Don’t Flush! Why Your Drug Disposal Method Matters

EPA Science Inventory

April 30th is the U.S. Drug Enforcement Administration’s National Drug Take-Back Day. All over the country there will be facilities accepting any unwanted or expired medications from 10:00 AM – 2:00 PM – it is the perfect opportunity to clean out your medicine cabinet while simu...

Physical and Psychological Health Following Military Sexual Assault: Recommendations for Care, Research, and Policy

DTIC Science & Technology

2013-01-01

samples from the victim, if drug -assisted rape is sus- pected (DoJ, 2004; Regan and Kelley, 2003; WHO, 2003). DoJ recommends scheduling a follow-up...acterized by use of force, threats, intimidation, or abuse of authority or when the victim does not or cannot consent. Sexual assault includes rape, forc...ible sodomy (oral or anal sex), and other unwanted sexual contact that is aggravated, abusive , or wrongful (including unwanted and inappropriate

[Unwanted Side Effects in Children and Youth Psychotherapy - Introduction and Recommendations].

PubMed

Bieda, Angela; Pflug, Verena; Scholten, Saskia; Lippert, Michael Wilhelm; Ladwig, Inga; Nestoriuc, Yvonne; Schneider, Silvia

2018-05-30

Psychotherapy in children and adolescents is effective, but unwanted effects can occur. Until now, psychotherapy research has neglected this important topic, although children and youths are in need of special protection. Unwanted effects caused by therapy are not systematically investigated and a corresponding conceptualization is missing. The aim of this article is to investigate whether the current classifications of unwanted effects of psychotherapy in adults are applicable to children and adolescents and to identify distinctive features. Furthermore, the adaptation of the Inventory for the Assessment of Negative Effects of Psychotherapy for children and adolescents (Children-INEP) is presented. Finally, steps for the information and prevention of unwanted, and negative effects of psychotherapy in children and adolescents are pointed out. © Georg Thieme Verlag KG Stuttgart · New York.

Examining the effects of drinking and interpersonal protective behaviors on unwanted sexual experiences in college women.

PubMed

Sell, Nichole M; Turrisi, Rob; Scaglione, Nichole M; Hultgren, Brittney A; Mallett, Kimberly A

2016-03-01

Recent evidence suggests interpersonal protective behaviors (IPBs) may be more effective than alcohol-based strategies at decreasing alcohol-related sexual consequences. However, no studies have examined individual IPBs to assess their unique influences on specific sexual consequences. The current study used a longitudinal design to examine the direct effects of typical weekly drinking and specific IPBs on unwanted sex. IPBs were also examined as moderators of the relationship between drinking and unwanted sex. Randomly sampled female drinkers attending a northeastern university (N=191) completed a baseline survey measuring typical weekly drinking and IPBs and a six-month follow-up assessing unwanted sex. Bootstrapped regression examined the effects. Drinking predicted unwanted sex after accounting for IPBs (range of bs=.008-.009, SE=.005, 95% CI [.000, .02]). Vigilance-related IPBs were negatively associated with unwanted sex after controlling for drinking (b=-.052, SE=.025, 95% CI [-.107, -.008]). The IPB "Talking to people who know one's potential dating or sexual partner to find out what s/he is like" significantly moderated the drinking-unwanted sex relationship (b=-.009, SE=.004, 95% CI [-.018, -.003]). At above-average drinking levels, women who used this IPB more frequently reported fewer episodes of unwanted sex. Findings revealed obtaining information about a potential partner significantly reduced the impact of drinking on unwanted sex for heavier drinkers. Future research examining how women implement this IPB may clarify its role in reducing unwanted sex. Copyright © 2015 Elsevier Ltd. All rights reserved.

Delivery of Cancer Therapeutics Using Nanotechnology

PubMed Central

Lim, Eun-Kyung; Jang, Eunji; Lee, Kwangyeol; Haam, Seungjoo; Huh, Yong-Min

2013-01-01

Nanoparticles have been investigated as drug carriers, because they provide a great opportunity due to their advantageous features: (i) various formulations using organic/inorganic materials, (ii) easy modification of targeting molecules, drugs or other molecules on them, (iii) effective delivery to target sites, resulting in high therapeutic efficacy and (iv) controlling drug release by external/internal stimuli. Because of these features, therapeutic efficacy can be improved and unwanted side effects can be reduced. Theranostic nanoparticles have been developed by incorporating imaging agents in drug carriers as all-in-one system, which makes it possible to diagnose and treat cancer by monitoring drug delivery behavior simultaneously. Recently, stimuli-responsive, activatable nanomaterials are being applied that are capable of producing chemical or physical changes by external stimuli. By using these nanoparticles, multiple tasks can be carried out simultaneously, e.g., early and accurate diagnosis, efficient cataloguing of patient groups of personalized therapy and real-time monitoring of disease progress. In this paper, we describe various types of nanoparticles for drug delivery systems, as well as theranostic systems. PMID:24300452

Identification and characterization of carprofen as a multitarget fatty acid amide hydrolase/cyclooxygenase inhibitor.

PubMed

Favia, Angelo D; Habrant, Damien; Scarpelli, Rita; Migliore, Marco; Albani, Clara; Bertozzi, Sine Mandrup; Dionisi, Mauro; Tarozzo, Glauco; Piomelli, Daniele; Cavalli, Andrea; De Vivo, Marco

2012-10-25

Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the nonsteroidal anti-inflammatory drug carprofen as a multitarget-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2, and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several derivatives of carprofen, sharing this multitarget activity. This may result in improved analgesic efficacy and reduced side effects (Naidu et al. J. Pharmacol. Exp. Ther.2009, 329, 48-56; Fowler, C. J.; et al. J. Enzyme Inhib. Med. Chem.2012, in press; Sasso et al. Pharmacol. Res.2012, 65, 553). The new compounds are among the most potent multitarget FAAH/COX inhibitors reported so far in the literature and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs.

Evaluation of the Military Criminal Investigative Organizations’ Adult Sexual Assault Investigation Policies

DTIC Science & Technology

2014-09-16

efforts as well as for the victim’s well-being. Officers shall not coerce victims to go to the hospital or to provide samples for drug screening. G...is suspected, it is critical to obtain a urine sample from the victim as soon as possible. G G G 52 Protocols for responding to illegal substance...includes rape, forcible sodomy (oral or anal sex), and other unwanted sexual contact that is aggravated, abusive , or wrongful (to include unwanted and

Correlates of Unwanted Births in Bangladesh: A Study through Path Analysis.

PubMed

Roy, Tapan Kumar; Singh, Brijesh P

2016-01-01

Unwanted birth is an important public health concern due to its negative association with adverse outcomes of mothers and children as well as socioeconomic development of a country. Although a number of studies have been investigated the determinants of unwanted births through logistic regression analysis, an extensive assessment using path model is lacking. In the current study, we applied path analysis to know the important covariates for unwanted births in Bangladesh. The study used data extracted from Bangladesh Demographic and Health Survey (BDHS) 2011. It considered sub-sample consisted of 7,972 women who had given most recent births five years preceding the date of interview or who were currently pregnant at survey time. Correlation analysis was used to find out the significant association with unwanted births. This study provided the factors affecting unwanted births in Bangladesh. The path model was used to determine the direct, indirect and total effects of socio-demographic factors on unwanted births. The result exhibited that more than one-tenth of the recent births were unwanted in Bangladesh. The differentials of unwanted births were women's age, education, age at marriage, religion, socioeconomic status, exposure of mass-media and use of family planning. In correlation analysis, it showed that unwanted births were positively correlated with women age and place of residence and these relationships were significant. On the contrary, unwanted births were inversely significantly correlated with education and social status. The total effects of endogenous variables such as women age, place of residence and use of family planning methods had favorable effect on unwanted births. Policymakers and program planners need to design programs and services carefully to reduce unwanted births in Bangladesh, especially, service should focus on helping those groups of women who were identified in the analysis as being at increased risks of unwanted births- older women, illiterate, low socioeconomic status, early age at marriage and rural poor susceptible women.

Lifitegrast: First LFA-1/ICAM-1 antagonist for treatment of dry eye disease.

PubMed

Paton, D M

2016-09-01

Dry eye disease is an extremely common condition affecting millions worldwide. The underlying pathophysiological mechanism is thought to be localized inflammation of the ocular surface resulting in the localization of T cells at this surface followed by their activation and subsequent liberation of cytokines. This effect on T cells results from the binding of lymphocyte function-associated antigen-1 (LFA-1) located on T cells to intercellular adhesion molecule 1 (ICAM-1) expressed on inflamed epithelium and endothelium, and on T cells. Lifitegrast is a T-cell integrin antagonist designed to mimic ICAM-1, thus blocking the interaction of LFA-1 and ICAM-1. Lifitegrast enters the systemic circulation to a limited extent thus reducing the likelihood of unwanted systemic reactions. Clinical trials in over 2,500 subjects with dry eye disease have shown that 5.0% lifitegrast given by ocular instillation causes a significant reduction in objective and subjective signs and symptoms of the disease. These beneficial effects are associated with a relatively low incidence of unwanted effects, almost all local in nature. In light of these findings, lifitegrast was approved by the Food and Drug Administration (FDA) in 2016 for the treatment of dry eye disease, the first drug with this mechanism of action to be so approved. Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.

Adverse Effects of Common Drugs: Dietary Supplements.

PubMed

Felix, Todd Matthew; Karpa, Kelly Dowhower; Lewis, Peter R

2015-09-01

Dietary supplement-induced adverse effects often resolve quickly after discontinuation of the offending product, especially in younger patients. The potential for unwanted outcomes can be amplified in elderly patients or those taking multiple prescription drugs, especially where interactions exist with drugs metabolized by cytochrome P450 enzymes. Attributing injury or illness to a specific supplement can be challenging, especially in light of multi-ingredient products, product variability, and variability in reporting, as well as the vast underreporting of adverse drug reactions. Clinicians prescribing a new drug or evaluating a patient with a new symptom complex should inquire about use of herbal and dietary supplements as part of a comprehensive evaluation. Clinicians should report suspected supplement-related adverse effects to the local or state health department, as well as the Food and Drug Administration's MedWatch program (available at https://www.safetyreporting.hhs.gov). Clinicians should consider discussing suspected adverse effects involving drugs, herbal products, or dietary supplements with their community- and hospital-based pharmacists, and explore patient management options with medical or clinical toxicology subspecialists. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Examining the Effects of Drinking and Interpersonal Protective Behaviors on Unwanted Sexual Experiences in College Women

PubMed Central

Sell, Nichole M.; Turrisi, Rob; Scaglione, Nichole M.; Hultgren, Brittney A.; Mallett, Kimberly A.

2015-01-01

Introduction Recent evidence suggests interpersonal protective behaviors (IPBs) may be more effective than alcohol-based strategies at decreasing alcohol-related sexual consequences. However, no studies have examined individual IPBs to assess their unique influences on specific sexual consequences. The current study used a longitudinal design to examine the direct effects of typical weekly drinking and specific IPBs on unwanted sex. IPBs were also examined as moderators of the relationship between drinking and unwanted sex. Methods Randomly sampled female drinkers attending a northeastern university (N = 191) completed a baseline survey measuring typical weekly drinking and IPBs and a six-month follow-up assessing unwanted sex. Bootstrapped regression examined the effects. Results Drinking predicted unwanted sex after accounting for IPBs (range of bs = .008-.009, SE = .005, 95% CI [.000, .02]). Vigilance-related IPBs were negatively associated with unwanted sex after controlling for drinking (b = −.052, SE = .025, 95% CI [−.107, −.008]). The IPB “Talking to people who know one’s potential dating or sexual partner to find out what s/he is like” significantly moderated the drinking - unwanted sex relationship (b = −.009, SE = .004, 95% CI [−.018, −.003]). At above- average drinking levels, women who used this IPB more frequently reported fewer episodes of unwanted sex. Conclusion Findings revealed obtaining information about a potential partner significantly reduced the impact of drinking on unwanted sex for heavier drinkers. Future research examining how women implement this IPB may clarify its role in reducing unwanted sex. PMID:26706612

Perceptions of sexual coercion: learning from young people in Ibadan, Nigeria.

PubMed

Ajuwon, A J; Akin-Jimoh, I; Olley, B O; Akintola, O

2001-05-01

This study explored the problem of sexual coercion from the perspectives of 77 young people aged 14-21 in Ibadan, Nigeria, the behaviours they perceive to be sexually coercive and the contexts in which these occur through four narrative workshops. Participants were drawn from two secondary schools and 15 apprentice workshops. All four groups identified similar coercive behaviours and developed narratives of the events that typically lead up to them. Behaviours included rape, unwanted touching, incest, assault, verbal abuse, threats, unwanted kissing; forced exposure to pornographic films, use of drugs for sedation and traditional charms for seduction, and insistence on abortion if unwanted pregnancy occurs. Men were typically the perpetrators and young women the victims. Perpetrators included acquaintances, boyfriends, neighbours, parents and relatives. All the narratives revealed the inability of young people to communicate effectively with each other and resolve differences. The results suggest the need for life-skills training that facilitates communication, seeks to redress gender power imbalances, teaches alternatives to coercion as a means of resolving conflict over sexual relations and respect for sexual and reproductive rights, and provides victims with information on appropriate services, support and referral.

Approaches to Mitigate the Unwanted Immunogenicity of Therapeutic Proteins during Drug Development.

PubMed

Salazar-Fontana, Laura I; Desai, Dharmesh D; Khan, Tarik A; Pillutla, Renuka C; Prior, Sandra; Ramakrishnan, Radha; Schneider, Jennifer; Joseph, Alexandra

2017-03-01

All biotherapeutics have the potential to induce an immune response. This immunological response is complex and, in addition to antibody formation, involves T cell activation and innate immune responses that could contribute to adverse effects. Integrated immunogenicity data analysis is crucial to understanding the possible clinical consequences of anti-drug antibody (ADA) responses. Because patient- and product-related factors can influence the immunogenicity of a therapeutic protein, a risk-based approach is recommended and followed by most drug developers to provide insight over the potential harm of unwanted ADA responses. This paper examines mitigation strategies currently implemented and novel under investigation approaches used by drug developers. The review describes immunomodulatory regimens used in the clinic to mitigate deleterious ADA responses to replacement therapies for deficiency syndromes, such as hemophilia A and B, and high risk classical infantile Pompe patients (e.g., cyclophosphamide, methotrexate, rituximab); novel in silico and in vitro prediction tools used to select candidates based on their immunogenicity potential (e.g., anti-CD52 antibody primary sequence and IFN beta-1a formulation); in vitro generation of tolerogenic antigen-presenting cells (APCs) to reduce ADA responses to factor VIII and IX in murine models of hemophilia; and selection of novel delivery systems to reduce in vivo ADA responses to highly immunogenic biotherapeutics (e.g., asparaginase). We conclude that mitigation strategies should be considered early in development for biotherapeutics based on our knowledge of existing clinical data for biotherapeutics and the immune response involved in the generation of these ADAs.

Drug-induced gingival overgrowth: The nemesis of gingiva unravelled.

PubMed

Bharti, Vipin; Bansal, Chhaya

2013-03-01

Drug-induced gingival overgrowth or enlargement manifests as abnormal growth of the gingiva due to an adverse drug reaction (ADR) in patients treated with anticonvulsants, immunosuppressants, and calcium channel blockers. As gingival enlargement develops, it affects the normal oral hygiene practice and may interfere with masticatory functions. It gradually becomes a source of pain and the condition often leads to disfiguration. Within the group of patients that develop this unwanted effect, there appears to be variability in the extent and severity of the gingival changes. It would seem pertinent to identify and explore possible risk factors and relating them with the treatment plan. This article throws light on respective drugs and their association with gingival overgrowth and approaches to treatment based on current knowledge and investigative observations.

State-of-the-art in design rules for drug delivery platforms: lessons learned from FDA-approved nanomedicines.

PubMed

Dawidczyk, Charlene M; Kim, Chloe; Park, Jea Ho; Russell, Luisa M; Lee, Kwan Hyi; Pomper, Martin G; Searson, Peter C

2014-08-10

The ability to efficiently deliver a drug to a tumor site is dependent on a wide range of physiologically imposed design constraints. Nanotechnology provides the possibility of creating delivery vehicles where these design constraints can be decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing targeting efficiency and efficacy. Here we review the design strategies of the two FDA-approved antibody-drug conjugates (Brentuximab vedotin and Trastuzumab emtansine) and the four FDA-approved nanoparticle-based drug delivery platforms (Doxil, DaunoXome, Marqibo, and Abraxane) in the context of the challenges associated with systemic targeted delivery of a drug to a solid tumor. The lessons learned from these nanomedicines provide an important insight into the key challenges associated with the development of new platforms for systemic delivery of anti-cancer drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Impact of Modafinil Add-on with Atypical Anti-psychotics on Excessive Daytime Drowsiness

PubMed Central

Prasuna, P Lakshmi; Sudhakar, TP

2015-01-01

Background: Atypical antipsychotic drugs are known to cause many side effects which include daytime drowsiness. So many add on drugs are tried to reduce the same. Materials and Methods: 72 patients who were on atypical antipsychotic drugs were randomly assigned to either Modafinil or placebo and were followed for a period of 12 weeks. Daytime drowsiness, was taken at baseline, week 3, and at week 12 by using VAS, EDD scales. Results: The results were analyzed and showed that the Modafinil add on therapy significantly reduced the daytime Drowsiness. Conclusions: Modafinil could be a potential candidate in selected group of patients to decrease some of the unwanted adverse events like daytime drowsiness produced by atypical antipsychotics. PMID:26702168

Elaborations on sexual assault on dates among Israeli students: risk, detrimental effect, and resilience factors.

PubMed

Shechory Bitton, Mally; Ben-David, Sarah

2014-12-01

The current study of 668 Israeli male and female students examines the prevalence of gendered risk factors for sexual assault (SA) on dates, posttraumatic stress disorder (PTSD) as a detrimental effect of SA, and self-efficacy as resiliency to refuse unwanted sex following SA. Two different sets of risk factors that increased the likelihood of SA on dates emerged from the hierarchical regression. Sexual experience, use of drugs, and private location increased the risk of being SA victims among males, whereas sexual experience, perceived provocative behavior, and alcohol use increased the risk among females. In addition, PTSD and self-efficacy to refuse unwanted sex following SA on dates were predicted by the extent of coercive sexual victimization. PTSD was also predicted by subjective perception of sexual behavior and rape myths, whereas efficacy was predicted by private location. The findings contribute to the literature by showing the contribution of various risk factors to experiencing SA, and by showing SA effect on PTSD and self-efficacy. © The Author(s) 2013.

Drug Reactions

MedlinePlus

Most of the time, medicines make our lives better. They reduce aches and pains, fight infections, and control problems such as high blood pressure or diabetes. But medicines can also cause unwanted reactions. One problem is ...

Microencapsulation of Drugs in the Microgravity Environment of the United States Space Shuttle.

DTIC Science & Technology

safety tested, and flew hardware we call the Microencapsulation in Space (MIS) experiment. The MIS experiment flew on Space Shuttle Discovery...of the same composition. From our experience, these improved properties should improve the release properties of microencapsulated drugs and...eliminate unwanted residual process aids. Furthermore, it is likely that microencapsulation in space will let us encapsulate drugs that cannot be microencapsulated on the earth

[Threshold value for reimbursement of costs of new drugs: cost-effectiveness research and modelling are essential links].

PubMed

Frederix, Geert W J; Hövels, Anke M; Severens, Johan L; Raaijmakers, Jan A M; Schellens, Jan H M

2015-01-01

There is increasing discussion in the Netherlands about the introduction of a threshold value for the costs per extra year of life when reimbursing costs of new drugs. The Medicines Committee ('Commissie Geneesmiddelen'), a division of the Netherlands National Healthcare Institute ('Zorginstituut Nederland'), advises on reimbursement of costs of new drugs. This advice is based upon the determination of therapeutic value of the drug and the results of economic evaluations. Mathematical models that predict future costs and effectiveness are often used in economic evaluations; these models can vary greatly in transparency and quality due to author assumptions. Standardisation of cost-effectiveness models is one solution to overcome the unwanted variation in quality. Discussions about the introduction of a threshold value can only be meaningful if all involved are adequately informed, and by high quality in cost-effectiveness research and, particularly, economic evaluations. Collaboration and discussion between medical specialists, patients or patient organisations, health economists and policy makers, both in development of methods and in standardisation, are essential to improve the quality of decision making.

Inhaled Micro/Nanoparticulate Anticancer Drug Formulations: An Emerging Targeted Drug Delivery Strategy for Lung Cancers.

PubMed

Islam, Nazrul; Richard, Derek

2018-05-24

Local delivery of drug to the target organ via inhalation offers enormous benefits in the management of many diseases. Lung cancer is the most common of all cancers and it is the leading cause of death worldwide. Currently available treatment systems (intravenous or oral drug delivery) are not efficient in accumulating the delivered drug into the target tumor cells and are usually associated with various systemic and dose-related adverse effects. The pulmonary drug delivery technology would enable preferential accumulation of drug within the cancer cell and thus be superior to intravenous and oral delivery in reducing cancer cell proliferation and minimising the systemic adverse effects. Site-specific drug delivery via inhalation for the treatment of lung cancer is both feasible and efficient. The inhaled drug delivery system is non-invasive, produces high bioavailability at low dose and avoids first pass metabolism of the delivered drug. Various anticancer drugs including chemotherapeutics, proteins and genes have been investigated for inhalation in lung cancers with significant outcomes. Pulmonary delivery of drugs from dry powder inhaler (DPI) formulation is stable and has high patient compliance. Herein, we report the potential of pulmonary drug delivery from dry powder inhaler (DPI) formulations inhibiting lung cancer cell proliferation at very low dose with reduced unwanted adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium.

PubMed

Rup, B; Pallardy, M; Sikkema, D; Albert, T; Allez, M; Broet, P; Carini, C; Creeke, P; Davidson, J; De Vries, N; Finco, D; Fogdell-Hahn, A; Havrdova, E; Hincelin-Mery, A; C Holland, M; H Jensen, P E; Jury, E C; Kirby, H; Kramer, D; Lacroix-Desmazes, S; Legrand, J; Maggi, E; Maillère, B; Mariette, X; Mauri, C; Mikol, V; Mulleman, D; Oldenburg, J; Paintaud, G; R Pedersen, C; Ruperto, N; Seitz, R; Spindeldreher, S; Deisenhammer, F

2015-09-01

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp). © 2015 British Society for Immunology.

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium

PubMed Central

Rup, B; Pallardy, M; Sikkema, D; Albert, T; Allez, M; Broet, P; Carini, C; Creeke, P; Davidson, J; De Vries, N; Finco, D; Fogdell-Hahn, A; Havrdova, E; Hincelin-Mery, A; C Holland, M; H Jensen, P E; Jury, E C; Kirby, H; Kramer, D; Lacroix-Desmazes, S; Legrand, J; Maggi, E; Maillère, B; Mariette, X; Mauri, C; Mikol, V; Mulleman, D; Oldenburg, J; Paintaud, G; R Pedersen, C; Ruperto, N; Seitz, R; Spindeldreher, S; Deisenhammer, F

2015-01-01

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; http://www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; http://www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp). PMID:25959571

Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications

PubMed Central

Labiris, N R; Dolovich, M B

2003-01-01

As the end organ for the treatment of local diseases or as the route of administration for systemic therapies, the lung is a very attractive target for drug delivery. It provides direct access to disease in the treatment of respiratory diseases, while providing an enormous surface area and a relatively low enzymatic, controlled environment for systemic absorption of medications. As a major port of entry, the lung has evolved to prevent the invasion of unwanted airborne particles from entering into the body. Airway geometry, humidity, mucociliary clearance and alveolar macrophages play a vital role in maintaining the sterility of the lung and consequently are barriers to the therapeutic effectiveness of inhaled medications. In addition, a drug's efficacy may be affected by where in the respiratory tract it is deposited, its delivered dose and the disease it may be trying to treat. PMID:14616418

The Discovery and Development of Drug Combinations for the Treatment of Various Diseases from Patent Literature (1980-Present).

PubMed

Kleczkowska, Patrycja; Kowalczyk, Agnieszka; Lesniak, Anna; Bujalska-Zadrozny, Magdalena

2017-01-01

The search for a miracle drug that would help to alleviate multiple ailments, dates back many thousands of years before our era and continues until today. Various techniques have been used to obtain a formulation, that would give the desired therapeutic effect. The most popular approach includes drug coctails and multicomponent drugs. Polytherapy is widely accapted as an effective tool for the treatment of several diseases, however it is often faced with important drawbacks that may sometimes result in fatal adverse effects associated with unpredictable drug interactions. Conversly, hybrid compounds were found to be an attractive way to counterbalance the unwanted side effects derived from the administration of individual drug components. Futhermore, they can serve as effective and improved remedies for patients suffering from several diseases simultaneously, as different receptorrelated pharmacophores are used as structural components. This review covers patent literature from 1980 till now that highlights the progress that has been made in the discovery of hybrid compounds potentially useful in the treatment on various disorders, including pain states, neurodegenerative or infectious diseases. Additionally, this review was further enriched with findings from original research papers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Formulation and delivery strategies of ibuprofen: challenges and opportunities.

PubMed

Irvine, Jake; Afrose, Afrina; Islam, Nazrul

2018-02-01

Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is mostly administered orally and topically to relieve acute pain and fever. Due to its mode of action this drug may be useful in the treatment regimens of other, more chronic conditions, like cystic fibrosis. This drug is poorly soluble in aqueous media and thus the rate of dissolution from the currently available solid dosage forms is limited. This leads to poor bioavailability at high doses after oral administration, thereby increasing the risk of unwanted adverse effects. The poor solubility is a problem for developing injectable solution dosage forms. Because of its poor skin permeability, it is difficult to obtain an effective therapeutic concentration from topical preparations. This review aims to give a brief insight into the status of ibuprofen dosage forms and their limitations, particle/crystallization technologies for improving formulation strategies as well as suggesting its incorporation into the pulmonary drug delivery systems for achieving better therapeutic action at low dose.

Identification and characterization of carprofen as a multi-target FAAH/COX inhibitor

PubMed Central

Favia, Angelo D.; Habrant, Damien; Scarpelli, Rita; Migliore, Marco; Albani, Clara; Bertozzi, Sine Mandrup; Dionisi, Mauro; Tarozzo, Glauco; Piomelli, Daniele; Cavalli, Andrea; De Vivo, Marco

2013-01-01

Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the non-steroid anti-inflammatory drug, carprofen, as a multi-target-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2 and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several racemic derivatives of carprofen, sharing this multi-target activity. This may result in improved analgesic efficacy and reduced side effects (Naidu, et al (2009) J Pharmacol Exp Ther 329, 48-56; Fowler, C.J. et al. (2012) J Enzym Inhib Med Chem Jan 6; Sasso, et al (2012) Pharmacol Res 65, 553). The new compounds are among the most potent multi-target FAAH/COXs inhibitors reported so far in the literature, and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs. PMID:23043222

Narrowband UV-B phototherapy in the treatment of cutaneous graft versus host disease.

PubMed

Grundmann-Kollmann, Marcella; Martin, Hans; Ludwig, Ralf; Klein, Stefan; Boehncke, Wolf-Henning; Hoelzer, Dieter; Kaufmann, Roland; Podda, Maurizio

2002-12-15

Graft versus host disease (GVHD) is an important problem following allogenic bone marrow transplantation (BMT). The beneficial effects of photochemotherapy with psoralens plus UVA irradiation (PUVA) have been described repeatedly; however, PUVA is limited by a wide range of unwanted effects. A novel improved form of UV-B phototherapy, narrowband UV-B, has been proven to be very effective in T-cell mediated dermatoses. Therefore, we investigated the effect of narrowband UV-B phototherapy (5 times per week) in 10 patients with cutaneous GVHD (grade 2-3) resistant to standard immunosuppressive drugs. It was tolerated well by all patients, and no side effects were observed. Skin lesions showed complete clearance in 7 out of 10 patients within 3 to 5 weeks. 3 patients showed significant improvement of GVHD. We suggest that narrowband UV-B phototherapy is a nonaggressive treatment that may benefit patients with cutaneous GVHD who already take high doses of immunosuppressive drugs.

Strategies of targeting oral drug delivery systems to the colon and their potential use for the treatment of colorectal cancer.

PubMed

Krishnaiah, Yellela S R; Khan, Mansoor A

2012-01-01

Colorectal cancer (CRC) is the third most common cause of cancer-related death in both men and women. Often, surgical intervention remains the choice in treating CRC. Traditional dosage forms used for treating CRC deliver drug to wanted as well as unwanted sites of drug action resulting in several adverse side effects. Targeted oral drug delivery systems are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific delivery of a drug to colon increases its concentration at the target site, and thus requires a lower dose with reduced incidence of side effects. The major obstacle to be overcome for successful targeting of drug to colon through oral route is that drug absorption/degradation must be avoided in stomach and small intestine before the dosage form reaches colon. The review includes discussion of physiological factors that must be considered when targeting drugs directly to colorectal region, an outline on drugs used for treatment and prevention of CRC, and a brief description of various types of colon-targeted oral drug delivery systems. The focus is on the assessment of various formulation approaches being investigated for oral colon-specific delivery of drugs used in the treatment and prevention of CRC.

Analysis of Hypericin-Mediated Effects and Implications for Targeted Photodynamic Therapy

PubMed Central

Mühleisen, Laura; Alev, Magdalena; Unterweger, Harald; Subatzus, Daniel; Pöttler, Marina; Friedrich, Ralf P.; Alexiou, Christoph; Janko, Christina

2017-01-01

The phototoxic effect of hypericin can be utilized for Photodynamic Therapy (PDT) of cancer. After intravenous application and systemic distribution of the drug in the patient’s body, the tumor site is exposed to light. Subsequently, toxic reactive oxygen species (ROS) are generated, inducing tumor cell death. To prevent unwanted activation of the drug in other regions of the body, patients have to avoid light during and after the treatment cycles, consequently impairing quality of life. Here, we characterize toxicity and hypericin-mediated effects on cancer cells in vitro and confirm that its effect clearly depends on concentration and illumination time. To reduce side effects and to increase therapy success, selective accumulation of hypericin in the tumor region is a promising solution. Loading hypericin on superparamagnetic iron oxide nanoparticles (SPIONs) and guiding them to the desired place using an external magnetic field might accomplish this task (referred to as Magnetic Drug Targeting (MDT)). Thus, using a double targeting strategy, namely magnetic accumulation and laser induced photoactivation, might improve treatment effectivity as well as specificity and reduce toxic side effects in future clinical applications. PMID:28661430

Analysis of Hypericin-Mediated Effects and Implications for Targeted Photodynamic Therapy.

PubMed

Mühleisen, Laura; Alev, Magdalena; Unterweger, Harald; Subatzus, Daniel; Pöttler, Marina; Friedrich, Ralf P; Alexiou, Christoph; Janko, Christina

2017-06-29

The phototoxic effect of hypericin can be utilized for Photodynamic Therapy (PDT) of cancer. After intravenous application and systemic distribution of the drug in the patient's body, the tumor site is exposed to light. Subsequently, toxic reactive oxygen species (ROS) are generated, inducing tumor cell death. To prevent unwanted activation of the drug in other regions of the body, patients have to avoid light during and after the treatment cycles, consequently impairing quality of life. Here, we characterize toxicity and hypericin-mediated effects on cancer cells in vitro and confirm that its effect clearly depends on concentration and illumination time. To reduce side effects and to increase therapy success, selective accumulation of hypericin in the tumor region is a promising solution. Loading hypericin on superparamagnetic iron oxide nanoparticles (SPIONs) and guiding them to the desired place using an external magnetic field might accomplish this task (referred to as Magnetic Drug Targeting (MDT)). Thus, using a double targeting strategy, namely magnetic accumulation and laser induced photoactivation, might improve treatment effectivity as well as specificity and reduce toxic side effects in future clinical applications.

How to acquire new biological activities in old compounds by computer prediction

NASA Astrophysics Data System (ADS)

Poroikov, V. V.; Filimonov, D. A.

2002-11-01

Due to the directed way of testing chemical compounds' in drug research and development many projects fail because serious adverse effects and toxicity are discovered too late, and many existing prospective activities remain unstudied. Evaluation of the general biological potential of molecules is possible using a computer program PASS that predicts more than 780 pharmacological effects, mechanisms of action, mutagenicity, carcinogenicity, etc. on the basis of structural formulae of compounds, with average accuracy ˜85%. PASS applications to both databases of available samples included hundreds of thousands compounds, and small collections of compounds synthesized by separate medicinal chemists are described. It is shown that 880 compounds from Prestwick chemical library represent a very diverse pharmacological space. New activities can be found in existing compounds by prediction. Therefore, on this basis, the selection of compounds with required and without unwanted properties is possible. Even when PASS cannot predict very new activities, it may recognize some unwanted actions at the early stage of R&D, providing the medicinal chemist with the means to increase the efficiency of projects.

Sperm-Hybrid Micromotor for Targeted Drug Delivery.

PubMed

Xu, Haifeng; Medina-Sánchez, Mariana; Magdanz, Veronika; Schwarz, Lukas; Hebenstreit, Franziska; Schmidt, Oliver G

2018-01-23

A sperm-driven micromotor is presented as a targeted drug delivery system, which is appealing to potentially treat diseases in the female reproductive tract. This system is demonstrated to be an efficient drug delivery vehicle by first loading a motile sperm cell with an anticancer drug (doxorubicin hydrochloride), guiding it magnetically, to an in vitro cultured tumor spheroid, and finally freeing the sperm cell to deliver the drug locally. The sperm release mechanism is designed to liberate the sperm when the biohybrid micromotor hits the tumor walls, allowing it to swim into the tumor and deliver the drug through the sperm-cancer cell membrane fusion. In our experiments, the sperm cells exhibited a high drug encapsulation capability and drug carrying stability, conveniently minimizing  toxic side effects and unwanted drug accumulation in healthy tissues. Overall, sperm cells are excellent candidates to operate in physiological environments, as they neither express pathogenic proteins nor proliferate to form undesirable colonies, unlike other cells or microorganisms. This sperm-hybrid micromotor is a biocompatible platform with potential application in gynecological healthcare, treating or detecting cancer or other diseases in the female reproductive system.

Neuropathic Pain and Lung Delivery of Nanoparticulate Drugs: An Emerging Novel Therapeutic Strategy.

PubMed

Islam, Nazrul; Abbas, Muzaffar; Rahman, Shafiqur

2017-01-01

Neuropathic pain is a chronic neurological disorder affecting millions of people around the world. The currently available pharmacologic agents for the treatment of neuropathic pain have limited efficacy and are associated with dose related unwanted adverse effects. Due to the limited access of drug molecules across blood-brain barrier, a small percentage of drug that is administered systematically, reaches the central nervous system in active form. These therapeutic agents also require daily treatment regimen that is inconvenient and potentially impact patient compliance. Application of nanoparticulate drugs for enhanced delivery system has been explored extensively in the last decades. Pulmonary delivery of nanomedicines for the management of various diseases has become an emerging treatment strategy that ensures the targeted delivery of drugs both for systemic and local effects with low dose and limited adverse effects. To the best of our knowledge, there are no inhaled drug products available on market for the treatment of neuropathic pain. The advantages of delivering therapeutics into deep lungs include non-invasive drug delivery, higher bioavailability with low dose, lower systemic toxicity, and potentially greater blood-brain barrier penetration. This review discusses and highlights the important issues on the application of emerging nanoparticulate lung delivery of drugs for the effective treatment of neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Nanoparticles and the blood coagulation system. Part II: safety concerns

PubMed Central

Ilinskaya, Anna N; Dobrovolskaia, Marina A

2014-01-01

Nanoparticle interactions with the blood coagulation system can be beneficial or adverse depending on the intended use of a nanomaterial. Nanoparticles can be engineered to be procoagulant or to carry coagulation-initiating factors to treat certain disorders. Likewise, they can be designed to be anticoagulant or to carry anticoagulant drugs to intervene in other pathological conditions in which coagulation is a concern. An overview of the coagulation system was given and a discussion of a desirable interface between this system and engineered nanomaterials was assessed in part I, which was published in the May 2013 issue of Nanomedicine. Unwanted pro- and anti-coagulant properties of nanoparticles represent significant concerns in the field of nanomedicine, and often hamper the development and transition into the clinic of many promising engineered nanocarriers. This part will focus on the undesirable effects of engineered nanomaterials on the blood coagulation system. We will discuss the relationship between the physicochemical properties of nanoparticles (e.g., size, charge and hydrophobicity) that determine their negative effects on the blood coagulation system in order to understand how manipulation of these properties can help to overcome unwanted side effects. PMID:23730696

Gender scripts and unwanted pregnancy among urban Kenyan women.

PubMed

Izugbara, Chimaraoke O; Ochako, Rhoune; Izugbara, Chibuogwu

2011-10-01

Women's lived experiences and lay accounts of unwanted pregnancy remain poorly interrogated. We investigated portrayals of unwanted pregnancy using narrative data gathered from 80 women in Nairobi, Kenya. Unwanted pregnancy had a diversity of significance for the women. Pregnancies were not simply unwanted because they occurred when women became pregnant without wanting to. Rather, pregnancies were considered unwanted largely because they had occurred in contexts that did not reinforce socially-sanctioned notions of motherhood and 'proper' procreation and/or revealed women's use of their sexuality in ways deemed culturally-inappropriate. Kenyan women's invocation of femininity scripts to explain unwanted pregnancy; the centrality of gender in everyday life in contemporary Kenya; women's and girls' poor access to effective family planning services; growing female poverty; and Kenya's restrictive abortion policy imply that unwanted pregnancy and its consequences will persist in the country. Addressing unwanted pregnancy and its consequences requires making accessible quality contraceptive and abortion services as well as sexuality information. It also calls for providers who understand the socio-cultural norms that circumscribe fertility and reproductive behaviours.

[Unwanted children].

PubMed

Sulová, L; Fait, T

2009-06-01

Aim of the study is review of knowledges about psychosocial aspects of unwanted pregnancy for child. Literary review. Department of psychology, Faculty of psychology, Charles University Prague. In our review article we give results of studies which evaluate physical, psychological and social aspects of beeing unwanted baby. Especially we show unique results of Prague study. The majority of studies confirm that unwanted children are significantly discriminated against wanted children. Unwanted children have more diseases, worse school result with identical inteligence quotient, higher frequency of nervous and psychosomatic disables and worse social adaptibility. Results of studies confirm order to find for every women safe and effective method for familly planning.

Unwanted sexual activity among married women in urban China.

PubMed

Parish, William L; Luo, Ye; Laumann, Edward O; Kew, Melissa; Yu, Zhiyuan

2007-05-01

This paper examines the prevalence, precursors, and consequences of unwanted marital sex activities in a national sample of 1,127 married urban Chinese women aged 20-64. During the lifetime of their current marriage, 32% reported ever experiencing unwanted spousal intercourse, with about one-fifth reporting that this unwanted intercourse ever involved force. Reports for the past year were 21% unwanted intercourse, 22% unwanted sex act(s), and 72% sex only to please the husband. The major risk factors for these activities were poor relationship quality (hitting, lack of daily intimacy and foreplay, and husband insensitivity to wife's sexual needs); a woman's negative attitudes towards sex, and weak bargaining position (low income share, husband's family of superior economic status, and no additional adults in home). In addition, unwanted activity was more common when women reported sexual dysfunctions (dryness, pain, low arousal, inorgasmia), were more educated, and had more permissive sex attitudes. Net of feedback effects, unwanted sexual activity diminished women's psychological well-being.

Drugs and the Environment: Stewardship and Sustainability

EPA Science Inventory

This report represents the first-ever comprehensive examination of the broad scope of issues surrounding the topic of disposal of unwanted, unneeded, leftover medications from consumer use and the countless ways in which the introduction of active pharmaceutical ingredients (API...

Tools for translation: non-viral materials for therapeutic mRNA delivery

NASA Astrophysics Data System (ADS)

Hajj, Khalid A.; Whitehead, Kathryn A.

2017-10-01

In recent years, messenger RNA (mRNA) has come into the spotlight as a versatile therapeutic with the potential to prevent and treat a staggering range of diseases. Billions of dollars have been invested in the commercial development of mRNA drugs, with ongoing clinical trials focused on vaccines (for example, influenza and Zika viruses) and cancer immunotherapy (for example, myeloma, leukaemia and glioblastoma). Although significant progress has been made in the design of in vitro-transcribed mRNA that retains potency while minimizing unwanted immune responses, the widespread use of mRNA drugs requires the development of safe and effective drug delivery vehicles. In this Review, we provide an overview of the field of mRNA therapeutics and describe recent advances in the development of synthetic materials that encapsulate and deliver mRNA payloads.

Why biosecurity matters: students' knowledge of biosecurity and implications for future engagement with biosecurity initiatives

NASA Astrophysics Data System (ADS)

Ram, Rajesh; France, Bev; Birdsall, Sally

2016-01-01

Background: Research on biosecurity is important as New Zealand's agricultural export-driven economy is susceptible to biosecurity threats. Because New Zealand is reliant on the primary industries to drive its economy, bovine diseases such as foot and mouth could have a devastating effect on the economy. Purpose: Making sure that the general public are aware of the importance of maintaining biosecurity is crucial in order to protect New Zealand's economy, human health, the environment, and social and cultural values. New Zealand Year 9 students' knowledge of biosecurity was gauged as these students represented the next generation of individuals tasked to maintain biosecurity in New Zealand. Design: A qualitative approach using the interpretive mode of inquiry was used to investigate the knowledge about biosecurity with New Zealand Year 9 students. Questionnaires and interviews were the data collection tools. Sample: One hundred and seventy-one students completed a questionnaire that consisted of Likert-type questions and open-ended questions. Nine students were interviewed about their knowledge. Results: The findings showed that New Zealand Year 9 students lacked specific knowledge about unwanted plants, animals and microorganisms. These students saw illicit drug plants as unwanted plants and mainly saw possums as unwanted animals in New Zealand. Their knowledge about unwanted microorganisms in New Zealand was dominated by human-disease-causing microbes. A lack of knowledge of biosecurity issues in New Zealand was seen as the major factor in these students limited understanding of biosecurity. Conclusions: Based on these findings, it can be said that knowledge of an issue is critical in enabling individuals to develop an understanding about biosecurity. Explicit teaching of biosecurity-related curriculum topics could provide New Zealand Year 9 students with an opportunity to develop knowledge about biosecurity in New Zealand.

Cyclosporine A: Novel concepts in its role in drug-induced gingival overgrowth

PubMed Central

Ponnaiyan, Deepa; Jegadeesan, Visakan

2015-01-01

Cyclosporine is a selective immunosuppressant that has a variety of applications in medical practice. Like phenytoin and the calcium channel blockers, the drug is associated with gingival overgrowth. This review considers the pharmacokinetics, pharmacodynamics, and unwanted effects of cyclosporine, in particular the action of the drug on the gingival tissues. In addition, elucidates the current concepts in mechanisms of cyclosporine-induced gingival overgrowth. Clinical and cell culture studies suggest that the mechanism of gingival overgrowth is a result of the interaction between the drug and its metabolites with susceptible gingival fibroblasts. Plaque-induced gingival inflammation appears to enhance this interaction. However, understanding of the pathogenesis of gingival overgrowth is incomplete at best. Hence, it would be pertinent to identify and explore possible risk factors relating to both prevalence and severity of drug-induced gingival overgrowth. Newer molecular approaches are needed to clearly establish the pathogenesis of gingival overgrowth and to provide novel information for the design of future preventive and therapeutic modalities. PMID:26759584

Cyclosporine A: Novel concepts in its role in drug-induced gingival overgrowth.

PubMed

Ponnaiyan, Deepa; Jegadeesan, Visakan

2015-01-01

Cyclosporine is a selective immunosuppressant that has a variety of applications in medical practice. Like phenytoin and the calcium channel blockers, the drug is associated with gingival overgrowth. This review considers the pharmacokinetics, pharmacodynamics, and unwanted effects of cyclosporine, in particular the action of the drug on the gingival tissues. In addition, elucidates the current concepts in mechanisms of cyclosporine-induced gingival overgrowth. Clinical and cell culture studies suggest that the mechanism of gingival overgrowth is a result of the interaction between the drug and its metabolites with susceptible gingival fibroblasts. Plaque-induced gingival inflammation appears to enhance this interaction. However, understanding of the pathogenesis of gingival overgrowth is incomplete at best. Hence, it would be pertinent to identify and explore possible risk factors relating to both prevalence and severity of drug-induced gingival overgrowth. Newer molecular approaches are needed to clearly establish the pathogenesis of gingival overgrowth and to provide novel information for the design of future preventive and therapeutic modalities.

Social support and pregnancy: II. Its relationship with depressive symptoms among Japanese women.

PubMed

Kitamura, T; Toda, M A; Shima, S; Sugawara, K; Sugawara, M

1998-02-01

In a questionnaire survey among 1329 first-trimester pregnant women, both the husband support measures and unwanted pregnancy ('stressor' agent in pregnancy) showed significant effects on an elevated score of the cognitive disturbance subscale of the Zung's self-rating depression scale (SDS), while only unwanted pregnancies showed an effect on an elevated score of the dysphoric mood subscale of the SDS. However, no interaction was observed between the husband support measures and unwanted pregnancy, therefore the effect of the husband's social support on the cognitive disturbance score was not that of a buffer, but rather a main effector. Finally, multiple regression analyses showed that the dysphoric mood score was preceded by unwanted pregnancy, premenstrual irritability, public self-consciousness, and maternal overprotection; while the cognitive disturbance score was preceded by unwanted pregnancy, husband reduced 'given' and 'giving' support, maternal reduced care and overprotection, paternal reduced care, low annual income, low private self-consciousness, and smoking. These findings suggest that the husband's support for a pregnant woman is effective only in reducing cognitive symptoms, and that different symptomatic constellations have different sets of psychosocial correlates.

Alternative approaches to conventional antiepileptic drugs in the management of paediatric epilepsy

PubMed Central

Kneen, R; Appleton, R E

2006-01-01

Over the last two decades, there has been a rapid expansion in the number and types of available antiepileptic drugs (AEDs), but there is increasing concern amongst parents and carers about their unwanted side effects. Seizure control is achieved in approximately 75% of children treated with conventional AEDs, but non‐conventional (or non‐standard) medical treatments, surgical procedures, dietary approaches, and other non‐pharmacological treatment approaches may have a role to play in those with intractable seizures or AED toxicity. Many of the approaches are largely common sense and are already incorporated into our current practice, including, for example, avoidance techniques and lifestyle advice, while others require further investigation or appear to be impractical in children. PMID:17056869

Flirting with disaster: short-term mating orientation and hostile sexism predict different types of sexual harassment.

PubMed

Diehl, Charlotte; Rees, Jonas; Bohner, Gerd

2012-01-01

We combine evolutionary and sociocultural accounts of sexual harassment, proposing that sexuality-related and hostility-related motives lead to different types of harassment. Specifically, men's short-term mating orientation (STMO) was hypothesized to predict only unwanted sexual attention but not gender harassment, whereas men's hostile sexism (HS) was hypothesized to predict both unwanted sexual attention and gender harassment. As part of an alleged computer-chat task, 100 male students could send sexualized personal remarks (representing unwanted sexual attention), sexist jokes (representing gender harassment), or nonharassing material to an attractive female target. Independently, participants' STMO, HS, and sexual harassment myth acceptance (SHMA) were assessed. Correlational and path analyses revealed that STMO specifically predicted unwanted sexual attention, whereas HS predicted both unwanted sexual attention and gender harassment. Furthermore, SHMA fully mediated the effect of HS on gender harassment, but did not mediate effects of STMO or HS on unwanted sexual attention. Results are discussed in relation to motivational explanations for sexual harassment and antiharassment interventions. © 2012 Wiley Periodicals, Inc.

77 FR 8264 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-14

... leukemia, hairy cell leukemia and pediatric acute lymphoblastic leukemia Competitive Advantages: Targeted... such as chemotherapy or radiation therapy. Unfortunately, the continued administration of immunotoxins... complex regional pain syndrome (CRPS). However the routine use of the drug is hindered by unwanted central...

Computational Approaches to Drug Repurposing and Pharmacology

PubMed Central

Hodos, Rachel A; Kidd, Brian A; Khader, Shameer; Readhead, Ben P; Dudley, Joel T

2016-01-01

Data in the biological, chemical, and clinical domains are accumulating at ever-increasing rates and have the potential to accelerate and inform drug development in new ways. Challenges and opportunities now lie in developing analytic tools to transform these often complex and heterogeneous data into testable hypotheses and actionable insights. This is the aim of computational pharmacology, which uses in silico techniques to better understand and predict how drugs affect biological systems, which can in turn improve clinical use, avoid unwanted side effects, and guide selection and development of better treatments. One exciting application of computational pharmacology is drug repurposing- finding new uses for existing drugs. Already yielding many promising candidates, this strategy has the potential to improve the efficiency of the drug development process and reach patient populations with previously unmet needs such as those with rare diseases. While current techniques in computational pharmacology and drug repurposing often focus on just a single data modality such as gene expression or drug-target interactions, we rationalize that methods such as matrix factorization that can integrate data within and across diverse data types have the potential to improve predictive performance and provide a fuller picture of a drug's pharmacological action. PMID:27080087

Phenotypic Screening Approaches to Develop Aurora Kinase Inhibitors: Drug Discovery Perspectives.

PubMed

Marugán, Carlos; Torres, Raquel; Lallena, María José

2015-01-01

Targeting mitotic regulators as a strategy to fight cancer implies the development of drugs against key proteins, such as Aurora-A and -B. Current drugs, which target mitosis through a general mechanism of action (stabilization/destabilization of microtubules), have several side effects (neutropenia, alopecia, and emesis). Pharmaceutical companies aim at avoiding these unwanted effects by generating improved and selective drugs that increase the quality of life of the patients. However, the development of these drugs is an ambitious task that involves testing thousands of compounds through biochemical and cell-based assays. In addition, molecules usually target complex biological processes, involving several proteins and different molecular pathways, further emphasizing the need for high-throughput screening techniques and multiplexing technologies in order to identify drugs with the desired phenotype. We will briefly describe two multiplexing technologies [high-content imaging (HCI) and flow cytometry] and two key processes for drug discovery research (assay development and validation) following our own published industry quality standards. We will further focus on HCI as a useful tool for phenotypic screening and will provide a concrete example of HCI assay to detect Aurora-A or -B selective inhibitors discriminating the off-target effects related to the inhibition of other cell cycle or non-cell cycle key regulators. Finally, we will describe other assays that can help to characterize the in vitro pharmacology of the inhibitors.

The use of lorcaserin in the management of obesity: a critical appraisal

PubMed Central

Bai, Bo; Wang, Yu

2011-01-01

Obesity is a chronic disease with a high prevalence in both developed and developing countries. Effective management of this worldwide epidemic will have a significant impact on the health care system globally. Lifestyle interventions, such as restricting calorie consumption and increasing physical activity, remain a major component of weight-reduction programs. The development of pharmacotherapy for the management of obesity is still at the infancy stage. Side effects have been the key issue for anti-obesity drugs previously withdrawn from the market. The focus of this review, lorcaserin, is a selective serotonin receptor agonist that is currently undergoing Phase III evaluations. The efficacy of this drug in reducing body weight and improving metabolic parameters of obese patients has been demonstrated in two recent clinical trials. The available evidence indicates that this drug does not show unwanted effects on heart valves or pulmonary artery pressure, and the treatment improves the risk factors for type 2 diabetes and cardiovascular diseases. Despite these promising results, additional experimental and clinical studies are critical for the approval of lorcaserin as a new anti-obesity monodrug therapy by the US Food and Drug Administration. PMID:21267355

The use of lorcaserin in the management of obesity: a critical appraisal.

PubMed

Bai, Bo; Wang, Yu

2010-12-20

Obesity is a chronic disease with a high prevalence in both developed and developing countries. Effective management of this worldwide epidemic will have a significant impact on the health care system globally. Lifestyle interventions, such as restricting calorie consumption and increasing physical activity, remain a major component of weight-reduction programs. The development of pharmacotherapy for the management of obesity is still at the infancy stage. Side effects have been the key issue for anti-obesity drugs previously withdrawn from the market. The focus of this review, lorcaserin, is a selective serotonin receptor agonist that is currently undergoing Phase III evaluations. The efficacy of this drug in reducing body weight and improving metabolic parameters of obese patients has been demonstrated in two recent clinical trials. The available evidence indicates that this drug does not show unwanted effects on heart valves or pulmonary artery pressure, and the treatment improves the risk factors for type 2 diabetes and cardiovascular diseases. Despite these promising results, additional experimental and clinical studies are critical for the approval of lorcaserin as a new anti-obesity monodrug therapy by the US Food and Drug Administration.

An Expanding World of Novel Psychoactive Substances: Opioids

PubMed Central

Zawilska, Jolanta B.

2017-01-01

The abuse of novel psychoactive substances (NPS) has been increasing dramatically worldwide since late 2000s. By the end of 2015, more than 560 NPS had been reported to the European Monitoring Centre for Drugs and Drug Addiction. Although the most popular compounds are synthetic cannabinoids and psychostimulatory derivatives of cathinone (so-called β-keto-amphetamines), novel synthetic opioids have recently emerged on the recreational drug market. They include fentanyl (a potent narcotic analgesic) and its analogs (e.g., acetylfentanyl, acryloylfentanyl, carfentanil, α-methylfentanyl, 3-methylfentanyl, furanylfentanyl, 4-fluorobutyrylfentanyl, 4-methoxybutyrylfentanyl, 4-chloroisobutyrylfentanyl, 4-fluoroisobutyrylfentanyl, tetrahydrofuranylfentanyl, cyclopentylfentanyl, and ocfentanil) and compounds with different chemical structures, such as AH-7921, MT-45, and U-47700. This survey provides an overview of the pharmacological properties, pattern of use, and desired and unwanted effects of the above-listed novel opioids. Special emphasis is given to cases of non-fatal and lethal intoxication involving these compounds. PMID:28713291

The development of Bruton's tyrosine kinase (BTK) inhibitors from 2012 to 2017: A mini-review.

PubMed

Liang, Chengyuan; Tian, Danni; Ren, Xiaodong; Ding, Shunjun; Jia, Minyi; Xin, Minhang; Thareja, Suresh

2018-05-10

Bruton's tyrosine kinase (BTK) has emerged as a promising drug target for multiple diseases, particularly haematopoietic malignancies and autoimmune diseases related to B lymphocytes. This review focuses on the diverse, small-molecule inhibitors of BTK kinase that have shown good prospects for clinical application. Individual examples of these inhibitors, including both reversible and irreversible inhibitors and a recently developed reversible covalent inhibitor of BTK, are discussed. Considerable progress has been made in the development of irreversible inhibitors, most of which target the SH3 pocket and the cysteine 481 residue of BTK. The present review also surveys the pharmacological advantages and deficiencies of both reversible and irreversible BTK drugs, with a focus on the structure-activity relationship (SARs) and binding modes of representative drugs, which could inspire critical thinking and new ideas for developing potent BTK inhibitors with less unwanted off-target effects. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Laser-ultrasonic technologies for medicine

NASA Astrophysics Data System (ADS)

Zharov, Vladimir P.; Latyshev, Alexei S.

1999-06-01

This review tackles the problem of further developing laser- ultrasonic medical technologies and gives the comparison of different laser and ultrasound combinations. The features of combined influence on biotissue are explicated with due regard for mechanic, ultrasonic (US), and thermal effects. The review present the effect of self-cleaning an optical fiber tip from the laser destruction products of biotissue, the result of research on the possibility of laser-US technology applications in endoscopy, and the ways of suppressing unwanted bending oscillations. Various spheres and peculiarities of applying laser-US technologies are discussed, including microsurgery, cosmetology, transcutaneous drug delivery, and the treatment of chronic prostatitis and infected wounds. Furthermore, the analysis of transcutaneous drug delivery methods employing a portable pulsed Er:YAG laser is presented. Drug diffusion has been shown to be enhanced under acoustic and US effects. The photo-vacuum drug injection mechanism recently suggested is discussed. It turned out that laser-US technology can be suitable for both impregnating the photosensitizer in local photodynamic therapy procedures and conducting microsurgery operations involving drug injection. Treatment of infectious processes based on the bactericidal action of photosensitizers and ultrasound due to the cavitation effect in solutions is described. An additional therapeutic effect can be achieved via the US intermingling of solutions with their simulations illumination by a matrix of red lasers or light diodes. An outlook on further developing laser-US technology and the ways of its apparatus realization are considered.

Drug Take Back in Hawai‘i: Partnership Between the University of Hawai‘i Hilo College of Pharmacy and the Narcotics Enforcement Division

PubMed Central

Batz, Forrest; Juarez, Deborah Taira; Ladao, Lani C

2014-01-01

Unused/unwanted medications in households and patient care facilities expose vulnerable populations, including children, elders, and pets, to potential harm through inadvertent ingestion, as well as the potential for theft and assault. Hawai‘i Administrative Rules prohibit the return of any prescription medications to retail pharmacies after dispensing. The Hawai‘i Narcotics Enforcement Division (NED) partnered with the University of Hawai‘i at Hilo Daniel K. Inouye College of Pharmacy (CoP) in eleven Drug Take Back events throughout the state. Most participants heard of the events via newspaper and television marketing. The most common methods of medication disposal are via trash or down household drains. Over 8,000 lbs of unused/unwanted medications was collected, identified and logged from 2011 through 2012. The majority of returned drugs were non-controlled substances (90%). Commonly returned medications included prescription cardiac medications such as simvastatin and lisinopril, non-prescription analgesics such as aspirin and ibuprofen, and dietary supplements such as vitamins and iron. Commonly returned controlled substance medications included narcotics such as hydrocodone/acetaminophen combinations and oxycodone, and sedative hypnotics such as zolpidem and lorazepam. PMID:24470984

Drug take back in Hawai'i: partnership between the University of Hawai'i Hilo College of Pharmacy and the Narcotics Enforcement Division.

PubMed

Ma, Carolyn S; Batz, Forrest; Juarez, Deborah Taira; Ladao, Lani C

2014-01-01

Unused/unwanted medications in households and patient care facilities expose vulnerable populations, including children, elders, and pets, to potential harm through inadvertent ingestion, as well as the potential for theft and assault. Hawai'i Administrative Rules prohibit the return of any prescription medications to retail pharmacies after dispensing. The Hawai'i Narcotics Enforcement Division (NED) partnered with the University of Hawai'i at Hilo Daniel K. Inouye College of Pharmacy (CoP) in eleven Drug Take Back events throughout the state. Most participants heard of the events via newspaper and television marketing. The most common methods of medication disposal are via trash or down household drains. Over 8,000 lbs of unused/unwanted medications was collected, identified and logged from 2011 through 2012. The majority of returned drugs were non-controlled substances (90%). Commonly returned medications included prescription cardiac medications such as simvastatin and lisinopril, non-prescription analgesics such as aspirin and ibuprofen, and dietary supplements such as vitamins and iron. Commonly returned controlled substance medications included narcotics such as hydrocodone/acetaminophen combinations and oxycodone, and sedative hypnotics such as zolpidem and lorazepam.

The hERG K+ channel: target and antitarget strategies in drug development.

PubMed

Raschi, Emanuel; Vasina, Valentina; Poluzzi, Elisabetta; De Ponti, Fabrizio

2008-03-01

The human ether-à-go-go related gene (hERG) K+ channel is of great interest for both basic researchers and clinicians because its blockade by drugs can lead to QT prolongation, which is a risk factor for torsades de pointes, a potentially life-threatening arrhythmia. A growing list of agents with "QT liability" have been withdrawn from the market or restricted in their use, whereas others did not even receive regulatory approval for this reason. Thus, hERG K+ channels have become a primary antitarget (i.e. an unwanted target) in drug development because their blockade causes potentially serious side effects. On the other hand, the recent identification and functional characterization of hERG K+ channels not only in the heart, but also in several other tissues (e.g. neurons, smooth muscle and cancer cells) may have far reaching implications for drug development for a possible exploitation of hERG as a target, especially in oncology and cardiology.

Highlights in Endocytosis of Nanostructured Systems.

PubMed

Voltan, Aline R; Alarcon, Kaila M; Fusco-Almeida, Ana M; Soares, Christiane P; Mendes-Giannini, Maria J S; Chorilli, Marlus

2017-01-01

The focus of this review is the cellular internalisation mechanism of nanostructured systems (NSs) and their endosomal escape for targeted drug delivery. Endocytosis is a cellular process of internalisation of different molecules and foreign microorganisms. It is currently being studied for drug delivery through nanostructured systems. The most commonly studied routes of cellular uptake are phagocytosis, macro-pinocytosis, clathrinmediated endocytosis, caveolin-mediated endocytosis, and clathrin and caveolinindependent endocytosis. The mechanism utilised by NSs for cellular entry depends on factors such as cell type and its physicochemical properties. Currently, with the development of drugs-loaded onto NSs, it has been possible to increase the therapeutic index against few diseases. The NSs can deliver the active drug at locations that conventional drugs cannot, thereby minimising unwanted side effects. On cellular entry of NSs, there is a possibility of an endosomal escape of the contents into the cytoplasm, a mechanism that can be exploited so that NSs can migrate intra-cellularly and deliver the drug to the target of interest. Designing endolysosomal escape strategy is not an easy task, but it is critical for the optimal pharmacological action on the target tissue. The cellular uptake of drugs is a very important factor in therapy. Although NSs have emerged as effective drug delivery vehicle for treatment of diseases, it is crucial to understand the mechanism of NSs endocytosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Regulation of Organic Anion Transporting Polypeptides (OATP) 1B1- and OATP1B3-Mediated Transport: An Updated Review in the Context of OATP-Mediated Drug-Drug Interactions.

PubMed

Alam, Khondoker; Crowe, Alexandra; Wang, Xueying; Zhang, Pengyue; Ding, Kai; Li, Lang; Yue, Wei

2018-03-14

Organic anion transporting polypeptides (OATP) 1B1 and OATP1B3 are important hepatic transporters that mediate the uptake of many clinically important drugs, including statins from the blood into the liver. Reduced transport function of OATP1B1 and OATP1B3 can lead to clinically relevant drug-drug interactions (DDIs). Considering the importance of OATP1B1 and OATP1B3 in hepatic drug disposition, substantial efforts have been given on evaluating OATP1B1/1B3-mediated DDIs in order to avoid unwanted adverse effects of drugs that are OATP substrates due to their altered pharmacokinetics. Growing evidences suggest that the transport function of OATP1B1 and OATP1B3 can be regulated at various levels such as genetic variation, transcriptional and post-translational regulation. The present review summarizes the up to date information on the regulation of OATP1B1 and OATP1B3 transport function at different levels with a focus on potential impact on OATP-mediated DDIs.

Regulation of Organic Anion Transporting Polypeptides (OATP) 1B1- and OATP1B3-Mediated Transport: An Updated Review in the Context of OATP-Mediated Drug-Drug Interactions

PubMed Central

Alam, Khondoker; Crowe, Alexandra; Wang, Xueying; Zhang, Pengyue; Ding, Kai; Li, Lang; Yue, Wei

2018-01-01

Organic anion transporting polypeptides (OATP) 1B1 and OATP1B3 are important hepatic transporters that mediate the uptake of many clinically important drugs, including statins from the blood into the liver. Reduced transport function of OATP1B1 and OATP1B3 can lead to clinically relevant drug-drug interactions (DDIs). Considering the importance of OATP1B1 and OATP1B3 in hepatic drug disposition, substantial efforts have been given on evaluating OATP1B1/1B3-mediated DDIs in order to avoid unwanted adverse effects of drugs that are OATP substrates due to their altered pharmacokinetics. Growing evidences suggest that the transport function of OATP1B1 and OATP1B3 can be regulated at various levels such as genetic variation, transcriptional and post-translational regulation. The present review summarizes the up to date information on the regulation of OATP1B1 and OATP1B3 transport function at different levels with a focus on potential impact on OATP-mediated DDIs. PMID:29538325

Drug-induced Liver Injury

PubMed Central

David, Stefan; Hamilton, James P

2011-01-01

Drug-induced liver injury (DILI) is common and nearly all classes of medications can cause liver disease. Most cases of DILI are benign, and improve after drug withdrawal. It is important to recognize and remove the offending agent as quickly as possible to prevent the progression to chronic liver disease and/or acute liver failure. There are no definite risk factors for DILI, but pre-existing liver disease and genetic susceptibility may predispose certain individuals. Although most patients have clinical symptoms that are identical to other liver diseases, some patients may present with symptoms of systemic hypersensitivity. Treatment of drug and herbal-induced liver injury consists of rapid drug discontinuation and supportive care targeted to alleviate unwanted symptoms. PMID:21874146

ACCUMULATION AND DISPOSAL OF LEFTOVER MEDICATIONS: A KEY ASPECT OF PHARMECOVIGILANCE

EPA Science Inventory

In this paper, we focus on one of the aspects of pharmEcovigilance that has been receiving growing attention, especially in the U.S. — the accumulation and disposal of unwanted, leftover medications. The magnitude of drug stockpiling and accumulation, and eventual disposal of lef...

Antisense oligonucleotide technologies in drug discovery.

PubMed

Aboul-Fadl, Tarek

2006-09-01

The principle of antisense oligonucleotide (AS-OD) technologies is based on the specific inhibition of unwanted gene expression by blocking mRNA activity. It has long appeared to be an ideal strategy to leverage new genomic knowledge for drug discovery and development. In recent years, AS-OD technologies have been widely used as potent and promising tools for this purpose. There is a rapid increase in the number of antisense molecules progressing in clinical trials. AS-OD technologies provide a simple and efficient approach for drug discovery and development and are expected to become a reality in the near future. This editorial describes the established and emerging AS-OD technologies in drug discovery.

Resisting Unwanted Sexual and Social Advances: Perspectives of College Women and Men.

PubMed

Orchowski, Lindsay M; Gidycz, Christine A; Kraft, Kathryn

2018-06-01

This study examines college men's ( N = 635) and women's ( N = 650) reports of women's resistance against unwanted sexual and social advances. Men completed surveys to assess (a) initiation of unwanted sexual contact with a female partner, (b) initiation of unwanted sexual intercourse with a female partner, (c) sexual situations where a female partner decided she did not want to proceed, (d) encouraging a woman to drink when they were aware that the woman did not want to, and (e) attempting to take a woman to an isolated location against her will. Women completed corresponding questionnaires regarding the receipt of such unwanted advances, the outcome of the situation, and the resistance tactics utilized. Many men (5%-46%) and women (15%-38%) initiated or experienced, respectively, at least one of the five unwanted sexual or social advances. Unwanted sexual and social advances most often stopped as a result of women's verbal and physical resistance. Few advances (0%-8%) stopped as a result of bystander intervention. In addition to decreasing men's likelihood of engaging in unwanted sexual and social advances, these data highlight the importance of educating women on the effectiveness of verbal and physical resistance tactics, and increasing the frequency of prosocial bystander action on college campuses.

Dual orexin receptor antagonists - promising agents in the treatment of sleep disorders.

PubMed

Pałasz, Artur; Lapray, Damien; Peyron, Christelle; Rojczyk-Gołębiewska, Ewa; Skowronek, Rafał; Markowski, Grzegorz; Czajkowska, Beata; Krzystanek, Marek; Wiaderkiewicz, Ryszard

2014-01-01

Insomnia is a serious medical and social problem, its prevalence in the general population ranges from 9 to 35% depending on the country and assessment method. Often, patients are subject to inappropriate and therefore dangerous pharmacotherapies that include prolonged administration of hypnotic drugs, benzodiazepines and other GABAA receptor modulators. This usually does not lead to a satisfactory improvement in patients' clinical states and may cause lifelong drug dependence. Brain state transitions require the coordinated activity of numerous neuronal pathways and brain structures. It is thought that orexin-expressing neurons play a crucial role in this process. Due to their interaction with the sleep-wake-regulating neuronal population, they can activate vigilance-promoting regions and prevent unwanted sleep intrusions. Understanding the multiple orexin modulatory effects is crucial in the context of pathogenesis of insomnia and should lead to the development of novel treatments. An important step in this process was the synthesis of dual antagonists of orexin receptors. Crucially, these drugs, as opposed to benzodiazepines, do not change the sleep architecture and have limited side-effects. This new pharmacological approach might be the most appropriate to treat insomnia.

A FRET-guided, NIR-responsive bubble-generating liposomal system for in vivo targeted therapy with spatially and temporally precise controlled release.

PubMed

Chuang, Er-Yuan; Lin, Chia-Chen; Chen, Ko-Jie; Wan, De-Hui; Lin, Kun-Ju; Ho, Yi-Cheng; Lin, Po-Yen; Sung, Hsing-Wen

2016-07-01

The nonspecific distribution of therapeutic agents and nontargeted heating commonly produce undesirable side effects during cancer treatment since the optimal timing of triggering the carrier systems is unknown. This work proposes a multifunctional liposomal system that can intracellularly and simultaneously deliver the therapeutic drug doxorubicin (DOX), heat, and a bubble-generating agent (ammonium bicarbonate, ABC) into targeted tumor cells to have a cytotoxic effect. Gold nanocages that are encapsulated in liposomes effectively convert near-infrared light irradiation into localized heat, which causes the decomposition of ABC and generates CO2 bubbles, rapidly triggering the release of DOX. Additionally, a hybridized Mucin-1 aptamer is conjugated on the surface of the test liposomes, which then function as a recognition probe to enhance the uptake of those liposomes by cells, and as a molecular beacon to signal when the internalized particles have been maximized, which is the optimal time for photothermally triggering the release of the drug following the systemic administration of the liposomes. Empirical results reveal that this combined treatment effectively controls targeted drug release in a spatially and temporally precise fashion and so significantly increases the potency of the drug while minimizing unwanted side effects, making it a promising treatment for cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-P-glycoprotein conjugated nanoparticles for targeting drug delivery in cancer treatment.

PubMed

Iangcharoen, Pantiwa; Punfa, Wanisa; Yodkeeree, Supachai; Kasinrerk, Watchara; Ampasavate, Chadarat; Anuchapreeda, Songyot; Limtrakul, Pornngarm

2011-10-01

Targeting therapeutics to specific sites can enhance the efficacy of drugs, reduce required doses as well as unwanted side effects. In this work, using the advantages of the specific affinity of an immobilized antibody to membrane P-gp in two different nanoparticle formulations were thus developed for targeted drug delivery to multi-drug resistant cervical carcinoma (KB-V1) cells. Further, this was compared to the human drug sensitive cervical carcinoma cell line (KB-3-1) cells. The two nanoparticle preparations were: NP1, anti-P-gp conjugated with poly (DL-lactic-coglycolic acid) (PLGA) nanoparticle and polyethylene glycol (PEG); NP2, anti-P-gp conjugated to a modified poloxamer on PLGA nanoparticles. The cellular uptake capacity of nanoparticles was confirmed by fluorescent microscopy. Comparing with each counterpart core particles, there was a higher fluorescence intensity of the targeted nanoparticles in KBV1 cells compared to KB-3-1 cells suggesting that the targeted nanoparticles were internalized into KB-V1 cells to a greater extent than KB-3-1 cell. The results had confirmed the specificity and the potential of the developed targeted delivery system for overcoming multi-drug resistance induced by overexpression of P-gp on the cell membrane.

Cell-Based Biohybrid Drug Delivery Systems: The Best of the Synthetic and Natural Worlds.

