, and hygiene education interventions to preventive mass drug administration of azithromycin for trachoma. Trials were identified from the PubMed database using a series of search terms. Three studies met the complete criteria for inclusion. Though all studies found a significant change in reduction of active trachoma prevalence, the research is still too limited to suggest the impact of the “F” and “E” components on trachoma prevalence and ultimately its effects on blindness.

  1. Studies on the metabolism and the toxicological analysis of the nootropic drug fipexide in rat urine using gas chromatography-mass spectrometry.

    Science.gov (United States)

    Staack, Roland F; Maurer, Hans H

    2004-05-25

    Qualitative studies are described on the metabolism and the toxicological analysis of the nootropic fipexide (FIP) in rat urine using gas chromatography-mass spectrometry (GC-MS). FIP was extensively metabolized to 1-(3,4-methylenedioxybenzyl)piperazine (MDBP), 4-chlorophenoxyacetic acid, 1-[2-(4-chlorophenoxy)acetyl]piperazine, N-(4-hydroxy-3-methoxy-benzyl)piperazine, piperazine, N-(3,4-methylenedioxybenzyl)ethylenediamine, and N-[2-(4-chlorophenoxy)acetyl]ethylenediamine. The authors' systematic toxicological analysis (STA) procedure using full-scan GC-MS after acid hydrolysis of one urine aliquot, liquid-liquid extraction and acetylation allowed the detection of FIP via its metabolites in rat urine after administration of a common FIP dose. Therefore, this qualitative procedure should also be suitable for detection of a FIP intake in human urine. Differentiation of an intake of FIP from that of other drugs which form common metabolites is discussed.

  2. Analysis of pesticide and veterinary drug residues in baby food by liquid chromatography coupled to Orbitrap high resolution mass spectrometry.

    Science.gov (United States)

    Gómez-Pérez, María Luz; Romero-González, Roberto; Luis Martínez, Vidal José; Garrido Frenich, Antonia

    2015-01-01

    Pesticide and veterinary drug residues have been simultaneously determined in several baby foods as meat, fish and vegetable-based baby food. A generic extraction method without clean-up step was applied. Moreover, the use of a representative matrix for proper quantification of all target compounds was studied and the best results were obtained when vegetable-based baby food was used as representative matrix, allowing the reliable quantification of more than 300 compounds. The method was validated and good recoveries were obtained for most of compounds at concentrations higher than 50 µg kg(-1). Limits of detection (LOD) ranged from 0.5 to 50 µg kg(-1), whereas limits of quantification (LOQ) were established between 10 and 100 µg kg(-1). Limits of identification (LOIs) ranged from 0.5 to 50 µg kg(-1). This method was applied to the analysis of 46 different baby food samples and no positive samples were found. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Drug binding and resistance mechanism of KIT tyrosine kinase revealed by hydrogen/deuterium exchange FTICR mass spectrometry.

    Science.gov (United States)

    Zhang, Hui-Min; Yu, Xiu; Greig, Michael J; Gajiwala, Ketan S; Wu, Joe C; Diehl, Wade; Lunney, Elizabeth A; Emmett, Mark R; Marshall, Alan G

    2010-04-01

    Mutations of the receptor tyrosine kinase KIT are linked to certain cancers such as gastrointestinal stromal tumors (GISTs). Biophysical, biochemical, and structural studies have provided insight into the molecular basis of resistance to the KIT inhibitors, imatinib and sunitinib. Here, solution-phase hydrogen/deuterium exchange (HDX) and direct binding mass spectrometry experiments provide a link between static structure models and the dynamic equilibrium of the multiple states of KIT, supporting that sunitinib targets the autoinhibited conformation of WT-KIT. The D816H mutation shifts the KIT conformational equilibrium toward the activated state. The V560D mutant exhibits two low energy conformations: one is more flexible and resembles the D816H mutant shifted toward the activated conformation, and the other is less flexible and resembles the wild-type KIT in the autoinhibited conformation. This result correlates with the V560D mutant exhibiting a sensitivity to sunitinib that is less than for WT KIT but greater than for KIT D816H. These findings support the elucidation of the resistance mechanism for the KIT mutants.

  4. Communication Style as an Antecedent to Reactance, Self-Efficacy, and Restoration of Freedom for Drug- and Alcohol-Involved Women on Probation and Parole.

    Science.gov (United States)

    Smith, Sandi W; Cornacchione, Jennifer J; Morash, Merry; Kashy, Deborah; Cobbina, Jennifer

    2016-05-01

    This study extends research on psychological reactance theory by examining probation and parole officer (PO) communication style as an antecedent to female offenders' reactance and 2 indicators of subsequent drug and alcohol abuse while serving probation or parole sentences. Structural equation modeling was conducted to test a mediational path model, the results of which demonstrated that perceptions of PO conversational communication style were negatively associated with reactance but positively associated with self-efficacy to avoid drugs and alcohol. Conversely, women who perceived their POs as having a conformity communication style were more likely to report higher levels of reactance and lower self-efficacy to avoid drugs and alcohol. Psychological reactance led to desire to restore freedom, whereas self-efficacy to avoid drugs and alcohol did not. Desire to restore freedom was linked with reports of using drugs and alcohol and violations of parole or probation for using drugs and alcohol. These findings highlight the importance of communication style as an antecedent to reactance and in the relationship between POs and offenders.

  5. Quantification of imatinib in human serum: validation of a high-performance liquid chromatography-mass spectrometry method for therapeutic drug monitoring and pharmacokinetic assays.

    Science.gov (United States)

    Rezende, Vinicius Marcondes; Rivellis, Ariane; Novaes, Mafalda Megumi Yoshinaga; de Alencar Fisher Chamone, Dalton; Bendit, Israel

    2013-01-01

    Imatinib mesylate has been a breakthrough treatment for chronic myeloid leukemia. It has become the ideal tyrosine kinase inhibitor and the standard treatment for chronic-phase leukemia. Striking results have recently been reported, but intolerance to imatinib and noncompliance with treatment remain to be solved. Molecular monitoring by quantitative real-time polymerase chain reaction is the gold standard for monitoring patients, and imatinib blood levels have also become an important tool for monitoring. A fast and cheap method was developed and validated using high-performance liquid chromatography-mass spectrometry for quantification of imatinib in human serum and tamsulosin as the internal standard. Remarkable advantages of the method includes use of serum instead of plasma, less time spent on processing and analysis, simpler procedures, and requiring reduced amounts of biological material, solvents, and reagents. Stability of the analyte was also studied. This research also intended to drive the validation scheme in clinical centers. The method was validated according to the requirements of the US Food and Drug Administration and Brazilian National Health Surveillance Agency within the range of 0.500-10.0 μg/mL with a limit of detection of 0.155 μg/mL. Stability data for the analyte are also presented. Given that the validated method has proved to be linear, accurate, precise, and robust, it is suitable for pharmacokinetic assays, such as bioavailability and bioequivalence, and is being successfully applied in routine therapeutic drug monitoring in the hospital service.

