WorldWideScience

Sample records for drug effect unveils

  1. Unveiling the truth: warnings reduce the repetition-based truth effect.

    Science.gov (United States)

    Nadarevic, Lena; Aßfalg, André

    2017-07-01

    Typically, people are more likely to consider a previously seen or heard statement as true compared to a novel statement. This repetition-based "truth effect" is thought to rely on fluency-truth attributions as the underlying cognitive mechanism. In two experiments, we tested the nature of the fluency-attribution mechanism by means of warning instructions, which informed participants about the truth effect and asked them to prevent it. In Experiment 1, we instructed warned participants to consider whether a statement had already been presented in the experiment to avoid the truth effect. However, warnings did not significantly reduce the truth effect. In Experiment 2, we introduced control questions and reminders to ensure that participants understood the warning instruction. This time, warning reduced, but did not eliminate the truth effect. Assuming that the truth effect relies on fluency-truth attributions, this finding suggests that warned participants could control their attributions but did not disregard fluency altogether when making truth judgments. Further, we found no evidence that participants overdiscount the influence of fluency on their truth judgments.

  2. Games Uniforms Unveiled

    Institute of Scientific and Technical Information of China (English)

    Linda

    2008-01-01

    The uniforms for Beijing Olympics’ workers, technical staff and volunteers have been unveiled to mark the 200-day countdown to the Games. The uniforms feature the key element of the clouds of promise and will be in three colors:red for Beijing Olympic Games Committee staff, blue

  3. Unveiling the Effects of Citizen Journalism Practice on College Students' Social Capital

    Science.gov (United States)

    Nah, Seungahn; Namkoong, Kang; Van Stee, Stephanie K.; Record, Rachael A.

    2014-01-01

    This study examined the effects of citizen journalism practices on social capital concerning nonprofit and voluntary organizations (i.e., satisfaction, trust, and engagement). Through a quasi-experimental design, the analyses revealed that students in the treatment group, in which participants engaged in citizen journalism practice, had greater…

  4. Culture and Next-generation sequencing-based drug susceptibility testing unveil high levels of drug-resistant-TB in Djibouti: results from the first national survey.

    Science.gov (United States)

    Tagliani, Elisa; Hassan, Mohamed Osman; Waberi, Yacine; De Filippo, Maria Rosaria; Falzon, Dennis; Dean, Anna; Zignol, Matteo; Supply, Philip; Abdoulkader, Mohamed Ali; Hassangue, Hawa; Cirillo, Daniela Maria

    2017-12-15

    Djibouti is a small country in the Horn of Africa with a high TB incidence (378/100,000 in 2015). Multidrug-resistant TB (MDR-TB) and resistance to second-line agents have been previously identified in the country but the extent of the problem has yet to be quantified. A national survey was conducted to estimate the proportion of MDR-TB among a representative sample of TB patients. Sputum was tested using XpertMTB/RIF and samples positive for MTB and resistant to rifampicin underwent first line phenotypic susceptibility testing. The TB supranational reference laboratory in Milan, Italy, undertook external quality assurance, genotypic testing based on whole genome and targeted-deep sequencing and phylogenetic studies. 301 new and 66 previously treated TB cases were enrolled. MDR-TB was detected in 34 patients: 4.7% of new and 31% of previously treated cases. Resistance to pyrazinamide, aminoglycosides and capreomycin was detected in 68%, 18% and 29% of MDR-TB strains respectively, while resistance to fluoroquinolones was not detected. Cluster analysis identified transmission of MDR-TB as a critical factor fostering drug resistance in the country. Levels of MDR-TB in Djibouti are among the highest on the African continent. High prevalence of resistance to pyrazinamide and second-line injectable agents have important implications for treatment regimens.

  5. Effects of Drugs

    Science.gov (United States)

    ... Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search ... who aren't yet born. Drug use can hurt the body and the brain, sometimes forever. Drug use can also lead to addiction, a long-lasting brain disease in which people ...

  6. Lord Shiva Statue Unveiled

    CERN Multimedia

    2004-01-01

    On 18 June, CERN unveiled an unusual new landmark, a 2m tall statue of the Indian deity Lord Shiva. The Director-General and Dr. Kakodkar watch as Mr.Chandrasekhar signs the Guest Book. The statue is a gift from India, celebrating CERN's long association with India which started in the 1960's and continues strongly today. It was unveiled by the Director General, Dr Robert Aymar, His Excellency Mr K. M. Chandrasekhar, Ambassador (WTO-Geneva) and Dr Anil Kakodkar, Chairman of the Atomic Energy Commission and Secretary, Dept of Atomic Energy, India. In the Hindu religion, this form of the dancing Lord Shiva is known as the Nataraj and symbolises Shakti, or life force. As a plaque alongside the statue explains, the belief is that Lord Shiva danced the Universe into existence, motivates it, and will eventually extinguish it. Carl Sagan drew the metaphor between the cosmic dance of the Nataraj and the modern study of the 'cosmic dance' of subatomic particles. The statue was made in India. The original sculpture was...

  7. Influence of drug colour on perceived drug effects and efficacy.

    Science.gov (United States)

    Tao, Da; Wang, Tieyan; Wang, Tieshan; Qu, Xingda

    2018-02-01

    A drug's physical characteristics, such as colour, could be factors influencing its therapeutic effects. It is not well understood whether people's expectations on drug effects and efficacy are affected by colour, especially among Chinese population. This study was conducted to examine people's expectations on drug effects and efficacy on the basis of drug colour, and to reveal possible gender differences in colour-related drug expectations. Participants (n = 224) were asked to classify seven single-coloured and six two-coloured capsules into one of four categories of drug effects, and to indicate the strength of drug efficacy. It is found that all the coloured capsules yielded non-chance distributions in classifications of drug effects, with six single-coloured and four two-coloured capsules associated with specific drug effects. Colour also conveyed differential strengths of drug efficacy in general and in relation to specific drug effects. There were gender differences in drug expectations for some colours and colour combinations. Practitioner Summary: Drug colour was found to have impacts on perceived drug effects and efficacy. The findings from the present study can be used by ergonomics practitioners to design appropriate drug colours in support of drug differentiation, therapeutic effects and medication adherence.

  8. The effect of post-mastectomy radiation therapy on breast implants: Unveiling biomaterial alterations with potential implications on capsular contracture

    Energy Technology Data Exchange (ETDEWEB)

    Ribuffo, Diego; Lo Torto, Federico [Department of Plastic Surgery, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); Giannitelli, Sara M. [Tissue Engineering Unit, Department of Engineering, Università Campus Bio-Medico di Roma, Via Álvaro del Portillo 21, 00128 Rome (Italy); Urbini, Marco; Tortora, Luca [Surface Analysis Laboratory, Department of Mathematics and Physics, University “Roma Tre”, Via della Vasca Navale 84, 00146 Rome (Italy); INFN — National Institute of Nuclear Physics, Section of Roma Tre, Via della Vasca Navale 84, 00146 Rome (Italy); Mozetic, Pamela; Trombetta, Marcella [Tissue Engineering Unit, Department of Engineering, Università Campus Bio-Medico di Roma, Via Álvaro del Portillo 21, 00128 Rome (Italy); Basoli, Francesco; Licoccia, Silvia [Department of Chemical Science and Technologies, University of Rome “Tor Vergata”, Via della Ricerca Scientifica 1, 00173 Rome (Italy); Tombolini, Vincenzo [Department of Radiation Oncology, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); Spencer-Lorillard Foundation, Viale Regina Elena 291, 00161 Rome (Italy); Cassese, Raffaele [Department of Radiation Oncology, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); Scuderi, Nicolò [Department of Plastic Surgery, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); and others

    2015-12-01

    Post-mastectomy breast reconstruction with expanders and implants is recognized as an integral part of breast cancer treatment. Its main complication is represented by capsular contracture, which leads to poor expansion, breast deformation, and pain, often requiring additional surgery. In such a scenario, the debate continues as to whether the second stage of breast reconstruction should be performed before or after post-mastectomy radiation therapy, in light of potential alterations induced by irradiation to silicone biomaterial. This work provides a novel, multi-technique approach to unveil the role of radiotherapy in biomaterial alterations, with potential involvement in capsular contracture. Following irradiation, implant shells underwent mechanical, chemical, and microstructural evaluation by means of tensile testing, Attenuated Total Reflectance Fourier Transform InfraRed spectroscopy (ATR/FTIR), Scanning Electron Microscopy (SEM), high resolution stylus profilometry, and Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS). Our findings are consistent with radiation-induced modifications of silicone that, although not detectable at the microscale, can be evidenced by more sophisticated nanoscale surface analyses. In light of these results, biomaterial irradiation cannot be ruled out as one of the possible co-factors underlying capsular contracture. - Highlights: • The debate continues whether to perform breast reconstruction before or after PMRT. • Radiation therapy may alter implant material, concurring to capsular contracture. • In this work, irradiated implants were investigated by a multi-technique approach. • Radiation-induced alterations could be evidenced by ATR/FTIR and ToF-SIMS. • Reported alteration might represent a co-factor underlying capsular contracture.

  9. Communication, Reasoning, and Planned Behaviors: Unveiling the Effect of Interactive Communication in an Anti-Smoking Social Media Campaign.

    Science.gov (United States)

    Namkoong, Kang; Nah, Seungahn; Record, Rachael A; Van Stee, Stephanie K

    2017-01-01

    This study examines direct and indirect effects of interactive communication in an antismoking social media campaign. To that end, we pose a multitheoretical framework that integrates communication mediation models and the Theory of Planned Behavior. To test the theorized model, we conducted an experiment using a two-group pretest-posttest design. Participants (N = 201) were randomly assigned into two experimental conditions: "campaign message reception only" as a control group and "message reception and social interaction" as a treatment group, in which the participants contributed to the antismoking campaign by posting their own campaign ideas and information they found through mediated and interpersonal communication. The findings show that interactive communication catalyzes the participants' information searching behaviors through diverse communication channels. In turn, increased media use plays a crucial role in changing their attitudes and perceived social norms about smoking behaviors, and eventually reducing smoking intention. This study affirms that the theory of planned behavior is effective in predicting behavioral intention and demonstrates the usefulness of a multitheoretical approach in interactive campaign research on social media.

  10. Unveiling the decoherence effect of noise on the entropic uncertainty relation and its control by partially collapsed operations

    Science.gov (United States)

    Chen, Min-Nan; Sun, Wen-Yang; Huang, Ai-Jun; Ming, Fei; Wang, Dong; Ye, Liu

    2018-01-01

    In this work, we investigate the dynamics of quantum-memory-assisted entropic uncertainty relations under open systems, and how to steer the uncertainty under different types of decoherence. Specifically, we develop the dynamical behaviors of the uncertainty of interest under two typical categories of noise; bit flipping and depolarizing channels. It has been shown that the measurement uncertainty firstly increases and then decreases with the growth of the decoherence strength in bit flipping channels. In contrast, the uncertainty monotonically increases with the increase of the decoherence strength in depolarizing channels. Notably, and to a large degree, it is shown that the uncertainty depends on both the systematic quantum correlation and the minimal conditional entropy of the observed subsystem. Moreover, we present a possible physical interpretation for these distinctive behaviors of the uncertainty within such scenarios. Furthermore, we propose a simple and effective strategy to reduce the entropic uncertainty by means of a partially collapsed operation—quantum weak measurement. Therefore, our investigations might offer an insight into the dynamics of the measurment uncertainty under decoherence, and be of importance to quantum precision measurement in open systems.

  11. Unveiling the stimulatory effects of tartrazine on human and bovine serum albumin fibrillogenesis: Spectroscopic and microscopic study

    Science.gov (United States)

    Al-Shabib, Nasser Abdulatif; Khan, Javed Masood; Alsenaidy, Mohammad A.; Alsenaidy, Abdulrahman M.; Khan, Mohd Shahnawaz; Husain, Fohad Mabood; Khan, Mohammad Rashid; Naseem, Mohammad; Sen, Priyankar; Alam, Parvez; Khan, Rizwan Hasan

    2018-02-01

    Amyloid fibrils are playing key role in the pathogenesis of various neurodegenerative diseases. Generally anionic molecules are known to induce amyloid fibril in several proteins. In this work, we have studied the effect of anionic food additive dye i.e., tartrazine (TZ) on the amyloid fibril formation of human serum albumins (HSA) and bovine serum albumin (BSA) at pHs 7.4 and 3.5. We have employed various biophysical methods like, turbidity measurements, Rayleigh Light Scattering (RLS), Dynamic Light Scattering (DLS), intrinsic fluorescence, Congo red assay, far-UV CD, transmission electron microscopy (TEM) and atomic force microscopy (AFM) to decipher the mechanism of TZ-induce amyloid fibril formation in both the serum albumins at pHs 7.4 and 3.5. The obtained results suggest that both the albumins forms amyloid-like aggregates in the presence of 1.0 to 15.0 mM of TZ at pH 3.5, but no amyloid fibril were seen at pH 7.4. The possible cause of TZ-induced amyloid fibril formation is electrostatic and hydrophobic interaction because sulfate group of TZ may have interacted electrostatically with positively charged amino acids of the albumins at pH 3.5 and increased protein-protein and protein-TZ interactions leading to amyloid fibril formation. The TEM, RLS and DLS results are suggesting that BSA forms bigger size amyloids compared to HSA, may be due to high surface hydrophobicity of BSA.

  12. Neurodevelopmental Effects of Antiepileptic Drugs.

    Science.gov (United States)

    Kellogg, Marissa; Meador, Kimford J

    2017-07-01

    Increasing evidence suggests that exposure to certain antiepileptic drugs (AEDs) during critical periods of development may induce transient or long-lasting neurodevelopmental deficits across cognitive, motor and behavioral domains. The developing nervous system may endure prolonged chronic exposure to AEDs during pregnancy (in utero) or during childhood, which can lead to neurodevelopmental defects such as congenital neural tube defects, lower IQ, language deficits, autism and ADHD. To date, valproate is the most widely recognized AED to significantly negatively affect neurodevelopment, and demonstrates greater adverse effects than any other AEDs that have been assessed. Although some AEDs appear to have low risk (i.e., lamotrigine, levetiracetam), other AEDs have been implicated in a variety of studies detailed below, and many AEDs have not been adequately assessed. The purpose of this review article is to summarize our current understanding of the neurodevelopmental effects of AEDs.

  13. The effects of drugs on nutrition

    African Journals Online (AJOL)

    Drug treatment can have a detrimental effect on nutritional status and drugs ... non-prescription medication dispensed due to chronic diseases such ... and cytochrome P450 in the liver, lungs and small intestine and ... Alcoholic beverages.

  14. Drug Repositioning for Effective Prostate Cancer Treatment.

    Science.gov (United States)

    Turanli, Beste; Grøtli, Morten; Boren, Jan; Nielsen, Jens; Uhlen, Mathias; Arga, Kazim Y; Mardinoglu, Adil

    2018-01-01

    Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-κB inhibition, Wnt/β-Catenin pathway inhibition, DNMT1 inhibition, and GSK-3β inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.