PubMed

Banskota, Samagya; Yousefpour, Parisa; Chilkoti, Ashutosh

2017-01-01

The goal of drug delivery is to deliver therapeutics to the site of disease while reducing unwanted side effects. In recent years, a diverse variety of synthetic nano and microparticles have been developed as drug delivery systems. The success of these systems for drug delivery lies in their ability to overcome biological barriers such as the blood-brain barrier, to evade immune clearance and avoid nonspecific biodistribution. This Review provides an overview of recent advances in the design of biohybrid drug delivery systems, which combine cells with synthetic systems to overcome some of these biological hurdles. Examples include eukaryotic cells, such as stem cells, red blood cells, immune cells, platelets, and cancer cells that are used to carry drug-loaded synthetic particles. Synthetic particles can also be cloaked with naturally derived cell membranes and thereby evade immune clearance, exhibit prolonged systemic circulation, and target specific tissues by capitalizing on the interaction/homing tendency of certain cells and their membrane components to particular tissues. Different designs of cell-based biohybrid systems and their applications, as well as their promise and limitations, are discussed herein. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Review of Nanoparticle Photosensitizer Drug Delivery Uptake Systems for Photodynamic Treatment of Lung Cancer.

PubMed

Gift, Mokwena Mpho; Ann, Kruger Cherie; Ivan, Mfouo-Tynga; Heidi, Abrahamse

2018-03-24

Lung cancer is a leading cause of cancer related deaths worldwide and so current research is focused on trying to improve treatment modalities, such as photodynamic therapy (PDT). PDT has 3 fundamental factors, namely a photosensitizer (PS) drug, light and oxygen. When a PS drug is administered to a patient, it can either passively or actively accumulate within a tumour site and once exposed to a specific wavelength of light, it is stimulated to produce reactive oxygen species (ROS), resulting in tumour destruction. However, the efficacy of ROS generation for tumour destruction is highly dependent on the accumulation of the PS in tumour cells. Thus PS selective / targeted uptake and delivery in tumour cells is a crucial factor in PDT cancer drug absorption studies. Generally, within non-targeted drug delivery mechanisms, only small amounts of PS is able to passively accumulates in tumour sites due to the enhanced permeability and retention (EPR) effect and the remainder distributes into healthy tissues, causing side effects. Thus to improve the efficacy of PDT, research is currently focused on the development of specific receptor based photosynthetic nanocarrier drugs, which promotes the active uptake and absorption of PS drugs in tumour sites only, avoiding unwanted side effects. The aim of this review is to focus on current non-targeted passive versus specifically active targeted PS nanoparticle drug delivery systems, that have been investigated for the PDT treatment of lung cancer and so to deduce its efficacy and recent advancements. Copyright © 2018. Published by Elsevier B.V.

Teens' Survey of Stores in the District of Columbia on Accessibility of Family Planning Methods.

ERIC Educational Resources Information Center

Center for Population Options, Washington, DC.

Access to and availability of contraceptive methods in stores play an important role in the prevention of AIDS, unwanted pregnancies, and other sexually transmitted diseases. Although teens are generally knowledgable about birth control, many encounter barriers when attempting to obtain contraceptive. Forty-five drug stores and 15 convenience…

Women and Substance Abuse. Technical Assistance Packet.

ERIC Educational Resources Information Center

Join Together, Boston, MA.

There are many issues concerning women of all ages and substance abuse. Women who abuse alcohol or other drugs are particularly at risk for sexual assault; unprotected sex; unwanted pregnancies; and sexually transmitted diseases. Females between the ages of 12 and 17 surpass males in their use of cigarettes; cocaine; crack; inhalants; and…

[Peroral and transdermal application of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of regional musculoskeletal pain syndromes].

PubMed

Hodinka, László; Bálint, Géza; Budai, Erika; Géher, Pál; Papp, Renáta; Somogyi, Péter; Szántó, Sándor; Vereckei, Edit

2017-12-01

In this review the available evidences regarding the most frequently applied medication (peroral and transdermal non-steroidal anti-inflammatory agents) for the most frequent musculoskeletal complaints (regional pain syndromes) have been collected for the appropriate medical professionals who are most frequently faced with these conditions (general practitioners, rheumatologists, orthopedics, occupational and sports medicine experts). The special population at risk (with repeated and high energy overuse because of occupational or sport activities) and the pathology of their syndromes are identified. Mode of action, pharmacological properties of the non-steroidal anti-inflammatory drugs and the unwanted effects of their application especially in infants and elderly are highlighted. Recommendations of the general and specific pain management guidelines have been selected and listed in the review. Orv Hetil. 2017; 158(Suppl. 3): 3-30.

Reasons why undergraduate women comply with unwanted, non-coercive sexual advances: A serial indirect effect model integrating sexual script theory and sexual self-control perspectives.

PubMed

Quinn-Nilas, Christopher; Kennett, Deborah J

2018-01-16

This study explored the predictors of young women's compliance with unwanted sexual activities, integrating the social with the cognitive and behavioral correlates of sexual compliance. In total, 222 young heterosexual women completed measures examining the Sexual Self-Control model, including reasons for consenting, sexual resourcefulness, and compliance with unwanted sex, as well as gender role measures pertaining to sexual script theory, including the sexual double standard, gender role stress, and virginity scripts. An exploratory analysis of serial indirect effects demonstrated that women scoring lower in sexual resourcefulness endorsed higher female gender role stress, which in turn was associated with higher endorsement of reasons for consent, translating into more frequent compliance with unwanted sexual activities. The relationship between one's ability to refuse and their decision to refuse appears quite complex. Understanding one's decision requires consideration of the social aspects of gender role endorsement.

Convection shapes the trade-off between antibiotic efficacy and the selection for resistance in spatial gradients.

PubMed

Gralka, Matti; Fusco, Diana; Martis, Stephen; Hallatschek, Oskar

2017-07-19

Since penicillin was discovered about 90 years ago, we have become used to using drugs to eradicate unwanted pathogenic cells. However, using drugs to kill bacteria, viruses or cancer cells has the serious side effect of selecting for mutant types that survive the drug attack. A crucial question therefore is how one could eradicate as many cells as possible for a given acceptable risk of drug resistance evolution. We address this general question in a model of drug resistance evolution in spatial drug gradients, which recent experiments and theories have suggested as key drivers of drug resistance. Importantly, our model takes into account the influence of convection, resulting for instance from blood flow. Using stochastic simulations, we study the fates of individual resistance mutations and quantify the trade-off between the killing of wild-type cells and the rise of resistance mutations: shallow gradients and convection into the antibiotic region promote wild-type death, at the cost of increasing the establishment probability of resistance mutations. We can explain these observed trends by modeling the adaptation process as a branching random walk. Our analysis reveals that the trade-off between death and adaptation depends on the relative length scales of the spatial drug gradient and random dispersal, and the strength of convection. Our results show that convection can have a momentous effect on the rate of establishment of new mutations, and may heavily impact the efficiency of antibiotic treatment.

Convection shapes the trade-off between antibiotic efficacy and the selection for resistance in spatial gradients

NASA Astrophysics Data System (ADS)

Gralka, Matti; Fusco, Diana; Martis, Stephen; Hallatschek, Oskar

2017-08-01

Since penicillin was discovered about 90 years ago, we have become used to using drugs to eradicate unwanted pathogenic cells. However, using drugs to kill bacteria, viruses or cancer cells has the serious side effect of selecting for mutant types that survive the drug attack. A crucial question therefore is how one could eradicate as many cells as possible for a given acceptable risk of drug resistance evolution. We address this general question in a model of drug resistance evolution in spatial drug gradients, which recent experiments and theories have suggested as key drivers of drug resistance. Importantly, our model takes into account the influence of convection, resulting for instance from blood flow. Using stochastic simulations, we study the fates of individual resistance mutations and quantify the trade-off between the killing of wild-type cells and the rise of resistance mutations: shallow gradients and convection into the antibiotic region promote wild-type death, at the cost of increasing the establishment probability of resistance mutations. We can explain these observed trends by modeling the adaptation process as a branching random walk. Our analysis reveals that the trade-off between death and adaptation depends on the relative length scales of the spatial drug gradient and random dispersal, and the strength of convection. Our results show that convection can have a momentous effect on the rate of establishment of new mutations, and may heavily impact the efficiency of antibiotic treatment.

Novel therapies in advanced renal cell carcinoma: management of adverse events from sorafenib and sunitinib.

PubMed

Ivanyi, Philipp; Winkler, Thomas; Ganser, Arnold; Reuter, Christoph; Grünwald, Viktor

2008-03-01

Sorafenib and Sunitinib are the first tyrosine kinase inhibitors licensed for the treatment of advanced renal cell carcinoma. In contrast to conventional chemotherapy, targeted therapies have distinct and specific side effects. Selective review in Medline and the data base of the American Society of Clinical Oncology on the treatment and side effects of tyrosine kinase inhibitors in renal cell carcinoma, drawing on the authors' own experience. Tyrosine kinase inhibitors are characterized by a variety of uncommon side effects, such as lassitude, mucosal inflammation and skin changes. The detection and treatment of adverse events are critical for interdisciplinary cancer treatment in order to ensure patients' safety. This article offers an overview of the unwanted effects of drug therapy in the management of renal cell carcinoma.

Engineered Context-Sensitive Agonism: Tissue-Selective Drug Signaling through a G Protein-Coupled Receptor.

PubMed

Seemann, Wiebke K; Wenzel, Daniela; Schrage, Ramona; Etscheid, Justine; Bödefeld, Theresa; Bartol, Anna; Warnken, Mareille; Sasse, Philipp; Klöckner, Jessica; Holzgrabe, Ulrike; DeAmici, Marco; Schlicker, Eberhard; Racké, Kurt; Kostenis, Evi; Meyer, Rainer; Fleischmann, Bernd K; Mohr, Klaus

2017-02-01

Drug discovery strives for selective ligands to achieve targeted modulation of tissue function. Here we introduce engineered context-sensitive agonism as a postreceptor mechanism for tissue-selective drug action through a G protein-coupled receptor. Acetylcholine M 2 -receptor activation is known to mediate, among other actions, potentially dangerous slowing of the heart rate. This unwanted side effect is one of the main reasons that limit clinical application of muscarinic agonists. Herein we show that dualsteric (orthosteric/allosteric) agonists induce less cardiac depression ex vivo and in vivo than conventional full agonists. Exploration of the underlying mechanism in living cells employing cellular dynamic mass redistribution identified context-sensitive agonism of these dualsteric agonists. They translate elevation of intracellular cAMP into a switch from full to partial agonism. Designed context-sensitive agonism opens an avenue toward postreceptor pharmacologic selectivity, which even works in target tissues operated by the same subtype of pharmacologic receptor. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Miniature short hairpin RNA screens to characterize antiproliferative drugs.

PubMed

Kittanakom, Saranya; Arnoldo, Anthony; Brown, Kevin R; Wallace, Iain; Kunavisarut, Tada; Torti, Dax; Heisler, Lawrence E; Surendra, Anuradha; Moffat, Jason; Giaever, Guri; Nislow, Corey

2013-08-07

The application of new proteomics and genomics technologies support a view in which few drugs act solely by inhibiting a single cellular target. Indeed, drug activity is modulated by complex, often incompletely understood cellular mechanisms. Therefore, efforts to decipher mode of action through genetic perturbation such as RNAi typically yields "hits" that fall into several categories. Of particular interest to the present study, we aimed to characterize secondary activities of drugs on cells. Inhibiting a known target can result in clinically relevant synthetic phenotypes. In one scenario, drug perturbation could, for example, improperly activate a protein that normally inhibits a particular kinase. In other cases, additional, lower affinity targets can be inhibited as in the example of inhibition of c-Kit observed in Bcr-Abl-positive cells treated with Gleevec. Drug transport and metabolism also play an important role in the way any chemicals act within the cells. Finally, RNAi per se can also affect cell fitness by more general off-target effects, e.g., via the modulation of apoptosis or DNA damage repair. Regardless of the root cause of these unwanted effects, understanding the scope of a drug's activity and polypharmacology is essential for better understanding its mechanism(s) of action, and such information can guide development of improved therapies. We describe a rapid, cost-effective approach to characterize primary and secondary effects of small-molecules by using small-scale libraries of virally integrated short hairpin RNAs. We demonstrate this principle using a "minipool" composed of shRNAs that target the genes encoding the reported protein targets of approved drugs. Among the 28 known reported drug-target pairs, we successfully identify 40% of the targets described in the literature and uncover several unanticipated drug-target interactions based on drug-induced synthetic lethality. We provide a detailed protocol for performing such screens and for analyzing the data. This cost-effective approach to mammalian knockdown screens, combined with the increasing maturation of RNAi technology will expand the accessibility of similar approaches in academic settings.

Current Pharmacological Approaches to Reduce Chorea in Huntington's Disease.

PubMed

Coppen, Emma M; Roos, Raymund A C

2017-01-01

There are currently no effective pharmacological agents available to stop or prevent the progression of Huntington's disease (HD), a rare hereditary neurodegenerative disorder. In addition to psychiatric symptoms and cognitive impairments, HD causes progressive motor disturbances, in particular choreiform movements, which are characterized by unwanted contractions of the facial muscles, trunk and extremities. Management of choreiform movements is usually advised if chorea interferes with daily functioning, causes social isolation, gait instability, falls, or physical injury. Although drugs to reduce chorea are available, only few randomized controlled studies have assessed the efficacy of these drugs, resulting in a high variety of prescribed drugs in clinical practice. The current pharmacological treatment options to reduce chorea in HD are outlined in this review, including the latest results on deutetrabenazine, a newly developed pharmacological agent similar to tetrabenazine, but with suggested less peak dose side effects. A review of the existing literature was conducted using the PubMed, Cochrane and Medline databases. In conclusion, mainly tetrabenazine, tiapride (in European countries), olanzapine, and risperidone are the preferred first choice drugs to reduce chorea among HD experts. In the existing literature, these drugs also show a beneficial effect on motor symptom severity and improvement of psychiatric symptoms. Generally, it is recommended to start with a low dose and increase the dose with close monitoring of any adverse effects. New interesting agents, such as deutetrabenazine and pridopidine, are currently under development and more randomized controlled trials are warranted to assess the efficacy on chorea severity in HD.

Reducing unwanted trauma memories by imaginal exposure or autobiographical memory elaboration: An analogue study of memory processes

PubMed Central

Ehlers, Anke; Mauchnik, Jana; Handley, Rachel

2012-01-01

Unwanted memories of traumatic events are a core symptom of post-traumatic stress disorder. A range of interventions including imaginal exposure and elaboration of the trauma memory in its autobiographical context are effective in reducing such unwanted memories. This study explored whether priming for stimuli that occur in the context of trauma and evaluative conditioning may play a role in the therapeutic effects of these procedures. Healthy volunteers (N = 122) watched analogue traumatic and neutral picture stories. They were then randomly allocated to 20 min of either imaginal exposure, autobiographical memory elaboration, or a control condition designed to prevent further processing of the picture stories. A blurred picture identification task showed that neutral objects that preceded traumatic pictures in the stories were subsequently more readily identified than those that had preceded neutral stories, indicating enhanced priming. There was also an evaluative conditioning effect in that participants disliked neutral objects that had preceded traumatic pictures more. Autobiographical memory elaboration reduced the enhanced priming effect. Both interventions reduced the evaluative conditioning effect. Imaginal exposure and autobiographical memory elaboration both reduced the frequency of subsequent unwanted memories of the picture stories. PMID:21227404

Combination of a proteomics approach and reengineering of meso scale network models for prediction of mode-of-action for tyrosine kinase inhibitors.

PubMed

Balabanov, Stefan; Wilhelm, Thomas; Venz, Simone; Keller, Gunhild; Scharf, Christian; Pospisil, Heike; Braig, Melanie; Barett, Christine; Bokemeyer, Carsten; Walther, Reinhard; Brümmendorf, Tim H; Schuppert, Andreas

2013-01-01

In drug discovery, the characterisation of the precise modes of action (MoA) and of unwanted off-target effects of novel molecularly targeted compounds is of highest relevance. Recent approaches for identification of MoA have employed various techniques for modeling of well defined signaling pathways including structural information, changes in phenotypic behavior of cells and gene expression patterns after drug treatment. However, efficient approaches focusing on proteome wide data for the identification of MoA including interference with mutations are underrepresented. As mutations are key drivers of drug resistance in molecularly targeted tumor therapies, efficient analysis and modeling of downstream effects of mutations on drug MoA is a key to efficient development of improved targeted anti-cancer drugs. Here we present a combination of a global proteome analysis, reengineering of network models and integration of apoptosis data used to infer the mode-of-action of various tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) cell lines expressing wild type as well as TKI resistance conferring mutants of BCR-ABL. The inferred network models provide a tool to predict the main MoA of drugs as well as to grouping of drugs with known similar kinase inhibitory activity patterns in comparison to drugs with an additional MoA. We believe that our direct network reconstruction approach, demonstrated on proteomics data, can provide a complementary method to the established network reconstruction approaches for the preclinical modeling of the MoA of various types of targeted drugs in cancer treatment. Hence it may contribute to the more precise prediction of clinically relevant on- and off-target effects of TKIs.

Combination of a Proteomics Approach and Reengineering of Meso Scale Network Models for Prediction of Mode-of-Action for Tyrosine Kinase Inhibitors

PubMed Central

Balabanov, Stefan; Wilhelm, Thomas; Venz, Simone; Keller, Gunhild; Scharf, Christian; Pospisil, Heike; Braig, Melanie; Barett, Christine; Bokemeyer, Carsten; Walther, Reinhard

2013-01-01

In drug discovery, the characterisation of the precise modes of action (MoA) and of unwanted off-target effects of novel molecularly targeted compounds is of highest relevance. Recent approaches for identification of MoA have employed various techniques for modeling of well defined signaling pathways including structural information, changes in phenotypic behavior of cells and gene expression patterns after drug treatment. However, efficient approaches focusing on proteome wide data for the identification of MoA including interference with mutations are underrepresented. As mutations are key drivers of drug resistance in molecularly targeted tumor therapies, efficient analysis and modeling of downstream effects of mutations on drug MoA is a key to efficient development of improved targeted anti-cancer drugs. Here we present a combination of a global proteome analysis, reengineering of network models and integration of apoptosis data used to infer the mode-of-action of various tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) cell lines expressing wild type as well as TKI resistance conferring mutants of BCR-ABL. The inferred network models provide a tool to predict the main MoA of drugs as well as to grouping of drugs with known similar kinase inhibitory activity patterns in comparison to drugs with an additional MoA. We believe that our direct network reconstruction approach, demonstrated on proteomics data, can provide a complementary method to the established network reconstruction approaches for the preclinical modeling of the MoA of various types of targeted drugs in cancer treatment. Hence it may contribute to the more precise prediction of clinically relevant on- and off-target effects of TKIs. PMID:23326482

Immunogenicity of biotherapy used in psoriasis: the science behind the scenes.

PubMed

Jullien, Denis; Prinz, Jörg C; Nestle, Frank O

2015-01-01

A potential limitation in the use of biologic drugs used to treat psoriasis is the development of anti-drug antibodies (ADAs). Many factors contribute to this unwanted immune response, from the product itself, to its mode of administration, the underlying disease, and patient characteristics. ADAs may decrease the efficacy of biologic drugs by neutralizing them or modifying their clearance and may account for hypersensitivity reactions. This article reviews the scientific basis of immunogenicity and the mechanisms by which it affects clinical outcomes. It also considers testing for immunogenicity and how biologic therapy of psoriasis may be tailored on the basis of immunogenicity.

Anticholinergic drugs and negative outcomes in the older population: from biological plausibility to clinical evidence.

PubMed

Collamati, Agnese; Martone, Anna Maria; Poscia, Andrea; Brandi, Vincenzo; Celi, Michela; Marzetti, Emanuele; Cherubini, Antonio; Landi, Francesco

2016-02-01

The use of medication with anticholinergic properties is widespread among older subjects. Many drugs of common use such as antispasmodics, bronchodilators, antiarrhythmics, antihistamines, anti-hypertensive drugs, antiparkinson agents, skeletal muscle relaxants, and psychotropic drugs have been demonstrated to have an anticholinergic activity. The most frequent adverse effects are dry mouth, nausea, vomiting, constipation, abdominal pain, urinary retention, blurred vision, tachycardia and neurologic impairment such as confusion, agitation and coma. A growing evidence from experimental studies and clinical observations suggests that drugs with anticholinergic properties can cause physical and mental impairment in the elderly population. However, the morbidity and management issues associated with unwanted anticholinergic activity are underestimated and frequently overlooked. Moreover, their possible relation with specific negative outcome in the elderly population is still not firmly established. The aim of the present review was to evaluate the relationship between the use of drugs with anticholinergic activity and negative outcomes in older persons. We searched PubMed and Cochrane combining the search terms "anticholinergic", "delirium", "cognitive impairment", "falls", "mortality" and "discontinuation". Medicines with anticholinergic properties may increase the risks of functional and cognitive decline, morbidity, institutionalization and mortality in older people. However, such evidences are still not conclusive probably due to possible confounding factors. In particular, more studies are needed to investigate the effects of discontinuation of drug with anticholinergic properties. Overall, minimizing anticholinergic burden should always be encouraged in clinical practice to improve short-term memory, confusion and delirium, quality of life and daily functioning.

Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

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

Fischer, L.; Deppert, W.R.; Pfeifer, D.

Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As workingmore » basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak antigestagenic activity. ► SULT1E1 is a significant marker for endometrial antiprogestin effects. ► Ishikawa cells are a tissue-specific approach for characterization of SPRMs. ► Chemicals acting as progesterone receptor antagonists may exert antifertility effects.« less

Tuberculosis: An Inorganic Medicinal Chemistry Perspective.

PubMed

Viganor, Livia; Skerry, Ciaran; McCann, Malachy; Devereux, Michael

2015-01-01

Tuberculosis (TB) which is caused by the resilient pathogen Mycobacterium tuberculosis (MTB) has re-emerged to become a leading public health problem in the world. The growing number of multi-drug resistant MTB strains and the more recently emerging problem with the extensively drug resistant strains of the pathogen are greatly undermining conventional anti-TB therapeutic strategies which are lengthy and expose patients to toxicity and other unwanted side effects. The search for new anti-TB drugs essentially involves either the repurposing of existing organic drugs which are now off patent and already FDA approved, the synthesis of modified analogues of existing organic drugs, with the aim of shortening and improving drug treatment for the disease, or the search for novel structures that offer the possibility of new mechanisms of action against the mycobacterium. Inorganic medicinal chemistry offers an alternative to organic drugs through opportunities for the design of therapeutics that target different biochemical pathways. The incorporation of metal ions into the molecular structure of a potential drug offers the medicinal chemist an opportunity to exploit structural diversity, have access to various oxidation states of the metal and also offer the possibility of enhancing the activity of an established organic drug through its coordination to the metal centre. In this review, we summarize what is currently known about the antitubercular capability of metal complexes, their mechanisms of action and speculate on their potential applications in the clinic.

An adaptive drug delivery design using neural networks for effective treatment of infectious diseases: a simulation study.

PubMed

Padhi, Radhakant; Bhardhwaj, Jayender R

2009-06-01

An adaptive drug delivery design is presented in this paper using neural networks for effective treatment of infectious diseases. The generic mathematical model used describes the coupled evolution of concentration of pathogens, plasma cells, antibodies and a numerical value that indicates the relative characteristic of a damaged organ due to the disease under the influence of external drugs. From a system theoretic point of view, the external drugs can be interpreted as control inputs, which can be designed based on control theoretic concepts. In this study, assuming a set of nominal parameters in the mathematical model, first a nonlinear controller (drug administration) is designed based on the principle of dynamic inversion. This nominal drug administration plan was found to be effective in curing "nominal model patients" (patients whose immunological dynamics conform to the mathematical model used for the control design exactly. However, it was found to be ineffective in curing "realistic model patients" (patients whose immunological dynamics may have off-nominal parameter values and possibly unwanted inputs) in general. Hence, to make the drug delivery dosage design more effective for realistic model patients, a model-following adaptive control design is carried out next by taking the help of neural networks, that are trained online. Simulation studies indicate that the adaptive controller proposed in this paper holds promise in killing the invading pathogens and healing the damaged organ even in the presence of parameter uncertainties and continued pathogen attack. Note that the computational requirements for computing the control are very minimal and all associated computations (including the training of neural networks) can be carried out online. However it assumes that the required diagnosis process can be carried out at a sufficient faster rate so that all the states are available for control computation.

Effects of planned, mistimed and unwanted pregnancies on the use of prenatal health services in sub-Saharan Africa: a multicountry analysis of Demographic and Health Survey data.

PubMed

Amo-Adjei, Joshua; Anamaale Tuoyire, Derek

2016-12-01

We analysed the extent of planned, mistimed and unwanted pregnancies and how they predict optimal use of prenatal (timing and number of antenatal) care services in 30 African countries. We pooled data from Demographic and Health Surveys conducted in 30 African countries between 2006 and 2015. We described the extent of mistimed and unwanted pregnancies and further used mixed effects logistic and Poisson regression estimation techniques to examine the impacts of planned, mistimed and unwanted pregnancies on the use of prenatal health services. In total, 73.65% of pregnancies in all countries were planned. Mistimed pregnancy ranged from 7.43% in Burkina Faso to 41.33% in Namibia. Unwanted pregnancies were most common in Swaziland (39.54%) and least common in Niger (0.74%). Timely (first trimester) initiation of ANC was 37% overall in all countries; the multicountry average number of ANC visits was optimal [4.1; 95% CI: 4.1-4.2] but with notable disparities between countries. Overall, mistimed and unwanted pregnancies were strongly associated with late ANC attendance and fewer visits women made in the pooled analysis. Unintended pregnancies are critical risks to achieving improved maternal health in respect of early and optimal ANC coverage for women in Africa. Programmes targeted at advancing coverage of ANC in Africa need to deploy contextually appropriate mechanisms to prevent unintended pregnancies. © 2016 John Wiley & Sons Ltd.

Emergency contraception: which is the best?

PubMed

Mittal, Suneeta

2016-12-01

Emergency contraception is a safe and effective method to prevent an unwanted pregnancy after an unprotected or inadequately protected sexual intercourse. Several methods for emergency contraception (EC) are currently registered in many countries for use in an emergency to prevent a pregnancy following an unprotected, possibly fertile intercourse or after a contraceptive accident like condom rupture. Different methods have varying modes of action, time frame of efficacy, dosage schedule and unwanted effects. Since several methods are available it is important to decide the best method. In this article the available literature on emergency contraception has been reviewed and an attempt has been made to discuss the need for emergency contraception and compare different options for emergency contraception in terms of their efficacy in pregnancy prevention, their safety profile and unwanted side effects. EC repeated use and initiating a regular method after EC use are also discussed. Emergency contraceptive methods include copper Intra-uterine devices (IUD) and different types of pills like estrogen progestin combination pill (Yuzpe Regimen), Progestin only pill (LNG), antiprogestin pill (Mifepristone), and progesterone modulator Uripristal Acetate (UPA). There is a marginal difference in the mechanism of action, efficacy including time frame and ability to protect from pregnancy with regular doses in obese women, drug interactions and side effects. These are discussed in detail. Copper IUD is the most effective emergency contraceptive with advantage of providing continued contraception. However, it cannot be used universally due to lack of infrastructure and a trained provider as well as not being suitable option for women at risk of sexually transmitted infections. Amongst different pills LNG is more effective with fewer side effects than Yuzpe regimen. LNG and UPA are comparable with similar efficacy and side effect profile. UPA has a wider window of efficacy, in LNG efficacy declines after 72 hours. UPA is more suitable for obese women. Mifepristone is effective but is registered as EC pill only in few countries and use is limited as it is also used as an abortion pill. Yuzpe regimen is the least effective of all contraceptive pills as EC, and works only till 72 hours of unprotected sex, but is useful in places where dedicated methods are not available, as it is easily accessible. Any combined pill can be used in this regimen except triphasic pill.

Prolonged cytotoxic effect of colchicine released from biodegradable microspheres.

PubMed

Muvaffak, Asli; Gurhan, Ismet; Hasirci, Nesrin

2004-11-15

One the main problems of cancer chemotherapy is the unwanted damage to normal cells caused by the high toxicities of anticancer drugs. Any system of controlled drug delivery that would reduce the total amount of drug required, and thus reduce the side effects, would potentially help to improve chemotherapy. In this respect, biodegradable gelatin microspheres were prepared by water/oil emulsion polymerization and by crosslinking with glutaraldehyde (GTA) as the drug-carrier system. Microspheres were loaded with colchicine, a model antimitotic drug, which was frequently used as an antimitotic agent in cancer research involving cell cultures. Microsphere sizes, swelling and degradation properties, drug-release kinetics, and cytotoxities were studied. Swelling characteristics of microspheres changed upon changing GTA concentration. A decrease in swelling values was recorded as GTA crosslink density was increased. In vitro drug release in PBS (0.01M, pH 7.4) showed rapid colchicine release up to approximately 83% (at t = 92 h) for microspheres with low GTA (0.05% v/v), whereas a slower release profile (only approximately 39%) was obtained for microspheres with high GTA (0.50% v/v) content, for the same period. Cytotoxicity tests with MCF-7, HeLa and H-82 cancer cell lines showed that free colchicine was very toxic, showing an approximately 100% lethal effect in both HeLa and H-82 cell lines and more than 50% decrease in viability in MCF-7 cells in 4 days. Indeed, entrapped colchicine indicated similar initial high toxic effect on cell viability in MCF-7 cell line and this effect became more dominant as colchicine continued to be released from microspheres in the same period. In conclusion, the control of the release rate of colchicine from gelatin microspheres was achieved under in vitro conditions by gelatin through the alteration of crosslinking conditions. Indeed, the results suggested the potential application of gelatin microspheres crosslinked with GTA as a sustained drug-delivery system for anticancer drugs for local chemotherapy administrations. (c) 2004 Wiley Periodicals, Inc.

The Women'S Perceptions About Unwanted Pregnancy: A Qualitative Study in Iran.

PubMed

Akbarzadeh, Marzieh; Yazdanpanahi, Zahra; Zarshenas, Ladan; Sharif, Farkhondeh

2015-09-28

Unwanted pregnancy has affected different aspects of our life. Researchers point out if a child's birth is unwanted, an increase in maternal issues can be observed. The aim of this study was to describe the women's viewpoints regarding unwanted pregnancy. This qualitative study using content analysis was employed in Shiraz University in 2013-2014. 20 women with unwanted pregnancy were chosen using purposeful sampling. Data were gathered through semi-structured interviews and trustworthiness of them was evaluated. Findings of this study, according to the participants' experience, revealed maternal emotions like embarrassment for getting pregnant, mother's own negative affection, concerns about missing family and other children, and terminating the pregnancy through illegal abortion, the husband's disagreement about the termination, blaming themselves for thinking about abortion or illegal abortion, and concern about their guilt feeling. Another finding was family problems like husband's behavior and his negative outlook towards his child and fetus. The next category belonged to anxiety about the future of their child, including economic, social and relational problems, and suppression of the children's logical expectations. The last finding was the lack of maternal emotional support. Unwanted pregnancy's effects on the mothers and infants' health are considerable. A closer observation by family and health care providers for unwanted pregnancies and its results is recommended; therefore, they should be taken care of as high risk pregnancies, requiring family support.

Herbal products in Canada. How safe are they?

PubMed Central

Kozyrskyj, A.

1997-01-01

OBJECTIVE: To examine existing evidence and inform family physicians about issues concerning herbal product use in Canada. QUALITY OF EVIDENCE: The Canadian Food and Drug Act and findings of an Expert Advisory Committee on Herbs and Botanical Preparations were consulted to provide an overview of the issues regarding herbal product regulation in Canada. Case reports of herbal toxicity were identified to illustrate some of the hazards of herbal products, and references provided to guide health professional in searching the literature for clinical trials that evaluate these drugs' efficacy. MAIN FINDINGS: Herbal products not registered as drugs in Canada are sold as foods and are exempt from the drug review process that evaluates product efficacy and safety. This places the public at risk of unwanted effects from the use of herbal products that are adulterated with other substances and of forgoing effective conventional therapy. Moreover, consumers are exposed to a plethora of information portraying herbal products as harmless. Some progress has been made to address these concerns by facilitating the registration of herbal products as drugs. CONCLUSIONS: Most herbal products that were evaluated were unsafe or ineffective, or no information was available to evaluate their efficacy. Despite the perception that herbal products are innocuous, family physicians need to be aware that herbal therapy can be harmful in order to help their patients make informed choices. Images p699-a PMID:9111986

Localized Cell and Drug Delivery for Auditory Prostheses

PubMed Central

Hendricks, Jeffrey L.; Chikar, Jennifer A.; Crumling, Mark A.; Raphael, Yehoash; Martin, David C.

2011-01-01

Localized cell and drug delivery to the cochlea and central auditory pathway can improve the safety and performance of implanted auditory prostheses (APs). While generally successful, these devices have a number of limitations and adverse effects including limited tonal and dynamic ranges, channel interactions, unwanted stimulation of non-auditory nerves, immune rejection, and infections including meningitis. Many of these limitations are associated with the tissue reactions to implanted auditory prosthetic devices and the gradual degeneration of the auditory system following deafness. Strategies to reduce the insertion trauma, degeneration of target neurons, fibrous and bony tissue encapsulation, and immune activation can improve the viability of tissue required for AP function as well as improve the resolution of stimulation for reduced channel interaction and improved place-pitch and level discrimination. Many pharmaceutical compounds have been identified that promote the viability of auditory tissue and prevent inflammation and infection. Cell delivery and gene therapy have provided promising results for treating hearing loss and reversing degeneration. Currently, many clinical and experimental methods can produce extremely localized and sustained drug delivery to address AP limitations. These methods provide better control over drug concentrations while eliminating the adverse effects of systemic delivery. Many of these drug delivery techniques can be integrated into modern auditory prosthetic devices to optimize the tissue response to the implanted device and reduce the risk of infection or rejection. Together, these methods and pharmaceutical agents can be used to optimize the tissue-device interface for improved AP safety and effectiveness. PMID:18573323

Biomedical Imaging in Implantable Drug Delivery Systems

PubMed Central

Zhou, Haoyan; Hernandez, Christopher; Goss, Monika; Gawlik, Anna; Exner, Agata A.

2015-01-01

Implantable drug delivery systems (DDS) provide a platform for sustained release of therapeutic agents over a period of weeks to months and sometimes years. Such strategies are typically used clinically to increase patient compliance by replacing frequent administration of drugs such as contraceptives and hormones to maintain plasma concentration within the therapeutic window. Implantable or injectable systems have also been investigated as a means of local drug administration which favors high drug concentration at a site of interest, such as a tumor, while reducing systemic drug exposure to minimize unwanted side effects. Significant advances in the field of local DDS have led to increasingly sophisticated technology with new challenges including quantification of local and systemic pharmacokinetics and implant-body interactions. Because many of these sought-after parameters are highly dependent on the tissue properties at the implantation site, and rarely represented adequately with in vitro models, new nondestructive techniques that can be used to study implants in situ are highly desirable. Versatile imaging tools can meet this need and provide quantitative data on morphological and functional aspects of implantable systems. The focus of this review article is an overview of current biomedical imaging techniques, including magnetic resonance imaging (MRI), ultrasound imaging, optical imaging, X-ray and computed tomography (CT), and their application in evaluation of implantable DDS. PMID:25418857

Antidiabetic activity of the mangrove species Ceriops decandra in alloxan-induced diabetic rats.

PubMed

Nabeel, Mannalamkunnath Alikunhi; Kathiresan, Kandasamy; Manivannan, Subramanian

2010-06-01

Diabetes is a series of disorders characterized by increased fasting and postprandial glucose concentration and insulin deficiency and/or decreased insulin action. Although there are a number of commercially available drugs for the treatment of diabetes, their long-term use may cause unwanted side effects. Consequently, many studies are underway to find natural remedies that can effectively reduce the intensity of diabetes. The aim of the present study was to evaluate the antidiabetic activity of the mangrove species Ceriops decandra. The effects of daily oral administration of an ethanolic extract from the leaves of C. decandra (30, 60, 120 mg/kg) for 30 days on blood glucose, hemoglobin (Hb), HbA1c, liver glycogen and some carbohydrate metabolic enzymes were evaluated in normal and alloxan-induced diabetic rats. The effects of these extracts were compared with the effect of 30-days treatment with 0.1 mg/kg, p.o., glibenclamide, a commercially available drug commonly used in the treatment of diabetes. Oral administration of 120 mg/kg extract modulated all the parameters evaluated to levels seen in control rats. The effects of 120 mg/kg extract were comparable to those of glibenclamide. The extract of the mangrove plant C. decandra exhibited promising antidiabetic activity and could be considered for further evaluation in clinical studies and drug development. © 2010 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

Amorfrutins are potent antidiabetic dietary natural products

PubMed Central

Weidner, Christopher; de Groot, Jens C.; Prasad, Aman; Freiwald, Anja; Quedenau, Claudia; Kliem, Magdalena; Witzke, Annabell; Kodelja, Vitam; Han, Chung-Ting; Giegold, Sascha; Baumann, Matthias; Klebl, Bert; Siems, Karsten; Müller-Kuhrt, Lutz; Schürmann, Annette; Schüler, Rita; Pfeiffer, Andreas F. H.; Schroeder, Frank C.; Büssow, Konrad; Sauer, Sascha

2012-01-01

Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease. PMID:22509006

Alcohol use before and during unwanted pregnancy

PubMed Central

Roberts, S.C.M.; Wilsnack, S.C.; Foster, D.G.; Delucchi, K.L.

2014-01-01

Background There is little information about pregnancy-related changes in alcohol use and factors contributing to changes among women with unwanted pregnancies. This study describes changes in alcohol use from before pregnancy recognition to during pregnancy and identifies important predictors of alcohol use severity among women with unwanted pregnancies. Methods Data are from the Turnaway Study of 956 women seeking pregnancy termination at 30 U.S. facilities between 2008 and 2010, some of whom were denied care because they were past the gestational limit of the facility where they were recruited and were still pregnant at the baseline interview, one week after termination-seeking. Predictors of alcohol use severity (a latent variable) were identified. Results 56% of the total sample reported any alcohol use the month before pregnancy recognition, with 23% reporting six or more drinks on an occasion. Among the total sample, 35% of those drinking before pregnancy recognition had quit and 20% had reduced one week after termination seeking. Among those denied terminations and still pregnant, 71% had quit and 14% had reduced. In a multivariate model predicting alcohol severity, younger age, still pregnant, one or more previous births, later gestation, childhood physical abuse, and marijuana and other drug use were associated with lower severity; having completed college, tobacco use, and recent physical violence were associated with higher severity. Conclusions The proportion of the total sample drinking before pregnancy recognition is similar to national samples of women of childbearing age while the proportion binge drinking appears higher. Of women denied terminations who were still pregnant, the proportion having quit is similar to other populations of pregnant women. More research is needed to examine whether pregnant women may be substituting alcohol for marijuana and other drugs. Interventions focusing on alcohol use severity during pregnancy may need to also focus on tobacco. PMID:25336245

Neuroticism explains unwanted variance in Implicit Association Tests of personality: possible evidence for an affective valence confound.

PubMed

Fleischhauer, Monika; Enge, Sören; Miller, Robert; Strobel, Alexander; Strobel, Anja

2013-01-01

Meta-analytic data highlight the value of the Implicit Association Test (IAT) as an indirect measure of personality. Based on evidence suggesting that confounding factors such as cognitive abilities contribute to the IAT effect, this study provides a first investigation of whether basic personality traits explain unwanted variance in the IAT. In a gender-balanced sample of 204 volunteers, the Big-Five dimensions were assessed via self-report, peer-report, and IAT. By means of structural equation modeling (SEM), latent Big-Five personality factors (based on self- and peer-report) were estimated and their predictive value for unwanted variance in the IAT was examined. In a first analysis, unwanted variance was defined in the sense of method-specific variance which may result from differences in task demands between the two IAT block conditions and which can be mirrored by the absolute size of the IAT effects. In a second analysis, unwanted variance was examined in a broader sense defined as those systematic variance components in the raw IAT scores that are not explained by the latent implicit personality factors. In contrast to the absolute IAT scores, this also considers biases associated with the direction of IAT effects (i.e., whether they are positive or negative in sign), biases that might result, for example, from the IAT's stimulus or category features. None of the explicit Big-Five factors was predictive for method-specific variance in the IATs (first analysis). However, when considering unwanted variance that goes beyond pure method-specific variance (second analysis), a substantial effect of neuroticism occurred that may have been driven by the affective valence of IAT attribute categories and the facilitated processing of negative stimuli, typically associated with neuroticism. The findings thus point to the necessity of using attribute category labels and stimuli of similar affective valence in personality IATs to avoid confounding due to recoding.

Shining Light on Nanotechnology to Help Repair and Regeneration

PubMed Central

Gupta, Asheesh; Avci, Pinar; Sadasivam, Magesh; Chandran, Rakkiyappan; Parizotto, Nivaldo; Vecchio, Daniela; Antunes-Melo, Wanessa C; Dai, Tianhong; Chiang, Long Y.; Hamblin, Michael R.

2012-01-01

Phototherapy can be used in two completely different but complementary therapeutic applications. While low level laser (or light) therapy (LLLT) uses red or near-infrared light alone to reduce inflammation, pain and stimulate tissue repair and regeneration, photodynamic therapy (PDT) uses the combination of light plus non-toxic dyes (called photosensitizers) to produce reactive oxygen species that can kill infectious microorganisms and cancer cells or destroy unwanted tissue (neo-vascularization in the choroid, atherosclerotic plaques in the arteries). The recent development of nanotechnology applied to medicine (nanomedicine) has opened a new front of advancement in the field of phototherapy and has provided hope for the development of nanoscale drug delivery platforms for effective killing of pathological cells and to promote repair and regeneration. Despite the well-known beneficial effects of phototherapy and nanomaterials in producing the killing of unwanted cells and promoting repair and regeneration, there are few reports that combine all three elements i.e. phototherapy, nanotechnology and, tissue repair and regeneration. However, these areas in all possible binary combinations have been addressed by many workers. The present review aims at highlighting the combined multi-model applications of phototherapy, nanotechnology and, reparative and regeneration medicine and outlines current strategies, future applications and limitations of nanoscale-assisted phototherapy for the management of cancers, microbial infections and other diseases, and to promote tissue repair and regeneration. PMID:22951919

Modeling Combined Immunosuppressive and Anti-inflammatory Effects of Dexamethasone and Naproxen in Rats Predicts the Steroid-Sparing Potential of Naproxen.

PubMed

Li, Xiaonan; DuBois, Debra C; Song, Dawei; Almon, Richard R; Jusko, William J; Chen, Xijing

2017-07-01

Dexamethasone (DEX), a widely prescribed corticosteroid, has long been the cornerstone of the treatment of inflammation and immunologic dysfunctions in rheumatoid arthritis. Corticosteroids are frequently used in combination with other antirheumatic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs to mitigate disease symptoms and minimize unwanted effects. We explored the steroid dose-sparing potential of the NSAID naproxen (NPX) with in vitro and in vivo studies. The single and joint suppressive effects of DEX and NPX on the in vitro mitogen-induced proliferation of T lymphocytes in blood and their anti-inflammatory actions on paw edema were investigated in female and male Lewis rats with collagen-induced arthritis (CIA). As expected, DEX was far more potent than NPX in these systems. Mathematical models incorporating an interaction term ψ were applied to quantitatively assess the nature and intensity of pharmacodynamic interactions between DEX and NPX. Modest synergistic effects of the two drugs were found in suppressing the mitogenic response of T lymphocytes. A pharmacokinetic/pharmacodynamic/disease progression model integrating dual drug inhibition quantitatively described the pharmacokinetics, time-course of single and joint anti-inflammatory effects (paw edema), and sex differences in CIA rats, and indicated additive effects of DEX and NPX. Further model simulations demonstrated the promising steroid-sparing potential of NPX in CIA rats, with the beneficial effects of the combination therapy more likely in males than females. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Transient receptor potential channels in sensory neurons are targets of the antimycotic agent clotrimazole.

PubMed

Meseguer, Victor; Karashima, Yuji; Talavera, Karel; D'Hoedt, Dieter; Donovan-Rodríguez, Tansy; Viana, Felix; Nilius, Bernd; Voets, Thomas

2008-01-16

Clotrimazole (CLT) is a widely used drug for the topical treatment of yeast infections of skin, vagina, and mouth. Common side effects of topical CLT application include irritation and burning pain of the skin and mucous membranes. Here, we provide evidence that transient receptor potential (TRP) channels in primary sensory neurons underlie these unwanted effects of CLT. We found that clinically relevant CLT concentrations activate heterologously expressed TRPV1 and TRPA1, two TRP channels that act as receptors of irritant chemical and/or thermal stimuli in nociceptive neurons. In line herewith, CLT stimulated a subset of capsaicin-sensitive and mustard oil-sensitive trigeminal neurons, and evoked nocifensive behavior and thermal hypersensitivity with intraplantar injection in mice. Notably, CLT-induced pain behavior was suppressed by the TRPV1-antagonist BCTC [(N-(-4-tertiarybutylphenyl)-4-(3-cholorpyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide)] and absent in TRPV1-deficient mice. In addition, CLT inhibited the cold and menthol receptor TRPM8, and blocked menthol-induced responses in capsaicin- and mustard oil-insensitive trigeminal neurons. The concentration for 50% inhibition (IC50) of inward TRPM8 current was approximately 200 nM, making CLT the most potent known TRPM8 antagonist and a useful tool to discriminate between TRPM8- and TRPA1-mediated responses. Together, our results identify TRP channels in sensory neurons as molecular targets of CLT, and offer means to develop novel CLT preparations with fewer unwanted sensory side effects.

Unintended pregnancy in the life-course perspective.

PubMed

Helfferich, Cornelia; Hessling, Angelika; Klindworth, Heike; Wlosnewski, Ines

2014-09-01

In this contribution unintended pregnancies are studied as a multidimensional concept from a life-course perspective. Standardized data on the prevalence of unwanted pregnancies in different stages of women's life course are combined with a qualitative analysis of the subjective meaning of "unwanted" and of subjective explanations of getting pregnant unintentionally. The study "frauen leben 3" on family planning in the life course of 20-44 year old women was conducted on behalf of the Federal Centre for Health Education (BZgA) from 2011 until 2014 in four federal states in Germany. A standardized questionnaire was used to collect retrospective information on 4794 pregnancies (including induced abortions), and biographical in-depth interviews provide qualitative information on 103 unwanted pregnancies. The standardized data were analyzed with bivariate methods and multivariate logistic regression models. The qualitative procedure to construct typologies of subjective meanings consisted of contrasting cases according to the generative approach of Grounded Theory. In contrast to unwanted pregnancies, mistimed pregnancies are characterized to a greater extent by negligence in the use of contraceptives, by a positive reaction to the pregnancy and by a more general desire to have a child. Four different subjective meanings of "unwanted" are constructed in qualitative analysis. The logistic regressions show that the selected factors that increase the likelihood of an unwanted pregnancy vary according to age and stage in the life course. The quantitative analysis reveals furthermore that relationship with a partner had a significant effect in all stages of the life course. The qualitative interviews specify the age- and life course-related aspects of these effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cannabinoids as Anticancer Drugs.

PubMed

Ramer, Robert; Hinz, Burkhard

2017-01-01

The endocannabinoid system encompassing cannabinoid receptors, endogenous receptor ligands (endocannabinoids), as well as enzymes conferring the synthesis and degradation of endocannabinoids has emerged as a considerable target for pharmacotherapeutical approaches of numerous diseases. Besides palliative effects of cannabinoids used in cancer treatment, phytocannabinoids, synthetic agonists, as well as substances that increase endogenous endocannabinoid levels have gained interest as potential agents for systemic cancer treatment. Accordingly, cannabinoid compounds have been reported to inhibit tumor growth and spreading in numerous rodent models. The underlying mechanisms include induction of apoptosis, autophagy, and cell cycle arrest in tumor cells as well as inhibition of tumor cell invasion and angiogenic features of endothelial cells. In addition, cannabinoids have been shown to suppress epithelial-to-mesenchymal transition, to enhance tumor immune surveillance, and to support chemotherapeutics' effects on drug-resistant cancer cells. However, unwanted side effects include psychoactivity and possibly pathogenic effects on liver health. Other cannabinoids such as the nonpsychoactive cannabidiol exert a comparatively good safety profile while exhibiting considerable anticancer properties. So far experience with anticarcinogenic effects of cannabinoids is confined to in vitro studies and animal models. Although a bench-to-bedside conversion remains to be established, the current knowledge suggests cannabinoid compounds to serve as a group of drugs that may offer significant advantages for patients suffering from cancer diseases. The present review summarizes the role of the endocannabinoid system and cannabinoid compounds in tumor progression. © 2017 Elsevier Inc. All rights reserved.

Novel antipsychotics: issues and controversies. Typicality of atypical antipsychotics.

PubMed Central

Stip, E

2000-01-01

The typicality of atypical antipsychotic drugs remains debatable. Preclinical studies and findings from randomized, controlled and open trials of clozapine, olanzapine, risperidone, quetiapine, sertindole, ziprasidone and a substituted benzamide were examined. A MEDLINE search was conducted using key words, including "extrapyramidal side effects," "cognition," "schizophrenia" and the generic drug names. Over 140 articles from peer-reviewed journals were reviewed, some of which were based on a meta-analysis. New-generation neuroleptic agents were found to have greater efficacy on the negative symptoms of schizophrenia and to cause fewer unwanted extrapyramidal side effects (EPS) than the traditional antipsychotic drugs. On one hand, atypical neuroleptic agents could be strictly defined as any neuroleptic agent with antipsychotic effects at a dosage that does not cause extrapyramidal side effects. Thus, clozapine is regarded as the "standard" atypical antipsychotic drug. On the other hand, typicality is about dimension rather than category, and we suggest the use of the term "spectrum of atypicality." For example, an emphasis is placed on quetiapine to illustrate where a new compound fits in this spectrum. Although dose-related, atypicality may be more a question of prescription attitude than of a specific characteristic of a compound. The degree to which a new compound is clinically superior to another atypical antipsychotic drug, in terms of improving positive, negative or affective symptoms, cognitive function and long-term outcome, will require further a priori hypotheses based on conceptual frameworks that are clinically meaningful. In addition, the results from industry-sponsored trials should be more comparable to those obtained from investigator-leading trials. Finally, the patient characteristics that define a patient's response to a specific antipsychotic drug are unknown. PMID:10740987

Trends in youth reports of sexual solicitations, harassment and unwanted exposure to pornography on the Internet.

PubMed

Mitchell, Kimberly J; Wolak, Janis; Finkelhor, David

2007-02-01

This study was designed to track trends in reports of unwanted sexual solicitations, harassment, and unwanted exposure to pornography via the Internet between 2000 and 2005 across various demographic sub-groups of youth. Cross-sectional data was collected in two equivalent national telephone surveys of 1500 Internet users, ages 10 through 17 years. Bivariate and multivariate analyses were used to determine whether the percentage of youth reporting specific unwanted Internet experiences had changed in 2005, as compared with 2000. The overall incidence and 5-year trends of reporting unwanted sexual solicitations, harassment, and unwanted exposure to pornography varied by age, gender, race, and household income. In particular, the decline in the percentage of youth reporting sexual solicitations was apparent for both boys and girls, all age groups, but not among minority youth and those living in less affluent households. The increase in harassment among particular sub-groups of youth was largely explained by increases in amount of Internet use over the past five years. The increase in unwanted exposure to pornography was particularly apparent among 10- to 12-year-olds, 16- to 17-year-olds, boys, and White, non-Hispanic youth. The decline in the percentage of youth reporting sexual solicitations may be the effect of education and law enforcement activity on this issue in the intervening years. Targeted prevention efforts for minority youth and those living in less affluent households need to be developed. The rise in unwanted pornography exposure may reflect technological changes such as digital photography, faster Internet connections and computer storage capacities, as well as the more aggressive marketing strategies of pornography merchants.

The Women’S Perceptions About Unwanted Pregnancy: A Qualitative Study in Iran

PubMed Central

Akbarzadeh, Marzieh; Yazdanpanahi, Zahra; Zarshenas, Ladan; Sharif, Farkhondeh

2016-01-01

Background: Unwanted pregnancy has affected different aspects of our life. Researchers point out if a child’s birth is unwanted, an increase in maternal issues can be observed. The aim of this study was to describe the women’s viewpoints regarding unwanted pregnancy. Method: This qualitative study using content analysis was employed in Shiraz University in 2013-2014. 20 women with unwanted pregnancy were chosen using purposeful sampling. Data were gathered through semi-structured interviews and trustworthiness of them was evaluated. Results: Findings of this study, according to the participants’ experience, revealed maternal emotions like embarrassment for getting pregnant, mother’s own negative affection, concerns about missing family and other children, and terminating the pregnancy through illegal abortion, the husband’s disagreement about the termination, blaming themselves for thinking about abortion or illegal abortion, and concern about their guilt feeling. Another finding was family problems like husband’s behavior and his negative outlook towards his child and fetus. The next category belonged to anxiety about the future of their child, including economic, social and relational problems, and suppression of the children’s logical expectations. The last finding was the lack of maternal emotional support. Conclusions: Unwanted pregnancy’s effects on the mothers and infants’ health are considerable. A closer observation by family and health care providers for unwanted pregnancies and its results is recommended; therefore, they should be taken care of as high risk pregnancies, requiring family support. PMID:26652070

Effectiveness of Family Planning Policies: The Abortion Paradox

PubMed Central

Bajos, Nathalie; Le Guen, Mireille; Bohet, Aline; Panjo, Henri; Moreau, Caroline

2014-01-01

Objective The relation between levels of contraceptive use and the incidence of induced abortion remains a topic of heated debate. Many of the contradictions are likely due to the fact that abortion is the end point of a process that starts with sexual activity, contraceptive use (or non-use), followed by unwanted pregnancy, a decision to terminate, and access to abortion. Trends in abortion rates reflect changes in each step of this process, and opposing trends may cancel each other out. This paper aims to investigate the roles played by the dissemination of contraception and the evolving norms of motherhood on changes in abortion rates. Methods Drawing data from six national probability surveys that explored contraception and pregnancy wantedness in France from 1978 through 2010, we used multivariate linear regression to explore the associations between trends in contraceptive rates and trends in (i) abortion rates, (ii) unwanted pregnancy rates, (iii) and unwanted birth rates, and to determine which of these 3 associations was strongest. Findings The association between contraceptive rates and abortion rates over time was weaker than that between contraception rates and unwanted pregnancy rates (p = 0.003). Similarly, the association between contraceptive rates and unwanted birth rates over time was weaker than that between contraceptive rates and unwanted pregnancy rates (p = 0.000). PMID:24670784

Quantitative targeting maps based on experimental investigations for a branched tube model in magnetic drug targeting

NASA Astrophysics Data System (ADS)

Gitter, K.; Odenbach, S.

2011-12-01

Magnetic drug targeting (MDT), because of its high targeting efficiency, is a promising approach for tumour treatment. Unwanted side effects are considerably reduced, since the nanoparticles are concentrated within the target region due to the influence of a magnetic field. Nevertheless, understanding the transport phenomena of nanoparticles in an artery system is still challenging. This work presents experimental results for a branched tube model. Quantitative results describe, for example, the net amount of nanoparticles that are targeted towards the chosen region due to the influence of a magnetic field. As a result of measurements, novel drug targeting maps, combining, e.g. the magnetic volume force, the position of the magnet and the net amount of targeted nanoparticles, are presented. The targeting maps are valuable for evaluation and comparison of setups and are also helpful for the design and the optimisation of a magnet system with an appropriate strength and distribution of the field gradient. The maps indicate the danger of accretion within the tube and also show the promising result of magnetic drug targeting that up to 97% of the nanoparticles were successfully targeted.

Albumin nanostructures as advanced drug delivery systems

PubMed Central

Karimi, Mahdi; Bahrami, Sajad; Ravari, Soodeh Baghaee; Zangabad, Parham Sahandi; Mirshekari, Hamed; Bozorgomid, Mahnaz; Shahreza, Somayeh; Sori, Masume; Hamblin, Michael R.

2016-01-01

Introduction One of the biggest impacts that the nanotechnology has made on medicine and biology, has been in the area of drug delivery systems (DDSs). Many drugs suffer from serious problems concerning insolubility, instability in biological environments, poor uptake into cells and tissues, suboptimal selectivity for targets and unwanted side effects. Nanocarriers can be designed as DDSs to overcome many of these drawbacks. One of the most versatile building blocks to prepare these nanocarriers is the ubiquitous, readily available and inexpensive protein, serum albumin. Areas covered This review covers the use of different types of albumin (human, bovine, rat, and chicken egg) to prepare nanoparticle and microparticle-based structures to bind drugs. Various methods have been used to modify the albumin structure. A range of targeting ligands can be attached to the albumin that can be recognized by specific cell receptors that are expressed on target cells or tissues. Expert opinion The particular advantages of albumin used in DDSs include ready availability, ease of chemical modification, good biocompatibility, and low immunogenicity. The regulatory approvals that have been received for several albumin-based therapeutic agents suggest that this approach will continue to be successfully explored. PMID:27216915

You Wouldn't Sober, You Shouldn't Drunk: A Behavioural Change Approach to Changing Attitudes and Responses to Unwanted Sexual Attention in Pubs and Clubs.

PubMed

Wood, Matthew; Shukla, Paurav

2017-11-01

The objective was to evaluate a campaign designed to influence social norms and re-establish boundaries around the issue of unwanted sexual attention in pubs and clubs. In particular, the campaign aimed to raise awareness, and reduce the acceptability, of unwanted sexual attention when drunk. A before-after-with-control group study design was used to evaluate campaign effectiveness. The data was further segmented to explore gender differences and between individuals who reported enjoying going out to get drunk and those who did not. The experimental group with campaign recall demonstrated a significant change in their attitudes to harmful drinking behaviours and unwanted sexual attention compared to the control group. A number of gender differences as well as drink-enjoyment-related differences pre- and post-campaign were observed. Female respondents who were able to recall the campaign demonstrated a significantly lower tolerance of unwanted sexual attention than those who were unable to recall it in either the experimental or control regions. The campaign had limited impact on people who enjoy drunken night outs (DNOs). However, those who do not enjoy DNOs demonstrated significantly higher negative attitudes towards harmful drinking post-campaign recall. The campaign was effective in shifting attitudes towards unwanted sexual attention and harmful drinking behaviour. This was particularly observed among female respondents and those who do not enjoy DNOs. Drinkaware's 'You Wouldn't Sober, You Shouldn't Drunk' behavioural change campaign targets young adults living in North-West England participating in 'drunken nights out'. The experimental group with campaign recall demonstrated a significant change in their attitudes to harmful drinking behaviours and unwanted sexual attention compared to the control group. © The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Risk factors and consequences of unwanted sex among university students: hooking up, alcohol, and stress response.

PubMed

Flack, William F; Daubman, Kimberly A; Caron, Marcia L; Asadorian, Jenica A; D'Aureli, Nicole R; Gigliotti, Shannon N; Hall, Anna T; Kiser, Sarah; Stine, Erin R

2007-02-01

This is the first study of unwanted sexual experiences in the collegiate "hooking-up" culture. In a representative sample of 178 students at a small liberal arts university. Twenty-three percent of women and 7% of men surveyed reported one or more experiences of unwanted sexual intercourse. Seventy-eight percent of unwanted vaginal, anal, and oral incidents took place while--"hooking up,"--whereas 78% of unwanted fondling incidents occurred at parties or bars. The most frequently endorsed reason for unwanted sexual intercourse was impaired judgment due to alcohol. The most frequently endorsed reason for unwanted fondling was that it happened before the perpetrator could be stopped. Of those affected by unwanted sexual intercourse or unwanted fondling, 46.7% and 19.2% reported unwanted memories, 50% and 32.7% reported avoidance and numbing responses, and 30% and 26.9% reported hyperarousal responses, respectively. A preliminary model of unwanted sex and collegiate social dynamics is proposed to provide a heuristic for further research.

Robust cladding light stripper for high-power fiber lasers using soft metals.

PubMed

Babazadeh, Amin; Nasirabad, Reza Rezaei; Norouzey, Ahmad; Hejaz, Kamran; Poozesh, Reza; Heidariazar, Amir; Golshan, Ali Hamedani; Roohforouz, Ali; Jafari, S Naser Tabatabaei; Lafouti, Majid

2014-04-20

In this paper we present a novel method to reliably strip the unwanted cladding light in high-power fiber lasers. Soft metals are utilized to fabricate a high-power cladding light stripper (CLS). The capability of indium (In), aluminum (Al), tin (Sn), and gold (Au) in extracting unwanted cladding light is examined. The experiments show that these metals have the right features for stripping the unwanted light out of the cladding. We also find that the metal-cladding contact area is of great importance because it determines the attenuation and the thermal load on the CLS. These metals are examined in different forms to optimize the contact area to have the highest possible attenuation and avoid localized heating. The results show that sheets of indium are very effective in stripping unwanted cladding light.

Cannabidiol as potential anticancer drug

PubMed Central

Massi, Paola; Solinas, Marta; Cinquina, Valentina; Parolaro, Daniela

2013-01-01

Over the past years, several lines of evidence support an antitumourigenic effect of cannabinoids including Δ9-tetrahydrocannabinol (Δ9-THC), synthetic agonists, endocannabinoids and endocannabinoid transport or degradation inhibitors. Indeed, cannabinoids possess anti-proliferative and pro-apoptotic effects and they are known to interfere with tumour neovascularization, cancer cell migration, adhesion, invasion and metastasization. However, the clinical use of Δ9-THC and additional cannabinoid agonists is often limited by their unwanted psychoactive side effects, and for this reason interest in non-psychoactive cannabinoid compounds with structural affinity for Δ9-THC, such as cannabidiol (CBD), has substantially increased in recent years. The present review will focus on the efficacy of CBD in the modulation of different steps of tumourigenesis in several types of cancer and highlights the importance of exploring CBD/CBD analogues as alternative therapeutic agents. PMID:22506672

Women's Responses to Unwanted Sexual Advances: The Role of Alcohol and Inhibition Conflict

ERIC Educational Resources Information Center

Davis, Kelly Cue; George, William H.; Norris, Jeanette

2004-01-01

In this study we investigated how alcohol consumption affects women's responses to unwanted sexual advances in a hypothetical dating situation. Sixty female social drinkers participated in a 2 times 2 between-subjects experiment, which examined the effects of moderate alcohol intoxication and relationship characteristics on behavioral responses to…

Gender and sexuality in the field: a female ethnographer's experience researching drug use in dance clubs.

PubMed

Perrone, Dina

2010-04-01

This article provides an account of a female ethnographer's experience accessing participants and observing drug-using behaviors in highly sexualized dance clubs. Specifically, it describes how the researcher as a gendered and sexualized self can compromise safety and inhibit access while also serving as an advantage to establishing rapport. The author describes how various methods were employed to appear as part of the cultural scene and access participants, while avoiding, and responding to, unwanted sexual advances. To address such challenges, the author provides both practical and procedural suggestions for researchers and research institutions.

Developmental defects in zebrafish for classification of EGF pathway inhibitors

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

Pruvot, Benoist; Curé, Yoann; Djiotsa, Joachim

2014-01-15

One of the major challenges when testing drug candidates targeted at a specific pathway in whole animals is the discrimination between specific effects and unwanted, off-target effects. Here we used the zebrafish to define several developmental defects caused by impairment of Egf signaling, a major pathway of interest in tumor biology. We inactivated Egf signaling by genetically blocking Egf expression or using specific inhibitors of the Egf receptor function. We show that the combined occurrence of defects in cartilage formation, disturbance of blood flow in the trunk and a decrease of myelin basic protein expression represent good indicators for impairmentmore » of Egf signaling. Finally, we present a classification of known tyrosine kinase inhibitors according to their specificity for the Egf pathway. In conclusion, we show that developmental indicators can help to discriminate between specific effects on the target pathway from off-target effects in molecularly targeted drug screening experiments in whole animal systems. - Highlights: • We analyze the functions of Egf signaling on zebrafish development. • Genetic blocking of Egf expression causes cartilage, myelin and circulatory defects. • Chemical inhibition of Egf receptor function causes similar defects. • Developmental defects can reveal the specificity of Egf pathway inhibitors.« less

[Persistent, excessive crying in 5-month-old infants and the pre-, peri- and postnatal adversities of their mothers in a high-risk sample].

PubMed

Sidor, Anna; Thiel-Bonney, Consolata; Kunz, Elisabeth; Eickhorst, Andreas; Cierpka, Manfred

2012-07-01

To investigate the relationship between persistent, excessive crying in 5-month-old infants and the pre- and perinatal adversities as well as postpartal mood of their mothers. A sample of 300 mother-child dyads was examined at infants' age of 18.5 weeks. All mothers exhibited psychosocial risks such as poverty, lack of social support, being underage, drug abuse or mental disorders. Excessive crying was assessed by the Wessel's «rule of threes». Pre-, peri- and postnatal problems were measured by self-report questionnaires. Multivariate data analysis revealed an increased risk for social adversities during pregnancy (OR = 17.66) and unwanted pregnancy (OR = 13.77). For the postnatal period persistent crying was associated with a higher rate of maternal postpartum depressive symptoms, maternal stress, dysfunctional mother-child interactions, perception of the infant as being «difficult» as well as bonding problems. The results point to the influence of prenatal stress in mothers and a primarily unwanted pregnancy on infants' persistent crying. An increased need for support is suggested in cases of considerably reduced well-being of the mother or bonding problems. The combined effect of prenatal variables and relationship variables influences the occurrence and perpetuation of early regulation problems.

Immunogenicity of therapeutics: a matter of efficacy and safety.

PubMed

Nechansky, Andreas; Kircheis, Ralf

2010-11-01

The unwanted immunogenicity of therapeutic proteins is a major concern regarding patient safety. Furthermore, pharmacokinetic, pharmacodynamic and clinical efficacy can be seriously affected by the immunogenicity of therapeutic proteins. Authorities have fully recognized this issue and demand appropriate and well-characterized assays to detect anti-drug antibodies (ADAs). We provide an overview of the immunogenicity topic in general, the regulatory background and insight into underlying immunological mechanisms and the limited ability to predict clinical immunogenicity a priori. Furthermore, we comment on the analytical testing approach and the status-quo of appropriate method validation. The review provides insight regarding the analytical approach that is expected by regulatory authorities overseeing immunogenicity testing requirements. Additionally, the factors influencing immunogenicity are summarized and key references regarding immunogenicity testing approaches and method validation are discussed. The unwanted immunogenicity of protein therapeutics is of major concern because of its potential to affect patient safety and drug efficacy. Analytical testing is sophisticated and requires more than one assay. Because immunogenicity in humans is hardly predictable, assay development has to start in a timely fashion and for clinical studies immunogenicity assay validation is mandatory prior to analyzing patient serum samples. Regarding ADAs, the question remains as to when such antibodies are regarded of clinical relevance and what levels are, if at all, acceptable. In summary, the detection of ADAs should raise the awareness of the physician concerning patient safety and of the sponsor/manufacture concerning the immunogenic potential of the drug product.

Formulation and Characterization of Aceclofenac -Aloe vera Transemulgel.

PubMed

Raju, Y Prasanna; Haritha, K; Satyanarayana, Rao P; Vandana, K R; Bindu, D Thushara; Vinesha, V; Chowdary, V Harini

2015-01-01

The present research was aimed to formulate aceclofenac transemulgel using Aloe vera as gel base. The prepared formulations were subjected to physical characterization, in-vitro and in-vivo assessment. Aceclofenac, a hydrophobic potential non steroidal anti inflammatory drug, causes ulceration upon chronic oral administration, could be formulated into transemulgel to enhance therapeutic efficacy and to lower the unwanted side effects. The transemulgel was prepared from aqueous Aloe vera gel and aceclofenac emulsion. The prepared transemulgel was evaluated for its pH, viscosity, drug content, skin irritation, in-vitro diffusion and accelerated stability studies. The prepared aceclofenac-Aloe vera tranemulgel and commercial aceclofenac gel were subjected to pharmacodynamic studies in albino rats of Wistar strain employing carrageenan induced left hind paw edema method to assess the anti-inflammatory effect. The transemulgel showed a pH of 6.78 and viscosity of 18 cps. In-vitro diffusion data revealed better permeation characteristics. Topical application of formulation found no skin irritation. Stability study has proved the integrity of the formulation. The prepared aceclofenac Aloe vera transemulgel showed better in-vitro drug release when compared with the commercial aceclofenac gel formulation. Anti-inflammatory activity in treated rats showed the significant paw volume reduction at p<0.05 compared with that of control. Thus, it is concluded that aceclofenac, a potential non steroidal anti inflammatory drug, showed high therapeutic efficiency when formulated into transemulgel using aqueous Aloe vera as gel base.

[Pharmacologic therapy of depression during pregnancy].

PubMed

Bellantuono, Cesario; Migliarese, Giovanni; Imperadore, Giuseppe

2006-02-01

The pregnancy is considered to be relatively high risk period for depressive episodes in women, particularly for those with pre-existing affective disorders. Epidemiological studies indicate that between 10% to 16% of pregnant women fulfil the diagnostic criteria for major depression and on average 20% is affected by an anxiety disorder. Pharmacological treatment of depression during pregnancy, however, brings with it certainties and dilemmas. It has been reported that untreated depression is associated with impaired feto-placental function, premature delivery, miscarriage, low fetal growth and perinatal unwanted effects. On the other hand, the use of antidepressant drugs in pregnancy might be at risk of major malformations (teratogenesis), neonatal toxicity, especially withdrawal symptoms and neuropsychological-behavioural impairment. In addition, the abrupt discontinuation of antidepressants, because of fear for adverse fetal effects, exposes women to serious clinical problems, in particular the disease relapse. A number of reviews indicates that among antidepressant drugs, the older SSRIs (in particular fluoxetine, sertraline, citalopram) seem to be avoided of teratogenic risks; for these reasons such drugs are nowadays considered of choice for the treatment of depression during pregnancy. Less information is available for other drugs, including triciclycs, venlafaxine, mirtazapine, bupropion, escitalopram and duloxetine. Withdrawal symptoms have been reported for all antidepressants; these symptoms, however, were self-limiting in majority of cases and had a favourable outcome. Inconclusive findings emerge, so far, from the few longitudinal studies focusing on the long-term neurodevelopment outcome in children.

Trigeminal pathways deliver a low molecular weight drug from the nose to the brain and orofacial structures.

PubMed

Johnson, Neil J; Hanson, Leah R; Frey, William H

2010-06-07

Intranasal delivery has been shown to noninvasively deliver drugs from the nose to the brain in minutes along the olfactory and trigeminal nerve pathways, bypassing the blood-brain barrier. However, no one has investigated whether nasally applied drugs target orofacial structures, despite high concentrations observed in the trigeminal nerve innervating these tissues. Following intranasal administration of lidocaine to rats, trigeminally innervated structures (teeth, temporomandibular joint (TMJ), and masseter muscle) were found to have up to 20-fold higher tissue concentrations of lidocaine than the brain and blood as measured by ELISA. This concentration difference could allow intranasally administered therapeutics to treat disorders of orofacial structures (i.e., teeth, TMJ, and masseter muscle) without causing unwanted side effects in the brain and the rest of the body. In this study, an intranasally administered infrared dye reached the brain within 10 minutes. Distribution of dye is consistent with dye entering the trigeminal nerve after intranasal administration through three regions with high drug concentrations in the nasal cavity: the middle concha, the maxillary sinus, and the choana. In humans the trigeminal nerve passes through the maxillary sinus to innervate the maxillary teeth. Delivering lidocaine intranasally may provide an effective anesthetic technique for a noninvasive maxillary nerve block. Intranasal delivery could be used to target vaccinations and treat disorders with fewer side effects such as tooth pain, TMJ disorder, trigeminal neuralgia, headache, and brain diseases.

Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator and Drugs: Insights from Cellular Trafficking.