  6. Determination of 82 veterinary drugs in swine waste lagoon sludge by ultra-high performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Li, Xiaowei; Guo, Ping; Shan, Yawen; Ke, Yuebin; Li, Hui; Fu, Qin; Wang, Yingyu; Liu, Tianhe; Xia, Xi

    2017-05-26

    This work reports the development of a multi-residue method for the identification and quantification of 82 veterinary drugs belonging to different chemical classes in swine waste lagoon. The proposed method applies a solid-phase extraction procedure with Oasis PRiME HLB cartridges that combines isolation of the compounds and sample clean-up in a single step. Analysis is performed by ultra-high performance liquid chromatography-tandem mass spectrometry, in one single injection with a chromatographic run time of only 9.5min. Linearity was studied in the range between 1 and 500μgkg -1 using standards prepared both in pure solvent and in the presence of matrix, showing coefficients of determination higher than 0.99 for all the analytes except for cefapirin in matrix. The average recoveries were in the range of 60-110% for most of the compounds tested with inter-day relative standard deviations below 17%. More than 97% of the investigated compounds had less or equal to a 5μgkg -1 quantitation limit in the studied matrix. Finally, the method was used with success to detect and quantify veterinary drugs residues in real samples with sulfonamides, quinolones, and tetracyclines being the most frequently determined compound groups. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Studies on the metabolism and toxicological detection of the designer drug 4-methylthioamphetamine (4-MTA) in human urine using gas chromatography-mass spectrometry.

    Science.gov (United States)

    Ewald, Andreas H; Peters, Frank T; Weise, Magdalene; Maurer, Hans H

    2005-09-25

    4-Methylthioamphetamine (4-MTA) is a scheduled designer drug that has appeared on the illicit drug market and led to several non-fatal or even fatal poisonings. Only few data are available on its metabolism. The first aim of this study was to identify the 4-MTA metabolites in human urine and then to study whether the authors' STA procedure is suitable for screening for and identification of 4-MTA and/or its metabolites in urine. After enzymatic cleavage of conjugates, solid-phase extraction (SPE) and acetylation the following metabolites could be identified by full-scan gas chromatography-mass spectrometry (GC-MS): deamino-oxo 4-MTA, deamino-hydroxy 4-MTA, ring hydroxy and beta-hydroxy 4-MTA. 4-MTA sulfoxide could be identified as possible artifact. In urine samples after enzymatic hydrolysis, acidic extraction, and methylation, 4-methylthiobenzoic acid could be identified. The authors' systematical toxicological analysis (STA) procedure using full-scan GC-MS after acid hydrolysis, liquid-liquid extraction (LLE) and acetylation allowed detection of 4-MTA as target analyte plus all the above-mentioned metabolites with the exception of 4-methylthiobenzoic acid. The extraction efficiency of 4-MTA was approximately 70% and the limit of detection (LOD) was 30 ng/ml (S/N 3).

  8. On-line solid-phase extraction coupled to hydrophilic interaction chromatography-mass spectrometry for the determination of polar drugs.

    Science.gov (United States)

    Fontanals, Núria; Marcé, Rosa M; Borrull, Francesc

    2011-09-02

    The present study describes the first fully automated method based on on-line solid-phase extraction (SPE) coupled to hydrophilic interaction chromatography-electrospray-mass spectrometry (HILIC-(ESI)MS) to determine a group of polar drugs that includes illicit drugs (such as cocaine, morphine, codeine and metabolites) and pharmaceuticals in environmental water samples. The SPE was performed using a highly retentive polymeric sorbent. The HILIC separation was optimised and the initial high organic content of the chromatographic mobile phase, was also suitable for the proper on-line elution of the analytes retained in the SPE column and for enhancing the ESI ionisation efficiency. This method allows the loading of samples of up to 250ml of ultrapure water or 10ml of environmental water samples spiked at low ngl(-1) levels of the analytes. The method yields near 100% recoveries for all the analytes. The method was also validated with environmental water samples with linear ranges from 5 to 1000ngl(-1) and limits of detection ≤2ngl(-1) for most of the compounds. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. New psychoactive substances as part of polydrug abuse within opioid maintenance treatment revealed by comprehensive high-resolution mass spectrometric urine drug screening.

    Science.gov (United States)

    Heikman, Pertti; Sundström, Mira; Pelander, Anna; Ojanperä, Ilkka

    2016-01-01

    At present, polydrug abuse comprises, besides traditional illicit drugs, new psychoactive substances (NPS) and non-prescribed psychotropic medicines (N-PPM). Polydrug abuse was comprehensively evaluated among opioid-dependent patients undergoing opioid maintenance treatment (OMT). Two hundred consecutively collected urine samples from 82 OMT patients (52 male) treated with methadone or buprenorphine-naloxone medication were studied using a liquid chromatography/time-of-flight mass spectrometry screening method. The method enables simultaneous detection of hundreds of abused substances covering the traditional drugs of abuse and many NPS as well as N-PPM. Ninety-two (45.8%) samples were positive for the abused substances. Benzodiazepines (29.0%), amphetamines (19.5%), cannabinoids (17.0%), NPS (13.0%), N-PPM (9.0%), and opioids (9.0%) were detected in different combinations. The simultaneous occurrence of up to three groups of abused substances was common (40.0%), and in one sample, all six groups were found. The stimulant NPS alpha-pyrrolidinovalerophenone was found in 10.0% and the sedative N-PPM pregabalin in 4.0% of the samples. The patients were seldom aware of what particular NPS they had abused. A widespread occurrence of abused substances beyond the ordinary was revealed. Identifying these patients is essential as polydrug abuse is a safety risk to the patient and may cause attrition from OMT. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Analysis of Veterinary Drug and Pesticide Residues Using the Ethyl Acetate Multiclass/Multiresidue Method in Milk by Liquid Chromatography-Tandem Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Husniye Imamoglu

    2016-01-01

    Full Text Available A rapid and simple multiclass, ethyl acetate (EtOAc multiresidue method based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS detection was developed for the determination and quantification of 26 veterinary drugs and 187 total pesticide residues in milk. Sample preparation was a simple procedure based on liquid–liquid extraction with ethyl acetate containing 0.1% acetic acid, followed by centrifugation and evaporation of the supernatant. The residue was dissolved in ethyl acetate with 0.1% acetic acid and centrifuged prior to LC-MS/MS analysis. Chromatographic separation of analytes was performed on an Inertsil X-Terra C18 column with acetic acid in methanol and water gradient. The repeatability and reproducibility were in the range of 2 to 13% and 6 to 16%, respectively. The average recoveries ranged from 75 to 120% with the RSD (n=18. The developed method was validated according to the criteria set in Commission Decision 2002/657/EC and SANTE/11945/2015. The validated methodology represents a fast and cheap alternative for the simultaneous analysis of veterinary drug and pesticide residues which can be easily extended to other compounds and matrices.

  11. Simultaneous determination of ten antihistamine drugs in human plasma using pipette tip solid-phase extraction and gas chromatography/mass spectrometry.

    Science.gov (United States)

    Hasegawa, Chika; Kumazawa, Takeshi; Lee, Xiao-Pen; Fujishiro, Masaya; Kuriki, Ayako; Marumo, Akemi; Seno, Hiroshi; Sato, Keizo

    2006-01-01

    Ten antihistamine drugs, diphenhydramine, orphenadrine, chlorpheniramine, diphenylpyraline, triprolidine, promethazine, homochlorcyclizine, cyproheptadine, cloperastine and clemastine, have been found to be extractable from human plasma samples using MonoTip C18 tips, inside which C18- bonded monolithic silica gel was fixed. Human plasma (0.1 mL) containing the ten antihistamines was mixed with 0.4 mL of distilled water and 25 microL of a 1 M potassium phosphate buffer (pH 8.0). After centrifugation of the mixture, the supernatant fraction was extracted to the C18 phase of the tip by 25 repeated aspirating/dispensing cycles using a manual micropipettor. The analytes retained on the C18 phase were then eluted with methanol by five repeated aspirating/dispensing cycles. The eluate was injected into a gas chromatography (GC) injector without evaporation and reconstitution steps, and was detected by a mass spectrometer with selected ion monitoring in the positive-ion electron impact mode. The separation of the ten drugs from each other and from impurities was generally satisfactory using a DB-1MS column (30 m x 0.32 mm i.d., film thickness 0.25 microm). The recoveries of the ten antihistamines spiked into plasma were 73.8-105%. The regression equations for the ten antihistamines showed excellent linearity with detection limits of 0.02-5.0 ng/0.1 mL. The within-day and day-to-day coefficients of variation for plasma were not greater than 9.9%. The data obtained from determination of diphenhydramine and chlorpheniramine in human plasma after oral administration of the drugs are also presented. Copyright 2006 John Wiley & Sons, Ltd.