  15. Interaction Effects of Students, Drugs and Alienation

    Science.gov (United States)

    Jones, Woodrow, Jr.

    1977-01-01

    This study examined the interaction effect of students, drugs, and alienation in a large university, i.e., the linkages of both social and political alienation with drug behavior. The interaction terms which composed these forms of alienation were evaluated as to their comparative ability to produce drug behavior. (Author)

  16. The Effects of Psychotropic Drugs.

    Science.gov (United States)

    Bonnardeaux, Jef-Louis

    1984-01-01

    Presents information on psychotropic drugs for individuals who are not specialists in pharmacology. Discusses: alcohol and barbituates; dependence and withdrawal; central nervous system depressors (anaesthetics, narcotic analgesics, sedatives and hypnotic drugs, tranquilizers), central nervous stimulants (amphetamines, cocaine, tobacco, caffeine),…

  17. [Management of adverse drug effects].

    Science.gov (United States)

    Schlienger, R G

    2000-09-01

    Adverse drug reactions (ADRs) are still considered one of the main problems of drug therapy. ADRs are associated with considerable morbidity, mortality, decreased compliance and therapeutic success as well as high direct and indirect medical costs. Several considerations have to come into play when managing a potential ADR. It is critical to establish an accurate clinical diagnosis of the adverse event. Combining information about drug exposure together with considering other possible causes of the reaction is crucial to establish a causal relationship between the reaction and the suspected drug. Identification of the underlying pathogenesis of an ADR together with the severity of the reaction will have profound implications on continuation of drug therapy after an ADR. Since spontaneous reports about ADRs are a key stone of a functioning post-marketing surveillance system and therefore play a key role in improving drug safety, health care professionals are highly encouraged to report ADRs to a local or national organization. However, because the majority of ADRs is dose-dependent and therefore preventable, individualization of pharmacotherapy may have a major impact on reducing such events.

  18. France: the programme of festivities is unveiled

    CERN Multimedia

    2004-01-01

    The programme of events to be held in the local French area in honour of CERN's fiftieth anniversary was unveiled in the CMS hall on 26 April at a ceremony attended by many local authority representatives.

  19. The lung effects of illicit drugs

    OpenAIRE

    Crista Laslo; Beatrice G. Ioan; Ovidiu G. Bratu; Bogdan Socea; Camelia Diaconu

    2018-01-01

    Illicit drugs use is a real public health issue, especially among young people. The totality of the drugs harmful effects on the body is difficult to quantify, especially because of poor epidemiological data and ethical concerns about the inclusion of consumers in clinical trials. However, health professionals need to be alert to identify, report and fight drug-related pathology. This article aims to draw attention to the lung pathology induced by the consumption of some of the most commonly ...

  20. Georges Charpak street sign unveiled

    CERN Multimedia

    Paola Catapano

    2011-01-01

    While it might not be the only French street named in honour of the late Georges Charpak, who passed away in September 2010 at the age of 87, the street chosen by the mayor of Saint-Genis-Pouilly is certainly the only one located directly opposite the CERN "campus". The road overlooks buildings on the CERN Meyrin site, where Georges Charpak spent most of his career as a physicist, conducting the research that won him the Nobel Prize in Physics in 1992.   From left to right: Sigurd Lettow, Dominique Charpak and the mayor of Saint-Genis-Pouilly. The unveiling took place on 17 October and was organised by the mayor of Saint-Genis-Pouilly. George Charpak’s wife, Dominique, and Sigurd Lettow, CERN Director of Administration and General Infrastructure, attended what was an intimate and touching ceremony. The mayor’s speech at the event praised Georges’ commitment to scientific education. The highlight of the event, however, was a witty and humorous ...

  1. Sexual side effects induced by psychotropic drugs

    DEFF Research Database (Denmark)

    Kristensen, Ellids

    2002-01-01

    The majority of psychotropic drugs entail sexual side effects. The sexual side effects may reduce quality of life and may give rise to non-compliance. For example, 30-60 per cent of patients treated with antidepressants are known to develop a sexual dysfunction. However, some psychotropic drugs...... with no or very few sexual side effects have begun to emerge. The treatment of sexual side effects induced by psychotropic drugs may consist of: modified sexual habits, reduction in dosage, switching to another medication, possibly in combination with different psychotropic agents, other varieties...

  2. The lung effects of illicit drugs

    Directory of Open Access Journals (Sweden)

    Crista Laslo

    2018-04-01

    Full Text Available Illicit drugs use is a real public health issue, especially among young people. The totality of the drugs harmful effects on the body is difficult to quantify, especially because of poor epidemiological data and ethical concerns about the inclusion of consumers in clinical trials. However, health professionals need to be alert to identify, report and fight drug-related pathology. This article aims to draw attention to the lung pathology induced by the consumption of some of the most commonly used illicit drugs: cocaine, heroin and cannabis.

  3. Hallucinatory Side Effects of ADHD Drugs

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-04-01

    Full Text Available Clinical trial and postmarketing surveillance data for drugs used in treatment of attention deficit hyperactivity disorder were analyzed to determine the frequency of hallucinations and other psychotic side effects, in a study at the US Food and Drug Administration, and Department of Health and Human Services, Maryland.

  4. Reference drug programs: Effectiveness and policy implications☆

    Science.gov (United States)

    Schneeweiss, Sebastian

    2010-01-01

    In the current economic environment, health care systems are constantly struggling to contain rapidly rising costs. Drug costs are targeted by a wide variety of measures. Many jurisdictions have implemented reference drug programs (RDPs) or similar therapeutic substitution programs. This paper summarizes the mechanism and rationale of RDPs and presents evidence of their economic effectiveness and clinical safety. RDPs for pharmaceutical reimbursement are based on the assumption that drugs within specified medication groups are therapeutically equivalent and clinically interchangeable and that a common reimbursement level can thus be established. If the evidence documents that a higher price for a given drug does not buy greater effectiveness or reduced toxicity, then under RDP such extra costs are not covered. RDPs or therapeutic substitutions based on therapeutic equivalence are seen as logical extensions of generic substitution that is based on bioequivalence of drugs. If the goal is to achieve full drug coverage for as many patients as possible in the most efficient manner, then RDPs in combination with prior authorization programs are safer and more effective than simplistic fiscal drug policies, including fixed co-payments, co-insurances, or deductibles. RDPs will reduce spending in the less innovative but largest market, while fully covering all patients. Prior authorization will ensure that patients with a specified indication will benefit from the most innovative therapies with full coverage. In practice, however, not all patients and drugs will fit exactly into one of the two categories. Therefore, a process of medically indicated exemptions that will consider full coverage should accompany an RDP. In the current economic environment, health care systems are constantly struggling to contain rapidly rising costs. Drug costs are targeted by a wide variety of measures. Many jurisdictions have implemented reference drug programs, and others are considering

  5. Unifying Theories of Psychedelic Drug Effects

    Directory of Open Access Journals (Sweden)

    Link R. Swanson

    2018-03-01

    Full Text Available How do psychedelic drugs produce their characteristic range of acute effects in perception, emotion, cognition, and sense of self? How do these effects relate to the clinical efficacy of psychedelic-assisted therapies? Efforts to understand psychedelic phenomena date back more than a century in Western science. In this article I review theories of psychedelic drug effects and highlight key concepts which have endured over the last 125 years of psychedelic science. First, I describe the subjective phenomenology of acute psychedelic effects using the best available data. Next, I review late 19th-century and early 20th-century theories—model psychoses theory, filtration theory, and psychoanalytic theory—and highlight their shared features. I then briefly review recent findings on the neuropharmacology and neurophysiology of psychedelic drugs in humans. Finally, I describe recent theories of psychedelic drug effects which leverage 21st-century cognitive neuroscience frameworks—entropic brain theory, integrated information theory, and predictive processing—and point out key shared features that link back to earlier theories. I identify an abstract principle which cuts across many theories past and present: psychedelic drugs perturb universal brain processes that normally serve to constrain neural systems central to perception, emotion, cognition, and sense of self. I conclude that making an explicit effort to investigate the principles and mechanisms of psychedelic drug effects is a uniquely powerful way to iteratively develop and test unifying theories of brain function.

  6. Unifying Theories of Psychedelic Drug Effects

    Science.gov (United States)

    Swanson, Link R.

    2018-01-01

    How do psychedelic drugs produce their characteristic range of acute effects in perception, emotion, cognition, and sense of self? How do these effects relate to the clinical efficacy of psychedelic-assisted therapies? Efforts to understand psychedelic phenomena date back more than a century in Western science. In this article I review theories of psychedelic drug effects and highlight key concepts which have endured over the last 125 years of psychedelic science. First, I describe the subjective phenomenology of acute psychedelic effects using the best available data. Next, I review late 19th-century and early 20th-century theories—model psychoses theory, filtration theory, and psychoanalytic theory—and highlight their shared features. I then briefly review recent findings on the neuropharmacology and neurophysiology of psychedelic drugs in humans. Finally, I describe recent theories of psychedelic drug effects which leverage 21st-century cognitive neuroscience frameworks—entropic brain theory, integrated information theory, and predictive processing—and point out key shared features that link back to earlier theories. I identify an abstract principle which cuts across many theories past and present: psychedelic drugs perturb universal brain processes that normally serve to constrain neural systems central to perception, emotion, cognition, and sense of self. I conclude that making an explicit effort to investigate the principles and mechanisms of psychedelic drug effects is a uniquely powerful way to iteratively develop and test unifying theories of brain function. PMID:29568270

  7. The undesirable effects of neuromuscular blocking drugs

    DEFF Research Database (Denmark)

    Claudius, C; Garvey, L H; Viby-Mogensen, J

    2009-01-01

    Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor...... in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect...... of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking...

  8. A side effect resource to capture phenotypic effects of drugs

    DEFF Research Database (Denmark)

    Kuhn, Michael; Campillos, Monica; Letunic, Ivica

    2010-01-01

    The molecular understanding of phenotypes caused by drugs in humans is essential for elucidating mechanisms of action and for developing personalized medicines. Side effects of drugs (also known as adverse drug reactions) are an important source of human phenotypic information, but so far research...

  9. Stop Negative Thinking Effects for Drug Dependence

    OpenAIRE

    Windiarti, Sri Endang; Indriati, Indriati; Surachmi, Fajar

    2013-01-01

    The purpose of this study was to determine the effect of therapy stop thinking negatively against drug addiction in Rehabilitation Orphanage Rumah Damai Gunung Pati Semarang. This research is quasy experiment with pretest - posttes without the control group design. Thirty respondents were taken to the reseach sujects. Stop thinking negative therapy before and after thebehavior of drug addiction there are differences (t = 0.00), so it can be stated that the therapy stop thinking negatively inf...

  10. The nocebo effect of drugs.

    Science.gov (United States)

    Planès, Sara; Villier, Céline; Mallaret, Michel

    2016-04-01

    While the placebo effect has been studied for a long time, much less is known about its negative counterpart, named the nocebo effect. However, it may be of particular importance because of its impact on the treatment outcomes and public health. We conducted a review on the nocebo effect using PubMed and other databases up to July 2014. The nocebo effect refers by definition to the induction or the worsening of symptoms induced by sham or active therapies. Examples are numerous and concerns both clinical trials and daily practice. The underlying mechanisms are, on one hand, psychological (conditioning and negative expectations) and, on the other hand, neurobiological (role of cholecystokinin, endogenous opioids and dopamine). Nocebo effects can modulate the outcome of a given therapy in a negative way, as do placebo effects in a positive way. The verbal and nonverbal communications of physicians contain numerous unintentional negative suggestions that may trigger a nocebo response. This raises the important issue of how physicians can at the same time obtain informed consent and minimize nocebo-related risks. Every physician has to deal with this apparent contradiction between primum non nocere and to deliver truthful information about risks. Meticulous identification of patients at risk, information techniques such as positive framing, contextualized informed consent, and even noninformation, is valuable.

  11. Arrhythmogenic effects of illicit drugs in athletes.

    Science.gov (United States)

    Furlanello, Francesco; Bentivegna, Stefano; Cappato, Riccardo; De Ambroggi, Luigi

    2003-12-01

    Cardiac arrhythmias are among the most important causes of non-eligibility to sports activities, and may be due to different causes (cardiomyopathies, myocarditis, coronary abnormalities, valvular diseases, primary electrical disorders, abuse of illicit drugs). The list of illicit drugs banned by the International Olympic Committee and yearly updated by the World Anti-Doping Agency includes the following classes: stimulants, narcotics, anabolic agents (androgenic steroids and others such as beta-2 stimulants), peptide hormones, mimetics and analogues, diuretics, agents with an antiestrogenic activity, masking agents. Almost all illicit drugs may cause, through a direct or indirect arrhythmogenic effect, in the short, medium or long term, a wide range of cardiac arrhythmias (focal or reentry type, supraventricular and/or ventricular), lethal or not, even in healthy subjects with no previous history of cardiac diseases. Therefore, given the widespread abuse of illicit drugs among athletes, in the management of arrhythmic athletes the cardiologist should always take into consideration the possibility that the arrhythmias be due to the assumption of illicit drugs (sometimes more than one type), especially if no signs of cardiac diseases are present. On the other hand, in the presence of latent underlying arrhythmogenic heart disease including some inherited cardiomyopathies at risk of sudden cardiac death, illicit drugs could induce severe cardiac arrhythmic effects.

  12. Nanomaterials potentiating standard chemotherapy drugs' effect

    Science.gov (United States)

    Kazantsev, S. O.; Korovin, M. S.

    2017-09-01

    Application of antitumor chemotherapeutic drugs is hindered by a number of barriers, multidrug resistance that makes effective drug deposition inside cancer cells difficult is among them. Recent research shows that potential efficiency of anticancer drugs can be increased with nanoparticles. This review is devoted to the application of nanoparticles for cancer treatment. Various types of nanoparticles currently used in medicine are reviewed. The nanoparticles that have been used for cancer therapy and targeted drug delivery to damaged sites of organism are described. Also, the possibility of nanoparticles application for cancer diagnosis that could help early detection of tumors is discussed. Our investigations of antitumor activity of low-dimensional nanostructures based on aluminum oxides and hydroxides are briefly reviewed.

  13. The Drug Effects Questionnaire: Psychometric Support across Three Drug Types

    Science.gov (United States)

    Morean, Meghan E.; de Wit, Harriet; King, Andrea C.; Sofuoglu, Mehmet; Rueger, Sandra Y.; O’Malley, Stephanie S.