PubMed

Bridges, Robert J; Bradbury, Neil A

2018-01-01

The eukaryotic cell is organized into membrane-delineated compartments that are characterized by specific cadres of proteins sustaining biochemically distinct cellular processes. The appropriate subcellular localization of proteins is key to proper organelle function and provides a physiological context for cellular processes. Disruption of normal trafficking pathways for proteins is seen in several genetic diseases, where a protein's absence for a specific subcellular compartment leads to organelle disruption, and in the context of an individual, a disruption of normal physiology. Importantly, several drug therapies can also alter protein trafficking, causing unwanted side effects. Thus, a deeper understanding of trafficking pathways needs to be appreciated as novel therapeutic modalities are proposed. Despite the promising efficacy of novel therapeutic agents, the intracellular bioavailability of these compounds has proved to be a potential barrier, leading to failures in treatments for various diseases and disorders. While endocytosis of drug moieties provides an efficient means of getting material into cells, the subsequent release and endosomal escape of materials into the cytosol where they need to act has been a barrier. An understanding of cellular protein/lipid trafficking pathways has opened up strategies for increasing drug bioavailability. Approaches to enhance endosomal exit have greatly increased the cytosolic bioavailability of drugs and will provide a means of investigating previous drugs that may have been shelved due to their low cytosolic concentration.

Prevalence of the prescription of potentially interacting drugs.

PubMed

Tragni, Elena; Casula, Manuela; Pieri, Vasco; Favato, Giampiero; Marcobelli, Alberico; Trotta, Maria Giovanna; Catapano, Alberico Luigi

2013-01-01

The use of multiple medications is becoming more common, with a correspondingly increased risk of untoward effects and drug-related morbidity and mortality. We aimed at estimating the prevalence of prescription of relevant potentially interacting drugs and at evaluating possible predictors of potentially interacting drug exposure. We retrospectively analyzed data on prescriptions dispensed from January 2004 to August 2005 to individuals of two Italian regions with a population of almost 2.1 million individuals. We identified 27 pairs of potentially interacting drugs by examining clinical relevance, documentation, and volume of use in Italy. Subjects who received at least one prescription of both drugs were selected. Co-prescribing denotes "two prescriptions in the same day", and concomitant medication "the prescription of two drugs with overlapping coverage". A logistic regression analysis was conducted to examine the predictors of potential Drug-Drug Interaction (pDDIs). 957,553 subjects (45.3% of study population) were exposed to at least one of the drugs/classes of the 27 pairs. Overall, pDDIs occurred 2,465,819 times. The highest rates of concomitant prescription and of co-prescription were for ACE inhibitors+NSAIDs (6,253 and 4,621/100,000 plan participants). Considering concomitance, the male/female ratio was <1 in 17/27 pairs (from 0.31 for NSAIDs-ASA+SSRI to 0.74 for omeprazole+clopidogrel). The mean age was lowest for methotrexate pairs (+omeprazole, 59.9 years; +NSAIDs-ASA, 59.1 years) and highest for digoxin+verapamil (75.4 years). In 13/27 pairs, the mean ages were ≥70 years. On average, subjects involved in pDDIs received ≥10 drugs. The odds of exposure were more frequently higher for age ≥65 years, males, and those taking a large number of drugs. A substantial number of clinically important pDDIs were observed, particularly among warfarin users. Awareness of the most prevalent pDDIs could help practitioners in preventing concomitant use, resulting in a better quality of drug prescription and potentially avoiding unwanted side effects.

[Antidepressant drugs and breastfeeding].

PubMed

Bellantuono, Cesario; Migliarese, Giovanni; Maggioni, Francesca; Imperadore, Giuseppe

2007-01-01

The post-partum period, as well as pregnancy, is associated with an increased risk of anxiety and/or affective disorders. Postnatal depression, frequently in co-morbidity with anxiety symptoms, is recognised as the most frequent form of maternal morbidity after delivery, with a prevalence rate estimated between 5% to 15%. Among antidepressant drugs, the SSRIs are considered the drugs of choice in the treatment of post-partum affective disorders, particularly in the major depression. It is, thus, crucial from a clinical standpoint to establish, in the newborn whose mother needs to be treated with an SSRI, the safety profile of these drugs during breastfeeding. The benefits of breastfeeding, on the other hand, both for the nursing mother and the infant, are in fact very well documented. Unfortunately, all antidepressant drugs, including SSRIs, cross into breast milk and the milk-to-plasma ratio, a measure proposed to establish the amount of drug transferred to maternal milk, does not seem to be a reliable parameter to predict the safety of these drugs. From the available literature, however, it seems that among SSRIs, paroxetina and sertralina offer the best safety profile, as these drugs has never been associated with unsafe reports in suckling infants. Despite these reassuring but preliminary data, more studies are needed to better assess the safety of the antidepressant drugs in the infants exposed during breastfeeding. As general rule, it is important to recommend if the mother wishes to breastfeed her infant while taking an antidepressant, that the baby should be closely monitored in order to detect, as soon as possible, any unwanted drug-related side effect.

Drug Interactions in Childhood Cancer

PubMed Central

Haidar, Cyrine; Jeha, Sima

2016-01-01

Children with cancer are increasingly benefiting from novel therapeutic strategies and advances in supportive care, as reflected in improvements in both their survival and quality of life. However, the continuous emergence of new oncology drugs and supportive care agents has also increased the possibility of deleterious drug interactions and healthcare providers need to practice extreme caution when combining medications. In this review, we discuss the most common interactions of chemotherapeutic agents with supportive care drugs such as anticonvulsants, antiemetics, uric acid–lowering agents, acid suppressants, antimicrobials, and pain management medications in pediatric oncology patients. As chemotherapy agents interact not only with medications but also with foods and herbal supplements that patients receive during the course of their treatment, we also briefly review such interactions and provide recommendations to avoid unwanted and potentially fatal interactions in children with cancer. PMID:20869315

Structure-based drug design targeting the cell membrane receptor GPBAR1: exploiting the bile acid scaffold towards selective agonism

NASA Astrophysics Data System (ADS)

di Leva, Francesco Saverio; Festa, Carmen; Renga, Barbara; Sepe, Valentina; Novellino, Ettore; Fiorucci, Stefano; Zampella, Angela; Limongelli, Vittorio

2015-11-01

Bile acids can regulate nutrient metabolism through the activation of the cell membrane receptor GPBAR1 and the nuclear receptor FXR. Developing an exogenous control over these receptors represents an attractive strategy for the treatment of enterohepatic and metabolic disorders. A number of dual GPBAR1/FXR agonists are known, however their therapeutic use is limited by multiple unwanted effects due to activation of the diverse downstream signals controlled by the two receptors. On the other hand, designing selective GPBAR1 and FXR agonists is challenging since the two proteins share similar structural requisites for ligand binding. Here, taking advantage of our knowledge of the two targets, we have identified through a rational drug design study a series of amine lithocholic acid derivatives as selective GPBAR1 agonists. The presence of the 3α-NH2 group on the steroidal scaffold is responsible for the selectivity over FXR unveiling unprecedented structural insights into bile acid receptors activity modulation.

Alien or American? Immigration Laws and Amerasian People.

DTIC Science & Technology

1985-08-01

of birth control . The basic fabric of . individual morality underlies these strongly held . .. . . . . . . * . . - . .*.~-,’..-i*--., 55...intent of this paper to explore the ethical and moral questions that permeate the controversy over birth control . The ethical problem that does...unplanned and unwanted births. Safe, effective birth control would theoretically have the potential to reduce the problem of unwanted ethnically-mixed

Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research.

PubMed

Maes, Michael; Nowak, Gabriel; Caso, Javier R; Leza, Juan Carlos; Song, Cai; Kubera, Marta; Klein, Hans; Galecki, Piotr; Noto, Cristiano; Glaab, Enrico; Balling, Rudi; Berk, Michael

2016-07-01

Meta-analyses confirm that depression is accompanied by signs of inflammation including increased levels of acute phase proteins, e.g., C-reactive protein, and pro-inflammatory cytokines, e.g., interleukin-6. Supporting the translational significance of this, a meta-analysis showed that anti-inflammatory drugs may have antidepressant effects. Here, we argue that inflammation and depression research needs to get onto a new track. Firstly, the choice of inflammatory biomarkers in depression research was often too selective and did not consider the broader pathways. Secondly, although mild inflammatory responses are present in depression, other immune-related pathways cannot be disregarded as new drug targets, e.g., activation of cell-mediated immunity, oxidative and nitrosative stress (O&NS) pathways, autoimmune responses, bacterial translocation, and activation of the toll-like receptor and neuroprogressive pathways. Thirdly, anti-inflammatory treatments are sometimes used without full understanding of their effects on the broader pathways underpinning depression. Since many of the activated immune-inflammatory pathways in depression actually confer protection against an overzealous inflammatory response, targeting these pathways may result in unpredictable and unwanted results. Furthermore, this paper discusses the required improvements in research strategy, i.e., path and drug discovery processes, omics-based techniques, and systems biomedicine methodologies. Firstly, novel methods should be employed to examine the intracellular networks that control and modulate the immune, O&NS and neuroprogressive pathways using omics-based assays, including genomics, transcriptomics, proteomics, metabolomics, epigenomics, immunoproteomics and metagenomics. Secondly, systems biomedicine analyses are essential to unravel the complex interactions between these cellular networks, pathways, and the multifactorial trigger factors and to delineate new drug targets in the cellular networks or pathways. Drug discovery processes should delineate new drugs targeting the intracellular networks and immune-related pathways.

Abortion and unwanted pregnancy in Adigrat Zonal Hospital, Tigray, north Ethiopia.

PubMed

Gessessew, Amanuel

2010-09-01

Unwanted pregnancy is associated with increased risk of maternal mortality and morbidity. This study was done to determine the causes of unwanted pregnancy and its impact on maternal health. A cross sectional study (February 1, 2002-January 31, 2004) was conducted on 907 patients with diagnosis of abortion and admitted to the gynecological ward of Adigrat zonal hospital, Tigray Region, Ethiopia. This accounts to 12.6% of all hospital and 60.6% of gynecological admissions. The majority of these women (69.8%) had unwanted pregnancy. Modern contraception methods were not in use in 76.2% of unwanted and 57.7% of wanted pregnancies (P = 0.008). Interference was reported in 81.4% of unwanted pregnancy. High incidence of complication was reported in patients with unwanted pregnancy. In this study it is found that unwanted pregnancy is associated with increased risk of maternal morbidity and mortality. The development and prompt implementation of a strategy that enables women to safely manage unwanted pregnancy is recommended.

Identification and Prioritization of Important Attributes of Disease-Modifying Drugs in Decision Making among Patients with Multiple Sclerosis: A Nominal Group Technique and Best-Worst Scaling.

PubMed

Kremer, Ingrid E H; Evers, Silvia M A A; Jongen, Peter J; van der Weijden, Trudy; van de Kolk, Ilona; Hiligsmann, Mickaël

2016-01-01

Understanding the preferences of patients with multiple sclerosis (MS) for disease-modifying drugs and involving these patients in clinical decision making can improve the concordance between medical decisions and patient values and may, subsequently, improve adherence to disease-modifying drugs. This study aims first to identify which characteristics-or attributes-of disease-modifying drugs influence patients´ decisions about these treatments and second to quantify the attributes' relative importance among patients. First, three focus groups of relapsing-remitting MS patients were formed to compile a preliminary list of attributes using a nominal group technique. Based on this qualitative research, a survey with several choice tasks (best-worst scaling) was developed to prioritize attributes, asking a larger patient group to choose the most and least important attributes. The attributes' mean relative importance scores (RIS) were calculated. Nineteen patients reported 34 attributes during the focus groups and 185 patients evaluated the importance of the attributes in the survey. The effect on disease progression received the highest RIS (RIS = 9.64, 95% confidence interval: [9.48-9.81]), followed by quality of life (RIS = 9.21 [9.00-9.42]), relapse rate (RIS = 7.76 [7.39-8.13]), severity of side effects (RIS = 7.63 [7.33-7.94]) and relapse severity (RIS = 7.39 [7.06-7.73]). Subgroup analyses showed heterogeneity in preference of patients. For example, side effect-related attributes were statistically more important for patients who had no experience in using disease-modifying drugs compared to experienced patients (p < .001). This study shows that, on average, patients valued effectiveness and unwanted effects as most important. Clinicians should be aware of the average preferences but also that attributes of disease-modifying drugs are valued differently by different patients. Person-centred clinical decision making would be needed and requires eliciting individual preferences.

Identification and Prioritization of Important Attributes of Disease-Modifying Drugs in Decision Making among Patients with Multiple Sclerosis: A Nominal Group Technique and Best-Worst Scaling

PubMed Central

Kremer, Ingrid E. H.; van der Weijden, Trudy; van de Kolk, Ilona

2016-01-01

Objectives Understanding the preferences of patients with multiple sclerosis (MS) for disease-modifying drugs and involving these patients in clinical decision making can improve the concordance between medical decisions and patient values and may, subsequently, improve adherence to disease-modifying drugs. This study aims first to identify which characteristics–or attributes–of disease-modifying drugs influence patients´ decisions about these treatments and second to quantify the attributes’ relative importance among patients. Methods First, three focus groups of relapsing-remitting MS patients were formed to compile a preliminary list of attributes using a nominal group technique. Based on this qualitative research, a survey with several choice tasks (best-worst scaling) was developed to prioritize attributes, asking a larger patient group to choose the most and least important attributes. The attributes’ mean relative importance scores (RIS) were calculated. Results Nineteen patients reported 34 attributes during the focus groups and 185 patients evaluated the importance of the attributes in the survey. The effect on disease progression received the highest RIS (RIS = 9.64, 95% confidence interval: [9.48–9.81]), followed by quality of life (RIS = 9.21 [9.00–9.42]), relapse rate (RIS = 7.76 [7.39–8.13]), severity of side effects (RIS = 7.63 [7.33–7.94]) and relapse severity (RIS = 7.39 [7.06–7.73]). Subgroup analyses showed heterogeneity in preference of patients. For example, side effect-related attributes were statistically more important for patients who had no experience in using disease-modifying drugs compared to experienced patients (p < .001). Conclusions This study shows that, on average, patients valued effectiveness and unwanted effects as most important. Clinicians should be aware of the average preferences but also that attributes of disease-modifying drugs are valued differently by different patients. Person-centred clinical decision making would be needed and requires eliciting individual preferences. PMID:27812117

A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets.

PubMed

Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

2011-01-01

Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH's intrinsic characteristics.

A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

PubMed Central

Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

2011-01-01

Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics. PMID:21720502

Novel Molecular Strategies and Targets for Opioid Drug Discovery for the Treatment of Chronic Pain

PubMed Central

Olson, Keith M.; Lei, Wei; Keresztes, Attila; LaVigne, Justin; Streicher, John M.

2017-01-01

Opioid drugs like morphine and fentanyl are the gold standard for treating moderate to severe acute and chronic pain. However, opioid drug use can be limited by serious side effects, including constipation, tolerance, respiratory suppression, and addiction. For more than 100 years, we have tried to develop opioids that decrease or eliminate these liabilities, with little success. Recent advances in understanding opioid receptor signal transduction have suggested new possibilities to activate the opioid receptors to cause analgesia, while reducing or eliminating unwanted side effects. These new approaches include designing functionally selective ligands, which activate desired signaling cascades while avoiding signaling cascades that are thought to provoke side effects. It may also be possible to directly modulate downstream signaling through the use of selective activators and inhibitors. Separate from downstream signal transduction, it has also been found that when the opioid system is stimulated, various negative feedback systems are upregulated to compensate, which can drive side effects. This has led to the development of multi-functional molecules that simultaneously activate the opioid receptor while blocking various negative feedback receptor systems including cholecystokinin and neurokinin-1. Other novel approaches include targeting heterodimers of the opioid and other receptor systems which may drive side effects, and making endogenous opioid peptides druggable, which may also reduce opioid mediated side effects. Taken together, these advances in our molecular understanding provide a path forward to break the barrier in producing an opioid with reduced or eliminated side effects, especially addiction, which may provide relief for millions of patients. PMID:28356897

Maternal Identity Formation in a Military Sample: A Longitudinal Perspective

DTIC Science & Technology

2006-06-08

effective interventions. Successful interventions to assist military wives with maternal adaptation and role adjustment will be possible with a greater 7...maternal identity formation and role adaptation. Despite the obvious need for focused interventions to assist women with maternal identity formation and...pregnancies tended to be unwanted and remain unwanted even in late gestation . In her sample, the women describing the greatest number of unplanned

Miniature Short Hairpin RNA Screens to Characterize Antiproliferative Drugs

PubMed Central

Kittanakom, Saranya; Arnoldo, Anthony; Brown, Kevin R.; Wallace, Iain; Kunavisarut, Tada; Torti, Dax; Heisler, Lawrence E.; Surendra, Anuradha; Moffat, Jason; Giaever, Guri; Nislow, Corey

2013-01-01

The application of new proteomics and genomics technologies support a view in which few drugs act solely by inhibiting a single cellular target. Indeed, drug activity is modulated by complex, often incompletely understood cellular mechanisms. Therefore, efforts to decipher mode of action through genetic perturbation such as RNAi typically yields “hits” that fall into several categories. Of particular interest to the present study, we aimed to characterize secondary activities of drugs on cells. Inhibiting a known target can result in clinically relevant synthetic phenotypes. In one scenario, drug perturbation could, for example, improperly activate a protein that normally inhibits a particular kinase. In other cases, additional, lower affinity targets can be inhibited as in the example of inhibition of c-Kit observed in Bcr-Abl−positive cells treated with Gleevec. Drug transport and metabolism also play an important role in the way any chemicals act within the cells. Finally, RNAi per se can also affect cell fitness by more general off-target effects, e.g., via the modulation of apoptosis or DNA damage repair. Regardless of the root cause of these unwanted effects, understanding the scope of a drug’s activity and polypharmacology is essential for better understanding its mechanism(s) of action, and such information can guide development of improved therapies. We describe a rapid, cost-effective approach to characterize primary and secondary effects of small-molecules by using small-scale libraries of virally integrated short hairpin RNAs. We demonstrate this principle using a “minipool” composed of shRNAs that target the genes encoding the reported protein targets of approved drugs. Among the 28 known reported drug−target pairs, we successfully identify 40% of the targets described in the literature and uncover several unanticipated drug−target interactions based on drug-induced synthetic lethality. We provide a detailed protocol for performing such screens and for analyzing the data. This cost-effective approach to mammalian knockdown screens, combined with the increasing maturation of RNAi technology will expand the accessibility of similar approaches in academic settings. PMID:23797109

Pharmacology and Clinical Drug Candidates in Redox Medicine

PubMed Central

Casas, Ana I.; Maghzal, Ghassan J.; Seredenina, Tamara; Kaludercic, Nina; Robledinos-Anton, Natalia; Di Lisa, Fabio; Stocker, Roland; Ghezzi, Pietro; Jaquet, Vincent; Cuadrado, Antonio

2015-01-01

Abstract Significance: Oxidative stress is suggested to be a disease mechanism common to a wide range of disorders affecting human health. However, so far, the pharmacotherapeutic exploitation of this, for example, based on chemical scavenging of pro-oxidant molecules, has been unsuccessful. Recent Advances: An alternative emerging approach is to target the enzymatic sources of disease-relevant oxidative stress. Several such enzymes and isoforms have been identified and linked to different pathologies. For some targets, the respective pharmacology is quite advanced, that is, up to late-stage clinical development or even on the market; for others, drugs are already in clinical use, although not for indications based on oxidative stress, and repurposing seems to be a viable option. Critical Issues: For all other targets, reliable preclinical validation and drug ability are key factors for any translation into the clinic. In this study, specific pharmacological agents with optimal pharmacokinetic profiles are still lacking. Moreover, these enzymes also serve largely unknown physiological functions and their inhibition may lead to unwanted side effects. Future Directions: The current promising data based on new targets, drugs, and drug repurposing are mainly a result of academic efforts. With the availability of optimized compounds and coordinated efforts from academia and industry scientists, unambiguous validation and translation into proof-of-principle studies seem achievable in the very near future, possibly leading towards a new era of redox medicine. Antioxid. Redox Signal. 23, 1113–1129. PMID:26415051

The Unwanted Child.

ERIC Educational Resources Information Center

Safonova, Tamara; Leparsky, E. A.

1998-01-01

This study examined mothers' attitudes toward pregnancy and outcomes of unwanted pregnancies in 1,454 women in Moscow (Russia). Unplanned and unwanted pregnancies greatly increased the risk of unfavorable pregnancy outcomes (especially prematurity and intrauterine developmental delay). The principal factor contributing to an unwanted pregnancy was…

Challenges in GC-MS analysis: Case studies on phenibut and ethylphenidate.

PubMed

Lee, Hui Zhi Shirley; Ong, Mei Ching; Lim, Jong Lee Wendy; Yap, Tiong Whei Angeline

2017-08-01

The challenges associated with drug analysis using GC-MS such as thermal degradation, cyclisation or unwanted side reactions causing potential erroneous identification have become evident in view of the high surge in new drugs available in the market. Two case studies illustrated how alternative methods or modifications to existing techniques can help to circumvent the limitations. In the first case study, phenibut which is a GABA analogue, cyclises to 4-phenyl-2-pyrrolidinone under thermal conditions. The identification of phenibut was achieved through derivatisation and identification of its TMS derivative. The second case study, thermal degradation was minimised on drugs of interest methylphenidate and ethylphenidate by reducing the injector port temperature to 200°C and maintaining the GC oven temperature at below 190°C in order to prevent thermal degradation of the drugs of interest. Copyright © 2017 Elsevier B.V. All rights reserved.

Histological assessment of follicular delivery of flutamide by solid lipid nanoparticles: potential tool for the treatment of androgenic alopecia.

PubMed

Hamishehkar, Hamed; Ghanbarzadeh, Saeed; Sepehran, Sasan; Javadzadeh, Yousef; Adib, Zahra Mardhiah; Kouhsoltani, Maryam

2016-01-01

Flutamide is a potent anti-androgen with the several unwanted side effects in systemic administration, therefore, it has attracted special interest in the development of topically applied formulations for the treatment of androgenic alopecia. The purpose of this study was to prepare and characterize the solid lipid nanoparticles (SLNs) of Flutamide for follicular targeting in the treatment of the androgenic alopecia. Flutamide-loaded SLNs, promising drug carriers for topical application were prepared by hot melt homogenization method. Drug permeation and accumulation in the exercised rat skin and histological study on the male hamsters were performed to assess drug delivery efficiency in vitro and in vivo, respectively. The optimized Flutamide-loaded SLNs (size 198 nm, encapsulation efficiency percentage 65% and loading efficiency percentage 3.27%) exhibited a good stability during the period of at least 2 months. The results of X-ray diffraction showed Flutamide amorphous state confirming uniform drug dispersion in the SLNs structure. Higher skin drug deposition (1.75 times) of SLN formulation compared to Flutamide hydroalcoholic solution represented better localization of the drug in the skin. The in vivo studies showed more new hair follicle growth by utilizing Flutamide-loaded SLNs than Flutamide hydroalcoholic solution which could be due to the higher accumulation of SLNs in the hair follicles as well as slowly and continues release of the Flutamide through the SLNs maximizing hair follicle exposure by antiandrogenic drug. It was concluded Flutamide-loaded SLN formulation can be used as a promising colloidal drug carriers for topical administration of Flutamide in the treatment of androgenic alopecia.

The roles of safety and compliance in determining effectiveness of topical therapy for psoriasis.

PubMed

Stein Gold, Linda; Corvari, Linda

2007-01-01

Topical therapies are the mainstays of treatment for most patients with psoriasis because they relieve symptoms and reduce the size and severity of lesions. The effectiveness of a therapeutic intervention is a function of drug efficacy (determined by randomized clinical trial results) and patient safety and compliance. Alterations in any parameter can have a substantial influence on clinical outcomes. However, topical agents can be associated with unwanted and potentially toxic side effects that make physicians reluctant to prescribe them, and patients intentionally discontinue treatment with these topical agents. To maximize effectiveness and improve patient safety, physicians may prescribe medications in combination, sequential, or rotational therapeutic regimens. This treatment strategy has the potential to improve the overall efficacy and safety of topical therapy; however, the effectiveness of this method may be compromised because the complexity of the therapeutic regimen may decrease patient compliance. Newer topical therapies that have a convenient once-daily dosing schedule are needed and will have important implications for patient compliance.

A Novel Nitronyl Nitroxide with Salicylic Acid Framework Attenuates Pain Hypersensitivity and Ectopic Neuronal Discharges in Radicular Low Back Pain.

PubMed

Han, Wen-Juan; Chen, Lei; Wang, Hai-Bo; Liu, Xiang-Zeng; Hu, San-Jue; Sun, Xiao-Li; Luo, Ceng

2015-01-01

Evidence has accumulated that reactive oxygen species and inflammation play crucial roles in the development of chronic pain, including radicular low back pain. Nonsteroid anti-inflammatory drugs (NSAIDs), for example, salicylic acid, aspirin, provided analgesic effects in various types of pain. However, long-term use of these drugs causes unwanted side effects, which limits their implication. Stable nitronyl (NIT) nitroxide radicals have been extensively studied as a unique and interesting class of new antioxidants for protection against oxidative damage. The present study synthesized a novel NIT nitroxide radical with salicylic acid framework (SANR) to provide synergistic effect of both antioxidation and antiinflammation. We demonstrated for the first time that both acute and repeated SANR treatment exerted dramatic analgesic effect in radicular low back pain mimicked by chronic compression of dorsal root ganglion in rats. This analgesic potency was more potent than that produced by classical NSAIDs aspirin and traditional nitroxide radical Tempol alone. Furthermore, SANR-induced behavioral analgesia is found to be mediated, at least in partial, by a reduction of ectopic spontaneous discharges in injured DRG neurons. Therefore, the synthesized NIT nitroxide radical coupling with salicylic acid framework may represent a novel potential therapeutic candidate for treatment of chronic pain, including radicular low back pain.

Prevalence of sexual coercion and its association with unwanted pregnancies among young pregnant females in Kampala, Uganda: a facility based cross-sectional study.

PubMed

Tusiime, Suzan; Musinguzi, Geofrey; Tinkitina, Benjamin; Mwebaza, Norah; Kisa, Rose; Anguzu, Ronald; Kiwanuka, Noah

2015-09-24

Sexual coercion is associated with sexually transmitted infections and unwanted pregnancies with consequential unsafe abortions and increased maternal morbidity and mortality. Current literature focuses mainly on its risk factors but less on its resultant deleterious health effects. We conducted a study to determine the prevalence of sexual coercion and its association with unwanted pregnancies among young pregnant women. In a cross-sectional study, four hundred and sixteen (416) consenting pregnant females aged 15-24 years attending antenatal clinics in Lubaga division Kampala district in Uganda were enrolled using systematic sampling. Quantitative and qualitative data on sexual coercion were collected by female interviewers. Adjusted Prevalence Proportion Ratios (Adj. PPRs) of unwanted pregnancy and associated 95 % confidence intervals were estimated by generalized linear models with log link function and Poisson family distribution using robust variance estimator. Quantitative data were analyzed using Stata version 10.0, while qualitative data were analyzed using manifest content analysis. Prevalence of sexual coercion was 24 % and was higher among those who had non consensual sexual debut (29.0 %) compared with those who had consensual sexual debut (22.6 %). The prevalence of unwanted pregnancy was 18.3 % and was higher among participants who had been sexually coerced relative to their counterparts (p < 0.001). History of sexual coercion in the past 12 months and non consensual sexual debut were associated with unwanted pregnancy [adj.PPR = 2.23, 95 % CI: (1.49-3.32)] and 1.72, 95 % CI: (1.16- 2.54)] respectively. Qualitative results indicated that different forms/contexts of sexual coercion, such as deception, transactional sex and physical force influenced unwanted pregnancies. This study highlights that a quarter of our participants in our quantitative study had experienced sexual coercion in the past twelve months and nearly a third of these, had history of non consensual sexual debut. Unwanted pregnancy was higher among the sexually coerced and those who had non consensual sexual debut. Sexual coercion among pregnant women aged 15-24 years in Kampala, Uganda is high and is significantly associated with unwanted pregnancy. Comprehensive sex education targeting young people (<25 years), along with availability and access to youth friendly centers may be useful in addressing sexual coercion and its negative outcomes.

Older People's Preferences for Side Effects Associated with Antimuscarinic Treatments of Overactive Bladder: A Discrete-Choice Experiment.

PubMed

Decalf, Veerle H; Huion, Anja M J; Benoit, Dries F; Denys, Marie-Astrid; Petrovic, Mirko; Everaert, Karel C M M

2017-08-01

Understanding the importance older people attribute to the different side effects associated with oral antimuscarinic treatments for overactive bladder (OAB) could help inform prescribers, healthcare policy makers and the drug industry. Our objective was to quantify the importance of the most prevalent cognitive and side effects of oral antimuscarinic treatments for OAB in older people. We conducted a discrete-choice experiment (DCE) with the assistance of an interviewer with community-dwelling and hospitalized older people aged >65 years. The DCE involved two hypothetical drugs for imaginary OAB, with three levels of four side effects for each drug, and the International Consultation on Incontinence Questionnaire-Overactive Bladder and EuroQol 5-Dimensions (EQ-5D) questionnaire were also administered. Data were analysed using a conditional logit model. In total, 276 older people participated in the study. The median age was 75 years (interquartile range [IQR] 69-80), 63% were women and 21% had OAB syndrome. The most unwanted side effect in the choice of antimuscarinics for OAB was severe cognitive effects, followed by severe constipation, severe blurred vision, severe dry mouth, moderate cognitive effects and moderate constipation. Severe cognitive effects were at least 1.7 times as important as severe constipation. Exploratory subgroup analysis showed that none of the attributes was found to be significant in people who scored as anxious or depressed on the EQ-5D, and preferences about cognitive effects, constipation and blurred vision were equal in people with and without OAB. Older people attribute more importance to loss of cognitive function as a possible side effect of antimuscarinic treatment than to the three most prevalent possible side effects of this treatment.

Systems biology impact on antiepileptic drug discovery.

PubMed

Margineanu, Doru Georg

2012-02-01

Systems biology (SB), a recent trend in bioscience research to consider the complex interactions in biological systems from a holistic perspective, sees the disease as a disturbed network of interactions, rather than alteration of single molecular component(s). SB-relying network pharmacology replaces the prevailing focus on specific drug-receptor interaction and the corollary of rational drug design of "magic bullets", by the search for multi-target drugs that would act on biological networks as "magic shotguns". Epilepsy being a multi-factorial, polygenic and dynamic pathology, SB approach appears particularly fit and promising for antiepileptic drug (AED) discovery. In fact, long before the advent of SB, AED discovery already involved some SB-like elements. A reported SB project aimed to find out new drug targets in epilepsy relies on a relational database that integrates clinical information, recordings from deep electrodes and 3D-brain imagery with histology and molecular biology data on modified expression of specific genes in the brain regions displaying spontaneous epileptic activity. Since hitting a single target does not treat complex diseases, a proper pharmacological promiscuity might impart on an AED the merit of being multi-potent. However, multi-target drug discovery entails the complicated task of optimizing multiple activities of compounds, while having to balance drug-like properties and to control unwanted effects. Specific design tools for this new approach in drug discovery barely emerge, but computational methods making reliable in silico predictions of poly-pharmacology did appear, and their progress might be quite rapid. The current move away from reductionism into network pharmacology allows expecting that a proper integration of the intrinsic complexity of epileptic pathology in AED discovery might result in literally anti-epileptic drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

The making of unwanted sex: gendered and neoliberal norms in college women's unwanted sexual experiences.

PubMed

Bay-Cheng, Laina Y; Eliseo-Arras, Rebecca K

2008-01-01

Building on extant research regarding the role of gendered norms in women's consent to unwanted sex with male partners as well as recent studies of how the sociopolitical discourse of neoliberalism shapes sexuality at the individual level, we conducted a thematic analysis of undergraduate women's (N = 22) descriptions of their experiences of unwanted sex. In accordance with previous research (Gavey, 2005; Martin, 1996; Phillips, 2000; Tolman, 2002), gendered norms (e.g., women's sexual passivity; subordination of women's sexual interests to those of men) played important roles (a) laying the foundation for unwanted sex, and (b) in-the-moment negotiations between partners. In an extension of the established literature regarding unwanted sex, we also noted the emergence of neoliberal norms (e.g., personal responsibility) in participants' discussions of unwanted sex after the fact. We use these results to argue that gender and neoliberal ideologies work in tandem to (re)produce women's consent to unwanted sex.

Organotin Polyethers as Biomaterials

PubMed Central

Carraher, Charles E.; Roner, Michael R.

2009-01-01

Organotin polyethers are easily synthesized employing interfacial polymerization systems involving the reaction of hydroxyl-containing Lewis bases and organotin halides. A wide variety of organotin-containing polymeric products have been synthesized including those derived from natural and synthetic polymers such as lignin, xylan, cellulose, dextran, and poly(vinyl alcohol). Others have been synthesized employing known drug diols such as dicumarol, DES, and dienestrol and a wide variety of synthetic diols. Included in these materials are the first water soluble organotin polymers. The organotin polyethers exhibit a wide range of biological activities. Some selectively inhibit a number of unwanted bacteria, including Staph. MRSA, and unwanted yeasts such as Candida albicans. Some also inhibit a variety of viruses including those responsible for herpes infections and smallpox. Others show good inhibition of a wide variety of cancer cell lines including cell lines associated with ovarian, colon, lung, prostrate, pancreatic and breast cancer. The synthesis, structural characterization, and biological characterization of these materials is described in this review.

Sources of and Remedies for Removing Unwanted Reflections in Millimeter Wave Images of Complex SOFI-Covered Space Shuttle Structures

NASA Technical Reports Server (NTRS)

Kharkovsky, S.; Zoughi, R.; Hepburn, Frank L.

2007-01-01

In the recent years, continuous-wave near-field and lens-focused millimeter wave imaging systems have been effectively used to demonstrate their utility for producing high-resolution images of metallic structures covered with spay on foam insulation (SOFI) such as the Space Shuttle external fuel tank. However, for some specific structures a certain interference -pattern may be superimposed on the produced images. There are methods by which the influence of this unwanted interference can be reduced, such as the incorporation of an incidence .angle and the proper use of signal polarization. This paper presents the basics of this problem and describes the use of the methods for reducing this unwanted influence through specific examples.

Emergency contraception - Potential for women's health

PubMed Central

Mittal, Suneeta

2014-01-01

Emergency contraception (EC) is a safe and effective method which is used to prevent unwanted pregnancy after unprotected sexual intercourse. Many of the unwanted pregnancies end in unsafe abortions. The search for an ideal contraceptive, which does not interfere with spontaneity or pleasure of the sexual act, yet effectively controls the fertility, is still continuing. Numerous contraceptive techniques are available, yet contraceptive coverage continues to be poor in India. Thus, even when not planning for a pregnancy, exposure to unprotected sex takes place often, necessitating the use of emergency contraception. This need may also arise due to failure of contraceptive method being used (condom rupture, diaphragm slippage, forgotten oral pills) or following sexual assault. Emergency contraception is an intervention that can prevent a large number of unwanted pregnancies resulting from failure of regular contraception or unplanned sexual activity, which in turn helps in reducing the maternal mortality and morbidity due to unsafe abortions. However, a concern has been expressed regarding repeated and indiscriminate usage of e-pill, currently the rational use of emergency contraception is being promoted as it is expected to make a significant dent in reducing the number of unwanted pregnancies and unsafe abortions. In fact, since the introduction of emergency contraception, the contribution of unsafe abortion towards maternal mortality has declined from 13 to 8 per cent. PMID:25673542

Emergency contraception - potential for women's health.

PubMed

Mittal, Suneeta

2014-11-01

Emergency contraception (EC) is a safe and effective method which is used to prevent unwanted pregnancy after unprotected sexual intercourse. Many of the unwanted pregnancies end in unsafe abortions. The search for an ideal contraceptive, which does not interfere with spontaneity or pleasure of the sexual act, yet effectively controls the fertility, is still continuing. Numerous contraceptive techniques are available, yet contraceptive coverage continues to be poor in India. Thus, even when not planning for a pregnancy, exposure to unprotected sex takes place often, necessitating the use of emergency contraception. This need may also arise due to failure of contraceptive method being used (condom rupture, diaphragm slippage, forgotten oral pills) or following sexual assault. Emergency contraception is an intervention that can prevent a large number of unwanted pregnancies resulting from failure of regular contraception or unplanned sexual activity, which in turn helps in reducing the maternal mortality and morbidity due to unsafe abortions. However, a concern has been expressed regarding repeated and indiscriminate usage of e-pill, currently the rational use of emergency contraception is being promoted as it is expected to make a significant dent in reducing the number of unwanted pregnancies and unsafe abortions. In fact, since the introduction of emergency contraception, the contribution of unsafe abortion towards maternal mortality has declined from 13 to 8 per cent.

47 CFR 95.635 - Unwanted radiation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Unwanted radiation. 95.635 Section 95.635... SERVICES Technical Regulations Technical Standards § 95.635 Unwanted radiation. Link to an amendment... Unwanted radiation. (d) * * * (1) * * * (v) Are more than 2.5 MHz outside of the 2360-2400 MHz band (for...

In vivo antinociceptive and anticonvulsant activity of extracts of Heliotropium strigosum.

PubMed

Khan, Haroon; Khan, Murad Ali; Hussain, Sajid; Gaffar, Rukhsana; Ashraf, Nadeem

2016-05-01

Natural healing agents are primarily focused to overcome unwanted side effects with synthetic drugs worldwide. In the proposed study, crude extracts and subsequent solvent fractions of Heliotropium strigosum were evaluated for antinociceptive and anticonvulsant activity in animal paradigms. In post acetic acid-induced writhing test, crude extract and fractions (hexane, ethyl acetate, and aqueous) demonstrated marked attenuation of nociception at test doses (50, 100, and 200 mg/kg i.p.). When challenged against thermally induced pain model, pretreatment of extracts exhibited prominent amelioration at test dose (50, 100, and 200 mg/kg i.p.). In both tests, inhibition of noxious stimulation was in a dose-dependent manner, and ethyl acetate fraction was most dominant. However, extracts did not antagonize the seizures and mortality induced by pentylenetetrazole. In conclusion, the extracts of H. strigosum illustrated significant antinociceptive effect in both centrally and peripherally acting pain models. © The Author(s) 2013.

Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

PubMed Central

Viola, Joana R.; Rafael, Diana F.; Wagner, Ernst; Besch, Robert; Ogris, Manfred

2013-01-01

Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed. PMID:23634303

Effects of pyrazole partial agonists on HCA(2) -mediated flushing and VLDL-triglyceride levels in mice.

PubMed

Li, Zhaosha; Blad, Clara C; van der Sluis, Ronald J; de Vries, Henk; Van Berkel, Theo J C; Ijzerman, Adriaan P; Hoekstra, Menno

2012-10-01

Niacin can effectively treat dyslipidaemic disorders. However, its clinical use is limited due to the cutaneous flushing mediated by the nicotinic acid receptor HCA(2) . In the current study, we evaluated two partial agonists for HCA(2) , LUF6281 and LUF6283, with respect to their anti-dyslipidaemic potential and cutaneous flushing effect. In vitro potency and efficacy studies with niacin and the two HCA(2) partial agonists were performed using HEK293T cells stably expressing human HCA(2) . Normolipidaemic C57BL/6 mice received either niacin or the HCA(2) partial agonists (400 mg·kg(-1) ·day(-1) ) once a day for 4 weeks for evaluation of their effects in vivo. Radioligand competitive binding assay showed K(i) values for LUF6281 and LUF6283 of 3 and 0.55 µM. [(35) S]-GTPγS binding revealed the rank order of their potency as niacin > LUF6283 > LUF6281. All three compounds reduced plasma VLDL-triglyceride concentrations similarly, while LUF6281 and LUF6283, in contrast to niacin, did not also exhibit the unwanted flushing side effect in C57BL/6 mice. Niacin reduced the expression of lipolytic genes HSL and ATGL in adipose tissue by 50%, whereas LUF6281 and LUF6283 unexpectedly did not. In contrast, the decrease in VLDL-triglyceride concentration induced by LUF6281 and LUF6283 was associated with a parallel >40% reduced expression of APOB within the liver. The current study identifies LUF6281 and LUF6283, two HCA(2) partial agonists of the pyrazole class, as promising drug candidates to achieve the beneficial lipid lowering effect of niacin without producing the unwanted flushing side effect. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Evidence for the efficacy and safety of topical herbal drugs in dermatology: Part I: Anti-inflammatory agents.

PubMed

Hörmann, H P; Korting, H C

1994-09-01

Topical herbal drugs have for centuries been used for treating skin ailments. Although they are currently widely accepted by patients, their scientific esteem among dermatologists in particular is limited. A variety of herbal drugs for topical application deserves consideration regarding their widespread use or their still ill-defined potential with respect to their benefit/risk ratio. Clinically, camomile (Chamomilla recutita) and hamamelis preparations look particularly well documented. While the final proof of efficacy in common dermatoses such as atopic dermatitis is still lacking, there is fairly ample evidence for their activity against cutaneous inflammation in man, as may be deduced from experiments with normal volunteers. With Hamamelis virginiana this looks paricularly promising, as unwanted effects related to the drug are virtually absent. With camomile preparations the degree of safety seems to depend largely on the plant used. Some herbal drugs clearly need further analysis until their value can be determined. This includes the frequently-used aloe preparations. This is the more remarkable as huge numbers of in vitro studies are available. Arnica is fairly unique in so far as the lack of proof of efficacy strongly contrasts to its sensitization potential. So far, in particular dermatitis and related disorders can be considered potential indications for topical herbal antiinflammatory drugs. Studies in psoriasis vulgaris should also be performed addressing long-term application. In this context such fairly ill-defined drugs as Mahonia deserve attention. Copyright © 1994 Gustav Fischer Verlag, Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

Polypharmacology in HIV inhibition: can a drug with simultaneous action against two relevant targets be an alternative to combination therapy?

PubMed

de Castro, Sonia; Camarasa, María-José

2018-04-25

HIV infection still has a serious health and socio-economical impact and is one of the primary causes of morbidity and mortality all over the world. HIV infection and the AIDS pandemic are still matters of great concern, especially in less developed countries where the access to highly active antiretroviral therapy (HAART) is limited. Patient compliance is another serious drawback. Nowadays, HAART is the treatment of choice although it is not the panacea. Despite the fact that it suppresses viral replication at undetectable viral loads and prevents progression of HIV infection into AIDS HAART has several pitfalls, namely, long-term side-effects, drug resistance development, emergence of drug-resistant viruses, low compliance and the intolerance of some patients to these drugs. Moreover, another serious health concern is the event of co-infection with more than one pathogen at the same time (e.g. HIV and HCV, HBV, herpes viruses, etc). Currently, the multi-target drug approach has become an exciting strategy to address complex diseases and overcome drug resistance development. Such multifunctional molecules combine in their structure pharmacophores that may simultaneously interfere with multiple targets and their use may eventually be more safe and efficacious than that involving a mixture of separate molecules because of avoidance or delay of drug resistance, lower incidence of unwanted drug-drug interactions and improved compliance. In this review we focus on multifunctional molecules with dual activity against different targets of the HIV life cycle or able to block replication, not only of HIV but also of other viruses that are often co-pathogens of HIV. The different approaches are documented by selected examples. Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

[Use of psychoactive substances and contraceptive methods by the Brazilian urban population, 2005].

PubMed

Bastos, Francisco I; Cunha, Cynthia B; Bertoni, Neilane

2008-06-01

To analyze the relationship between utilization patterns for condoms and other contraceptive methods and the consumption of alcohol and drugs. Exploratory study based on data from a probabilistic sample of 5,040 interviewees aged 16 to 65 years living in large urban regions of Brazil in 2005. The data were collected by means of questionnaires. The chi-square automatic interaction classification tree technique was used to study the use of condoms among interviewees of both sexes and other contraceptive methods among women, at the time of the last vaginal sexual intercourse. Among young and middle-aged adults of both sexes and young men in stable relationships, condom use was less frequent among those who said they used psychoactive substances (alcohol and/or illegal drugs). The possible modulating effect of psychoactive substances on contraceptive practices among mature women seems to be more straightforward, compared to the more subtle effects observed among younger women, for whom the different social classes they belonged to seemed to play a more important role. Despite the limitations resulting from an exploratory study, the fact that this was a representative sample of the urban population of Brazil and not from vulnerable populations, reinforces the need to implement integrated public policies directed towards the general population, with regard to preventing drug consumption, alcohol abuse, sexually transmitted infections, HIV/AIDS and unwanted pregnancy and promoting sexual and reproductive health.

The effect of sodium thiopental as a GABA mimetic drug in neonatal period on expression of GAD65 and GAD67 genes in hippocampus of newborn and adult male rats.

PubMed

Naseri, Masoud; Parham, Abbas; Moghimi, Ali

2017-09-01

Development of the nervous system in human and most animals is continued after the birth. Critical role of this period in generation and specialization of the neuronal circuits is confirmed in numerous studies. Any pharmacological intervention in this period may result in structural, functional or behavioral abnormalities. In this study, sodium thiopental a GABA mimetic drug was administrated to newborn rats and their GAD65 and GAD67 expression in hippocampus was evaluated before and after puberty. Newborn male Wistar rats were received sodium thiopental (35 mg/kg) daily for 11 days (from 4 to 14 days after birth). Expression of GAD65 and GAD67 in their hippocampus was compared with control groups in 15 and 45 days after birth with RT-qPCR method. Significant down regulation of GAD65 and GAD67 gene expression was observed in treated rats compared with control group in 45 days after birth animals. But no significant difference was shown between experimental and control groups 15 days after birth animals. The effect of sodium thiopental on GAD65 and GAD67 expression only at adult rats showed a latent period of influence which can be attributed to dosage or intension of sodium thiopental neurotoxicity. Significant down regulation of GAD65 and GAD67 showed unwanted effect of sodium thiopental as GABA mimetic drug in critical period of development.

Biocompatibility of functionalized boron phosphate (BPO4) nanoparticles for boron neutron capture therapy (BNCT) application.

PubMed

Achilli, Cesare; Grandi, Stefania; Ciana, Annarita; Guidetti, Gianni F; Malara, Alessandro; Abbonante, Vittorio; Cansolino, Laura; Tomasi, Corrado; Balduini, Alessandra; Fagnoni, Maurizio; Merli, Daniele; Mustarelli, Piercarlo; Canobbio, Ilaria; Balduini, Cesare; Minetti, Giampaolo

2014-04-01

Boron neutron capture therapy (BNCT) is a radiotherapy treatment based on the accumulation in the tumor of a (10)B-containing drug and subsequent irradiation with low energy neutrons, which bring about the decay of (10)B to (7)Li and an α particle, causing the death of the neoplastic cell. The effectiveness of BNCT is limited by the low delivery and accumulation of the used boron-containing compounds. Here we report the development and the characterization of BPO4 nanoparticles (NPs) as a novel possible alternative drug for BNCT. An extensive analysis of BPO4 NP biocompatibility was performed using both mature blood cells (erythrocytes, neutrophils and platelets) and a model of hematopoietic progenitor cells. A time- and concentration-dependent cytotoxicity study was performed on neoplastic coloncarcinoma and osteosarcoma cell lines. BPO4 functionalization with folic acid, introduced to improve the uptake by tumor cells, appeared to effectively limit the unwanted effects of NPs on the analyzed blood components. Boron neutron capture therapy (BNCT) is a radiotherapy treatment modality based on the accumulation of a (10)B-containing drug and subsequent irradiation with low energy neutrons, inducing the decay of (10)B to (7)Li and an α particle, causing neoplastic cell death. This team of authors reports on a folic acid functionalized BPO4 nanoparticle with improved characteristics compared with conventional BNCT approaches, as demonstrated in tumor cell lines, and hopefully to be followed by translational human studies. © 2014.

Spinal anesthesia: an evergreen technique.

PubMed

Di Cianni, Simone; Rossi, Maria; Casati, Andrea; Cocco, Caterina; Fanelli, Guido

2008-04-01

Spinal anesthesia is a simple technique that provides a deep and fast surgical block through the injection of small doses of local anesthetic solution into the subarachnoid space. The purpose of this review is to provide an overview on recent developments on local anesthetic drugs, side effects, and special techniques of intrathecal anesthesia. Spinal anesthesia can be considered adequately safe, and severe complications are reasonably rare. The cardiovascular effects associated with sympathetic block are more frequent, but successfully treated with volume expansion and administration of vasoactive drugs. It is clear that the total dose of local anesthetic injected into the subarachnoid space is the most important determinant of both therapeutic and unwanted effects of spinal anesthesia. Several studies have also demonstrated the efficacy and safety of using small doses of long acting agents, such as bupivacaine or ropivacaine, to produce an adequately short spinal block in outpatients. Levopivacaine, the pure S(-)-enantiomer of racemic bupivacaine showed a lower risk of cardiovascular and central nervous system (CNS) toxicity than bupivacaine. In the last years we have assisted important changes in the health care organization, with most of the surgical procedures performed on outpatients or on elderly patients with concomitant diseases. This forced us to change the indications and clinical use of intrathecal anesthesia techniques, which have been modified according to the changing needs of surgery. The development of new drugs and special techniques for spinal anesthesia will further improve the clinical use of this old but evergreen technique.

Vasodilator Therapy: Nitrates and Nicorandil.

PubMed

Tarkin, Jason M; Kaski, Juan Carlos

2016-08-01

Nitrates have been used to treat symptoms of chronic stable angina for over 135 years. These drugs are known to activate nitric oxide (NO)-cyclic guanosine-3',-5'-monophasphate (cGMP) signaling pathways underlying vascular smooth muscle cell relaxation, albeit many questions relating to how nitrates work at the cellular level remain unanswered. Physiologically, the anti-angina effects of nitrates are mostly due to peripheral venous dilatation leading to reduction in preload and therefore left ventricular wall stress, and, to a lesser extent, epicardial coronary artery dilatation and lowering of systemic blood pressure. By counteracting ischemic mechanisms, short-acting nitrates offer rapid relief following an angina attack. Long-acting nitrates, used commonly for angina prophylaxis are recommended second-line, after beta-blockers and calcium channel antagonists. Nicorandil is a balanced vasodilator that acts as both NO donor and arterial K(+) ATP channel opener. Nicorandil might also exhibit cardioprotective properties via mitochondrial ischemic preconditioning. While nitrates and nicorandil are effective pharmacological agents for prevention of angina symptoms, when prescribing these drugs it is important to consider that unwanted and poorly tolerated hemodynamic side-effects such as headache and orthostatic hypotension can often occur owing to systemic vasodilatation. It is also necessary to ensure that a dosing regime is followed that avoids nitrate tolerance, which not only results in loss of drug efficacy, but might also cause endothelial dysfunction and increase long-term cardiovascular risk. Here we provide an update on the pharmacological management of chronic stable angina using nitrates and nicorandil.

Self-microemulsifying drug delivery system and nanoemulsion for enhancing aqueous miscibility of Alpinia galanga oil.

PubMed

Khumpirapang, Nattakanwadee; Pikulkaew, Surachai; Müllertz, Anette; Rades, Thomas; Okonogi, Siriporn

2017-01-01

Alpinia galanga oil (AGO) possesses various activities but low aqueous solubility limits its application particularly in aquatic animals. AGO has powerful activity on fish anesthesia. Ethanol used for enhancing water miscible of AGO always shows severe side effects on fish. The present study explores the development of self-microemulsifying drug delivery systems (SMEDDS) and nanoemulsions (NE) to deliver AGO for fish anesthesia with less or no alcohol. Pseudoternary phase diagrams were constructed to identify the best SMEDDS-AGO formulation, whereas NE-AGO were developed by means of high-energy emulsification. The mean droplet size of the best SMEDDS-AGO was 82 ± 0.5 nm whereas that of NE-AGO was 48 ± 1.6 nm. The anesthetic effect of the developed SMEDDS-AGO and NE-AGO in koi (Cyprinus carpio) was evaluated and compared with AGO ethanolic solution (EtOH-AGO). It was found that the time of induction the fish to reach the surgical stage of anesthesia was dose dependent. NE-AGO showed significantly higher activity than SMEDDS-AGO and EtOH-AGO, respectively. EtOH-AGO caused unwanted hyperactivity in the fish. This side effect did not occur in the fish anesthetized with SMEDDS-AGO and NE-AGO. In conclusion, SMEDDS and NE are promising delivery systems for AGO.

Self-microemulsifying drug delivery system and nanoemulsion for enhancing aqueous miscibility of Alpinia galanga oil

PubMed Central

Khumpirapang, Nattakanwadee; Pikulkaew, Surachai; Müllertz, Anette; Rades, Thomas

2017-01-01

Alpinia galanga oil (AGO) possesses various activities but low aqueous solubility limits its application particularly in aquatic animals. AGO has powerful activity on fish anesthesia. Ethanol used for enhancing water miscible of AGO always shows severe side effects on fish. The present study explores the development of self-microemulsifying drug delivery systems (SMEDDS) and nanoemulsions (NE) to deliver AGO for fish anesthesia with less or no alcohol. Pseudoternary phase diagrams were constructed to identify the best SMEDDS-AGO formulation, whereas NE-AGO were developed by means of high-energy emulsification. The mean droplet size of the best SMEDDS-AGO was 82 ± 0.5 nm whereas that of NE-AGO was 48 ± 1.6 nm. The anesthetic effect of the developed SMEDDS-AGO and NE-AGO in koi (Cyprinus carpio) was evaluated and compared with AGO ethanolic solution (EtOH-AGO). It was found that the time of induction the fish to reach the surgical stage of anesthesia was dose dependent. NE-AGO showed significantly higher activity than SMEDDS-AGO and EtOH-AGO, respectively. EtOH-AGO caused unwanted hyperactivity in the fish. This side effect did not occur in the fish anesthetized with SMEDDS-AGO and NE-AGO. In conclusion, SMEDDS and NE are promising delivery systems for AGO. PMID:29190663

Analysis and modification of a single-mesh gear fatigue rig for use in diagnostic studies

NASA Technical Reports Server (NTRS)

Zakrajsek, James J.; Townsend, Dennis P.; Oswald, Fred B.; Decker, Harry J.

1992-01-01

A single-mesh gear fatigue rig was analyzed and modified for use in gear mesh diagnostic research. The fatigue rig allowed unwanted vibration to mask the test-gear vibration signal, making it difficult to perform diagnostic studies. Several possible sources and factors contributing to the unwanted components of the vibration signal were investigated. Sensor mounting location was found to have a major effect on the content of the vibration signal. In the presence of unwanted vibration sources, modal amplification made unwanted components strong. A sensor location was found that provided a flatter frequency response. This resulted in a more useful vibration signal. A major network was performed on the fatigue rig to reduce the influence of the most probable sources of the noise in the vibration signal. The slave gears were machined to reduce weight and increase tooth loading. The housing and the shafts were modified to reduce imbalance, looseness, and misalignment in the rotating components. These changes resulted in an improved vibration signal, with the test-gear mesh frequency now the dominant component in the signal. Also, with the unwanted sources eliminated, the sensor mounting location giving the most robust representation of the test-gear meshing energy was found to be at a point close to the test gears in the load zone of the bearings.

Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control: Recommendations for patient information☆☆☆

PubMed Central

Barron, Anthony J.; Zaman, Nabeela; Cole, Graham D.; Wensel, Roland; Okonko, Darlington O.; Francis, Darrel P.

2013-01-01

Background Patients trying life-preserving agents such as beta-blockers may be discouraged by listings of harmful effects provided in good faith by doctors, drug information sheets, and media. We systematically review the world experience of side-effect information in blinded, placebo-controlled beta-blockade in heart failure. We present information for a physician advising a patient experiencing an unwanted symptom and suspecting the drug. Methods We searched Medline for double-blinded randomized trials of beta-blocker versus placebo in heart failure reporting side-effects. We calculated, per 100 patients reporting the symptom on beta-blockade, how many would have experienced it on placebo: the “proportion of symptoms non-pharmacological”. Results 28 of the 33 classically-described side-effects are not significantly more common on beta-blockers than placebo. Of the 100 patients developing dizziness on beta-blockers, 81 (95% CI 73–89) would have developed it on placebo. For diarrhoea this proportion is 82/100 (70–95), and hyperglycaemia 83/100 (68–98). For only two side-effects is this under half (i.e. predominantly due to beta-blocker): bradycardia (33/100, CI 21–44) and intermittent claudication (41/100, 2–81). At least 6 so-called side-effects are less common on beta-blocker than placebo, including depression (reduced by 35%, p < 0.01) and insomnia (by 27%, p = 0.01). Conclusions Clinicians might reconsider whether it is scientifically and ethically correct to warn a patient that a drug might cause them a certain side-effect, when randomized controlled trials show no significant increase, or indeed a significant reduction. A better informed consultation could, in patients taking beta-blockers, alleviate suffering. In patients who might otherwise not take the drug, it might prevent deaths. PMID:23796325

Indolealkylamines: biotransformations and potential drug-drug interactions.

PubMed

Yu, Ai-Ming

2008-06-01

Indolealkylamine (IAA) drugs are 5-hydroxytryptamine (5-HT or serotonin) analogs that mainly act on the serotonin system. Some IAAs are clinically utilized for antimigraine therapy, whereas other substances are notable as drugs of abuse. In the clinical evaluation of antimigraine triptan drugs, studies on their biotransformations and pharmacokinetics would facilitate the understanding and prevention of unwanted drug-drug interactions (DDIs). A stable, principal metabolite of an IAA drug of abuse could serve as a useful biomarker in assessing intoxication of the IAA substance. Studies on the metabolism of IAA drugs of abuse including lysergic acid amides, tryptamine derivatives and beta-carbolines are therefore emerging. An important role for polymorphic cytochrome P450 2D6 (CYP2D6) in the metabolism of IAA drugs of abuse has been revealed by recent studies, suggesting that variations in IAA metabolism, pharmaco- or toxicokinetics and dynamics can arise from distinct CYP2D6 status, and CYP2D6 polymorphism may represent an additional risk factor in the use of these IAA drugs. Furthermore, DDIs with IAA agents could occur additively at the pharmaco/toxicokinetic and dynamic levels, leading to severe or even fatal serotonin toxicity. In this review, the metabolism and potential DDIs of these therapeutic and abused IAA drugs are described.

Near infrared light-mediated photoactivation of cytotoxic Re(i) complexes by using lanthanide-doped upconversion nanoparticles.

PubMed

Hu, Ming; Zhao, Jixian; Ai, Xiangzhao; Budanovic, Maja; Mu, Jing; Webster, Richard D; Cao, Qian; Mao, Zongwan; Xing, Bengang

2016-09-13

Platinum-based chemotherapy, although it has been well proven to be effective in the battle against cancer, suffers from limited specificity, severe side effects and drug resistance. The development of new alternatives with potent anticancer effects and improved specificity is therefore urgently needed. Recently, there are some new chemotherapy reagents based on photoactive Re(i) complexes which have been reported as promising alternatives to improve specificity mainly attributed to the spatial and temporal activation process by light irradiation. However, most of them respond to short-wavelength light (e.g. UV, blue or green light), which may cause unwanted photo damage to cells. Herein, we demonstrate a system for near-infrared (NIR) light controlled activation of Re(i) complex cytotoxicity by integration of photoactivatable Re(i) complexes and lanthanide-doped upconversion nanoparticles (UCNPs). Upon NIR irradiation at 980 nm, the Re(i) complex can be locally activated by upconverted UV light emitted from UCNPs and subsequently leads to enhanced cell lethality. Cytotoxicity studies showed effective inactivation of both drug susceptible human ovarian carcinoma A2780 cells and cisplatin resistant subline A2780cis cells by our UCNP based system with NIR irradiation, and there was minimum light toxicity observed in the whole process, suggesting that such a system could provide a promising strategy to control localized activation of Re(i) complexes and therefore minimize potential side effects.

MEDICATION DISPOSAL AS A SOURCE FOR DRUGS AS ...

EPA Pesticide Factsheets

The major routes by which pharmaceuticals enter the environment are excretion, bathing, anddisposal of leftover, unwanted medications. Pharmaceuticals designed for humans and animalsoften remain unused. Leftover, accumulated drugs represent potentially environmentallyunsound disposal and suboptimal delivery of health care. They also can pose acute exposurerisks for humans and wildlife. Active pharmaceutical ingredients (APIs) directly enter theenvironment primarily via sewage. Among the three routes of entry, the relative contributions ofeach are poorly understood. In contrast to excretion, which as a source comprises continual lowlevelcontributions from multitudes of people, drug disposal comprises acute but transient andepisodic contributions from fewer people. The only route that is subject most easily to pollutionprevention or source control measures is disposal.A major unknown with respect to drugs as pollutants is what fractions of drug residues occurringin the ambient environment result from discarding leftover drugs. No studies exist that provideobjective data from well-defined populations to support any type of conclusion. Given theimportance of environmental stewardship to sustainability, a means for assessing the relativecontributions of APIs resulting from disposal would be useful in justifying the resources thatmight be devoted to controlling this source - - for example, by way of consumer

Low-dose prazosin alone and in combination with propranolol or naltrexone: effects on ethanol and sucrose seeking and self-administration in the P rat.

PubMed

Verplaetse, Terril L; Czachowski, Cristine L

2015-08-01

Evidence suggests that the noradrenergic system mediates ethanol reinforcement. However, preclinical studies suggest that noradrenergic antagonists block other oral reinforcers indicating possible unwanted secondary medication effects. This study examined combinations of low-dose prazosin with propranolol or naltrexone using a behavioral paradigm that separately assesses reinforcer seeking and self-administration. Male alcohol-preferring (P) rats (n = 20/experiment) were trained to complete a response requirement (RR) resulting in access to 1 % sucrose (n = 10) or 10 % ethanol (n = 10) for 20 min. Rats received vehicle, prazosin alone (0.125, 0.25, 0.5, and 1.0 mg/kg, intraperitoneally (IP)), or prazosin in combination with propranolol (5 mg/kg (IP); Exp. 1) or in combination with naltrexone (0.03 mg/kg, subcutaneously (SC); Exp. 2). For Exp. 1, prazosin alone effectively decreased sucrose seeking more than ethanol seeking, but decreased ethanol self-administration only. Propranolol alone effectively decreased ethanol seeking more than sucrose seeking and decreased ethanol intake only. At some dose combinations, there was a greater attenuation of ethanol and sucrose intake relative to either drug alone. For Exp. 2, prazosin alone and naltrexone alone were effective in decreasing ethanol seeking and intake only. Combination treatment was more effective than either drug alone at decreasing ethanol seeking and consumption and sucrose intake, but not sucrose seeking. Propranolol and naltrexone alone were specific to ethanol indicating that low doses of either medication may be beneficial in treating alcohol use disorders. Prazosin in combination with propranolol or naltrexone was more effective than either drug alone and also reduced sucrose-reinforced behaviors. These data suggest that the noradrenergic system is a viable target for developing treatment approaches for problem drinkers.

Low-Dose Prazosin Alone and in Combination with Propranolol or Naltrexone: Effects on Ethanol- and Sucrose-Seeking and Self-Administration in the P Rat

PubMed Central

Verplaetse, Terril L.; Czachowski, Cristine L.

2015-01-01

Rationale Evidence suggests that the noradrenergic system mediates ethanol-reinforcement. However, preclinical studies suggest that noradrenergic antagonists block other oral reinforcers indicating possible unwanted secondary medication effects. Methods This study examined combinations of low-dose prazosin with propranolol or naltrexone using a behavioral paradigm that separately assesses reinforcer-seeking and self-administration. Male alcohol-preferring (P) rats (n=20/experiment) were trained to complete a response requirement (RR) resulting in access to 1% sucrose (n=10) or 10% ethanol (n=10) for 20min. Rats received vehicle, prazosin alone (0.125, 0.25, 0.5, 1.0 mg/kg; intraperitoneally (IP)) or prazosin in combination with propranolol (5 mg/kg (IP); Exp1) or in combination with naltrexone (0.03 mg/kg (subcutaneously (SC); Exp2). Results For Exp1, prazosin alone effectively decreased sucrose-seeking more than ethanol-seeking, but decreased ethanol self-administration only. Propranolol alone effectively decreased ethanol-seeking more than sucrose-seeking and decreased ethanol intake only. At some dose combinations, there was a greater attenuation of ethanol and sucrose intake relative to either drug alone. For Exp2, prazosin alone and naltrexone alone were effective in decreasing ethanol-seeking and intake only. Combination treatment was more effective than either drug alone at decreasing ethanol-seeking and consumption and sucrose intake, but not sucrose-seeking. Conclusions Propranolol and naltrexone alone were specific to ethanol indicating that low doses of either medication may be beneficial in treating alcohol use disorders. Prazosin in combination with propranolol or naltrexone was more effective than either drug alone, but also reduced sucrose-reinforced behaviors. These data suggest that the noradrenergic system is a viable target for developing treatment approaches for problem drinkers. PMID:25743758

Development of an ionic-liquid-based dispersive liquid-liquid microextraction method for the determination of antichagasic drugs in human breast milk: Optimization by central composite design.

PubMed

Padró, Juan M; Pellegrino Vidal, Rocío B; Echevarria, Romina N; Califano, Alicia N; Reta, Mario R

2015-05-01

Chagas disease constitutes a major public health problem in Latin America. Human breast milk is a biological sample of great importance for the analysis of therapeutic drugs, as unwanted exposure through breast milk could result in pharmacological effects in the nursing infant. Thus, the goal of breast milk drug analysis is to inquire to which extent a neonate may be exposed to a drug during lactation. In this work, we developed an analytical technique to quantify benznidazole and nifurtimox (the two antichagasic drugs currently available for medical treatment) in human breast milk, with a simple sample pretreatment followed by an ionic-liquid-based dispersive liquid-liquid microextraction combined with high-performance liquid chromatography and UV detection. For this technique, the ionic liquid 1-octyl-3-methylimidazolium hexafluorophosphate has been used as the "extraction solvent." A central composite design was used to find the optimum values for the significant variables affecting the extraction process: volume of ionic liquid, volume of dispersant solvent, ionic strength, and pH. At the optimum working conditions, the average recoveries were 77.5 and 89.7%, the limits of detection were 0.06 and 0.09 μg/mL and the interday reproducibilities were 6.25 and 5.77% for benznidazole and nifurtimox, respectively. The proposed methodology can be considered sensitive, simple, robust, accurate, and green. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The addictive dimensionality of obesity.

PubMed

Volkow, Nora D; Wang, Gene-Jack; Tomasi, Dardo; Baler, Ruben D

2013-05-01

Our brains are hardwired to respond and seek immediate rewards. Thus, it is not surprising that many people overeat, which in some can result in obesity, whereas others take drugs, which in some can result in addiction. Though food intake and body weight are under homeostatic regulation, when highly palatable food is available, the ability to resist the urge to eat hinges on self-control. There is no homeostatic regulator to check the intake of drugs (including alcohol); thus, regulation of drug consumption is mostly driven by self-control or unwanted effects (i.e., sedation for alcohol). Disruption in both the neurobiological processes that underlie sensitivity to reward and those that underlie inhibitory control can lead to compulsive food intake in some individuals and compulsive drug intake in others. There is increasing evidence that disruption of energy homeostasis can affect the reward circuitry and that overconsumption of rewarding food can lead to changes in the reward circuitry that result in compulsive food intake akin to the phenotype seen with addiction. Addiction research has produced new evidence that hints at significant commonalities between the neural substrates underlying the disease of addiction and at least some forms of obesity. This recognition has spurred a healthy debate to try and ascertain the extent to which these complex and dimensional disorders overlap and whether or not a deeper understanding of the crosstalk between the homeostatic and reward systems will usher in unique opportunities for prevention and treatment of both obesity and drug addiction. Published by Elsevier Inc.

Implicit and explicit appraisals of the importance of intrusive thoughts.

PubMed

Teachman, Bethany A; Woody, Sheila R; Magee, Joshua C

2006-06-01

To evaluate cognitive theories of obsessions, the current study experimentally manipulated appraisals of the importance of intrusive thoughts. Undergraduate students (N = 156) completed measures of obsessive-compulsive disorder (OCD) symptoms and beliefs and were primed with a list of commonly reported unwanted thoughts. Participants were then informed that unwanted thoughts are either (1) significant and indicative of their personal values, or (2) meaningless, or participants (3) received no instructions about unwanted thoughts. Participants then completed implicit and explicit measures of self-evaluation and interpretations of their unwanted thoughts. Results indicated that the manipulation shifted implicit appraisals of unwanted thoughts in the expected direction, but not self-evaluations of morality or dangerousness. Interestingly, explicit self-esteem and beliefs about the significance of unwanted thoughts were associated with measures of OCD beliefs, whereas implicit self-evaluations of dangerousness were better predicted by the interaction of pre-existing OCD beliefs with the manipulation. Results are discussed in terms of divergent predictors of implicit and explicit responses to unwanted thoughts.

Excessive or unwanted hair in women

MedlinePlus

Hypertrichosis; Hirsutism; Hair - excessive (women); Excessive hair in women; Hair - women - excessive or unwanted ... much of this hormone, you may have unwanted hair growth. In most cases, the exact cause is ...

Micelles based on methoxy poly(ethylene glycol)-cholesterol conjugate for controlled and targeted drug delivery of a poorly water soluble drug.

PubMed

Li, Junming; He, Zhiyao; Yu, Shui; Li, Shuangzhi; Ma, Qing; Yu, Yiyi; Zhang, Jialin; Li, Rui; Zheng, Yu; He, Gu; Song, Xiangrong

2012-10-01

In this study, quercetin (QC) with cancer chemoprevention effect and anticancer potential was loaded into polymeric micelles of methoxy poly(ethylene glycol)-cholesterol conjugate (mPEG-Chol) in order to increase its water solubility. MPEG-Chol with lower critical micelle concentration (CMC) value (4.0 x 10(-7) M - 13 x 10(-7) M) was firstly synthesized involving two steps of chemical modification on cholesterol by esterification, and then QC was incorporated into mPEG-Chol micelles by self-assembly method. After the process parameters were optimized, QC-loaded micelles had higher drug loading (3.66%) and entrapment efficiency (93.51%) and nano-sized diameter (116 nm). DSC analysis demonstrated that QC had been incorporated non-covalently into the micelles and existed as an amorphous state or a solid solution in the polymeric matrix. The freeze-dried formulation with addition of 1% (w/v) mannitol as cryoprotectant was successfully developed for the long-term storage of QC-loaded micelles. Compared to free QC, QC-loaded micelles could release QC more slowly. Moreover, the release of QC from micelles was slightly faster in PBS at pH 5 than that in PBS at pH 7.4, which implied that QC-loaded micelles might be pH-sensitive and thereby selectively deliver QC to tumor tissue with unwanted side effects. Therefore, mPEG-Chol was a promising micellar vector for the controlled and targeted drug delivery of QC to tumor and QC-loaded micelles were also worth being further investigated as a potential formulation for cancer chemoprevention and treatment.

Risk Factors and Consequences of Unwanted Sex among University Students: Hooked up, Alcohol, and Stress Response

ERIC Educational Resources Information Center

Flack, William F., Jr.; Daubman, Kimberly A.; Caron, Marcia L.; Asadorian, Jenica A.; D'Aureli, Nicole R.; Gigliotti, Shannon N.; Hall, Anna T.; Kiser, Sarah; Stine, Erin R.