  12. The law of mass action and the pharmacological concentration-effect curve: resolving the paradox of apparently non-dose-related adverse drug reactions.

    Science.gov (United States)

    Aronson, Jeffrey K; Ferner, Robin E

    2016-01-01

    Adverse drug reactions are sometimes described as being 'non-dose-related' because no relationship has been found between increasing doses and either the intensity of the response or the proportion of individuals in whom the response occurs; furthermore, hypersensitivity reactions are often regarded as being non-dose-related, even if different doses have not been studied. However, the law of mass action implies that all pharmacological effects are concentration related and should increase in intensity with increasing dose. We set out to explain this paradox. We searched for published adverse drug reactions that have been described as non-dose-related and analysed them. We identified four categories of explanations that resolve the paradox: (i) the reaction is not real; it may have occurred by chance or there may be methodological problems, such as bias or confounding factors; (ii) the dose-response curve for the adverse effect reaches a maximum at doses lower than were studied (i.e. a hypersusceptibility reaction); this underpins the use of test doses to predict the possibility of an adverse reaction at therapeutic doses; (iii) susceptibility to the adverse reaction differs widely among individuals; and (iv) imprecision or inaccuracy in the measurement of either dose or effect obscures dose responsiveness. This last explanation encompasses: (a) reactions related to cumulative dose; (b) dissociation between dose and concentration through saturable pharmacokinetics; and (c) variability in the measurement of the effect. If an adverse drug reaction appears to be non-dose-related, the reasons should be sought, having these mechanisms in mind. © 2015 The British Pharmacological Society.

  13. Validation of an ultra-high-performance liquid chromatography-tandem mass spectrometry method to quantify illicit drug and pharmaceutical residues in wastewater using accuracy profile approach.

    Science.gov (United States)

    Hubert, Cécile; Roosen, Martin; Levi, Yves; Karolak, Sara

    2017-06-02

    The analysis of biomarkers in wastewater has become a common approach to assess community behavior. This method is an interesting way to estimate illicit drug consumption in a given population: by using a back calculation method, it is therefore possible to quantify the amount of a specific drug used in a community and to assess the consumption variation at different times and locations. Such a method needs reliable analytical data since the determination of a concentration in the ngL -1 range in a complex matrix is difficult and not easily reproducible. The best analytical method is liquid chromatography - mass spectrometry coupling after solid-phase extraction or on-line pre-concentration. Quality criteria are not specially defined for this kind of determination. In this context, it was decided to develop an UHPLC-MS/MS method to analyze 10 illicit drugs and pharmaceuticals in wastewater treatment plant influent or effluent using a pre-concentration on-line system. A validation process was then carried out using the accuracy profile concept as an innovative tool to estimate the probability of getting prospective results within specified acceptance limits. Influent and effluent samples were spiked with known amounts of the 10 compounds and analyzed three times a day for three days in order to estimate intra-day and inter-day variations. The matrix effect was estimated for each compound. The developed method can provide at least 80% of results within ±25% limits except for compounds that are degraded in influent. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Analysis of veterinary drug and pesticide residues in animal feed by high-resolution mass spectrometry: comparison between time-of-flight and Orbitrap.

    Science.gov (United States)

    Gómez-Pérez, María Luz; Romero-González, Roberto; Martínez Vidal, José Luis; Garrido Frenich, Antonia

    2015-01-01

    The use of medium-high-resolution mass spectrometers (M-HRMS) provides many advantages in multi-residue analysis. A comparison between two mass spectrometers, medium-resolution (MRMS) time-of-flight (TOF) and high-resolution (HRMS) Orbitrap, has been carried out for the analysis of toxic compounds in animal feed. More than 300 compounds belonging to several classes of veterinary drugs (VDs) and pesticides have been determined in different animal feed samples using a generic extraction method. The use of a clean-up procedure has been evaluated in both instruments, and several validation parameters have been established, such as the matrix effect, linearity, recovery and sensitivity. Finally, both instruments have been used during the analysis of 18 different feed samples (including chicken, hen, rabbit and horse). Some VDs (sulfadiazine, trimethoprim, robenidine and monensin sodium) and one pesticide (chlorpyrifos) have been identified. In general, better results were obtained using the Orbitrap, such as sensitivity (1-12.5 µg kg(-1)) and recovery values (60-125%). Moreover, this analyser had several software tools, which reduced the time for data processing and were easy to use, performing quick screening for more than 450 compounds in less than 5 min. However, some disadvantages such as the high cost and a decrease in the number of detected compounds at low concentrations must be taken into account.

  15. Applications of Isotope Ratio Mass Spectrometry in Sports Drug Testing Accounting for Isotope Fractionation in Analysis of Biological Samples.

    Science.gov (United States)

    Piper, Thomas; Thevis, Mario

    2017-01-01

    The misuse of anabolic-androgenic steroids (AAS) in sports aiming at enhancing athletic performance has been a challenging matter for doping control laboratories for decades. While the presence of a xenobiotic AAS or its metabolite(s) in human urine immediately represents an antidoping rule violation, the detection of the misuse of endogenous steroids such as testosterone necessitates comparably complex procedures. Concentration thresholds and diagnostic analyte ratios computed from urinary steroid concentrations of, e.g., testosterone and epitestosterone have aided identifying suspicious doping control samples in the past. These ratios can however also be affected by confounding factors and are therefore not sufficient to prove illicit steroid administrations. Here, carbon and, in rare cases, hydrogen isotope ratio mass spectrometry (IRMS) has become an indispensable tool. Importantly, the isotopic signatures of pharmaceutical steroid preparations commonly differ slightly but significantly from those found with endogenously produced steroids. By comparing the isotope ratios of endogenous reference compounds like pregnanediol to that of testosterone and its metabolites, the unambiguous identification of the urinary steroids' origin is accomplished. Due to the complex urinary matrix, several steps in sample preparation are inevitable as pure analyte peaks are a prerequisite for valid IRMS determinations. The sample cleanup encompasses steps such as solid phase or liquid-liquid extraction that are presumably not accompanied by isotopic fractionation processes, as well as more critical steps like enzymatic hydrolysis, high-performance liquid chromatography fractionation, and derivatization of analytes. In order to exclude any bias of the analytical results, each step of the analytical procedure is optimized and validated to exclude, or at least result in constant, isotopic fractionation. These efforts are explained in detail. © 2017 Elsevier Inc. All rights reserved.

  16. A straightforward, validated liquid chromatography coupled to tandem mass spectrometry method for the simultaneous detection of nine drugs of abuse and their metabolites in hair and nails.