    2013-01-01

    Rationale The Drug Effects Questionnaire (DEQ) is widely used in studies of acute subjective response (SR) to a variety of substances, but the format of the DEQ varies widely across studies, and details of its psychometric properties are lacking. Thus, the field would benefit from demonstrating the reliability and validity of the DEQ for use across multiple substances. Objective The current study evaluated the psychometric properties of several variations of DEQ items, which assessed the extent to which participants (1) feel any substance effect(s), (2) feel high, (3) like the effects, (4) dislike the effects, and (5) want more of the substance using 100mm Visual Analog Scales. Methods DEQ data from three placebo-controlled studies were analyzed to examine SR to amphetamine, nicotine, and alcohol. We evaluated the internal structure of the DEQ for use with each substance as well as relationships between scale items, measures of similar constructs, and substance-related behaviors. Results Results provided preliminary psychometric support for items assessing each DEQ construct (FEEL, HIGH, DISLIKE, LIKE, and MORE). Conclusions Based on the study results, we identify several common limitations of extant variants of the DEQ and recommend an improved version of the measure. The simplicity and brevity of the DEQ combined with its promising psychometric properties support its use in future SR research across a variety of substances. PMID:23271193

  14. Effects of Psychostimulant Drugs on Developing Brain

    Directory of Open Access Journals (Sweden)

    Ibrahim Durukan

    2013-08-01

    Full Text Available Although psychostimulants have been used for the treatment of attention deficit hyperactivity disorder for approximately 70 years, little is known about the long term effects of these drugs on developing brain. The observable effects of psychostimulants are influenced by the timing of exposure, the age of examination after drug exposure and sex. Preclinical studies point out that chronic psychostimulant exposure before adolescence cause reverse sensitization or tolerance and this leads to reduction in stimulant effectiveness in adolesecence and adulthood. Preclinical studies show the potential long term effects of psychostimulants. But it is necessary to investigate the relationship between preclinical effects and clinical practice. A developmental approach is needed to understand the impact of pediatric medications on the brain that includes assessment at multiple ages to completely characterize the long term effects of these medications. The aim of this paper is to review the effects of psychostimulants on developing brain.

  15. Germany unveils €18bn research plan

    Science.gov (United States)

    Banks, Michael

    2009-07-01

    The German government has unveiled an ambitious plan to inject a total of €18bn into teaching and research over the next decade. The German chancellor Angela Merkel, who has a degree in physics, announced that she was releasing the funds despite concerns from her social-democrat coalition partners that financing the package could be difficult in the economic downturn.

  16. Sex, Drugs, and Cognition: Effects of Marijuana†

    OpenAIRE

    Anderson, Beth M.; Rizzo, Matthew; Block, Robert I.; Pearlson, Godfrey D.; O'Leary, Daniel S.

    2010-01-01

    Despite the knowledge that many drugs affect men and women differently, few studies exploring the effects of marijuana use on cognition have included women. Findings from both animal and human studies suggest marijuana may have more marked effects in women. This study examined sex differences in the acute effects of marijuana on cognition in 70 (n= 35 male, 35 female) occasional users of marijuana. Tasks were chosen to tap a wide variety of cognitive domains affected by sex and/or marijuana i...

  17. Effecting attitudinal change towards rational drug use.

    Science.gov (United States)

    Singh, T; Natu, M V

    1995-01-01

    Attitudes of 40 interns towards rational drug use (RDU) were assessed, using a standardized Likert type scale. The assessment was repeated after 4 months to evaluate the effect of usual working conditions of the hospital. After this period, the attitudes had slided towards negative side (p attitudes of test group returned towards positive side (p attitudes.

  18. Cardiovascular Effects of Performance-Enhancing Drugs.

    Science.gov (United States)

    La Gerche, André; Brosnan, Maria J

    2017-01-03

    Exercise and competitive sports should be associated with a wide range of health benefits with the potential to inspire a positive community health legacy. However, the reputation of sports is being threatened by an ever-expanding armamentarium of agents with real or perceived benefits in performance enhancement. In addition to the injustice of unfair advantage for dishonest athletes, significant potential health risks are associated with performance-enhancing drugs. Performance-enhancing drugs may have an effect on the cardiovascular system by means of directly altering the myocardium, vasculature, and metabolism. However, less frequently considered is the potential for indirect effects caused through enabling athletes to push beyond normal physiological limits with the potential consequence of exercise-induced arrhythmias. This review will summarize the known health effects of PEDs but will also focus on the potentially greater health threat posed by the covert search for performance-enhancing agents that have yet to be recognized by the World Anti-Doping Agency. History has taught us that athletes are subjected to unmonitored trials with experimental drugs that have little or no established efficacy or safety data. One approach to decrease drug abuse in sports would be to accept that there is a delay from when athletes start experimenting with novel agents to the time when authorities become aware of these drugs. This provides a window of opportunity for athletes to exploit with relative immunity. It could be argued that all off-label use of any agent should be deemed illegal. © 2016 American Heart Association, Inc.

  19. Cash boost to Great British science unveiled

    CERN Multimedia

    2002-01-01

    "Trade and Industry Secretary, Patricia Hewitt today unveiled new plans for the DTI's record science budget over the next three years, to keep Britain at the forefront of world science. The plans include funding to develop life saving new health techniques, to seek alternative energy sources, to help our rural economy, to develop the computers of tomorrow and boost business with the next generation of leading edge technologies" (1 page).

  20. Analysis of drug effects on neurotransmitter release

    International Nuclear Information System (INIS)

    Rowell, P.; Garner, A.

    1986-01-01

    The release of neurotransmitter is routinely studied in a superfusion system in which serial samples are collected and the effects of drugs or other treatments on the amount of material in the superfusate is determined. With frequent sampling interval, this procedure provides a mechanism for dynamically characterizing the release process itself. Using automated data collection in conjunction with polyexponential computer analysis, the equation which describes the release process in each experiment is determined. Analysis of the data during the nontreated phase of the experiment allows an internal control to be used for accurately assessing any changes in neurotransmitter release which may occur during a subsequent treatment phase. The use of internal controls greatly improves the signal to noise ratio and allows determinations of very low concentrations of drugs on small amounts of tissue to be made. In this presentation, the effects of 10 μM nicotine on 3 H-dopamine release in rat nucleus accumbens is described. The time course, potency and efficacy of the drug treatment is characterized using this system. Determinations of the exponential order of the release as well as the rate constants allow one to study the mechanism of the release process. A description of 3 H-dopamine release in normal as well as Ca ++ -free medium is presented

  1. Psychiatric Adverse Effects of Dermatological Drugs

    Directory of Open Access Journals (Sweden)

    Mine Özmen

    2010-07-01

    Full Text Available Dermatological drugs, mostly corticosteroids and isotretinoin, cause different psychiatric adverse effects. During steroid therapy, a wide range of psychiatric conditions, from minor clinical symptoms like insomnia and anxiety to serious psychiatric syndromes like psychosis and delirium might be seen. In medical literature, a causal connection is usually suggested between “isotretinoin”, which is used for treatment of acne vulgaris and depression and suicide attempts. However, there are no statistically significant double-blind randomized studies that support this connection. Clinicians must know patient’s psychiatric history before using any dermatological treatment known as causing psychiatric adverse effects, and psychiatric consultation should be established whenever necessary.

  2. Effect of drugs on orthodontic tooth movement

    Directory of Open Access Journals (Sweden)

    Siti Sarah Aulia Amrullah

    2016-06-01

    Full Text Available Orthodontic tooth movement is basically a biological response to mechanical forces given to the teeth in orthodontic treatment, which involving the periodontal tissue and alveolar bone, resulting in the release of numerous substances from the dental tissues and surrounding structure. Remodeling changes in periodontal tissues are considered to be essential in effecting orthodontic tooth movement which is the base of orthodontic correction. Molecules produced in various diseased tissues or drugs and nutrients consumed regularly by patients, can influence mechanically stressed periodontal tissue through the circulation and interact with target cell combination of which may be inhibitory, additive or synergize. Medications might have an important influence on the rate of tooth movement, and information on their consumption is essential to adequately discuss treatment planning with patients. Therefore it is imperative to the practitioners being in medical profession, must pay close attention to the drug consumption history of every patient before and during the course of treatment.

  3. The Economic Side Effects of Dangerous Drug Announcements.

    OpenAIRE

    Dranove, David; Olsen, Chris

    1994-01-01

    Immediately prior to the passage of the 1962 Food and Drug Administration Amendments, there were a number of drugs recalled from markets worldwide. Announcements about the dangerous side effects of these drugs were associated with lower-share prices for their manufacturers and the industry as a whole. We perform several analyses to sort out alternative explanations for the observed declines. We find that dangerous drug announcements had no effect on the sales of other drugs and didn't affect ...

  4. Unveiling Cebuano Traditional Healing Practices

    Directory of Open Access Journals (Sweden)

    ZachiaRaiza Joy S. Berdon

    2016-02-01

    Full Text Available This study aims to identify the features of Cebuano’s traditional healing practices. Specifically, it also answers the following objectives: analyze traditional healing in Cebuano’s perspectives, explain the traditional healing process practiced in terms of the traditional healers’ belief, and extrapolate perceptions of medical practitioners toward traditional healing. This study made use of qualitative approach, among five traditional healers who performed healing for not less than ten years, in the mountain barangays of Cebu City. These healers served as the primary informants who were selected because of their popularity in healing. The use of open-ended interview in local dialect and naturalistic observation provided a free listing of their verbatim accounts were noted and as primary narratives. Participation in the study was voluntary and participants were interviewed privately after obtaining their consent. The Cebuano traditional healing practices or “panambal” comprise the use of “himolso” (pulse-checking, “palakaw” (petition, “pasubay” (determining what causes the sickness and its possible means of healing, “pangalap” (searching of medicinal plants for “palina” (fumigation, “tayhop” (gentle-blowing, “tutho” (saliva-blowing,“tuob” (boiling, “orasyon” (mystical prayers, “hilot” (massage, and “barang” (sorcery. Though traditional with medical science disapproval, it contributes to a mystical identity of Cebuano healers, as a manifestation of folk Catholicism belief, in order to do a good legacy to the community that needs help. For further study, researchers may conduct further the studies on the: curative effects of medicinal plants in Cebu, psychological effect pulsechecking healed persons by the mananambal, and unmasking the other features of traditional healing.

  5. Drug target identification using side-effect similarity

    DEFF Research Database (Denmark)

    Campillos, Monica; Kuhn, Michael; Gavin, Anne-Claude

    2008-01-01

    Targets for drugs have so far been predicted on the basis of molecular or cellular features, for example, by exploiting similarity in chemical structure or in activity across cell lines. We used phenotypic side-effect similarities to infer whether two drugs share a target. Applied to 746 marketed...... drugs, a network of 1018 side effect-driven drug-drug relations became apparent, 261 of which are formed by chemically dissimilar drugs from different therapeutic indications. We experimentally tested 20 of these unexpected drug-drug relations and validated 13 implied drug-target relations by in vitro...... binding assays, of which 11 reveal inhibition constants equal to less than 10 micromolar. Nine of these were tested and confirmed in cell assays, documenting the feasibility of using phenotypic information to infer molecular interactions and hinting at new uses of marketed drugs....

  6. Unveiling aerosol-cloud interactions - Part 2: Minimising the effects of aerosol swelling and wet scavenging in ECHAM6-HAM2 for comparison to satellite data

    Science.gov (United States)

    Neubauer, David; Christensen, Matthew W.; Poulsen, Caroline A.; Lohmann, Ulrike

    2017-11-01

    Aerosol-cloud interactions (ACIs) are uncertain and the estimates of the ACI effective radiative forcing (ERFaci) magnitude show a large variability. Within the Aerosol_cci project the susceptibility of cloud properties to changes in aerosol properties is derived from the high-resolution AATSR (Advanced Along-Track Scanning Radiometer) data set using the Cloud-Aerosol Pairing Algorithm (CAPA) (as described in our companion paper) and compared to susceptibilities from the global aerosol climate model ECHAM6-HAM2 and MODIS-CERES (Moderate Resolution Imaging Spectroradiometer - Clouds and the Earth's Radiant Energy System) data. For ECHAM6-HAM2 the dry aerosol is analysed to mimic the effect of CAPA. Furthermore the analysis is done for different environmental regimes. The aerosol-liquid water path relationship in ECHAM6-HAM2 is systematically stronger than in AATSR-CAPA data and cannot be explained by an overestimation of autoconversion when using diagnostic precipitation but rather by aerosol swelling in regions where humidity is high and clouds are present. When aerosol water is removed from the analysis in ECHAM6-HAM2 the strength of the susceptibilities of liquid water path, cloud droplet number concentration and cloud albedo as well as ERFaci agree much better with those of AATSR-CAPA or MODIS-CERES. When comparing satellite-derived to model-derived susceptibilities, this study finds it more appropriate to use dry aerosol in the computation of model susceptibilities. We further find that the statistical relationships inferred from different satellite sensors (AATSR-CAPA vs. MODIS-CERES) as well as from ECHAM6-HAM2 are not always of the same sign for the tested environmental conditions. In particular the susceptibility of the liquid water path is negative in non-raining scenes for MODIS-CERES but positive for AATSR-CAPA and ECHAM6-HAM2. Feedback processes like cloud-top entrainment that are missing or not well represented in the model are therefore not well

  7. Effect of Contemporary Social Environment, Drug Abuse and ...

    African Journals Online (AJOL)

    Effect of Contemporary Social Environment, Drug Abuse and Cultism on the Health of ... This health situation comes as results of substance abuse which these ... the patent medicine stores, from hard drugs like (marijuana, cannabis) or others ...

  8. Systematic identification of proteins that elicit drug side effects

    DEFF Research Database (Denmark)

    Kuhn, Michael; Al Banchaabouchi, Mumna; Campillos, Monica

    2013-01-01

    Side effect similarities of drugs have recently been employed to predict new drug targets, and networks of side effects and targets have been used to better understand the mechanism of action of drugs. Here, we report a large-scale analysis to systematically predict and characterize proteins...... that cause drug side effects. We integrated phenotypic data obtained during clinical trials with known drug-target relations to identify overrepresented protein-side effect combinations. Using independent data, we confirm that most of these overrepresentations point to proteins which, when perturbed, cause......) is responsible for hyperesthesia in mice, which, in turn, can be prevented by a drug that selectively inhibits HTR7. Taken together, we show that a large fraction of complex drug side effects are mediated by individual proteins and create a reference for such relations....

  9. Target Essentiality and Centrality Characterize Drug Side Effects

    OpenAIRE

    Wang, Xiujuan; Thijssen, Bram; Yu, Haiyuan

    2013-01-01

    Author Summary The ultimate goal of medical research is to develop effective treatments for disease with minimal side effects. Currently, about 20% of drug candidates failed at clinical trial phases II and III due to safety issues. Therefore, understanding the determining factors of drug side effects is of paramount importance to human health and the pharmaceutical industry. Here, we present the first systematic study to uncover key factors leading to drug side effects within the framework of...