2007-01-01

This is the first study of unwanted sexual experiences in the collegiate "hooking-up" culture. In a representative sample of 178 students at a small liberal arts university. Twenty-three percent of women and 7% of men surveyed reported one or more experiences of unwanted sexual intercourse. Seventy-eight percent of unwanted vaginal, anal, and oral…

Haloperidol-induced striatal Nur77 expression in a non-human primate model of tardive dyskinesia

PubMed Central

Mahmoudi, Souha; Blanchet, Pierre J.; Lévesque, Daniel

2015-01-01

Tardive dyskinesia (TD) is a delayed and potentially irreversible motor complication arising in patients chronically exposed to antipsychotic drugs. As several modern (so-called atypical) antipsychotic drugs are common offenders, the widening clinical indications for prescription as well as exposure of vulnerable individuals, TD will remain a significant drug-induced unwanted side effect. In addition, the pathophysiology of TD remains elusive and therapeutics difficult. Based on rodent experiments, we have previously shown that the transcriptional factor Nur77 (also known as NGFI-B or Nr4a1) is induced in the striatum following antipsychotic drug exposure as part of a long-term neuroadaptive process. To confirm this, we exposed adult capuchin (Cebus apella) monkeys to prolonged treatments with haloperidol (median 18.5 months, N=11) or clozapine (median 6 months, N=6). Six untreated animals were used as controls. Six haloperidol-treated animals developed mild TD movements similar to those found in humans. No TD was observed in the clozapine group. Postmortem analysis of Nur77 expression measured by in situ hybridization revealed a stark contrast between the two drugs, as Nur77 mRNA levels in the caudate-putamen were strongly upregulated in animals exposed to haloperidol while spared following clozapine treatment. Interestingly, within the haloperidol-treated group, TD-free animals showed higher Nur77 expression in putamen subterritories compared to dyskinetic animals. This suggests that Nur77 expression might be associated with a reduced risk to TD in this experimental model and could provide a novel target for drug intervention. PMID:23551242

Estimating the Availability of Potential Homes for Unwanted Horses in the United States

PubMed Central

Weiss, Emily; Dolan, Emily D.; Mohan-Gibbons, Heather; Gramann, Shannon; Slater, Margaret R.

2017-01-01

Simple Summary There are approximately 200,000 unwanted horses annually in the United States. Many are shipped to slaughter, enter rescue facilities, or are held on federal lands. This study aimed to estimate a potential number of available homes for unwanted horses in order to examine broadly the viability of pursuing re-homing policies as an option for the thousands of unwanted horses in the U.S. The results of this survey suggest there could be an estimated 1.2 million homes who have both the perceived resources and desire to house an unwanted horse. This number exceeds the approximately 200,000 unwanted horses living each year in the United States. These data suggest that efforts to reduce unwanted horses could involve matching such horses with adoptive homes and enhancing opportunities to keep horses in the homes they already have. Abstract There are approximately 200,000 unwanted horses annually in the United States. This study aimed to better understand the potential homes for horses that need to be re-homed. Using an independent survey company through an Omnibus telephone (land and cell) survey, we interviewed a nationally projectable sample of 3036 adults (using both landline and cellular phone numbers) to learn of their interest and capacity to adopt a horse. Potential adopters with interest in horses with medical and/or behavioral problems and self-assessed perceived capacity to adopt, constituted 0.92% of the total sample. Extrapolating the results of this survey using U.S. Census data, suggests there could be an estimated 1.25 million households who have both the self-reported and perceived resources and desire to house an unwanted horse. This number exceeds the estimated number of unwanted horses living each year in the United States. This study points to opportunities and need to increase communication and support between individuals and organizations that have unwanted horses to facilitate re-homing with people in their community willing to adopt them. PMID:28726730

"Come on Baby. You Know I Love You": African American Women's Experiences of Communication with Male Partners and Disclosure in the Context of Unwanted Sex.

PubMed

Gutzmer, Kyle; Ludwig-Barron, Natasha T; Wyatt, Gail E; Hamilton, Alison B; Stockman, Jamila K

2016-05-01

We examined African American women's experiences of communication with their male intimate partners a couple of hours before and after an incident of unwanted sex. We also examined women's experiences of disclosure following an incident of unwanted sex. Semi-structured qualitative interviews were conducted with a community-based sample of sexually active African American women (n = 19) reporting at least one incident of sexual coercion (i.e., being pressured into unwanted sex without consent) by an intimate male partner since the age of 18. Our analysis was guided by "the sexual division of power" from Connell's (1987) theory of gender and power. Data were analyzed inductively by examining the interviews for common themes in the following domains: communication before the unwanted sex, communication after the unwanted sex, and disclosure to others. Men pressured partners for unwanted sex through verbal and non-verbal tactics, ranging from pestering and blunt requests for sex to verbal bullying and violence. Many women responded by clearly saying no. However, many women also described eventually ceasing to resist their partners and engaging in unwanted sex. After the unwanted sex, men actively and passively avoided discussing the incident. Although many women discussed the unwanted sex with family and friends, less women disclosed to trained professionals. In some cases, women did not discuss the incident with anyone at all. These findings indicate that, when addressing sexual violence against women, there is a need to target men as well as the norms of masculinity that underpin physical and sexual violence against women.

“Come on baby. You know I love you”: African American Women's Experiences of Communication with Male Partners and Disclosure in the Context of Unwanted Sex

PubMed Central

Gutzmer, Kyle; Ludwig-Barron, Natasha T.; Wyatt, Gail E.; Hamilton, Alison B.; Stockman, Jamila K.

2016-01-01

We examined African American women's experiences of communication with their male intimate partners a couple of hours before and after an incident of unwanted sex. We also examined women's experiences of disclosure following an incident of unwanted sex. Semi-structured qualitative interviews were conducted with a community-based sample of sexually active African American women (n=19) reporting at least one incident of sexual coercion (i.e., being pressured into unwanted sex without consent) by an intimate male partner since the age of 18. Our analysis was guided by “the sexual division of power” from the Theory of Gender and Power. Data were analyzed inductively by examining the interviews for common themes in the following domains: communication before the unwanted sex, communication after the unwanted sex, and disclosure to others. Men pressured partners for unwanted sex through verbal and nonverbal tactics, ranging from pestering and blunt requests for sex to verbal bullying and violence. Many women responded by clearly saying no. However, many women also described eventually ceasing to resist their partners and engaging in unwanted sex. After the unwanted sex, men actively and passively avoided discussing the incident. Although many women discussed the unwanted sex with family and friends, less women disclosed to trained professionals. In some cases, women did not discuss the incident with anyone at all. These findings indicate that, when addressing sexual violence against women, there is a need to target men as well as the norms of masculinity that underpin physical and sexual violence against women. PMID:26892099

Consequences for children of their birth planning status.

PubMed

Baydar, N

1995-01-01

Of 1,327 children younger than two in 1986 whose mothers were participants in the National Longitudinal Survey of Youth, 61% were wanted, 34% were mistimed and 5% were unwanted. Planning status is associated with the level of developmental resources the child receives at home: At ages one and older, mistimed and unwanted children score significantly lower on a scale measuring opportunity for skill development and on a scale measuring nonauthoritarian parenting style than their wanted peers; by preschool age, they also have significantly less-positive relationships with their mothers. Measures of the direct effects of planning status on development also indicate that mistimed and unwanted children are at a disadvantage: Those younger than two have higher mean scores for fearfulness than wanted infants and lower scores for positive affect; unintended preschoolers score lower on a measure of receptive vocabulary.

Improved anti-tumor activity and safety profile of a paclitaxel-loaded glycyrrhetinic acid-graft-hyaluronic acid conjugate as a synergistically targeted drug delivery system.

PubMed

Zhang, Li; Zhou, Jian-Ping; Yao, Jing

2015-12-01

The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid (HGA) conjugate for intravenous paclitaxel (PTX) delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles (PTX/HGAs) were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer cells. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio (TIR) being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. In conclusion, PTX/HGAs demonstrated inhibitory effects tumor growth without unwanted side effects, suggesting that HGA conjugates hold a great potential as a delivery carrier for cancer chemotherapeutics to improve therapeutic efficacy and minimize adverse effects. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Therapeutic outcomes, assessments, risk factors and mitigation efforts of immunogenicity of therapeutic protein products.

PubMed

Yin, Liusong; Chen, Xiaoying; Vicini, Paolo; Rup, Bonita; Hickling, Timothy P

2015-06-01

Therapeutic protein products (TPPs) are of considerable value in the treatment of a variety of diseases, including cancer, hemophilia, and autoimmune diseases. The success of TPP mainly results from prolonged half-life, increased target specificity and decreased intrinsic toxicity compared with small molecule drugs. However, unwanted immune responses against TPP, such as generation of anti-drug antibody, can impact both drug efficacy and patient safety, which has led to requirements for increased monitoring in regulatory studies and clinical practice, termination of drug development, or even withdrawal of marketed products. We present an overview of current knowledge on immunogenicity of TPP and its impact on efficacy and safety. We also discuss methods for measurement and prediction of immunogenicity and review both product-related and patient-related risk factors that affect its development, and efforts that may be taken to mitigate it. Lastly, we discuss gaps in knowledge and technology and what is needed to fill these. Copyright © 2015 Elsevier Inc. All rights reserved.

Unintended messages in online advertising to youth: illicit drug imagery in a Canadian sports marketing campaign.

PubMed

Auger, Nathalie; Daniel, Mark; Knäuper, Bärbel; Dourian, Tara; Raynault, Marie-France

2015-04-01

We assessed the potential for harmful messages in online advertisements targeted to youth, using the example of the Canadian "Light It Up" marketing campaign from a large sports corporation. We undertook a cluster randomized controlled trial of 20 secondary school classes in Montreal, Canada. Classes were randomly allocated to view a "Light It Up" advertisement (n = 205) or a neutral comparison advertisement (n = 192). The main outcome measures were self-reports of illicit drug messages in the advertisements. Of the students, 22.9% reported that the "Light It Up" advertisement contained illicit drug messages compared with 1.0% for the comparison advertisement (relative risk, 22.0; 95% confidence interval, 6.5-74.9). Although meant to promote sports, youth in this study believed that the "Light It Up" advertisement was related to illicit drugs. The campaign illustrates how advertisements may inadvertently market unwanted behaviors to children. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Analysis of the meal-dependent intragastric performance of a gastric-retentive tablet assessed by magnetic resonance imaging.

PubMed

Steingoetter, A; Kunz, P; Weishaupt, D; Mäder, K; Lengsfeld, H; Thumshirn, M; Boesiger, P; Fried, M; Schwizer, W

2003-10-01

Modern medical imaging modalities can trace labelled oral drug dosage forms in the gastrointestinal tract, and thus represent important tools for the evaluation of their in vivo performance. The application of gastric-retentive drug delivery systems to improve bioavailability and to avoid unwanted plasma peak concentrations of orally administered drugs is of special interest in clinical and pharmaceutical research. To determine the influence of meal composition and timing of tablet administration on the intragastric performance of a gastric-retentive floating tablet using magnetic resonance imaging in the sitting position. A tablet formulation was labelled with iron oxide particles as negative magnetic resonance contrast marker to allow the monitoring of the tablet position in the food-filled human stomach. Labelled tablet was administered, together with three different solid meals, to volunteers seated in a 0.5-T open-configuration magnetic resonance system. Volunteers were followed over a 4-h period. Labelled tablet was detectable in all subjects throughout the entire study. The tablet showed persistent good intragastric floating performance independent of meal composition. Unfavourable timing of tablet administration had a minor effect on the intragastric tablet residence time and floating performance. Magnetic resonance imaging can reliably monitor and analyse the in vivo performance of labelled gastric-retentive tablets in the human stomach.

Liposomal nanomedicines.

PubMed

Fenske, David B; Cullis, Pieter R

2008-01-01

Liposomal nanoparticles (LNs) encapsulating therapeutic agents, or liposomal nanomedicines, represent an advanced class of drug delivery systems, with several formulations presently on the market and many more in clinical trials. Over the past 20 years, a variety of techniques have been developed for encapsulating both conventional drugs (such as anticancer drugs and antibiotics) and the new genetic drugs (plasmid DNA containing therapeutic genes, antisense oligonucleotides and small interfering RNA) within LNs. If the LNs possess certain properties, they tend to accumulate at sites of disease, such as tumours, where the endothelial layer is 'leaky' and allows extravasation of particles with small diameters. These properties include a diameter centred on 100 nm, a high drug-to-lipid ratio, excellent retention of the encapsulated drug, and a long (> 6 h) circulation lifetime. These properties permit the LNs to protect their contents during circulation, prevent contact with healthy tissues, and accumulate at sites of disease. The authors discuss recent advances in this field involving conventional anticancer drugs, as well as applications involving gene delivery, stimulation of the immune system and silencing of unwanted gene expression. Liposomal nanomedicines have the potential to offer new treatments in such areas as cancer therapy, vaccine development and cholesterol management.

Potential of glyburide to reduce intracerebral edema in brain metastases.

PubMed

Boggs, Drexell Hunter; Simard, J Marc; Steven, Andrew; Mehta, Minesh P

2014-04-01

Metastatic disease to the brain results in significant morbidity because of edema in the central nervous system. Current anti-edema therapies are either expensive or result in unwanted long-term side effects. Sulfonylurea receptor 1 (Sur1) is a transmembrane protein that, when activated in the central nervous system, allows for unregulated sodium influx into cells, a process that has been linked to cytotoxic edema formation in ischemic stroke, subarachnoid hemorrhage, spinal cord injury, traumatic brain injury, and, most recently, brain metastases. In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema.

Examining intendedness among pregnancies ending in spontaneous abortion.

PubMed

Flink-Bochacki, Rachel; Meyn, Leslie A; Chen, Beatrice A; Achilles, Sharon L; Chang, Judy C; Borrero, Sonya

2017-08-01

Spontaneous abortion (SAB) affects over 1 million US women each year, yet little is known about the intendedness of these pregnancies. We examined prevalence and correlates of unintended and unwanted pregnancies ending in SAB. We used nationally-representative cross-sectional data of US women aged 15-44 from the 2011-2013 National Survey of Family Growth to examine pregnancies ending in SAB. We used modified Poisson regression models to evaluate associations between demographic and pregnancy characteristics with unintended and unwanted pregnancy. Among 1351 pregnancies ending in SAB, 44.5% were unintended (i.e. unwanted or occurring sooner than desired). Younger women with SAB were more likely to report unintended pregnancies than women 30-44 years, and women 15-19 years reported unintended pregnancy most often [adjusted relative risk (aRR)=3.0; 95% confidence interval (CI): 2.2-4.1]. Unintended pregnancy was two times more likely among unmarried than married women [never married: aRR=2.2; 95% CI: 1.7-2.7; previously married: aRR=2.2; 95% CI: 1.7-3.0]. Other factors associated with unintended pregnancy were multiparity compared to nulliparity [aRR=2.6; 95% CI: 1.7-4.1 for ≥3 children; aRR=1.8; 95% CI: 1.3-2.5 for 2 children] and inter-pregnancy interval ≤12 months compared to >12 months [aRR=1.4; 95% CI: 1.2-1.7]. We found similar associations with unwanted pregnancies ending in SAB (15.3% of pregnancies). Neither race/ethnicity nor socioeconomic indicators were independently associated with unintended or unwanted pregnancy ending in SAB. Many pregnancies ending in spontaneous abortion are unintended and/or unwanted. Women with pregnancy loss, like all reproductive-aged women, should receive comprehensive counseling about reproductive planning and contraception. Similar to all pregnancies, nearly half of pregnancies ending in spontaneous abortion are unintended and/or unwanted, suggesting that many women experiencing spontaneous abortion may benefit from a review of family planning desires and the provision of reproductive planning counseling and effective contraception to prevent future undesired pregnancy. Copyright © 2017 Elsevier Inc. All rights reserved.

Fatty acids rehabilitated long-term neurodegenerative: like symptoms in olfactory bulbectomized rats.

PubMed

Yehuda, Shlomo; Rabinovitz, Sharon

2015-05-01

Our previous study demonstrated that an olfactory bulbectomy in rats induced short-term, multifaceted, devastating Alzheimer's-like effects, which included cognitive impairment, hyperactivity, hyperthermia, and increased levels of homocysteine and pro-inflammatory cytokines, including IL-17A. In addition, the rats exhibited an increase in the hyperphosphorylation of brain Tau proteins and in the number of neurofibrillary tangles. Here, we examined the long-term effects of the surgery and found that olfactory bulbectomy also rendered the rats to become anemic with brain iron overload. Additionally, a significant reduction in the membrane fluidity index in frontal cortex synaptosomes was found. Treatment with a mixture of n - 3/n - 6 of fatty acids restored the unwanted effect. The beneficial effects of fatty acids are mediated via the effects of fatty acids on the neuronal membrane structure and fluidity. These findings are similar to Alzheimer's symptoms, which suggest this model can be used as an animal model for Alzheimer's disease. We recommend using this model to scan potential new anti-Alzheimer's drugs.

Analytical Pitfalls of Therapeutic Drug Monitoring of Thiopurines in Patients With Inflammatory Bowel Disease

PubMed Central

Meijer, Berrie; Mulder, Chris J. J.; van Bodegraven, Adriaan A.; de Boer, Nanne K. H.

2017-01-01

Abstract: The use of thiopurines in the treatment of inflammatory bowel disease (IBD) can be optimized by the application of therapeutic drug monitoring. In this procedure, 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) metabolites are monitored and related to therapeutic response and adverse events, respectively. Therapeutic drug monitoring of thiopurines, however, is hampered by several analytical limitations resulting in an impaired translation of metabolite levels to clinical outcome in IBD. Thiopurine metabolism is cell specific and requires nucleated cells and particular enzymes for 6-TGN formation. In the current therapeutic drug monitoring, metabolite levels are assessed in erythrocytes, whereas leukocytes are considered the main target cells of these drugs. Furthermore, currently used methods do not distinguish between active nucleotides and their unwanted residual products. Last, there is a lack of a standardized laboratorial procedure for metabolite assessment regarding the substantial instability of erythrocyte 6-TGN. To improve thiopurine therapy in patients with IBD, it is necessary to understand these limitations and recognize the general misconceptions in this procedure. PMID:29040228

An ambiguous monolith - the Swedish drug issue as a political battleground 1965-1981.

PubMed

Edman, Johan

2013-09-01

The drug problem has been a highly ideologized topic in the political debate in Sweden ever since the mid-1960s. The aim of the article is to investigate dominant conceptions of drugs, drug use, society and the individual in the political discussions on drug use in Sweden during the years 1965-1981. The empirical basis for the textual analysis consists of 146 parliamentary bills and 135 parliamentary protocols. The unwanted drug appear as a sensitive litmus paper, an indication that something had gone wrong in society and as a suggestion of how the good society could be accomplished. The drug problem was connected to ideological core values such as class struggle, Christianity or criticism of urbanism and modernity. The analysis suggests that the drug problem was used as political ammunition, to pick holes in political opponents and to highlight one's own ideological stance. The hegemonic conversational order, the consensual spirit and the agreement that this was the most serious problem, did not hamper these political moves. Rather, the cross-party conception of the problem's severity and accelerating deterioration contributed to a common ground for political arguments and ideological visions. It also meant that the political discussions moved away from the more obvious drug policy issues. Copyright © 2013 Elsevier B.V. All rights reserved.

Diagnosing and treating depression in epilepsy.

PubMed

Elger, Christian E; Johnston, Samantha A; Hoppe, Christian

2017-01-01

At least one third of patients with active epilepsy suffer from significant impairment of their emotional well-being. A targeted examination for possible depression (irrespective of any social, financial or personal burdens) can identify patients who may benefit from medical attention and therapeutic support. Reliable screening instruments such as the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) are suitable for the timely identification of patients needing help. Neurologists should be capable of managing mild to moderate comorbid depression but referral to mental health specialists is mandatory in severe and difficult-to-treat depression, or if the patient is acutely suicidal. In terms of the therapeutic approach, it is essential first to optimize seizure control and minimize unwanted antiepileptic drug-related side effects. Psychotherapy for depression in epilepsy (including online self-treatment programs) is underutilized although it has proven effective in ten well-controlled trials. In contrast, the effectiveness of antidepressant drugs for depression in epilepsy is unknown. However, if modern antidepressants are used (e.g. SSRI, SNRI, NaSSA), concerns about an aggravation of seizures and or problematic interactions with antiepileptic drugs seem unwarranted. Epilepsy-related stress ("burden of epilepsy") explains depression in many patients but acute and temporary seizure-related states of depression or suicidality have also been reported. Limbic encephalitits may cause isolated mood alteration without any recognizable psychoetiological background indicating a possible role of neuroinflammation. This review will argue that, overall, a bio-psycho-social model best captures the currently available evidence relating to the etiology and treatment of depression as a comorbidity of epilepsy. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Salivary Secretory Disorders, Inducing Drugs, and Clinical Management

PubMed Central

Miranda-Rius, Jaume; Brunet-Llobet, Lluís; Lahor-Soler, Eduard; Farré, Magí

2015-01-01

Background: Salivary secretory disorders can be the result of a wide range of factors. Their prevalence and negative effects on the patient's quality of life oblige the clinician to confront the issue. Aim: To review the salivary secretory disorders, inducing drugs and their clinical management. Methods: In this article, a literature search of these dysfunctions was conducted with the assistance of a research librarian in the MEDLINE/PubMed Database. Results: Xerostomia, or dry mouth syndrome, can be caused by medication, systemic diseases such as Sjögren's Syndrome, glandular pathologies, and radiotherapy of the head and neck. Treatment of dry mouth is aimed at both minimizing its symptoms and preventing oral complications with the employment of sialogogues and topical acting substances. Sialorrhea and drooling, are mainly due to medication or neurological systemic disease. There are various therapeutic, pharmacologic, and surgical alternatives for its management. The pharmacology of most of the substances employed for the treatment of salivary disorders is well-known. Nevertheless, in some cases a significant improvement in salivary function has not been observed after their administration. Conclusion: At present, there are numerous frequently prescribed drugs whose unwanted effects include some kind of salivary disorder. In addition, the differing pathologic mechanisms, and the great variety of existing treatments hinder the clinical management of these patients. The authors have designed an algorithm to facilitate the decision making process when physicians, oral surgeons, or dentists face these salivary dysfunctions. PMID:26516310

Depressive symptoms as a side effect of the sustained release form of methylphenidate in a 7-year-old boy with attention-deficit hyperactivity disorder.

PubMed

Lakić, Aneta

2012-02-01

Hyperkinetic disorder or attention-deficit hyperactivity disorder (ADHD) is a clinical entity consisting of a cluster of symptoms including hyperactivity, attention disorder and impulse control disorder group. In the context of ADHD etiology we may say that genetic, clinical and imaging studies point out a disruption of the brain dopamine system, which is corroborated by the clinical effectiveness of stimulant drugs, which increase extracellular dopamine in the brain. Basically, it is a biological and not psychological disorder, which is important both for the comprehension and therapeutical approach to this problem. Today, the best recommended approach regarding children with ADHD is a combination of two therapeutic modalities: pharmacotherapy and behavioral treatment. The first-choice drugs for this disorder belong to the group of sympathomimetics--psychostimulants and atomoxetine (more recently). As the first-choice therapy, methylphenydate in sustained release form has numerous advantages. Like all drugs, methylphenidate has its unwanted side effects. Most common are: loss of appetite, weight loss, sleeping disorders, irritability, headache. These side effects are well-known and documented in the literature. By analysing the available literature we have found cases of psychiatric side effects such as: psychosis, mania, visual hallucinations, agitation, suicidal ideas. We have not found examples of ADHD in children who use increased dosage of sustained release of methylphenidate leading to depressive symptomatology. On the other side, methylphenidate may be prescribed for off-label use in treatment-resistant cases of depression. The case of a 7-year-old boy diagnosed with ADHD was on a minimal dose of sustained release form of methylphenidate. After initial titration of the drug, i.e. after raising the dose to the next level the boy developed clinical signs of depression. The treatment was ceased and depressive symptoms were withdrawed. Manifestation of depressive symptomatology after dose increasement of sustained release form of methylphenidate in a 7-year-old boy with ADHD represents an uncommon side effect. Precise drug activity mechanisms responsible for the appearance of these symptoms remains to be explained.

mRNA expression of dopamine receptors in peripheral blood lymphocytes of computer game addicts.

PubMed

Vousooghi, Nasim; Zarei, Seyed Zeinolabedin; Sadat-Shirazi, Mitra-Sadat; Eghbali, Fatemeh; Zarrindast, Mohammad Reza

2015-10-01

Excessive playing of computer games like some other behaviors could lead to addiction. Addictive behaviors may induce their reinforcing effects through stimulation of the brain dopaminergic mesolimbic pathway. The status of dopamine receptors in the brain may be parallel to their homologous receptors in peripheral blood lymphocytes (PBLs). Here, we have investigated the mRNA expression of dopamine D3, D4 and D5 receptors in PBLs of computer game addicts (n = 20) in comparison to normal subjects (n = 20), using a real-time PCR method. The results showed that the expression level of D3 and D4 dopamine receptors in computer game addicts were not statistically different from the control group. However, the expression of the mRNA of D5 dopamine receptor was significantly down-regulated in PBLs of computer game addicts and reached 0.42 the amount of the control group. It is concluded that unlike with drug addiction, the expression levels of the D3 and D4 dopamine receptors in computer game addicts are not altered compared to the control group. However, reduced level of the D5 dopamine receptor in computer game addicts may serve as a peripheral marker in studies where the confounding effects of abused drugs are unwanted.

Property distribution of drug-related chemical databases*

NASA Astrophysics Data System (ADS)

Oprea, Tudor I.

2000-04-01

The process of compound selection and prioritization is crucial for both combinatorial chemistry (CBC) and high throughput screening (HTS). Compound libraries have to be screened for unwanted chemical structures, as well as for unwanted chemical properties. Property extrema can be eliminated by using property filters, in accordance with their actual distribution. Property distribution was examined in the following compound databases: MACCS-II Drug Data Report (MDDR), Current Patents Fast-alert, Comprehensive Medicinal Chemistry, Physician Desk Reference, New Chemical Entities, and the Available Chemical Directory (ACD). The ACDF and MDDRF subsets were created by removing reactive functionalities from the ACD and MDDR databases, respectively. The ACDF subset was further filtered by keeping only molecules with a `drug-like' score [Ajay et al., J. Med. Chem., 41 (1998) 3314; Sadowski and Kubinyi, J. Med. Chem., 41 (1998) 3325] below 0.8. The following properties were examined: molecular weight (MW), the calculated octanol/water partition coefficient (CLOGP), the number of rotatable (RTB) and rigid bonds (RGB), the number of rings (RNG), and the number of hydrogen bond donors (HDO) and acceptors (HAC). Of these, MW and CLOGP follow a Gaussian distribution, whereas all other descriptors have an asymmetric (truncated Gaussian) distribution. Four out of five compounds in ACDF and MDDRF pass the `rule of 5' test, a probability scheme that estimates oral absorption proposed by Lipinski et al. [Adv. Drug Deliv. Rev., 23 (1997) 3]. Because property distributions of HDO, HAC, MW and CLOGP (used in the `rule of 5' test) do not differ significantly between these datasets, the `rule of 5' does not distinguish `drugs' from `nondrugs'. Therefore, Pareto analyses were performed to examine skewed distributions in all compound collections. Seventy percent of the `drug-like' compounds were found between the following limits: 0 ≤ HDO ≤ 2, 2 ≤ HAC ≤ 9, 2 ≤ RTB ≤ 8, and 1 ≤ RNG ≤ 4, respectively. The number of launched drugs in MDDR having 0 ≤ HDO ≤ 2 is 4.8 times higher than the number of drugs having 3 ≤ HDO ≤ 5. Skewed distributions can be exploited to focus on the `drug-like space': 62.68% of ACDF (`nondrug-like') compounds have 0 ≤ RNG ≤ 2, and RGB ≤ 17, while 28.88% of ACDF compounds have 3 ≤ RNG ≤ 13, and 18 ≤ RGB ≤ 56. By contrast, 61.22% of MDDRF compounds have RNG ≥ 3, and RGB ≥ 18, and only 24.73% of MDDRF compounds have 0 ≤ RNG ≤ 2 rings, and RGB ≤ 17. The probability of identifying `drug-like' structures increases with molecular complexity.

The co-occurrence of Internet harassment and unwanted sexual solicitation victimization and perpetration: associations with psychosocial indicators.

PubMed

Ybarra, Michele L; Espelage, Dorothy L; Mitchell, Kimberly J

2007-12-01

Previous research in offline environments suggests that there may be an overlap in bullying and sexual harassment perpetration and victimization; however to what extent this may be true for perpetration and victimization of Internet harassment and unwanted sexual solicitation is unknown. The Growing Up with Media survey is a national cross-sectional online survey of 1,588 youth, 10-15 years old, who have used the Internet at least once in the last 6 months. Cluster analysis was conducted with four scales: Internet harassment perpetration, Internet harassment victimization, unwanted sexual solicitation perpetration, and unwanted sexual solicitation victimization. A four-cluster solution was identified: youth with little to no involvement (n = 1326; 81.7%); perpetrator-victims of Internet harassment (n = 205; 14.3%); victims of both Internet harassment and unwanted sexual solicitation (n = 45; 3.1%); and perpetrator-victims of Internet harassment and unwanted sexual solicitation (n = 12; .9%). Involvement in Internet harassment and unwanted sexual solicitation was associated with concurrent reports of psychosocial problems including substance use; involvement in offline victimization and perpetration of relational, physical, and sexual aggression; delinquent peers; a propensity to respond to stimuli with anger; poor emotional bond with caregivers; and poor caregiver monitoring as compared with youth with little to no involvement. This was especially true for perpetrator-victims of Internet harassment and unwanted sexual solicitation. Findings were replicated using a frequency-based definition of involvement, suggesting that cluster analysis is useful in identifying subgroups of youth and can be used to guide frequency-based definitions, which are easier to implement across study samples. The majority of youth are not frequently involved in Internet harassment or unwanted sexual solicitation either as victims or as perpetrators. Among those who are, however, psychosocial problems are apparent. Perpetrator-victims of Internet harassment and unwanted sexual solicitation have emerged as a particularly important group for adolescent health professionals to be aware of, identify, and treat or refer into services immediately.

Effects of nicotine in combination with drugs described as positive allosteric nicotinic acetylcholine receptor modulators in vitro: discriminative stimulus and hypothermic effects in mice.

PubMed

Moerke, Megan J; de Moura, Fernando B; Koek, Wouter; McMahon, Lance R

2016-09-05

Some drugs that are positive allosteric nAChR modulators in vitro, desformylflustrabromine (dFBr), PNU-120596 and LY 2087101, have not been fully characterized in vivo. These drugs were examined for their capacity to share or modify the hypothermic and discriminative stimulus effects of nicotine (1mg/kg s.c.) in male C57Bl/6J mice. Nicotine, dFBr, and PNU-120596 produced significant hypothermia, whereas LY 2087101 (up to 100mg/kg) did not. Nicotine dose-dependently increased nicotine-appropriate responding and decreased response rate; the respective ED50 values were 0.56mg/kg and 0.91mg/kg. The modulators produced no more than 38% nicotine-appropriate responding up to doses that disrupted operant responding. Rank order potency was the same for hypothermia and rate-decreasing effects: nicotine>dFBr>PNU-120596=LY 2087101. Mecamylamine and the α4β2 nAChR antagonist dihydro-β-erythroidine, but not the α7 antagonist methyllycaconitine, antagonized the hypothermic effects of nicotine. In contrast, mecamylamine did not antagonize the hypothermic effects of the modulators. The combined discriminative stimulus effects of DFBr and nicotine were synergistic, whereas the combined hypothermic effects of nicotine with either dFBr or PNU-120596 were infra-additive. PNU-120596 did not modify the nicotine discriminative stimulus, and LY 2087101 did not significantly modify either effect of nicotine. Positive modulation of nicotine at nAChRs by PNU-120596 and LY 2087101 in vitro does not appear to confer enhancement of the nAChR-mediated hypothermic or discriminative stimulus effects of nicotine. However, dFBr appears to be a positive allosteric modulator of some behavioral effects of nicotine at doses of dFBr smaller than the doses producing unwanted effects (e.g. hypothermia) through non-nAChR mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of nicotine in combination with drugs described as positive allosteric nicotinic acetylcholine receptor modulators in vitro: discriminative stimulus and hypothermic effects in mice

PubMed Central

Moerke, Megan J.; de Moura, Fernando B.; Koek, Wouter; McMahon, Lance R.

2016-01-01

Some drugs that are positive allosteric nAChR modulators in vitro, desformylflustrabromine (dFBr), PNU-120596 and LY 2087101, have not been fully characterized in vivo. These drugs were examined for their capacity to share or modify the hypothermic and discriminative stimulus effects of nicotine (1 mg/kg s.c.) in male C57Bl/6J mice. Nicotine, dFBr, and PNU-120596 produced significant hypothermia, whereas LY 2087101 (up to 100 mg/kg) did not. Nicotine dose-dependently increased nicotine-appropriate responding and decreased response rate; the respective ED50 values were 0.56 mg/kg and 0.91 mg/kg. The modulators produced no more than 38% nicotine-appropriate responding up to doses that disrupted operant responding. Rank order potency was the same for hypothermia and rate-decreasing effects: nicotine>dFBr>PNU-120596=LY 2087101. Mecamylamine and the α4β2 nAChR antagonist dihydro-β-erythroidine, but not the α7 antagonist methyllycaconitine, antagonized the hypothermic effects of nicotine. In contrast, mecamylamine did not antagonize the hypothermic effects of the modulators. The combined discriminative stimulus effects of DFBr and nicotine were synergistic, whereas the combined hypothermic effects of nicotine with either dFBr or PNU-120596 were infra-additive. PNU-120596 did not modify the nicotine discriminative stimulus, and LY 2087101 did not significantly modify either effect of nicotine. Positive modulation of nicotine at nAChRs by PNU-120596 and LY 2087101 in vitro does not appear to confer enhancement of the nAChR-mediated hypothermic or discriminative stimulus effects of nicotine. However, dFBr appears to be a positive allosteric modulator of some behavioral effects of nicotine at doses of dFBr smaller than the doses producing unwanted effects (e.g. hypothermia) through non-nAChR mechanisms. PMID:27238974

47 CFR 95.635 - Unwanted radiation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Unwanted radiation. 95.635 Section 95.635 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PERSONAL RADIO SERVICES Technical Regulations Technical Standards § 95.635 Unwanted radiation. (a) In addition to the...

47 CFR 95.635 - Unwanted radiation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Unwanted radiation. 95.635 Section 95.635 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PERSONAL RADIO SERVICES Technical Regulations Technical Standards § 95.635 Unwanted radiation. (a) In addition to the...

47 CFR 95.635 - Unwanted radiation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Unwanted radiation. 95.635 Section 95.635 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PERSONAL RADIO SERVICES Technical Regulations Technical Standards § 95.635 Unwanted radiation. (a) In addition to the...

47 CFR 95.635 - Unwanted radiation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Unwanted radiation. 95.635 Section 95.635 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PERSONAL RADIO SERVICES Technical Regulations Technical Standards § 95.635 Unwanted radiation. (a) In addition to the...

Target validation: linking target and chemical properties to desired product profile.

PubMed

Wyatt, Paul G; Gilbert, Ian H; Read, Kevin D; Fairlamb, Alan H

2011-01-01

The discovery of drugs is a lengthy, high-risk and expensive business taking at least 12 years and is estimated to cost upwards of US$800 million for each drug to be successfully approved for clinical use. Much of this cost is driven by the late phase clinical trials and therefore the ability to terminate early those projects destined to fail is paramount to prevent unwanted costs and wasted effort. Although neglected diseases drug discovery is driven more by unmet medical need rather than financial considerations, the need to minimise wasted money and resources is even more vital in this under-funded area. To ensure any drug discovery project is addressing the requirements of the patients and health care providers and delivering a benefit over existing therapies, the ideal attributes of a novel drug needs to be pre-defined by a set of criteria called a target product profile. Using a target product profile the drug discovery process, clinical study design, and compound characteristics can be defined all the way back through to the suitability or druggability of the intended biochemical target. Assessment and prioritisation of the most promising targets for entry into screening programmes is crucial for maximising chances of success.

Sentinel events predicting later unwanted sex among girls: A national survey in Haiti, 2012.

PubMed

Sumner, Steven A; Marcelin, Louis H; Cela, Toni; Mercy, James A; Lea, Veronica; Kress, Howard; Hillis, Susan D

2015-12-01

Sexual violence against children is a significant global public health problem, yet limited studies exist from low-resource settings. In Haiti we conducted the country's first, nationally representative survey focused on childhood violence to help inform the development of a national action plan for violence against children. The Haiti Violence Against Children Survey was a household-level, multistage, cluster survey among youth age 13-24. In this analysis we sought to determine whether sexual violence sentinel events (unwanted sexual touching or unwanted attempted sex) were predictive of later unwanted, completed, penetrative sex in Haiti. We also sought to explore characteristics of sentinel events and help-seeking behavior among Haitian children. Multivariable logistic regression was used to test associations between sentinel events and later unwanted, completed, penetrative sex. Overall, 1,457 females reported on experiences of sexual violence occurring in childhood (before age 18). A sentinel event occurred in 40.4% of females who experienced subsequent unwanted completed sex. Females experiencing a sentinel event were approximately two and a half times more likely to experience later unwanted completed sex (adjusted odds ratio=2.40, p=.004) compared to individuals who did not experience a sentinel event. The mean lag time from first sentinel event to first unwanted completed sex was 2.3 years. Only half (54.6%) of children experiencing a sentinel event told someone about their experience of sexual violence. Among children, sentinel events occur frequently before later acts of completed unwanted sex and may represent a useful point of intervention. Reporting of sexual violence by children in Haiti is low and can be improved to better act on sentinel events. Published by Elsevier Ltd.

Inhaled sildenafil as an alternative to oral sildenafil in the treatment of pulmonary arterial hypertension (PAH).

PubMed

Rashid, Jahidur; Patel, Brijeshkumar; Nozik-Grayck, Eva; McMurtry, Ivan F; Stenmark, Kurt R; Ahsan, Fakhrul

2017-03-28

The practice of treating PAH patients with oral or intravenous sildenafil suffers from the limitations of short dosing intervals, peripheral vasodilation, unwanted side effects, and restricted use in pediatric patients. In this study, we sought to test the hypothesis that inhalable poly(lactic-co-glycolic acid) (PLGA) particles of sildenafil prolong the release of the drug, produce pulmonary specific vasodilation, reduce the systemic exposure of the drug, and may be used as an alternative to oral sildenafil in the treatment of PAH. Thus, we prepared porous PLGA particles of sildenafil using a water-in-oil-in-water double emulsion solvent evaporation method with polyethyleneimine (PEI) as a porosigen and characterized the formulations for surface morphology, respirability, in-vitro drug release, and evaluated for in vivo absorption, alveolar macrophage uptake, and safety. PEI increased the particle porosity, drug entrapment, and produced drug release for 36h. Fluorescent particles showed reduced uptake by alveolar macrophages. The polymeric particles were safe to rat pulmonary arterial smooth muscle cell and to the lungs, as evidenced by the cytotoxicity assay and analyses of the injury markers in the bronchoalveolar lavage fluid, respectively. Intratracheally administered sildenafil particles elicited more pulmonary specific and sustained vasodilation in SUGEN-5416/hypoxia-induced PAH rats than oral, intravenous, or intratracheal plain sildenafil did, when administered at the same dose. Overall, true to the hypothesis, this study shows that inhaled PLGA particles of sildenafil can be administered, as a substitute for oral form of sildenafil, at a reduced dose and longer dosing interval. Copyright © 2017 Elsevier B.V. All rights reserved.

Presence of Cx43 in extracellular vesicles reduces the cardiotoxicity of the anti-tumour therapeutic approach with doxorubicin

PubMed Central

Martins-Marques, Tania; Pinho, Maria Joao; Zuzarte, Monica; Oliveira, Carla; Pereira, Paulo; Sluijter, Joost P. G.; Gomes, Celia; Girao, Henrique

2016-01-01

Extracellular vesicles (EVs) are major conveyors of biological information, mediating local and systemic cell-to-cell communication under physiological and pathological conditions. These endogenous vesicles have been recognized as prominent drug delivery vehicles of several therapeutic cargoes, including doxorubicin (dox), presenting major advantages over the classical approaches. Although dox is one of the most effective anti-tumour agents in the clinical practice, its use is very often hindered by its consequent dramatic cardiotoxicity. Despite significant advances witnessed in the past few years, more comprehensive studies, supporting the therapeutic efficacy of EVs, with decreased side effects, are still scarce. The main objective of this study was to evaluate the role of the gap junction protein connexin43 (Cx43) in mediating the release of EV content into tumour cells. Moreover, we investigated whether Cx43 improves the efficiency of dox-based anti-tumour treatment, with a concomitant decrease of cardiotoxicity. In the present report, we demonstrate that the presence of Cx43 in EVs increases the release of luciferin from EVs into tumour cells in vitro and in vivo. In addition, using cell-based approaches and a subcutaneous mouse tumour model, we show that the anti-tumour effect of dox incorporated into EVs is similar to the administration of the free drug, regardless the presence of Cx43. Strikingly, we demonstrate that the presence of Cx43 in dox-loaded EVs reduces the cardiotoxicity of the drug. Altogether, these results bring new insights into the concrete potential of EVs as therapeutic vehicles and open new avenues toward the development of strategies that help to reduce unwanted side effects. PMID:27702427

[Antiplatelet properties of nitrogen monoxide].

PubMed

Adrie, C

1996-11-01

Nitric (correction of nitrous) oxide (NO) plays a fundamental part in the haemostatic equilibrium between the endothelium and platelets, an equilibrium of established clinical importance in cardiovascular disease. NO stimulates the enzyme guanylate cyclase which is responsible for synthesis of GMPc, the increase of which results in platelet inhibition. Synthesis of NO may have endogenous auto or paracrine origine from platelets or endothelial cells and participates in the local regulation of platelet function in association with other products of endothelial or platelet synthesis. Exogenous administration is common in therapeutics either in molecules which release NO (nitrate derivatives, sodium nitropruside, molsidomine, etc) or by NO gas administered by inhalation. The antiplatelet effect of NO has been clearly demonstrated in vitro, in vivo or ex vivo, in animals and humans, and probably explains, at least partially, the efficacy of nitrate derivatives in ischaemic coronary artery disease. Nevertheless, the platelet inhibition observed with intravenous NO releasing drugs is associated with potentially harmful systemic hypotension. Platelet inhibition by inhalation of NO could be an alternative means of avoiding this unwanted effect.

Proton Pump Inhibitors in cancer patients: How useful they are? A review of the most common indications for their use.

PubMed

Numico, Gianmauro; Fusco, Vittorio; Franco, Pierfrancesco; Roila, Fausto

2017-03-01

Proton-Pump Inhibitors (PPIs) are commonly prescribed in the general population and in cancer patients. A supposed role in the prevention of gastric mucosal damage apparently justify their use in patients undergoing cytotoxic chemotherapy, steroids and radiotherapy on the gastro-duodenal region. They are frequently given also to patients admitted to Intensive Care Units, for the prevention of stress-related gastric ulcers. The evidence about these use of gastroprotection is reviewed. In the majority of the cases the prescription of PPIs is not justified. In two circumstances (chemotherapy and stress-related gastric disease) randomized studies have shown a protective action of PPIs although this effect did not translate into the reduction of serious clinical consequences. PPIs are not free of toxic effects that are acknowledged by an expanding literature. Also the interaction with anticancer drugs is a potential source of unwanted consequences. Copyright © 2017 Elsevier B.V. All rights reserved.

DRUG USAGE AND DISPOSAL: OVERVIEW OF ...

EPA Pesticide Factsheets

This article provides the background for understanding the many complex variables that combine to cause pollution of the environment with the active ingredients from pharmaceuticals. It also summarizes the many approaches that could potentially reduce this pollution. Significantly, actions designed for pollution prevention or pollution reduction hold the potential to also reduce healthcare expenses, improve therapeutic outcomes, and moderate the long-persisting national problem of morbidity and mortality caused by poisonings of infants, children, adults, pets, and sometimes wildlife. These collateral benefits are important to this discussion beacuse one of the major unknowns regarding trhe various pollution control actions (such as reducing generation and disposal of unwanted drugs) is whether they would actually result in significantly reduced pollution. The main driving force for reducing pollution may have more to do with human health and safety. Presentation

Characterization of Aptamer BC 007 Substance and Product Using Circular Dichroism and Nuclear Magnetic Resonance Spectroscopy.

PubMed

Weisshoff, Hardy; Wenzel, Katrin; Schulze-Rothe, Sarah; Nikolenko, Heike; Davideit, Hanna; Becker, Niels-Peter; Göttel, Peter; Srivatsa, G Susan; Dathe, Margitta; Müller, Johannes; Haberland, Annekathrin

2018-04-18

Possible unwanted folding of biopharmaceuticals during manufacturing and storage has resulted in analysis schemes compared to small molecules that include bioanalytical characterization besides chemical characterization. Whether bioanalytical characterization is required for nucleotide-based drugs, may be decided on a case-by-case basis. Nucleotide-based pharmaceuticals, if chemically synthesized, occupy an intermediate position between small-molecule drugs and biologics. Here, we tested whether a physicochemical characterization of a nucleotide-based drug substance, BC 007, was adequate, using circular dichroism (CD) spectroscopy. Nuclear magnetic resonance confirmed CD data in one experimental setup. BC 007 forms a quadruplex structure under specific external conditions, which was characterized for its stability and structural appearance also after denaturation using CD and nuclear magnetic resonance. The amount of the free energy (ΔG 0 ) involved in quadruplex formation of BC 007 was estimated at +8.7 kJ/mol when dissolved in water and +1.4 kJ/mol in 154 mM NaCl, indicating structural instability under these conditions. However, dissolution of the substance in 5 mM of KCl reduced the ΔG 0 to -5.6 kJ/mol due to the stabilizing effect of cations. These results show that positive ΔG 0 of quadruplex structure formation in water and aqueous NaCl prevents BC 007 from preforming stable 3-dimensional structures, which could potentially affect drug function. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

A cross-sectional study examining the extent of unwanted sexual attention and unhealthy intimate relationships among female university students.

PubMed

Hayden, Kelly; Graham, Melissa; Lamaro, Greer

2016-05-17

Issue addressed: Unwanted sexual attention and unhealthy intimate relationships have the potential to have serious negative health consequences. To date, there has been scant focus on these issues among university students in Australia. The aim of the current study was to describe the extent of unwanted sexual attention and unhealthy intimate relationships experienced in their lifetime by female university students aged 18-25 years. Methods: A cross-sectional study was undertaken involving 465 female students aged 18-25 years. Students were recruited through one faculty within a Victorian university and invited to complete an anonymous online questionnaire. Results: Sixty-seven per cent (n = 312) of female students reported experiencing unwanted sexual attention in their lifetime. The most common form of unwanted sexual attention was kissing or touching over clothes (98%; n = 306). Over 43% (n = 124) of the female students reported that the experience of unwanted sexual experience occurred after their protests were ignored. Thirty per cent (n = 135) of the female students reported experiencing at least one element of an unhealthy intimate relationship. Conclusions: The high rates of unwanted sexual attention and unhealthy intimate relationships among female university students is of concern given the negative impact such events can have on individual's physical, emotional and social well being. So what?: Public health and health promotion action is required to prevent female students from experiencing unwanted sexual attention and unhealthy intimate relationships, and to address the negative health and well being consequences.

Unintended pregnancy and prenatal care: a study from a maternity hospital in Turkey.

PubMed

Erol, Nermin; Durusoy, Raika; Ergin, Işıl; Döner, Banu; Ciçeklioğlu, Meltem

2010-08-01

To evaluate factors associated with pregnancy intention and its effects on source, content and adequacy of prenatal care for women who delivered in a large maternity hospital in Izmir, Turkey. This cross-sectional survey was carried out using a questionnaire administered face-to-face to 351 women who had given birth in Konak Maternity Hospital in May 2002. Nearly half (47.3%) of the pregnancies were unintended: 31.3% were mistimed, and 16.0% unwanted. Women's and husbands' older age and lower education, lower social class, women's recent migration to Izmir, lower household income and absence of social security had a negative impact on pregnancy intention. Women with unwanted pregnancies had started procreating earlier; they had more pregnancies, deliveries, children and intentional abortions (p < 0.05). Number and contents of prenatal visits increased as intention status improved. When controlled for socio-demographic variables, women with unwanted pregnancies had less prenatal care, received less education during prenatal visits and had less iron and vitamin supplementation (p < 0.05) whereas mistimed pregnancies did not significantly differ from intended pregnancies. Unwanted pregnancies constitute a risk group that should be identified early in pregnancy. Ensuring an adequate and satisfactory prenatal care for all requires appropriate measures to be taken by public health authorities.

Triangular Assessment of the Etiology of Induced Abortion in Iran: A Qualitative Study

PubMed Central

Motaghi, Zahra; Keramat, Afsaneh; Shariati, Mohammad; Yunesian, Masud

2013-01-01

Background About 46 million induced abortions occur in the world annually. The studies have reported 80000 cases of induced abortions in Iran annually. Objectives This qualitative study was conducted to identify the causes of unsafe abortion in Iran from the standpoint of three groups of experts, women with a history of abortion or unwanted pregnancy and service providers. Patients and Methods A total of 72 in-depth semi structured interviews were conducted in 2012 in Tehran and Shahroud. After coordination with 8 experts, sampling from them was done using the Snowballing method in their offices. Sampling from 28 married and 10 engaged women with a history of unwanted pregnancy or unsafe abortion and 12 providers was done in health care centers and a in number of gynecologists’ and midwives’ offices. Sampling from women with a history of unwanted pregnancy or unsafe abortion such as single women, HIV positive women and drug users, and women who had sexual intercourse for money was started by referring to the social rehabilitation center for women and continued using the snowballing method due to difficulties in accessing them. Participants were from different ethnic groups including Fars, Gilaks, Mazandarani, Arab, Azerbaijani, and Lor. Content analysis was performed on collected data. Results Based on the results of the interviews, participants have abortion for following reasons: 1. Wanted pregnancy (sub categories: fetal abnormalities, Concern about fetal health and lack of trust to prenatal diagnostic methods, Fetal sex, Lack of independent and free decision making regarding pregnancy in women, 2. Unwanted pregnancy (sub-categories: Socio-economic factors, Beliefs and feelings, Lack of information about family planning) 3. Predisposing factors (sub-categories: Lack of information on religious aspects of abortion, Easy access to easy abortion methods). Some people, despite having unwanted pregnancy due to social, economic, cultural and family grounds, continued their pregnancy and did not have an abortion for the following reasons: Religious beliefs, Beliefs (fear of punishment in the afterlife and believing in fate) , Attachment to the unborn baby, Influence of the other people’s opinions (physician, mother or spouse) Late diagnosis of pregnancy, Unsuccessful abortion attempts (Self-treatment, Unsuccessful medical abortion), Economic weakness and arbitrary treatment. Conclusions In the present study, women who continued their pregnancy despite being unwanted were also interviewed. Although they had the same social, economic, cultural, and family problems as women with a history of unsafe abortion and had easy access to abortion, analysis showed that the difference in religious beliefs between the two groups was the most important factor that led women to choose two different approaches. The authors believe that in-depth analysis of people’s beliefs and opinions in this regard and correction of false beliefs plays a crucial role in decreasing the rate of unsafe abortion. PMID:24719694

45 CFR 650.9 - Unwanted inventions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 3 2014-10-01 2014-10-01 false Unwanted inventions. 650.9 Section 650.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.9 Unwanted inventions. (a) The Foundation will normally allow any patent rights not wanted by the awardee or...

45 CFR 650.9 - Unwanted inventions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 3 2013-10-01 2013-10-01 false Unwanted inventions. 650.9 Section 650.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.9 Unwanted inventions. (a) The Foundation will normally allow any patent rights not wanted by the awardee or...

45 CFR 650.9 - Unwanted inventions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 3 2012-10-01 2012-10-01 false Unwanted inventions. 650.9 Section 650.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.9 Unwanted inventions. (a) The Foundation will normally allow any patent rights not wanted by the awardee or...

40 CFR 262.208 - Removing containers of unwanted material from the laboratory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Laboratories Owned by Eligible Academic Entities § 262.208 Removing containers of unwanted material from the laboratory. (a) Removing containers of unwanted material on a regular schedule. An eligible academic entity... months of each container's accumulation start date. (b) The eligible academic entity must specify in Part...

40 CFR 262.208 - Removing containers of unwanted material from the laboratory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Laboratories Owned by Eligible Academic Entities § 262.208 Removing containers of unwanted material from the laboratory. (a) Removing containers of unwanted material on a regular schedule. An eligible academic entity... months of each container's accumulation start date. (b) The eligible academic entity must specify in Part...

40 CFR 262.208 - Removing containers of unwanted material from the laboratory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Laboratories Owned by Eligible Academic Entities § 262.208 Removing containers of unwanted material from the laboratory. (a) Removing containers of unwanted material on a regular schedule. An eligible academic entity... months of each container's accumulation start date. (b) The eligible academic entity must specify in Part...

Unwanted sexual attention at work and long-term sickness absence: a follow-up register-based study.

PubMed

Hogh, Annie; Conway, Paul Maurice; Clausen, Thomas; Madsen, Ida Elisabeth Huitfeldt; Burr, Hermann

2016-07-30

The current understanding of the relationship between unwanted sexual attention at work and long-term sickness absence (LTSA) is limited for three reasons: 1) the under-researched role of unwanted sexual attention perpetrated by individuals outside the work organization; 2) a widespread use of self-reported measures of sickness absence, with an unclear identification of sickness absence episodes of long duration; 3) the cross-sectional design of most existing studies. The aim of this study was therefore to investigate the relationship between self-reported unwanted sexual attention at work and subsequent LTSA (≥3 weeks), stratifying by gender and source of exposure (i.e., colleagues, managers and/or subordinates vs. clients/customers/patients). This prospective study is based on a pooled sample of 14,605 employees from three Danish surveys conducted in 2000, 2004 and 2005, providing a total of 19,366 observations. A single questionnaire-based item was used to assess exposure to unwanted sexual attention. The pooled dataset was merged with Danish register data on LTSA. The risk of first-onset episode of LTSA (up to 18 months after baseline) in connection with unwanted sexual attention was examined using Cox proportional hazards models. We estimated Hazard ratios (HR) and 95 % confidence intervals (95 % CI) adjusted for age, influence at work, work pace, occupational group and mode of data collection. We also adjusted for repeated measures from individual respondents by stratifying the Cox models by wave of survey. Unwanted sexual attention from colleagues, managers and/or subordinates predicted LTSA among men (HR 2.66; 95 % CI 1.42-5.00). Among women, an elevated but non-statistically significant risk of LTSA (HR 1.18; 95 % CI 0.65-2.14) was found. Unwanted sexual attention from clients/customers/patients did not predict LTSA, neither among men nor among women. The findings indicate a significantly elevated risk of LTSA, among men only, in relation to exposure to unwanted sexual attention from colleagues, managers and/or subordinates. This study therefore suggests both individual and organizational costs associated with unwanted sexual attention at work. Due to the low prevalence of unwanted sexual attention, larger studies with more statistical power are needed to confirm (or disconfirm) the present findings.

Chirality detection of enantiomers using twisted optical metamaterials

NASA Astrophysics Data System (ADS)

Zhao, Yang; Askarpour, Amir N.; Sun, Liuyang; Shi, Jinwei; Li, Xiaoqin; Alù, Andrea

2017-01-01

Many naturally occurring biomolecules, such as amino acids, sugars and nucleotides, are inherently chiral. Enantiomers, a pair of chiral isomers with opposite handedness, often exhibit similar physical and chemical properties due to their identical functional groups and composition, yet show different toxicity to cells. Detecting enantiomers in small quantities has an essential role in drug development to eliminate their unwanted side effects. Here we exploit strong chiral interactions with plasmonic metamaterials with specifically designed optical response to sense chiral molecules down to zeptomole levels, several orders of magnitude smaller than what is typically detectable with conventional circular dichroism spectroscopy. In particular, the measured spectra reveal opposite signs in the spectral regime directly associated with different chiral responses, providing a way to univocally assess molecular chirality. Our work introduces an ultrathin, planarized nanophotonic interface to sense chiral molecules with inherently weak circular dichroism at visible and near-infrared frequencies.

Chirality detection of enantiomers using twisted optical metamaterials

PubMed Central

Zhao, Yang; Askarpour, Amir N.; Sun, Liuyang; Shi, Jinwei; Li, Xiaoqin; Alù, Andrea

2017-01-01

Many naturally occurring biomolecules, such as amino acids, sugars and nucleotides, are inherently chiral. Enantiomers, a pair of chiral isomers with opposite handedness, often exhibit similar physical and chemical properties due to their identical functional groups and composition, yet show different toxicity to cells. Detecting enantiomers in small quantities has an essential role in drug development to eliminate their unwanted side effects. Here we exploit strong chiral interactions with plasmonic metamaterials with specifically designed optical response to sense chiral molecules down to zeptomole levels, several orders of magnitude smaller than what is typically detectable with conventional circular dichroism spectroscopy. In particular, the measured spectra reveal opposite signs in the spectral regime directly associated with different chiral responses, providing a way to univocally assess molecular chirality. Our work introduces an ultrathin, planarized nanophotonic interface to sense chiral molecules with inherently weak circular dichroism at visible and near-infrared frequencies. PMID:28120825

Condom use within marriage: a neglected HIV intervention.

PubMed Central

Ali, Mohamed M.; Cleland, John; Shah, Iqbal H.

2004-01-01

OBJECTIVE: To assess the contraceptive effectiveness of condoms versus oral contraceptive pills and estimate the reproductive consequences of a major shift from pill to condom use. METHODS: Secondary analysis was performed on nationally representative cross-sectional surveys of women in 16 developing countries. FINDINGS: In the 16 countries, the median per cent of married couples currently using condoms was 2%, compared with 13% for the pill. Condom users reported a higher 12-month failure and higher method-related discontinuation rates than pill users (9% and 44% vs 6% and 30%, respectively). Condom users were more likely to report subsequent abortion following failure (21% vs 14%), and also more likely to switch rapidly to another method (76% vs 58%). The reproductive consequences, in terms of abortion and unwanted births, of a hypothetical reversal of the relative prevalence of condom and pill were estimated to be minor. The main reason for this unexpected result is that the majority of abortions and unwanted births arise from non-use of any contraceptive method. CONCLUSION: A massive shift from the more effective oral contraceptive pills to the less effective condom would not jeopardize policy goals of reducing abortions and unwanted births. However, such a shift would potentially have an added benefit of preventing human immunodeficiency virus (HIV) infections, especially in countries with generalized HIV epidemics. PMID:15112006

Assessment of surface concentrations in resorbable ocular implants: controlled drug delivery devices for 5-fluorouracil (5-FU)

NASA Astrophysics Data System (ADS)

Milne, Peter J.; Gautier, Sandrine; Parel, Jean-Marie A.; Jallet, Valerie

1997-05-01

The antineoplastic drug 5-fluorouracil (5-fluoro- 2,4,(1H,3H)-pyrimidinedione; 5-FU) has been used to control proliferation of penetrating fibroblasts and to prevent channel closure following glaucoma filtration surgery (trabeculectomy) or laser sclerectomy. Because of the toxicity of the drug, administration of low dosages slowly over time, at the site of the desired treatment, is indicated for optimum efficacy. Repeated injections of low dosages of the drug represent an undesirable intervention and may also result in unwanted toxicity to the corneal epithelium. A suitable biocompatible and resorbable polymer matrix composed of a poly (D,L-lactic-co-glycolic acid: PLGA) has been admixed with varying amounts of 5-FU and cast as shapes suitable for intracorneal implantation. Slow biodegradation of this polymer over a one to two week period has been shown to result in an acceptably slow drug release mechanism. An issue arising during the clinical evaluation of the efficacy of this drug delivery system was how best to quantify the concentration of 5-FU and its distribution spatially in the solid implant. FT-IR and FT-Raman spectroscopies distinguishes between the drug and the polymer matrix and were used to differentiate and quantitate the 5-FU concentration of the implants.

FAF-Drugs3: a web server for compound property calculation and chemical library design

PubMed Central

Lagorce, David; Sperandio, Olivier; Baell, Jonathan B.; Miteva, Maria A.; Villoutreix, Bruno O.

2015-01-01

Drug attrition late in preclinical or clinical development is a serious economic problem in the field of drug discovery. These problems can be linked, in part, to the quality of the compound collections used during the hit generation stage and to the selection of compounds undergoing optimization. Here, we present FAF-Drugs3, a web server that can be used for drug discovery and chemical biology projects to help in preparing compound libraries and to assist decision-making during the hit selection/lead optimization phase. Since it was first described in 2006, FAF-Drugs has been significantly modified. The tool now applies an enhanced structure curation procedure, can filter or analyze molecules with user-defined or eight predefined physicochemical filters as well as with several simple ADMET (absorption, distribution, metabolism, excretion and toxicity) rules. In addition, compounds can be filtered using an updated list of 154 hand-curated structural alerts while Pan Assay Interference compounds (PAINS) and other, generally unwanted groups are also investigated. FAF-Drugs3 offers access to user-friendly html result pages and the possibility to download all computed data. The server requires as input an SDF file of the compounds; it is open to all users and can be accessed without registration at http://fafdrugs3.mti.univ-paris-diderot.fr. PMID:25883137

The role of myofibroblasts in wound healing, contraction and its clinical implications in cleft palate repair.

PubMed

Chitturi, Ravi Teja; Balasubramaniam, A Murali; Parameswar, R Arjun; Kesavan, G; Haris, K T Muhamed; Mohideen, Khadijah

2015-03-01

Myofibroblasts after its discovery in 1971 as the principal cell for wound healing has come a long way as far as research is concerned. The primary focus of research has been regarding preventing certain unwanted effects of this cell such as wound contraction and scarring. As far as the oral and maxillofacial region is concerned, the primary concern of this untoward effect is during repair of cleft palate surgically which results impaired development of palate and the dentoalveolar structures. This review focuses on the basic aspects of myofibroblasts such as its origin, formation, function in wound healing, role in wound contraction and ways by which its unwanted effects can be overcome to improve the quality of the post surgical complications of cleft palate surgery.

Inducing cell death in vitro in cancer cells by targeted delivery of cytochrome c via a transferrin conjugate

PubMed Central

Delgado, Yamixa; Sharma, Rohit Kumar; Sharma, Shweta; Guzmán, Solimar Liz Ponce De León; Tinoco, Arthur D.; Griebenow, Kai

2018-01-01

One of the major drawbacks of many of the currently used cancer drugs are off-target effects. Targeted delivery is one method to minimize such unwanted and detrimental events. To actively target lung cancer cells, we have developed a conjugate of the apoptosis inducing protein cytochrome c with transferrin because the transferrin receptor is overexpressed by many rapidly dividing cancer cells. Cytochrome c and transferrin were cross-linked with a redox sensitive disulfide bond for the intra-cellular release of the protein upon endocytosis by the transferrin receptor. Confocal results demonstrated the cellular uptake of the cytochrome c-transferrin conjugate by transferrin receptor overexpressing A549 lung cancer cells. Localization studies further validated that this conjugate escaped the endosome. Additionally, an in vitro assay showed that the conjugate could induce apoptosis by activating caspase-3. The neo-conjugate not only maintained an IC50 value similar to the well known drug cisplatin (50 μM) in A549 cancer cells but also was nontoxic to the normal lung (MRC5) cells. Our neo-conjugate holds promise for future development to target cancers with enhanced transferrin receptor expression. PMID:29649293

The genomic response of skeletal muscle to methylprednisolone using microarrays: tailoring data mining to the structure of the pharmacogenomic time series

PubMed Central

DuBois, Debra C; Piel, William H; Jusko, William J

2008-01-01

High-throughput data collection using gene microarrays has great potential as a method for addressing the pharmacogenomics of complex biological systems. Similarly, mechanism-based pharmacokinetic/pharmacodynamic modeling provides a tool for formulating quantitative testable hypotheses concerning the responses of complex biological systems. As the response of such systems to drugs generally entails cascades of molecular events in time, a time series design provides the best approach to capturing the full scope of drug effects. A major problem in using microarrays for high-throughput data collection is sorting through the massive amount of data in order to identify probe sets and genes of interest. Due to its inherent redundancy, a rich time series containing many time points and multiple samples per time point allows for the use of less stringent criteria of expression, expression change and data quality for initial filtering of unwanted probe sets. The remaining probe sets can then become the focus of more intense scrutiny by other methods, including temporal clustering, functional clustering and pharmacokinetic/pharmacodynamic modeling, which provide additional ways of identifying the probes and genes of pharmacological interest. PMID:15212590

Depoliticising the political: Market solutions and the retreat of Swedish institutional drug treatment from state management.

PubMed

Edman, Johan

2016-06-01

This article examines developments in the Swedish drug treatment services in 1982-2000 and explores the ways in which political initiatives and the state administration's management have contributed to the major privatisations of institutional drug treatment during this period. The empirical basis for the textual analysis lies in official reports, parliamentary material and archived records from the Stockholm County Administrative Board's management of treatment facilities. The major privatisations of drug treatment services in the 1980s were both unintentional and unwanted and mainly arose from a lack of bureaucratic control and ideological anchorage. The privatisations were, however, reinforced by ideologically driven NPM-oriented political initiatives in the 1990s. The market-oriented treatment services have failed to fulfil the needs for diversity and availability within a publicly financed sector, which deals with unevenly informed and often socio-economically weak citizens. New management models in this field must ensure that ideological considerations are taken into account to meet politically decided goals and means. Copyright © 2016 Elsevier B.V. All rights reserved.

Generative Recurrent Networks for De Novo Drug Design.

PubMed

Gupta, Anvita; Müller, Alex T; Huisman, Berend J H; Fuchs, Jens A; Schneider, Petra; Schneider, Gisbert

2018-01-01

Generative artificial intelligence models present a fresh approach to chemogenomics and de novo drug design, as they provide researchers with the ability to narrow down their search of the chemical space and focus on regions of interest. We present a method for molecular de novo design that utilizes generative recurrent neural networks (RNN) containing long short-term memory (LSTM) cells. This computational model captured the syntax of molecular representation in terms of SMILES strings with close to perfect accuracy. The learned pattern probabilities can be used for de novo SMILES generation. This molecular design concept eliminates the need for virtual compound library enumeration. By employing transfer learning, we fine-tuned the RNN's predictions for specific molecular targets. This approach enables virtual compound design without requiring secondary or external activity prediction, which could introduce error or unwanted bias. The results obtained advocate this generative RNN-LSTM system for high-impact use cases, such as low-data drug discovery, fragment based molecular design, and hit-to-lead optimization for diverse drug targets. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Intraperitoneal delivery of platinum with in-situ crosslinkable hyaluronic acid gel for local therapy of ovarian cancer

PubMed Central

Cho, Eun Jung; Sun, Bo; Doh, Kyung-Oh; Wilson, Erin M.; Torregrosa-Allen, Sandra; Elzey, Bennett D.; Yeo, Yoon

2014-01-01

Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of solid carcinomas confined within the peritoneal cavity, with potential benefits in locoregional and systemic management of residual tumors. In this study, we intended to increase local retention of platinum in the peritoneal cavity over a prolonged period of time using a nanoparticle form of platinum and an in-situ crosslinkable hyaluronic acid gel. Hyaluronic acid was chosen as a carrier due to the biocompatibility and biodegradability. We confirmed a sustained release of platinum from the nanoparticles (PtNPs) and nanoparticle/gel hybrid (PtNP/gel), receptor-mediated endocytosis of PtNPs, and retention of the gel in the peritoneal cavity over 4 weeks--conditions desirable for a prolonged local delivery of platinum. However, PtNPs and PtNP/gel did not show a greater anti-tumor efficacy than CDDP solution administered at the same dose but rather caused a slight increase in tumor burdens at later time points, which suggests a potential involvement of empty carriers and degradation products in the growth of residual tumors. This study alerts that although several materials considered biocompatible and safe are used as drug carriers, they may have unwanted biological effects on the residual targets once the drug is exhausted; therefore, more attention should be paid to the selection of the drug carriers. PMID:25453960

Intraperitoneal delivery of platinum with in-situ crosslinkable hyaluronic acid gel for local therapy of ovarian cancer.

PubMed

Cho, Eun Jung; Sun, Bo; Doh, Kyung-Oh; Wilson, Erin M; Torregrosa-Allen, Sandra; Elzey, Bennett D; Yeo, Yoon

2015-01-01

Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of solid carcinomas confined within the peritoneal cavity, with potential benefits in locoregional and systemic management of residual tumors. In this study, we intended to increase local retention of platinum in the peritoneal cavity over a prolonged period of time using a nanoparticle form of platinum and an in-situ crosslinkable hyaluronic acid gel. Hyaluronic acid was chosen as a carrier due to the biocompatibility and biodegradability. We confirmed a sustained release of platinum from the nanoparticles (PtNPs) and nanoparticle/gel hybrid (PtNP/gel), receptor-mediated endocytosis of PtNPs, and retention of the gel in the peritoneal cavity over 4 weeks: conditions desirable for a prolonged local delivery of platinum. However, PtNPs and PtNP/gel did not show a greater anti-tumor efficacy than CDDP solution administered at the same dose but rather caused a slight increase in tumor burdens at later time points, which suggests a potential involvement of empty carriers and degradation products in the growth of residual tumors. This study alerts that although several materials considered biocompatible and safe are used as drug carriers, they may have unwanted biological effects on the residual targets once the drug is exhausted; therefore, more attention should be paid to the selection of drug carriers. Copyright © 2014 Elsevier Ltd. All rights reserved.

45 CFR 650.9 - Unwanted inventions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Unwanted inventions. 650.9 Section 650.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.9 Unwanted inventions. (a) The Foundation will normally allow any patent rights not wanted by the awardee or inventor to be dedicated to the public...

45 CFR 650.9 - Unwanted inventions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 3 2011-10-01 2011-10-01 false Unwanted inventions. 650.9 Section 650.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.9 Unwanted inventions. (a) The Foundation will normally allow any patent rights not wanted by the awardee or inventor to be dedicated to the public...

40 CFR 262.215 - Unwanted material that is not solid or hazardous waste.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Unwanted material that is not solid or... (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS APPLICABLE TO GENERATORS OF HAZARDOUS WASTE Alternative... Eligible Academic Entities § 262.215 Unwanted material that is not solid or hazardous waste. (a) If an...

40 CFR 262.215 - Unwanted material that is not solid or hazardous waste.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Unwanted material that is not solid or... (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS APPLICABLE TO GENERATORS OF HAZARDOUS WASTE Alternative... Eligible Academic Entities § 262.215 Unwanted material that is not solid or hazardous waste. (a) If an...

Modeling Patient-Specific Magnetic Drug Targeting Within the Intracranial Vasculature

PubMed Central

Patronis, Alexander; Richardson, Robin A.; Schmieschek, Sebastian; Wylie, Brian J. N.; Nash, Rupert W.; Coveney, Peter V.

2018-01-01

Drug targeting promises to substantially enhance future therapies, for example through the focussing of chemotherapeutic drugs at the site of a tumor, thus reducing the exposure of healthy tissue to unwanted damage. Promising work on the steering of medication in the human body employs magnetic fields acting on nanoparticles made of paramagnetic materials. We develop a computational tool to aid in the optimization of the physical parameters of these particles and the magnetic configuration, estimating the fraction of particles reaching a given target site in a large patient-specific vascular system for different physiological states (heart rate, cardiac output, etc.). We demonstrate the excellent computational performance of our model by its application to the simulation of paramagnetic-nanoparticle-laden flows in a circle of Willis geometry obtained from an MRI scan. The results suggest a strong dependence of the particle density at the target site on the strength of the magnetic forcing and the velocity of the background fluid flow. PMID:29725303

Modeling Patient-Specific Magnetic Drug Targeting Within the Intracranial Vasculature.