    Science.gov (United States)

    Cappelle, Delphine; De Doncker, Mireille; Gys, Celine; Krysiak, Kamelia; De Keukeleire, Steven; Maho, Walid; Crunelle, Cleo L; Dom, Geert; Covaci, Adrian; van Nuijs, Alexander L N; Neels, Hugo

    2017-04-01

    Hair and nails allow for a stable accumulation of compounds over time and retrospective investigation of past exposure and/or consumption. Owing to their long window of detection (weeks to months), analysis of these matrices can provide information complementary to blood and urine analysis or can be used in standalone when e.g. elimination from the body has already occurred. Drugs of abuse are often used together and, therefore, multi-analyte methods capable of detecting several substances and their metabolites in a single run are of importance. This paper presents the development and validation of a method based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for the simultaneous detection of nine drugs of abuse and their metabolites in hair and nails. We focused on a simple and straightforward sample preparation to reduce costs, and allow application in routine laboratory practice. Chromatographic and mass spectrometric parameters, such as column type, mobile phase, and multiple reaction monitoring transitions were optimized. The method was validated according to the European Medicine Agency guidelines with an assessment of specificity, limit of quantification (LOQ), linearity, accuracy, precision, carry-over, matrix effects, recovery, and process efficiency. Linearity ranged from 25 to 20 000 pg mg -1 hair and from 50 to 20 000 pg mg -1 nails, and the lowest calibration point achieved the requirements for the LOQ (25 pg mg -1 for hair and 50 pg mg -1 for nails). Although it was not the main focus of the article, the reliability of the method was proven through successful participation in a proficiency test, and by investigation of authentic hair and nail samples from self-reported drug users. In the future, the method should allow comparison between the two matrices to acquire an in-depth knowledge of nail analysis and to define cutoff levels for nail analysis, as they exist for hair. Copyright © 2017 Elsevier B.V. All rights

  17. Development of an achiral supercritical fluid chromatography method with ultraviolet absorbance and mass spectrometric detection for impurity profiling of drug candidates. Part I: Optimization of mobile phase composition.

    Science.gov (United States)

    Lemasson, Elise; Bertin, Sophie; Hennig, Philippe; Boiteux, Hélène; Lesellier, Eric; West, Caroline

    2015-08-21

    Supercritical fluid chromatography (SFC) is a very useful tool in the purpose of impurity profiling of drug candidates, as an adequate selection of stationary phases can provide orthogonal separations so as to maximize the chances to see all impurities. The purpose of the present work is to develop a method for chemical purity assessment. The first part, presented here, focuses on mobile phase selection to ensure adequate elution and detection of drug-like molecules, while the second part focuses on stationary phase selection for optimal separation and orthogonality. The use of additives in the carbon dioxide - solvent mobile phase in SFC is now commonplace, and enables in particular to increase the number of eluted compounds and to improve peak shapes. The objective of this first part was to test different additives (acids, bases, salts and water) for their chromatographic performance assessed in gradient elution with a diode-array detector, but also for the mass responses obtained with a single-quadrupole mass detector, equipped with an electrospray ionization source (Waters ACQUITY QDa). In this project, we used a selection of one hundred and sixty compounds issued from Servier Research Laboratories to screen a set of columns and additives in SFC with a Waters ACQUITY UPC(2) system. The selected columns were all high-performance columns (1.7-1.8μm with totally porous particles or 2.6-2.7μm with superficially porous particles) with a variety of stationary phase chemistries. Initially, eight additives dissolved in the methanol co-solvent were tested on a UPC(2) ACQUITY UPC(2) HSS C18 SB column. A Derringer desirability function was used to classify the additives according to selected criteria: elution capability, peak shapes, UV baseline drift, and UV and mass responses (signal-to-noise ratios). Following these tests, the two best additives (ammonium acetate and ammonium hydroxide) were tested on a larger number of columns (10) where the two additives appeared

  18. Screening for illicit drugs in pooled human urine and urinated soil samples and studies on the stability of urinary excretion products of cocaine, MDMA, and MDEA in wastewater by hyphenated mass spectrometry techniques

    DEFF Research Database (Denmark)

    Mardal, Marie; Kinyua, Juliet; Ramin, Pedram

    2017-01-01

    ) is useful to detect consumed drugs and identify targets of illicit drugs use. The aims of the study were (1) to screen PU and urinated soil (US) samples collected at festivals for illicit drug excretion products using hyphenated techniques; (2) to develop and validate a hydrophilic interaction liquid...... chromatography – mass spectrometry / mass spectrometry (HILIC-MS/MS) method of quantifying urinary targets of identified drugs in wastewater; and (3) to conduct a 24 h stability study, using PU and US to better reflect the chemical environment for targets in wastewater. Cocaine (COC) and ecstasy-like compounds....... The results suggest HMMA as analytical target for MDMA consumption in WBE, due to its stability in wastewater and its excretion as the main phase I metabolite of MDMA. Copyright © 2016 John Wiley & Sons, Ltd....

  19. A single LC-tandem mass spectrometry method for the simultaneous determination of 14 antimalarial drugs and their metabolites in human plasma.

    Science.gov (United States)

    Hodel, E M; Zanolari, B; Mercier, T; Biollaz, J; Keiser, J; Olliaro, P; Genton, B; Decosterd, L A

    2009-04-01

    Among the various determinants of treatment response, the achievement of sufficient blood levels is essential for curing malaria. For helping us at improving our current understanding of antimalarial drugs pharmacokinetics, efficacy and toxicity, we have developed a liquid chromatography-tandem mass spectrometry method (LC-MS/MS) requiring 200mul of plasma for the simultaneous determination of 14 antimalarial drugs and their metabolites which are the components of the current first-line combination treatments for malaria (artemether, artesunate, dihydroartemisinin, amodiaquine, N-desethyl-amodiaquine, lumefantrine, desbutyl-lumefantrine, piperaquine, pyronaridine, mefloquine, chloroquine, quinine, pyrimethamine and sulfadoxine). Plasma is purified by a combination of protein precipitation, evaporation and reconstitution in methanol/ammonium formate 20mM (pH 4.0) 1:1. Reverse-phase chromatographic separation of antimalarial drugs is obtained using a gradient elution of 20mM ammonium formate and acetonitrile both containing 0.5% formic acid, followed by rinsing and re-equilibration to the initial solvent composition up to 21min. Analyte quantification, using matrix-matched calibration samples, is performed by electro-spray ionization-triple quadrupole mass spectrometry by selected reaction monitoring detection in the positive mode. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effect variability, overall process efficiency, standard addition experiments as well as antimalarials short- and long-term stability in plasma. The reactivity of endoperoxide-containing antimalarials in the presence of hemolysis was tested both in vitro and on malaria patients samples. With this method, signal intensity of artemisinin decreased by about 20% in the presence of 0.2% hemolysed red-blood cells in plasma, whereas its derivatives were essentially not affected. The method is precise (inter-day CV%: 3.1-12.6%) and sensitive

  20. Multiple Reaction Monitoring Mode Based Liquid Chromatography-Mass Spectrometry Method for Simultaneous Quantification of Brassinolide and Other Plant Hormones Involved in Abiotic Stresses

    OpenAIRE

    Kasote, Deepak M.; Ghosh, Ritesh; Chung, Jun Young; Kim, Jonggeun; Bae, Inhwan; Bae, Hanhong

    2016-01-01

    Plant hormones are the key regulators of adaptive stress response. Abiotic stresses such as drought and salt are known to affect the growth and productivity of plants. It is well known that the levels of plant hormones such as zeatin (ZA), abscisic acid (ABA), salicylic acid (SA), jasmonic acid (JA), and brassinolide (BR) fluctuate upon abiotic stress exposure. At present, there is not any single suitable liquid chromatography-mass spectrometry (LC-MS) method for simultaneous analysis of BR a...