  10. Drug-drug interaction may explain failed antibiotic effectiveness - an ...

    African Journals Online (AJOL)

    The in vivo effect of co-administration of the NSAIDs (acetyl salicylic acid (ASA), piroxicam, indomethacin and paracetamol) with ciprofloxacin against Staphylococcus aureus in Swiss mice, rendered neutropenic by pre-treatment with cyclophosphamide, was evaluated using animal model. Using the murine thigh model, ...

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

    Directory of Open Access Journals (Sweden)

    Jeanette Prinz

    2016-09-01

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

  12. The role of drug profiles as similarity metrics: applications to repurposing, adverse effects detection and drug-drug interactions.

    Science.gov (United States)

    Vilar, Santiago; Hripcsak, George

    2017-07-01

    Explosion of the availability of big data sources along with the development in computational methods provides a useful framework to study drugs' actions, such as interactions with pharmacological targets and off-targets. Databases related to protein interactions, adverse effects and genomic profiles are available to be used for the construction of computational models. In this article, we focus on the description of biological profiles for drugs that can be used as a system to compare similarity and create methods to predict and analyze drugs' actions. We highlight profiles constructed with different biological data, such as target-protein interactions, gene expression measurements, adverse effects and disease profiles. We focus on the discovery of new targets or pathways for drugs already in the pharmaceutical market, also called drug repurposing, in the interaction with off-targets responsible for adverse reactions and in drug-drug interaction analysis. The current and future applications, strengths and challenges facing all these methods are also discussed. Biological profiles or signatures are an important source of data generation to deeply analyze biological actions with important implications in drug-related studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Accounting for the drug life cycle and future drug prices in cost-effectiveness analysis.

    Science.gov (United States)

    Hoyle, Martin

    2011-01-01

    Economic evaluations of health technologies typically assume constant real drug prices and model only the cohort of patients currently eligible for treatment. It has recently been suggested that, in the UK, we should assume that real drug prices decrease at 4% per annum and, in New Zealand, that real drug prices decrease at 2% per annum and at patent expiry the drug price falls. It has also recently been suggested that we should model multiple future incident cohorts. In this article, the cost effectiveness of drugs is modelled based on these ideas. Algebraic expressions are developed to capture all costs and benefits over the entire life cycle of a new drug. The lifetime of a new drug in the UK, a key model parameter, is estimated as 33 years, based on the historical lifetime of drugs in England over the last 27 years. Under the proposed methodology, cost effectiveness is calculated for seven new drugs recently appraised in the UK. Cost effectiveness as assessed in the future is also estimated. Whilst the article is framed in mathematics, the findings and recommendations are also explained in non-mathematical language. The 'life-cycle correction factor' is introduced, which is used to convert estimates of cost effectiveness as traditionally calculated into estimates under the proposed methodology. Under the proposed methodology, all seven drugs appear far more cost effective in the UK than published. For example, the incremental cost-effectiveness ratio decreases by 46%, from £61, 900 to £33, 500 per QALY, for cinacalcet versus best supportive care for end-stage renal disease, and by 45%, from £31,100 to £17,000 per QALY, for imatinib versus interferon-α for chronic myeloid leukaemia. Assuming real drug prices decrease over time, the chance that a drug is publicly funded increases over time, and is greater when modelling multiple cohorts than with a single cohort. Using the methodology (compared with traditional methodology) all drugs in the UK and New

  14. Unveiling protein functions through the dynamics of the interaction network.

    Directory of Open Access Journals (Sweden)

    Irene Sendiña-Nadal

    Full Text Available Protein interaction networks have become a tool to study biological processes, either for predicting molecular functions or for designing proper new drugs to regulate the main biological interactions. Furthermore, such networks are known to be organized in sub-networks of proteins contributing to the same cellular function. However, the protein function prediction is not accurate and each protein has traditionally been assigned to only one function by the network formalism. By considering the network of the physical interactions between proteins of the yeast together with a manual and single functional classification scheme, we introduce a method able to reveal important information on protein function, at both micro- and macro-scale. In particular, the inspection of the properties of oscillatory dynamics on top of the protein interaction network leads to the identification of misclassification problems in protein function assignments, as well as to unveil correct identification of protein functions. We also demonstrate that our approach can give a network representation of the meta-organization of biological processes by unraveling the interactions between different functional classes.

  15. Changing effects of direct-to-consumer broadcast drug advertising information sources on prescription drug requests.

    Science.gov (United States)

    Lee, Annisa Lai

    2009-06-01

    This study tracks the changes of the effects of 4 information sources for direct-to-consumer drug advertising on patients' requests for prescription drugs from physicians since the inception of the "Guidance for Industry about Consumer-directed Broadcast Advertisements." The Guidance advises pharmaceuticals to use four information sources for consumers to seek further information to supplement broadcast drug advertisements: small-print information, the Internet, a toll-free number, and health-care providers (nurses, doctors, and pharmacists). Logistic models were created by using survey data collected by the Food and Drug Administration in 1999 and 2002. Results show that throughout the years, health-care providers remain the most used and strongest means associated with patients' direct requests for nonspecific and specific prescription drugs from doctors. The small-print information source gains power and changes from an indirect means associated with patients' discussing drugs with health-care providers to a direct means associated with patients' asking about nonspecific and specific drugs from their doctors. The Internet is not directly related to drug requests, but the effect of its association with patients seeking information from health-care providers grew 11-fold over the course of the study. The toll-free number lost its power altogether for both direct request for a prescription drug and further discussion with health-care providers. Patient demographics will be considered for specific policy implications.

  16. Effects of drugs on platelet function.

    Science.gov (United States)

    Morse, E E

    1977-01-01

    Numerous drugs and chemicals affect the function of human blood platelets. The mechanism of action of some medications is partly understood. Aspirin is the most frequently involved drug. It appears to interfere with the platelet release reaction by acetylation of a platelet membrane protein which may be involved in the synthesis of prostaglandins. Other anti-inflammatory drugs, including indomethacin, phenylbutazone, ibuprophen (Motrin) and clonixin, also interfere with the release reaction but have a shorter acting course than aspirin. Some drugs stimulate adenylcyclase (gliclazide) or block phosphodiesterase, (dipyridamole, caffeine) both of which actions lead to an increase in adenosine cyclic 3':5' monophosphate (cAMP) and decrease aggregation by adenosine diphosphate (ADP). These interactions should be known to clinical scientists since patients using these medicaments may manifest abnormal platelet function tests in the laboratory and mild hemorrhagic syndromes in the clinic.

  17. Anti-VEGF drugs: evidence for effectiveness

    OpenAIRE

    Evans, Jennifer; Virgili, Gianni

    2014-01-01

    Anti-vascular endothelial growth factors (anti-VEGF) are targeted biological drugs (e.g. monoclonal antibodies) that prevent the growth of new vessels by inhibiting VEGF. VEGF is a cytokine (cell-signalling protein) that promotes the growth of, and leakage from, new vessels. Currently there are three anti-VEGF drugs licensed for use in eye disease: pegaptanib, aflibercept, ranibizumab and one that is not licensed but is commonly used off-label (bevacizumab).

  18. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  19. The anti-hepatitis drug use effect and inventory management optimization from the perspective of hospital drug supply chain.

    Science.gov (United States)

    Liu, Zhanyu

    2017-09-01

    By analyzing the current hospital anti hepatitis drug use, dosage, indications and drug resistance, this article studied the drug inventory management and cost optimization. The author used drug utilization evaluation method, analyzed the amount and kind distribution of anti hepatitis drugs and made dynamic monitoring of inventory. At the same time, the author puts forward an effective scheme of drug classification management, uses the ABC classification method to classify the drugs according to the average daily dose of drugs, and implements the automatic replenishment plan. The design of pharmaceutical services supply chain includes drug procurement platform, warehouse management system and connect to the hospital system through data exchange. Through the statistical analysis of drug inventory, we put forward the countermeasures of drug logistics optimization. The results showed that drug replenishment plan can effectively improve drugs inventory efficiency.

  20. Unveiling DNA structural properties of promoter regions of ...

    Indian Academy of Sciences (India)

    Aditya Kumar

    Unveiling DNA structural properties of promoter regions of prokaryotic transcriptome and their role in gene expression. Aditya Kumar. Assistant Professor. Molecular Biology & Biotechnology. Tezpur University. Tezpur – 784028, Assam ...

  1. Quantitative prediction of drug side effects based on drug-related features.

    Science.gov (United States)

    Niu, Yanqing; Zhang, Wen

    2017-09-01

    Unexpected side effects of drugs are great concern in the drug development, and the identification of side effects is an important task. Recently, machine learning methods are proposed to predict the presence or absence of interested side effects for drugs, but it is difficult to make the accurate prediction for all of them. In this paper, we transform side effect profiles of drugs as their quantitative scores, by summing up their side effects with weights. The quantitative scores may measure the dangers of drugs, and thus help to compare the risk of different drugs. Here, we attempt to predict quantitative scores of drugs, namely the quantitative prediction. Specifically, we explore a variety of drug-related features and evaluate their discriminative powers for the quantitative prediction. Then, we consider several feature combination strategies (direct combination, average scoring ensemble combination) to integrate three informative features: chemical substructures, targets, and treatment indications. Finally, the average scoring ensemble model which produces the better performances is used as the final quantitative prediction model. Since weights for side effects are empirical values, we randomly generate different weights in the simulation experiments. The experimental results show that the quantitative method is robust to different weights, and produces satisfying results. Although other state-of-the-art methods cannot make the quantitative prediction directly, the prediction results can be transformed as the quantitative scores. By indirect comparison, the proposed method produces much better results than benchmark methods in the quantitative prediction. In conclusion, the proposed method is promising for the quantitative prediction of side effects, which may work cooperatively with existing state-of-the-art methods to reveal dangers of drugs.

  2. Nutritional conditioning : The effect of fasting on drug metabolism

    NARCIS (Netherlands)

    Lammers, L.A.

    2018-01-01

    The studies described in this thesis focus on the effect of fasting, as nutritional modulator, on drug metabolism. Drug metabolism varies considerably between and within patients, which may result in treatment failure or, conversely, in untoward side effects. Many factors contribute to the

  3. The SIDER database of drugs and side effects

    DEFF Research Database (Denmark)

    Kuhn, Michael; Letunic, Ivica; Jensen, Lars Juhl

    2016-01-01

    , targets and side effects into a more complete picture of the therapeutic mechanism of actions of drugs and the ways in which they cause adverse reactions. To this end, we have created the SIDER ('Side Effect Resource', http://sideeffects.embl.de) database of drugs and ADRs. The current release, SIDER 4......% of which can be compared to the frequency under placebo treatment. SIDER furthermore contains a data set of drug indications, extracted from the package inserts using Natural Language Processing. These drug indications are used to reduce the rate of false positives by identifying medical terms that do...

  4. Quantifying the effects of antiangiogenic and chemotherapy drug combinations on drug delivery and treatment efficacy.

    Science.gov (United States)

    Yonucu, Sirin; Yιlmaz, Defne; Phipps, Colin; Unlu, Mehmet Burcin; Kohandel, Mohammad

    2017-09-01

    Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise. In order to explore the effect of microenvironmental conditions and drug scheduling on normalization benefit, we build a mathematical model that incorporates tumor growth, angiogenesis and IFP. We administer various theoretical combinations of antiangiogenic agents and cytotoxic nanoparticles through heterogeneous vasculature that displays a similar morphology to tumor vasculature. We observe differences in drug extravasation that depend on the scheduling of combined therapy; for concurrent therapy, total drug extravasation is increased but in adjuvant therapy, drugs can penetrate into deeper regions of tumor.

  5. Effectiveness of hepatoprotective drugs for anti-tuberculosis drug-induced hepatotoxicity: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Zenya Saito

    2016-11-01

    Full Text Available Abstract Background The effectiveness of hepatoprotective drugs for DIH (drug induced hepatotoxicity during tuberculosis treatment is not clear. We evaluated the effectiveness of hepatoprotective drugs by comparing the period until the normalization of hepatic enzymes between patients who were prescribed with the hepatoprotective drugs after DIH was occurred and patients who were not prescribed with the hepatoprotective drugs. Methods During 2006–2010, 389 patients with active tuberculosis were included in this study. DIH was defined as elevation of peak serum aspartate aminotransferase (AST and/or alanine aminotransferase (ALT of more than twice the upper limit of normal (ULN. We divided the patients into the severe (peak serum AST and/or ALT elevation of >5 times the ULN, moderate (peak serum AST and/or ALT elevation of >3 to ≤5 times the ULN, and mild DIH groups (peak serum AST and/or ALT elevation of >2 to ≤3 times the ULN. We compared the average period until the normalization of hepatic enzymes between patient subgroups with and without hepatoprotective drugs (ursodeoxycholic acid: UDCA, stronger neo-minophagen C: SNMC, and glycyrrhizin. Results In the severe group, there was no significant difference in the average period until the normalization between subgroups with and without hepatoprotective drugs (21.4 ± 10.8 vs 21.5 ± 11.1 days, P = 0.97. In the mild group, the period was longer in the subgroup with hepatoprotective drugs than that without hepatoprotective drugs (15.7 ± 6.2 vs 12.4 ± 7.9 days, P = 0.046. Conclusion Regardless of the severity, hepatoprotective drugs did not shorten the period until the normalization of hepatic enzymes.

  6. Heat effects on drug delivery across human skin

    Science.gov (United States)

    Hao, Jinsong; Ghosh, Priyanka; Li, S. Kevin; Newman, Bryan; Kasting, Gerald B.; Raney, Sam G.

    2016-01-01

    Introduction Exposure to heat can impact the clinical efficacy and/or safety of transdermal and topical drug products. Understanding these heat effects and designing meaningful in vitro and in vivo methods to study them are of significant value to the development and evaluation of drug products dosed to the skin. Areas covered This review provides an overview of the underlying mechanisms and the observed effects of heat on the skin and on transdermal/topical drug delivery, thermoregulation and heat tolerability. The designs of several in vitro and in vivo heat effect studies and their results are reviewed. Expert opinion There is substantial evidence that elevated temperature can increase transdermal/topical drug delivery. However, in vitro and in vivo methods reported in the literature to study heat effects of transdermal/topical drug products have utilized inconsistent study conditions, and in vitro models require better characterization. Appropriate study designs and controls remain to be identified, and further research is warranted to evaluate in vitro-in vivo correlations and the ability of in vitro models to predict in vivo effects. The physicochemical and pharmacological properties of the drug(s) and the drug product, as well as dermal clearance and heat gradients may require careful consideration. PMID:26808472

  7. Cost-effectiveness and pricing of antibacterial drugs.

    Science.gov (United States)

    Verhoef, Talitha I; Morris, Stephen

    2015-01-01

    Growing resistance to antibacterial agents has increased the need for the development of new drugs to treat bacterial infections. Given increasing pressure on limited health budgets, it is important to study the cost-effectiveness of these drugs, as well as their safety and efficacy, to find out whether or not they provide value for money and should be reimbursed. In this article, we systematically reviewed 38 cost-effectiveness analyses of new antibacterial agents. Most studies showed the new antibacterial drugs were cost-effective compared to older generation drugs. Drug pricing is a complicated process, involving different stakeholders, and has a large influence on cost-effectiveness. Value-based pricing is a method to determine the price of a drug at which it can be cost-effective. It is currently unclear what the influence of value-based pricing will be on the prices of new antibacterial agents, but an important factor will be the definition of 'value', which as well as the impact of the drug on patient health might also include other factors such as wider social impact and the health impact of disease. © 2015 The Authors. Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.