PubMed

Patronis, Alexander; Richardson, Robin A; Schmieschek, Sebastian; Wylie, Brian J N; Nash, Rupert W; Coveney, Peter V

2018-01-01

Drug targeting promises to substantially enhance future therapies, for example through the focussing of chemotherapeutic drugs at the site of a tumor, thus reducing the exposure of healthy tissue to unwanted damage. Promising work on the steering of medication in the human body employs magnetic fields acting on nanoparticles made of paramagnetic materials. We develop a computational tool to aid in the optimization of the physical parameters of these particles and the magnetic configuration, estimating the fraction of particles reaching a given target site in a large patient-specific vascular system for different physiological states (heart rate, cardiac output, etc.). We demonstrate the excellent computational performance of our model by its application to the simulation of paramagnetic-nanoparticle-laden flows in a circle of Willis geometry obtained from an MRI scan. The results suggest a strong dependence of the particle density at the target site on the strength of the magnetic forcing and the velocity of the background fluid flow.

Nanotechnology and the Treatment of HIV Infection

PubMed Central

Parboosing, Raveen; Maguire, Glenn E. M.; Govender, Patrick; Kruger, Hendrik G.

2012-01-01

Suboptimal adherence, toxicity, drug resistance and viral reservoirs make the lifelong treatment of HIV infection challenging. The emerging field of nanotechnology may play an important role in addressing these challenges by creating drugs that possess pharmacological advantages arising out of unique phenomena that occur at the “nano” scale. At these dimensions, particles have physicochemical properties that are distinct from those of bulk materials or single molecules or atoms. In this review, basic concepts and terms in nanotechnology are defined, and examples are provided of how nanopharmaceuticals such as nanocrystals, nanocapsules, nanoparticles, solid lipid nanoparticles, nanocarriers, micelles, liposomes and dendrimers have been investigated as potential anti-HIV therapies. Such drugs may, for example, be used to optimize the pharmacological characteristics of known antiretrovirals, deliver anti-HIV nucleic acids into infected cells or achieve targeted delivery of antivirals to the immune system, brain or latent reservoirs. Also, nanopharmaceuticals themselves may possess anti-HIV activity. However several hurdles remain, including toxicity, unwanted biological interactions and the difficulty and cost of large-scale synthesis of nanopharmaceuticals. PMID:22590683

Prediction of unwanted pregnancies using logistic regression, probit regression and discriminant analysis

PubMed Central

Ebrahimzadeh, Farzad; Hajizadeh, Ebrahim; Vahabi, Nasim; Almasian, Mohammad; Bakhteyar, Katayoon

2015-01-01

Background: Unwanted pregnancy not intended by at least one of the parents has undesirable consequences for the family and the society. In the present study, three classification models were used and compared to predict unwanted pregnancies in an urban population. Methods: In this cross-sectional study, 887 pregnant mothers referring to health centers in Khorramabad, Iran, in 2012 were selected by the stratified and cluster sampling; relevant variables were measured and for prediction of unwanted pregnancy, logistic regression, discriminant analysis, and probit regression models and SPSS software version 21 were used. To compare these models, indicators such as sensitivity, specificity, the area under the ROC curve, and the percentage of correct predictions were used. Results: The prevalence of unwanted pregnancies was 25.3%. The logistic and probit regression models indicated that parity and pregnancy spacing, contraceptive methods, household income and number of living male children were related to unwanted pregnancy. The performance of the models based on the area under the ROC curve was 0.735, 0.733, and 0.680 for logistic regression, probit regression, and linear discriminant analysis, respectively. Conclusion: Given the relatively high prevalence of unwanted pregnancies in Khorramabad, it seems necessary to revise family planning programs. Despite the similar accuracy of the models, if the researcher is interested in the interpretability of the results, the use of the logistic regression model is recommended. PMID:26793655

Prediction of unwanted pregnancies using logistic regression, probit regression and discriminant analysis.

PubMed

Ebrahimzadeh, Farzad; Hajizadeh, Ebrahim; Vahabi, Nasim; Almasian, Mohammad; Bakhteyar, Katayoon

2015-01-01

Unwanted pregnancy not intended by at least one of the parents has undesirable consequences for the family and the society. In the present study, three classification models were used and compared to predict unwanted pregnancies in an urban population. In this cross-sectional study, 887 pregnant mothers referring to health centers in Khorramabad, Iran, in 2012 were selected by the stratified and cluster sampling; relevant variables were measured and for prediction of unwanted pregnancy, logistic regression, discriminant analysis, and probit regression models and SPSS software version 21 were used. To compare these models, indicators such as sensitivity, specificity, the area under the ROC curve, and the percentage of correct predictions were used. The prevalence of unwanted pregnancies was 25.3%. The logistic and probit regression models indicated that parity and pregnancy spacing, contraceptive methods, household income and number of living male children were related to unwanted pregnancy. The performance of the models based on the area under the ROC curve was 0.735, 0.733, and 0.680 for logistic regression, probit regression, and linear discriminant analysis, respectively. Given the relatively high prevalence of unwanted pregnancies in Khorramabad, it seems necessary to revise family planning programs. Despite the similar accuracy of the models, if the researcher is interested in the interpretability of the results, the use of the logistic regression model is recommended.

Delivery of Hydrogen Sulfide by Ultrasound Targeted Microbubble Destruction Attenuates Myocardial Ischemia-reperfusion Injury

PubMed Central

Chen, Gangbin; Yang, Li; Zhong, Lintao; Kutty, Shelby; Wang, Yuegang; Cui, Kai; Xiu, Jiancheng; Cao, Shiping; Huang, Qiaobing; Liao, Wangjun; Liao, Yulin; Wu, Juefei; Zhang, Wenzhu; Bin, Jianping

2016-01-01

Hydrogen sulfide (H2S) is an attractive agent for myocardial ischemia-reperfusion injury, however, systemic delivery of H2S may cause unwanted side effects. Ultrasound targeted microbubble destruction has become a promising tool for organ specific delivery of bioactive substance. We hypothesized that delivery of H2S by ultrasound targeted microbubble destruction attenuates myocardial ischemia-reperfusion injury and could avoid unwanted side effects. We prepared microbubbles carrying hydrogen sulfide (hs-MB) with different H2S/C3F8 ratios (4/0, 3/1, 2/2, 1/3, 0/4) and determined the optimal ratio. Release of H2S triggered by ultrasound was investigated. The cardioprotective effect of ultrasound targeted hs-MB destruction was investigated in a rodent model of myocardial ischemia-reperfusion injury. The H2S/C3F8 ratio of 2/2 was found to be an optimal ratio to prepare stable hs-MB with higher H2S loading capability. Ultrasound targeted hs-MB destruction triggered H2S release and increased the concentration of H2S in the myocardium and lung. Ultrasound targeted hs-MB destruction limited myocardial infarct size, preserved left ventricular function and had no influence on haemodynamics and respiratory. This cardioprotective effect was associated with alleviation of apoptosis and oxidative stress. Delivery of H2S to the myocardium by ultrasound targeted hs-MB destruction attenuates myocardial ischemia-reperfusion injury and may avoid unwanted side effects. PMID:27469291

Sexual abstinence: What is the understanding and views of secondary school learners in a semi-rural area of North West Province, South Africa?

PubMed Central

Mokwena, Kebogile; Morabe, Mamaponesa

2016-01-01

Abstract Among strategies to prevent HIV, other sexually transmitted infections (STIs) and unwanted pregnancies, are programs that promote sexual abstinence among adolescents. However, literature suggests that there may be differences in the understanding of abstinence across adolescents, and this study sought to explore the understanding of sexual abstinence among both male and female learners in a secondary school in a semi-rural area of North West Province, South Africa. Focus group discussions were used to collect data from learners who were in grades 8–10 at the time of the study. The findings are that the learners in this area understand sexual abstinence as the decision not to have sex, and this was associated with prevention of HIV, STIs and unwanted pregnancies, which ensures a better future. Barriers to sexual abstinence include peer pressure, myths and wrong perceptions about sex, influence of drugs and alcohol and the influence of television. Based on how it is delivered, school-based sex education was viewed as both an enabler and barrier to sexual abstinence. It is recommended that programs to promote sexual abstinence be strengthened and such programs be community-based. PMID:27315574

Sexual abstinence: What is the understanding and views of secondary school learners in a semi-rural area of North West Province, South Africa?

PubMed

Mokwena, Kebogile; Morabe, Mamaponesa

2016-12-01

Among strategies to prevent HIV, other sexually transmitted infections (STIs) and unwanted pregnancies, are programs that promote sexual abstinence among adolescents. However, literature suggests that there may be differences in the understanding of abstinence across adolescents, and this study sought to explore the understanding of sexual abstinence among both male and female learners in a secondary school in a semi-rural area of North West Province, South Africa. Focus group discussions were used to collect data from learners who were in grades 8-10 at the time of the study. The findings are that the learners in this area understand sexual abstinence as the decision not to have sex, and this was associated with prevention of HIV, STIs and unwanted pregnancies, which ensures a better future. Barriers to sexual abstinence include peer pressure, myths and wrong perceptions about sex, influence of drugs and alcohol and the influence of television. Based on how it is delivered, school-based sex education was viewed as both an enabler and barrier to sexual abstinence. It is recommended that programs to promote sexual abstinence be strengthened and such programs be community-based.

Effect of feeders in 3D modeling of low impedance multilayer CPW transmission line

NASA Astrophysics Data System (ADS)

Zaini, R. I.; Kyabaggu, P. B. K.; Sinulingga, E. P.

2018-02-01

Improved characteristics with low dissipation loss MMICs are highly desirable for wireless communications. However, the current industrial MMIC design is mainly based on microstrip concept which suffered from parasitic and unwanted phenomenon especially at higher frequency (>20 GHz). On the other hand, for future wireless technology, higher frequency operation is required and on-wafer microwave characterizations as well as precise modeling of 3D Multilayer CPW components are vital. This project concerns with understanding of the microwave characteristics behavior of Multilayer CPW components in MMIC applications. Feeder effect as unwanted parts in the characteristics has been investigated to determine its relation with the half wavelength resonance of the Multilayer CPW Low Impedance Transmission Line.

Cyber-Defense: A Taxonomy of Tactics for Managing Cyberstalking.

PubMed

Tokunaga, Robert S; Aune, Krystyna S

2015-06-16

Cyberstalking research has revealed information about who is perpetrating what offense to whom. This study adds to research on cyberstalking by exploring how victims respond to the unwanted pursuit. The reflections of cyberstalking victims were content analyzed to answer research questions about different risk management behaviors, their effectiveness, and their relationship with specific cyberstalking behaviors. Findings indicated that victims used seven general management tactics of which ignore/avoidance, active technological disassociation, and help seeking were the most common. Using technology to move away from pursuers was reported as the most effective tactic for managing the unwanted relational pursuit. The results also suggested that victims' management responses were associated with the type of behaviors experienced. © The Author(s) 2015.

40 CFR 262.206 - Labeling and management standards for containers of unwanted material in the laboratory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Labeling and management standards for containers of unwanted material in the laboratory. 262.206 Section 262.206 Protection of Environment... the laboratory to assure safe storage of the unwanted material, to prevent leaks, spills, emissions to...

Sex Differences in the Experience of Unwanted Sexual Attention and Behaviors during Childhood

ERIC Educational Resources Information Center

Whealin, Julia M.; Zinzow, Heidi M.; Salstrom, Seoka A.; Jackson, Joan L.

2007-01-01

Girls receive considerable amounts of unwanted sexual attention (UWSA) and behaviors (UWSB). Less is known about boys' unwanted sexual experiences. The primary goal of this study was to obtain a descriptive profile of the types and perpetrators of childhood UWSA/B. Secondary goals were to examine sex differences in emotional reactions to UWSA/B…

Xenobiotic-metabolizing enzymes in plants and their role in uptake and biotransformation of veterinary drugs in the environment.

PubMed

Bártíková, Hana; Skálová, Lenka; Stuchlíková, Lucie; Vokřál, Ivan; Vaněk, Tomáš; Podlipná, Radka

2015-08-01

Many various xenobiotics permanently enter plants and represent potential danger for their organism. For that reason, plants have evolved extremely sophisticated detoxification systems including a battery of xenobiotic-metabolizing enzymes. Some of them are similar to those in humans and animals, but there are several plant-specific ones. This review briefly introduces xenobiotic-metabolizing enzymes in plants and summarizes present information about their action toward veterinary drugs. Veterinary drugs are used worldwide to treat diseases and protect animal health. However, veterinary drugs are also unwantedly introduced into environment mostly via animal excrements, they persist in the environment for a long time and may impact on the non-target organisms. Plants are able to uptake, transform the veterinary drugs to non- or less-toxic compounds and store them in the vacuoles and cell walls. This ability may protect not only plant themselves but also other organisms, predominantly invertebrates and wild herbivores. The aim of this review is to emphasize the importance of plants in detoxification of veterinary drugs in the environment. The results of studies, which dealt with transport and biotransformation of veterinary drugs in plants, are summarized and evaluated. In conclusion, the risks and consequences of veterinary drugs in the environment and the possibilities of phytoremediation technologies are considered and future perspectives are outlined.

Removing inter-subject technical variability in magnetic resonance imaging studies.

PubMed

Fortin, Jean-Philippe; Sweeney, Elizabeth M; Muschelli, John; Crainiceanu, Ciprian M; Shinohara, Russell T

2016-05-15

Magnetic resonance imaging (MRI) intensities are acquired in arbitrary units, making scans non-comparable across sites and between subjects. Intensity normalization is a first step for the improvement of comparability of the images across subjects. However, we show that unwanted inter-scan variability associated with imaging site, scanner effect, and other technical artifacts is still present after standard intensity normalization in large multi-site neuroimaging studies. We propose RAVEL (Removal of Artificial Voxel Effect by Linear regression), a tool to remove residual technical variability after intensity normalization. As proposed by SVA and RUV [Leek and Storey, 2007, 2008, Gagnon-Bartsch and Speed, 2012], two batch effect correction tools largely used in genomics, we decompose the voxel intensities of images registered to a template into a biological component and an unwanted variation component. The unwanted variation component is estimated from a control region obtained from the cerebrospinal fluid (CSF), where intensities are known to be unassociated with disease status and other clinical covariates. We perform a singular value decomposition (SVD) of the control voxels to estimate factors of unwanted variation. We then estimate the unwanted factors using linear regression for every voxel of the brain and take the residuals as the RAVEL-corrected intensities. We assess the performance of RAVEL using T1-weighted (T1-w) images from more than 900 subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI), as well as healthy controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We compare RAVEL to two intensity-normalization-only methods: histogram matching and White Stripe. We show that RAVEL performs best at improving the replicability of the brain regions that are empirically found to be most associated with AD, and that these regions are significantly more present in structures impacted by AD (hippocampus, amygdala, parahippocampal gyrus, enthorinal area, and fornix stria terminals). In addition, we show that the RAVEL-corrected intensities have the best performance in distinguishing between MCI subjects and healthy subjects using the mean hippocampal intensity (AUC=67%), a marked improvement compared to results from intensity normalization alone (AUC=63% and 59% for histogram matching and White Stripe, respectively). RAVEL is promising for many other imaging modalities. Published by Elsevier Inc.

Planning to break unwanted habits: habit strength moderates implementation intention effects on behaviour change.

PubMed

Webb, Thomas L; Sheeran, Paschal; Luszczynska, Aleksandra

2009-09-01

Implementation intention formation promotes effective goal striving and goal attainment. However, little research has investigated whether implementation intentions promote behaviour change when people possess strong antagonistic habits. Experiment 1 developed relatively habitual responses that, after a task switch, had a detrimental impact on task performance. Forming an if-then plan reduced the negative impact of habit on performance. However, the effect of forming implementation intentions was smaller among participants who possessed strong habits as compared to participants who had weaker habits. Experiment 2 provided a field test of the role of habit strength in moderating the relationship between implementation intentions and behaviour in the context of smoking. Implementation intentions reduced smoking among participants with weak or moderate smoking habits, but not among participants with strong smoking habits. In summary, habit strength moderates the effectiveness of if-then plan formation in breaking unwanted habits.

GLPG0492, a novel selective androgen receptor modulator, improves muscle performance in the exercised-mdx mouse model of muscular dystrophy.

PubMed

Cozzoli, Anna; Capogrosso, Roberta Francesca; Sblendorio, Valeriana Teresa; Dinardo, Maria Maddalena; Jagerschmidt, Catherine; Namour, Florence; Camerino, Giulia Maria; De Luca, Annamaria

2013-06-01

Anabolic drugs may counteract muscle wasting and dysfunction in Duchenne muscular dystrophy (DMD); however, steroids have unwanted side effects. We focused on GLPG0492, a new non-steroidal selective androgen receptor modulator that is currently under development for musculo-skeletal diseases such as sarcopenia and cachexia. GLPG0492 was tested in the exercised mdx mouse model of DMD in a 4-week trial at a single high dose (30 mg/kg, 6 day/week s.c.), and the results were compared with those from the administration of α-methylprednisolone (PDN; 1 mg/kg, i.p.) and nandrolone (NAND, 5 mg/kg, s.c.). This assessment was followed by a 12-week dose-dependence study (0.3-30 mg/kg s.c.). The outcomes were evaluated in vivo and ex vivo on functional, histological and biochemical parameters. Similar to PDN and NAND, GLPG0492 significantly increased mouse strength. In acute exhaustion tests, a surrogate of the 6-min walking test used in DMD patients, GLPG0492 preserved running performance, whereas vehicle- or comparator-treated animals showed a significant increase in fatigue (30-50%). Ex vivo, all drugs resulted in a modest but significant increase of diaphragm force. In parallel, a decrease in the non-muscle area and markers of fibrosis was observed in GLPG0492- and NAND-treated mice. The drugs exerted minor effects on limb muscles; however, electrophysiological biomarkers were ameliorated in extensor digitorum longus muscle. The longer dose-dependence study confirmed the effect on mdx mouse strength and resistance to fatigue and demonstrated the efficacy of lower drug doses on in vivo and ex vivo functional parameters. These results support the interest of further studies of GLPG0492 as a potential treatment for DMD. Copyright © 2013 Elsevier Ltd. All rights reserved.

Preventing unsafe abortion and limiting its consequences: what can be done?

PubMed

Misago, C

1994-12-01

The continued illegality of induced abortion in Latin America has led to substantial, preventable maternal mortality and morbidity. The first strategy for preventing unsafe clandestine abortion is to reduce the incidence of unwanted pregnancy through measures such as improved access to effective contraception, post-abortion family planning counseling, health education campaigns aimed at promoting condom use among young people, involvement of men in family planning decision making, biomedical research on safer and more effective male and female contraceptive methods, and empowering women to demand the use of condoms or avoid unwanted intercourse. The second strategy is to reduce abortion-related mortality and morbidity through more effective clinical management of incomplete illegal abortions, introduction of menstrual regulation services, formation of women's solidarity groups aimed at discouraging the practice of self-induced abortion, and, ultimately, abortion legalization.

Current treatments in diabetic macular oedema: systematic review and meta-analysis

PubMed Central

Ford, John Alexander; Lois, Noemi; Royle, Pamela; Clar, Christine; Shyangdan, Deepson; Waugh, Norman

2013-01-01

Objectives The aim of this systematic review is to appraise the evidence for the use of anti-VEGF drugs and steroids in diabetic macular oedema (DMO) as assessed by change in best corrected visual acuity (BCVA), central macular thickness and adverse events Data source MEDLINE, EMBASE, Web of Science with Conference Proceedings and the Cochrane Library (inception to July 2012). Certain conference abstracts and drug regulatory web sites were also searched. Study eligibility criteria, participants and interventions Randomised controlled trials were used to assess clinical effectiveness and observational trials were used for safety. Trials which assessed triamcinolone, dexamethasone, fluocinolone, bevacizumab, ranibizumab, pegaptanib or aflibercept in patients with DMO were included. Study appraisal and synthesis methods Risk of bias was assessed using the Cochrane risk of bias tool. Study results are narratively described and, where appropriate, data were pooled using random effects meta-analysis. Results Anti-VEGF drugs are effective compared to both laser and placebo and seem to be more effective than steroids in improving BCVA. They have been shown to be safe in the short term but require frequent injections. Studies assessing steroids (triamcinolone, dexamethasone and fluocinolone) have reported mixed results when compared with laser or placebo. Steroids have been associated with increased incidence of cataracts and intraocular pressure rise but require fewer injections, especially when steroid implants are used. Limitations The quality of included studies varied considerably. Five of 14 meta-analyses had moderate or high statistical heterogeneity. Conclusions and implications of key findings The anti-VEGFs ranibizumab and bevacizumab have consistently shown good clinical effectiveness without major unwanted side effects. Steroid results have been mixed and are usually associated with cataract formation and  intraocular pressure increase. Despite the current wider spectrum of treatments for DMO, only a small proportion of patients recover good vision (≥20/40), and thus the search for new therapies needs to continue. PMID:23457327

Cytotoxicity of lapachol metabolites produced by probiotics.

PubMed

Oliveira Silva, E; Cruz de Carvalho, T; Parshikov, I A; Alves dos Santos, R; Silva Emery, F; Jacometti Cardoso Furtado, N A

2014-07-01

Probiotics are currently added to a variety of functional foods to provide health benefits to the host and are commonly used by patients with gastrointestinal complaints or diseases. The therapeutic effects of lapachol continue to inspire studies to obtain derivatives with improved bioactivity and lower unwanted effects. Therefore, the general goal of this study was to show that probiotics are able to convert lapachol and are important to assess the effects of bacterial metabolism on drug performance and toxicity. The microbial transformations of lapachol were carried out by Bifidobacterium sp. and Lactobacillus acidophilus and different metabolites were produced in mixed and isolated cultures. The cytotoxic activities against breast cancer and normal fibroblast cell lines of the isolated metabolites (4α-hydroxy-2,2-dimethyl-5-oxo-2,3,4,4α,5,9β-hexahydroindeno[1,2-β]pyran-9β-carboxilic acid, a new metabolite produced by mixed culture and dehydro-α-lapachone produced by isolated cultures) were assessed and compared with those of lapachol. The new metabolite displayed a lower activity against a breast cancer cell line (IC50 = 532.7 μmol l(-1) ) than lapachol (IC50 = 72.3 μmol l(-1) ), while dehydro-α-lapachone (IC50 = 10.4 μmol l(-1) ) displayed a higher activity than lapachol. The present study is the first to demonstrate that probiotics are capable of converting lapachol into the most effective cytotoxic compound against a breast cancer cell line. Probiotics have been used in dairy products to promote human health and have the ability to metabolize drugs and other xenobiotics. Naphthoquinones, such as lapachol, are considered privileged scaffolds due to their high propensity to interact with biological targets. The present study is the first to demonstrate that probiotics are capable of converting lapachol into the most effective cytotoxic compound against a breast cancer cell line. The developed approach highlights the importance of probiotics to assess the effects of bacterial metabolism on drug performance and toxicity. © 2014 The Society for Applied Microbiology.

Wanted and unwanted fertility in Bolivia: does ethnicity matter?

PubMed

McNamee, Catherine B

2009-12-01

In Bolivia, the total fertility rate (TFR) among indigenous populations is higher than that among the nonindigenous population. It is important to investigate whether this difference is attributable to ethnic differences in wanted or unwanted fertility. Data from the 2003 Bolivian Demographic and Health Survey were used to estimate women's wanted and unwanted TFRs. Logistic regression analyses were conducted to examine whether women's, men's and couples' characteristics were associated with use of any contraceptive method and modern methods. The TFRs for indigenous and nonindigenous women were 1.5 and 1.7, [corrected] respectively. The wanted fertility rate for indigenous women was nearly the same as that for nonindigenous women (2.8 and 1.4, [corrected] respectively); virtually all of the ethnic difference in the TFRs was attributable to the ethnic difference in unwanted fertility. The proportion of women in need of contraception was greater among indigenous women than among nonindigenous women (26% vs. 19%). In logistic regression analyses, male fertility preferences explained only a small part of the ethnic difference in contraceptive use. Women's, men's and couples' preferences contribute only marginally to unwanted fertility, suggesting that structural factors act as obstacles to preventing unwanted fertility.

Unwanted sexual experiences and cognitive appraisals that evoke mental contamination.

PubMed

Ishikawa, Ryotaro; Kobori, Osamu; Shimizu, Eiji

2015-01-01

Mental contamination is a psychological sense of contamination that involves an internal, emotional feeling of dirtiness that may be evoked by unwanted thoughts and images, such as sexual assaults. This study aimed to investigate which types of unwanted sexual experiences evoke the strongest mental contamination, and to test the hypothesis that cognitive appraisals of an unwanted sexual experience predict indices of mental contamination (i.e. feeling of dirtiness, urge to wash, internal negative emotions, and external negative emotions). 148 female participants were asked to recall their most distressing unwanted sexual experiences. Indices of mental contamination and cognitive appraisals of the experience were then assessed. Our findings indicated that individuals recalling experiences related to rape felt more intense feelings of dirtiness than individuals recalling other types of unwanted sexual experience, such as verbal sexual assault, visual sexual assault, and forcible touching/frottage. In addition, hierarchical regression analyses demonstrated that a cognitive appraisal of perceived violation predicted all of the indices of mental contamination after controlling anxiety, depression, and fear of contact contamination. The present study demonstrated that an individual is at greatest risk of mental contamination if she has experienced rape/attempted rape, and if she makes a cognitive appraisal of violation regarding the incident.

An overview of unwanted female hair.

PubMed

Blume-Peytavi, U

2011-12-01

Unwanted facial hair (UFH) is an important but often overlooked issue, with over 40% of women experiencing some degree of UFH. In the female population a wide spectrum of unwanted hair concerns is represented - from biologically normal but undesirable to excessive unwanted hair with an underlying pathology. While women may seek to manage unwanted hair across their bodies, UFH is a particular concern, due to its negative impact on perceived femininity. There may not always be a direct correlation between degree of severity diagnosed objectively by the physician and level of concern and impact upon the patient. This review discusses the spectrum of facial hair experience and outlines the clinical approach to unwanted hair management including UFH. It highlights the importance of a treatment regimen which should respond to the causation factors and needs of the individual. This will lead to a holistic treatment approach including evaluation of the implementation of emotional coping strategies and on-going support, lifestyle modifications, pharmacological interventions (to address underlying pathologies) and the use of cosmetic hair removal methods as either a stand-alone or adjunct treatment as appropriate to the individual. © 2011 The Author. BJD © 2011 British Association of Dermatologists.

The Sensitivity of Measures of Unwanted and Unintended Pregnancy Using Retrospective and Prospective Reporting: Evidence from Malawi

PubMed Central

Sennott, Christie

2015-01-01

A thorough understanding of the health implications of unwanted and unintended pregnancies is constrained by our ability to accurately identify them. Commonly used techniques for measuring such pregnancies are subject to two main sources of error: the ex post revision of preferences after a pregnancy and the difficulty of identifying preferences at the time of conception. This study examines the implications of retrospective and prospective measurement approaches, which are vulnerable to different sources of error, on estimates of unwanted and unintended pregnancies. We use eight waves of closely-spaced panel data from young women in southern Malawi to generate estimates of unwanted and unintended pregnancies based on fertility preferences measured at various points in time. We then compare estimates using traditional retrospective and prospective approaches to estimates obtained when fertility preferences are measured prospectively within months of conception. The 1,062 young Malawian women in the sample frequently changed their fertility preferences. The retrospective measures slightly underestimated unwanted and unintended pregnancies compared to the time-varying prospective approach; in contrast the fixed prospective measures overestimated them. Nonetheless, most estimates were similar in aggregate, suggesting that frequent changes in fertility preferences need not lead to dramatically different estimates of unwanted and unintended pregnancy. Greater disagreement among measures emerged when classifying individual pregnancies. Carefully designed retrospective measures are not necessarily more problematic for measuring unintended and unwanted fertility than are more expensive fixed prospective ones. PMID:25636647

Identification and evaluation of drug-supplement interactions in Hungarian hospital patients.

PubMed

Végh, Anna; Lankó, Erzsébet; Fittler, András; Vida, Róbert György; Miseta, Ildikó; Takács, Gábor; Botz, Lajos

2014-04-01

The increasing number of patients taking supplementary products together with prescribed medicines has become a new challenge for health care systems. These products may influence therapy outcomes by inducing unwanted effects. Particularly concerning is the potential for harmful interactions between prescribed medicines and supplementary products. The aims of the study were to evaluate supplement use, to identify and analyse potential interactions, and to assess the efficiency of computerised interaction screening. Participants of the study were inpatients and outpatients of a Hungarian university hospital. A cross-sectional point-of-care survey of 200 patients was carried out. Data was collected through personal interviews and a review of the medical records. Drug-drug, drug-supplement and supplement-supplement interactions were analysed with three interaction databases (Lexi-Interact Online, Medscape Drug Interaction Checker and Mediris). Prevalence of supplementary product use, number of medicines and supplementary products per patient, procurement sources of products, number of potentially severe interactions. There was a marked difference between data obtained from patient interviews and the medical records. 85.5 % of the surveyed patients took supplementary products during the 2 weeks prior to the interview. The average number of prescribed medicines and supplementary products were 7.8 and 2.5, respectively. Women were more likely to take supplements than men. There was no significant difference in supplement use between patients under or over 60 years, between inpatients and outpatients and among patients in various wards. 39.4 % of supplementary products were purchased outside a regulated pharmacy environment. Potentially severe drug-supplement interactions were detected with 45.2 % of supplement users; however the majority of interactions were not included in one or the other of the three databases. In addition to that the risk ratings of the same interactions varied greatly between databases. A significant number of patients are exposed to potential drug interactions with supplementary products; however interagreement among interaction databases is poor. Our data suggest that a full medication history should specifically address the intake of supplements.

Purification of metal-organic framework materials

DOEpatents

Farha, Omar K.; Hupp, Joseph T.

2012-12-04

A method of purification of a solid mixture of a metal-organic framework (MOF) material and an unwanted second material by disposing the solid mixture in a liquid separation medium having a density that lies between those of the wanted MOF material and the unwanted material, whereby the solid mixture separates by density differences into a fraction of wanted MOF material and another fraction of unwanted material.

Purification of metal-organic framework materials

DOEpatents

Farha, Omar K.; Hupp, Joseph T.

2015-06-30

A method of purification of a solid mixture of a metal-organic framework (MOF) material and an unwanted second material by disposing the solid mixture in a liquid separation medium having a density that lies between those of the wanted MOF material and the unwanted material, whereby the solid mixture separates by density differences into a fraction of wanted MOF material and another fraction of unwanted material.

Sex and drugs in popular movies: an analysis of the top 200 films

PubMed Central

Gunasekera, Hasantha; Chapman, Simon; Campbell, Sharon

2005-01-01

We analyse the portrayal of sex and drug use in the most popular movies of the last 20 years using the Internet Movie Database list of the top 200 movies of all time. Films released or set prior to the HIV era (pre 1983), animated, not about humans or G/PG rated, were excluded. Films were reviewed by one of two teams of two observers using a data extraction sheet tested for inter-rater reliability. Sexual activity, sexually transmitted disease (STD) prevention, birth control measures, drug use and any consequences discussed or depicted were recorded. There were 53 sex episodes in 28 (32%) of the 87 movies reviewed. There was only one suggestion of condom use, which was the only reference to any form of birth control. There were no depictions of important consequences of unprotected sex such as unwanted pregnancies, HIV or other STDs. Movies with cannabis (8%) and other non-injected illicit drugs (7%) were less common than those with alcohol intoxication (32%) and tobacco use (68%) but tended to portray their use positively and without negative consequences. There were no episodes of injected drug use. Sex depictions in popular movies of the last two decades lacked safe sex messages. Drug use, though infrequent, tended to be depicted positively. The social norm being presented is concerning given the HIV and illicit drug pandemics. PMID:16199815

Risk factors for unplanned and unwanted teenage pregnancies occurring over two years of follow-up among a cohort of young South African women.

PubMed

Christofides, Nicola J; Jewkes, Rachel K; Dunkle, Kristin L; McCarty, Frances; Jama Shai, Nwabisa; Nduna, Mzikazi; Sterk, Claire

2014-01-01

Although teenage pregnancies in South Africa have declined, the short and longer term health and social consequences are a potential public health concern. This longitudinal study aimed to describe the range of risk and protective factors for incident unwanted and unplanned pregnancies occurring over 2 years of follow-up among a cohort of adolescent women in the Eastern Cape, South Africa. It also investigated the relationship between gender inequality and gender-based violence and subsequent unplanned and unwanted pregnancies among the cohort. Teenage girls, aged 15-18 years (n=19), who were volunteer participants in a cluster randomized controlled trial and who had data from at least one follow-up were included in this analysis. To assess risk and protective factors for incident unwanted or unplanned pregnancies, we constructed multivariate polytomous regression models adjusting for sampling clusters as latent variables. Covariates included age, having a pregnancy prior to baseline, education, time between interviews, study intervention arm, contraceptive use, experience of intimate partner violence, belief that the teenage girl and her boyfriend are mutual main partners, and socioeconomic status. Overall, 174 pregnancies occurred over the 2-year follow-up period. Beliefs about relationship control were not associated with unwanted and unplanned pregnancies, nor were experiences of forced first sex or coerced sex under the age of 15. Hormonal contraception was protective against unplanned pregnancies (OR 0.40; 95% CI 0.21-0.79); however, using condoms was not protective. Physical abuse (OR 1.69; 95% CI 1.05-2.72) was a risk factor for, and having a pregnancy prior to baseline was protective against an unwanted pregnancy (OR 0.25; 95% CI 0.07-0.80). Higher socioeconomic status was protective for both unplanned and unwanted pregnancies (OR 0.69; 95% CI 0.58-0.83 and OR 0.78; 95% CI 0.64-0.96). Believing that the teenage girl and her boyfriend were mutual main partners doubled the odds of reporting both an unplanned and unwanted pregnancy (OR 2.58 95% CI 1.07-6.25, and OR 2.21 95% CI 1.13-4.29). Although some of the measures of gender inequity were not associated with unplanned and unwanted pregnancies, there is evidence of the role of both gender power and socioeconomic status. This was evident in teenage girls who experienced physical violence being more likely to have an unwanted pregnancy. Interventions to prevent teenage pregnancies need to be tailored by socioeconomic status because some teenagers may see having a pregnancy as a way to have a more secure future. Interventions that engage with relationship dynamics of teenagers are essential if unwanted and unplanned pregnancies are to be prevented.

Reproductive consequences of unwanted sexual debut among young adult women from Metro Cebu, Philippines.

PubMed

Wiles, Melissa; Agustin, Sonny; Narasimhan, Subasri; Gipson, Jessica D

2018-04-18

The circumstances surrounding sexual debut influence subsequent sexual and reproductive outcomes. We analysed longitudinal data from 397 women who participated in the Cebu Longitudinal Health and Nutrition Survey in Cebu, Philippines to examine associations between unwanted first sex and number of pregnancies, unintended pregnancy, and use of modern contraception. 72% of women reported unwanted first sex. Women whose first sex was unwanted had increased odds of unintended pregnancy compared to women whose first sex was wanted (aOR = 2.2, 95% CI 1.3, 3.6). Nationally-representative surveys should include culturally-relevant questions about sexual debut to inform public health programmes aimed at improving sexual/reproductive health.

Childhood maltreatment history as a risk factor for sexual harassment among U.S. Army soldiers.

PubMed

Rosen, L N; Martin, L

1998-01-01

Four different types of childhood maltreatment were examined as predictors of unwanted sexual experiences and acknowledged sexual harassment among male and female active duty soldiers in the United States Army. Predictor variables included childhood sexual abuse, physical-emotional abuse, physical neglect, and emotional neglect. Three types of unwanted sexual experiences in the workplace were examined as outcome variables: gender harassment, unwanted sexual attention, and coercion. Both sexual and physical-emotional abuse during childhood were found to be predictors of unwanted sexual experiences and of acknowledged sexual harassment in the workplace. Among female soldiers, the most severe type of unwanted experience-coercion-was predicted only by childhood physical-emotional abuse. Among male soldiers childhood sexual abuse was the strongest predictor of coercion. A greater variety of types of childhood maltreatment predicted sexual harassment outcomes for male soldiers. Childhood maltreatment and adult sexual harassment were predictors of psychological well-being for soldiers of both genders.

Should multifetal pregnancy reduction be used for prevention of preterm deliveries in triplet or higher order multiple pregnancies?

PubMed

Papiernik, E; Grangé, G; Zeitlin, J

1998-01-01

This article reviews the arguments for the use of multifetal pregnancy reduction (MFPR) for the prevention of preterm deliveries in triplet and higher order multiple pregnancies and evaluates its effectiveness based on data from published studies. The arguments in favour of pregnancy reduction are based on the substantial mortality and morbidity associated with these pregnancies. Triplets and higher order multiples have increased rates of preterm delivery and intrauterine growth retardation, both of which are independent risk factors for death and handicap. Even controlling for gestational age, rates of mortality and handicap are higher for multiples than for singletons. Moreover, the family's risk of losing a child or having a handicapped child is greater because there are more infants at risk. MFPR effectively lowers these risk by reducing the frequency of preterm delivery. However, its effectiveness may be limited. In some studies, the proportion of preterm deliveries in reduced pregnancies remains above levels found in spontaneous twin or singleton pregnancies and MFPR does not appear to reduce the prevalence of low birth weight. Furthermore, the procedure itself has unwanted side effects: it increases the risk of miscarriage, premature rupture of the membranes and causes adverse psychological effects such as grief or depression for many patients. The authors note that a majority of the higher order multiple pregnancies result from a medical intervention in the first place, either through IVF techniques or the use of ovulation stimulation drugs. Although MFPR is an effective measure for reducing the substantial morbidity and mortality associated with higher order multiple pregnancies, preventive methods, such as limiting to 2 the number of embryos transferred for IVF and better control of the use of ovulation induction drugs, remain more effective and less intrusive.

Negative Effects of Psychological Treatments: An Exploratory Factor Analysis of the Negative Effects Questionnaire for Monitoring and Reporting Adverse and Unwanted Events

PubMed Central

Kottorp, Anders; Boettcher, Johanna; Andersson, Gerhard; Carlbring, Per

2016-01-01

Research conducted during the last decades has provided increasing evidence for the use of psychological treatments for a number of psychiatric disorders and somatic complaints. However, by focusing only on the positive outcomes, less attention has been given to the potential of negative effects. Despite indications of deterioration and other adverse and unwanted events during treatment, little is known about their occurrence and characteristics. Hence, in order to facilitate research of negative effects, a new instrument for monitoring and reporting their incidence and impact was developed using a consensus among researchers, self-reports by patients, and a literature review: the Negative Effects Questionnaire. Participants were recruited via a smartphone-delivered self-help treatment for social anxiety disorder and through the media (N = 653). An exploratory factor analysis was performed, resulting in a six-factor solution with 32 items, accounting for 57.64% of the variance. The derived factors were: symptoms, quality, dependency, stigma, hopelessness, and failure. Items related to unpleasant memories, stress, and anxiety were experienced by more than one-third of the participants. Further, increased or novel symptoms, as well as lack of quality in the treatment and therapeutic relationship rendered the highest self-reported negative impact. In addition, the findings were discussed in relation to prior research and other similar instruments of adverse and unwanted events, giving credence to the items that are included. The instrument is presently available in eleven different languages and can be freely downloaded and used from www.neqscale.com. PMID:27331907

Negative Effects of Psychological Treatments: An Exploratory Factor Analysis of the Negative Effects Questionnaire for Monitoring and Reporting Adverse and Unwanted Events.

PubMed

Rozental, Alexander; Kottorp, Anders; Boettcher, Johanna; Andersson, Gerhard; Carlbring, Per

2016-01-01

Research conducted during the last decades has provided increasing evidence for the use of psychological treatments for a number of psychiatric disorders and somatic complaints. However, by focusing only on the positive outcomes, less attention has been given to the potential of negative effects. Despite indications of deterioration and other adverse and unwanted events during treatment, little is known about their occurrence and characteristics. Hence, in order to facilitate research of negative effects, a new instrument for monitoring and reporting their incidence and impact was developed using a consensus among researchers, self-reports by patients, and a literature review: the Negative Effects Questionnaire. Participants were recruited via a smartphone-delivered self-help treatment for social anxiety disorder and through the media (N = 653). An exploratory factor analysis was performed, resulting in a six-factor solution with 32 items, accounting for 57.64% of the variance. The derived factors were: symptoms, quality, dependency, stigma, hopelessness, and failure. Items related to unpleasant memories, stress, and anxiety were experienced by more than one-third of the participants. Further, increased or novel symptoms, as well as lack of quality in the treatment and therapeutic relationship rendered the highest self-reported negative impact. In addition, the findings were discussed in relation to prior research and other similar instruments of adverse and unwanted events, giving credence to the items that are included. The instrument is presently available in eleven different languages and can be freely downloaded and used from www.neqscale.com.

Sexual Attitudes and Contraceptive Practices.

ERIC Educational Resources Information Center

Byrne, Donn

1978-01-01

Discusses barriers to effective contraception, such as informational, emotional, and imaginative factors, and what might be done to avoid unwanted pregnancies by using these factors in positive programs and behaviors. (Author/RK)

Parameters affecting mechanical and thermal responses in bone drilling: A review.

PubMed

Lee, JuEun; Chavez, Craig L; Park, Joorok

2018-04-11

Surgical bone drilling is performed variously to correct bone fractures, install prosthetics, or for therapeutic treatment. The primary concern in bone drilling is to extract donor bone sections and create receiving holes without damaging the bone tissue either mechanically or thermally. We review current results from experimental and theoretical studies to investigate the parameters related to such effects. This leads to a comprehensive understanding of the mechanical and thermal aspects of bone drilling to reduce their unwanted complications. This review examines the important bone-drilling parameters of bone structure, drill-bit geometry, operating conditions, and material evacuation, and considers the current techniques used in bone drilling. We then analyze the associated mechanical and thermal effects and their contributions to bone-drilling performance. In this review, we identify a favorable range for each parameter to reduce unwanted complications due to mechanical or thermal effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Unwanted childbearing and household food insecurity in the United States

PubMed Central

Patel, SA; Surkan, PJ

2015-01-01

Household food insecurity is a population health concern disproportionately affecting families with children in the United States. Unwanted childbearing may place unanticipated strain on families to meet basic needs, heightening the risk for household food insecurity. We investigated the association between mother’s and father’s report of unwanted childbearing and exposure to household food insecurity among children residing in two-parent households in the United States. Data from the Early Childhood Longitudinal Study - Birth Cohort, a nationally representative cohort of US children (n~6,150) were used to estimate the odds of household food insecurity when children were aged 9 months and 2 years, separately, based on parental report of unwanted childbearing. The majority of children were reported as wanted by both parents (74.4%). Of the sample, report of unwanted childbearing by father-only was 20.0%, mother-only was 3.4%, and joint mother and father was 2.2%. Household food insecurity was higher when children were 9 months compared to 2 years. In adjusted models accounting for confounders, children born to mothers and fathers who jointly reported unwanted childbearing were at higher odds of exposure to household food insecurity at 9 months (AOR=3.31; 95% CI: 1.97,5.57) and 2 years (AOR=2.52; 95% CI: 1.12,5.68). In two-parent households, we found children raised by parents reporting unwanted childbearing were more likely to be exposed to food insecurity and potentially related stressors. Further studies that prospectively measure wantedness before the child’s birth will aid in confirming the direction of this association. PMID:25138233

Predictors of mistimed, and unwanted pregnancies among women of childbearing age in Rufiji, Kilombero, and Ulanga districts of Tanzania.

PubMed

Exavery, Amon; Kanté, Almamy Malick; Njozi, Mustafa; Tani, Kassimu; Doctor, Henry V; Hingora, Ahmed; Phillips, James F

2014-08-08

While unintended pregnancies pose a serious threat to the health and well-being of families globally, characteristics of Tanzanian women who conceive unintentionally are rarely documented. This analysis identifies factors associated with unintended pregnancies-both mistimed and unwanted-in three rural districts of Tanzania. A cross-sectional survey of 2,183 random households was conducted in three Tanzanian districts of Rufiji, Kilombero, and Ulanga in 2011 to assess women's health behavior and service utilization patterns. These households produced 3,127 women age 15+ years from which 2,199 gravid women aged 15-49 were selected for the current analysis. Unintended pregnancies were identified as either mistimed (wanted later) or unwanted (not wanted at all). Correlates of mistimed, and unwanted pregnancies were identified through Chi-squared tests to assess associations and multinomial logistic regression for multivariate analysis. Mean age of the participants was 32.1 years. While 54.1% of the participants reported that their most recent pregnancy was intended, 32.5% indicated their most recent pregnancy as mistimed and 13.4% as unwanted. Multivariate analysis revealed that young age (<20 years), and single marital status were significant predictors of both mistimed and unwanted pregnancies. Lack of inter-partner communication about family planning increased the risk of mistimed pregnancy significantly, and multi-gravidity was shown to significantly increase the risk of unwanted pregnancy. About one half of women in Rufiji, Kilombero, and Ulanga districts of Tanzania conceive unintentionally. Women, especially the most vulnerable should be empowered to avoid pregnancy at their own will and discretion.

Sleep deprivation as an experimental model system for psychosis: Effects on smooth pursuit, prosaccades, and antisaccades.

PubMed

Meyhöfer, Inga; Kumari, Veena; Hill, Antje; Petrovsky, Nadine; Ettinger, Ulrich

2017-04-01

Current antipsychotic medications fail to satisfactorily reduce negative and cognitive symptoms and produce many unwanted side effects, necessitating the development of new compounds. Cross-species, experimental behavioural model systems can be valuable to inform the development of such drugs. The aim of the current study was to further test the hypothesis that controlled sleep deprivation is a safe and effective model system for psychosis when combined with oculomotor biomarkers of schizophrenia. Using a randomized counterbalanced within-subjects design, we investigated the effects of 1 night of total sleep deprivation in 32 healthy participants on smooth pursuit eye movements (SPEM), prosaccades (PS), antisaccades (AS), and self-ratings of psychosis-like states. Compared with a normal sleep control night, sleep deprivation was associated with reduced SPEM velocity gain, higher saccadic frequency at 0.2 Hz, elevated PS spatial error, and an increase in AS direction errors. Sleep deprivation also increased intra-individual variability of SPEM, PS, and AS measures. In addition, sleep deprivation induced psychosis-like experiences mimicking hallucinations, cognitive disorganization, and negative symptoms, which in turn had moderate associations with AS direction errors. Taken together, sleep deprivation resulted in psychosis-like impairments in SPEM and AS performance. However, diverging somewhat from the schizophrenia literature, sleep deprivation additionally disrupted PS control. Sleep deprivation thus represents a promising but possibly unspecific experimental model that may be helpful to further improve our understanding of the underlying mechanisms in the pathophysiology of psychosis and aid the development of antipsychotic and pro-cognitive drugs.

Use Of Green Porphyrinsto Treat Neovasculature In The Eyes

DOEpatents

Levy, Julia; Miller, Joan W.; Gradoudas, Evangelos S.; Hasan, Tayyaba; Schmidt-Erfurth, Ursula

1998-08-25

Photodynamic therapy of conditions of the eye characterized by unwanted neovasculature, such as age-related macular degeneration, is effective using green porphyrins as photoactive agents, preferably as liposomal compositions.

Pharmacological and Toxicological Profile of Harmane-β-Carboline Alkaloid: Friend or Foe.

PubMed

Khan, Haroon; Patel, Seema; Kamal, Mohammad A

2017-01-01

The plant secondary metabolites have an outstanding therapeutic potential and success over the years. In fact, it is the foundation of numerous clinically used drugs. Similarly, these is a general perception that these products are inherent safety. However, such products might have toxic/unwanted lethal effects therefore, along with biological relevance, toxicological evaluation is equally important for clinical applications. Therefore, harmane- β-carboline alkaloid was investigated for both therapeutic and toxicological potential. The literature related to the therapeutic/toxicological effects of the alkaloid was searched using various scientific data bases including Google, ScienceDirect, PubMed, SpringerLink, ASC. The peer reviewed articles were only selected. The harmane-β-carboline alkaloid has shown several pharmacological activities such as antianxiety, antidepressant, antiplatelet, antidiabetic, acetylcholinesterase and myeloperoxidase inhibition, antioxidant, antiparasitic, hypotensive, morphine withdrawal syndrome alleviation, and antinociceptive effects. On the other hand, it exhibited tremorogenic effect, for a symptom of Parkinson's disease. Adverse effect of the alkaloid on learning and memory have also been observed. All together, it is, concluded in this review that harmane elicited marked pharmacological effects but simultaneously, it possessed some serious side effects that could be the primary hurdle in the way of its clinical testing. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Preclinical to Human Translational Pharmacology of the Novel M1 Positive Allosteric Modulator MK-7622.

PubMed

Uslaner, Jason M; Kuduk, Scott D; Wittmann, Marion; Lange, Henry S; Fox, Steve V; Min, Chris; Pajkovic, Natasa; Harris, Dawn; Cilissen, Caroline; Mahon, Chantal; Mostoller, Kate; Warrington, Steve; Beshore, Douglas C

2018-06-01

The current standard of care for treating Alzheimer's disease is acetylcholinesterase inhibitors, which nonselectively increase cholinergic signaling by indirectly enhancing activity of nicotinic and muscarinic receptors. These drugs improve cognitive function in patients, but also produce unwanted side effects that limit their efficacy. In an effort to selectively improve cognition and avoid the cholinergic side effects associated with the standard of care, various efforts have been aimed at developing selective M 1 muscarinic receptor activators. In this work, we describe the preclinical and clinical pharmacodynamic effects of the M 1 muscarinic receptor-positive allosteric modulator, MK-7622. MK-7622 attenuated the cognitive-impairing effects of the muscarinic receptor antagonist scopolamine and altered quantitative electroencephalography (qEEG) in both rhesus macaque and human. For both scopolamine reversal and qEEG, the effective exposures were similar between species. However, across species the minimum effective exposures to attenuate the scopolamine impairment were lower than for qEEG. Additionally, there were differences in the spectral power changes produced by MK-7622 in rhesus versus human. In sum, these results are the first to demonstrate translation of preclinical cognition and target modulation to clinical effects in humans for a selective M 1 muscarinic receptor-positive allosteric modulator. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Emergency contraception amongst female college students--knowledge, attitude and practice.

PubMed

Nibabe, Wendwosen T; Mgutshini, Tennyson

2014-03-19

Unwanted teenage pregnancies have a notable detrimental impact on the learners' trajectory and have been associated with jeopardising the students' educational progress and future career prospects. These pregnancies are mostly unplanned and unintended and many are terminated, either legally or illegally. The aim of this study was to explore the contributory role played by the knowledge, attitude and practices of female college students with respect to the utilisation of emergency contraceptives. Three tertiary institutions in Dessie, Ethiopia. Quantitative self-administered questionnaires were used to collect descriptive data from 352 female college students. The study revealed that there was a high percentage (78.3%) of unwanted pregnancies amongst those engaging in sex. Significantly, nearly half (43.3%) of these unwanted pregnancies resulted in abortion. Only 10% of the students sampled admitted to ever having used emergency contraception. Even though more than half (69.9%) of the students knew about emergency contraception, only 27% of them felt confident that they understood when it was most effective. These and other observed findings confirm the need for improvement of female college students' knowledge and timely utilisation of emergency contraception.

Surgical abortion in second trimester: initial experiences in Nepal.

PubMed

Shrivastava, V; Bajracharya, L; Thapa, S

2010-01-01

In spite of legalising abortion and making safe abortion available at affordable price at accessible distance to almost everyone, unsafe abortion especially second trimester abortion is still a big health problem in Nepal. The objective of the study is to fi nd the demographic profile, reasons for seeking abortion and to see the effectiveness of Misoprostol in preparing the cervix. A prospective study was done in the two second trimester abortion trainings conducted in Maternity hospital, Kathmandu. Total 57 clients had second trimester abortion performed. Information was collected from structured questionnaire and then data was analysed. Commonest reason for seeking abortion was, multiparity (61.4%). Common reasons for second trimester abortion were, completed family size with unwanted pregnancy (61.4%), unwanted pregnancy in married (10.52%) unwanted pregnancy in unmarried (5.26%). Second trimester abortion is one of the most common procedures performed in reproductive-aged women and when performed by a skilled provider in the appropriate setting, it is one of the safest surgeries, if it is well supported by change in policy of the country and acceptability of the people.

Home and Parenting Resources Available to Siblings Depending on Their Birth Intention Status

PubMed Central

Barber, Jennifer S.; East, Patricia L.

2011-01-01

This study examines the differential availability of family and parenting resources to children depending on their birth planning status. It uses data from the National Longitudinal Survey of Youth (NLSY) that assessed family and HOME resources for 3,134 mothers and their 5,890 children, of whom 63% were reported as intended at conception, 27% as mistimed, and 10% as unwanted. Results confirm previous findings that children born as a result of unintended pregnancies (both mistimed and unwanted) have fewer total resources and fewer cognitive and emotional supports than children born as a result of intended pregnancies, net of family background controls. Fixed effects (within-mother) models show that unwanted and mistimed children had fewer parental resources than their intended siblings. Our results also indicate decreases in parental emotional resources to an older child after the birth of a mistimed younger sibling. Findings suggest that cognitive and emotional resources are differentially available to children within a family depending on their intention status, and that unintended births may lead to a decrease in parental resources for older children in the household. PMID:19489912

Adaptive top-down suppression of hippocampal activity and the purging of intrusive memories from consciousness.

PubMed

Benoit, Roland G; Hulbert, Justin C; Huddleston, Ean; Anderson, Michael C

2015-01-01

When reminded of unwanted memories, people often attempt to suppress these experiences from awareness. Prior work indicates that control processes mediated by the dorsolateral prefrontal cortex (DLPFC) modulate hippocampal activity during such retrieval suppression. It remains unknown whether this modulation plays a role in purging an intrusive memory from consciousness. Here, we combined fMRI and effective connectivity analyses with phenomenological reports to scrutinize a role for adaptive top-down suppression of hippocampal retrieval processes in terminating mnemonic awareness of intrusive memories. Participants either suppressed or recalled memories of pictures depicting faces or places. After each trial, they reported their success at regulating awareness of the memory. DLPFC activation was greatest when unwanted memories intruded into consciousness and needed to be purged, and this increased engagement predicted superior control of intrusive memories over time. However, hippocampal activity was decreased during the suppression of place memories only. Importantly, the inhibitory influence of the DLPFC on the hippocampus was linked to the ensuing reduction in intrusions of the suppressed memories. Individuals who exhibited negative top-down coupling during early suppression attempts experienced fewer involuntary memory intrusions later on. Over repeated suppressions, the DLPFC-hippocampus connectivity grew less negative with the degree that they no longer had to purge unwanted memories from awareness. These findings support a role of DLPFC in countermanding the unfolding recollection of an unwanted memory via the suppression of hippocampal processing, a mechanism that may contribute to adaptation in the aftermath of traumatic experiences.

A check valve controlled laser-induced microjet for uniform transdermal drug delivery

NASA Astrophysics Data System (ADS)

Ham, Hwi-chan; Jang, Hun-jae; Yoh, Jack J.

2017-12-01

A narrow nozzle ejects a microjet of 150 μm in diameter with a velocity of 140 m/s a by the laser-induced bubble expansion in the designed injector. The pulsed form of the driving force at a period of 10 Hz from the connected Er:YAG laser makes it possible for multiple microjet ejections aimed at delivery of drugs into a skin target. The pulsed actuation of the microjet generation is however susceptible to the air leak which can cause the outside air to enter into the momentarily de-pressurized nozzle, leading to a significant reduction of the microjet speed during the pulsed administering of the drug. In the present study, we designed a ball-check valve injector which is less prone to an unwanted air build up inside the nozzle by controlling the nozzle pressure to remain above ambient pressure at all times. The new device is rigorously compared against the reported performance of the previous injector and has shown to maintain about 97% of the initial microjet speed regardless of the number of shots administered; likewise, the drug penetration depth into a porcine skin is improved to 1.5 to 2.25 times the previously reported penetration depths.

Ethylphenidate: availability, patterns of use, and acute effects of this novel psychoactive substance.

PubMed

Ho, James H; Bailey, George P; Archer, John R H; Dargan, Paul I; Wood, David M

2015-10-01

Ethylphenidate is a novel psychoactive substance that is an analogue of methylphenidate. This paper describes its availability, patterns of use, and acute effects. Searches of the scientific and grey literature (publicly accessible Internet resources) were undertaken, using the keywords "Ethylphenidate", "Ethyl phenidate", "Ethyl phenyl(piperidin-2-yl)acetate", and "Nopaine", to identify information on the prevalence and patterns of use, desired effects, and toxicity of ethylphenidate. An Internet snapshot survey was performed on 10 February 2015 to provide information on availability and cost of ethylphenidate. The literature search identified 1 case series of acute recreational ethylphenidate toxicity, 1 case report of ethylphenidate dependence, 1 qualitative analysis of user reports on Internet drug forums, 2 conference abstracts for surveillance studies, 1 report of two cases of ethylphenidate detected in post-mortem analyses, and 198 user reports on Internet discussion forums and social media sites. The Internet snapshot survey found 83 websites selling ethylphenidate, with purchase prices ranging from £28.20 ± 0.63 (€37.71 ± 0.85) per gram for a 500-mg amount to £2.64 ± 0.57 (€3.53 ± 0.77) per gram for 1 kg. The published cases and Internet user reports suggest the acute effects of ethylphenidate are similar to other stimulant drugs; the most common route of use was by nasal insufflation. The most common desired effects were euphoria, stimulation, and increased concentration, sociability, and energy levels; the most common unwanted effects included anxiety, palpitations, insomnia, and paranoia. This review of the scientific and grey literature has demonstrated that the acute harms associated with its use are stimulant in nature and that ethylphenidate is widely available to users over the Internet, with significant discounts for bulk purchases.

A rapid, Web-based method for obtaining patient views on effects and side-effects of antidepressants.

PubMed

Rizo, Carlos; Deshpande, Amol; Ing, Alton; Seeman, Neil

2011-04-01

This project was undertaken to develop a rapid method for obtaining a widespread sample of patient views on the efficacy and side-effects of antidepressants. A Web-based method is described for rapidly and objectively obtaining patient views on the effects and side-effects of treatment with antidepressants. The method entails a systematized search of many URLs (Uniform Resource Locators, or Web page addresses), using keywords and phrases to extract the named drug and symptom that are reliably relevant to the medication being taken by the individual reporting the experience online. Unwanted medical conditions (e.g., cancer) are excluded. Three successive searches of thousands of Web pages revealed a cumulative total of 835 "mentions" of patient experience on duloxetine, 756 for venlafaxine, 637 for citalopram, 636 for sertraline, 559 for paroxetine, 457 for fluoxetine, 318 for desvenlafaxine, 289 for fluvoxamine, and 210 for mirtazapine, in association with various symptoms. A comparison of the associated symptoms for each of the antidepressants found that the prevalence of the combined factor of fatigue, drowsiness, tiredness or lethargy ranged from 6.4±0.8% down to 2.9±0.15% of the mentions, where the S.E. was derived from three repeats of the Web-based analysis. The prevalence of dizziness or vertigo ranged from 7.6±0.8% down to 1.9±0.3% of the mentions. Given the increasing number of patient narratives about drug experiences on open-access Web forums, this rapid novel method will have increasing utility in post-marketing surveillance and in comparing the effects of psychiatric medications. Copyright © 2010 Elsevier B.V. All rights reserved.

Principles of light energy management

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

Davis, N.

1994-12-31

A review is presented on methods to minimize the effects of excess energy associated with lighting systems for plant growth. Information on lamp efficiencies and methods for separating and collecting unwanted heat is included.

Concurrent Use of Herbal and Orthodox Medicines among Residents of Tamale, Northern Ghana, Who Patronize Hospitals and Herbal Clinics

PubMed Central

Ibrahim, Mohammed; Ibrahim, Halimatu-Sadia; Habib, Rabiatu Hamisu; Gbedema, Stephen Yao

2018-01-01

Despite the development of more researched and formulated orthodox medicines, herbal medicines continue to be well patronized for persons across the world with some patrons concurrently using both forms, oblivious of the unwanted effects that may occur. Using a multistage sampling procedure, a semistructured questionnaire was used to collect data in April 2016 from 240 informants from three selected hospitals and three herbal clinics in Tamale, a city in northern Ghana. Using Statistical Package for the Social Sciences, binary logistic regression was used to determine sociodemographic predictors of concurrent use of herbal and orthodox medicines. Orthodox medicines were the drug of choice for 54.2% and 49.2% of patrons of hospitals and herbal clinics, respectively. Also, 67.5% of herbal clinic patrons used orthodox medicines, while 25.0% of hospital attendees used herbal medications prior to their visit to the health facilities. Up to 17.9% of respondents concurrently used herbal and orthodox medicines for their prevailing ailment with age, less than 30 years being the only predictor of this habit (p = 0.015; 95% CI, 1.183–4.793; cOR = 2.4). All health professionals including those in herbal clinics should therefore be interested in the drug history of their clients. PMID:29743917

Photo-mediated ultrasound therapy (PUT): a novel method of selectively treating neovascularization (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhang, Haonan; Hu, Zi Zhong; Li, Jia; Mordovanakis, Aghapi G.; Yang, Xinmai; Paulus, Yannis M.; Wang, Xueding

2017-02-01

Retinal and choroidal neovascularization play a pivotal role in the leading causes of blindness including macular degeneration and diabetic retinopathy (DR). Current therapy by focal laser photocoagulation can damage the normal surrounding cells, such as the photoreceptor inner and outer segments which are adjacent to the retinal pigment epithelium (RPE), due to the use of high laser energy and millisecond pulse duration. Therapies with pharmaceutical agents involve systemic administration of drugs, which can cause adverse effects and patients may become drug-resistant. We have developed a noninvasive photo-mediated ultrasound therapy (PUT) technique as a localized antivascular method, and applied it to remove micro blood vessels in the retina. PUT takes advantage of the high native optical contrast among biological tissues, and has the unique capability to self-target microvessels without causing unwanted damages to the surrounding tissues. This technique promotes cavitation activity in blood vessels by synergistically applying nanosecond laser pulses and ultrasound bursts. Through the interaction between cavitation and blood vessel wall, blood clots in microvessels and vasoconstriction can be induced. As a result, microvessels can be occluded. In comparison with other techniques that involves cavitation, both laser and ultrasound energy needed in PUT is significantly lower, and hence improves the safety in therapy.

Mitragynine Attenuates Withdrawal Syndrome in Morphine-Withdrawn Zebrafish

PubMed Central

Khor, Beng-Siang; Amar Jamil, Mohd Fadzly; Adenan, Mohamad Ilham; Chong Shu-Chien, Alexander

2011-01-01

A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway. PMID:22205946

Insurance Companies Fighting the Peer Review Empire without any Validity: the Case for Addiction and Pain Modalities in the face of an American Drug Epidemic.

PubMed

Blum, K; Jacobs, W; Modestino, E J; DiNubile, N; Baron, D; McLaughlin, T; Siwicki, D; Elman, I; Moran, M; Braverman, E R; Thanos, P K; Badgaiyan, R D

2018-10-04

The United States are amid an opioid overdose epidemic; we are challenged to provide non-addicting/non-pharmacological alternatives to assist in pain attenuation. There are proven strategies available to manage chronic pain effectively without opioids. Utilization review providers for insurance companies often ignore medicine based scientific peer-reviewed studies that warn against the chronic use of opioid medications, as well as the lack of evidence to support long-term use of opioids for pain. This paradigm must change if we are to indeed change the drug-embracing culture in American chronic pain management. A barrier to treatment is pushback on the part of insurance companies especially as it relates to fighting against pain relief alternatives compared to classical analgesic agents. Pain specialists in the U.S., are compelled to find alternative solutions to help pain victims without promoting unwanted tolerance to analgesics and subsequent biological induction of the "addictive brain." It is noteworthy that reward center of the brain plays a crucial role in the modulation of nociception, and that adaptations in dopaminergic circuitry may affect several sensory and affective components of chronic pain syndromes. Possibly knowing a patient's genetic addiction risk score (GARS™) could eliminate guessing as it relates to becoming addicted.

Hormonal contraception and HIV acquisition risk: implications for individual users and public policies.

PubMed

Jain, Anrudh K

2012-12-01

A recent observational study among HIV-1 serodiscordant couples (uninfected women living with an infected partner) raised concerns about the safety of injectable contraceptives, especially depot medroxyprogesterone acetate (DMPA). The purpose of this paper is to assess the implications of potentially elevated risk of Human Immunodeficiency Virus (HIV) acquisition with the use of hormonal contraceptives for individual users and public policies. Two indicators expressing costs (additional unwanted births and additional maternal deaths) in terms of the same unit of benefit (per 100 HIV infections averted) are estimated by using data on competing risks of unwanted birth and HIV acquisition associated with the use of various contraceptive methods. Elevated HIV acquisition risks associated with hormonal contraception observed in the observational studies of family planning users, sex workers and HIV-1 serodiscordant couples are used. Other relevant data for Kenya, South Africa and Zimbabwe are used to illustrate the potential effect of withdrawal of DMPA at the population level. Both the risks of unwanted birth and HIV acquisition with sterilization, intrauterine devices (IUDs) and implants at the individual level are lower than those with DMPA. A shift from DMPA to an oral contraceptive (OC) or male condom by an individual could result in about 600 and a shift to no method in about 5400 additional unwanted births per 100 HIV infections averted. At the population level, the withdrawal of DMPA from Kenya, for example, could result in 7600 annual additional unwanted births and 40 annual additional maternal deaths per 100 HIV infections averted. Individual DMPA users may be advised to shift to sterilization, IUD or implant depending upon their reproductive needs and circumstances, but not to no method, OC or even condom alone. At the macro level, the decision to withdraw DMPA from family planning programs in sub-Saharan Africa is not warranted. Copyright © 2012 Elsevier Inc. All rights reserved.

Risk factors for unplanned and unwanted teenage pregnancies occurring over two years of follow-up among a cohort of young South African women

PubMed Central

Christofides, Nicola J.; Jewkes, Rachel K.; Dunkle, Kristin L.; McCarty, Frances; Shai, Nwabisa Jama; Nduna, Mzikazi; Sterk, Claire

2014-01-01

Background Although teenage pregnancies in South Africa have declined, the short and longer term health and social consequences are a potential public health concern. This longitudinal study aimed to describe the range of risk and protective factors for incident unwanted and unplanned pregnancies occurring over 2 years of follow-up among a cohort of adolescent women in the Eastern Cape, South Africa. It also investigated the relationship between gender inequality and gender-based violence and subsequent unplanned and unwanted pregnancies among the cohort. Objective Teenage girls, aged 15–18 years (n=19), who were volunteer participants in a cluster randomized controlled trial and who had data from at least one follow-up were included in this analysis. To assess risk and protective factors for incident unwanted or unplanned pregnancies, we constructed multivariate polytomous regression models adjusting for sampling clusters as latent variables. Covariates included age, having a pregnancy prior to baseline, education, time between interviews, study intervention arm, contraceptive use, experience of intimate partner violence, belief that the teenage girl and her boyfriend are mutual main partners, and socioeconomic status. Results Overall, 174 pregnancies occurred over the 2-year follow-up period. Beliefs about relationship control were not associated with unwanted and unplanned pregnancies, nor were experiences of forced first sex or coerced sex under the age of 15. Hormonal contraception was protective against unplanned pregnancies (OR 0.40; 95% CI 0.21–0.79); however, using condoms was not protective. Physical abuse (OR 1.69; 95% CI 1.05–2.72) was a risk factor for, and having a pregnancy prior to baseline was protective against an unwanted pregnancy (OR 0.25; 95% CI 0.07–0.80). Higher socioeconomic status was protective for both unplanned and unwanted pregnancies (OR 0.69; 95% CI 0.58–0.83 and OR 0.78; 95% CI 0.64–0.96). Believing that the teenage girl and her boyfriend were mutual main partners doubled the odds of reporting both an unplanned and unwanted pregnancy (OR 2.58 95% CI 1.07–6.25, and OR 2.21 95% CI 1.13–4.29). Conclusion Although some of the measures of gender inequity were not associated with unplanned and unwanted pregnancies, there is evidence of the role of both gender power and socioeconomic status. This was evident in teenage girls who experienced physical violence being more likely to have an unwanted pregnancy. Interventions to prevent teenage pregnancies need to be tailored by socioeconomic status because some teenagers may see having a pregnancy as a way to have a more secure future. Interventions that engage with relationship dynamics of teenagers are essential if unwanted and unplanned pregnancies are to be prevented. PMID:25150027

The use of supplements and performance and image enhancing drugs in fitness settings: A exploratory cross-sectional investigation in the United Kingdom.

PubMed

Mooney, Roisin; Simonato, Pierluigi; Ruparelia, Risha; Roman-Urrestarazu, Andres; Martinotti, Giovanni; Corazza, Ornella

2017-05-01

The strive for perfection is prevalent in the fitness industry. This study aimed to explore the use of products to enhance performance alongside exposure to exercise addiction, appearance anxiety and self-esteem in fitness settings. An online survey was prepared and piloted before wider dissemination in fitness clubs via snowballing and selected mailing lists. A list of commonly used products, including Performance and Image Enhancing Drugs (PIEDs) was provided. Exercise addiction (Exercise Addiction Inventory; EAI), anxiety levels (Appearance Anxiety Inventory; AAI) and their self-esteem (Rosenberg's Self-Esteem Scale; RSE) were also measured. 377 questionnaires were completed. A significant number of participants declared the use products either to lose weight (16%) or to reach their fitness goals (41%). The Internet played a major role in both the supply of information and the provision of the enhancement products (33.7%) and side effects were reported (10.5%). Only a limited number of participants sought a medical opinion about taking products (5.1%). EAI scores were high (m=20.02 ± 4.1), AAI (m=15.98 ± 4.8) showed an intermediate level of anxiety, while self-esteem was low (RSE m=12.59 ± 2.2). This pilot study identified the emergence of a new drug trend in fitness settings and showed a potential relationship to exercise addiction, anxiety disorders and low self-esteem. The Internet played a crucial role in disseminating often untested products, including PIEDs without medical supervision and unwanted side-effects were reported. More studies in the field are required in order to safeguard public health and inform policy making. Copyright © 2017 John Wiley & Sons, Ltd.

Amiodarone in the treatment of refractory supraventricular and ventricular arrhythmias

PubMed Central

Wheeler, P. J.; Ingram, D. V.; Puritz, R.; Chamberlain, D. A.

1979-01-01

Amiodarone is an antiarrhythmic agent unrelated to other drugs in current use. It has been little used in Britain, and no formal clinical trials have been possible because the drug has not been licensed by the Committee on Safety of Medicines. Nevertheless it has unique properties which can be valuable in the treatment of a wide spectrum of arrhythmias, particularly supraventricular tachycardias. Amiodarone has a slow onset of action and is cumulative. A sustained action is therefore achieved without the need for frequent maintenance dosage. Fifty patients have been treated with amiodarone in maintenance doses ranging from 200 mg on alternate days to 200 mg twice daily either alone, or in combination with conventional therapy. All were resistant to conventional therapy alone or could not be treated with usual agents because of unwanted drug effects. Of 27 patients with supraventricular arrhythmias, 18 were completely controlled and the other 9 were markedly improved. Six of 8 patients with recurrent life-threatening ventricular arrhythmias were well controlled symptomatically. Results were predictably less satisfactory in 15 high risk post-infarction patients with malignant arrhythmias and severe myocardial damage, but 6 were probably improved as a result of amiodarone. All patients on maintenance therapy for 3 months or more developed corneal microdeposits. None has any visual symptoms or other ocular defect, and treatment has not been curtailed as a result of this well recognized effect which is believed to be reversible and benign. Amiodarone can control patients with otherwise refractory arrhythmias including some which are life-threatening. Formal clinical trials are needed to define accurately its future role in the prevention and treatment of serious rhythm disorders of the heart. PMID:432163

Surfactants, not size or zeta-potential influence blood-brain barrier passage of polymeric nanoparticles.