  1. Application of a hybrid ordered mesoporous silica as sorbent for solid-phase multi-residue extraction of veterinary drugs in meat by ultra-high-performance liquid chromatography coupled to ion-trap tandem mass spectrometry.

    Science.gov (United States)

    Casado, Natalia; Morante-Zarcero, Sonia; Pérez-Quintanilla, Damián; Sierra, Isabel

    2016-08-12

    A quick, sensitive and selective analytical reversed-phase multi-residue method using ultra-high performance liquid chromatography coupled to an ion-trap mass spectrometry detector (UHPLC-IT-MS/MS) operating in both positive and negative ion mode was developed for the simultaneous determination of 23 veterinary drug residues (β-blockers, β-agonists and Non-Steroidal Anti-inflammatory Drugs (NSAIDs)) in meat samples. The sample treatment involved a liquid-solid extraction followed by a solid-phase extraction (SPE) procedure. SBA-15 type mesoporous silica was synthetized and modified with octadecylsilane, and the resulting hybrid material (denoted as SBA-15-C18) was applied and evaluated as SPE sorbent in the purification of samples. The materials were comprehensively characterized, and they showed a high surface area, high pore volume and a homogeneous distribution of the pores. Chromatographic conditions and extraction procedure were optimized, and the method was validated according to the Commission Decision 2002/657/EC. The method detection limits (MDLs) and the method quantification limits (MQLs) were determined for all the analytes in meat samples and found to range between 0.01-18.75μg/kg and 0.02-62.50μg/kg, respectively. Recoveries for 15 of the target analytes ranged from 71 to 98%. In addition, for comparative purpose SBA-15-C18 was evaluated towards commercial C18 amorphous silica. Results revealed that SBA-15-C18 was clearly more successful in the multi-residue extraction of the 23 mentioned analytes with higher recovery values. The method was successfully tested to analyze prepacked preparations of mince bovine meat. Traces of propranolol, ketoprofen and diclofenac were detected in some samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Analysis of 44 drugs of abuse and metabolites in wastewater and river water using a hybrid quadrupole time-of-flight tandem mass spectrometry

    Science.gov (United States)

    Andres-Costa, M. Jesus; Andreu, Vicente; Picó, Yolanda

    2016-04-01

    The presence of drugs of abuse in the aquatic environment has been recognized as an important issue for the ecosystem due their possible negative effect on it (Richardson, 2011). Incomplete removal of these substances during wastewater treatment could be one of the causes of their release in the environment (Zuccato and Castiglioni, 2009). Pollution by illicit drug residues at very low concentrations is generalized in populated areas, with potential risks for human health and the environment (Zuccato, 2008; Castiglioni et al 2007).The aim of this study was to screen and quantify 44 drugs of abuse and metabolites of wastewater samples using a hybrid quadrupole time-of-flight tandem mass spectrometry and furthermore carry out a post-target screening to identify additional compounds present in the water samples. Wastewater samples were collected from the influent and effluent of three wastewater treatment plants (WWTPs) in Valencia and river water samples form Turia River Basin. Illicit drugs were extracted by solid-phase extraction (SPE). The chromatography was performed with an Agilent 1260 Infinity ultra high performance liquid chromatography (UHPLC). The UHPLC system was coupled to a hybrid quadrupole time-of-flight ABSciex Triple TOFTM 5600. All analytes were analyzed in positive mode. Acquiring full scan MS data was employed for quantification of drugs of abuse, and automatic data dependent information product ion spectra (IDA-MS/MS) was checked for identifying emerging illicit drugs and other compounds in water samples. The use of a database containing 1212 compounds achieved high confidence results for a wide number of contaminants. In the present study, the presence of compounds that belong to amphetamines group (amphetamine, methamphetamine, ephedrine, MDMA, MDA and MDEA), tryptamines (bufotenine), pirrolidinophenone group (α-PVP and 4'-MePHP), arylcyclohexylamines (ketamine), cocainics (cocaine, benzoylecgonine, cocaethylene and ecgonine methyl ester) and

  3. ENERGY-DEPENDENT PROCESSES INVOLVED IN REDUCED DRUG ACCUMULATION IN MULTIDRUG-RESISTANT HUMAN LUNG-CANCER CELL-LINES WITHOUT P-GLYCOPROTEIN EXPRESSION

    NARCIS (Netherlands)

    VERSANTVOORT, CHM; BROXTERMAN, HJ; PINEDO, HM; DEVRIES, EGE; FELLER, N; KUIPER, CM; LANKELMA, J

    1992-01-01

    Mechanisms contributing to reduced cytotoxic drug accumulation were studied in two multidrug-resistant (MDR) human lung cancer cell lines without P-glycoprotein expression. In these (non-small cell) SW-1573/ 2R120 and (small cell) GLC4/ADR MDR cells, the steady-state accumulation of

  4. Qualitative and Quantitative Drug residue analyses: Florfenicol in white-tailed deer (Odocoileus virginianus) and supermarket meat by liquid chromatography tandem-mass spectrometry.

    Science.gov (United States)

    Anderson, Shanoy C; Subbiah, Seenivasan; Gentles, Angella; Austin, Galen; Stonum, Paul; Brooks, Tiffanie A; Brooks, Chance; Smith, Ernest E

    2016-10-15

    A method for confirmation and detection of Florfenicol amine residues in white-tailed deer tissues was developed and validated in our laboratory. Tissue samples were extracted with ethyl acetate and cleaned up on sorbent (Chem-elut) cartridges. Liguid chromatography (LC) separation was achieved on a Zorbax Eclipse plus C18 column with gradient elution using a mobile phase composed of ammonium acetate in water and methanol at a flow rate of 300μL/min. Qualitative and quantitative analyses were carried out using liquid chromatography - heated electrospray ionization(HESI) and atmospheric pressure chemical ionization (APCI)-tandem mass spectrometry in the multiple reaction monitoring (MRM) interface. The limits of detection (LODs) for HESI and APCI probe were 1.8ng/g and 1.4ng/g respectively. Limits of quantitation (LOQs) for HESI and APCI probe were 5.8ng/g and 3.4ng/g respectively. Mean recovery values ranged from 79% to 111% for APCI and 30% to 60% for HESI. The validated method was used to determine white-tailed deer florfenicol tissue residue concentration 10-days after exposure. Florfenicol tissue residues concentration ranged from 0.4 to 0.6μg/g for liver and 0.02-0.05μg/g for muscle and a trace in blood samples. The concentration found in the tested edible tissues were lower than the maximum residual limit (MRL) values established by the federal drug administration (FDA) for bovine tissues. In summary, the resulting optimization procedures using the sensitivity of HESI and APCI probes in the determination of florfenicol in white-tailed deer tissue are the most compelling conclusions in this study, to the extent that we have applied this method in the evaluation of supermarket samples drug residue levels as a proof of principle. Copyright © 2016. Published by Elsevier B.V.