  8. Illicit drugs and the media: models of media effects for use in drug policy research.

    Science.gov (United States)

    Lancaster, Kari; Hughes, Caitlin E; Spicer, Bridget; Matthew-Simmons, Francis; Dillon, Paul

    2011-07-01

    Illicit drugs are never far from the media gaze and although identified almost a decade ago as 'a new battleground' for the alcohol and other drug (AOD) field there has been limited research examining the role of the news media and its effects on audiences and policy. This paper draws together media theories from communication literature to examine media functions. We illustrate how each function is relevant for media and drugs research by drawing upon the existing literature examining Australian media coverage during the late 1990s of escalating heroin-related problems and proposed solutions. Media can influence audiences in four key ways: by setting the agenda and defining public interest; framing issues through selection and salience; indirectly shaping individual and community attitudes towards risk; and feeding into political debate and decision making. Each has relevance for the AOD field. For example, media coverage of the escalating heroin-related problems in Australia played a strong role in generating interest in heroin overdoses, framing public discourse in terms of a health and/or criminal issue and affecting political decisions. Implications AND CONCLUSION: Media coverage in relation to illicit drugs can have multifarious effects. Incorporating media communication theories into future research and actions is critical to facilitate understanding of the short- and long-term impacts of media coverage on illicit drugs and the avenues by which the AOD field can mitigate or inform future media debates on illicit drugs. © 2010 Australasian Professional Society on Alcohol and other Drugs.

  9. Effects of Multidimensional Family Therapy (MDFT) on Nonopioid Drug Abuse:

    DEFF Research Database (Denmark)

    Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint

    2015-01-01

    trials. Meta-analytic methods were used to quantitatively synthesize study results.  Results: The search yielded five studies that met inclusion criteria. MDFT was found to be more effective than other treatments on drug abuse problem severity and drug use frequency in the short run but not in the long...... run and demonstrated positive effects on treatment retention compared to control conditions.  Discussion: While additional research is needed, the review offers support for MDFT as a treatment to young nonopioid drug abusers. The number of studies included in this review was limited, however......Purpose: This review evaluates the evidence of the effects of multidimensional family therapy (MDFT) on drug use reduction in young people for the treatment of nonopioid drug use.  Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized...

  10. Intracellular Drug Bioavailability: Effect of Neutral Lipids and Phospholipids.

    Science.gov (United States)

    Treyer, Andrea; Mateus, André; Wiśniewski, Jacek R; Boriss, Hinnerk; Matsson, Pär; Artursson, Per

    2018-06-04

    Intracellular unbound drug concentrations are the pharmacologically relevant concentrations for targets inside cells. Intracellular drug concentrations are determined by multiple processes, including the extent of drug binding to intracellular structures. The aim of this study was to evaluate the effect of neutral lipid (NL) and phospholipid (PL) levels on intracellular drug disposition. The NL and/or PL content of 3T3-L1 cells were enhanced, resulting in phenotypes (in terms of morphology and proteome) reminiscent of adipocytes (high NL and PL) or mild phospholipidosis (only high PL). Intracellular bioavailability ( F ic ) was then determined for 23 drugs in these cellular models and in untreated wild-type cells. A higher PL content led to higher intracellular drug binding and a lower F ic . The induction of NL did not further increase drug binding but led to altered F ic due to increased lysosomal pH. Further, there was a good correlation between binding to beads coated with pure PL and intracellular drug binding. In conclusion, our results suggest that PL content is a major determinant of drug binding in cells and that PL beads may constitute a simple alternative to estimating this parameter. Further, the presence of massive amounts of intracellular NLs did not influence drug binding significantly.

  11. Gender differences in the effects of cardiovascular drugs

    DEFF Research Database (Denmark)

    Tamargo, Juan; Rosano, G.; Thomas, W

    2017-01-01

    . A better understanding of these sex-related differences is fundamental to improve the safety and efficacy of cardiovascular drugs and for developing proper individualized cardiovascular therapeutic strategies both in men and women. This review briefly summarize gender differences in the pharmacokinetics......Although sex-specific differences in cardiovascular medicine are well-known, the exact influences of sex on the effect of cardiovascular drugs remain unclear. Women and men differ in body composition and physiology (hormonal influences during the menstrual cycle, menopause and pregnancy...... and pharmacodynamics of cardiovascular drugs and provides recommendations to close the gaps in our understanding of sex-specific differences in drug efficacy and safety....

  12. The effects of drugs on human models of emotional processing: an account of antidepressant drug treatment.

    Science.gov (United States)

    Pringle, Abbie; Harmer, Catherine J

    2015-12-01

    Human models of emotional processing suggest that the direct effect of successful antidepressant drug treatment may be to modify biases in the processing of emotional information. Negative biases in emotional processing are documented in depression, and single or short-term dosing with conventional antidepressant drugs reverses these biases in depressed patients prior to any subjective change in mood. Antidepressant drug treatments also modulate emotional processing in healthy volunteers, which allows the consideration of the psychological effects of these drugs without the confound of changes in mood. As such, human models of emotional processing may prove to be useful for testing the efficacy of novel treatments and for matching treatments to individual patients or subgroups of patients.

  13. Effect of gamma irradiation on drugs

    International Nuclear Information System (INIS)

    Crucq, A.S.; Deridder, V.; Engalytcheff, A.; Slegers, C.; Tilquin, P.

    2005-01-01

    Several drugs (ceftazidime, vancomycin, glucagon, erythromycin and dobutamine) were studied in order to determine their radiostability. The methods used to measure the degradation of the drug were the potency and the colour change after irradiation. Electron spin resonance (ESR) is currently being used to detect irradiated foodstuffs and may be a promising technique to detect irradiated drugs. Trapped radicals in cefazolin sodium were studied and quantified by ESR for this purpose. It is proposed that the trapped radicals play an important role in the formation of the final radiolytic compounds. The potency of ceftazidime was not significantly modified after an irradiation of 25 kGy, whereas the potency of erythromycin and dobutamine decreased slightly. Glucagon was revealed to be radiosensitive with a significant decrease in its potency after irradiation. The visible spectra of glucagon and dobutamine did not change significantly after irradiation. The absorbance of erythromycin and vancomycin increased after irradiation. According to European Pharmacopoeia standards, the colour change of ceftazidime is unacceptable. The ESR spectra reveal that the trapped radicals in cefazolin sodium are characteristic of an irradiation. The radical concentration is dependent on the irradiation dose and decays over time. Radical concentration in cefazolin sodium was reduced by 99% after 100 days of storage. These radicals are responsible for about 13% of the measured final radiolytic product. Ionic reactions could also lead to final radiolytic products. (author)

  14. The effect of membrane diffusion potential change on anionic drugs ...

    African Journals Online (AJOL)

    The effect of membrane potential change on anionic drugs Indomethacin and barbitone induced human erythrocyte shape change and red cell uptake of drug has been studied using microscopy and spectrophotometry techniques respectively. The membrane potential was changed by reducing the extracellular chloride ...

  15. Measuring Effects of a Skills Training Intervention for Drug Abusers.

    Science.gov (United States)

    Hawkins, J. David; And Others

    1986-01-01

    A test was conducted of a supplemental skills training and social-network-development aftercare program with 130 drug abusers from four residential therapeutic communities. The intervention produced positive effects on subjects' performance at the conclusion of treatment. Performance improved in situations involving avoidance of drug use, coping…

  16. Pro-cognitive drug effects modulate functional brain network organization

    Science.gov (United States)

    Giessing, Carsten; Thiel, Christiane M.

    2012-01-01

    Previous studies document that cholinergic and noradrenergic drugs improve attention, memory and cognitive control in healthy subjects and patients with neuropsychiatric disorders. In humans neural mechanisms of cholinergic and noradrenergic modulation have mainly been analyzed by investigating drug-induced changes of task-related neural activity measured with functional magnetic resonance imaging (fMRI). Endogenous neural activity has often been neglected. Further, although drugs affect the coupling between neurons, only a few human studies have explicitly addressed how drugs modulate the functional connectome, i.e., the functional neural interactions within the brain. These studies have mainly focused on synchronization or correlation of brain activations. Recently, there are some drug studies using graph theory and other new mathematical approaches to model the brain as a complex network of interconnected processing nodes. Using such measures it is possible to detect not only focal, but also subtle, widely distributed drug effects on functional network topology. Most important, graph theoretical measures also quantify whether drug-induced changes in topology or network organization facilitate or hinder information processing. Several studies could show that functional brain integration is highly correlated with behavioral performance suggesting that cholinergic and noradrenergic drugs which improve measures of cognitive performance should increase functional network integration. The purpose of this paper is to show that graph theory provides a mathematical tool to develop theory-driven biomarkers of pro-cognitive drug effects, and also to discuss how these approaches can contribute to the understanding of the role of cholinergic and noradrenergic modulation in the human brain. Finally we discuss the “global workspace” theory as a theoretical framework of pro-cognitive drug effects and argue that pro-cognitive effects of cholinergic and noradrenergic drugs

  17. Principles that underpin effective school-based drug education.

    Science.gov (United States)

    Midford, Richard; Munro, Geoffrey; McBride, Nyanda; Snow, Pamela; Ladzinski, Ursula

    2002-01-01

    This study identifies the conceptual underpinnings of effective school-based drug education practice in light of contemporary research evidence and the practical experience of a broad range of drug education stakeholders. The research involved a review of the literature, a national survey of 210 Australian teachers and others involved in drug education, and structured interviews with 22 key Australian drug education policy stakeholders. The findings from this research have been distilled and presented as a list of 16 principles that underpin effective drug education. In broad terms, drug education should be evidence-based, developmentally appropriate, sequential, and contextual. Programs should be initiated before drug use commences. Strategies should be linked to goals and should incorporate harm minimization. Teaching should be interactive and use peer leaders. The role of the classroom teacher is central. Certain program content is important, as is social and resistance skills training. Community values, the social context of use, and the nature of drug harm have to be addressed. Coverage needs to be adequate and supported by follow-up. It is envisaged that these principles will provide all those involved in the drug education field with a set of up-to-date, research-based guidelines against which to reference decisions on program design, selection, implementation, and evaluation.

  18. Effect of oils on drug absorption

    OpenAIRE

    Palin, K.J.

    1981-01-01

    Oil and emulsion vehicles have been shown to alter the oral absorption of many drugs. This may be due to enhanced lymph flow and/or altered gastro-intestinal motility in the presence of the oils. The oral absorption of a model compound (DOT) in the presence of three chemically different oils, arachis oil, Miglyol 812 and liquid paraffin was investigated in rats, the influence of lymphatic absorption and gastro-intestinal motility being determined. The findings were applied to the for.mulation...

  19. Intratumor heterogeneity alters most effective drugs in designed combinations.

    Science.gov (United States)

    Zhao, Boyang; Hemann, Michael T; Lauffenburger, Douglas A

    2014-07-22

    The substantial spatial and temporal heterogeneity observed in patient tumors poses considerable challenges for the design of effective drug combinations with predictable outcomes. Currently, the implications of tissue heterogeneity and sampling bias during diagnosis are unclear for selection and subsequent performance of potential combination therapies. Here, we apply a multiobjective computational optimization approach integrated with empirical information on efficacy and toxicity for individual drugs with respect to a spectrum of genetic perturbations, enabling derivation of optimal drug combinations for heterogeneous tumors comprising distributions of subpopulations possessing these perturbations. Analysis across probabilistic samplings from the spectrum of various possible distributions reveals that the most beneficial (considering both efficacy and toxicity) set of drugs changes as the complexity of genetic heterogeneity increases. Importantly, a significant likelihood arises that a drug selected as the most beneficial single agent with respect to the predominant subpopulation in fact does not reside within the most broadly useful drug combinations for heterogeneous tumors. The underlying explanation appears to be that heterogeneity essentially homogenizes the benefit of drug combinations, reducing the special advantage of a particular drug on a specific subpopulation. Thus, this study underscores the importance of considering heterogeneity in choosing drug combinations and offers a principled approach toward designing the most likely beneficial set, even if the subpopulation distribution is not precisely known.

  20. Molecular Mechanism: ERK Signaling, Drug Addiction, and Behavioral Effects.

    Science.gov (United States)

    Sun, Wei-Lun; Quizon, Pamela M; Zhu, Jun

    2016-01-01

    Addiction to psychostimulants has been considered as a chronic psychiatric disorder characterized by craving and compulsive drug seeking and use. Over the past two decades, accumulating evidence has demonstrated that repeated drug exposure causes long-lasting neurochemical and cellular changes that result in enduring neuroadaptation in brain circuitry and underlie compulsive drug consumption and relapse. Through intercellular signaling cascades, drugs of abuse induce remodeling in the rewarding circuitry that contributes to the neuroplasticity of learning and memory associated with addiction. Here, we review the role of the extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase, and its related intracellular signaling pathways in drug-induced neuroadaptive changes that are associated with drug-mediated psychomotor activity, rewarding properties and relapse of drug seeking behaviors. We also discuss the neurobiological and behavioral effects of pharmacological and genetic interferences with ERK-associated molecular cascades in response to abused substances. Understanding the dynamic modulation of ERK signaling in response to drugs may provide novel molecular targets for therapeutic strategies to drug addiction. Copyright © 2016. Published by Elsevier Inc.

  1. Entry time effects and follow-on drug competition.

    Science.gov (United States)

    Andrade, Luiz Flavio; Sermet, Catherine; Pichetti, Sylvain

    2016-01-01

    Pharmaceutical firms have been criticized for concentrating efforts of R&D on the so-called me-too or follow-on drugs. There have been many comments for and against the dissemination of these incremental innovations but few papers have broached the subject from an econometric point of view, possibly because identification of me-too or follow-on drugs is not so obvious. This paper focuses on the impact of entry order on follow-on drug competition in the French market between the years 2001 and 2007. More precisely, this study examines the effects on market share of first entrants in the follow-on drug market and how this possible competitive advantage changes over time. First results are coherent with theoretical microeconomic issues concerning the importance of being first. We find evidence that first movers in the follow-on drug market have the ability to capture and maintain greater market share for a long period of time. The hierarchical market position of follow-on drugs does not seem to be affected by generic drug emergence. From a dynamic perspective, our analysis shows that market share is positively correlated with the ability of follow-on drugs to set prices higher than the average follow-on drug prices in a specific therapeutic class, which means that market power remains considerably important for first movers. Moreover, we found that the optimum level of innovation to maximize market share is the highest one.