PubMed

Voigt, Nadine; Henrich-Noack, Petra; Kockentiedt, Sarah; Hintz, Werner; Tomas, Jürgen; Sabel, Bernhard A

2014-05-01

Nanoparticles (NP) can deliver drugs across the blood-brain barrier (BBB), but little is known which of the factors surfactant, size and zeta-potential are essential for allowing BBB passage. To this end we designed purpose-built fluorescent polybutylcyanoacrylate (PBCA) NP and imaged the NP's passage over the blood-retina barrier - which is a model of the BBB - in live animals. Rats received intravenous injections of fluorescent PBCA-NP fabricated by mini-emulsion polymerisation to obtain various NP's compositions that varied in surfactants (non-ionic, anionic, cationic), size (67-464nm) and zeta-potential. Real-time imaging of retinal blood vessels and retinal tissue was carried out with in vivo confocal neuroimaging (ICON) before, during and after NP's injection. Successful BBB passage with subsequent cellular labelling was achieved if NP were fabricated with non-ionic surfactants or cationic stabilizers but not when anionic compounds were added. NP's size and charge had no influence on BBB passage and cell labelling. This transport was not caused by an unspecific opening of the BBB because control experiments with injections of unlabelled NP and fluorescent dye (to test a "door-opener" effect) did not lead to parenchymal labelling. Thus, neither NP's size nor chemo-electric charge, but particle surface is the key factor determining BBB passage. This result has important implications for NP engineering in medicine: depending on the surfactant, NP can serve one of two opposite functions: while non-ionic tensides enhance brain up-take, addition of anionic tensides prevents it. NP can now be designed to specifically enhance drug delivery to the brain or, alternatively, to prevent brain penetration so to reduce unwanted psychoactive effects of drugs or prevent environmental nanoparticles from entering tissue of the central nervous system. Copyright © 2014 Elsevier B.V. All rights reserved.

Effective Risk Management in Innovative Projects: A Case Study of the Construction of Energy-efficient, Sustainable Building of the Laboratory of Intelligent Building in Cracow

NASA Astrophysics Data System (ADS)

Krechowicz, Maria

2017-10-01

Many construction projects fail to meet deadlines or they exceed the assumed budget. This scenario is particularly common in the case of innovative projects, in which too late identification of a high risk of delays and exceeding the assumed costs makes a potentially profitable project untenable. A high risk level, far exceeding the level of risk in standard non-innovative projects, is a characteristic feature of the realization phase of innovative projects. This is associated not only with greater complexity of the design and construction phases, but also with the problems with application of new technologies and prototype solutions, lack of qualified personnel with suitable expertise in specialized areas, and with the ability to properly identify the gaps between available and required knowledge and skills. This paper discusses the process of effective risk management in innovative projects on the example of the realization phase of an innovative, energy-efficient and sustainable building of the Laboratory of Intelligent Building in Cracow - DLJM Lab, from the point of view of DORBUD S.A., its general contractor. In this paper, a new approach to risk management process for innovative construction projects is proposed. Risk management process was divided into five stages: gathering information, identification of the important unwanted events, first risk assessment, development and choice of risk reaction strategies, assessment of the residual risk after introducing risk reactions. 18 unwanted events in an innovative construction project were identified. The first risk assessment was carried out using two-parametric risk matrix, in which the probability of unwanted event occurrence and its consequences were analysed. Three levels of risks were defined: tolerable, controlled and uncontrolled. Risk reactions to each defined unwanted event were developed. The following risk reaction types were considered: risk retention, risk reduction, risk transfer and risk elimination. Three-parametric risk matrix was developed to make it possible to assess risk after implementing risk reactions. The possibility of implementing risk management was inversely proportional to the probability of unwanted event occurrence and its contribution to the project outcome. Introducing this risk management strategy allowed to significantly reduce the risk of the innovative construction project. It proved to be an effective tool to reduce risk to an acceptable level. It had a significant contribution to carrying out the project within the assumed time, budget and quality standards.

Rotational Spectrum and Carbon Atom Structure of Dihydroartemisinic Acid

NASA Astrophysics Data System (ADS)

Evangelisti, Luca; Seifert, Nathan A.; Spada, Lorenzo; Pate, Brooks

2016-06-01

Dihydroartemisinic acid (DHAA, C15H24O2, five chiral centers) is a precursor in proposed low-cost synthetic routes to the antimalarial drug artemisinin. In one reaction process being considered in pharmaceutical production, DHAA is formed from an enantiopure sample of artemisinic acid through hydrogenation of the alkene. This reaction needs to properly set the stereochemistry of the asymmetric carbon for the synthesis to produce artemisinin. A recrystallization process can purify the diastereomer mixture of the hydrogenation reaction if the unwanted epimer is produced in less than 10% abundance. There is a need in the process analytical chemistry to rapidly (less than 1 min) measure the diastereomer excess and current solutions, such a HPLC, lack the needed measurement speed. The rotational spectrum of DHAA has been measured at 300:1 signal-to-noise ratio in a chirped-pulsed Fourier transform microwave spectrometer operating from 2-8 GHz using simple heating of the compound. The 13C isotope analysis provides a carbon atom structure that confirms the diastereomer. This structure is in excellent agreement with quantum chemistry calculations at the B2PLYPD3/ 6-311++G** level of theory. The DHAA spectrum is expected to be fully resolved from the unwanted diastereomer raising the potential for fast diastereomer excess measurement by rotational spectroscopy in the pharmaceutical production process.

Relationship between Unwanted Pregnancy and Health-Related Quality of Life in Pregnant Women.

PubMed

Ali, Azizi

2016-06-01

To determine the relationship between unwanted pregnancy and health-related quality of life in pregnant women. Case-control study. Department of Community Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran, from October 2013 to July 2014. Of the pregnant women who presented to primary healthcare centers of Kermanshah, Iran to receive prenatal care at 6 - 10 weeks of their pregnancy, those with unwanted pregnancy were selected as cases and those with wanted pregnancy were selected as control group. The selection process was done using multi-stage stratified random sampling. Frequency matching was applied to match the two groups. Quality of life was measured by the SF-36 questionnaire and was compared by the t-test. Relationship power between pregnancy type (wanted or unwanted pregnancy) and impairment of quality of life subscales as the outcome was assessed using odds ratio (OR). Frequency distribution of matched variables was not statistically different between the two studied groups. Mean scores of mental component summary and physical component summary as well as eight subscales (physical functioning, role, bodily pain, general health, vitality, social functioning, role emotional, and mental health) were lower in the unwanted pregnancy group compared to women with wanted pregnancy (p < 0.001). The highest high impairment odds ratio was highest for the mental component summary (MCS) (OR = 9.19; 95% CI = 5.17- 16.32) and vitality subscale (OR = 5.2; 95% CI = 2.89- 9.33). Mental health of the pregnant women with unwanted pregnancy is affected more than their physical health. Mental health in women with unwanted pregnancy is 9.19 times more likely to be reduced. Among mental health subscales, vitality (energy/fatigue) showed the highest decrease.

The role of poor sleep in the relation between workplace bullying/unwanted sexual attention and long-term sickness absence.

PubMed

Nabe-Nielsen, Kirsten; Grynderup, Matias Brødsgaard; Lange, Theis; Andersen, Johan Hviid; Bonde, Jens Peter; Conway, Paul Maurice; Garde, Anne Helene; Høgh, Annie; Kaerlev, Linda; Rugulies, Reiner; Hansen, Åse Marie

2016-08-01

While exposure to bullying and unwanted sexual attention was previously found to increase the risk of sickness absence, the underlying mechanisms are largely unknown. Poor sleep can be a consequence of stressful exposures and a cause of poor health, and poor sleep is also a determinant of insufficient recovery. Therefore, the present study investigated whether poor sleep mediates and/or moderates the association between bullying and unwanted sexual attention, on the one hand, and long-term sickness absence (LTSA), on the other hand. We used questionnaire data from 7650 individuals contributing with 15,040 2-year observation periods. Workplace bullying, unwanted sexual attention, disturbed sleep, and difficulties awakening were measured at three time points, and participants were followed in registers to measure the occurrence of LTSA, defined as ≥30 consecutive days of sickness absence during the subsequent 2 years. The odds of LTSA were significantly increased by workplace bullying (OR 1.77; 95 % CI 1.50-2.12) and unwanted sexual attention (OR 1.55; 95 % CI 1.06-2.29). Together, disturbed sleep and difficulties awakening mediated 12.8 % (95 % CI 8.1-19.8) of the association between bullying and long-term sickness absence, and 8.5 % (95 % CI -0.45 to 37.1) of the association between unwanted sexual attention and long-term sickness absence in the fully adjusted model. Neither disturbed sleep nor difficulties awakening moderated these associations. As expected, bullying and unwanted sexual attention were prospectively associated with long-term sickness absence. Only a small part of this association was mediated by poor sleep.

Domestic Violence, Unwanted Pregnancy and Pregnancy Termination among Urban Women of Bangladesh

PubMed Central

2013-01-01

Objective This paper explores the relationship between domestic violence against women inflicted by husbands, unwanted pregnancy and pregnancy termination of Bangladeshi urban women. Materials and methods The study used the nationally representative 2007 Bangladesh Demographic and Health Survey (BDHS) data. The BDHS covered a representative sample of 10,996 ever married women from rural and urban areas. The BDHS used a separate module to collect information from women regarding domestic violence. The survey gathered information of domestic violence from 1,013 urban women which are the basis of the study. Simple cross tabulation, bivariate and multivariate statistical analyses were performed to analyzing data. Results Overall, the lifetime prevalence of domestic violence was 47.5%. Of the most recent pregnancies, 15.6% were unwanted and 16.0% of the women terminated pregnancy in their marital life. The multivariate binary logistic regression analyses yielded quantitatively important and reliable estimate of unwanted pregnancy and pregnancy termination. The regression analyses yielded significantly (p < 0.05) increased risk of unwanted pregnancy only for physical violence (OR = 2.35, 95% CI = 1.28-4.32) and for both physical and sexual violence (OR = 2.27, 95% CI = 1.02-5.28), and higher risk of pregnancy termination for only physical violence (OR = 1.41, 95% CI = 0.95-2.10) and for both physical and sexual violence (OR = 1.81, 95% CI = 1.07-3.04) than women who were never abused. Current age, higher parity and early marriage are also important determinants of unwanted pregnancy and pregnancy termination. Conclusion Violence against women inflicted by husbands is commonplace in Bangladesh. Any strategy to reduce the burden of unwanted pregnancy and induced abortion should include prevention of violence against women and strengthening women's sexual and reproductive health. PMID:24971097

Postmarketing surveillance in developing countries.

PubMed

Meirik, O

1988-01-01

Authorities in developing countries need to monitor the possible adverse consequences of the increasing use of drugs in their countries. Definite differences exist in the risk-benefit ratios for developed and developing countries, particularly with fertility-regulating drugs. Some physicians believe that the increased risk of thrombosis associated with oral contraceptives (OCs) should not be considered as important in developing countries due to the fact that the background level of venous thrombosis is so low in developing countries that even a 50- or 100-fold increase in relative risk would neither be detectable nor important compared to the risk of unwanted pregnancy. In addition, evidence exists of geographically linked factors in the etiology of some adverse drug reactions (ADRs). Authorities in Brazil, India, Indonesia, Pakistan, the Philippines, Thailand, and Venezuela have established voluntary ADR reporting systems. Several developing countries also actively follow the World Health Organization's International Drug Monitoring Program and have access to its data base. A number of other methodological approaches to postmarketing surveillance are in use in addition to voluntary ADR reporting systems. These include cross-sectional surveys, studies of temporal and geographic correlations of diseases and drug use, and case-control and cohort studies. Each of these approaches offers specific advantages. Postmarketing surveillance should begin at the time new drugs, including contraceptive methods are introduced. Surveillance needs to be an integral part of plans for the introduction of new contraceptive methods in settings where the infrastructure to carry out such surveillance is in place. 3 major public sector agencies, Family Health International, the Population Council, and the World Health Organization, developed a plan to obtain funding for the postmarketing surveillance of a contraceptive implant, Norplant-R. A controlled cohort study will be conducted in 6-10 developing countries. The pilot phase of the surveillance began in 1987. The project objective is to detect possible adverse effects of Norplant-R as well as any health benefits of the method. It also will assess the feasibility of the cohort methodology for postmarketing surveillance in developing countries.

Poly(NIPAm-AMPS) nanoparticles for targeted delivery of anti-inflammatory cell penetrating peptides

NASA Astrophysics Data System (ADS)

Bartlett, Rush Lloyd, II

Inflammatory diseases such as osteoarthritis and rheumatoid arthritis cause $127.8 billion in US healthcare expenditures each year and are the cause of disability for 27% of disabled persons in the United States. Current treatment options rarely halt disease progression and often result in significant unwanted and debilitating side effects. Our laboratory has previously developed a family of cell penetrating peptides (CPPs) which inhibit the activity of mitogen activated protein kinase activate protein kinase 2 (MK2). MK2 mediates the inflammatory response by activating Tristetraprline (TTP). Once activated, TTP rapidly stabilizes AU rich regions of pro-inflammatory cytokine mRNA which allows translation of pro-inflammatory cytokines to occur. Blocking MK2 with our labs CPPs yields a decrease in inflammatory activity but CPPs by are highly non specific and prone to rapid enzymatic degradation in vivo.. In order to increase the potency of MK2 inhibiting CPPs we have developed a novel nanoparticle drug carrier composed of poly(N-isopropylacrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid). This drug carrier has been shown to have preliminary efficacy in vitro and ex vivo for suppressing pro-inflammatory cytokine production when releasing CPPs. This thesis will present progress made on three aims: Specific Aim 1) Create and validate a NIPAm based drug delivery system that mimics the binding and release previously observed between cell penetrating peptides and glycosaminoglycans. Specific Aim 2) Engineer degradability into poly(NIPAm-AMPS) nanoparticles to enable more drug to be released and qualify that system in vitro. Specific Aim 3) Validate poly(NIPAm-AMPS) nanoparticles for targeted drug delivery in an ex vivo inflammatory model. Overall we have developed a novel anionic nanoparticle system that is biocompatible and efficient at loading and releasing cell penetrating peptides to inflamed tissue. Once loaded with a CPP the nanoparticle drug complex is capable of targeting diseased tissue and preventing the production of pro-inflammatory cytokines in both in vitro and ex vivo models.

System and Method for Suppression of Unwanted Noise in Ground Test Facilities

NASA Technical Reports Server (NTRS)

Zaman, Khairul B. M. Q. (Inventor); Clem, Michelle M. (Inventor); Fagan, Amy F. (Inventor)

2015-01-01

Systems and methods for the suppression of unwanted noise from a jet discharging into a duct are disclosed herein. The unwanted noise may be in the form of excited duct modes or howl due to super resonance. A damper member is used to reduce acoustic velocity perturbations at the velocity anti-node, associated with the half-wave resonance of the duct, weakening the resonance condition and reducing the amplitudes of the spectral peaks.

[Antibiotic Residue in Environmental Water in Vietnam].

PubMed

Harada, Kazuo

2018-01-01

　The increasing prevalence of antimicrobial resistance (AMR) has caused intractable infections worldwide. Nearly 50% of the healthy population of Southeast Asia carries extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. The overuse of antimicrobial agents in the agriculture, aquaculture, and medical care sectors causes environmental pollution, facilitating the spread of AMR. However, there is a lack of data pertaining to antimicrobial residues in environmental water in such regions. We investigated a total of 49 chemicals, including β-lactams, sulfonamides, quinolones, and tetracyclines. Water samples were collected from rivers in city centers, and ponds in livestock and aquaculture farms, in Ha Noi, Thai Binh, and Can Tho in Vietnam. We detected antimicrobial agents at 87 of 111 sampling sites (78.4%). Among the target analytes, sulfamethoxazole, sulfamethazine, trimethoprim, cephalexin, and ofloxacin were detected frequently. The residual levels of each antimicrobial agent ranged from 0.1 to 10000 ng/L. Moreover, we detected multi-drug resistant E. coli in fishes sampled from these rivers, suggesting unwanted effects of antimicrobial residues in the environment.

Nanomedicines for cancer therapy: state-of-the-art and limitations to pre-clinical studies that hinder future developments

NASA Astrophysics Data System (ADS)

Dawidczyk, Charlene; Russell, Luisa; Searson, Peter

2014-08-01

The ability to efficiently deliver a drug or gene to a tumor site is dependent on a wide range of factors including circulation time, interactions with the mononuclear phagocyte system, extravasation from circulation at the tumor site, targeting strategy, release from the delivery vehicle, and uptake in cancer cells. Nanotechnology provides the possibility of creating delivery systems where the design constraints are decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing tumor accumulation, and improving efficacy. The physico-chemical properties of nanoparticle-based delivery platforms introduce additional complexity associated with pharmacokinetics and tumor accumulation. To assess the impact of nanoparticle-based delivery systems, we first review the design strategies and pharmacokinetics of FDA-approved nanomedicines. Next we review nanomedicines under development, summarizing the range of nanoparticle platforms, strategies for targeting, and pharmacokinetics. We show how the lack of uniformity in preclinical trials prevents systematic comparison and hence limits advances in the field.

Nanotechnology for photodynamic therapy: a perspective from the Laboratory of Dr. Michael R. Hamblin in the Wellman Center for Photomedicine at Massachusetts General Hospital and Harvard Medical School.

PubMed

Hamblin, Michael R; Chiang, Long Y; Lakshmanan, Shanmugamurthy; Huang, Ying-Ying; Garcia-Diaz, Maria; Karimi, Mahdi; de Souza Rastelli, Alessandra Nara; Chandran, Rakkiyappan

2015-08-01

The research interests of the Hamblin Laboratory are broadly centered on the use of different kinds of light to treat many different diseases. Photodynamic therapy (PDT) uses the combination of dyes with visible light to produce reactive oxygen species and kill bacteria, cancer cells and destroy unwanted tissue. Likewise, UV light is also good at killing especially pathogens. By contrast, red or near-infrared light can have the opposite effect, to act to preserve tissue from dying and can stimulate healing and regeneration. In all these applications, nanotechnology is having an ever-growing impact. In PDT, self-assembled nano-drug carriers (micelles, liposomes, etc.) play a great role in solubilizing the photosensitizers, metal nanoparticles can carry out plasmon resonance enhancement, and fullerenes can act as photosensitizers, themselves. In the realm of healing, single-walled carbon nanotubes can be electrofocused to produce nano-electonic biomedical devices, and nanomaterials will play a great role in restorative dentistry.

Reducing blood viscosity with magnetic fields

NASA Astrophysics Data System (ADS)

Tao, R.; Huang, K.

2011-07-01

Blood viscosity is a major factor in heart disease. When blood viscosity increases, it damages blood vessels and increases the risk of heart attacks. Currently, the only method of treatment is to take drugs such as aspirin, which has, however, several unwanted side effects. Here we report our finding that blood viscosity can be reduced with magnetic fields of 1 T or above in the blood flow direction. One magnetic field pulse of 1.3 T lasting ˜1 min can reduce the blood viscosity by 20%-30%. After the exposure, in the absence of magnetic field, the blood viscosity slowly moves up, but takes a couple of hours to return to the original value. The process is repeatable. Reapplying the magnetic field reduces the blood viscosity again. By selecting the magnetic field strength and duration, we can keep the blood viscosity within the normal range. In addition, such viscosity reduction does not affect the red blood cells’ normal function. This technology has much potential for physical therapy.

When is a medicine unwanted, how is it disposed, and how might safe disposal be promoted? Insights from the Australian population.

PubMed

Bettington, Emilie; Spinks, Jean; Kelly, Fiona; Gallardo-Godoy, Alejandra; Nghiem, Son; Wheeler, Amanda J

2017-12-19

Objective The aim of the present study was to explore disposal practices of unwanted medicines in a representative sample of Australian adults, compare this with previous household waste surveys and explore awareness of the National Return and Disposal of Unwanted Medicines (RUM) Project. Methods A 10-min online survey was developed, piloted and conducted with an existing research panel of adult individuals. Survey questions recorded demographics, the presence of unwanted medicines in the home, medicine disposal practices and concerns about unwanted medicines. Descriptive statistical analyses and rank-ordered logit regression were conducted. Results Sixty per cent of 4302 respondents reported having unwanted medicines in their household. Medicines were primarily kept just in case they were needed again and one-third of these medicines were expired. Two-thirds of respondents disposed of medicines with the household garbage and approximately one-quarter poured medicines down the drain. Only 17.6% of respondents had heard of the RUM Project, although, once informed, 91.7% stated that they would use it. Respondents ranked the risk of unintended ingestion as the most important public health message for future social marketing campaigns. Conclusions Respondents were largely unaware of the RUM Project, yet were willing to use it once informed. Limited awareness could lead to environmental or public health risks, and targeted information campaigns are needed. What is known about the topic? There is a growing international evidence base on how people dispose of unwanted medicines and the negative consequences, particularly the environmental effects of inappropriate disposal. Although insight into variation in disposal methods is increasing, knowledge of how people perceive risks and awareness of inappropriate disposal methods is more limited. What does this paper add? This study provides evidence of inappropriate medicines disposal and potential stockpiling of medicines in Australian households that could contribute to environmental and/or public health risks. It also reveals possible trends towards a higher frequency of inappropriate disposal practices in the Australian context. Insights into respondents' perceptions of associated risks and awareness of a national scheme for appropriate disposal of medicines have not previously been reported. What are the implications for practitioners? The findings of the present study provide important insights for all health professionals as stakeholders in the quality use of medicines. It is important for those health professionals who assist consumers to manage their medicines to have strategies in place that routinely identify potential stockpiling and inform consumers about appropriate methods of medicines disposal. Although the findings of this study are specific to the Australian context, they may usefully inform policy, public health campaigns and the individual practices of health professionals and other stakeholders in promoting the quality use of medicines nationally and internationally.

Benten v. Kessler: the RU 486 import case.

PubMed

Pine, R N

1992-01-01

On July 1, 1992, the case of Benten v. Kessler was filed in the US District Court in New York. The case arose out of an attempt by abortion rights activist Lawrence Lader to call public attention to the US Food and Drug Administration's (FDA) ban on importation of the abortifacient drug mifepristone known as RU-486. The ban expresses the anti abortion stance of the Reagan and Bush administrations and creates a hostile climate for the development of new drugs related to reproductive health and reproductive choice. Plaintiffs in the Benten case sought public accountability by the FDA for its adoption of a ban of a safe and effective drug for unwanted pregnancy. Although the case did not succeed in retrieving the confiscated RU-486 pills for Leona Benten, in its opinion issued on July 14, 1992, the New York district court judge concluded that the import ban did not appear to be based on concern with the safety or effectiveness of RU-486, describing the FDA's process of adopting the import ban as a sink of illegality. On July 17, 1992, 7 Justices of the Supreme Court, with justices Blackmun and Stevens dissenting, joined in a per curiam opinion denying the application and foreclosing further personal relief for Leona Benten. This was the best result possible short of an all out victory for Leona Benten. The Court ruled against plaintiffs in their argument that notice and comment were required, but left entirely open plaintiffs' claims that the import ban is arbitrary and capricious under the Administrative Procedure Act and that the ban is unconstitutional in that it unduly burdens the right to terminate pregnancy. This backdrop creates a healthy skepticism about the prospects for the introduction of RU-486 into the US in the near future as well as about the fairness of government processes in areas of concern to women. Public health considerations, not politics, should determine access to health care.

Eyewitness identification in simultaneous and sequential lineups: an investigation of position effects using receiver operating characteristics.

PubMed

Meisters, Julia; Diedenhofen, Birk; Musch, Jochen

2018-04-20

For decades, sequential lineups have been considered superior to simultaneous lineups in the context of eyewitness identification. However, most of the research leading to this conclusion was based on the analysis of diagnosticity ratios that do not control for the respondent's response criterion. Recent research based on the analysis of ROC curves has found either equal discriminability for sequential and simultaneous lineups, or higher discriminability for simultaneous lineups. Some evidence for potential position effects and for criterion shifts in sequential lineups has also been reported. Using ROC curve analysis, we investigated the effects of the suspect's position on discriminability and response criteria in both simultaneous and sequential lineups. We found that sequential lineups suffered from an unwanted position effect. Respondents employed a strict criterion for the earliest lineup positions, and shifted to a more liberal criterion for later positions. No position effects and no criterion shifts were observed in simultaneous lineups. This result suggests that sequential lineups are not superior to simultaneous lineups, and may give rise to unwanted position effects that have to be considered when conducting police lineups.

Single-molecule fluorescence study of the inhibition of the oncogenic functionality of STAT3

NASA Astrophysics Data System (ADS)

Liu, Baoxu; Badali, Daniel; Fletcher, Steven; Avadisian, Miriam; Gunning, Patrick; Gradinaru, Claudiu

2009-06-01

Signal-Transducer-and-Activator-of-Transcription 3 (STAT3) protein plays an important role in the onset of cancers such as leukemia and lymphoma. In this study, we aim to test the effectiveness of a novel peptide drug designed to tether STAT3 to the phospholipid bilayer of the cell membrane and thus inhibit unwanted transcription. As a first step, STAT3 proteins were successfully labelled with tetramethylrhodamine (TMR), a fluorescent dye with suitable photostability for single molecule studies. The effectiveness of labelling was determined using fluorescence correlation spectroscopy in a custom built confocal microscope, from which diffusion times and hydrodynamic radii of individual proteins were determined. A newly developed fluorescein derivative label (F-NAc) has been designed to be incorporated into the structure of the peptide drug so that peptide-STAT3 interactions can be examined. This dye is spectrally characterized and is found to be well suited for its application to this project, as well as other single-molecule studies. The membrane localization via high-affinity cholesterol-bound small-molecule binding agents can be demonstrated by encapsulating TMR-labeled STAT3 and inhibitors within a vesicle model cell system. To this end, unilaminar lipid vesicles were examined for size and encapsulation ability. Preliminary results of the efficiency and stability of the STAT3 anchoring in lipid membranes obtained via quantitative confocal imaging and single-molecule spectroscopy using a custom-built multiparameter fluorescence microscope are reported here.

Synthesis and biochemical analysis of 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro-N-hydroxy-octanediamides as inhibitors of human histone deacetylases.

PubMed

Henkes, Leonhard M; Haus, Patricia; Jäger, Felix; Ludwig, Joachim; Meyer-Almes, Franz-Josef

2012-01-15

Inhibition of human histone deacetylases (HDACs) has emerged as a novel concept in the chemotherapeutic treatment of cancer. Two chemical entities, SAHA (ZOLINZA, Merck) and romidepsin (Istodax, Celgene) have been recently approved by the FDA as first-in-class drugs against cutaneous T-cell lymphoma. Clinical use of these drugs revealed several side effects including gastro-intestinal symptoms, fatigue, thrombocytopenia, thrombosis. Romidepsin is associated with an yet unresolved cardiotoxicity issue. A general hypothesis for the diminishment of unwanted adverse effects and an improved therapeutical window suggests the development of more isotype selective inhibitors. In this study the first time HDAC inhibitors with perfluorinated spacers between the zinc chelating moiety and the aromatic capping group were synthesized and tested against representatives of HDAC classes I, IIa and IIb. Competitive binding assays and a combined approach by using blind docking and molecular dynamics support binding of the perfluorinated analogs of SAHA to the active site of the HDAC-like amidohydrolase from Bordetella/Alcaligenes and presumably also to human HDACs. In contrast to the alkyl spacer of SAHA and derivatives, the perfluorinated alkyl spacer seems to contribute to or facilitate the induction of selectivity for class II, particularly class IIa, HDACs even though the overall potency of the perfluorinated SAHA analogs in this study against human HDACs remained still rather moderate in the micromolar range. Copyright © 2011 Elsevier Ltd. All rights reserved.

Xylan-regulated delivery of human keratinocyte growth factor-2 to the inflamed colon by the human anaerobic commensal bacterium Bacteroides ovatus.

PubMed

Hamady, Zaed Z R; Scott, Nigel; Farrar, Mark D; Lodge, J Peter A; Holland, Keith T; Whitehead, Terence; Carding, Simon R

2010-04-01

Human growth factors are potential therapeutic agents for various inflammatory disorders affecting the gastrointestinal tract. However, they are unstable when administered orally and systemic administration requires high doses increasing the risk of unwanted side effects. Live microorganism-based delivery systems can overcome these problems although they suffer from the inability to control heterologous protein production and there are concerns regarding biosafety and environmental contamination. To overcome these limitations we have developed a new live bacteria drug-delivery system using the human commensal gut bacterium Bacteroides ovatus engineered to secrete human growth factors in response to dietary xylan. The anaerobic nature of B ovatus provides an inherent biosafety feature. B ovatus strains expressing human keratinocyte growth factor-2, which plays a central role in intestinal epithelial homeostasis and repair (BO-KGF), were generated by homologous recombination and evaluated using the dextran sodium sulfate (DSS)-induced model of intestinal epithelial injury and colitis. In response to xylan BO-KGF produced biologically active KGF both in vitro and in vivo. In DSS treated mice administration of xylan and BO-KGF had a significant therapeutic effect in reducing weight loss, improving stool consistency, reducing rectal bleeding, accelerating healing of damaged epithelium, reducing inflammation and neutrophil infiltration, reducing expression of pro-inflammatory cytokines, and accelerating production of goblet cells. BO-KGF and xylan treatment also had a marked prophylactic effect limiting the development of inflammation and disruption of the epithelial barrier. This novel, diet-regulated, live bacterial drug delivery system may be applicable to treating various bowel disorders.

Pharmacological Activity and Clinical Use of PDRN

PubMed Central

Squadrito, Francesco; Bitto, Alessandra; Irrera, Natasha; Pizzino, Gabriele; Pallio, Giovanni; Minutoli, Letteria; Altavilla, Domenica

2017-01-01

PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta (Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions. In vitro and in vivo experiments have suggested that PDRN most relevant mechanism of action is the engagement of adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A2A receptors is a unique property of PDRN and seems to be linked to DNA origin, molecular weight and manufacturing process. In this context, PDRN represents a new advancement in the pharmacotherapy. In fact adenosine and dipyridamole are non-selective activators of adenosine receptors and they may cause unwanted side effects; while regadenoson, the only other A2A receptor agonist available, has been approved by the FDA as a pharmacological stress agent in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a mixture of oligonucleotides, has different molecular weight, a DNA of different origin and does not share the same wound healing stimulating effects of PDRN. The present review analyses the more relevant experimental and clinical evidences carried out to characterize PDRN therapeutic effects. PMID:28491036

Sexual and reproductive health and HIV/AIDS risk perception in the Malawi tourism industry.

PubMed

Bisika, Thomas

2009-06-01

Malawi has for a long time relied on agriculture for the generation of foreign exchange. Due to varied reasons like climate change, the Malawi government has, therefore, identified tourism as one way of boosting foreign exchange earnings and is already in the process of developing the sector especially in the area of ecotourism. However, tourism is associated with increasing prostitution, drug abuse and a whole range of other sexual and reproductive health (SRH) problems such as teenage pregnancies, HIV/AIDS and sexually transmitted infections (STIs). This paper examines the knowledge, attitudes, practices and behaviour as well as risk perceptions associated with HIV/AIDS, sexually transmitted infections and unwanted pregnancies among staff in the tourism industry and communities around tourist facilities in Malawi. The study was descriptive in nature and used both qualitative and quantitative research methods. The qualitative methods involved in-depth interviews and focus group discussions. The quantitative technique employed a survey of 205 purposively selected subjects from the tourism sector. The study concludes that people in the tourism sector are at high risk of HIV/AIDS, sexually transmitted infections and unwanted pregnancies and should be considered as a vulnerable group. The study further observes that this group of people has not adopted behaviours that can protect them from HIV/AIDS, sexually transmitted infections and unwanted pregnancies although there is high demand for voluntary counselling and testing (VCT) which offers a very good entry point for HIV prevention and treatment in the tourism sector. The study recommends that a comprehensive tourism policy covering tourists, employees and communities around tourist facilities is required. Such a policy should address the rights of HIV infected employees and the provision of prevention and treatment services for HIV/AIDS and STIs as well as a broad range of SRH and family planning services especially the condom which offers dual protection for pregnancy and STIs including HIV.

Sexual Orientation Disparities in Mistimed and Unwanted Pregnancy Among Adult Women.

PubMed

Everett, Bethany G; McCabe, Katharine F; Hughes, Tonda L

2017-09-01

Many sexual minority women, regardless of sexual identity, engage in heterosexual behavior across the life course, which provides them opportunities to experience an unintended pregnancy. In addition, sexual minority women are more likely than others to report characteristics that may make them vulnerable to unintended pregnancy. Little research, however, has examined whether the risk of unintended pregnancy is elevated among these women. Using data from the 2006-2010 National Survey of Family Growth, logistic regression models were fitted to examine sexual orientation disparities in mistimed and unwanted pregnancies among 9,807 women aged 20-45; mixed-effects hazard models assessed disparities in the intention status of 5,238 pregnancies among these women by maternal sexual orientation. Compared with heterosexual women reporting only male partners, heterosexual women who have sex with women had higher odds of reporting a mistimed pregnancy (odds ratio, 1.4), and bisexual women had higher odds of reporting an unwanted pregnancy (1.8). When compared with pregnancies reported by heterosexual women with only male partners, those reported by heterosexual women who have sex with women were more likely to be mistimed (hazard ratio, 1.7), and those reported by bisexual and lesbian women were more likely to be unwanted (1.7-4.4). Compared with heterosexuals who have sex with men only, adult sexual minority women are at equal or greater risk of reporting an unintended pregnancy. More research addressing the reproductive health care needs of sexual minority women is needed to develop strategies to improve family planning for this population. Copyright © 2017 by the Guttmacher Institute.

Effect of calf purchase and other herd-level risk factors on mortality, unwanted early slaughter, and use of antimicrobial group treatments in Swiss veal calf operations.

PubMed

Lava, M; Pardon, B; Schüpbach-Regula, G; Keckeis, K; Deprez, P; Steiner, A; Meylan, M

2016-04-01

The objective of this survey was to determine herd level risk factors for mortality, unwanted early slaughter, and metaphylactic application of antimicrobial group therapy in Swiss veal calves in 2013. A questionnaire regarding farm structure, farm management, mortality and antimicrobial use was sent to all farmers registered in a Swiss label program setting requirements for improved animal welfare and sustainability. Risk factors were determined by multivariable logistic regression. A total of 619 veal producers returned a useable questionnaire (response rate=28.5%), of which 40.9% only fattened their own calves (group O), 56.9% their own calves and additional purchased calves (group O&P), and 2.3% only purchased calves for fattening (group P). A total number of 19,077 calves entered the fattening units in 2013, of which 21.7%, 66.7%, and 11.6% belonged to groups O, O&P, and P, respectively. Mortality was 0% in 322 herds (52.0%), between 0% and 3% in 47 herds (7.6%), and ≥3% in 250 herds (40.4%). Significant risk factors for mortality were purchasing calves, herd size, higher incidence of BRD, and access to an outside pen. Metaphylaxis was used on 13.4% of the farms (7.9% only upon arrival, 4.4% only later in the fattening period, 1.1% upon arrival and later), in 3.2% of the herds of group O, 17.9% of those in group O&P, and 92.9% of those of group P. Application of metaphylaxis upon arrival was positively associated with purchase (OR=8.9) and herd size (OR=1.2 per 10 calves). Metaphylaxis later in the production cycle was positively associated with group size (OR=2.9) and risk of respiratory disease (OR=1.2 per 10% higher risk) and negatively with the use of individual antimicrobial treatment (OR=0.3). In many countries, purchase and a large herd size are inherently connected to veal production. The Swiss situation with large commercial but also smaller herds with little or no purchase of calves made it possible to investigate the effect of these factors on mortality and antimicrobial drug use. The results of this study show that a system where small farms raise the calves from their own herds has a substantial potential to improve animal health and reduce antimicrobial drug use. Copyright © 2016 Elsevier B.V. All rights reserved.

Examining the geographical heterogeneity associated with risk of mistimed and unwanted pregnancy in Ghana.

PubMed

Amoako Johnson, Fiifi; Madise, Nyovani J

2009-03-01

After a decade of fertility decline, Ghana's fertility and the level of unmet need for contraception stalled in mid-transition in the late 1990s. Although the literature acknowledges this, the geographical patterns in unmet need have not been adequately documented. Spatial analysis of unmet need can reveal differences in usage and provision of contraceptive commodities, thereby pointing to geographical areas where contraceptive programmes should be strengthened. This study examines the geographical variation of the risk of mistimed and unwanted pregnancies between rural communities and also between urban communities of the three ecological zones of Ghana. The study also investigates if geographical differences in the risks of mistimed and unwanted pregnancies changed during the period when unmet need stalled at the national level. A multilevel regression model was applied to pooled data from the 1998 and 2003 Ghana Demographic and Health Surveys to examine the determinants of the risk of unintended pregnancies, while controlling for clustering of outcomes within communities. The results show that between the two surveys, there was no significant change in the levels of risk of mistimed and unwanted pregnancy. However, geographical heterogeneity in the risk of mistimed and unwanted pregnancy was observed, after controlling for relevant predictors. This showed concentration of mistimed pregnancies in some rural communities relative to others, and variation in the risk of unwanted pregnancies between urban communities. The results give a clear indication that bridging the inequality gap in contraceptive use requires programmes that are area-specific.

Can't control yourself? Monitor those bad habits.

PubMed

Quinn, Jeffrey M; Pascoe, Anthony; Wood, Wendy; Neal, David T

2010-04-01

What strategies can people use to control unwanted habits? Past work has focused on controlling other kinds of automatic impulses, especially temptations. The nature of habit cuing calls for certain self-control strategies. Because the slow-to-change memory trace of habits is not amenable to change or reinterpretation, successful habit control involves inhibiting the unwanted response when activated in memory. In support, two episode-sampling diary studies demonstrated that bad habits, unlike responses to temptations, were controlled most effectively through spontaneous use of vigilant monitoring (thinking "don't do it," watching carefully for slipups). No other strategy was useful in controlling strong habits, despite that stimulus control was effective at inhibiting responses to temptations. A subsequent experiment showed that vigilant monitoring aids habit control, not by changing the strength of the habit memory trace but by heightening inhibitory, cognitive control processes. The implications of these findings for behavior change interventions are discussed.

Emergency contraception amongst female college students – knowledge, attitude and practice

PubMed Central

Nibabe, Wendwosen T.

2014-01-01

Background Unwanted teenage pregnancies have a notable detrimental impact on the learners’ trajectory and have been associated with jeopardising the students’ educational progress and future career prospects. These pregnancies are mostly unplanned and unintended and many are terminated, either legally or illegally. Aim The aim of this study was to explore the contributory role played by the knowledge, attitude and practices of female college students with respect to the utilisation of emergency contraceptives. Setting Three tertiary institutions in Dessie, Ethiopia. Methods Quantitative self-administered questionnaires were used to collect descriptive data from 352 female college students. Results The study revealed that there was a high percentage (78.3%) of unwanted pregnancies amongst those engaging in sex. Significantly, nearly half (43.3%) of these unwanted pregnancies resulted in abortion. Only 10% of the students sampled admitted to ever having used emergency contraception. Even though more than half (69.9%) of the students knew about emergency contraception, only 27% of them felt confident that they understood when it was most effective. Conclusion These and other observed findings confirm the need for improvement of female college students’ knowledge and timely utilisation of emergency contraception. PMID:26245395

The adverse health effects of synthetic cannabinoids with emphasis on psychosis-like effects.

PubMed

van Amsterdam, Jan; Brunt, Tibor; van den Brink, Wim

2015-03-01

Cannabis use is associated with an increased risk of psychosis in vulnerable individuals. Cannabis containing high levels of the partial cannabinoid receptor subtype 1 (CB1) agonist tetrahydrocannabinol (THC) is associated with the induction of psychosis in susceptible subjects and with the development of schizophrenia, whereas the use of cannabis variants with relatively high levels of cannabidiol (CBD) is associated with fewer psychotic experiences. Synthetic cannabinoid receptor agonists (SCRAs) are full agonists and often more potent than THC. Moreover, in contrast to natural cannabis, SCRAs preparations contain no CBD so that these drugs may have a higher psychosis-inducing potential than cannabis. This paper reviews the general toxicity profile and the adverse effects of SCRAs with special emphasis on their psychosis-inducing risk. The review shows that, compared with the use of natural cannabis, the use of SCRAs may cause more frequent and more severe unwanted negative effects, especially in younger, inexperienced users. Psychosis and psychosis-like conditions seem to occur relatively often following the use of SCRAs, presumably due to their high potency and the absence of CBD in the preparations. Studies on the relative risk of SCRAs compared with natural cannabis to induce or evoke psychosis are urgently needed. © The Author(s) 2015.

Medical countermeasures for unwanted CBRN exposures: Part I chemical and biological threats with review of recent countermeasure patents.

PubMed

Singh, Vijay K; Garcia, Melissa; Wise, Stephen Y; Seed, Thomas M

2016-12-01

The threat of chemical, biological, radiological, and nuclear (CBRN) warfare has been addressed as the uppermost risk to national security since the terrorist attacks on 11 September 2001. Despite significant scientific advances over the past several decades toward the development of safe, non-toxic and effective countermeasures to combat CBRN threats, relatively few countermeasures have been approved by the US Food and Drug Administration (US FDA). Therefore, countermeasures capable of protecting the population from the effects of CBRN attack remain a significant unmet medical need. Chemical and biological (CB) threat agents can be particularly hazardous due to their effectiveness in small quantities and ease of distribution. Area covered: This article reviews the development of countermeasures for CB threats and highlights specific threats for which at least one countermeasure has been approved following the FDA Animal Rule. Patents of CB countermeasures since 2010 have been included. Expert opinion: Nine CB countermeasures have received FDA approval for use in humans following the Animal Rule, and a number of promising CB countermeasures are currently under development. In the next few years, we should expect to have multiple countermeasures approved by the FDA for each indication allowing for more flexible and effective treatment options.

Effect of a novel low-energy pulsed-light device for home-use hair removal.

PubMed

Alster, Tina S; Tanzi, Elizabeth L

2009-03-01

Removal of unwanted hair is the most popular skin treatment worldwide. Over the past decade, various lasers and light sources for epilation have been advocated for use in an office setting, although most people continue to treat unwanted hair with a variety of temporary physical methods (e.g., waxing, shaving) in a home setting, presumably due to cost and convenience factors. To evaluate the safety and efficacy of a low-energy pulsed-light device intended for home-use hair removal. Twenty women (skin phototypes I-IV) with dark terminal hair in nonfacial sites (axilla, forearms, inguinal region, legs) self-administered three treatments at 2-week intervals using a handheld intense-pulsed-light device. Matched untreated skin sites were also studied. Hair counts and clinical photographs were obtained pretreatment and at 1, 3, and 6 months after the third treatment. Side effects and patient satisfaction scores were recorded. All patients showed a positive clinical response to treatment, with reduction of unwanted hair. No reduction of hair was noted in untreated matched areas. Hair counts were reduced 37.8% to 53.6% 6 months after the three treatments. Skin region influenced clinical response, with lower legs exhibiting greater hair reduction than arms and inguinal and axillary areas. Mild erythema was experienced in 25% of patients, but no other side effects or complications were encountered. Patient satisfaction scores were high, with all patients stating that they would purchase the device for future home use. CONCLUSIONS Low-energy pulsed light can be applied safely and effectively for at-home hair removal in a variety of nonfacial locations and skin phototypes I-IV.

Pretreatment with remifentanil, fentanyl, or lidocaine to prevent withdrawal after rocuronium using venous occlusion technique in children and adolescents: a prospective randomized placebo-controlled double-blind study.

PubMed

Abu-Halaweh, S A; Aloweidi, A K; Qudaisat, I Y; Al-Hussami, M O; Al Zaben, K R; Abu-Halaweh, A S

2014-12-01

Pain caused by intravenous injection of the muscle relaxant rocuronium bromide is common in children and adolescents. The cause of this unwanted effect is still unclear, and different pretreatment drugs have been administered in attempts to alleviate this side effect, with varying degrees of success. This study used a 60-s venous occlusion technique to evaluate the effectiveness of pretreatment with lidocaine, fentanyl, or remifentanil in preventing pain-induced withdrawal caused by intravenous injection of rocuronium bromide during the induction of general anesthesia. One hundred and one child and adolescent patients, ASA Ι-II, requiring various surgical procedures under general anesthesia with muscle relaxation and mechanical ventilation, were enrolled. Patients were allocated randomly using computer-generated randomization into one of four pretreatment groups: a remifentanil group (1 µg/kg, n = 25), fentanyl group (1 µg/kg, n = 26), lidocaine 1% group (0.5 mg/kg, n = 25), and normal saline group (n = 25). Drug doses were prepared in normal saline to a total volume of 5 ml. Venous occlusion was applied 10 cm above the venous access site. Pretreatment drugs were injected and retained for 60 s at the site of injection by an anesthetist blinded to group allocation. After release of the tourniquet, rocuronium (0.5 mg/kg) was then injected over 5 s, and withdrawal was recorded by another anesthetist blinded to group allocation. Descriptive statistics, analysis of variance, and a chi-squared test were used to statistically analyze the results as appropriate. Compared to normal saline, all other pretreatment groups scored a significantly lower mean of withdrawal response (P < 0.001). Lidocaine was superior to both remifentanil (P < 0.05) and fentanyl (P < 0.05) in suppressing the withdrawal response to rocuronium injection. Remifentanil was superior to fentanyl in suppressing the withdrawal response caused by rocuronium injection (P < 0.001). Using a venous occlusion technique for 60 s, lidocaine was found to be most effective in preventing the withdrawal effect caused by rocuronium injection in children and adolescents. Lidocaine was superior to remifentanil which, in turn, was more effective than fentanyl.

Śodhana: An Ayurvedic process for detoxification and modification of therapeutic activities of poisonous medicinal plants

PubMed Central

Maurya, Santosh Kumar; Seth, Ankit; Laloo, Damiki; Singh, Narendra Kumar; Gautam, Dev Nath Singh; Singh, Anil Kumar

2015-01-01

Ayurveda involves the use of drugs obtained from plants, animals, and mineral origin. All the three sources of drugs can be divided under poisonous and nonpoisonous category. There are various crude drugs, which generally possess unwanted impurities and toxic substances, which can lead to harmful health problems. Many authors have reported that not all medicinal plants are safe to use since they can bear many toxic and harmful phytoconstituents in them. Śodhana (detoxification/purification) is the process, which involves the conversion of any poisonous drug into beneficial, nonpoisonous/nontoxic ones. Vatsanābha (Aconitum species), Semecarpus anacardium, Strychnos nux-vomica, Acorus calamus, Abrus precatorius etc., are some of the interesting examples of toxic plants, which are still used in the Indian system of medicine. Aconite, bhilawanols, strychnine, β–asarone, abrin are some of the toxic components present in these plants and are relatively toxic in nature. Śodhana process involves the purification as well as reduction in the levels of toxic principles which sometimes results in an enhanced therapeutic efficacy. The present review is designed to extensively discuss and understand the scientific basis of the alternative use of toxic plants as a medicine after their purification process. PMID:26283803

Deployable micro-traps to sequester motile bacteria

NASA Astrophysics Data System (ADS)

di Giacomo, Raffaele; Krödel, Sebastian; Maresca, Bruno; Benzoni, Patrizia; Rusconi, Roberto; Stocker, Roman; Daraio, Chiara

2017-04-01

The development of strategies to reduce the load of unwanted bacteria is a fundamental challenge in industrial processing, environmental sciences and medical applications. Here, we report a new method to sequester motile bacteria from a liquid, based on passive, deployable micro-traps that confine bacteria using micro-funnels that open into trapping chambers. Even in low concentrations, micro-traps afford a 70% reduction in the amount of bacteria in a liquid sample, with a potential to reach >90% as shown by modelling improved geometries. This work introduces a new approach to contain the growth of bacteria without chemical means, an advantage of particular importance given the alarming growth of pan-drug-resistant bacteria.

Deployable micro-traps to sequester motile bacteria

PubMed Central

Di Giacomo, Raffaele; Krödel, Sebastian; Maresca, Bruno; Benzoni, Patrizia; Rusconi, Roberto; Stocker, Roman; Daraio, Chiara

2017-01-01

The development of strategies to reduce the load of unwanted bacteria is a fundamental challenge in industrial processing, environmental sciences and medical applications. Here, we report a new method to sequester motile bacteria from a liquid, based on passive, deployable micro-traps that confine bacteria using micro-funnels that open into trapping chambers. Even in low concentrations, micro-traps afford a 70% reduction in the amount of bacteria in a liquid sample, with a potential to reach >90% as shown by modelling improved geometries. This work introduces a new approach to contain the growth of bacteria without chemical means, an advantage of particular importance given the alarming growth of pan-drug-resistant bacteria. PMID:28378786

Deployable micro-traps to sequester motile bacteria.

PubMed

Di Giacomo, Raffaele; Krödel, Sebastian; Maresca, Bruno; Benzoni, Patrizia; Rusconi, Roberto; Stocker, Roman; Daraio, Chiara

2017-04-05

The development of strategies to reduce the load of unwanted bacteria is a fundamental challenge in industrial processing, environmental sciences and medical applications. Here, we report a new method to sequester motile bacteria from a liquid, based on passive, deployable micro-traps that confine bacteria using micro-funnels that open into trapping chambers. Even in low concentrations, micro-traps afford a 70% reduction in the amount of bacteria in a liquid sample, with a potential to reach >90% as shown by modelling improved geometries. This work introduces a new approach to contain the growth of bacteria without chemical means, an advantage of particular importance given the alarming growth of pan-drug-resistant bacteria.

[European representations of birth control and abortions in Islamic societies and harems in the modern period].

PubMed

Soares, Marina Juliana de Oliveira

2017-01-01

Throughout the modern period, Islamic women (whether they lived in palaces or normal houses) resorted to measures to prevent conception or to induce abortion when pregnancy occurred. They used herbs and abortifacient drugs or relied on help from other women to eliminate unwanted pregnancies. Such practices were recorded by Europeans - in some cases, doctors - who traveled to Islamic regions and described these scenes in their narratives. In addition to abortions, infanticide was also observed in the imperial palaces. Here we discuss how these sources described birth control, and how they investigated the lascivious harem, a recurring trope in orientalist literature, from a medical perspective.

Arresting Evolution.

PubMed

Bull, James J; Barrick, Jeffrey E

2017-12-01

Evolution in the form of selective breeding has long been harnessed as a useful tool by humans. However, rapid evolution can also be a danger to our health and a stumbling block for biotechnology. Unwanted evolution can underlie the emergence of drug and pesticide resistance, cancer, and weeds. It makes live vaccines and engineered cells inherently unreliable and unpredictable, and therefore potentially unsafe. Yet, there are strategies that have been and can possibly be used to stop or slow many types of evolution. We review and classify existing population genetics-inspired methods for arresting evolution. Then, we discuss how genome editing techniques enable a radically new set of approaches to limit evolution. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Blockade of protease-activated receptor-4 (PAR4) provides robust antithrombotic activity with low bleeding.

PubMed

Wong, Pancras C; Seiffert, Dietmar; Bird, J Eileen; Watson, Carol A; Bostwick, Jeffrey S; Giancarli, Mary; Allegretto, Nick; Hua, Ji; Harden, David; Guay, Jocelyne; Callejo, Mario; Miller, Michael M; Lawrence, R Michael; Banville, Jacques; Guy, Julia; Maxwell, Brad D; Priestley, E Scott; Marinier, Anne; Wexler, Ruth R; Bouvier, Michel; Gordon, David A; Schumacher, William A; Yang, Jing

2017-01-04

Antiplatelet agents are proven efficacious treatments for cardiovascular and cerebrovascular diseases. However, the existing drugs are compromised by unwanted and sometimes life-threatening bleeding that limits drug usage or dosage. There is a substantial unmet medical need for an antiplatelet drug with strong efficacy and low bleeding risk. Thrombin is a potent platelet agonist that directly induces platelet activation via the G protein (heterotrimeric guanine nucleotide-binding protein)-coupled protease-activated receptors PAR1 and PAR4. A PAR1 antagonist is approved for clinical use, but its use is limited by a substantial bleeding risk. Conversely, the potential of PAR4 as an antiplatelet target has not been well characterized. Using anti-PAR4 antibodies, we demonstrated a low bleeding risk and an effective antithrombotic profile with PAR4 inhibition in guinea pigs. Subsequently, high-throughput screening and an extensive medicinal chemistry effort resulted in the discovery of BMS-986120, an orally active, selective, and reversible PAR4 antagonist. In a cynomolgus monkey arterial thrombosis model, BMS-986120 demonstrated potent and highly efficacious antithrombotic activity. BMS-986120 also exhibited a low bleeding liability and a markedly wider therapeutic window compared to the standard antiplatelet agent clopidogrel tested in the same nonhuman primate model. These preclinical findings define the biological role of PAR4 in mediating platelet aggregation. In addition, they indicate that targeting PAR4 is an attractive antiplatelet strategy with the potential to treat patients at a high risk of atherothrombosis with superior safety compared with the current standard of care. Copyright © 2017, American Association for the Advancement of Science.

Intimate partner violence and unwanted pregnancy, miscarriage, induced abortion, and stillbirth among a national sample of Bangladeshi women.

PubMed

Silverman, J G; Gupta, J; Decker, M R; Kapur, N; Raj, A

2007-10-01

To estimate (1) lifetime prevalence of physical and sexual victimisation from husbands among a national sample of Bangladeshi women, (2) associations of unwanted pregnancy and experiences of husband violence, and (3) associations of miscarriage, induced abortion, and fetal death/stillbirth and such victimisation. Cross-sectional, nationally representative study utilizing matched husband-wife data from the 2004 MEASURE Bangladesh Demographic Health Survey. Bangladesh. Married Bangladeshi women ages 13-40 years old (n = 2677). Bivariate and multivariate logistic regression analysis. Relations of intimate partner violence to unwanted pregnancy, miscarriage, induced abortion and stillbirth. Three out of four (75.6%) Bangladeshi women experienced violence from husbands. Less educated, poorer, and Muslim women were at greatest risk. Women experiencing violence from husbands were more likely to report both unwanted pregnancy (ORs(adj) 1.46-1.54) and a pregnancy loss in the form of miscarriage, induced abortion, or stillbirth (ORs(adj) 1.43-1.69). Assessed individually, miscarriage was more likely among victimised women (OR(adj) 1.81). A nonsignificant trend was detected for increased risk of induced abortion (OR(adj) 1.64); stillbirth was unrelated to violence from husbands. Intimate partner violence is extremely prevalent and relates to unwanted pregnancy and higher rates of pregnancy loss or termination, particularly miscarriages, among Bangladeshi women. Investigation of mechanisms responsible for these associations will be critical to developing interventions to improve maternal, fetal, and neonatal health. Such programmes may be vital to reducing the significant health and social costs associated with both husband violence and unwanted and adverse pregnancy outcomes.

Unwanted pregnancy and traditional self-induced abortion methods known among women aged 15 to 49.

PubMed

Sensoy, Nazli; Dogan, Nurhan; Sen, Kubra; Aslan, Halit; Tore-Baser, Ayca

2015-05-01

To determine the traditional methods known and used to terminate an unwanted pregnancy and the fertility characteristics of married women. The descriptive cross-sectional study was conducted in Turkey at Afyonkarahisar Zübeyde Hanim Child and Maternity Hospital's outpatient clinic between December 27, 2010 and January 7, 2011, and comprised married women aged 17 to 49 who presented for an examination. Questions related to socio-demographic and fertility characteristics as well as known and used traditional abortion methods were included in the questionnaire which was administered through face-to-face interviews. SPSS 18.0 was used for statistical analysis. The median age of the 600 women in the study was 29.5 (range: 17-49) years. Overall, 134 (22.3%) women had experienced an unwanted pregnancy. In 53 (39.6%) cases, the unwanted pregnancy had occurred between the ages of 30 and 39, and 116(86.6%) women had married when they were between 15 and 24 (p< 0.008) years old. Pregnancy had been concluded normally in 78(58.2%)women with an unwanted pregnancy and 34(35.8%)preferred the withdrawal method for contraception. Traditional abortion methods were known to 413(68.8%)women, but only 8(1.3%) had used any of them. The harms of using a traditional abortion method were known to 464(77.3%)women. Very few women used traditional abortion methods to terminate pregnancy. Knowing the characteristics of women and their need for family planning should be the first priority for the prevention of unwanted pregnancies.

Sexual violence and use of contraception among women with unwanted pregnancy in an Ngo Clinic, Addis Ababa.

PubMed

Dessalegn, Solomon; Kumbi, Solomon; Surur, Feruz

2008-10-01

Sexual violence is one of the most prevalent but underreported incidents. One among many consequences of sexual violence is unwanted pregnancy. To describe events related to and factors associated with sexual violence among women with unwanted pregnancy and describe knowledge and use of contraception among these women with unwanted pregnancy. This cross-sectional study was done at one NGO clinic in Addis Ababa. Data was collected from women with unwanted pregnancy seeking termination of pregnancy using a structured questionnaire in March 2003. Sociodemographic variables were analyzed with selected variables related to sexual violence, knowledge and practice of contraception among these women seeking termination of pregnancy. Of the 394 women seeking termination of pregnancy, there was unwelcome kiss in 26.9%, attempted rape in 23.9% and completed rape in 18.3%. Most, 63/72 (87.5%), of the victims of completed rape were below 25 years of age. A linear trend was observed with increasing age (P < 0.05, X2 = 24.365). Unmarried and economically dependent groups were more vulnerable to rape related pregnancy, P < 0.05. Only 18/72 (25%) reported to the police. Psychological problems were common in women with completed rape. Suicidal thoughts was reported by 8/72 (11%). Only 84/394 (21.3%) used contraceptives of which 29/84 (34.5%) used emergency contraceptives. Unwanted pregnancy as a result of rape was observed more in younger, unmarried and economically dependent women. Use of contraception including emergency contraception, reporting to legal authorities and health professionals was low.

The Science of Prescribed Fire: to Enable a Different Kind of Control

Treesearch

Timothy E. Paysen; Marcia G. Narog; Jack D. Cohen

1998-01-01

A paradigm shift from fire suppression to fire suppression and prescription requires a shift in emphasis from simply controlling wildfire occurrence and spread to one that includes controlling characteristics of prescribed fire. Suppression focuses on preventing unwanted effects that might result from wildfire occurrence. Prescription promotes desired effects by...

The politics and strategy of industry self-regulation: the pharmaceutical industry's principles for ethical direct-to-consumer advertising as a deceptive blocking strategy.

PubMed

Arnold, Denis G; Oakley, James L

2013-06-01

As the pharmaceutical industry lobbies European regulators to permit direct-to-consumer advertising (DTCA) of prescription drugs in the European Union, we found that five leading companies violated industry-developed and -promulgated standards for ethical advertising in the United States. Utilizing multiple data sources and methods, we demonstrate a consistent failure by companies that market erectile dysfunction drugs to comply with the industry's guiding principles for ethical DTCA over a four-year period despite pledges of compliance by company leaders. Noncompliance resulted in children being exposed to sexually themed promotional messages more than 100 billion times. We argue that the guidelines are a coordinated effort by the industry to prevent unwanted federal regulation, and we introduce the concept of a blocking strategy to explain company behavior and to advance theoretical understanding of firms' public affairs strategies. We recommend policy responses to prevent deceptive practices, protect children from adult content, and promote genuine health care education.

Automatic alignment of individual peaks in large high-resolution spectral data sets

NASA Astrophysics Data System (ADS)

Stoyanova, Radka; Nicholls, Andrew W.; Nicholson, Jeremy K.; Lindon, John C.; Brown, Truman R.

2004-10-01

Pattern recognition techniques are effective tools for reducing the information contained in large spectral data sets to a much smaller number of significant features which can then be used to make interpretations about the chemical or biochemical system under study. Often the effectiveness of such approaches is impeded by experimental and instrument induced variations in the position, phase, and line width of the spectral peaks. Although characterizing the cause and magnitude of these fluctuations could be important in its own right (pH-induced NMR chemical shift changes, for example) in general they obscure the process of pattern discovery. One major area of application is the use of large databases of 1H NMR spectra of biofluids such as urine for investigating perturbations in metabolic profiles caused by drugs or disease, a process now termed metabonomics. Frequency shifts of individual peaks are the dominant source of such unwanted variations in this type of data. In this paper, an automatic procedure for aligning the individual peaks in the data set is described and evaluated. The proposed method will be vital for the efficient and automatic analysis of large metabonomic data sets and should also be applicable to other types of data.

Cannabidiol: a promising drug for neurodegenerative disorders?

PubMed

Iuvone, Teresa; Esposito, Giuseppe; De Filippis, Daniele; Scuderi, Caterina; Steardo, Luca

2009-01-01

Neurodegenerative diseases represent, nowadays, one of the main causes of death in the industrialized country. They are characterized by a loss of neurons in particular regions of the nervous system. It is believed that this nerve cell loss underlies the subsequent decline in cognitive and motor function that patients experience in these diseases. A range of mutant genes and environmental toxins have been implicated in the cause of neurodegenerative disorders but the mechanism remains largely unknown. At present, inflammation, a common denominator among the diverse list of neurodegenerative diseases, has been implicated as a critical mechanism that is responsible for the progressive nature of neurodegeneration. Since, at present, there are few therapies for the wide range of neurodegenerative diseases, scientists are still in search of new therapeutic approaches to the problem. An early contribution of neuroprotective and antiinflammatory strategies for these disorders seems particularly desirable because isolated treatments cannot be effective. In this contest, marijuana derivatives have attracted special interest, although these compounds have always raised several practical and ethical problems for their potential abuse. Nevertheless, among Cannabis compounds, cannabidiol (CBD), which lacks any unwanted psychotropic effect, may represent a very promising agent with the highest prospect for therapeutic use.

Inhaler technique: facts and fantasies. A view from the Aerosol Drug Management Improvement Team (ADMIT).

PubMed

Levy, Mark L; Dekhuijzen, P N R; Barnes, P J; Broeders, M; Corrigan, C J; Chawes, B L; Corbetta, L; Dubus, J C; Hausen, Th; Lavorini, F; Roche, N; Sanchis, J; Usmani, Omar S; Viejo, J; Vincken, W; Voshaar, Th; Crompton, G K; Pedersen, Soren

2016-04-21

Health professionals tasked with advising patients with asthma and chronic obstructive pulmonary disease (COPD) how to use inhaler devices properly and what to do about unwanted effects will be aware of a variety of commonly held precepts. The evidence for many of these is, however, lacking or old and therefore in need of re-examination. Few would disagree that facilitating and encouraging regular and proper use of inhaler devices for the treatment of asthma and COPD is critical for successful outcomes. It seems logical that the abandonment of unnecessary or ill-founded practices forms an integral part of this process: the use of inhalers is bewildering enough, particularly with regular introduction of new drugs, devices and ancillary equipment, without unnecessary and pointless adages. We review the evidence, or lack thereof, underlying ten items of inhaler 'lore' commonly passed on by health professionals to each other and thence to patients. The exercise is intended as a pragmatic, evidence-informed review by a group of clinicians with appropriate experience. It is not intended to be an exhaustive review of the literature; rather, we aim to stimulate debate, and to encourage researchers to challenge some of these ideas and to provide new, updated evidence on which to base relevant, meaningful advice in the future. The discussion on each item is followed by a formal, expert opinion by members of the ADMIT Working Group.

The welfare significance of the castration of cattle: a review.

PubMed

Stafford, K J; Mellor, D J

2005-10-01

Castration is an ancient husbandry procedure used to produce docile cattle for draught work, to reduce unwanted breeding, and to modify carcass quality. All the physical methods used to castrate cattle have side-effects and cause pain. The plasma cortisol response to castration using Burdizzo clamps and, by inference, the acute pain experienced, is less than that caused by surgical, rubber-ring or latex-band castration. The cortisol response may be influenced by the age of the animal castrated, but this has not been well defined. Local anaesthesia virtually eliminates the cortisol response, and thus the acute pain, caused by rubber-ring or latex-band castration, but needs to be combined with a systemic analgesic such as the non-steroidal anti-inflammatory drug ketoprofen to eliminate the cortisol response to Burdizzo or surgical castration. When used alone, ketoprofen sometimes reduces the cortisol response to Burdizzo or surgical castration but may need to be accompanied by local anaesthesia to eliminate the pain-induced behaviour seen during the castration process itself. Thus, pharmacological methods are available to virtually eliminate the acute pain experienced by calves during the 12 h following castration. The use of these methods is an additional cost for farmers and may be limited by the availability of drugs for farmers to use and the scarcity of veterinarians in farm animal practice.

Stable RNA nanoparticles as potential new generation drugs for cancer therapy☆

PubMed Central

Shu, Yi; Pi, Fengmei; Sharma, Ashwani; Rajabi, Mehdi; Haque, Farzin; Shu, Dan; Leggas, Markos; Evers, B. Mark; Guo, Peixuan

2014-01-01

Human genome sequencing revealed that only ~1.5% of the DNA sequence coded for proteins. More and more evidence has uncovered that a substantial part of the 98.5% so-called “junk” DNAs actually code for noncoding RNAs. Two milestones, chemical drugs and protein drugs, have already appeared in the history of drug development, and it is expected that the third milestone in drug development will be RNA drugs or drugs that target RNA. This review focuses on the development of RNA therapeutics for potential cancer treatment by applying RNA nanotechnology. A therapeutic RNA nanoparticle is unique in that its scaffold, ligand, and therapeutic component can all be composed of RNA. The special physicochemical properties lend to the delivery of siRNA, miRNA, ribozymes, or riboswitches; imaging using fluogenenic RNA; and targeting using RNA aptamers. With recent advances in solving the chemical, enzymatic, and thermodynamic stability issues, RNA nanoparticles have been found to be advantageous for in vivo applications due to their uniform nano-scale size, precise stoichiometry, polyvalent nature, low immunogenicity, low toxicity, and target specificity. In vivo animal studies have revealed that RNA nanoparticles can specifically target tumors with favorable pharmacokinetic and pharmacodynamic parameters without unwanted accumulation in normal organs. This review summarizes the key studies that have led to the detailed understanding of RNA nanoparticle formation as well as chemical and thermodynamic stability issue. The methods for RNA nanoparticle construction, and the current challenges in the clinical application of RNA nanotechnology, such as endosome trapping and production costs, are also discussed. PMID:24270010

Patient participation in a clinic-based community pharmacy medication take-back program.

PubMed

Lystlund, Stefanie; Stevens, Eric; Planas, Lourdes G; Marcy, Todd R

2014-01-01

To describe patient interest and involvement in participating in a clinic-based community pharmacy drug take-back program to dispose of unused, unwanted, or expired (UUE) medications and to identify patients' reasons for participating in the program. A convenience sample of patients at the University of Oklahoma Family Medicine Pharmacy was recruited to complete a needs assessment survey regarding interest in drug take-back programs and current practices for handling UUE medications. Participants who purchased a postage-paid drug disposal envelope were asked to complete a program survey identifying sources of UUE medications, experience with drug take-back programs, and reasons for participation. These participants were later contacted for a follow-up telephone survey regarding their experience with the program and medications sent back. 62 needs assessment surveys were collected. 61% of patients reported interest in a drug take-back program. 57% reported having no UUE medications at home. Commonly reported UUE handling practices included disposal in the garbage (53.2%) or sewer (29.0%) and home storage (17.7%). 15 disposal envelopes were sold to 10 participants whose most common reasons for participation included concern about the safety of household members, accidental or intentional ingestion, and environmental impact. For 4 patients who returned a median of 9.5 prescriptions, the most common class of returned drugs was antibiotics (19.0%). Interest in drug take-back programs exists, but awareness and availability of continuous programs is limited. Programs may be more successful if offered at no cost to patients. Future studies are needed on the types of medications sent back and specific reasons for accumulation.

The clinical outcome of skeletal anchorage in interceptive treatment (in growing patients) for class III malocclusion.

PubMed

Meyns, J; Brasil, D M; Mazzi-Chaves, J F; Politis, C; Jacobs, R

2018-04-27

A systematic review of the literature was performed regarding the clinical outcome (effectiveness) of bone anchorage devices in interceptive treatment for class III malocclusion. A search of Embase, PubMed and Web of Science databases yielded 285 papers. An additional two articles were retrieved through manual searching of the reference lists. After initial abstract selection, 32 potentially eligible articles were screened in detail, resulting in a final number of eight articles included in this review. Insufficient evidence was found regarding the effects of skeletal anchorage in interceptive class III treatment to support definitive conclusions on long-term skeletal effects and stability. In the short term, it seems that bone anchors can provide more skeletal effect with less dentoalveolar compensations and less unwanted vertical changes. This does not always exclude the use of a face mask. The use of miniscrews as skeletal anchorage device does not seem to provide more skeletal effect, although it could minimize the unwanted dental effects in the upper jaw. No information regarding the need for orthognathic surgery, orthodontic treatment time or patient compliance and complications was found in the selected articles. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Efficacy, patient-reported outcomes and safety profile of ATX-101 (deoxycholic acid), an injectable drug for the reduction of unwanted submental fat: results from a phase III, randomized, placebo-controlled study.

PubMed

Ascher, B; Hoffmann, K; Walker, P; Lippert, S; Wollina, U; Havlickova, B

2014-12-01

Unwanted submental fat (SMF) may result in an unattractive chin profile and dissatisfaction with appearance. An approved and rigorously tested non-surgical method for SMF reduction is lacking. To evaluate the efficacy and safety of ATX-101 for the pharmacological reduction of unwanted SMF in a phase III randomized, double-blind, placebo-controlled study. Patients (n = 360) with moderate or severe SMF were randomized to receive ATX-101 1 or 2 mg/cm(2) or placebo injected into their SMF for up to four treatments ~28 days apart, with a 12-week follow-up. Coprimary efficacy endpoints were the proportions of treatment responders, defined as a ≥1-point reduction in SMF on the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS), and those satisfied with their appearance in association with their face and chin after treatment on the Subject Self-Rating Scale (SSRS score ≥4). Secondary efficacy endpoints included a ≥1-point improvement in SMF on the Patient-Reported Submental Fat Rating Scale (PR-SMFRS) and changes in the Patient-Reported Submental Fat Impact Scale (PR-SMFIS). Additional patient-reported outcomes and changes in the Skin Laxity Rating Scale were recorded. Adverse events (AEs) and laboratory test results were monitored. Compared with placebo, a greater proportion of patients treated with ATX-101 1 and 2 mg/cm(2) showed a ≥1-point improvement in CR-SMFRS (58.3% and 62.3%, respectively, vs. 34.5% with placebo; P < 0.001) and patient satisfaction (SSRS score ≥4) with the appearance of their face and chin (68.3% and 64.8%, respectively, vs. 29.3%; P < 0.001). Patient-reported secondary efficacy endpoints showed significant improvements in SMF severity (PR-SMFRS; P = 0.009 for ATX-101 1 mg/cm(2) , P < 0.001 for ATX-101 2 mg/cm(2) vs. placebo) and emotions and perceived self-image (PR-SMFIS; P < 0.001). No overall worsening of skin laxity was observed. AEs were mostly transient, mild to moderate in intensity and localized to the treatment area. ATX-101 was effective and well tolerated, and may be an alternative to surgery for patients desiring improvement of their submental profile. © 2014 The Authors Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of the European Academy of Dermatology and Venereology.