  5. Factors Associated with Non-Participation and Non-Adherence in Directly Observed Mass Drug Administration for Malaria in The Gambia

    Science.gov (United States)

    Dierickx, Susan; Gryseels, Charlotte; Mwesigwa, Julia; O’Neill, Sarah; Bannister-Tyrell, Melanie; Ronse, Maya; Jaiteh, Fatou; Gerrets, René; D’Alessandro, Umberto; Grietens, Koen Peeters

    2016-01-01

    Introduction The potential benefits of Mass Drug Administration (MDA) for malaria elimination are being considered in several malaria endemic countries where a decline in malaria transmission has been reported. For this strategy to work, it is important that a large proportion of the target population participates, requiring an in-depth understanding of factors that may affect participation and adherence to MDA programs. Methodology This social science study was ancillary to a one-round directly observed MDA campaign with dihydroartemisinin-piperaquine, carried out in 12 villages in rural Gambia between June and August 2014. The social science study employed a mixed-methods approach combining qualitative methods (participant observation and in-depth interviewing) and quantitative methods (structured follow-up interviews among non-participating and non-adhering community members). Results Of 3942 people registered in the study villages, 67.9% adhered to the three consecutive daily doses. For the remaining villagers, 12.6% did not attend the screening, 3.5% was not eligible and 16% did not adhere to the treatment schedule. The main barriers for non-participation and adherence were long and short-term mobility of individuals and specific subgroups, perceived adverse drug reactions and rumors, inconveniences related to the logistics of MDA (e.g. waiting times) and the perceived lack of information about MDA. Conclusion While, there was no fundamental resistance from the target communities, adherence was 67.9%. This shows the necessity of understanding local perceptions and barriers to increase its effectiveness. Moreover, certain of the constraining factors were socio-spatially clustered which might prove problematic since focal areas of residual malaria transmission may remain allowing malaria to spread to adjacent areas where transmission had been temporarily interrupted. PMID:26866685

  6. Factors Associated with Non-Participation and Non-Adherence in Directly Observed Mass Drug Administration for Malaria in The Gambia.

    Directory of Open Access Journals (Sweden)

    Susan Dierickx

    Full Text Available The potential benefits of Mass Drug Administration (MDA for malaria elimination are being considered in several malaria endemic countries where a decline in malaria transmission has been reported. For this strategy to work, it is important that a large proportion of the target population participates, requiring an in-depth understanding of factors that may affect participation and adherence to MDA programs.This social science study was ancillary to a one-round directly observed MDA campaign with dihydroartemisinin-piperaquine, carried out in 12 villages in rural Gambia between June and August 2014. The social science study employed a mixed-methods approach combining qualitative methods (participant observation and in-depth interviewing and quantitative methods (structured follow-up interviews among non-participating and non-adhering community members.Of 3942 people registered in the study villages, 67.9% adhered to the three consecutive daily doses. For the remaining villagers, 12.6% did not attend the screening, 3.5% was not eligible and 16% did not adhere to the treatment schedule. The main barriers for non-participation and adherence were long and short-term mobility of individuals and specific subgroups, perceived adverse drug reactions and rumors, inconveniences related to the logistics of MDA (e.g. waiting times and the perceived lack of information about MDA.While, there was no fundamental resistance from the target communities, adherence was 67.9%. This shows the necessity of understanding local perceptions and barriers to increase its effectiveness. Moreover, certain of the constraining factors were socio-spatially clustered which might prove problematic since focal areas of residual malaria transmission may remain allowing malaria to spread to adjacent areas where transmission had been temporarily interrupted.

  7. Method development and validation of liquid chromatography-tandem/mass spectrometry for aldosterone in human plasma: Application to drug interaction study of atorvastatin and olmesartan combination

    Directory of Open Access Journals (Sweden)

    Rakesh Das

    2014-01-01

    Full Text Available In the present investigation, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS method was developed for the quantification of aldosterone (ALD a hormone responsible for blood pressure in human plasma. The developed method was validated and extended for application on human subjects to study drug interaction of atorvastatin (ATSV and olmesartan (OLM on levels of ALD. The ALD in plasma was extracted by liquid-liquid extraction with 5 mL dichloromethane/ethyl ether (60/40% v/v. The chromatographic separation of ALD was carried on Xterra, RP-Column C18 (150 mm× 4.6 mm × 3.5 μm at 30°C followed by four-step gradient program composed of methanol and water. Step 1 started with 35% methanol for first 1 min and changed linearly to 90% in next 1.5 min in Step 2. Step 3 lasted for next 2 min with 90% methanol. The method finally concluded with Step 4 to achieve initial concentration of methanol that is, 35% thus contributing the total method run time of 17.5 min. The flow rate was 0.25 mL/min throughout the process. The developed method was validated for specificity, accuracy, precision, stability, linearity, sensitivity, and recovery. The method was linear and found to be acceptable over the range of 50-800 ng/mL. The method was successfully applied for the drug interaction study of ATSV + OLM in combination against OLM treatment on blood pressure by quantifying changes in levels of ALD in hypertensive patients. The study revealed levels of ALD were significantly higher in ATSV + OLM treatment condition when compared to OLM as single treated condition. This reflects the reason of low effectiveness of ATSV + OLM in combination instead of synergistic activity.

  8. Forensic Drug Identification, Confirmation and Quantification Using Fully Integrated Gas Chromatography with Fourier Transform Infrared Detection and Mass Spectrometric Detection (GC-FT-IR-MS).

    Science.gov (United States)

    Lanzarotta, Adam; Lorenz, Lisa; Voelker, Sarah; Falconer, Travis M; Batson, JaCinta S

    2018-01-01

    This manuscript is a continuation of a recent study that described the use of fully integrated gas chromatography with direct deposition Fourier transform infrared detection and mass spectrometric detection (GC-FT-IR-MS) to identify and confirm the presence of sibutramine and AB-FUBINACA. The purpose of the current study was to employ the GC-FT-IR portion of the same instrument to quantify these compounds, thereby demonstrating the ability to identify, confirm, and quantify drug substances using a single GC-FT-IR-MS unit. The performance of the instrument was evaluated by comparing quantitative analytical figures of merit to those measured using an established, widely employed method for quantifying drug substances, high performance liquid chromatography with ultraviolet detection (HPLC-UV). The results demonstrated that GC-FT-IR was outperformed by HPLC-UV with regard to sensitivity, precision, and linear dynamic range (LDR). However, sibutramine and AB-FUBINACA concentrations measured using GC-FT-IR were not significantly different at the 95% confidence interval compared to those measured using HPLC-UV, which demonstrates promise for using GC-FT-IR as a semi-quantitative tool at the very least. The most significant advantage of GC-FT-IR compared to HPLC-UV is selectivity; a higher level of confidence regarding the identity of the analyte being quantified is achieved using GC-FT-IR. Additional advantages of using a single GC-FT-IR-MS instrument for identification, confirmation, and quantification are efficiency, increased sample throughput, decreased consumption of laboratory resources (solvents, chemicals, consumables, etc.), and thus cost.

  9. What Is Needed to Eradicate Lymphatic Filariasis? A Model-Based Assessment on the Impact of Scaling Up Mass Drug Administration Programs.