  2. Impact of pharmaceutical cocrystals: the effects on drug pharmacokinetics.

    Science.gov (United States)

    Shan, Ning; Perry, Miranda L; Weyna, David R; Zaworotko, Michael J

    2014-09-01

    Pharmaceutical cocrystallization has emerged in the past decade as a new strategy to enhance the clinical performance of orally administered drugs. A pharmaceutical cocrystal is a multi-component crystalline material in which the active pharmaceutical ingredient is in a stoichiometric ratio with a second compound that is generally a solid under ambient conditions. The resulting cocrystal exhibits different solid-state thermodynamics, leading to changes in physicochemical properties that offer the potential to significantly modify drug pharmacokinetics. The impact of cocrystallization upon drug pharmacokinetics has not yet been well delineated. Herein, we compile previously published data to address two salient questions: what effect does cocrystallization impart upon physicochemical properties of a drug substance and to what degree can those effects impact its pharmacokinetics. Cocrystals can impact various aspects of drug pharmacokinetics, including, but not limited to, drug absorption. The diversity of solid forms offered through cocrystallization can facilitate drastic changes in solubility and pharmacokinetics. Therefore, it is unsurprising that cocrystal screening is now a routine step in early-stage drug development. With the increasing recognition of pharmaceutical cocrystals from clinical, regulatory and legal perspectives, the systematic commercialization of cocrystal containing drug products is just a matter of time.

  3. [Effect of anticholinergic drugs on cognitive impairment in the elderly].

    Science.gov (United States)

    López-Álvarez, Jorge; Zea Sevilla, María Ascensión; Agüera Ortiz, Luis; Fernández Blázquez, Miguel Ángel; Valentí Soler, Meritxell; Martínez-Martín, Pablo

    2015-01-01

    The use of anticholinergic drugs is common in the elderly, even in people with cognitive impairment. A systematic search was conducted in PubMed (anticholinergic effects, anticholinergic and dementia) to define the effects of anticholinergic drugs in the elderly. We emphasized the search in patterns of use, the combined use with AChEIs, the measurement of the Serum Anticholinergic Activity, and the short-term and long-term cognitive effects. The conclusions are that the use of anticholinergic drugs is common in the elderly, even more so than the medical prescription of AChEIs in Alzheimer's disease. The use of anticholinergic drugs may result in cognitive impairment. In long-term use it may generate a worsening of cognitive functions. It can lead to a wrong diagnosis of mild cognitive impairment or dementia, and they can also initiate signs of dementia. Greater cognitive effects appear when there is a previous deficit, but cognitive effects from anticholinergic drugs disappear in severe dementia. The presence of ApoEɛ4 increases the vulnerability for cognitive impairment when these drugs are employed. Copyright © 2013 SEP y SEPB. Published by Elsevier España. All rights reserved.

  4. Mechanistic models enable the rational use of in vitro drug-target binding kinetics for better drug effects in patients.

    Science.gov (United States)

    de Witte, Wilhelmus E A; Wong, Yin Cheong; Nederpelt, Indira; Heitman, Laura H; Danhof, Meindert; van der Graaf, Piet H; Gilissen, Ron A H J; de Lange, Elizabeth C M

    2016-01-01

    Drug-target binding kinetics are major determinants of the time course of drug action for several drugs, as clearly described for the irreversible binders omeprazole and aspirin. This supports the increasing interest to incorporate newly developed high-throughput assays for drug-target binding kinetics in drug discovery. A meaningful application of in vitro drug-target binding kinetics in drug discovery requires insight into the relation between in vivo drug effect and in vitro measured drug-target binding kinetics. In this review, the authors discuss both the relation between in vitro and in vivo measured binding kinetics and the relation between in vivo binding kinetics, target occupancy and effect profiles. More scientific evidence is required for the rational selection and development of drug-candidates on the basis of in vitro estimates of drug-target binding kinetics. To elucidate the value of in vitro binding kinetics measurements, it is necessary to obtain information on system-specific properties which influence the kinetics of target occupancy and drug effect. Mathematical integration of this information enables the identification of drug-specific properties which lead to optimal target occupancy and drug effect in patients.

  5. Marijuana and Cocaine Effect Expectancies and Drug Use Patterns.

    Science.gov (United States)

    Schafer, John; Brown, Sandra A.

    1991-01-01

    Content analyzed self-reports from 704 college students and used results to develop Marijuana Effect Expectancy Questionnaire and Cocaine Effect Expectancy Questionnaire. Identified six marijuana expectancies and five cocaine expectancies. Drug effect expectancies distinguished between patterns of nonuse and varying degrees of use of these two…

  6. Stabilizing Agents for Drug Nanocrystals: Effect on Bioavailability

    Directory of Open Access Journals (Sweden)

    Annika Tuomela

    2016-05-01

    Full Text Available Drug nanocrystals are a versatile option for drug delivery purposes, and while the number of poorly soluble drug materials is all the time increasing, more research in this area is performed. Drug nanocrystals have a simple structure—a solid drug core is surrounded by a layer of stabilizing agent. However, despite the considerably simple structure, the selection of an appropriate stabilizer for a certain drug can be challenging. Mostly, the stabilizer selection is based purely on the requirement of physical stability, e.g., maintaining the nanosized particle size as long as possible after the formation of drug nanocrystals. However, it is also worth taking into account that stabilizer can affect the bioavailability in the final formulation via interactions with cells and cell layers. In addition, formation of nanocrystals is only one process step, and for the final formulation, more excipients are often added to the composition. The role of the stabilizers in the final formulation can be more than only stabilizing the nanocrystal particle size. A good example is the stabilizer’s role as cryoprotectant during freeze drying. In this review, the stabilizing effect, role of stabilizers in final nanocrystalline formulations, challenges in reaching in vitro–in vivo correlation with nanocrystalline products, and stabilizers’ effect on higher bioavailability are discussed.

  7. May disordered protein cause serious drug side effect?

    Science.gov (United States)

    Tou, Weng Ieong; Chen, Calvin Yu-Chian

    2014-04-01

    Insomnia is a self-reported disease where patients lose their ability to initiate and maintain sleep, leading to daytime performance impairment. Several drug targets to ameliorate insomnia symptoms have been discovered; however, these drug targets lead to serious side effects. Thus, we characterize the structural properties of these sleep-related receptors and the clock complex and discuss a possible drug design that will reduce side effects. Computational prediction shows that disordered property is shared. Over 30% of the structure of CLOCK, PER1/2/3, BMAL-1, muscarinic acetylcholine receptor-M1, melatonin receptor and casein kinase I are structurally disordered (the remaining proteins represent insomnia drugs might be closely related to the protein architecture. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Effect and Safety of Shihogyejitang for Drug Resistant Childhood Epilepsy

    Directory of Open Access Journals (Sweden)

    Jinsoo Lee

    2016-01-01

    Full Text Available Objective. Herbal medicine has been widely used to treat drug resistant epilepsy. Shihogyejitang (SGT has been commonly used to treat epilepsy. We investigated the effect and safety of SGT in children with drug resistant epilepsy. Design. We reviewed medical records of 54 patients with epilepsy, who failed to respond to at least two antiepileptic drugs and have been treated with SGT between April 2006 and June 2014 at the Department of Pediatric Neurology, I-Tomato Hospital, Korea. Effect was measured by the response rate, seizure-free rate, and retention rate at six months. We also checked adverse events, change in antiepileptic drugs use, and the variables related to the outcome. Results. Intent-to-treat analysis showed that, after six months, 44.4% showed a >50% seizure reduction, 24.1% including seizure-free, respectively, and 53.7% remained on SGT. Two adverse events were reported, mild skin rash and fever. Focal seizure type presented significantly more positive responses when compared with other seizure types at six months (p=0.0284, Fisher’s exact test. Conclusion. SGT is an effective treatment with excellent tolerability for drug resistant epilepsy patients. Our data provide evidence that SGT may be used as alternative treatment option when antiepileptic drug does not work in epilepsy children.

  9. Drug Facts

    Medline Plus

    Full Text Available ... Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, ... Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug Use and Kids ...

  10. Does the placebo effect modulate drug bioavailability? Randomized cross-over studies of three drugs.

    Science.gov (United States)

    Hammami, Muhammad M; Yusuf, Ahmed; Shire, Faduma S; Hussein, Rajaa; Al-Swayeh, Reem

    2017-05-23

    Medication effect is the sum of its drug, placebo, and drug*placebo interaction effects. It is conceivable that the interaction effect involves modulating drug bioavailability; it was previously observed that being aware of caffeine ingestion may prolong caffeine plasma half-life. This study was set to evaluate such concept using different drugs. Balanced single-dose, two-period, two-group, cross-over design was used to compare the pharmacokinetics of oral cephalexin, ibuprofen, and paracetamol, each described by its name (overt) or as placebo (covert). Volunteers and study coordinators were deceived as to study aim. Drug concentrations were determined blindly by in-house, high performance liquid chromatography assays. Terminal-elimination half-life (t ½ ) (primary outcome), maximum concentration (C max ), C max first time (T max ), terminal-elimination-rate constant (λ), area-under-the-concentration-time-curve, to last measured concentration (AUC T ), extrapolated to infinity (AUC I ), or to T max of overt drug (AUC Overttmax ), and C max /AUC I were calculated blindly using standard non-compartmental method. Covert-vs-overt effect on drug pharmacokinetics was evaluated by analysis-of-variance (ANOVA, primary analysis), 90% confidence interval (CI) using the 80.00-125.00% bioequivalence range, and percentage of individual pharmacokinetic covert/overt ratios that are outside the +25% range. Fifty, 30, and 50 healthy volunteers (18%, 10%, and 6% females, mean (SD) age 30.8 (6.2), 31.4 (6.6), and 31.2 (5.4) years) participated in 3 studies on cephalexin, ibuprofen, and paracetamol, respectively. Withdrawal rate was 4%, 0%, and 4%, respectively. Eighteen blood samples were obtained over 6, 10, and 14 h in each study period of the three drugs, respectively. ANOVA showed no significant difference in any pharmacokinetic parameter for any of the drugs. The 90% CIs for AUC T , AUC I , C max , AUC Overttmax , and C max /AUC I were within the bioequivalence range, except

  11. Unveiling Reality of the Mind: Cultural Arbitrary of Consumerism

    Science.gov (United States)

    Choi, Su-Jin

    2012-01-01

    This paper discusses the cultural arbitrary of consumerism by focusing on a personal realm. That is, I discuss what consumerism appeals to and how it flourishes in relation to our minds. I argue that we need to unveil reality of the mind, be aware of ourselves in relation to the perpetuation of consumerism, in order to critically intervene in the…

  12. Book review: Unveiling the Whale: Discourses on Whales and Whaling

    Science.gov (United States)

    John Schelhas

    2012-01-01

    Whaling represents one of the most internationally controversial and highly polarized environmental issues of recent times. Arne Kalland, in Unveiling the Whale: Discourses on Whales and Whaling, examines the whaling issue from the perspective of a pro-whaling country with an emphasis on analysis of discourse in international arenas, primarily the International Whaling...

  13. Proofpoint unveils the industry's most advanced anti-spam laboratory

    CERN Multimedia

    2003-01-01

    "Proofpoint, Inc., the leader in large enterprise anti-spam solutions, today unveiled its Anti-Spam Laboratory, the world's most advanced center for spam research and analysis, and the first to be based on advanced Machine Learning science" (1 page).

  14. First National Picture of Trends in the Humanities Is Unveiled

    Science.gov (United States)

    Howard, Jennifer

    2009-01-01

    When it comes to hard data about what they do, policy makers and educators in the humanities have been mostly left out in the cold, forced to rely on isolated statistics that do not give an overview of the field. That changed this month, as the American Academy of Arts and Sciences unveiled the prototype of its long-awaited Humanities Indicators…

  15. Brain serotonin, psychoactive drugs, and effects on reproduction.

    Science.gov (United States)

    Ayala, María Elena

    2009-12-01

    Serotonin, a biogenic amine, is present in significant amounts in many structures of the CNS. It is involved in regulation of a wide variety of physiological functions, such as sensory and motor functions, memory, mood, and secretion of hormones including reproductive hormones. It has also been implicated in the etiology of a range of psychiatric disorders such as anxiety, depression, and eating disorders, along with other conditions such as obesity and migraine. While some drugs that affect serotonin, such as fenfluramine and fluoxetine, have been successfully used in treatment of a range of psychiatric diseases, others, such as the amphetamine analogues MDMA and METH, are potent psychostimulant drugs of abuse. Alterations in serotonergic neurons caused by many of these drugs are well characterized; however, little is known about the reproductive consequences of such alterations. This review evaluates the effects of drugs such as MDMA, pCA, fenfluramine, and fluoxetine on serotonergic transmission in the brain, examines the relationships of these drug effects with the neuroendocrine mechanisms modulating reproductive events such as gonadotropin secretion, ovulation, spermatogenesis, and sexual behavior in animal models, and discusses possible reproductive implications of these drugs in humans.

  16. Drugs and Pregnancy: The Effects of Nonmedical Use of Drugs on Pregnancy, Childbirth, and Neonates. National Institute on Drug Abuse Research Issues 5.

    Science.gov (United States)

    Ferguson, Patricia, Ed.; And Others

    The National Institute on Drug Abuse presents this report as the fifth in a series intended to summarize the empirical research findings and major theoretical approaches relating to the the issues of drug use and abuse. Included in this volume are summaries of the major research findings concerning the effects of nonmedical drug use on pregnancy.…

  17. Effects of parent drug use and personality on toddler adjustment.

    Science.gov (United States)

    Brook, J S; Whiteman, M; Shapiro, J; Cohen, P

    1996-03-01

    The interrelation between parental drug use and parental personality and the effects on 18-month-old children's adjustment were examined. Data on the parents were available at four points in time: Time 1 at mean age 6.1 years, Time 2 at mean age 13.7 years, Time 3 at mean age 16.4 years, and at Time 4 at mean age 22.2 years. Data on their toddlers at 18 months of age were also available. Structured interviews were used to assess personality and drug use and the toddlers' adjustment. Time 3 parental personality traits were related to Time 4 personality traits, which in turn were related to toddler adjustment. The influence of parental alcohol involvement (Time 3) on toddler adjustment was mediated by parental personality (Times 3 and 4) and parental alcohol problems (Time 4). Interactive effects demonstrated that protective parental personality traits (nondrug conducive) enhanced the effects of low parental drug use, resulting in the highest amounts of toddler adjustment. There are significant pathways between parental personality and drug use and toddler adjustment. Parental protective factors enhance the effect of parental low drug use on toddler adjustment.