Efficacy, patient-reported outcomes and safety profile of ATX-101 (deoxycholic acid), an injectable drug for the reduction of unwanted submental fat: results from a phase III, randomized, placebo-controlled study

PubMed Central

Ascher, B; Hoffmann, K; Walker, P; Lippert, S; Wollina, U; Havlickova, B

2014-01-01

Background Unwanted submental fat (SMF) may result in an unattractive chin profile and dissatisfaction with appearance. An approved and rigorously tested non-surgical method for SMF reduction is lacking. Objective To evaluate the efficacy and safety of ATX-101 for the pharmacological reduction of unwanted SMF in a phase III randomized, double-blind, placebo-controlled study. Methods Patients (n = 360) with moderate or severe SMF were randomized to receive ATX-101 1 or 2 mg/cm2 or placebo injected into their SMF for up to four treatments ∼28 days apart, with a 12-week follow-up. Coprimary efficacy endpoints were the proportions of treatment responders, defined as a ≥1-point reduction in SMF on the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS), and those satisfied with their appearance in association with their face and chin after treatment on the Subject Self-Rating Scale (SSRS score ≥4). Secondary efficacy endpoints included a ≥1-point improvement in SMF on the Patient-Reported Submental Fat Rating Scale (PR-SMFRS) and changes in the Patient-Reported Submental Fat Impact Scale (PR-SMFIS). Additional patient-reported outcomes and changes in the Skin Laxity Rating Scale were recorded. Adverse events (AEs) and laboratory test results were monitored. Results Compared with placebo, a greater proportion of patients treated with ATX-101 1 and 2 mg/cm2 showed a ≥1-point improvement in CR-SMFRS (58.3% and 62.3%, respectively, vs. 34.5% with placebo; P < 0.001) and patient satisfaction (SSRS score ≥4) with the appearance of their face and chin (68.3% and 64.8%, respectively, vs. 29.3%; P < 0.001). Patient-reported secondary efficacy endpoints showed significant improvements in SMF severity (PR-SMFRS; P = 0.009 for ATX-101 1 mg/cm2, P < 0.001 for ATX-101 2 mg/cm2 vs. placebo) and emotions and perceived self-image (PR-SMFIS; P < 0.001). No overall worsening of skin laxity was observed. AEs were mostly transient, mild to moderate in intensity and localized to the treatment area. Conclusion ATX-101 was effective and well tolerated, and may be an alternative to surgery for patients desiring improvement of their submental profile. PMID:24605812

Cannabis and cannabinoids: pharmacology and rationale for clinical use.

PubMed

Pertwee, R G

1999-10-01

It is now known that there are at least two types of cannabinoid receptors. These are CB1 receptors, present mainly on central and peripheral neurones, and CB2 receptors, present mainly on immune cells. Endogenous cannabinoid receptor agonists ('endocannabinoids') have also been identified. The discovery of this 'endogenous cannabinoid system' has led to the development of selective CB1 and CB2 receptor ligands and fueled renewed interest in the clinical potential of cannabinoids. Two cannabinoid CB1 receptor agonists are already used clinically, as antiemetics or as appetite stimulants. These are D 9 - tetrahydrocannabinol (THC) and nabilone. Other possible uses for CB1 receptor agonists include the suppression of muscle spasm/spasticity associated with multiple sclerosis or spinal cord injury, the relief of chronic pain and the management of glaucoma and bronchial asthma. CB1 receptor antagonists may also have clinical applications, e. g. as appetite suppressants and in the management of schizophrenia or disorders of cognition and memory. So too may CB2 receptor ligands and drugs that activate cannabinoid receptors indirectly by augmenting endocannabinoid levels at cannabinoid receptors. When taken orally, THC seems to undergo variable absorption and to have a narrow 'therapeutic window' (dose range in which it is effective without producing significant unwanted effects). This makes it difficult to predict an oral dose that will be both effective and tolerable to a patient and indicates a need for better cannabinoid formulations and modes of administration. For the therapeutic potential of cannabis or CB1 receptor agonists to be fully exploited, it will be important to establish objectively and conclusively (a) whether these agents have efficacy against selected symptoms that is of clinical significance and, if so, whether the benefits outweigh the risks, (b) whether cannabis has therapeutic advantages over individual cannabinoids, (c) whether there is a need for additional drug treatments to manage any of the disorders against which cannabinoids are effective, and (d) whether it will be possible to develop drugs that have reduced psychotropic activity and yet retain the ability to act through CB1 receptors to produce their sought-after effects. Copyright 1999 S. Karger GmbH, Freiburg

40 CFR 262.214 - Laboratory management plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Waste Determination and Accumulation of Unwanted Material for Laboratories Owned by Eligible Academic Entities § 262.214 Laboratory management plan. An eligible academic entity must develop and retain a... a site-specific document that describes how the eligible academic entity will manage unwanted...

40 CFR 262.214 - Laboratory management plan.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Waste Determination and Accumulation of Unwanted Material for Laboratories Owned by Eligible Academic Entities § 262.214 Laboratory management plan. An eligible academic entity must develop and retain a... a site-specific document that describes how the eligible academic entity will manage unwanted...

40 CFR 262.214 - Laboratory management plan.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Waste Determination and Accumulation of Unwanted Material for Laboratories Owned by Eligible Academic Entities § 262.214 Laboratory management plan. An eligible academic entity must develop and retain a... a site-specific document that describes how the eligible academic entity will manage unwanted...

Home and parenting resources available to siblings depending on their birth intention status.

PubMed

Barber, Jennifer S; East, Patricia L

2009-01-01

This study examines the differential availability of family and parenting resources to children depending on their birth planning status. The National Longitudinal Survey of Youth data were analyzed, 3,134 mothers and their 5,890 children (M = 7.1 years, range = 1 month-14.8 years), of whom 63% were intended at conception, 27% were mistimed, and 10% were unwanted. Fixed-effects models show that unwanted and mistimed children had fewer resources than intended siblings. Parents' emotional resources to older children decreased after the birth of a mistimed sibling. Findings suggest that cognitive and emotional resources are differentially available to children within a family depending on intention status and that unintended births lead to decreased parental resources for older children in the household.

Calcium and Cancer Prevention: Strengths and Limits of the Evidence

MedlinePlus

... to unwanted side effects . The U.S. Department of Agriculture’s 1994–1996 Continuing Survey of Food Intakes by ... record_id=5776&page=71 . U.S. Department of Agriculture. Data tables: Results from USDA’s 1994–96 Continuing ...

Predictors of mistimed, and unwanted pregnancies among women of childbearing age in Rufiji, Kilombero, and Ulanga districts of Tanzania

PubMed Central

2014-01-01

Background While unintended pregnancies pose a serious threat to the health and well-being of families globally, characteristics of Tanzanian women who conceive unintentionally are rarely documented. This analysis identifies factors associated with unintended pregnancies—both mistimed and unwanted—in three rural districts of Tanzania. Methods A cross-sectional survey of 2,183 random households was conducted in three Tanzanian districts of Rufiji, Kilombero, and Ulanga in 2011 to assess women’s health behavior and service utilization patterns. These households produced 3,127 women age 15+ years from which 2,199 gravid women aged 15–49 were selected for the current analysis. Unintended pregnancies were identified as either mistimed (wanted later) or unwanted (not wanted at all). Correlates of mistimed, and unwanted pregnancies were identified through Chi-squared tests to assess associations and multinomial logistic regression for multivariate analysis. Results Mean age of the participants was 32.1 years. While 54.1% of the participants reported that their most recent pregnancy was intended, 32.5% indicated their most recent pregnancy as mistimed and 13.4% as unwanted. Multivariate analysis revealed that young age (<20 years), and single marital status were significant predictors of both mistimed and unwanted pregnancies. Lack of inter-partner communication about family planning increased the risk of mistimed pregnancy significantly, and multi-gravidity was shown to significantly increase the risk of unwanted pregnancy. Conclusions About one half of women in Rufiji, Kilombero, and Ulanga districts of Tanzania conceive unintentionally. Women, especially the most vulnerable should be empowered to avoid pregnancy at their own will and discretion. PMID:25102924

In Silico Models for Ecotoxicity of Pharmaceuticals.

PubMed

Roy, Kunal; Kar, Supratik

2016-01-01

Pharmaceuticals and their active metabolites are one of the significantly emerging environmental toxicants. The major routes of entry of pharmaceuticals into the environment are industries, hospitals, or direct disposal of unwanted or expired drugs made by the patient. The most important and distinct features of pharmaceuticals are that they are deliberately designed to have an explicit mode of action and designed to exert an effect on humans and other living systems. This distinctive feature makes pharmaceuticals and their metabolites different from other chemicals, and this necessitates the evaluation of the direct effects of pharmaceuticals in various environmental compartments as well as to living systems. In this background, the alarming situation of ecotoxicity of diverse pharmaceuticals have forced government and nongovernment regulatory authorities to recommend the application of in silico methods to provide quick information about the risk assessment and fate properties of pharmaceuticals as well as their ecological and indirect human health effects. This chapter aims to offer information regarding occurrence of pharmaceuticals in the environment, their persistence, environmental fate, and toxicity as well as application of in silico methods to provide information about the basic risk management and fate prediction of pharmaceuticals in the environment. Brief ideas about toxicity endpoints, available ecotoxicity databases, and expert systems employed for rapid toxicity predictions of ecotoxicity of pharmaceuticals are also discussed.

Intravenous non-opioid analgesia for peri- and postoperative pain management: a scientific review of intravenous acetaminophen and ibuprofen

PubMed Central

Koh, Wonuk; Nguyen, Kimngan Pham

2015-01-01

Pain is a predictable consequence following operations, but the management of postoperative pain is another challenge for anesthesiologists and inappropriately controlled pain may lead to unwanted outcomes in the postoperative period. Opioids are indeed still at the mainstream of postoperative pain control, but solely using only opioids for postoperative pain management may be connected with risks of complications and adverse effects. As a consequence, the concept of multimodal analgesia has been proposed and is recommended whenever possible. Acetaminophen is one of the most commonly used analgesic and antipyretic drug for its good tolerance and high safety profiles. The introduction of intravenous form of acetaminophen has led to a wider flexibility of its use during peri- and postoperative periods, allowing the early initiation of multimodal analgesia. Many studies have revealed the efficacy, safety and opioid sparing effects of intravenous acetaminophen. Intravenous ibuprofen has also shown to be well tolerated and demonstrated to have significant opioid sparing effects during the postoperative period. However, the number of randomized controlled trials confirming the efficacy and safety is small and should be used in caution in certain group of patients. Intravenous acetaminophen and ibuprofen are important options for multimodal postoperative analgesia, improving pain and patient satisfaction. PMID:25664148

Intravenous non-opioid analgesia for peri- and postoperative pain management: a scientific review of intravenous acetaminophen and ibuprofen.

PubMed

Koh, Wonuk; Nguyen, Kimngan Pham; Jahr, Jonathan S

2015-02-01

Pain is a predictable consequence following operations, but the management of postoperative pain is another challenge for anesthesiologists and inappropriately controlled pain may lead to unwanted outcomes in the postoperative period. Opioids are indeed still at the mainstream of postoperative pain control, but solely using only opioids for postoperative pain management may be connected with risks of complications and adverse effects. As a consequence, the concept of multimodal analgesia has been proposed and is recommended whenever possible. Acetaminophen is one of the most commonly used analgesic and antipyretic drug for its good tolerance and high safety profiles. The introduction of intravenous form of acetaminophen has led to a wider flexibility of its use during peri- and postoperative periods, allowing the early initiation of multimodal analgesia. Many studies have revealed the efficacy, safety and opioid sparing effects of intravenous acetaminophen. Intravenous ibuprofen has also shown to be well tolerated and demonstrated to have significant opioid sparing effects during the postoperative period. However, the number of randomized controlled trials confirming the efficacy and safety is small and should be used in caution in certain group of patients. Intravenous acetaminophen and ibuprofen are important options for multimodal postoperative analgesia, improving pain and patient satisfaction.

Silymarin and its active component silibinin act as novel therapeutic alternatives for salivary gland cancer by targeting the ERK1/2-Bim signaling cascade.

PubMed

Choi, Eun-Sun; Oh, Sejun; Jang, Boonsil; Yu, Hyun-Ju; Shin, Ji-Ae; Cho, Nam-Pyo; Yang, In-Hyoung; Won, Dong-Hoon; Kwon, Hye-Jeong; Hong, Seong Doo; Cho, Sung-Dae

2017-06-01

Approximately 20% of all salivary gland cancer patients who are treated with current treatment modalities will ultimately develop metastases. Its most common form, mucoepidermoid carcinoma (MEC) is a highly aggressive tumor with an overall 5-year survival rate of ~30%. Until now, several chemotherapeutic drugs have been tested for the treatment of salivary gland tumors, but the results have been disappointing and the drugs often cause unwanted side effects. Therefore, several recent studies have focused on the potential of alternative and/or complementary therapeutic options, including the use of silymarin. The effects of silymarin and its active component silibinin on salivary gland cancer-derived MC3 and HN22 cells and their underlying molecular mechanisms were examined using trypan blue exclusion, 4'-6-diamidino-2-phenylindole (DAPI) staining, Live/Dead, Annexin V/PI staining, mitochondrial membrane potential (ΔΨm) measurement, quantitative RT-PCR, soft agar colony formation and Western blotting analyses. We found that silymarin and silibinin dramatically increased the expression of the pro-apoptotic protein Bim in a concentration- and time-dependent manner and, concomitantly, induced apoptosis in MC3 and HN22 cells. We also found that ERK1/2 signaling inhibition successfully sensitized these cells to the apoptotic effects of silymarin and silibinin, which indicates that the ERK1/2 signaling pathway may act as an upstream regulator that modulates the silymarin/silibinin-induced Bim signaling pathway. Taken together, we conclude that ERK1/2 signaling pathway inhibition by silymarin and silibinin increases the expression of the pro-apoptotic Bcl-2 family member Bim which, subsequently, induces mitochondria-mediated apoptosis in salivary gland cancer-derived cells.

A Risky Boundary: Unwanted Sexual Behaviour among Youth

ERIC Educational Resources Information Center

de Bruijn, Paula; Burrie, Ingrid; van Wel, Frits

2006-01-01

The aim of this research was to explore unwanted sexual behaviour amongst young people. Sexual aggression was operationalized at three levels: "verbal", "non-verbal/intimidating" and "physically violent". A total of 1,700 Dutch adolescents completed a questionnaire that included six clusters of possible determinants…

Reexamining issues of conceptualization and willing consent: the hidden role of coercion in experiences of sexual acquiescence.

PubMed

Conroy, Nicole E; Krishnakumar, Ambika; Leone, Janel M

2015-07-01

This study problematizes the literature's conceptualization of sexual compliance, predominantly defined as willing participation in, and consent to, unwanted sexual activity in the absence of immediate partner pressure. Using a feminist theoretical framework, we argue that covert forms of social coercion, including normalized expectations for heterosexual women to participate in sexual activity and maintain relationship satisfaction, ultimately pressure women into participating in unwanted sexual activity. In other words, immediate partner pressure is not necessary for a sexually coercive experience to occur. Results of the current study indicate that relationship control and media influence significantly predict sexual acquiescence, and women acquiesce to unwanted sexual activity in an effort to maintain relationships and partner satisfaction as well as to avoid negative outcomes. Women cite various forms of social coercion, such as fulfilling sexual scripts and relationship obligations, as primary reasons for participating in unwanted sexual activity without resisting their partners. © The Author(s) 2014.

Adult Sexual Experiences as a Mediator Between Child Abuse and Current Secretory Immunoglobulin A Levels.

PubMed

Waldron, Jonathan C; Scarpa, Angela; Kim-Spoon, Jungmeen; Coe, Christopher L

2016-03-01

The current study investigated whether a history of child abuse is a predictor of adult immune status, with unwanted adult sexual experiences as a proximal mediator. Participants included 89 young adult women (M(age) = 19.24) who were classified as having experienced no child abuse, child physical abuse, or child sexual abuse, based upon self-reported victimization history before 14 years of age. Participants also reported on unwanted sexual experiences in young adulthood and provided four saliva samples, which were collected over two consecutive days to determine secretory immunoglobulin A (sIgA). Age and negative life events were considered as covariates. The results indicated that adult sexual victimization partially mediated the relationship between child abuse (physical and sexual) and sIgA. Specifically, child abuse experiences predicted more adult sexual victimization experiences, which in turn predicted lower sIgA levels. These findings support long-term health effects of victimization, and suggest that the influence of child abuse on sIgA may be perpetuated through adult victimization. Prevention efforts should aim to empower child maltreatment survivors with skills to prevent adult re-victimization. By thwarting future unwanted sexual experiences in adulthood, individuals will be better protected from the health impairments associated with early abuse experiences. © The Author(s) 2014.

A dual-mode disturbance-accommodating controller for the Hubble Space Telescope

NASA Astrophysics Data System (ADS)

Addington, Stewart; Johnson, C. D.

Cyclic thermal expansions and mechanical stiction effects in the Solar Arrays on the Hubble Space Telescope (HST) are triggering repeated occurrences of damped, relaxation-type flex-body vibrations of the solar arrays. Those solar array vibrations are, in turn, causing unwanted, oscillating disturbance torques on the HST main body, which cause unwanted deviations of the telescope from its specified pointing direction. In this paper we propose two strategies one can adopt in designing a telescope-pointing controller to cope with the aforementioned disturbances: (1) a `total isolation' (TI) control strategy whereby the HST controller torques are designed to adaptively counteract and cancel-out the persistent disturbing torques that are causing the unwanted telescope motions, and (2) an `array damping' (AD) control strategy whereby the HST controller torques are used to actively augment the natural dampening of the solar array vibrations and the attendant telescope motions, between triggerings of the stiction-related flex-body relaxation oscillations. Using the principles of Disturbance-Accommodating Control (DAC) Theory a dual-mode controller for a generic, planar-motion (single-axis) model of the HST is proposed. This controller incorporates both the TI and AD modes of disturbance-accommodation. Simulation studies of the closed-loop system using generic parameter values clearly indicate, qualitatively, the enhanced pointing-performance such a controller can achieve.

[Unwanted adolescent pregnancy and post-partum utilization of contraceptive methods].

PubMed

Núñez-Urquiza, Rosa María; Hernández-Prado, Bernardo; García-Barrios, Cecilia; González, Dolores; Walker, Dylis

2003-01-01

To describe the proportion of unwanted pregnancies among all pregnant adolescents, its association with sociodemographic characteristics, and the use of post-partum contraceptive methods. A cross-sectional study was conducted among 220 women between 13 and 19 years of age, in two semi-urban municipalities of the State of Morelos, Mexico, interviewed between 1992 and 1994. Women were interviewed at home, six to twelve weeks after their delivery date. Women were asked whether they had wanted their last pregnancy, and about knowledge and use of contraceptive methods after delivery. Adolescent pregnancies accounted for 17% of all births registered in these two municipalities. Among all adolescent mother 22.73% reported that their pregnancy had not been wanted. A positive association was found between the lack of access to health services provided by public medical insurance systems (Instituto Mexicano del Seguro Social IMSS and Instituto de Seguridad y Servicios Sociales para los Trabajadores del Estado ISSSTE) and unwanted pregnancy (adjusted OR = 3.03, 95% CI (1.31, 7.) An association was also found between living in an urban community (adjusted OR = 2.16, 95% CI (1.08, 4.33) and an unwanted pregnancy. Among all adolescent mothers, 91.3% were familiar with "the pill" as a contraceptive method; 84.72% knew about the IUD, and 63.68% knew about the condom. However, only 35% of them were actually using an effective contraceptive method six weeks after delivery. No difference in frequency of contraceptive use was found among the adolescent mothers, according to whether they wanted their last pregnancy. Only 43.39% of mothers who delivered at hospitals or health centers were using an effective contraceptive method. These findings suggest that there is a great potential for family planning programs to target adolescents, and that the use of contraceptive methods after delivery should be promoted among adolescent mothers, especially those lacking access to public medical insurance and those living in semi-urban settings. It is also recommended to conduct studies on family planning education programs that can be introduced earlier in the school system in Mexico.

Normalization of RNA-seq data using factor analysis of control genes or samples

PubMed Central

Risso, Davide; Ngai, John; Speed, Terence P.; Dudoit, Sandrine

2015-01-01

Normalization of RNA-seq data has proven essential to ensure accurate inference of expression levels. Here we show that usual normalization approaches mostly account for sequencing depth and fail to correct for library preparation and other more-complex unwanted effects. We evaluate the performance of the External RNA Control Consortium (ERCC) spike-in controls and investigate the possibility of using them directly for normalization. We show that the spike-ins are not reliable enough to be used in standard global-scaling or regression-based normalization procedures. We propose a normalization strategy, remove unwanted variation (RUV), that adjusts for nuisance technical effects by performing factor analysis on suitable sets of control genes (e.g., ERCC spike-ins) or samples (e.g., replicate libraries). Our approach leads to more-accurate estimates of expression fold-changes and tests of differential expression compared to state-of-the-art normalization methods. In particular, RUV promises to be valuable for large collaborative projects involving multiple labs, technicians, and/or platforms. PMID:25150836

Effect of the breakup context on unwanted pursuit behavior perpetration between former partners.

PubMed

De Smet, Olivia; Buysse, Ann; Brondeel, Ruben

2011-07-01

Former partners comprise the most important subgroup of stalkers. However, contextual factors related to the breakup are hardly examined to explain ex-partner pursuit. In a community sample of 194 separated persons, about one-fifth perpetrated at least one unwanted pursuit behavior in the past 2 weeks. Being female, lowly educated, and socially undesirable raised the number of perpetrated behaviors. Beyond these effects, the number of behaviors increased when the cause of the break was attributed to the ex-partner or external factors and when the ex was appraised as the breakup initiator. Breakup reasons, the ex-partner's lack in meeting family obligations and own infidelity, also related to pursuit behaviors albeit inferior to subjective attributions and appraisals of initiation. Finally, participants who felt more anxious or lonely negative showed more behaviors. The results enlighten that the breakup context gains further attention. Clinical treatment might benefit from fostering cognitive reconstructions and breakup adjustment. © 2011 American Academy of Forensic Sciences.

Removal of unwanted fluid

NASA Astrophysics Data System (ADS)

Subudhi, Sudhakar; Sreenivas, K. R.; Arakeri, Jaywant H.

2013-01-01

This work is concerned with the removal of unwanted fluid through the source-sink pair. The source consists of fluid issuing out of a nozzle in the form of a jet and the sink is a pipe that is kept some distance from the source pipe. Of concern is the percentage of source fluid sucked through the sink. The experiments have been carried in a large glass water tank. The source nozzle diameter is 6 mm and the sink pipe diameter is either 10 or 20 mm. The horizontal and vertical separations and angles between these source and sink pipes are adjustable. The flow was visualized using KMnO4 dye, planer laser induced fluorescence and particle streak photographs. To obtain the effectiveness (that is percentage of source fluid entering the sink pipe), titration method is used. The velocity profiles with and without the sink were obtained using particle image velocimetry. The sink flow rate to obtain a certain effectiveness increase dramatically with lateral separation. The sink diameter and the angle between source and the sink axes don't influence effectiveness as much as the lateral separation.

Dapagliflozin (Forxiga) for type 2 diabetes?

PubMed

2013-09-01

In the UK, diabetes mellitus affects around 3 million people, of whom over 90% have type 2 diabetes. Aims of treatment include minimising long-term complications (e.g. cardiovascular disease, blindness, chronic kidney disease, premature mortality) and avoiding unwanted effects of treatment (e.g. severe hypoglycaemia, weight gain). Management of diabetes includes patient support and education; addressing symptoms; lifestyle modification; targeting associated risk factors for cardiovascular disease; and surveillance for, and management of, complications including treatment-related hypoglycaemia. Dapagliflozin (Forxiga) belongs to a new class of oral glucose-lowering drugs that inhibit renal glucose reabsorption and promote glycosuria. It is licensed in the UK in adults with type 2 diabetes as monotherapy when diet and exercise alone do not provide adequate glycaemic control and who are unable to tolerate metformin; or, as add-on therapy, with other glucose-lowering agents including insulin, when these, with diet and exercise, do not provide adequate glycaemic control. The company's advertising materials claim that dapagliflozin provides a "novel method of controlling excess glucose" with "secondary benefit of weight loss". Here, we review the evidence for the use of dapagliflozin in the management of type 2 diabetes mellitus.

Individual Biomarkers Using Molecular Personalized Medicine Approaches.

PubMed

Zenner, Hans P

2017-01-01

Molecular personalized medicine tries to generate individual predictive biomarkers to assist doctors in their decision making. These are thought to improve the efficacy and lower the toxicity of a treatment. The molecular basis of the desired high-precision prediction is modern "omex" technologies providing high-throughput bioanalytical methods. These include genomics and epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, imaging, and functional analyses. In most cases, producing big data also requires a complex biomathematical analysis. Using molecular personalized medicine, the conventional physician's check of biomarker results may no longer be sufficient. By contrast, the physician may need to cooperate with the biomathematician to achieve the desired prediction on the basis of the analysis of individual big data typically produced by omex technologies. Identification of individual biomarkers using molecular personalized medicine approaches is thought to allow a decision-making for the precise use of a targeted therapy, selecting the successful therapeutic tool from a panel of preexisting drugs or medical products. This should avoid the treatment of nonresponders and responders that produces intolerable unwanted effects. © 2017 S. Karger AG, Basel.

Hypnotic Effect of Ocimum basilicum on Pentobarbital-Induced Sleep in Mice.

PubMed

Askari, Vahid Reza; Baradaran Rahimi, Vafa; Ghorbani, Ahmad; Rakhshandeh, Hassan

2016-07-01

Sleep disorders are accompanied by several complications, and currently used soporific drugs can induce unwanted effects such as psychomotor impairment, tolerance, amnesia, and rebound insomnia. The present study was carried out to investigate if Ocimum basilicum has a sleep-prolonging effect. This work was an experimental study on 72 mice which were randomly divided into 9 groups: saline (control); diazepam (3 mg/kg, positive control); hydro-alcoholic extract (HAE) of Ocimum basilicum (25, 50, or 100 mg/kg); ethyl acetate fraction (EAF, 50 mg/kg); n-butanol fraction (NBF, 50 mg/kg); water fraction (WF, 50 mg/kg); and saline containing 10% DMSO (vehicle for EAF and NBF). All the test compounds were injected intraperitoneally (IP) 30 minutes before pentobarbital administration (30 mg/kg). Duration and latency of pentobarbital-induced sleep were recorded. Also, LD50 of HAE was determined and the cytotoxicity of HAE was tested on neural and fibroblast cells using the MTT assay. HAE increased the duration of pentobarbital-induced sleep at doses of 25, 50, and 100 mg/kg (P < 0.001). The hypnotic effect of HAE was comparable to that induced by diazepam. Similarly, WF, EAF, and NBF at 50 mg/kg could increase sleep duration. The sleep latency was decreased by HAE (P < 0.01 - P < 0.001) and NBF (P < 0.001), but not by WF and EAF. The LD50 value for HAE was found to be 2.4 g/kg. HAE had no effect on the viability of neuronal PC12 cells and L929 fibroblast cells. The present data demonstrated that Ocimum basilicum potentiates sleeping behaviors without any cytotoxicity. The main component (s) responsible for the hypnotic effects of this plant is most likely a non-polar agent (s) which is found in NBF. Isolation of the active constituents may yield a novel sedative drug.

Hypnotic Effect of Ocimum basilicum on Pentobarbital-Induced Sleep in Mice

PubMed Central

Askari, Vahid Reza; Baradaran Rahimi, Vafa; Ghorbani, Ahmad; Rakhshandeh, Hassan

2016-01-01

Background Sleep disorders are accompanied by several complications, and currently used soporific drugs can induce unwanted effects such as psychomotor impairment, tolerance, amnesia, and rebound insomnia. Objectives The present study was carried out to investigate if Ocimum basilicum has a sleep-prolonging effect. Materials and Methods This work was an experimental study on 72 mice which were randomly divided into 9 groups: saline (control); diazepam (3 mg/kg, positive control); hydro-alcoholic extract (HAE) of Ocimum basilicum (25, 50, or 100 mg/kg); ethyl acetate fraction (EAF, 50 mg/kg); n-butanol fraction (NBF, 50 mg/kg); water fraction (WF, 50 mg/kg); and saline containing 10% DMSO (vehicle for EAF and NBF). All the test compounds were injected intraperitoneally (IP) 30 minutes before pentobarbital administration (30 mg/kg). Duration and latency of pentobarbital-induced sleep were recorded. Also, LD50 of HAE was determined and the cytotoxicity of HAE was tested on neural and fibroblast cells using the MTT assay. Results HAE increased the duration of pentobarbital-induced sleep at doses of 25, 50, and 100 mg/kg (P < 0.001). The hypnotic effect of HAE was comparable to that induced by diazepam. Similarly, WF, EAF, and NBF at 50 mg/kg could increase sleep duration. The sleep latency was decreased by HAE (P < 0.01 - P < 0.001) and NBF (P < 0.001), but not by WF and EAF. The LD50 value for HAE was found to be 2.4 g/kg. HAE had no effect on the viability of neuronal PC12 cells and L929 fibroblast cells. Conclusions The present data demonstrated that Ocimum basilicum potentiates sleeping behaviors without any cytotoxicity. The main component (s) responsible for the hypnotic effects of this plant is most likely a non-polar agent (s) which is found in NBF. Isolation of the active constituents may yield a novel sedative drug. PMID:27651944

Engineering antigen-specific immunological tolerance.

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

Kontos, Stephan; Grimm, Alizee J.; Hubbell, Jeffrey A.

2015-05-01

Unwanted immunity develops in response to many protein drugs, in autoimmunity, in allergy, and in transplantation. Approaches to induce immunological tolerance aim to either prevent these responses or reverse them after they have already taken place. We present here recent developments in approaches, based on engineered peptides, proteins and biomaterials, that harness mechanisms of peripheral tolerance both prophylactically and therapeutically to induce antigenspecific immunological tolerance. These mechanisms are based on responses of B and T lymphocytes to other cells in their immune environment that result in cellular deletion or ignorance to particular antigens, or in development of active immune regulatorymore » responses. Several of these approaches are moving toward clinical development, and some are already in early stages of clinical testing.« less

Drinking Motivations and Experiences of Unwanted Sexual Advances among Undergraduate Students

ERIC Educational Resources Information Center

Novik, Melinda G.; Howard, Donna E.; Boekeloo, Bradley O.

2011-01-01

This study examined the relationship between drinking motivations and college students' experiences with unwanted sexual advances. Undergraduates, from a public university in the mid-Atlantic region, who reported recent (30 day) alcohol use (n = 289) completed an online survey midway through the spring 2007 academic semester. Experiencing an…

The Role of Learned Resourcefulness in Helping Female Undergraduates Deal with Unwanted Sexual Activity

ERIC Educational Resources Information Center

Kennett, Deborah J.; Humphreys, Terry P.; Patchell, Meghan

2009-01-01

We examined the relationship between learned resourcefulness skills and the manner in which undergraduate heterosexual women handle unwanted sexual advances/activity. Participants consisted of 150 females completing a set of questionnaires assessing general learned resourcefulness, sexual giving-in experience, sexual resourcefulness, sexual…

Primary Prevention vs. Intervention.

ERIC Educational Resources Information Center

Harris, Irving B.

This address was delivered at a conference held at the Columbia University (New York City) Graduate School of Journalism. The decision about abortion, it was stated, involves more than the particular woman who is pregnant with an unwanted fetus. Because of the impact of unwanted children on education, crime and violence, and public costs, the…

DO School-Wide Positive Behavioral Interventions and Supports, NOT Exclusionary Discipline Practices

ERIC Educational Resources Information Center

Nese, Rhonda N. T.; McIntosh, Kent

2016-01-01

All educators will inevitably face unwanted student behavior that they need to address. A ubiquitous response to unwanted behavior is exclusionary discipline practices, including time-out, office discipline referrals, and suspensions. However, extensive research has demonstrated that these practices are associated with negative outcomes, including…

Cognitive Defusion versus thought Distraction in the Mitigation of Learned Helplessness

ERIC Educational Resources Information Center

Hooper, Nic; McHugh, Louise

2013-01-01

Recent research suggests that attempting to avoid unwanted psychological events is maladaptive. Contrastingly, cognitive defusion, which is an acceptance-based method for managing unwanted thoughts, may provide a plausible alternative. The current study was designed to compare defusion and experiential avoidance as strategies for coping with…

Off-label prescribing patterns of antiemetics in children: a multicenter study in Italy.

PubMed

Zanon, Davide; Gallelli, Luca; Rovere, Francesca; Paparazzo, Rossella; Maximova, Natalia; Lazzerini, Marzia; Reale, Antonio; Corsetti, Tiziana; Renna, Salvatore; Emanueli, Tullia; Mannelli, Francesco; Manteghetti, Francesco; Da Dalt, Liviana; Palleria, Caterina; Banchieri, Nicola; Urbino, Antonio; Miglietta, Mario; Cardoni, Giovanni; Pompilio, Adriana; Arrighini, Alberto; Lazzari, Clara; Messi, Gianni

2013-03-01

Acute gastroenteritis (AG) represents both the main cause of acute vomiting in children under 3 years old and a major cause of access to the emergency department. Even if several drugs may be able to reduce the emesis, the pharmacological treatment of vomiting in children remains a controversial issue, and several drugs are prescribed outside their authorized drug label with respect dosage, age, indication, or route of administration and are named as off-label. The aim of present study was to assess the off-label use of antiemetic drugs in patients less than 18 years with vomiting related to AG. This study was carried out in eight pediatric emergency departments in Italy. The following data were obtained crossing the pharmacy distribution records with emergency departments' patient data: sex and age of the patients and detailed information for each drug used (indication, dose, frequency, and route of administration). We recorded that antiemetic drugs were prescribed in every year, particularly in children up to 2 years old, and compared with both literature data and data sheet; 30 % of the administered antiemetics were used off-label. In particular, domperidone was the only antiemetic used labeled for AG treatment in pediatric patients, while metoclopramide and ondansetron have been off-label for both age and indications (i.e., AG treatment). In conclusion, we documented an off-label use of antiemetics in children, and this could represents a problem of safety for the patient and a legal risk for the prescribing physician if patients have an unwanted or bad outcome from treatment.

Teen Pregnancy Prevention and Feminist Values.

ERIC Educational Resources Information Center

Ortiz, Elizabeth T.

The problem of high rates of unwanted and unplanned adolescent pregnancy continues unchecked in the United States, with severe negative consequences for the young mothers, their children, and society. Prevention programs for teenage pregnancy have been less than effective. This study investigated the relationship between feminist values and…

Risks associated with the environmental release of pharmaceuticals on the U.S. Food and Drug Administration "flush list".

PubMed

Khan, Usman; Bloom, Raanan A; Nicell, James A; Laurenson, James P

2017-12-31

A select few prescription drugs can be especially harmful and, in some cases, fatal with just one dose when not used as prescribed. Therefore, the U. S. Food and Drug Administration (FDA) recommends that expired, unwanted, or otherwise unused portions of most of these drugs be disposed of quickly through a take-back program. If such an option is not readily available, FDA recommends that they be flushed down the sink or toilet. The goal of the current investigation was to evaluate the ecological and human-health risks associated with the environmental release of the 15 active pharmaceutical ingredients (APIs) currently on the FDA "flush list". The evaluation suggests that even when highly conservative assumptions are used-including that the entire API mass supplied for clinical use is flushed, all relevant sources in addition to clinical use of the API are considered, and no metabolic loss, environmental degradation, or dilution of wastewater effluents are used in estimating environmental concentrations-most of these APIs present a negligible eco-toxicological risk, both as individual compounds and as a mixture. For a few of these APIs, additional eco-toxicological data will need to be developed. Using similar conservative assumptions for human-health risks, all 15 APIs present negligible risk through ingestion of water and fish. Published by Elsevier B.V.

Glutathione-mediated release of Bodipy® from PEG cofunctionalized gold nanoparticles

PubMed Central

Kumar, Dhiraj; Meenan, Brian J; Dixon, Dorian

2012-01-01

Gold nanoparticles synthesized via sodium citrate reduction of chloroauric acid (HAuCl4) were functionalized with either various concentrations of thiol-terminated Bodipy® FL L-cystine (0.5, 1.0, 1.5, and 2.0 μg/mL) or Bodipy-poly(ethylene glycol) at concentrations of 0.5–18.75, 1.0–12.50, and 1.5–6.25 μg/mL to form a mixed monolayer of BODIPY-PEG. Thiol-terminated Bodipy, a fluorescing molecule, was used as the model drug, while PEG is widely used in drug-delivery applications to shield nanoparticles from unwanted immune responses. Understanding the influence of PEG-capping on payload release is critical because it is the most widely used type of nanoparticle functionalization in drug delivery studies. It has been previously reported that glutathione can trigger release of thiol-bound payloads from gold nanoparticles. Bodipy release from Bodipy capped and from Bodipy-PEG functionalized gold nanoparticles was studied at typical intracellular glutathione levels. It was observed that the addition of PEG capping inhibits the initial burst release observed in gold nanoparticles functionalized only with Bodipy and inhibits nanoparticle aggregation. Efficient and controlled payload release was observed in gold nanoparticles cofunctionalized with only a limited amount of PEG, thus enabling the coattachment of large amounts of drug, targeting groups or other payloads. PMID:22915847

Targeting the folate receptor: improving efficacy in inorganic medicinal chemistry.

PubMed

Carron, Pauraic Mc; Crowley, Aisling; O'Shea, Denis; McCann, Malachy; Howe, Orla; Hunt, Mary; Devereux, Michael

2018-02-09

The discovery of the high-affinity, high-specificity folate receptor in mamalian kidney cells, coupled with the ability of folate to enter cells by folate receptor-mediated endocytosis and the subsequent elucidation of the folate receptor's overexpression in specific cancer cell types; heralded the arrival of the area of chemotherapeutic folate targeting. The application of purely organic folate-based small-molecule drug conjugates that selectively target the folate receptor, which is over expressed in several diseases such as cancer, is well established. The application of inorganic folate-targeted drugs offers significant potential to expand and enhance this therapeutic approach. From the data made available to date, it is apparent that this aspect of inorganic medicinal chemistry is in its youth but has the capability to contribute greatly to cancer research, both in therapy and diagnosis. The union of folate-receptor targeting and inorganic medicine may also lead to the development of treatments for disorders such as chronic-inflammation, tuberculosis, neurodegenerative disease and leishmaniasis. In this review, we summarize what is known about the coordination chemistry of folic acid and the therapeutic potential of such complexes. We also describe approaches adopted to conjugate platinum drugs to folate- or folate-carrier- systems and their prospective ability to overcome problems associated with unwanted side-effects and resistance by improving their delivery and/or selectivity. The literature pertaining to non-platinum metal complex conjugates with folic acid is also reviewed revealing that this is an area that offers significant potential to develop targeted therapeutic approaches in areas such as chemotherapy and molecular imaging for diagnostics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Genotoxicity studies on DNA-interactive telomerase inhibitors with application as anti-cancer agents.

PubMed

Harrington, Dean J; Cemeli, Eduardo; Carder, Joanna; Fearnley, Jamie; Estdale, Sian; Perry, Philip J; Jenkins, Terence C; Anderson, Diana

2003-01-01

Telomerase-targeted strategies have aroused recent interest in anti-cancer chemotherapy, because DNA-binding drugs can interact with high-order tetraplex rather than double-stranded (duplex) DNA targets in tumour cells. However, the protracted cell-drug exposure times necessary for clinical application require that telomerase inhibitory efficacy must be accompanied by both low inherent cytotoxicity and the absence of mutagenicity/genotoxicity. For the first time, the genotoxicity of a number of structurally diverse DNA-interactive telomerase inhibitors is examined in the Ames test using six Salmonella typhimurium bacterial strains (TA1535, TA1537, TA1538, TA98, TA100, and TA102). DNA damage induced by each agent was also assessed using the Comet assay with human lymphocytes. The two assay procedures revealed markedly different genotoxicity profiles that are likely to reflect differences in metabolism and/or DNA repair between bacterial and mammalian cells. The mutational spectrum for a biologically active fluorenone derivative, shown to be mutagenic in the TA100 strain, was characterised using a novel and rapid assay method based upon PCR amplification of a fragment of the hisG46 allele, followed by RFLP analysis. Preliminary analysis indicates that the majority (84%) of mutations induced by this compound are C --> A transversions at position 2 of the missense proline codon of the hisG46 allele. However, despite its genotoxic bacterial profile, this fluorenone agent gave a negative response in the Comet assay, and demonstrates how unwanted systemic effects (e.g., cytotoxicity and genotoxicity) can be prevented or ameliorated through suitable molecular fine-tuning of a candidate drug in targeted human tumour cells. Copyright 2003 Wiley-Liss, Inc.

Efficacy of a new oral lubricant solution in the management of psychotropic drug-induced xerostomia: a randomized controlled trial.

PubMed

Mouly, Stéphane J; Orler, Jean-Baptiste; Tillet, Yves; Coudert, Anne-Claude; Oberli, Frantz; Preshaw, Phillip; Bergmann, Jean-François

2007-10-01

Xerostomia is a subjective sensation of mouth dryness often occurring as an unwanted effect of psychotropic drugs. The clinical efficacy and acceptability of a new oxygenated glycerol triester (OGT) oral spray (1 or 2 sprays up to 4 times daily) in the treatment of xerostomia was compared with those of a commercially available artificial saliva substitute (ASS [Saliveze]) in a 2-week, open-labeled, randomized, parallel-group study. Clinical assessment of xerostomia included evaluation of mouth dryness by means of a 10-cm-long visual analog scale, objective blinded assessment of the oral tissue condition by a dental hygienist by means of a 4-point ordinal scale, and subjective patient-based assessment of dry mouth symptoms by means of dichotomous responses to a questionnaire. [Day 14 - baseline] patient-based mouth dryness score was the primary end point. Seventy-four patients (41 women and 33 men, 44 +/- 15 years) undergoing long-term psychotropic drug treatment were consecutively enrolled. At day 14, OGT resulted in better efficacy than ASS in mouth dryness score (mean difference, 1.2 +/- 0.4; P = 0.006), speech difficulties (mean difference, 1.2 +/- 0.4; P = 0.005), taste (mean difference, 1.1 +/- 0.4; P = 0.02), and overall mouth condition (mean difference, 1.4 +/- 0.9; P = 0.005). Taste of OGT was better than that of ASS (mean difference, 1.4 +/- 0.6; P = 0.04), as was OGT acceptability (mean difference, 1.4 +/- 0.9; P = 0.005). Oxygenated glycerol triester lubricant oral spray was superior to a commercially available ASS in improving xerostomia and overall condition of the oral tissue.

Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report.

PubMed

Reiman, Amanda; Welty, Mark; Solomon, Perry

2017-01-01

Introduction: Prescription drug overdoses are the leading cause of accidental death in the United States. Alternatives to opioids for the treatment of pain are necessary to address this issue. Cannabis can be an effective treatment for pain, greatly reduces the chance of dependence, and eliminates the risk of fatal overdose compared to opioid-based medications. Medical cannabis patients report that cannabis is just as effective, if not more, than opioid-based medications for pain. Materials and Methods: The current study examined the use of cannabis as a substitute for opioid-based pain medication by collecting survey data from 2897 medical cannabis patients. Discussion : Thirty-four percent of the sample reported using opioid-based pain medication in the past 6 months. Respondents overwhelmingly reported that cannabis provided relief on par with their other medications, but without the unwanted side effects. Ninety-seven percent of the sample "strongly agreed/agreed" that they are able to decrease the amount of opiates they consume when they also use cannabis, and 81% "strongly agreed/agreed" that taking cannabis by itself was more effective at treating their condition than taking cannabis with opioids. Results were similar for those using cannabis with nonopioid-based pain medications. Conclusion: Future research should track clinical outcomes where cannabis is offered as a viable substitute for pain treatment and examine the outcomes of using cannabis as a medication assisted treatment for opioid dependence.

The application of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the stratum corneum.

PubMed

Goh, Choon Fu; Craig, Duncan Q M; Hadgraft, Jonathan; Lane, Majella E

2017-02-01

Drug permeation through the intercellular lipids, which pack around and between corneocytes, may be enhanced by increasing the thermodynamic activity of the active in a formulation. However, this may also result in unwanted drug crystallisation on and in the skin. In this work, we explore the combination of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the skin. Ex vivo permeation studies of saturated solutions of diclofenac sodium (DF Na) in two vehicles, propylene glycol (PG) and dimethyl sulphoxide (DMSO), were carried out in porcine ear skin. Tape stripping and ATR-FTIR spectroscopy were conducted simultaneously to collect spectral data as a function of skin depth. Multivariate data analysis was applied to visualise and categorise the spectral data in the region of interest (1700-1500cm -1 ) containing the carboxylate (COO - ) asymmetric stretching vibrations of DF Na. Spectral data showed the redshifts of the COO - asymmetric stretching vibrations for DF Na in the solution compared with solid drug. Similar shifts were evident following application of saturated solutions of DF Na to porcine skin samples. Multivariate data analysis categorised the spectral data based on the spectral differences and drug crystallisation was found to be confined to the upper layers of the skin. This proof-of-concept study highlights the utility of ATR-FTIR spectroscopy in combination with multivariate data analysis as a simple and rapid approach in the investigation of drug deposition in the skin. The approach described here will be extended to the study of other actives for topical application to the skin. Copyright © 2016 Elsevier B.V. All rights reserved.

Unwanted pregnancy and induced abortion among young women 16-22 years old in Greece: a retrospective study of the risk factors.

PubMed

Salakos, N; Koumousidis, A; Bakalianou, K; Paltoglou, G; Kalampokas, T; Iavazzo, C

2010-01-01

Unwanted pregnancies and the subsequent induced abortions are common problems of our youths in modern Greece. The aim of this study was to recognize the risk factors of the problem in an effort to find the best possible solution out of this social dead end. We interviewed 1,320 young female individuals and analyzed their answers using statistical analysis. Several useful conclusions were reached concerning the forces that are involved in unwanted pregnancy/induced abortions. We have tried to underline the strategy to combat the problem. Sexual education and the proper use of contraception remain the essential tools in this effort.

Predictors of unwanted exposure to online pornography and online sexual solicitation of youth.

PubMed

Chang, Fong-Ching; Chiu, Chiung-Hui; Miao, Nae-Fang; Chen, Ping-Hung; Lee, Ching-Mei; Chiang, Jeng-Tung

2016-06-01

This study examined factors associated with the unwanted exposure to online pornography and unwanted online sexual solicitation victimization and perpetration of youth in Taiwan. A total of 2315 students from 26 high schools were assessed in the 10th grade, with follow-up performed in the 11th grade. Self-administered questionnaires were collected. Multivariate analysis results indicated that higher levels of online game use, pornography media exposure, Internet risk behaviors, depression, and cyberbullying experiences predicted online sexual solicitation victimization, while higher levels of Internet chat room use, pornography media exposure, Internet risk behaviors, cyberbullying experiences, and offline sexual harassment predicted online sexual solicitation perpetration. © The Author(s) 2014.

Adolescents' Psychological Health and Experiences with Unwanted Sexual Behavior at School

ERIC Educational Resources Information Center

Timmerman, Greetje

2004-01-01

This paper examines the relationship between experiences with unwanted sexual behavior at school and adolescents' health. Adolescent boys and girls (N = 2,808) participated in a 1998/1999 survey of secondary school students in two regions of The Netherlands. The psychological issues investigated included psychosomatic problems and self-esteem. It…

The Impact of State Abortion Policies on Teen Pregnancy Rates

ERIC Educational Resources Information Center

Medoff, Marshall

2010-01-01

The availability of abortion provides insurance against unwanted pregnancies since abortion is the only birth control method which allows women to avoid an unwanted birth once they are pregnant. Restrictive state abortion policies, which increase the cost of obtaining an abortion, may increase women's incentive to alter their pregnancy avoidance…

Signal Frequency Spectra with Audacity®

ERIC Educational Resources Information Center

Gailey, Alycia

2015-01-01

The primary objective of the activity presented here is to allow students to explore the frequency components of various simple signals, with the ultimate goal of teaching them how to remove unwanted noise from a voice signal. Analysis of the frequency components of a signal allows students to design filters that remove unwanted components of a…

Exploring Patterns of Unwanted Behaviours in Adults with Prader-Willi Syndrome

ERIC Educational Resources Information Center

Pignatti, Riccardo; Mori, Ileana; Bertella, Laura; Grugni, Graziano; Giardino, Daniela; Molinari, Enrico

2013-01-01

Background: Obsessive-compulsive (O-C) traits, and excessive food intake are well known behavioural manifestations among individuals with Prader-Willi Syndrome (PWS). Other unwanted behaviours are also frequently observed, but they need a more specific investigation, especially in the adult population. Methods: The behaviour of 31 PWS adults was…

Pulse stuttering as a remedy for aliased ground backscatter

NASA Astrophysics Data System (ADS)

Bowhill, S. A.

1983-12-01

An algorithm that aides in the removal of ground scatter from low frequency Mesosphere, Stratosphere, Troposphere (MST) radar signals is examined. The unwanted ground scatter is shown as a sequence of velocity plots which are almost typical at the various altitudes. The interpulse period is changed in a cyclic way, thereby destroying the coherence of the unwanted signal. The interpulse period must be changed by an amount at least equal to the transmitted pulse width, and optimum performance is obtained when the number of different interpulse period occupies a time span greater than the coherence time of the unwanted signal. Since a 20-msec pulse width is used, it was found convenient to cycle through 50 pulses, the interpulse period changing from 2 msec to 3 msec during the 1/8-second time. This particular pattern of interpulse periods was provided by a software radar controller. With application of this algorithm, the unwanted scatter signal becomes incoherent from one pulse to the next, and therefore is perceived as noise by the coherent integrator and correlator.

Pulse stuttering as a remedy for aliased ground backscatter

NASA Technical Reports Server (NTRS)

Bowhill, S. A.

1983-01-01

An algorithm that aides in the removal of ground scatter from low frequency Mesosphere, Stratosphere, Troposphere (MST) radar signals is examined. The unwanted ground scatter is shown as a sequence of velocity plots which are almost typical at the various altitudes. The interpulse period is changed in a cyclic way, thereby destroying the coherence of the unwanted signal. The interpulse period must be changed by an amount at least equal to the transmitted pulse width, and optimum performance is obtained when the number of different interpulse period occupies a time span greater than the coherence time of the unwanted signal. Since a 20-msec pulse width is used, it was found convenient to cycle through 50 pulses, the interpulse period changing from 2 msec to 3 msec during the 1/8-second time. This particular pattern of interpulse periods was provided by a software radar controller. With application of this algorithm, the unwanted scatter signal becomes incoherent from one pulse to the next, and therefore is perceived as noise by the coherent integrator and correlator.

Translating data on antihypertensive drugs into clinical practice.

PubMed

Weber, M A

1998-06-01

Two problems in the treatment of hypertension continue to be largely unsolved. The first, and more simple, is our inability to adequately control blood pressure in the majority of hypertensive patients. This not only reflects the difficulty of retaining patients in effective treatment programs, but also of convincing physicians to strive for optimal blood pressure levels. There is a continuing need for new antihypertensive drugs and combinations to help accomplish these goals. The second major problem is that the major clinical endpoints, including coronary events and renal failure, have not been adequately reduced by traditional therapies. Standard regimens, particularly those including diuretics, have protected against strokes and heart failure. Our improved understanding of vascular biology in hypertension has directed interest to the mechanisms in hypertensive patients that might accelerate atherosclerosis and vascular events in these individuals. This involves addressing the concomitant metabolic risk factors that comprise the "Hypertension Syndrome," and, perhaps of equal importance, finding therapies that directly inhibit unwanted types of growth and proliferative activities within the walls of critical arteries. Many substances within the endothelium and the vascular wall may participate as initiators or mediators of pathology, but most information thus far has focused on the renin-angiotensin system. Angiotensin converting enzyme inhibitors (and potentially angiotensin receptor blockers) have provided coronary and renal protection in various cardiovascular conditions, though not yet in formal hypertension trials. Calcium channel blockers have also shown promise, including recent stroke and cardiovascular benefits in patients with isolated systolic hypertension, but, again, definitive coronary data in hypertension are awaited. Unless concomitant conditions mandate the selection of a particular antihypertensive drug class, physicians currently have a dilemma: should they choose drugs from older classes that have not provided full protection? Or, should they prescribe newer agents with exciting potential but with, as yet, unproved endpoint benefits in hypertension? Until currently ongoing prospective trials of antihypertensive therapy are completed, physicians must be guided by their own interpretations of the available data.

Environments, risk and health harms: a qualitative investigation into the illicit use of anabolic steroids among people using harm reduction services in the UK.

PubMed

Kimergård, Andreas; McVeigh, Jim

2014-06-04

The illicit use of anabolic steroids among the gym population continues to rise, along with the number of steroid using clients attending harm reduction services in the UK. This presents serious challenges to public health. Study objectives were to account for the experiences of anabolic steroid users and investigate how 'risk environments' produce harm. Qualitative face-to-face interviews with 24 users of anabolic steroids engaged with harm reduction services in the UK. Body satisfaction was an important factor when deciding to start the use of anabolic steroids. Many users were unaware of the potential dangers of using drugs from the illicit market, whereas some had adopted a range of strategies to negotiate the hazards relating to the use of adulterated products, including self-experimentation to gauge the perceived efficacy and unwanted effects of these drugs. Viewpoints, first-hand anecdotes, norms and practices among groups of steroid users created boundaries of 'sensible' drug use, but also promoted practices that may increase the chance of harms occurring. Established users encouraged young users to go to harm reduction services but, at the same time, promoted risky injecting practices in the belief that this would enhance the efficacy of anabolic steroids. Current steroid-related viewpoints and practices contribute to the risk environment surrounding the use of these drugs and may undermine the goal of current public health strategies including harm reduction interventions. The level of harms among anabolic steroid users are determined by multiple and intertwining factors, in addition to the harms caused by the pharmacological action or injury and illness associated with incorrect injecting techniques. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Library Optimization in EDXRF Spectral Deconvolution for Multi-element Analysis of Ambient Aerosols

EPA Science Inventory

In multi-element analysis of atmospheric aerosols, attempts are made to fit overlapping elemental spectral lines for many elements that may be undetectable in samples due to low concentrations. Fitting with many library reference spectra has the unwanted effect of raising the an...

Implementation of Mobile Phones in Education

ERIC Educational Resources Information Center

Gábor, Korösi; Péter, Esztelecki

2015-01-01

It is well-known that mobile phone usage during lessons is, according to social standards, unwanted not only in several countries worldwide but also in Serbia. The Ministry of Education cannot handle effectively mobile phones, tablets, and other potential alternative educational methods or supplements. Thus, the easiest solution has become…

Current Trends in Intense Pulsed Light

PubMed Central

2012-01-01

Intense pulsed light technologies have evolved significantly since their introduction to the medical community 20 years ago. Now such devices can be used safely and effectively for the cosmetic treatment of many vascular lesions, unwanted hair, and pigmented lesions. Newer technologies often give results equal to those of laser treatments. PMID:22768357

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

Kertzscher, G; Beddar, S

Purpose: To study the promising potential of inorganic scintillator detectors (ISDs) and investigate various unwanted luminescence properties which may compromise their accuracy. Methods: The ISDs were comprised of a ruby crystal coupled to a polymethyl methacrylate (PMMA) fiber-optic cable and a charged coupled device camera. A new type of ISD was manufactured and included a long-pass filter that was sandwiched between the crystal and the fiber-optic cable. The purpose of the filter was to suppress the Cerenkov and fluorescence background light induced in the PMMA (the stem signal) from striking the ruby crystal, generating unwanted ruby excitation. A variety ofmore » experiments were performed to characterize the ruby based ISDs. The relative contribution of the induced ruby signal and the stem signal were quantified while exposing the detector and a bare fiber-optic cable to a high dose rate (HDR) brachytherapy (BT) source, respectively. The unwanted ruby excitation was quantified while irradiating the fiber-optic cable with the detector volume shielded. Other experiments addressed time-dependent luminescence properties and a comparison to other commonly used organic scintillator detectors (BCF-12, BCF-60). Results: When the BT source dwelled 0.5 cm away from the fiber-optic cable, the unwanted ruby excitation amounted to >5% of the total signal if the source-distance from the scintillator was >7 cm. However, the unwanted excitation was suppressed to <1% if the ISD incorporated an optic filter. The stem signal was suppressed with a 20 nm band-pass filter and was <3% as long as the source-distance was <7 cm. The ruby based ISDs generated signal up to 20(40) times that of BCF-12(BCF-60). Conclusion: The study presents solutions to unwanted luminescence properties of ruby based ISDs for HDR BT. An optic filter should be sandwiched between the scintillator volume and the fiber-optic cable to prevent the stem signal to excite the ruby crystal.« less

Determinants of unwanted pregnancies in India using matched case-control designs

PubMed Central

2012-01-01

Background In India, while the total fertility rate has been declined from 3.39 in 1992–93 to 2.68 in 2005–06, the prevalence of unintended pregnancy is still stagnant over the same period. A review of existing literature shows that within the country, there are variations in fertility preferences between different regions. Also there is a strong argument that the availability of a health facility at the village level plays an important role in reshaping the fertility behavior of women. Keeping in mind the fact that there is no information at the village level (which is the lowest geographical boundary) in the recent round of National Family Health Survey (NFHS-3), the specific objective of this study is to examine the impact of individual and household level variables on unwanted pregnancies without controlling the village level variation. Further, once the village level variation (i.e. unobserved variation) has been controlled, it is necessary to study whether there has been any alteration in the contribution of factors from earlier results of without adjusting the village level variation. Methods This paper attempts to examine the associated factors of unwanted pregnancies, without matching the village and after matching the village, by using the matched case–control design. Nationwide data from India’s latest NFHS-3 conducted during 2005–06 was used for the present study. Frequency and pair wise matching has been applied in the present paper and conditional logistic regression analysis was used to work out the models and to find out the factors associated with unwanted pregnancies. Results A major finding of this study was that 1:3 case–control study (without matching the village) shows that women belonging to non Hindu/Muslim religion, Scheduled Tribe, women who have experienced child loss and if the previous birth interval is 24 through 36 months were significant predictors of unwanted pregnancy. However, this relationship did not hold significant after village wise matching. Other factors such as Muslim religion, women and their partners with high school education and above, women belonging to the richest wealth index and if the sex of the last child was female, emerge as significant predictors of unwanted pregnancies. Conclusions This study clearly underscores the importance of adjusting the village (PSU) level variation in explaining unwanted pregnancies. PMID:22883933

Determinants of unwanted pregnancies in India using matched case-control designs.

PubMed

Dixit, Priyanka; Ram, Faujdar; Dwivedi, Laxmi Kant

2012-08-11

In India, while the total fertility rate has been declined from 3.39 in 1992-93 to 2.68 in 2005-06, the prevalence of unintended pregnancy is still stagnant over the same period. A review of existing literature shows that within the country, there are variations in fertility preferences between different regions. Also there is a strong argument that the availability of a health facility at the village level plays an important role in reshaping the fertility behavior of women. Keeping in mind the fact that there is no information at the village level (which is the lowest geographical boundary) in the recent round of National Family Health Survey (NFHS-3), the specific objective of this study is to examine the impact of individual and household level variables on unwanted pregnancies without controlling the village level variation. Further, once the village level variation (i.e. unobserved variation) has been controlled, it is necessary to study whether there has been any alteration in the contribution of factors from earlier results of without adjusting the village level variation. This paper attempts to examine the associated factors of unwanted pregnancies, without matching the village and after matching the village, by using the matched case-control design. Nationwide data from India's latest NFHS-3 conducted during 2005-06 was used for the present study. Frequency and pair wise matching has been applied in the present paper and conditional logistic regression analysis was used to work out the models and to find out the factors associated with unwanted pregnancies. A major finding of this study was that 1:3 case-control study (without matching the village) shows that women belonging to non Hindu/Muslim religion, Scheduled Tribe, women who have experienced child loss and if the previous birth interval is 24 through 36 months were significant predictors of unwanted pregnancy. However, this relationship did not hold significant after village wise matching. Other factors such as Muslim religion, women and their partners with high school education and above, women belonging to the richest wealth index and if the sex of the last child was female, emerge as significant predictors of unwanted pregnancies. This study clearly underscores the importance of adjusting the village (PSU) level variation in explaining unwanted pregnancies.

[Historic, cultural, legal, psychosocial and educational aspects of induced abortion].

PubMed

Aguirre Zozaya, F; Iglesias, M; Reyes, R M; Iturralde, G; Martínez, M; Pineda Hernández, C

1980-08-01

The history of abortion is a very long one. Every people and nation used different and widely varied methods during the centuries to get rid of unwanted pregnancies. Unfortunately, in most instances, the great majority of these methods was equivalent to zero effectiveness, or, too often, to suicide. Legal aspects of induced abortion have changed considerably with the passing of time and according to countries; these days 36% of the world countries admit abortion on request, 24% for specific reasons only, 16% for medical reasons only, and 8% still consider it an illegal practice. In Mexico abortion is legal only when pregnancy would imply death of the mother, when it is the result of rape of minors, or when it is done on women with very serious mental pathology. Obviously abortion is not the solution to unwanted pregnancies; an improvement in the socioeconomic condition and in the quality of life of many people would be a much better, and more difficult, approach to the solution. Psychosocial factors of abortion involve concepts which are difficult to define, such as those of the wanted or of the unwanted child, and can cause problems which are very difficult to handle. Health education, and sex education in particular, should not only teach the fundamentals of reproduction, but respect and consideration for the phenomenon of procreation, and a strong sense of personal and social responsibility toward family planning.

Probing the structural and molecular basis of nucleotide selectivity by human mitochondrial DNA polymerase γ

PubMed Central

Sohl, Christal D.; Szymanski, Michal R.; Mislak, Andrea C.; Shumate, Christie K.; Amiralaei, Sheida; Schinazi, Raymond F.; Anderson, Karen S.; Yin, Y. Whitney

2015-01-01

Nucleoside analog reverse transcriptase inhibitors (NRTIs) are the essential components of highly active antiretroviral (HAART) therapy targeting HIV reverse transcriptase (RT). NRTI triphosphates (NRTI-TP), the biologically active forms, act as chain terminators of viral DNA synthesis. Unfortunately, NRTIs also inhibit human mitochondrial DNA polymerase (Pol γ), causing unwanted mitochondrial toxicity. Understanding the structural and mechanistic differences between Pol γ and RT in response to NRTIs will provide invaluable insight to aid in designing more effective drugs with lower toxicity. The NRTIs emtricitabine [(-)-2,3′-dideoxy-5-fluoro-3′-thiacytidine, (-)-FTC] and lamivudine, [(-)-2,3′-dideoxy-3′-thiacytidine, (-)-3TC] are both potent RT inhibitors, but Pol γ discriminates against (-)-FTC-TP by two orders of magnitude better than (-)-3TC-TP. Furthermore, although (-)-FTC-TP is only slightly more potent against HIV RT than its enantiomer (+)-FTC-TP, it is discriminated by human Pol γ four orders of magnitude more efficiently than (+)-FTC-TP. As a result, (-)-FTC is a much less toxic NRTI. Here, we present the structural and kinetic basis for this striking difference by identifying the discriminator residues of drug selectivity in both viral and human enzymes responsible for substrate selection and inhibitor specificity. For the first time, to our knowledge, this work illuminates the mechanism of (-)-FTC-TP differential selectivity and provides a structural scaffold for development of novel NRTIs with lower toxicity. PMID:26124101

Disclosing Unwanted Sexual Experiences: Results from a National Sample of Adolescent Women

ERIC Educational Resources Information Center

Kogan, Steven M.

2004-01-01

Objective: The aims of this study are to identify factors that influence the disclosures made by female survivors of unwanted sexual experiences (USE) in childhood and adolescence. The predictors of both the timing of disclosure (short delay, long delay, non-disclosure) and the recipient of the disclosure (disclosing ever to an adult, disclosing…

Unsafe in the Camouflage Tower: Sexual Victimization and Perceptions of Military Academy Leadership

ERIC Educational Resources Information Center

Snyder, Jamie A.; Fisher, Bonnie S.; Scherer, Heidi L.; Daigle, Leah E.

2012-01-01

Few studies have examined sexual victimization among cadets and midshipmen at the three U.S. Military Academies. Self-report data from the 2005 Service Academy Sexual Assault Survey of Cadets and Midshipmen (n = 5,220) were used to examine the extent of unwanted sexual attention, sexual harassment, unwanted sexual contact, sexual coercion, and…

Acoustics in Research Facilities--Control of Wanted and Unwanted Sound. Laboratory Design Notes.

ERIC Educational Resources Information Center

Newman, Robert B.

Common and special acoustics problems are discussed in relation to the design and construction of research facilities. Following a brief examination of design criteria for the control of wanted and unwanted sound, the technology for achieving desired results is discussed. Emphasis is given to various design procedures and materials for the control…

40 CFR 262.210 - Making the hazardous waste determination in the laboratory before the unwanted material is...

Code of Federal Regulations, 2013 CFR

2013-07-01

...)(3) for acute hazardous waste, or § 261.5(g)(3) for hazardous waste. (e) An unwanted material that is... 40 Protection of Environment 27 2013-07-01 2013-07-01 false Making the hazardous waste....210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED...

40 CFR 262.210 - Making the hazardous waste determination in the laboratory before the unwanted material is...

Code of Federal Regulations, 2014 CFR

2014-07-01

...)(3) for acute hazardous waste, or § 261.5(g)(3) for hazardous waste. (e) An unwanted material that is... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Making the hazardous waste....210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED...

40 CFR 262.210 - Making the hazardous waste determination in the laboratory before the unwanted material is...

Code of Federal Regulations, 2012 CFR

2012-07-01

...)(3) for acute hazardous waste, or § 261.5(g)(3) for hazardous waste. (e) An unwanted material that is... 40 Protection of Environment 27 2012-07-01 2012-07-01 false Making the hazardous waste....210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED...

40 CFR 262.210 - Making the hazardous waste determination in the laboratory before the unwanted material is...

Code of Federal Regulations, 2010 CFR

2010-07-01

...)(3) for acute hazardous waste, or § 261.5(g)(3) for hazardous waste. (e) An unwanted material that is... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Making the hazardous waste....210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED...

40 CFR 262.210 - Making the hazardous waste determination in the laboratory before the unwanted material is...

Code of Federal Regulations, 2011 CFR

2011-07-01

...)(3) for acute hazardous waste, or § 261.5(g)(3) for hazardous waste. (e) An unwanted material that is... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Making the hazardous waste....210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED...

Reconsolidation of drug memories

PubMed Central

Sorg, Barbara A.

2012-01-01

Persistent, unwanted memories are believed to be key contributors to drug addiction and the chronic relapse problem over the lifetime of the addict. Contrary to the long-held idea that memories are static and fixed, new studies in the last decade have shown that memories are dynamic and changeable. However, they are changeable only under specific conditions. When a memory is retrieved (reactivated), it becomes labile for a period of minutes to hours and then is reconsolidated to maintain long-term memory. Recent findings indicate that even well-established long-term memories may be susceptible to disruption by interfering with reconsolidation through delivery of certain amnestic agents during memory retrieval. Here I review the growing literature on memory reconsolidation in animal models of addiction, including sensitization, conditioned place preference and self-administration. I also discuss (a) several issues that need to be considered in interpreting the findings from reconsolidation studies and (b) future challenges and directions for memory reconsolidation studies in the field of addiction. The findings indicate promise for using this approach as a therapy for disrupting the long-lasting memories that can trigger relapse. PMID:22342780

[Acting out and psychoactive substances: alcohol, drugs, illicit substances].

PubMed

Gillet, C; Polard, E; Mauduit, N; Allain, H

2001-01-01

In humans, some psychotropic agents (alcohol, drugs, illicit substances) have been suggested to play a role in the occurrence of major behavioural disorders, mainly due to the suppression of psychomotor inhibition. Behavioural disinhibition is a physiological mechanism which allows humans to behave appropriately according to a given environmental situation. The behavioural disinhibition induced by either therapeutic dosage or misuse involves the loss of restraint over certain types of social behaviour and may increase the risk of auto or hetero-aggression and acting out. The increased use of psychotropic agents in recent years and the occurrence of unwanted effects are worrying and must be detected and evaluated. The objective of the present study was to establish a causal relationship between psychoactive substance use and occurrence of major behavioural disorders, such as paradoxical rage reactions and suicidal behaviour, based on a literature analysis. It consisted of reviewing reports of drug-induced violent reactions in healthy volunteers and demonstrating, where possible, a cause-effect relationship. Patients with schizophrenia and psychopathic personalities were not included in our study since psychiatric comorbidity could influence behavioural responses. Psychotropic agents included drugs, licit and illicit substances already associated with violence in the past. Many reports used the "Go/No Go test" to evaluate the disinhibiting effect of psychotropic substances; this allows the "cognitive mapping" of drugs. The results suggest that only alcohol, antidepressants, benzodiazepines and cocaïne are related to aggressive behaviour. The best known precipitant of behavioural disinhibition is alcohol, which induces aggressive behaviour. However, there are large differences between individuals, and attentional mechanisms are now recognised as being important in mediating the effects of alcohol. Suicidal tendency as an adverse antidepressant reaction is rare, especially with atypical antidepressants. However, the risk of acting out exists and the responsibility of antidepressant agents in the genesis of suicidal tendencies is now established. The disinhibiting effects of benzodiazepines are well-known and proven by clinical trials. It's a "model" of acting out, and the causal relationship is undeniable. That cocaïne is related to violent behaviour is demonstrated by its pharmacological actions on CNS. The chronic use of cocaïne induces "a limbic dyscontrol syndrome" based on the altered activity of limbic structures. On the contrary, we could not demonstrate a causal relationship between aggression and either cannabis, ecstasy or phencyclidine. Cannabis abusers look particularly for euphoria and relaxing effects. Aggression as an adverse cannabis reaction is very rare and occurs in most cases in association with other drugs and in predisposed individuals. Ecstasy use may lead to long-term alterations of neuronal function in the human CNS and cause psychiatric disorders. However, there is insufficient information about long-term use of ecstasy to estimate its role in the occurrence of behavioural disorders. Clinical and forensic assumptions about phencyclidine and violence were not warranted. However, the substance-effect relationships can be criticized in the case of alcohol, antidepressants, benzodiazepines and cocaïne. In fact, individual, social and psychiatric factors exert an influence on behaviour that is superior to the pharmacological effect of psychotropic agents. The most important parameter in drug-induced behavioural disinhibition is dosage, but mode of administration is also important. In addition, polysubstance abuse is very common. Substances may be taken simultaneously and alcohol is frequently combined with drugs. The combinations of substances result in multiple interactions, and very little is known about the effects of these interactions on violence in humans. Co-occurrence of substance abuse and other mental disorders is also very frequent. Multiple substance abuse should be avoided, because potential interactions between two or more drugs are more likely to cause violent behaviour. In the future, a specific treatment of these deleterious phenomena will have to be considered in order to reduce drug-induced iatrogenic behavioural disorders.

Novel ion channel targets in atrial fibrillation.

PubMed

Hancox, Jules C; James, Andrew F; Marrion, Neil V; Zhang, Henggui; Thomas, Dierk

2016-08-01

Atrial fibrillation (AF) is the most common arrhythmia in humans. It is progressive and the development of electrical and structural remodeling makes early intervention desirable. Existing antiarrhythmic pharmacological approaches are not always effective and can produce unwanted side effects. Additional atrial-selective antiarrhythmic strategies are therefore desirable. Evidence for three novel ion channel atrial-selective therapeutic targets is evaluated: atrial-selective fast sodium channel current (INa) inhibition; small conductance calcium-activated potassium (SK) channels; and two-pore (K2P) potassium channels. Data from animal models support atrial-ventricular differences in INa kinetics and also suggest atrial-ventricular differences in sodium channel β subunit expression. Further work is required to determine whether intrinsic atrial-ventricular differences in human INa exist or whether functional differences occur due to distinct atrial and ventricular action and resting potentials. SK and K2P channels (particularly K2P 3.1) offer potentially attractive atrial-selective targets. Work is needed to identify the underlying basis of SK current that contributes to (patho)physiological atrial repolarization and settings in which SK inhibition is anti- versus pro-arrhythmic. Although K2P3.1 appears to be a promising target with comparatively selective drugs for experimental use, a lack of selective pharmacology hinders evaluation of other K2P channels as potential atrial-selective targets.