    Directory of Open Access Journals (Sweden)

    Randee J Kastner

    Full Text Available Lymphatic filariasis (LF is a neglected tropical disease for which more than a billion people in 73 countries are thought to be at-risk. At a global level, the efforts against LF are designed as an elimination program. However, current efforts appear to aim for elimination in some but not all endemic areas. With the 2020 goal of elimination looming, we set out to develop plausible scale-up scenarios to reach global elimination and eradication. We predict the duration of mass drug administration (MDA necessary to reach local elimination for a variety of transmission archetypes using an existing model of LF transmission, estimate the number of treatments required for each scenario, and consider implications of rapid scale-up.We have defined four scenarios that differ in their geographic coverage and rate of scale-up. For each scenario, country-specific simulations and calculations were performed that took into account the pre-intervention transmission intensity, the different vector genera, drug regimen, achieved level of population coverage, previous progress toward elimination, and potential programmatic delays due to mapping, operations, and administration.Our results indicate that eliminating LF by 2020 is unlikely. If MDA programs are drastically scaled up and expanded, the final round of MDA for LF eradication could be delivered in 2028 after 4,159 million treatments. However, if the current rate of scale-up is maintained, the final round of MDA to eradicate LF may not occur until 2050.Rapid scale-up of MDA will decrease the amount of time and treatments required to reach LF eradication. It may also propel the program towards success, as the risk of failure is likely to increase with extended program duration.

  10. Multi-residue analysis of drugs of abuse in wastewater and surface water by solid-phase extraction and liquid chromatography-positive electrospray ionisation tandem mass spectrometry.

    Science.gov (United States)

    Baker, David R; Kasprzyk-Hordern, Barbara

    2011-03-25

    A new-multi residue method was developed for the environmental monitoring of 65 stimulants, opiod and morphine derivatives, benzodiazepines, antidepressants, dissociative anaesthetics, drug precursors, human urine indicators and their metabolites in wastewater and surface water. The proposed analytical methodology offers rapid analysis for a large number of compounds, with low limits of quantification and utilises only one solid-phase extraction-ultra performance liquid chromatography-positive electrospray ionisation tandem mass spectrometry (SPE-LC-MS/MS) method, thus overcoming the drawbacks of previously published procedures. The method employed solid phase extraction with the usage of Oasis MCX sorbent and subsequent ultra performance liquid chromatography-positive electrospray ionisation tandem mass spectrometry. The usage of a 1.7 μm particle size column (1 mm×150 mm) resulted in very low flow rates (0.04 mLmin(-1)), and as a consequence gave good sensitivity, low mobile phase consumption and short retention times for all compounds (from 2.9 to 23.1 min). High SPE recoveries (>60%) were obtained for the majority of compounds. The mean correlation coefficients of the calibration curves were typically higher than 0.997 and showed good linearity in the range 0-1000 μgL(-1). The method limits of detection ranged from 0.1 ngL(-1) for compounds including cocaine, benzoylecgonine, norbenzoylecgonine and 2-oxo-3-hydroxy-LSD to 100 ngL(-1) for caffeine. Method quantification limits ranged from 0.5 to 154.2 ngL(-1). Intra- and inter-day repeatabilities were on average less than 10%. The method accuracy range was within -33.1 to 30.1%. The new multi-residue method was used to analyse drugs of abuse in wastewater and river water in the UK environment. Of the targeted 65 compounds, 46 analytes were detected at levels above the method quantification limit (MQL) in wastewater treatment plant (WWTP) influent, 43 in WWTP effluent and 36 compounds in river water. Copyright

  11. Effects of mixing between low and high mass scalar mesons for radiative decays involving f{sub 0}(980) and a{sub 0}(980)

    Energy Technology Data Exchange (ETDEWEB)

    Teshima, T.; Kitamura, I; Morisita, N. [Chubu University, Kasugai (Japan). Dept. of Applied Physics

    2005-07-01

    Assuming f{sub 0}(980) and a{sub 0}(980) are mainly qqq-barq-bar low mass scalar mesons and mixed with qq-bar high mass scalar mesons, we analyzed the mixing effects for {phi} {yields}f{sub 0}(980){gamma}, {phi} {yields} a{sub 0}(980){gamma}, f{sub 0}(980) {yields} {gamma}{gamma} and a{sub 0}(980) {yields} {gamma}{gamma}. Used the vector meson dominance model (VDM), these decay amplitudes are expressed by coupling parameters B describing the S(qqq-barq-bar scalar meson)-V(vector meson)-V(vector meson) coupling and B' describing the S'(qq-bar scalar meson)-V-V coupling. If the magnitudes for B and B' are {approx} 2.8GeV{sup -1} and {approx} 12GeV{sup -1}, respectively, the mixing angle between a{sub 0}(980) and a{sub 0}(1450) are {approx} 9 deg, and the mixing parameter {lambda}{sub 01} causing the mixing between I = 0 qqq-barq-bar state and qq-bar state is {approx} 0.24GeV{sup 2} , the experimental data for these radiative decays are interpreted consistently. (author)

  12. Mass spectrometric studies on the in vivo metabolism and excretion of SIRT1 activating drugs in rat urine, dried blood spots, and plasma samples for doping control purposes.

    Science.gov (United States)

    Höppner, Sebastian; Delahaut, Philippe; Schänzer, Wilhelm; Thevis, Mario

    2014-01-01

    The NAD(+) depending enzyme SIRT1 regulates the mitochondrial biogenesis, fat and glucose metabolism through catalyzing the deacetylation of several metabolism-related protein-substrates. Recently, synthetic activators of SIRT1 referred to as STACs (Sirtuin activating compounds, e.g. SRT2104) were identified and tested in clinical studies for the treatment of aging-related diseases such as type 2 diabetes, Alzheimer's and obesity. Although the mechanism of SIRT1 activation by small molecules has caused considerable controversy, STACs demonstrated a significant performance enhancement in mice experiments including an improvement of endurance, muscle strength, and locomotor behavior. Due to their potential to increase exercise tolerance in healthy individuals, SIRT1 activators are currently being monitored by anti-doping authorities. In the present study, the in vivo metabolic clearance of three SIRT1 activators was investigated in rats by the collection of urine, DBS (dried blood spots) and plasma samples following a single oral administration. The resulting metabolic products were studied by positive electrospray ionization - (tandem) mass spectrometry and confirmed by the comparison with in vitro generated metabolites using human and rat liver microsomal preparations. Subsequently, a screening procedure for five SIRT1 activators and the metabolite M1-SRT1720 in DBS specimens was developed. Liquid-liquid-extraction and liquid chromatography/tandem mass spectrometry was employed based on diagnostic ion transitions recorded in multiple reaction monitoring mode and two deuterated internal standards namely d8-SRT1720 and d8-M1-SRT1720 were utilized. The doping control assay was characterized with regard to specificity, limit of detection (10-50ng/ml), recovery (65-83%) and imprecision (7-20%) and ion suppression/enhancement effects (drug testing applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Integrative Analyses of miRNA-mRNA Interactions Reveal let-7b, miR-128 and MAPK Pathway Involvement in Muscle Mass Loss in Sex-Linked Dwarf Chickens

    Science.gov (United States)

    Luo, Wen; Lin, Shumao; Li, Guihuan; Nie, Qinghua; Zhang, Xiquan

    2016-01-01

    The sex-linked dwarf (SLD) chicken is an ideal model system for understanding growth hormone (GH)-action and growth hormone receptor (GHR) function because of its recessive mutation in the GHR gene. Skeletal muscle mass is reduced in the SLD chicken with a smaller muscle fiber diameter. Our previous study has presented the mRNA and miRNA expression profiles of the SLD chicken and normal chicken between embryo day 14 and seven weeks of age. However, the molecular mechanism of GHR-deficient induced muscle mass loss is still unclear, and the key molecules and pathways underlying the GHR-deficient induced muscle mass loss also remain to be illustrated. Here, by functional network analysis of the differentially expressed miRNAs and mRNAs between the SLD and normal chickens, we revealed that let-7b, miR-128 and the MAPK pathway might play key roles in the GHR-deficient induced muscle mass loss, and that the reduced cell division and growth are potential cellular processes during the SLD chicken skeletal muscle development. Additionally, we also found some genes and miRNAs involved in chicken skeletal muscle development, through the MAPK, PI3K-Akt, Wnt and Insulin signaling pathways. This study provides new insights into the molecular mechanism underlying muscle mass loss in the SLD chickens, and some regulatory networks that are crucial for chicken skeletal muscle development. PMID:26927061

  14. Cooperativity effect involving drug-DNA/RNA intermolecular interaction: A B3LYP-D3 and MP2 theoretical investigation on ketoprofen⋯cytosine⋯H2O system.