  18. Recommendations on the effect of antidiabetic drugs in bone.

    Science.gov (United States)

    Rozas-Moreno, Pedro; Reyes-García, Rebeca; Jódar-Gimeno, Esteban; Varsavsky, Mariela; Luque-Fernández, Inés; Cortés-Berdonces, María; Muñoz-Torres, Manuel

    2017-03-01

    To provide recommendations on the effect of antidiabetic drugs on bone fragility to help select the most adequate antidiabetic treatment, especially in diabetic patients with high risk of fracture. Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. The GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) was used to establish both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each antidiabetic drug: AND "osteoporosis", "fractures", "bone mineral density", "bone markers", "calciotropic hormones". Papers in English with publication date before 30 April 2016 were reviewed. Recommendations were jointly discussed by the Working Group. The document summaries the data on the potential effects of antidiabetic drugs on bone metabolism and fracture risk. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

    Science.gov (United States)

    Subramaniam, B; Claudius, J S

    1990-03-08

    Cancer therapy using chemotherapeutic drugs frequently involves injection of the drug into the body through some intravenous mode of administration, viz, continuous (drip) infusion or single/multiple bolus injection(s). An understanding of the effect of the various modes of administration upon tumor penetration of drug is essential to rational design of drug therapy. This paper investigates drug penetration into a model tumor of slab geometry (between two capillaries) in which the overall transport rate of drug is limited by intra-tumor transport characterized by an effective diffusion coefficient. Employing the method of Finite Fourier Transforms (FFT), analytical solutions have been obtained for transient drug distribution in both the plasma and the tumor following three modes of administration, viz, continuous infusion, single bolus injection and equally-spaced equal-dose multiple bolus injections, of a given amount of drug. The qualitative trends exhibited by the plasma drug distribution profiles are consistent with reported experimental studies. Two concepts, viz, the dimensionless decay constant and the plasma/tumor drug concentration trajectories, are found to be particularly useful in the rational design of drug therapy. The dimensionless decay constant provides a measure of the rate of drug decay in the plasma relative to the rate of drug diffusion into the tumor and is thus characteristic of the tumor/drug system. The magnitude of this parameter dictates the choice of drug administration mode for minimizing drug decay in the plasma while simultaneously maximizing drug transport into the tumor. The concentration trajectories provide a measure of the plasma drug concentration relative to the tumor drug concentration at various times following injection. When the tumor drug concentration exceeds the plasma drug concentration, the drug will begin to diffuse out of the tumor. Knowledge of the time at which this diffusion reversal occurs is especially useful

  20. Data analysis unveils a new stylized fact in foreign currency markets

    Science.gov (United States)

    Nacher, J. C.; Ochiai, T.

    2012-09-01

    The search for stylized facts (i.e., simplified empirical facts) is of capital importance in econophysics because the stylized facts constitute the experimental empirical body on which theories and models should be tested. At the moment they are too few and this is an important limitation to the progress in the field. In this work, we unveil a new stylized fact, which consists of resistance effect and breaking-acceleration effect that implicitly requires a long memory feature in price movement. By analyzing a vast amount of historical data, we demonstrate that the financial market tends to exceed a past (historical) extreme price less often than expected by a classic short-memory model (e.g., Black-Scholes model). We call it resistance effect. However, when the market does it, we predict that the average volatility at that time point will be much higher (accelerates more). It means, in average, volatility accelerates more when the price breaks the highest (lowest) value. We refer to this as breaking-acceleration effect. These observed empirical facts are actually an effect which may arise from technical trading and psychological effects. Taken together, these results indicate that, beyond the predictive capability of this unveiled stylized fact, traditional short-memory models do not faithfully capture the market dynamics.

  1. An attention-based effective neural model for drug-drug interactions extraction.

    Science.gov (United States)

    Zheng, Wei; Lin, Hongfei; Luo, Ling; Zhao, Zhehuan; Li, Zhengguang; Zhang, Yijia; Yang, Zhihao; Wang, Jian

    2017-10-10

    Drug-drug interactions (DDIs) often bring unexpected side effects. The clinical recognition of DDIs is a crucial issue for both patient safety and healthcare cost control. However, although text-mining-based systems explore various methods to classify DDIs, the classification performance with regard to DDIs in long and complex sentences is still unsatisfactory. In this study, we propose an effective model that classifies DDIs from the literature by combining an attention mechanism and a recurrent neural network with long short-term memory (LSTM) units. In our approach, first, a candidate-drug-oriented input attention acting on word-embedding vectors automatically learns which words are more influential for a given drug pair. Next, the inputs merging the position- and POS-embedding vectors are passed to a bidirectional LSTM layer whose outputs at the last time step represent the high-level semantic information of the whole sentence. Finally, a softmax layer performs DDI classification. Experimental results from the DDIExtraction 2013 corpus show that our system performs the best with respect to detection and classification (84.0% and 77.3%, respectively) compared with other state-of-the-art methods. In particular, for the Medline-2013 dataset with long and complex sentences, our F-score far exceeds those of top-ranking systems by 12.6%. Our approach effectively improves the performance of DDI classification tasks. Experimental analysis demonstrates that our model performs better with respect to recognizing not only close-range but also long-range patterns among words, especially for long, complex and compound sentences.

  2. Adolescent Initiation of Drug Use: Effects of Prenatal Cocaine Exposure

    Science.gov (United States)

    Richardson, Gale A.; Larkby, Cynthia; Goldschmidt, Lidush; Day, Nancy L.

    2013-01-01

    Objective: To investigate the direct effects of prenatal cocaine exposure (PCE) on adolescent drug use, while controlling for other predictors of adolescent use. Method: Data are from a longitudinal study of PCE in which women and their offspring were assessed throughout childhood. Adolescents were interviewed at 15 years about their age at…

  3. Book Review: The Drug Effect | Kriegler | South African Crime ...

    African Journals Online (AJOL)

    Title: The Drug Effect: Health, Crime and Society Editors: Suzanne Fraser and David Moore Publisher: Cambridge University Press Price: R500.00 (incl. VAT and postage) Pages: 260. Availability: Published. Available through all academic bookstores. ISBN: 978-0-521-15605-9 ...

  4. The Effects of Antiepileptic Drugs on Classroom Performance

    Science.gov (United States)

    Titus, Jeffrey B.; Thio, Liu Lin

    2009-01-01

    Epilepsy is one of the most common neurological disorders in children, and it has been associated with an increased risk of cognitive, psychiatric, and learning problems. Although side effects of antiepileptic drugs (AEDs) have been long studied in adults, an understanding of how they manifest in children is only beginning to emerge. Careful…

  5. Modulatory effect of polymer type and composition on drug release ...

    African Journals Online (AJOL)

    The purpose of this study was to investigate the effects of polymer type and composition on drug release from the matrix of diclofenac sodium sustained release tablets formulated using three different granulation methods. Ten (10) batches of diclofenac sodium tablets (F01 - F10) were prepared by melt granulation, ...

  6. Effect of drugs on the thyroid function tests

    International Nuclear Information System (INIS)

    Cardoso, G.P.; Faria, A.C.S. de; Carvalho, M.C. de; Guimaraes, M.M.; Cordeiro, J.G.H.; Santa Casa do Rio de Janeiro

    1984-01-01

    The effects of drugs in the results of thyroid function tests, which could lead to misinterpretation of the real clinical state of the patients, are reviewed. The aspects of the metabolism of the thyreoidean hormones which could be related to these alterations are presented. (Author) [pt

  7. Dissolution enhancement of drugs. part i: technologies and effect of ...

    African Journals Online (AJOL)

    and steam aided granulation. In these techniques carrier plays an important role in improving solubility and dissolution rate. Polymers, superdisintegrants, surfactants are extensively studied in recent years for dissolution enhancement in drugs. This part of this review discusses technological overview and effect of polymers,

  8. Bone effects of biologic drugs in rheumatoid arthritis.

    Science.gov (United States)

    Corrado, Addolorata; Neve, Anna; Maruotti, Nicola; Cantatore, Francesco Paolo

    2013-01-01

    Biologic agents used in the treatment of rheumatoid arthritis (RA) are able to reduce both disease activity and radiographic progression of joint disease. These drugs are directed against several proinflammatory cytokines (TNF α , IL-6, and IL-1) which are involved both in the pathogenesis of chronic inflammation and progression of joint structural damage and in systemic and local bone loss typically observed in RA. However, the role of biologic drugs in preventing bone loss in clinical practice has not yet clearly assessed. Many clinical studies showed a trend to a positive effect of biologic agents in preventing systemic bone loss observed in RA. Although the suppression of inflammation is the main goal in the treatment of RA and the anti-inflammatory effects of biologic drugs exert a positive effect on bone metabolism, the exact relationship between the prevention of bone loss and control of inflammation has not been clearly established, and if the available biologic drugs against TNF α , IL-1, and IL-6 can exert their effect on systemic and local bone loss also through a direct mechanism on bone cell metabolism is still to be clearly defined.

  9. Using human genetics to predict the effects and side-effects of drugs

    DEFF Research Database (Denmark)

    Stender, Stefan; Tybjærg-Hansen, Anne

    2016-01-01

    PURPOSE OF REVIEW: 'Genetic proxies' are increasingly being used to predict the effects of drugs. We present an up-to-date overview of the use of human genetics to predict effects and adverse effects of lipid-targeting drugs. RECENT FINDINGS: LDL cholesterol lowering variants in HMG-Coenzyme A re...

  10. Is immunotherapy an opportunity for effective treatment of drug addiction?

    Science.gov (United States)

    Zalewska-Kaszubska, Jadwiga

    2015-11-27

    Immunotherapy has a great potential of becoming a new therapeutic strategy in the treatment of addiction to psychoactive drugs. It may be used to treat addiction but also to prevent neurotoxic complications of drug overdose. In preclinical studies two immunological methods have been tested; active immunization, which relies on the administration of vaccines and passive immunization, which relies on the administration of monoclonal antibodies. Until now researchers have succeeded in developing vaccines and/or antibodies against addiction to heroin, cocaine, methamphetamine, nicotine and phencyclidine. Their effectiveness has been confirmed in preclinical studies. At present, clinical studies are being conducted for vaccines against nicotine and cocaine and also anti-methamphetamine monoclonal antibody. These preclinical and clinical studies suggest that immunotherapy may be useful in the treatment of addiction and drug overdose. However, there are a few problems to be solved. One of them is controlling the level of antibodies due to variability between subjects. But even obtaining a suitable antibody titer does not guarantee the effectiveness of the vaccine. Additionally, there is a risk of intentional or unintentional overdose. As vaccines prevent passing of drugs through the blood/brain barrier and thereby prevent their positive reinforcement, some addicted patients may erroneously seek higher doses of psychoactive substances to get "high". Consequently, vaccination should be targeted at persons who have a strong motivation to free themselves from drug dependency. It seems that immunotherapy may be an opportunity for effective treatment of drug addiction if directed to adequate candidates for treatment. For other addicts, immunotherapy may be a very important element supporting psycho- and pharmacotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Oral fluid drug tests: effects of adulterants and foodstuffs.

    Science.gov (United States)

    Wong, Raphael C; Tran, Minhchau; Tung, James K

    2005-06-10

    An on-site oral fluid drug screen, Oratect, was used to investigate the effects of adulterants and foodstuffs on oral fluid test results. Common foods, beverages, food ingredients, cosmetics and hygienic products were demonstrated not to cause false positive results when tested 30 min after their consumption. Evaluations of two commercial oral fluid adulterants, "Clear Choice Fizzy Flush" and "Test'in Spit n Kleen Mouthwash" suggest their mechanism of action is the clearing of residual drugs of abuse compounds through rinsing of the oral cavity. They do not directly destroy the drug compounds or change the pH of the oral fluid. It is also suggested that a common mouthwash would perform similar action.

  12. [Plasma lipoproteins as drug carriers. Effect of phospholipid formulations].

    Science.gov (United States)

    Torkhovskaia, T I; Ipatova, O M; Medvedeva, N V; Ivanov, V S; Ivanova, L I

    2010-01-01

    The extensive development of nanotechnologies in the last two decades has brought about new understanding of plasma lipoproteins (LP) as natural drug nanocarriers that escape interaction with immune and reticuloendothelial systems. Drugs bound to LP (especially LDL) can more actively penetrate into cells of many cancer and inflammation tissues with enhanced expression or/and dysregulation of B,E receptors or possibly scavenger SR-BI receptors. Relevant studies are focused on the development of new dosage forms by conjugating lipophilic drugs either with isolated plasma LP or with their model formulations, such as nanoemulsions, mimetics, lipid nanospheres, etc. Some authors include in these particles serum or recombinant apoproteins, peptides, and modified polymer products. As shown recently, protein-free lipid nanoemulsions in plasma take up free apoA and apoE. Complexes with various LP also form after direct administration of lypophilic drugs into blood especially those enclosed in phospholipid formulations, e.g. liposomes. Results of evaluation of some lipophilic dugs (mainly cytostatics, amphotericin B, cyclosporine A, etc.) are discussed. Original data are presented on the influence of phospholipid formulations on the distribution of doxorubicin and indomethacin between LP classes after in vitro incubation in plasma. On the whole, the review illustrates the importance of research on LP and phospholi pid forms as drug nanocarriers to be used to enhance effect of therapy.

  13. Effect of the anticarcinogenic drug 6-mercaptopurine on mineral metabolism

    International Nuclear Information System (INIS)

    Amemiya, K.

    1987-01-01

    The effect of 6-mercaptopurine (6-MP) on mineral metabolism was investigated using rats and mice. A single 6-mercaptopurine injection in pregnant rats on day 11 of gestation proved to be highly teratogenic. At term, fetuses from 6-MP injected dams had lower livers zinc concentrations than non-injected or vehicle injected controls while dams showed no differences in liver zinc. Fetuses from dams injected with 6-MP and fed supplemental levels of zinc had a lower frequency of malformations and had higher hepatic zinc concentrations than fetuses from dams fed less zinc with drug injection. Non-pregnant mice injected with 6-MP had higher zinc concentrations compared to controls. In addition, iron, copper and calcium concentrations were higher in the livers of 6-MP injected mice than in controls, indicating that the drug affected several elements. Hepatic concentrations of metallothionein (MT) were also elevated in 6-MP injected mice, suggesting that the change in zinc concentrations associated with drug administration was the result of a drug induction of MT. Dams injected with 6-MP on day 13 of pregnancy had livers which retained more of an absorbed dose of 65 zinc than non-injected dams. Plasma from these drug injected dams also retained less of the absorbed dose than control dams. In contrast, day 14 from dams injected with 6-MP, retained less of an absorbed dose than control embryos

  14. Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study.