Preconception management of thyroid dysfunction.

PubMed

Okosieme, Onyebuchi E; Khan, Ishrat; Taylor, Peter N

2018-04-29

Uncorrected thyroid dysfunction in pregnancy has well-recognized deleterious effects on foetal and maternal health. The early gestation period is one of the critical foetal vulnerability during which maternal thyroid dysfunction may have lasting repercussions. Accordingly, a pragmatic preconception strategy is key for ensuring optimal thyroid disease outcomes in pregnancy. Preconception planning in women with hypothyroidism should pre-empt and mirror the adaptive changes in the thyroid gland by careful levothyroxine dose adjustments to ensure adequate foetal thyroid hormone delivery in pregnancy. In hyperthyroidism, the goal of preconception therapy is to control hyperthyroidism while curtailing the unwanted side effects of foetal and maternal exposure to antithyroid drugs. Thus, pregnancy should be deferred until a stable euthyroid state is achieved, and definitive therapy with radioiodine or surgery should be considered in women with Graves' disease planning future pregnancy. Women with active disease who are imminently trying to conceive should be switched to propylthiouracil either preconception or at conception in order to minimize the risk of birth defects from carbimazole or methimazole exposure. Optimal strategies for women with borderline states of thyroid dysfunction namely subclinical hypothyroidism, isolated hypothyroxinaemia and thyroid autoimmunity remain uncertain due to the dearth of controlled interventional trials. Future trial designs should aspire to recruit and initiate therapy before conception or as early as possible in pregnancy. © 2018 John Wiley & Sons Ltd.

Non-psychotropic analgesic drugs from the endocannabinoid system: "magic bullet" or "multiple-target" strategies?

PubMed

Starowicz, Katarzyna; Di Marzo, Vincenzo

2013-09-15

The exploitation of preparations of Cannabis sativa to combat pain seems to date back to time immemorial, although their psychotropic effects, which are at the bases of their recreational use and limit their therapeutic use, are at least as ancient. Indeed, it has always been different to tease apart the unwanted central effects from the therapeutic benefits of Δ⁹-tetrahydrocannabinol (THC), the main psychotropic component of cannabis. The discovery of the cannabinoid receptors and of their endogenous ligands, the endocannabinoids, which, unlike THC, play a pro-homeostatic function in a tissue- and time-selective manner, offered the opportunity to develop new analgesics from synthetic inhibitors of endocannabinoid inactivation. The advantages of this approach over direct activation of cannabinoid receptors as a therapeutic strategy against neuropathic and inflammatory pain are discussed here along with its potential complications. These latter have been such that clinical success has been achieved so far more rapidly with naturally occurring THC or endocannabinoid structural analogues acting at a plethora of cannabinoid-related and -unrelated molecular targets, than with selective inhibitors of endocannabinoid enzymatic hydrolysis, thus leading to revisit the potential usefulness of "multi-target" versus "magic bullet" compounds as new analgesics. © 2013 Elsevier B.V. All rights reserved.

Performance analysis of microcomputer based differential protection of UHV lines under selective phase switching

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

Bhatti, A.A.

1990-04-01

This paper examines the effects of primary and secondary fault quantities as well s of mutual couplings of neighboring circuits on the sensitivity of operation and threshold settings of a microcomputer based differential protection of UHV lines under selective phase switching. Microcomputer based selective phase switching allows the disconnection of minimum number of phases involved in a fault and requires the autoreclosing of these phases immediately after the extinction of secondary arc. During a primary fault a heavy current contribution to the healthy phases tends to cause an unwanted tripping. Faulty phases physically disconnected constitute an isolated fault which beingmore » coupled to the system affects the current and voltage levels of the healthy phases still retained in the system and may cause an unwanted tripping. The microcomputer based differential protection, appears to have poor performance when applied to uncompensated lines employing selective pole switching.« less

Optimisation of a low cost SLM for diffraction efficiency and ghost order suppression

NASA Astrophysics Data System (ADS)

Bowman, R.; D'Ambrosio, V.; Rubino, E.; Jedrkiewicz, O.; di Trapani, P.; Padgett, M. J.

2011-11-01

Spatial Light Modulators (SLMs) are a powerful tool in many optics laboratories, but due to the technology required for their fabrication, they are usually very expensive. Recently some inexpensive devices have been produced, however their phase shift range is less than 2π, leading to a loss of diffraction efficiency for the SLM. We show how to improve the first order diffraction efficiency of such an SLM by adjusting the blazing function, and obtain a 1.5 times increase in first order diffracted power. Even a perfect SLM with 2π phase throw can produce undesired effects in some situations; for example in holographic optical tweezers it is common to find unwanted "ghost spots" near to the array of first-order spots. Modulating the amplitude, by spatially modulating the blazing function, allows us to suppress the ghost spots. This increases the contrast between desired and unwanted spots by more than an order of magnitude.

Colon-targeted delivery of cyclosporine A using dual-functional Eudragit® FS30D/PLGA nanoparticles ameliorates murine experimental colitis.

PubMed

Naeem, Muhammad; Bae, Junhwan; Oshi, Murtada A; Kim, Min-Soo; Moon, Hyung Ryong; Lee, Bok Luel; Im, Eunok; Jung, Yunjin; Yoo, Jin-Wook

2018-01-01

Colon-targeted oral nanoparticles (NPs) have emerged as an ideal, safe, and effective therapy for ulcerative colitis (UC) owing to their ability to selectively accumulate in inflamed colonic mucosa. Cyclosporine A (CSA), an immunosuppressive agent, has long been used as rescue therapy in severe steroid-refractory UC. In this study, we developed CSA-loaded dual-functional polymeric NPs composed of Eudragit ® FS30D as a pH-sensitive polymer for targeted delivery to the inflamed colon, and poly(lactic-co-glycolic acid) (PLGA) as a sustained-release polymer. CSA-loaded Eudragit FS30D nanoparticles (ENPs), PLGA nanoparticles (PNPs), and Eudragit FS30D/PLGA nanoparticles (E/PNPs) were prepared using the oil-in-water emulsion method. Scanning electron microscope images and zeta size data showed successful preparation of CSA-loaded NPs. PNPs exhibited a burst drug release of >60% at pH 1.2 (stomach pH) in 0.5 h, which can lead to unwanted systemic absorption and side effects. ENPs effectively inhibited the burst drug release at pH 1.2 and 6.8 (proximal small intestine pH); however, nearly 100% of the CSA in ENPs was released rapidly at pH 7.4 (ileum-colon pH) owing to complete NP dissolution. In contrast to single-functional PNPs and ENPs, the dual-functional E/PNPs minimized burst drug release (only 18%) at pH 1.2 and 6.8, and generated a sustained release at pH 7.4 thereafter. Importantly, in distribution studies in the gastrointestinal tracts of mice, E/PNPs significantly improved CSA distribution to the colon compared with PNPs or ENPs. In a mouse model of colitis, E/PNP treatment improved weight loss and colon length, and decreased rectal bleeding, spleen weight, histological scoring, myeloperoxidase activity, macrophage infiltration, and expression of proinflammatory cytokines compared with PNPs or ENPs. Overall, this work confirms the benefits of CSA-loaded E/PNPs for efficiently delivering CSA to the colon, suggesting their potential for UC therapy.

[High-grade pressure sores in frail older high-risk persons. A retrospective postmortem case-control-study].

PubMed

Von Renteln-Kruse, W; Krause, T; Anders, J; Kühl, M; Heinemann, A; Püschel, K

2004-04-01

Some old persons at risk do develop, but others, at comparable risk, do not develop high-grade pressure sores. To evaluate potentially different risk factors, we performed a post mortem case-control study in old persons who developed high-grade pressure sores within six months until 14 days before death. Consecutive cases with pressure sores grade >/=3 and potential controls at comparably high risk for pressure sores were examined before cremation. After written informed consent had been obtained by the next relatives, all available nursing and medical records of the deceased were thoroughly evaluated. Cases and controls were matched according to age, gender, immobility, and cachexia.A total of 100 cases with 71 pressure sores grade 3 and 29 pressure sores grade 4 were compared to 100 controls with 27 pressure sores grade

Resurgence of instrumental behavior after an abstinence contingency

PubMed Central

Bouton, Mark E.; Schepers, Scott T.

2014-01-01

In resurgence, an extinguished instrumental behavior (R1) recovers when a behavior that replaced it (R2) is also extinguished. The phenomenon may be relevant to understanding relapse that can occur after the termination of “contingency management” treatments, in which unwanted behavior (e.g., substance abuse) is reduced by reinforcing alternative behavior. When reinforcement is discontinued, the unwanted behavior might resurge. However, unlike most resurgence experiments, contingency management treatments also introduce a negative contingency in which reinforcers are not delivered unless the client has abstained from the unwanted behavior. Two experiments with rats therefore examined the effects of adding a negative “abstinence” contingency to the resurgence design. During response elimination, R2 was not reinforced unless R1 had not been emitted for a minimum period of time (45, 90, or 135 s). In both experiments, adding such a contingency to simple R1 extinction reduced, but did not eliminate, resurgence. Experiment 2 found the same effect in a yoked group that could earn reinforcers for R2 at the same points in time, but without the requirement to abstain from R1. Thus, the negative contingency per se did not contribute. Results suggest that the contingency reduced resurgence by making reinforcers more difficult to earn and more widely spaced in time. This could have allowed the animal to learn that R1 was extinguished in the “context” of infrequent reinforcement—a context more like that of resurgence testing. The results are thus consistent with a contextual (renewal) account of resurgence. The method might provide a better model of relapse after termination of a contingency management treatment. PMID:24366673

Resurgence of instrumental behavior after an abstinence contingency.

PubMed

Bouton, Mark E; Schepers, Scott T

2014-06-01

In resurgence, an extinguished instrumental behavior (R1) recovers when a behavior that has replaced it (R2) is also extinguished. The phenomenon may be relevant to understanding relapse that can occur after the termination of "contingency management" treatments, in which an unwanted behavior (e.g., substance abuse) is reduced by reinforcing an alternative behavior. When reinforcement is discontinued, the unwanted behavior might resurge. However, unlike most resurgence experiments, contingency management treatments also introduce a negative contingency, in which reinforcers are not delivered unless the client has abstained from the unwanted behavior. In two experiments with rats, we therefore examined the effects of adding a negative "abstinence" contingency to the resurgence design. During response elimination, R2 was not reinforced unless R1 had not been emitted for a minimum period of time (45, 90, or 135 s). In both experiments, adding such a contingency to simple R1 extinction reduced, but did not eliminate, resurgence. In Experiment 2, we found the same effect in a yoked group that could earn reinforcers for R2 at the same points in time as the negative-contingency group, but without the requirement to abstain from R1. Thus, the negative contingency per se did not contribute to the reduction in resurgence. These results suggest that the contingency reduced resurgence by making reinforcers more difficult to earn and more widely spaced in time. This could have allowed the animal to learn that R1 was extinguished in the "context" of infrequent reinforcement-a context more like that of resurgence testing. The results are thus consistent with a contextual (renewal) account of resurgence. The method might provide a better model of relapse after termination of a contingency management treatment.

Discovery and Development of Natural Products and their Derivatives as Photosensitizers for Photodynamic Therapy.

PubMed

Xiao, Qicai; Wu, Juan; Pang, Xin; Jiang, Yue; Wang, Pan; Leung, Albert W; Gao, Liqian; Jiang, Sheng; Xu, Chuanshan

2018-01-01

Photodynamic therapy (PDT) has been developed as an alternative modality for the management of neoplastic and nonneoplastic diseases. It is a minimally invasive treatment that involves the interaction of a non-toxic photosensitizer (PS), light and molecular oxygen to generate reactive oxygen species (ROS), resulting in the destruction of unwanted cells and tissues. Discovery and development of new PSs with optimized properties are much crucial for achieving a desirable therapeutic efficacy. This review describes the photochemical and photobiological mechanisms of PDT, and outlines the recent progress in discovery and development of natural products and their derivatives as phototherapeutic drugs. The potential limitations and future perspectives of PDT in clinical application are also presented and discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Clinical pharmacokinetics and pharmacodynamics of celecoxib: a selective cyclo-oxygenase-2 inhibitor.

PubMed

Davies, N M; McLachlan, A J; Day, R O; Williams, K M

2000-03-01

Celecoxib, a nonsteroidal anti-inflammatory drug (NSAID), is the first specific inhibitor of cyclo-oxygenase-2 (COX-2) approved to treat patients with rheumatism and osteoarthritis. Preliminary data suggest that celecoxib also has analgesic and anticancer properties. The selective inhibition of COX-2 is thought to lead to a reduction in the unwanted effects of NSAIDs. Upper gastrointestinal complication rates in clinical trials are significantly lower for celecoxib than for traditional nonselective NSAIDs (e.g. naproxen, ibuprofen and diclofenac). The rate of absorption of celexocib is moderate when given orally (peak plasma drug concentration occurs after 2 to 4 hours), although the extent of absorption is not known. Celexocib is extensively protein bound, primarily to plasma albumin, and has an apparent volume of distribution of 455+/-166L in humans. The area under the plasma concentration-time curve (AUC) of celecoxib increases in proportion to increasing oral doses between 100 and 800mg. Celecoxib is eliminated following biotransformation to carboxylic acid and glucuronide metabolites that are excreted in urine and faeces, with little drug (2%) being eliminated unchanged in the urine. Celecoxib is metabolised primarily by the cytochrome P450 (CYP) 2C9 isoenzyme and has an elimination half-life of about 11 hours in healthy individuals. Racial differences in drug disposition and pharmacokinetic changes in the elderly have been reported for celecoxib. Plasma concentrations (AUC) of celecoxib appear to be 43% lower in patients with chronic renal insufficiency [glomerular filtration rate 2.1 to 3.6 L/h (35 to 60 ml/min)] compared with individuals with healthy renal function, with a 47% increase in apparent clearance. Compared with healthy controls, it has been reported that the steady-state AUC is increased by approximately 40% and 180% in patients with mild and moderate hepatic impairment, respectively. Celecoxib does not appear to interact with warfarin, ketoconazole or methotrexate; however, clinically significant drug interactions with fluconazole and lithium have been documented. As celecoxib is metabolised by CYP2C9, increased clinical vigilance is required during the coadministration of other substrates or inhibitors of this enzyme.

Kinase-activating and kinase-impaired cardio-facio-cutaneous syndrome alleles have activity during zebrafish development and are sensitive to small molecule inhibitors.

PubMed

Anastasaki, Corina; Estep, Anne L; Marais, Richard; Rauen, Katherine A; Patton, E Elizabeth

2009-07-15

The Ras/MAPK pathway is critical for human development and plays a central role in the formation and progression of most cancers. Children born with germ-line mutations in BRAF, MEK1 or MEK2 develop cardio-facio-cutaneous (CFC) syndrome, an autosomal dominant syndrome characterized by a distinctive facial appearance, heart defects, skin and hair abnormalities and mental retardation. CFC syndrome mutations in BRAF promote both kinase-activating and kinase-impaired variants. CFC syndrome has a progressive phenotype, and the availability of clinically active inhibitors of the MAPK pathway prompts the important question as to whether such inhibitors might be therapeutically effective in the treatment of CFC syndrome. To study the developmental effects of CFC mutant alleles in vivo, we have expressed a panel of 28 BRAF and MEK alleles in zebrafish embryos to assess the function of human disease alleles and available chemical inhibitors of this pathway. We find that both kinase-activating and kinase-impaired CFC mutant alleles promote the equivalent developmental outcome when expressed during early development and that treatment of CFC-zebrafish embryos with inhibitors of the FGF-MAPK pathway can restore normal early development. Importantly, we find a developmental window in which treatment with a MEK inhibitor can restore the normal early development of the embryo, without the additional, unwanted developmental effects of the drug.

Nanotoxicity: a growing need for study in the endocrine system.

PubMed

Lu, Xuefei; Liu, Ying; Kong, Xiangjun; Lobie, Peter E; Chen, Chunying; Zhu, Tao

2013-05-27

Nanomaterials (NMs) are engineered for commercial purposes such as semiconductors, building materials, cosmetics, and drug carriers, while natural nanoparticles (NPs) already exist in the environment. Due to their unique physicochemical properties, they may interact actively with biological systems. Some of these interactions might be detrimental to human health, and therefore studies on the potential 'nanotoxicity' of these materials in different organ systems are warranted. The purpose of developing the concept of nanotoxicity is to recognize and evaluate the hazards and risks of NMs and evaluate safety. This review will summarize and discuss recent reports derived from cell lines or animal models concerning the effects of NMs on, and their application in, the endocrine system of mammalian and other species. It will present an update on current studies of the effects of some typical NMs-such as metal-based NMs, carbon-based NMs, and dendrimers-on endocrine functions, in which some effects are adverse or unwanted and others are favorable or intended. Disruption of endocrine function is associated with adverse health outcomes including reproductive failure, metabolic syndrome, and some types of cancer. Further investigations are therefore required to obtain a thorough understanding of any potential risk of pathological endocrine disruption from products containing NMs. This review aims to provide impetus for further studies on the interactions of NMs with endocrine functions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intrusiveness of Behavioral Treatments for Children with Autism and Developmental Disabilities: An Initial Investigation

ERIC Educational Resources Information Center

Mayton, Michael R.; Carter, Stacy L.; Zhang, Jie; Wheeler, John J.

2014-01-01

The behaviors frequently displayed by students with autism can place them at risk for overly reactive behavior interventions with unwanted side effects. The current study examined the level of intrusiveness of behavioral treatments developed for 198 students with disabilities from 13 different states. Results demonstrated that students diagnosed…

EFFECT OF ALTERNATING WETTING AND DRYING IRRIGATION METHODS ON PHOTOSYNTHESIS AND TEMPERATURE OF RICE AND WEED PLANTS.

USDA-ARS?s Scientific Manuscript database

Reduced input systems such as alternating wetting and drying (AWD) and furrow irrigation can potentially reduce water costs and limit the release of greenhouse gases in rice production, but also can introduce unwanted crop stresses that compromise crop yield and quality, as well as introducing compl...

Forestry Herbicides

Treesearch

Jerry L. Michael; William L. Boyer

1983-01-01

If you own or manage pine timberlands in the South, you know only too well that unwanted vegetation can be stubborn when you arc trying to reforest, convert a stand, or improve pine growth by reducing competition. Are you aware. however, that many forestry herbicides are proving effective in eliminating this undesirable vegetation, both before and after pine...

Brain Gym: Pseudoscientific Practice

ERIC Educational Resources Information Center

Kroeze, Kevin; Hyatt, Keith J.; Lambert, M. Chuck

2016-01-01

There is an abundance of scams and pseudoscientific practices promising seemingly magical cures for whatever ails a person. A short viewing of late night television will readily reveal a whole host of scams that may be more effective at relieving the viewer of the cash in his or her pocket than alleviating any unwanted symptoms. Unfortunately,…

Avoiding unwanted vicinity effects with attract-and-kill tactics for harlequin bug, Murgantia histrionica (Hahn)

USDA-ARS?s Scientific Manuscript database

In the development of an attract-and-kill approach for the management of harlequin bug (HB), Murgantia histrionica (Hahn), we evaluated attraction and retention of HB by pheromone-baited traps in the field. In release-recapture and on-farm experiments, traps combining collard plants with commercial ...

Tree-breeding technique: some effects of continuous bagging

Treesearch

Jonathan W. Wright

1951-01-01

In tree-breeding operations, it is standard practice to protect the tree flowers with vegetable parchment or sausage-casing bags during the pollination period so no unwanted pollen can get to them. Since the bags often damage the tree, they are usually removed as soon as the pollination period ends - within 2 or 3 weeks.

Effect of synthetic auxin herbicides on seed development and viability in genetically-engineered glyphosate-resistant alfalfa

USDA-ARS?s Scientific Manuscript database

Feral populations of cultivated crops have the potential to function as bridges and reservoirs that contribute to the unwanted movement of novel genetically engineered (GE) traits. Recognizing that feral alfalfa has the potential to lower genetic purity in alfalfa seed production fields when it is g...

Effect of ammate on unwanted growth in oak--yellow-poplar stands in New Jersey

Treesearch

S. Little; H. A. Somes

1954-01-01

Stands of mixed oaks and yellow-poplar form the most valuable forest crop on many sites in central and northern New Jersey and in the Delaware Valley of southern New Jersey. However, these stands often contain shrubs and low-value hardwood trees that prevent satisfactory restocking of cutover areas.

A technique for thermal desorption analyses suitable for thermally-labile, volatile compounds

USDA-ARS?s Scientific Manuscript database

Our group has for some time studied below ground plant produced volatile signals affecting nematode and insect behavior. The research requires repeated sampling of intact plant/soil systems in the lab as well as the field with the help of probes to minimize unwanted effects on the systems we are stu...

Phosphoproteomics and Bioinformatics Analyses of Spinal Cord Proteins in Rats with Morphine Tolerance

PubMed Central

Liaw, Wen-Jinn; Tsao, Cheng-Ming; Huang, Go-Shine; Wu, Chin-Chen; Ho, Shung-Tai; Wang, Jhi-Joung; Tao, Yuan-Xiang; Shui, Hao-Ai

2014-01-01

Introduction Morphine is the most effective pain-relieving drug, but it can cause unwanted side effects. Direct neuraxial administration of morphine to spinal cord not only can provide effective, reliable pain relief but also can prevent the development of supraspinal side effects. However, repeated neuraxial administration of morphine may still lead to morphine tolerance. Methods To better understand the mechanism that causes morphine tolerance, we induced tolerance in rats at the spinal cord level by giving them twice-daily injections of morphine (20 µg/10 µL) for 4 days. We confirmed tolerance by measuring paw withdrawal latencies and maximal possible analgesic effect of morphine on day 5. We then carried out phosphoproteomic analysis to investigate the global phosphorylation of spinal proteins associated with morphine tolerance. Finally, pull-down assays were used to identify phosphorylated types and sites of 14-3-3 proteins, and bioinformatics was applied to predict biological networks impacted by the morphine-regulated proteins. Results Our proteomics data showed that repeated morphine treatment altered phosphorylation of 10 proteins in the spinal cord. Pull-down assays identified 2 serine/threonine phosphorylated sites in 14-3-3 proteins. Bioinformatics further revealed that morphine impacted on cytoskeletal reorganization, neuroplasticity, protein folding and modulation, signal transduction and biomolecular metabolism. Conclusions Repeated morphine administration may affect multiple biological networks by altering protein phosphorylation. These data may provide insight into the mechanism that underlies the development of morphine tolerance. PMID:24392096

Effects of metabotropic glutamate receptor ligands on male sexual behavior in rats.

PubMed

Li, Xia; Higley, Amanda; Song, Rui; Xi, Zheng-Xiong

2013-03-01

Metabotropic glutamate receptors (mGluRs), particularly mGluR2/3, mGluR5 and mGluR7, have received much attention in medication development for the treatment of drug addiction and other neuropsychiatric diseases. However, little is known as to whether mGluR ligands also alter natural sexual behavior, a possible unwanted effect when used in humans. In the present study, we used classical copulatory behaviors to evaluate the effects of LY379268 (a selective mGluR2/3 agonist), MPEP (a selective mGluR5 antagonist) and AMN082 (a selective mGluR7 agonist), on male sexual performance in rats. We found that systemic administration of LY379268 (1, 3 mg/kg, i.p.) had no effect, while MPEP (20 mg/kg, but not 10 mg/kg, i.p.) and AMN082 (10, 20 mg/kg, but not 3 mg/kg) produced a significant and dose-dependent reduction in both sex-seeking and sex-performance behaviors, manifested as an increase in mount or intromission latency and time required for ejaculation, and a reduction in mount or intromission frequency. This inhibition lasted for about 30-60 min. These findings suggest that compounds that target mGluR5 or mGluR7, but not mGluR2/3, may have short-term inhibitory effects on male sexual performance. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. Published by Elsevier Ltd.

The urgent need to improve the tools to assess clinical benefit and value of cancer treatment.

PubMed

Sobrero, Alberto; Puccini, Alberto; Bregni, Giacomo; Bruzzi, Paolo

2017-09-01

There are several controversies in the assessment of the benefit, value and sustainability of cancer drugs. First, there is a surprising disagreement on the impact of drugs on the overall outcome of cancer treatment. Second, raising the bar of efficacy in clinical trials is claimed by many, but at the same time, being conservative appears justified as well, given the overall benefit of multiple incremental gains, typically observed in advanced solid tumours. Third, sustainability of cancer drug cost is a prohibitive challenge, but no major successful action has been taken so far. The reason for these controversies can be understood using concepts borrowed from psychological and cognitive sciences: each stakeholder has different perspectives generated by different availability biases; this implies different priorities, leading people to think, choose and act differently. Providing an 'objective' assessment of the benefit and value of a cancer drug makes sense only if the perspective adopted is clearly identified. The American Society of Clinical Oncology (ASCO) scale fits the patients' perspective by helping individual patients to choose the most valuable therapeutic option for their condition. Conversely, the European Society for Medical Oncology (ESMO) scale has a public health perspective: ranking the clinical benefit of oncologic drugs to identify those agents that should be available in every EU country. Because this scale is being adopted for reimbursement purposes in several European regions, the current major methodological problems of the scale should urgently be corrected to avoid unwanted societal consequences. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prioritizing pharmacokinetic drug interaction precipitants in natural products: application to OATP inhibitors in grapefruit juice

PubMed Central

Johnson, Emily J.; Won, Christina S.; Köck, Kathleen; Paine, Mary F.

2017-01-01

Natural products, including botanical dietary supplements and exotic drinks, represent an ever-increasing share of the health care market. The parallel ever-increasing popularity of self-medicating with natural products increases the likelihood of co-consumption with conventional drugs, raising concerns for unwanted natural product-drug interactions. Assessing the drug interaction liability of natural products is challenging due to the complex and variable chemical composition inherent to these products, necessitating a streamlined preclinical testing approach to prioritize precipitant individual constituents for further investigation. Such an approach was evaluated in the current work to prioritize constituents in the model natural product, grapefruit juice, as inhibitors of intestinal organic anion-transporting peptide (OATP)-mediated uptake. Using OATP2B1-expressing MDCKII cells and the probe substrate estrone 3-sulfate, IC50s were determined for constituents representative of the flavanone (naringin, naringenin, hesperidin), furanocoumarin (bergamottin, 6′,7′-dihydroxybergamottin), and polymethoxyflavone (nobiletin and tangeretin) classes contained in grapefruit juice juice. Nobiletin was the most potent (IC50, 3.7 μM); 6′,7′-dihydroxybergamottin, naringin, naringenin, and tangeretin were moderately potent (IC50, 20–50 μM); and bergamottin and hesperidin were the least potent (IC50, >300 μM) OATP2B1 inhibitors. Intestinal absorption simulations based on physiochemical properties were used to determine ratios of unbound concentration to IC50 for each constituent within enterocytes and to prioritize in order of pre-defined cut-off values. This streamlined approach could be applied to other natural products that contain multiple precipitants of natural product-drug interactions. PMID:28032362

The effects of suppressing intrusive thoughts on dream content, dream distress and psychological parameters.

PubMed

Kröner-Borowik, Tana; Gosch, Stefanie; Hansen, Kathrin; Borowik, Benjamin; Schredl, Michael; Steil, Regina

2013-10-01

Suppressing unwanted thoughts can lead to an increased occurrence of the suppressed thought in dreams. This is explainable by the ironic control theory, which theorizes why the suppression of thoughts might make them more persistent. The present study examined the influence of thought suppression on dream rebound, dream distress, general psychiatric symptomatology, depression, sleep quality and perceived stress. Thirty healthy participants (good sleepers) were investigated over a period of 1 week. Half were instructed to suppress an unwanted thought 5 min prior to sleep, whereas the other half were allowed to think of anything at all. Dream content was assessed through a dream diary. Independent raters assessed whether or not the dreams were related to the suppressed target thought. The results demonstrated increased target-related dreams and a tendency to have more distressing dreams in the suppression condition. Moreover, the data imply that thought suppression may lead to significantly increased general psychiatric symptomatology. No significant effects were found for the other secondary outcomes. © 2013 European Sleep Research Society.

Mesoscopic modeling of the response of human dental enamel to mid-infrared radiation

NASA Astrophysics Data System (ADS)

Vila Verde, Ana; Ramos, Marta; Stoneham, A. M.

2006-03-01

Ablation of human dental enamel, a composite biomaterial with water pores, is of significant importance in minimally invasive laser dentistry but progress in the area is hampered by the lack of optimal laser parameters. We use mesoscopic finite element models of this material to study its response to mid-infrared radiation. Our results indicate that the cost-effective, off-the-shelf CO2 laser at λ = 10.6 μm may in fact ablate enamel precisely, reproducibly and with limited unwanted side effects such as cracking or heating, provided that a pulse duration of 10 μs is used. Furthermore, our results also indicate that the Er:YAG laser (λ = 2.94 μm), currently popular for laser dentistry, may in fact cause unwanted deep cracking in the enamel when regions with unusually high water content are irradiated, and also provide an explanation for the large range of ablation threshold values observed for this material. The model may be easily adapted to study the response of any composite material to infrared radiation and thus may be useful for the scientific community.

Prevalence and Determinants of Unintended Pregnancy Among Women in South-Western Nigeria.

PubMed

Lamina, M A

2015-09-01

To study the prevalence of unwanted pregnancy in urban and rural settlements in Southwestern Nigeria. A prospective cross-sectional study of women within reproductive age. Community-based study of unwanted pregnancy was conducted in 2012. They were women of reproductive age who had experienced unintended and/or unwanted pregnancies and they were randomly selected from rural and urban areas of Ogun state in Nigeria. A semi-structured questionnaire was used for data collection. The prevalence of unintended/unwanted pregnancy, associated factors including the views, perception and attitudes of community members in both urban and rural settlements and the pattern of help-seeking behavior on the problem. The age range of respondents was 15-48 years (mean age 31.2± 6.7 years). One thousand, two hundred and twenty-one (51.6%) of the respondents were married. The percentage of illiterate respondents was 3.5% in urban area and 4.1% in rural area. There was a statistically significant association between level of education and use of a method to avoid or delay pregnancy (p < 0.001). The prevalence of unintended pregnancy was 35.9% while that of induced abortion was 33.5%. Quality of service was the most important factor in the choice of a place for pregnancy termination in urban and rural areas. Economic reasons were often cited as reasons women make use of abortion services. Unwanted pregnancy constitutes a problem, even at the community level. The high contraceptive awareness should be translated to an increased use so as to bridge the large gap of unmet need.

Trends in youth internet victimization: findings from three youth internet safety surveys 2000-2010.

PubMed

Jones, Lisa M; Mitchell, Kimberly J; Finkelhor, David

2012-02-01

The purpose of this research was to explore the trends in youth reports of unwanted online sexual solicitation, harassment, and exposure to pornography over time. The study was based on three separate cross-sectional national telephone surveys of approximately 1,500 youth Internet users, aged 10 through 17 years. Data were collected in 2000, 2005, and 2010. Nine percent of youth reported an unwanted sexual solicitation in 2010. This continued the decline in unwanted sexual solicitations that occurred between 2000 (19%) and 2005 (13%), resulting in a total 50% decrease between 2000 and 2010. Twenty-three percent of youth reported an unwanted exposure to pornography, a decline from 34% in 2005, following an increase between 2000 and 2005 (25% to 34%). However, marking the only trend to show an increase over the past 5 years, 11% of youth reported an online harassment experience, which was an increase from 9% in 2005, and 6% in 2000. Some differences in these trends were noted for subgroups of youth across age, gender, and race. The trends in unwanted experiences online over the past decade identified by three Youth Internet Safety Surveys may contradict impressions that the general population, professionals, and the media have about what is happening. Trends provide evidence for some optimism that protective adaptations to the online environment have been successful; however, online harassment appears to be increasing for youth, particularly girls, and may require additional mobilization. Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Does It Matter What You Call It? The Relationship Between Labeling Unwanted Sexual Experiences and Distress

ERIC Educational Resources Information Center

Harned, Melanie S.

2004-01-01

Using cross-sectional data from 2 samples of women attending a university (N = 1,395), the author examined the relationship among women's labeling of their unwanted sexual experiences (USEs) with dating partners and a variety of psychological and school-related outcomes. Three competing path analysis models were tested to determine whether the…

Lithium purification technique

DOEpatents

Keough, Robert F.; Meadows, George E.

1985-01-01

A method for purifying liquid lithium to remove unwanted quantities of nitrogen or aluminum. The method involves precipitation of aluminum nitride by adding a reagent to the liquid lithium. The reagent will be either nitrogen or aluminum in a quantity adequate to react with the unwanted quantity of the impurity to form insoluble aluminum nitride. The aluminum nitride can be mechanically separated from the molten liquid lithium.

Lithium purification technique

DOEpatents

Keough, R.F.; Meadows, G.E.

1984-01-10

A method for purifying liquid lithium to remove unwanted quantities of nitrogen or aluminum. The method involves precipitation of aluminum nitride by adding a reagent to the liquid lithium. The reagent will be either nitrogen or aluminum in a quantity adequate to react with the unwanted quantity of the impurity to form insoluble aluminum nitride. The aluminum nitride can be mechanically separated from the molten liquid lithium.

From Latin Americans to Latinos: Latin American Immigration in US: The Unwanted Children

ERIC Educational Resources Information Center

Moraña, Ana

2007-01-01

It is my understanding that Latin American immigrants in the United States, during the contested process of becoming Latinos (US citizens or the offspring of Latin Americans born in US) are for the most part socially portrayed as unwanted, messy children who need to be educated before they can become American citizens. Whether they can be called…

40 CFR 262.206 - Labeling and management standards for containers of unwanted material in the laboratory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... chemical reaction, (B) Whether the unwanted material has been used or is unused, (C) A description of the... the air, adverse chemical reactions, and dangerous situations that may result in harm to human health... contents of the container include, but are not limited to: (A) The name of the chemical(s), (B) The type or...

40 CFR 262.206 - Labeling and management standards for containers of unwanted material in the laboratory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... chemical reaction, (B) Whether the unwanted material has been used or is unused, (C) A description of the... the air, adverse chemical reactions, and dangerous situations that may result in harm to human health... contents of the container include, but are not limited to: (A) The name of the chemical(s), (B) The type or...

40 CFR 262.206 - Labeling and management standards for containers of unwanted material in the laboratory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... chemical reaction, (B) Whether the unwanted material has been used or is unused, (C) A description of the... the air, adverse chemical reactions, and dangerous situations that may result in harm to human health... contents of the container include, but are not limited to: (A) The name of the chemical(s), (B) The type or...

40 CFR 262.206 - Labeling and management standards for containers of unwanted material in the laboratory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... chemical reaction, (B) Whether the unwanted material has been used or is unused, (C) A description of the... the air, adverse chemical reactions, and dangerous situations that may result in harm to human health... contents of the container include, but are not limited to: (A) The name of the chemical(s), (B) The type or...

The Prevalence of Childhood Sexual Abuse and Adolescent Unwanted Sexual Contact among Boys and Girls Living in Victoria, Australia

ERIC Educational Resources Information Center

Moore, Elya E.; Romaniuk, Helena; Olsson, Craig A.; Jayasinghe, Yasmin; Carlin, John B.; Patton, George C.

2010-01-01

Objectives: Childhood sexual abuse (CSA) is associated with both short- and long-term adverse mental and physical health consequences, yet there remains considerable controversy about the prevalence of CSA in the general population. There is also little prospective data on unwanted sexual contact (USC) collected during adolescence. Methods: Data…

"The Red Zone": Temporal Risk for Unwanted Sex among College Students

ERIC Educational Resources Information Center

Flack, William F., Jr.; Caron, Marcia L.; Leinen, Sarah J.; Breitenbach, Katherine G.; Barber, Ann M.; Brown, Elaine N.; Gilbert, Caitlin T.; Harchak, Taylor F.; Hendricks, Melissa M.; Rector, Catherine E.; Schatten, Heather T.; Stein, Heather C.

2008-01-01

The "red zone" usually refers to the first few weeks of the first semester at college, when female students are believed to be at greatest risk for experiencing unwanted sex. We tested this notion using data from a survey study of 207 first-and second-year students (121 women, 84 men) at a small, liberal arts university. Results demonstrated only…

Legal Briefing: Unwanted Cesareans and Obstetric Violence.

PubMed

Pope, Thaddeus Mason

2017-01-01

A capacitated pregnant woman has a nearly unqualified right to refuse a cesarean section. Her right to say "no" takes precedence over clinicians' preferences and even over clinicians' concerns about fetal health. Leading medical societies, human rights organizations, and appellate courts have all endorsed this principle. Nevertheless, clinicians continue to limit reproductive liberty by forcing and coercing women to have unwanted cesareans. This "Legal Briefing" reviews recent court cases involving this type of obstetric violence. I have organized these court cases into the following six categories: 1. Epidemic of Unwanted Cesareans 2. Court-Ordered Cesareans 3. Physician-Coerced Cesareans 4. Physician-Ordered Cesareans 5. Cesareans for Incapacitated Patients 6. Cesareans for Patients in a Vegetative State or Who Are Brain Dead. Copyright 2017 The Journal of Clinical Ethics. All rights reserved.

Sex differences in the experience of unwanted sexual attention and behaviors during childhood.

PubMed

Whealin, Julia M; Zinzow, Heidi M; Salstrom, Seoka A; Jackson, Joan L

2007-01-01

Girls receive considerable amounts of unwanted sexual attention (UWSA) and behaviors (UWSB). Less is known about boys' unwanted sexual experiences. The primary goal of this study was to obtain a descriptive profile of the types and perpetrators of childhood UWSA/B. Secondary goals were to examine sex differences in emotional reactions to UWSA/B and influence of perpetrator. As many as 100 male and 100 female undergraduates completed the Exposure to Sexual Attention Scale and the Emotional Reaction Checklist. Results indicated that the majority of participants experienced UWSA/B during childhood, with females reporting higher rates of UWSB than males. Sex differences were also observed regarding types of perpetrators and emotional reactions. Findings are discussed as they relate to the sociocultural norms in which children are reared.

Microoxidation in wine production.

PubMed

Kilmartin, Paul A

2010-01-01

Microoxygenation (MOX) is now widely applied for the maturation of red wines as an alternative to barrel aging. The proposed improvements in wine quality arising from MOX include color stabilization, removal of unwanted off-odors, and improvements in wine mouthfeel. In this review, an outline is provided of oxygenation systems, particularly microbullage and polymer membrane delivery, and of the current understanding of wine oxidation processes. A summary of the results from published studies into red wine MOX is then provided, beginning with observations on O(2) and acetaldehyde accumulation, and the moderating effect of added sulfur dioxide. Effects upon red wine color, particularly the more rapid formation of polymeric pigments and higher color retention, have been consistently demonstrated in MOX studies, along with further effects on specific polyphenol compounds. A few reports have recently examined the effect of MOX on red wine aromas, but these have yet to identify compounds that consistently change in a manner that would explain sensory observations regarding a lowering of herbaceous and reductive odors. Likewise, tannin analyses have been undertaken in several studies, but explanations of the decline in wine astringency remain to be developed. The accelerated growth of unwanted microorganisms has also been examined in a limited number of studies, but no major problems have been identified in this area. Copyright © 2010 Elsevier Inc. All rights reserved.

Ethnoracial Disparities in Sexual Assault among Asian-Americans and Native Hawaiians/Other Pacific Islanders

PubMed Central

Crisanti, Annette S.; Frueh, B. Christopher; Gundaya, Debbie; Salvail, Florentina R.; Triffleman, Elisa G.

2010-01-01

Context Ethnoracial differences may exist in exposure to trauma and post-traumatic outcomes. However, Asian-Americans and Native Hawaiians/Other Pacific Islanders (NHOPI) are vastly underrepresented in research pertaining to trauma and health status sequelae. Objective To determine whether there are ethnoracial disparities in sexual trauma exposure and its sequelae for health and functioning among Asian-Americans and NHOPI. Design, Setting, Participants We examined data on sexual assault exposure from the 2006–2007 Hawai`i Behavioral Risk Factor Surveillance System (H-BRFSS), cross-sectional adult community-based probability sample (n = 12,573). Data were collected via computer-assisted random-digit landline telephone survey. Survey response rate was found to be about 48% in 2006 and 52% in 2007. Main Outcome Measures Demographic information, the Sexual Violence Module regarding unwanted sexual experiences, and questions about health lifestyles, chronic diseases and disability, and health status and quality of life. Results Participants were 42.3% White, 14.4% NHOPI, and 39.3% Asian-American. NHOPI had a higher 12-month period prevalence (2.24 per 100, CI=1.32–3.78) of any unwanted sexual experience, but a lower prevalence estimate and odds ratio for any lifetime unwanted sexual experience (prevalence: 9.38 per 100, CI=7.59–11.55; odds ratio: 0.61, CI=0.47–0.81) relative to Whites, after adjusting for age, gender, income and education level. Asian-Americans had lower prevalence estimates for 12-month period prevalence (0.78 per 100, CI=0.44–1.39), and lower lifetime prevalence estimates and odds ratios (prevalence: 3.91 per 100, CI=3.23–4.72; odds ratio: 0.27, CI=0.21–0.34). 12-month and lifetime prevalence estimate any unwanted sexual experiences for Whites were 0.71 per 100 (CI=0.45–1.12) and 12.01 per 100 (CI=10.96–13.14), respectively. Sexual assault experiences were highly associated with adverse health status sequelae (e.g., disability, poor general health), but there were no significant ethnoracial disparities on self-reported health outcomes among those with a lifetime history of unwanted sexual experiences. Conclusions Data revealed significant ethnoracial differences among Whites, Asian-Americans, and NHOPIs on unwanted sexual experiences, with relative risk differing by time period. This pattern of disparity could represent early stages of a new trend in local assaultive behaviors toward NHOPIs and merits attention. Across all ethnoracial groups, a lifetime history of any unwanted sexual experience is associated with a wide range of adverse health status sequelae. PMID:21208575

Is the Marginal Child More Likely to Be Murdered? An Examination of State Abortion Ratios and Infant Homicide

ERIC Educational Resources Information Center

Kalist, David E.; Molinari, Noelle A.

2006-01-01

We examine whether abortion removes from the population those infants most at risk of homicide. As part of our identification strategy, we find that abortion reduces the number of unwanted births, estimating that 1 percent increase in the abortion ratio reduces unwanted births by approximately 0.35 percent. Using cross-sectional time-series data…

Risk of Unwanted Sex for College Women: Evidence for a Red Zone

ERIC Educational Resources Information Center

Kimble, Matthew; Neacsiu, Andrada D.; Flack, William F., Jr.; Horner, Jessica

2008-01-01

Objective: University and college health and counseling centers frequently warn female students about the "red zone"--a period early in a student's first year at college during which she may be at higher risk for unwanted sexual experiences (UWS). The authors designed this study to assess temporal risk for UWS in 1st- and 2nd-year college women.…

Reduction of unwanted submental fat with ATX-101 (deoxycholic acid), an adipocytolytic injectable treatment: results from a phase III, randomized, placebo-controlled study*

PubMed Central

Rzany, B; Griffiths, T; Walker, P; Lippert, S; McDiarmid, J; Havlickova, B

2014-01-01

Summary Background Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence for their use. An injectable approach with ATX-101 (deoxycholic acid) is under investigation. Objectives To evaluate the efficacy and safety of ATX-101 for the reduction of unwanted SMF. Methods In this double-blind, placebo-controlled, phase III study, 363 patients with moderate/severe SMF were randomized to receive ATX-101 (1 or 2 mg cm−2) or placebo injections into their SMF at up to four treatment sessions ∽28 days apart, with a 12-week follow-up. The co-primary efficacy endpoints were the proportions of treatment responders [patients with ≥ 1-point improvement in SMF on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)] and patients satisfied with their face and chin appearance on the Subject Self-Rating Scale (SSRS). Secondary endpoints included skin laxity, calliper measurements and patient-reported outcomes. Adverse events were monitored. Results Significantly more ATX-101 recipients met the primary endpoint criteria vs. placebo: on the clinician scale, 59·2% and 65·3% of patients treated with ATX-101 1 and 2 mg cm−2, respectively, were treatment responders vs. 23·0% for placebo (CR-SMFRS;P < 0·001); on the patient scale, 53·3% and 66·1%, respectively, vs. 28·7%, were satisfied with their face/chin appearance (SSRS;P < 0·001). Calliper measurements showed a significant reduction in SMF (P < 0·001), skin laxity was not worsened and patients reported improvements in the severity and psychological impact of SMF with ATX-101 vs. placebo. Most adverse events were transient and associated with the treatment area. Conclusions ATX-101 was effective and well tolerated for nonsurgical SMF reduction. What's already known about this topic? Unwanted submental fat (SMF) is considered aesthetically unappealing. Liposuction and face-lift are effective treatments for SMF reduction but are invasive and not suitable for all patients, whereas nonsurgical alternatives lack robust clinical evidence related to their safety and efficacy. ATX-101, a proprietary formulation of synthetically derived deoxycholic acid, is the first nonsurgical treatment for SMF reduction to be investigated in randomized, placebo-controlled clinical studies. What does this study add? This study provides the first data from a large-scale, randomized, placebo-controlled, phase III study of an injectable therapy for SMF reduction in a field currently lacking a sound evidence base. ATX-101 was superior to placebo for the clinician- and patient-evaluated reduction of unwanted SMF and led to improved patient perception about their appearance. ATX-101 was well tolerated; treatment-associated adverse events were mainly transient and localized injection-site reactions. PMID:24147933

A demographic survey of unwanted horses in Ireland 2005-2010

PubMed Central

2012-01-01

Background The Irish Horse Industry expanded during the Celtic Tiger boom years, then contracted in the current economic recession. High value horses were traditionally controlled through sale at public auction, private sales and sales to dealers; these are now also being reduced by decreases in production (> 40%), and increases in retirement, re-homing, euthanasia and disposal through Category 2 plants and abattoirs. The absence or banning of horse abattoirs has been shown to have very significant welfare social and economic consequences in the USA. This study described the currently available data on the demographics of unwanted horses in Ireland from 2005 to 2010. Results The majority of horses euthanised by practicing veterinarians are destroyed on medical grounds but the number euthanised at the request of welfare groups and the state, as well as welfare related calls and the number of horses involved in these calls and subsequent visits is increasing reflecting the increasing involvement of the veterinary profession in equine welfare. Welfare groups have limited resources and do not have a tradition of recording data, but they too have reported increasing calls, visits and numbers of horses per visit. Welfare groups provide significant service to equine welfare and the community. Local Authorities report similar trends. Over 300 horses were found dead or required immediate or subsequent euthanasia following welfare group and local authority visits in 2010, which is of national concern. The majority of local authority interfaces with unwanted horses are with urban (60%) rather than rural (40%) horses. Mortality figures are poor indicators of non-fatal neglect. More horses were admitted into the care of local authorities than welfare groups, reflecting significant state and taxpayer investment in the control of low value horses. Category 2 plants and abattoirs represent a significant state investment in licensing and control in the national interest. Abattoirs provide an increasingly important and essential service for the disposal of unwanted horses. Despite the increase in unwanted horses, Ireland is a minority contributor to the EU slaughter total. Conclusions There is a need for annual demographic data compilation and review of the numbers of unwanted horses and ponies within the horse industry to assist policy makers and legislators. PMID:22385906

Reasoning with Vectors: A Continuous Model for Fast Robust Inference.

PubMed

Widdows, Dominic; Cohen, Trevor

2015-10-01

This paper describes the use of continuous vector space models for reasoning with a formal knowledge base. The practical significance of these models is that they support fast, approximate but robust inference and hypothesis generation, which is complementary to the slow, exact, but sometimes brittle behavior of more traditional deduction engines such as theorem provers. The paper explains the way logical connectives can be used in semantic vector models, and summarizes the development of Predication-based Semantic Indexing, which involves the use of Vector Symbolic Architectures to represent the concepts and relationships from a knowledge base of subject-predicate-object triples. Experiments show that the use of continuous models for formal reasoning is not only possible, but already demonstrably effective for some recognized informatics tasks, and showing promise in other traditional problem areas. Examples described in this paper include: predicting new uses for existing drugs in biomedical informatics; removing unwanted meanings from search results in information retrieval and concept navigation; type-inference from attributes; comparing words based on their orthography; and representing tabular data, including modelling numerical values. The algorithms and techniques described in this paper are all publicly released and freely available in the Semantic Vectors open-source software package.

Improved Plaque Assay Identifies a Novel Anti-Chlamydia Ceramide Derivative with Altered Intracellular Localization

PubMed Central

Banhart, Sebastian; Saied, Essa M.; Martini, Andrea; Koch, Sophia; Aeberhard, Lukas; Madela, Kazimierz; Arenz, Christoph

2014-01-01

Chlamydia trachomatis is a medically important human pathogen causing different diseases, including trachoma, the leading cause of preventable blindness in developing countries, and sexually transmitted infections that can lead to infertility and ectopic pregnancies. There is no vaccine against C. trachomatis at present. Broad-spectrum antibiotics are used as standard therapy to treat the infection but have unwanted side effects, such as inducing persistent or recurring infections and affecting the host microbiome, necessitating the development of novel anti-Chlamydia therapies. Here, we describe the establishment of a robust, fast, and simple plaque assay using liquid overlay medium (LOM) for the identification of anti-Chlamydia compounds. Using the LOM plaque assay, we identified nitrobenzoxadiazole (NBD)-labeled 1-O-methyl-ceramide-C16 as a compound that efficiently inhibits C. trachomatis replication without affecting the viability of the host cell. Further detailed analyses indicate that 1-O-methyl-NBD-ceramide-C16 acts outside the inclusion. Thereby, 1-O-methyl-NBD-ceramide-C16 represents a lead compound for the development of novel anti-Chlamydia drugs and furthermore constitutes an agent to illuminate sphingolipid trafficking pathways in Chlamydia infections. PMID:25001308

Reasoning with Vectors: A Continuous Model for Fast Robust Inference

PubMed Central

Widdows, Dominic; Cohen, Trevor

2015-01-01

This paper describes the use of continuous vector space models for reasoning with a formal knowledge base. The practical significance of these models is that they support fast, approximate but robust inference and hypothesis generation, which is complementary to the slow, exact, but sometimes brittle behavior of more traditional deduction engines such as theorem provers. The paper explains the way logical connectives can be used in semantic vector models, and summarizes the development of Predication-based Semantic Indexing, which involves the use of Vector Symbolic Architectures to represent the concepts and relationships from a knowledge base of subject-predicate-object triples. Experiments show that the use of continuous models for formal reasoning is not only possible, but already demonstrably effective for some recognized informatics tasks, and showing promise in other traditional problem areas. Examples described in this paper include: predicting new uses for existing drugs in biomedical informatics; removing unwanted meanings from search results in information retrieval and concept navigation; type-inference from attributes; comparing words based on their orthography; and representing tabular data, including modelling numerical values. The algorithms and techniques described in this paper are all publicly released and freely available in the Semantic Vectors open-source software package.1 PMID:26582967

Electron attachment to antipyretics: Possible implications of their metabolic pathways

NASA Astrophysics Data System (ADS)

Pshenichnyuk, Stanislav A.; Modelli, Alberto

2012-06-01

The empty-level structures and formation of negative ion states via resonance attachment of low-energy (0-15 eV) electrons into vacant molecular orbitals in a series of non-steroidal anti-inflammatory drugs (NSAIDs), namely aspirin, paracetamol, phenacetin, and ibuprofen, were investigated in vacuo by electron transmission and dissociative electron attachment (DEA) spectroscopies, with the aim to model the behavior of these antipyretic agents under reductive conditions in vivo. The experimental findings are interpreted with the support of density functional theory calculations. The negative and neutral fragments formed by DEA in the gas phase display similarities with the main metabolites of these commonly used NSAIDs generated in vivo by the action of cytochrome P450 enzymes, as well as with several known active agents. It is concluded that xenobiotic molecules which possess pronounced electron-accepting properties could in principle follow metabolic pathways which parallel the gas-phase dissociative decay channels observed in the DEA spectra at incident electron energies below 1 eV. Unwanted side effects as, e.g., hepatoxicity or carcinogenicity produced by the NSAIDs under study in human organism are discussed within the "free radical model" framework, reported earlier to describe the toxic action of the well-known model toxicant carbon tetrachloride.

Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report

PubMed Central

Reiman, Amanda; Welty, Mark; Solomon, Perry

2017-01-01

Abstract Introduction: Prescription drug overdoses are the leading cause of accidental death in the United States. Alternatives to opioids for the treatment of pain are necessary to address this issue. Cannabis can be an effective treatment for pain, greatly reduces the chance of dependence, and eliminates the risk of fatal overdose compared to opioid-based medications. Medical cannabis patients report that cannabis is just as effective, if not more, than opioid-based medications for pain. Materials and Methods: The current study examined the use of cannabis as a substitute for opioid-based pain medication by collecting survey data from 2897 medical cannabis patients. Discussion: Thirty-four percent of the sample reported using opioid-based pain medication in the past 6 months. Respondents overwhelmingly reported that cannabis provided relief on par with their other medications, but without the unwanted side effects. Ninety-seven percent of the sample “strongly agreed/agreed” that they are able to decrease the amount of opiates they consume when they also use cannabis, and 81% “strongly agreed/agreed” that taking cannabis by itself was more effective at treating their condition than taking cannabis with opioids. Results were similar for those using cannabis with nonopioid-based pain medications. Conclusion: Future research should track clinical outcomes where cannabis is offered as a viable substitute for pain treatment and examine the outcomes of using cannabis as a medication assisted treatment for opioid dependence. PMID:28861516

Are pregnancy intentions associated with transitions into and out of marriage?

PubMed Central

Maddow-Zimet, Isaac; Lindberg, Laura; Kost, Kathryn; Lincoln, Alicia

2015-01-01

CONTEXT Beyond associations with health outcomes, pregnancy intentions may be associated with social outcomes, including marital transitions. METHODS Linked data from the 2004-2008 Oklahoma Pregnancy Risk Assessment Monitoring System (PRAMS) survey and The Oklahoma Toddler Survey (TOTS) from 2006-2010 were used to examine a four category measure of women’s pregnancy intentions (intended, mistimed <2 years, mistimed >=2 years, unwanted) and changes in marital status between conception, birth and age two. Analyses were stratified by marital status at conception (married, N=3,617; unmarried, N=2,123). Propensity score methods were used to adjust for confounding factors, and logistic regressions were used to estimate the association between pregnancy intention and marital formation and dissolution at birth and child’s age two. RESULTS Intention status was associated with mothers’ marital transitions by child’s age two, both in analyses unadjusted and adjusted for confounding background characteristics. In adjusted models, among women married at conception, those with a birth resulting from an unwanted pregnancy were more likely (OR=2.2) than those with an intended pregnancy to transition out of marriage by the time their child was age two. Among women unmarried at conception, those with an unwanted pregnancy were less likely (OR=.4) than those with an intended pregnancy to marry before the child was age two. Births resulting from mistimed pregnancies were not significantly associated with marital transitions. CONCLUSIONS Women with a child resulting from an unwanted pregnancy are less likely to marry, and less likely to stay married, than women with an intended birth. Future assessments of the consequences of unintended childbearing should distinguish between mistimed and unwanted births. PMID:26929138

78 FR 50213 - Service Rules for Advanced Wireless Services H Block-Implementing Section 6401 of the Middle...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-16

... ``interference'' to mean ``[t]he effect of unwanted energy due to one or a combination of emissions, radiations... in one band will seriously degrade, obstruct, or repeatedly interrupt operations in another band... parameters designed such that the presence of the new operators' signals ``would not be perceptible to the...

An Overview of Peace Education in Turkey: Definitions, Difficulties, and Suggestions--A Qualitative Analysis

ERIC Educational Resources Information Center

Demir, Semra

2011-01-01

In modern world, advances and changes experienced in social, political, and economic domains cannot be effective in diminishing the unwanted behaviors displayed by individuals in a society. This underpins the need for creating a peace culture based on equality, justice, democracy, human rights, tolerance, and solidarity in a society. The purpose…

Chapter 10. Herbicides for plant control

Treesearch

John F. Vallentine

2004-01-01

Herbicides can be an effective, necessary, and environmentally sound tool for the control of weeds and brush on rangelands (Young and others 1981b). As a result, chemical control is a widely used means of removing unwanted or noxious plants from range and other pasture lands. Selective plant control by mechanical, biological, fire, or manual means should also be...

Word-of-mouth marketing: low-cost technique proves an effective way to promote teen clinic.

PubMed

2006-01-01

From the outset, the team at the Longmont (CO) Teen Clinic faced a two-fold marketing dilemma. The first problem was a small budget. As a nonprofit with limited funds, the staff knew that they would have to get creative to effectively reach their target audience and fulfill the clinic's mission of battling unwanted teen pregnancies and sexually transmitted diseases (STD) among area women aged 19 and younger.

The Effect of Soil Properties on Metal Bioavailability: Field Scale Validation to Support Regulatory Acceptance

DTIC Science & Technology

2014-06-01

unacceptable levels of the toxic metal(loid)s arsenic (As), cadmium (Cd), chromium (Cr), and lead (Pb). With the exception of Pb contaminated soils, human...remediation and closure. Lead (Pb), arsenic (As), chromium (Cr), and cadmium (Cd) are toxic (i.e., capable of producing an unwanted, deleterious effect...lagoon are contaminated with high concentrations of lead , chromium, and cadmium . 14 Deseret Chemical Depot: The Deseret Chemical Depot is

Measuring the effects of Coulomb repulsion via signal decay in an atmospheric pressure laser ionization ion mobility spectrometer.

PubMed

Ihlenborg, Marvin; Schuster, Ann-Kathrin; Grotemeyer, Juergen; Gunzer, Frank

2018-01-01

Using lasers in ion mobility spectrometry offers a lot of advantages compared to standard ionization sources. Especially, the ion yield can be drastically increased. It can, however, reach levels where the Coulomb repulsion leads to unwanted side effects. Here, we investigate how the Coulomb repulsion can be detected apart from the typical signal broadening by measuring effects created already in the reaction region and comparing them with corresponding finite element method simulations.

Perinatal mortality--a suitable index of health worldwide?

PubMed

Savage, A

1986-11-22

As a result of cultural factors, perinatal mortality may not be the most appropriate measure of health. Comparisons of the health of different countries should not be based on only 1 criterion unless general attitudes are the same. In developed countries, where abortion is widely available, unwanted pregnancies are handled before delivery. In some developing countries in Africa, however, population control may take the form of allowing a newborn to die of starvation, for example. Given this cultural difference, Third World countries rank lowest in perinatal health. It is suggested that mortality and morbidity should be calculated decade by decade before an index is derived. A 20-year old from a developing country, where there is no drug problem and attempted suicide is rare, might receive a higher health rating than his counterpart in developed countries.

Highly selective SGLT2 inhibitor dapagliflozin reduces seizure activity in pentylenetetrazol-induced murine model of epilepsy.

PubMed

Erdogan, Mumin Alper; Yusuf, Dimas; Christy, Joanna; Solmaz, Volkan; Erdogan, Arife; Taskiran, Emin; Erbas, Oytun

2018-06-07

Worldwide, over 10 million individuals suffer from drug-resistant epilepsy. New therapeutic strategies are needed to address this debilitating disease. Inhibition of sodium-glucose linked transporters (SGLTs), which are variably expressed in the brain, has been demonstrated to reduce seizure activity in murine models of epilepsy. Here we investigated the effects of dapagliflozin, a highly competitive SGLT2 inhibitor currently used as a drug for diabetes mellitus, on seizure activity in rats with pentylenetetrazol (PTZ) induced seizures. Laboratory rats (n = 48) were evenly randomized into two experiments, each with four study arms: (1) a vehicle-treated (placebo) arm infused with saline; (2) a control arm infused with PTZ; (3) a treatment arm with PTZ and dapagliflozin at 75 mg/kg, and (4) another treatment arm with PTZ and dapagliflozin at 150 mg/kg. Study subjects were assessed for seizures either via EEG as measured by spike wave percentage (SWP), or clinically via Racine's scales scores (RSS) and time to first myoclonic jerk (TFMJ). Rats treated with dapagliflozin had lower mean SWP on EEG (20.4% versus 75.3% for untreated rats). Behaviorally, treatment with dapagliflozin improved means RSS (2.33 versus 5.5) and mean TFMJ (68.3 versus 196.7 s). All of these findings were statistically significant with p-values of < 0.0001. There was a trend towards even better seizure control with the higher dose of dapagliflozin at 150 mg/kg, however this was not consistently statistically significant. Dapagliflozin decreased seizure activity in rats with PTZ-induced seizures. This may be explained by the anti-seizure effects of decreased glucose availability and a reduction in sodium transport across neuronal membranes which can confer a stabilizing effect against excitability and unwanted depolarization. The potential clinical role of dapagliflozin and other SGLT2 inhibitors as anti-seizure medications should be further explored.

Managing multimorbidity in primary care in patients with chronic respiratory conditions.

PubMed

Morrison, Deborah; Agur, Karolina; Mercer, Stewart; Eiras, Andreia; González-Montalvo, Juan I; Gruffydd-Jones, Kevin

2016-09-15

The term multimorbidity is usually defined as the coexistence of two or more chronic conditions within an individual, whereas the term comorbidity traditionally describes patients with an index condition and one or more additional conditions. Multimorbidity of chronic conditions markedly worsens outcomes in patients, increases treatment burden and increases health service costs. Although patients with chronic respiratory disease often have physical comorbidities, they also commonly experience psychological problems such as depression and anxiety. Multimorbidity is associated with increased health-care utilisation and specifically with an increased number of prescription drugs in individuals with multiple chronic conditions such as chronic obstructive pulmonary disease. This npj Primary Care Respiratory Medicine Education Section case study involves a patient in a primary care consultation presenting several common diseases prevalent in people of this age. The patient takes nine different drugs at this moment, one or more pills for each condition, which amounts to polypharmacy. The problems related with polypharmacy recommend that a routine medication review by primary care physicians be performed to reduce the risk of adverse effects of polypharmacy among those with multiple chronic conditions. The primary care physician has the challenging role of integrating all of the clinical problems affecting the patient and reviewing all medicaments (including over-the-counter medications) taken by the patient at any point in time, and has the has the key to prevent the unwanted consequences of polypharmacy. Multimorbid chronic disease management can be achieved with the use of care planning, unified disease templates, use of information technology with appointment reminders and with the help of the wider primary care and community teams.

Selective, retrieval-independent disruption of methamphetamine-associated memory by actin depolymerization.

PubMed

Young, Erica J; Aceti, Massimiliano; Griggs, Erica M; Fuchs, Rita A; Zigmond, Zachary; Rumbaugh, Gavin; Miller, Courtney A

2014-01-15

Memories associated with drugs of abuse, such as methamphetamine (METH), increase relapse vulnerability to substance use disorder. There is a growing consensus that memory is supported by structural and functional plasticity driven by F-actin polymerization in postsynaptic dendritic spines at excitatory synapses. However, the mechanisms responsible for the long-term maintenance of memories, after consolidation has occurred, are largely unknown. Conditioned place preference (n = 112) and context-induced reinstatement of self-administration (n = 19) were used to assess the role of F-actin polymerization and myosin II, a molecular motor that drives memory-promoting dendritic spine actin polymerization, in the maintenance of METH-associated memories and related structural plasticity. Memories formed through association with METH but not associations with foot shock or food reward were disrupted by a highly-specific actin cycling inhibitor when infused into the amygdala during the postconsolidation maintenance phase. This selective effect of depolymerization on METH-associated memory was immediate, persistent, and did not depend upon retrieval or strength of the association. Inhibition of non-muscle myosin II also resulted in a disruption of METH-associated memory. Thus, drug-associated memories seem to be actively maintained by a unique form of cycling F-actin driven by myosin II. This finding provides a potential therapeutic approach for the selective treatment of unwanted memories associated with psychiatric disorders that is both selective and does not rely on retrieval of the memory. The results further suggest that memory maintenance depends upon the preservation of polymerized actin. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Drug and chemical residues in domestic animals.

PubMed

Mussman, H C

1975-02-01

Given the large number of chemical substances that may find their way into the food supply, a system is needed to monitor their presence. The U. S. Department of Agriculture's Meat and Poultry Inspection Program routinely tests for chemical residues in animals coming to slaughter. Pesticides, heavy metals, growth promotants (hormones and hormonelike agents), and antibiotics are included. Samples are taken statistically so that inferences as to national incidence of residues can be drawn. When a problem is identified, a more selective sampling is designed to help follow up on the initial regulatory action. In testing for pesticides, only DDT and dieldrin are found with any frequency and their levels are decreasing; violative residues of any chlorinated hydrocarbon are generally a result of an industrial accident rather than agricultural usage. Analyses for heavy metals have revealed detectable levels of mercury, lead, and others, but none at levels that are considered a health hazard. Of the hormone or hormonelike substances, only diethylstilbestrol has been a residue problem and its future is uncertain. The most extensive monitoring for veterinary drugs is on the antimicrobials, including sulfonamides, streptomycin, and the tetracycline group of antibiotics that constitute the bulk of the violations; their simultaneous use prophylactically and therapeutically has contributed to the problem in certain cases. A strong, well-designed user education program on proper application of pesticides, chemicals, and veterinary drugs appears to be one method of reducing the incidence of unwanted residues.

Noise from a Supersonic Round Jet Discharging Into a Duct

NASA Technical Reports Server (NTRS)

Zaman, K. B. M. Q.; Fagan, A. F.

2014-01-01

In an effort to understand an 'unwanted noise' problem occasionally encountered in ground test facilities, the interaction of a jet flow with a duct is studied in a model scale experiment. While the interaction of subsonic jets was studied earlier, that of supersonic jets is considered in this paper. The effect of the presence of a cylindrical duct in the path of the jet is studied through sound pressure level spectral measurements as well as schlieren flow visualization. When the jet involves screech tones the placement of the duct is found to make only minor effects on the tones themselves as well as on the high frequency noise. However, there is increased energy at low frequencies. The increase in low frequency noise becomes clearer when screech is eliminated from the jet by two small tabs placed at the nozzle exit. It is shown that spectral peaks and increased sound pressure levels occur at frequencies corresponding to the axial acoustic resonance modes of the duct. These peaks persist into the supersonic regime, however, their amplitudes diminish relative to increasing spectral amplitudes at other frequencies with increasing jet Mach number. A wire-mesh screen attached to the end of the duct effectively suppresses such unwanted noise at subsonic as well as supersonic conditions.

RNAi Experiments in D. melanogaster: Solutions to the Overlooked Problem of Off-Targets Shared by Independent dsRNAs

PubMed Central

Seinen, Erwin; Burgerhof, Johannes G. M.; Jansen, Ritsert C.; Sibon, Ody C. M.

2010-01-01

Background RNAi technology is widely used to downregulate specific gene products. Investigating the phenotype induced by downregulation of gene products provides essential information about the function of the specific gene of interest. When RNAi is applied in Drosophila melanogaster or Caenorhabditis elegans, often large dsRNAs are used. One of the drawbacks of RNAi technology is that unwanted gene products with sequence similarity to the gene of interest can be down regulated too. To verify the outcome of an RNAi experiment and to avoid these unwanted off-target effects, an additional non-overlapping dsRNA can be used to down-regulate the same gene. However it has never been tested whether this approach is sufficient to reduce the risk of off-targets. Methodology We created a novel tool to analyse the occurance of off-target effects in Drosophila and we analyzed 99 randomly chosen genes. Principal Findings Here we show that nearly all genes contain non-overlapping internal sequences that do show overlap in a common off-target gene. Conclusion Based on our in silico findings, off-target effects should not be ignored and our presented on-line tool enables the identification of two RNA interference constructs, free of overlapping off-targets, from any gene of interest. PMID:20957038

Prioritizing pharmacokinetic drug interaction precipitants in natural products: application to OATP inhibitors in grapefruit juice.

PubMed

Johnson, Emily J; Won, Christina S; Köck, Kathleen; Paine, Mary F

2017-04-01

Natural products, including botanical dietary supplements and exotic drinks, represent an ever-increasing share of the health-care market. The parallel ever-increasing popularity of self-medicating with natural products increases the likelihood of co-consumption with conventional drugs, raising concerns for unwanted natural product-drug interactions. Assessing the drug interaction liability of natural products is challenging due to the complex and variable chemical composition inherent to these products, necessitating a streamlined preclinical testing approach to prioritize precipitant individual constituents for further investigation. Such an approach was evaluated in the current work to prioritize constituents in the model natural product, grapefruit juice, as inhibitors of intestinal organic anion-transporting peptide (OATP)-mediated uptake. Using OATP2B1-expressing MDCKII cells (Madin-Darby canine kidney type II) and the probe substrate estrone 3-sulfate, IC 50s were determined for constituents representative of the flavanone (naringin, naringenin, hesperidin), furanocoumarin (bergamottin, 6',7'-dihydroxybergamottin) and polymethoxyflavone (nobiletin and tangeretin) classes contained in grapefruit juice. Nobiletin was the most potent (IC 50 , 3.7 μm); 6',7'-dihydroxybergamottin, naringin, naringenin and tangeretin were moderately potent (IC 50 , 20-50 μm); and bergamottin and hesperidin were the least potent (IC 50 , >300 μm) OATP2B1 inhibitors. Intestinal absorption simulations based on physiochemical properties were used to determine the ratios of unbound concentration to IC 50 for each constituent within enterocytes and to prioritize in order of pre-defined cut-off values. This streamlined approach could be applied to other natural products that contain multiple precipitants of natural product-drug interactions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Zinc-finger nuclease-mediated gene correction using single AAV vector transduction and enhancement by Food and Drug Administration-approved drugs

PubMed Central

Ellis, BL; Hirsch, ML; Porter, SN; Samulski, RJ; Porteus, MH

2016-01-01

An emerging strategy for the treatment of monogenic diseases uses genetic engineering to precisely correct the mutation(s) at the genome level. Recent advancements in this technology have demonstrated therapeutic levels of gene correction using a zinc-finger nuclease (ZFN)-induced DNA double-strand break in conjunction with an exogenous DNA donor substrate. This strategy requires efficient nucleic acid delivery and among viral vectors, recombinant adeno-associated virus (rAAV) has demonstrated clinical success without pathology. However, a major limitation of rAAV is the small DNA packaging capacity and to date, the use of rAAV for ZFN gene delivery has yet to be reported. Theoretically, an ideal situation is to deliver both ZFNs and the repair substrate in a single vector to avoid inefficient gene targeting and unwanted mutagenesis, both complications of a rAAV co-transduction strategy. Therefore, a rAAV format was generated in which a single polypeptide encodes the ZFN monomers connected by a ribosome skipping 2A peptide and furin cleavage sequence. On the basis of this arrangement, a DNA repair substrate of 750 nucleotides was also included in this vector. Efficient polypeptide processing to discrete ZFNs is demonstrated, as well as the ability of this single vector format to stimulate efficient gene targeting in a human cell line and mouse model derived fibroblasts. Additionally, we increased rAAV-mediated gene correction up to sixfold using a combination of Food and Drug Administration-approved drugs, which act at the level of AAV vector transduction. Collectively, these experiments demonstrate the ability to deliver ZFNs and a repair substrate by a single AAV vector and offer insights for the optimization of rAAV-mediated gene correction using drug therapy. PMID:22257934