    Science.gov (United States)

    Zhen, Jun-Ping; Wei, Xiao-Chun; Shi, Wen-Jing; Huang, Zhu-Yuan; Jin, Bo; Zhou, Yu-Kun

    2017-11-14

    In order to examine the origin of the drug action and design new DNA/RNA-targeted drugs, the cooperativity effect involving drug-DNA/RNA intermolecular interaction in ketoprofen⋯cytosine⋯H 2 O ternary system were investigated by the B3LYP, B3LYP-D3, and MP2 methods with the 6-311++G(2d,p) basis set. The thermodynamic cooperativity was also evaluated at 310.15 K. The N-H⋯O, O-H⋯O, O-H⋯N, C-H⋯N, and C-H⋯O H bonds coexist in ternary complexes. The intermolecular interactions obtained by B3LYP-D3 are close to those calculated by MP2. The steric effects and van der Waals interactions have little influence on the cooperativity effects. The anti-cooperativity effect in ket⋯cyt⋯H 2 O is far more notable than the cooperativity effect, and the stability of the cyclic structure with anti-cooperativity effect is higher than that of the linear structure with cooperativity effect, as is confirmed by the AIM (atoms in molecules) and RDG (reduced density gradient) analysis. Thus, it can be inferred that, in the presence of H 2 O, the anti-cooperativity effect plays a dominant role in the drug-DNA/RNA interaction, and the nature of the hydration in the binding of drugs to DNA/RNA bases is the H-bonding anti-cooperativity effect. Furthermore, the drug always links simultaneously with DNA/RNA base and H 2 O, and only in this way can the biological activity of drugs play a role. In most cases, the enthalpy change is the major factor driving the cooperativity, as is different from most of biomacromolecule complexes.

  15. A poor metabolizer of both CYP2C19 and CYP2D6 identified by mechanistic pharmacokinetic simulation in a fatal drug poisoning case involving venlafaxine

    DEFF Research Database (Denmark)

    Jornil, J; Nielsen, T S; Rosendal, I

    2013-01-01

    pharmacokinetic simulations suggested that the low metabolite ratio was the result of combined poor metabolizer (PM) status of cytochrome P450 (CYP) 2C19 and CYP2D6. This hypothesis was confirmed by genetic analysis. Simulations revealed that it was likely that the combined missing CYP2D6 and CYP2C19 activity...... would cause higher concentrations of VEN, but the simulations also suggested that there could be additional reasons to explain the high VEN concentration found in this case. Thus, it seems likely that the potentially toxic VEN concentration was caused by reduced metabolic capacity. The simulations...... combined with genotyping were considered very useful in this fatal drug poisoning case. Keywords CYP2D6; CYP2C19; Venlafaxine; Poor metabolizer; Drug poisoning; Mechanistic pharmacokinetic simulation --------------------------------------------------------------------------------...

  16. [Analysis of causes of the involvement in prophylactic examinations and the evaluation of the value of the body mass and the blood pressure at residents of Sanok district].

    Science.gov (United States)

    Smoleń, Ewa

    2014-02-01

    Prophylactic examinations allowing for the evaluation of the medical condition and the diagnosis of symptoms of illness in the preclinical stage is a crucial element of the prevention. The early diagnosis of disorders is improving the effectiveness of medicinal actions and rehabilitation, enhancing the possibility of getting well. It is of special importance in cardiovascular diseases which in Poland are recognised late and have become a fundamental health hazard. The aim of study was to evaluate causes of the participation in open days in the aspect of sociodemographic conditioning of residents of Sanok district and conducting the evaluation of their body mass and values of the blood pressure. The research was conducted in 2009 and in 2010 including the group of 215 persons during open days of the special hospital of the Independent Public Centre of Health Care in Sanok. In the accumulation of empirical material method of the diagnostic survey was used with applying the author's questionnaire of the survey form. The following techniques were applied: conducting a survey and the measurement of biophysical features (of body mass, height, blood pressure) with using measuring devices. Collected data were subjected to a statistical analysis with applying the chi-square test. The ease of access and desire for performing examinations and expectation of the evaluation of the medical condition decided in the main measure about the participation in this initiative. The greatest demand was for advice of the cardiologist. The correct BMI indicator has most often been evaluated in the group of people of the singleness and country dwellers. The obesity has more often been identified at persons after divorce, being married and of residents of cities. Almost at the every second person an arterial hypertension of blood was stated. Majority of the examined had the correct concentration of glucose in the blood on an empty stomach. Risk factors of cardiovascular diseases identified

  17. Method for manufacturing carrier containing e.g. proteins for human during oral drug delivery operation for food and drug administration application in pharmaceutical industry, involves providing active ingredient to core layer

    DEFF Research Database (Denmark)

    2015-01-01

    delivery operation for a food and drug administration (FDA) application in a pharmaceutical industry. ADVANTAGE - The method enables allowing an individual micro-structure stuck in an embossing stamp to be demolded under the conditions such that demolding operation is done by treating elastically...

  18. Soil transmitted helminths and scabies in Zanzibar, Tanzania following mass drug administration for lymphatic filariasis - a rapid assessment methodology to assess impact

    Science.gov (United States)

    2012-01-01

    Background Ivermectin and albendazole are used in annual mass drug administration (MDA) for the lymphatic filariasis elimination programmes in African countries co-endemic for onchocerciasis, but have additional impact on soil transmitted helminths and the ectoparasitic mite which causes scabies. Assessing these collateral impacts at scale is difficult due to the insensitivity of available parasite detection techniques. Methods The numbers of cases diagnosed with intestinal helminths and scabies and who received prescriptions for treatment were evaluated in 50 health centres in Zanzibar. Records were examined from 2000, prior to the initiation of MDA to 2005, after six rounds of MDA for lymphatic filariasis had taken place. Results Health centre records showed a consistent decline in the number of cases of intestinal helminths and scabies diagnosed by community health workers in Zanzibar and the number of prescriptions issued across five age groups. A 90-98% decline in soil transmitted helminths and 68-98% decline in scabies infections were recorded. Poisson regression models aggregated to both the island-level and district-level indicated that the decline was statistically significant. Conclusions The described method of examining health centre records has the potential for use on a large scale, despite limitations, as a rapid method to evaluate the impacts resulting from both lymphatic filariasis and onchocerciasis MDA. This would result in a reduction in the need for parasitological evaluations to determine prevalence and intensity. PMID:23259465

  19. Gas chromatography-electron ionization-mass spectrometry quantitation of valproic acid and gabapentin, using dried plasma spots, for therapeutic drug monitoring in in-home medical care.

    Science.gov (United States)

    Ikeda, Kayo; Ikawa, Kazuro; Yokoshige, Satoko; Yoshikawa, Satoshi; Morikawa, Norifumi

    2014-12-01

    A simpl