    Science.gov (United States)

    Hon, Chun-Yip; Chua, Prescillia Ps; Danyluk, Quinn; Astrakianakis, George

    2014-06-01

    Occupational exposure to antineoplastic drugs has been documented to result in various adverse health effects. Despite the implementation of control measures to minimize exposure, detectable levels of drug residual are still found on hospital work surfaces. Cleaning these surfaces is considered as one means to minimize the exposure potential. However, there are no consistent guiding principles related to cleaning of contaminated surfaces resulting in hospitals to adopt varying practices. As such, this pilot study sought to evaluate current cleaning protocols and identify those factors that were most effective in reducing contamination on drug preparation surfaces. Three cleaning variables were examined: (1) type of cleaning agent (CaviCide®, Phenokil II™, bleach and chlorhexidine), (2) application method of cleaning agent (directly onto surface or indirectly onto a wipe) and (3) use of isopropyl alcohol after cleaning agent application. Known concentrations of antineoplastic drugs (either methotrexate or cyclophosphamide) were placed on a stainless steel swatch and then, systematically, each of the three cleaning variables was tested. Surface wipes were collected and quantified using high-performance liquid chromatography-tandem mass spectrometry to determine the percent residual of drug remaining (with 100% being complete elimination of the drug). No one single cleaning agent proved to be effective in completely eliminating all drug contamination. The method of application had minimal effect on the amount of drug residual. In general, application of isopropyl alcohol after the use of cleaning agent further reduced the level of drug contamination although measureable levels of drug were still found in some cases.

  15. Universe unveiled the cosmos in my bubble bath

    CERN Document Server

    Vishveshwara, C V

    2015-01-01

    The bubbles were swirling all around me, massaging my body. As I luxuriated in this fantastic bath, I gasped realizing that those bubbles carried with them miniature galaxies bringing the entire Cosmos into my bathtub... Alfie is back. And so are George and other characters from the author’s previous book Einstein’s Enigma or Black Holes in My Bubble Bath. While the present book, Universe Unveiled - The Cosmos in My Bubble Bath, is completely independent, its storyline can be considered a sequel to the previous one. The scientific content spanning ancient world models to the most recent mysteries of cosmology is presented in an entirely nontechnical and descriptive style through the discussions between Alfie, the enlightened learner, and George, professor of astrophysics. Fantasies, based on these discussions that cover the scientific facts, are created by the magical bubble baths taken by Alfie. Universe Unveiled blends accurate science with philosophy, drama, humour, and fantasy to create an exciting co...

  16. ESA Unveils Its New Comet Chaser.

    Science.gov (United States)

    1999-07-01

    The objective is to study one of these primordial objects at close quarters by placing a lander on its surface and chasing, with an orbiter, the comet for millions of kilometres through space. Comets - among the oldest (4.6 billion years!) and last altered objects in the solar system - are regarded as the building blocks from which the planets formed. Thus the Rosetta's discoveries will allow the scientists to learn more about birth and evolution of the planets and about the origin of life on the Earth. The final design of the Rosetta orbiter will be revealed for the first time at the Royal Society in London on 1 July when a 1:4 scale model will be unveiled by ESA's Director of Science, Prof.. Roger Bonnet. (The full size version of the spacecraft is 32 metres across, so large that it would stretch the entire width of a football pitch. Almost 90 of this is accounted for by the giant solar panels which are needed to provide electrical power in the dark depths of the Solar System). "Rosetta is a mission of major scientific importance," said Prof. Bonnet. "It will build on the discoveries made by Giotto and confirm ESA's leading role in the exploration of the Solar System and the Universe as a whole." The timing of this event has been chosen to coincide with the London meeting of the Rosetta Science Working Team and the second Earth flyby of the now non-operational Giotto spacecraft. In addition, the opening of the British Museum's 'Cracking Codes' Exhibition, for which the Rosetta Stone is the centrepiece, is set to take place on 10 July. The Rosetta mission. Rosetta is the third Cornerstone in ESA's 'Horizon 2000' long-term scientific programme. It will be launched by Ariane 5 rocket from Kourou spaceport in French Guiana in January 2003. In order to gain sufficient speed to reach the distant comet, Rosetta will require gravity assists from the Earth (twice) and Mars. After swinging around Mars in May 2005, Rosetta will return to Earth's vicinity in October 2005 and

  17. Effect of Drug Loading Method and Drug Physicochemical Properties on the Material and Drug Release Properties of Poly (Ethylene Oxide Hydrogels for Transdermal Delivery

    Directory of Open Access Journals (Sweden)

    Rachel Shet Hui Wong

    2017-07-01

    Full Text Available Novel poly (ethylene oxide (PEO hydrogel films were synthesized via UV cross-linking with pentaerythritol tetra-acrylate (PETRA as cross-linking agent. The purpose of this work was to develop a novel hydrogel film suitable for passive transdermal drug delivery via skin application. Hydrogels were loaded with model drugs (lidocaine hydrochloride (LID, diclofenac sodium (DIC and ibuprofen (IBU via post-loading and in situ loading methods. The effect of loading method and drug physicochemical properties on the material and drug release properties of medicated film samples were characterized using scanning electron microscopy (SEM, swelling studies, differential scanning calorimetry (DSC, fourier transform infrared spectroscopy (FT-IR, tensile testing, rheometry, and drug release studies. In situ loaded films showed better drug entrapment within the hydrogel network and also better polymer crystallinity. High drug release was observed from all studied formulations. In situ loaded LID had a plasticizing effect on PEO hydrogel, and films showed excellent mechanical properties and prolonged drug release. The drug release mechanism for the majority of medicated PEO hydrogel formulations was determined as both drug diffusion and polymer chain relaxation, which is highly desirable for controlled release formulations.

  18. Prescription drugs for human use generally recognized as safe and effective and not misbranded: drugs used in research: radioactive drugs for certain research uses; amended reporting requirements

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    This amendment revises the reporting requirements for research studies in which radioactive drugs are used. It deletes the requirement for detailed measurements and calculations for each subject in the study; instead, it permits submission of data on a representative subject. The effect will be to decrease the burden in reporting required of the Radioactive Drug Research Committee, but still provide the agency with data to evaluate the risk attributable to radioactive drugs

  19. Drugs affecting prelamin A processing: Effects on heterochromatin organization

    International Nuclear Information System (INIS)

    Mattioli, Elisabetta; Columbaro, Marta; Capanni, Cristina; Santi, Spartaco; Maraldi, Nadir M.; D'Apice, M. Rosaria; Novelli, Giuseppe; Riccio, Massimo; Squarzoni, Stefano; Foisner, Roland; Lattanzi, Giovanna

    2008-01-01

    Increasing interest in drugs acting on prelamin A has derived from the finding of prelamin A involvement in severe laminopathies. Amelioration of the nuclear morphology by inhibitors of prelamin A farnesylation has been widely reported in progeroid laminopathies. We investigated the effects on chromatin organization of two drugs inhibiting prelamin A processing by an ultrastructural and biochemical approach. The farnesyltransferase inhibitor FTI-277 and the non-peptidomimetic drug N-acetyl-S-farnesyl-L-cysteine methylester (AFCMe) were administered to cultured control human fibroblasts for 6 or 18 h. FTI-277 interferes with protein farnesylation causing accumulation of non-farnesylated prelamin A, while AFCMe impairs the last cleavage of the lamin A precursor and is expected to accumulate farnesylated prelamin A. FTI-277 caused redistribution of heterochromatin domains at the nuclear interior, while AFCMe caused loss of heterochromatin domains, increase of nuclear size and nuclear lamina thickening. At the biochemical level, heterochromatin-associated proteins and LAP2α were clustered at the nuclear interior following FTI-277 treatment, while they were unevenly distributed or absent in AFCMe-treated nuclei. The reported effects show that chromatin is an immediate target of FTI-277 and AFCMe and that dramatic remodeling of chromatin domains occurs following treatment with the drugs. These effects appear to depend, at least in part, on the accumulation of prelamin A forms, since impairment of prelamin A accumulation, here obtained by 5-azadeoxycytidine treatment, abolishes the chromatin effects. These results may be used to evaluate downstream effects of FTIs or other prelamin A inhibitors potentially useful for the therapy of laminopathies

  20. REBAMIPIDE: EFFECTIVE DRUG PREVENTION OF NSAID ENTEROPATHY IS POSSIBLE

    Directory of Open Access Journals (Sweden)

    E. V. Moroz

    2016-01-01

    Full Text Available Prevention of gastrointestinal tract (GIT complications is the most important element for the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs and low-dose aspirin (LDA. Proton pump inhibitors (PPIs have long been the only medication to prevent these complications. However, PPIs are only effective in preventing and treating upper GIT diseases (NSAID gastropathy rather than small intestinal injury (NSAID enteropathy. Rebamipide has emerged as a novel agent to protect the gastrointestinal mucosa today. The effect of the drug differs from that of PPIs: it is a typical gastroand enteroprotector that enhances the synthesis of endogenous prostaglandins and possesses a significant anti-inflammatory potential. Rebamipide has long been widely used by doctors inJapan,South Korea, andChinaas an effective and safe agent for the treatment of many diseases of the digestive system. There is a strong evidence base for the efficacy of rebamipide in preventing and treating NSAID gastropathy and NSAID enteropathy (including LDA-induced injuries. Controlled studies have found that the drug is not inferior to the classic gastroprotective agent misoprostol, significantly outperforming the latter in its tolerability. This review describes the mechanism of action of rebamipide and main clinical trials of its therapeutic effect in NSAID gastropathy and NSAID enteropathy. 

  1. Antidiabetic Effect of Galantamine: Novel Effect for a Known Centrally Acting Drug.

    Directory of Open Access Journals (Sweden)

    Mennatallah A Ali

    Full Text Available The cholinergic anti-inflammatory pathway is one of the putative biochemical pathways that link diabetes with Alzheimer disease. Hence, we aimed to verify the potential antidiabetic effect of galantamine, unveil the possible mechanisms and evaluate its interaction with vildagliptin. The n5-STZ rat model was adopted and the diabetic animals were treated with galantamine and/or vildagliptin for 4 weeks. Galantamine lowered the n5-STZ-induced elevation in body weight, food/water intake, serum levels of glucose, fructosamine, and ALT/AST, as well as AChE in the tested organs. Moreover, it modulated successfully the lipid profile assessed in serum, liver, and muscle, and increased serum insulin level, as well as % β-cell function, in a pattern similar to that of vildagliptin. Additionally, galantamine confirmed its antioxidant (Nrf2, TAC, MDA, anti-inflammatory (NF-κB, TNF-α, visfatin, adiponectin and anti-apoptotic (caspase-3, cytochrome c capabilities by altering the n5-STZ effect on all the aforementioned parameters. On the molecular level, galantamine/vildagliptin have improved the insulin (p-insulin receptor, p-Akt, GLUT4/GLUT2 and Wnt/β-catenin (p-GSK-3β, β-catenin signaling pathways. On almost all parameters, the galantamine effects surpassed that of vildagliptin, while the combination regimen showed the best effects. The present results clearly proved that galantamine modulated glucose/lipid profile possibly through its anti-oxidant, -apoptotic, -inflammatory and -cholinesterase properties. These effects could be attributed partly to the enhancement of insulin and Wnt/β-catenin signaling pathways. Galantamine can be strongly considered as a potential antidiabetic agent and as an add-on therapy with other oral antidiabetics.

  2. The effect of antiepileptic drugs on cognitive functions

    Directory of Open Access Journals (Sweden)

    A. S. Kotov

    2013-01-01

    Full Text Available Impaired cognitive function is a common problem in epileptic patients. The exact cause of cognitive impairment in case of epilepsy has not been explored fully, but there is no doubt that a role in this is played by three factors: the disease underlying epilepsy; epileptic seizures proper; and negative side effects of antiepileptic drugs. Their cognitive effects are one of the major problems affecting the tolerance of therapy. The review considers the effects of phenobarbital, phenytoin, carbamazepine, valproates, oxcarbazepine, topiramate, lamotrigine, and levetiracetam in terms of their action on the cognitive function of healthy volunteers and epileptic patients.

  3. Expression of Genes for Drug Transporters in the Human Female Genital Tract and Modulatory Effect of Antiretroviral Drugs.

    Science.gov (United States)

    Hijazi, Karolin; Cuppone, Anna M; Smith, Kieron; Stincarelli, Maria A; Ekeruche-Makinde, Julia; De Falco, Giulia; Hold, Georgina L; Shattock, Robin; Kelly, Charles G; Pozzi, Gianni; Iannelli, Francesco

    2015-01-01

    Anti-retroviral (ARV) -based microbicides are one of the strategies pursued to prevent HIV-1 transmission. Delivery of ARV drugs to subepithelial CD4+ T cells at concentrations for protection is likely determined by drug transporters expressed in the cervicovaginal epithelium. To define the role of drug transporters in mucosal disposition of topically applied ARV-based microbicides, these must be tested in epithelial cell line-based biopharmaceutical assays factoring the effect of relevant drug transporters. We have characterised gene expression of influx and efflux drug transporters in a panel of cervicovaginal cell lines and compared this to expression in cervicovaginal tissue. We also investigated the effect of dapivirine, darunavir and tenofovir, currently at advanced stages of microbicides development, on expression of drug transporters in cell lines. Expression of efflux ABC transporters in cervical tissue was best represented in HeLa, Ect1/E6E7 and End1/E6E7 cell lines. Expression of influx OCT and ENT transporters in ectocervix matched expression in Hela while expression of influx SLCO transporters in vagina was best reflected in VK2/E6E7 cell line. Stimulation with darunavir and dapivirine upregulated MRP transporters, including MRP5 involved in transport of tenofovir. Dapivirine also significantly downregulated tenofovir substrate MRP4 in cervical cell lines. Treatment with darunavir and dapivirine showed no significant effect on expression of BCRP, MRP2 and P-glycoprotein implicated in efflux of different ARV drugs. Darunavir strongly induced expression in most cell lines of CNT3 involved in cell uptake of nucleotide/nucleoside analogue reverse transcriptase inhibitors and SLCO drug transporters involved in cell uptake of protease inhibitors. This study provides insight into the suitability of cervicovaginal cell lines for assessment of ARV drugs in transport kinetics studies. The modulatory effect of darunavir and dapivirine on expression of drug

  4. [Failure mode and effects analysis on computerized drug prescriptions].

    Science.gov (United States)

    Paredes-Atenciano, J A; Roldán-Aviña, J P; González-García, Mercedes; Blanco-Sánchez, M C; Pinto-Melero, M A; Pérez-Ramírez, C; Calvo Rubio-Burgos, Miguel; Osuna-Navarro, F J; Jurado-Carmona, A M

    2015-01-01

    To identify and analyze errors in drug prescriptions of patients treated in a "high resolution" hospital by applying a Failure mode and effects analysis (FMEA).Material and methods A multidisciplinary group of medical specialties and nursing analyzed medical records where drug prescriptions were held in free text format. An FMEA was developed in which the risk priority index (RPI) was obtained from a cross-sectional observational study using an audit of the medical records, carried out in 2 phases: 1) Pre-intervention testing, and (2) evaluation of improvement actions after the first analysis. An audit sample size of 679 medical records from a total of 2,096 patients was calculated using stratified sampling and random selection of clinical events. Prescription errors decreased by 22.2% in the second phase. FMEA showed a greater RPI in "unspecified route of administration" and "dosage unspecified", with no significant decreases observed in the second phase, although it did detect, "incorrect dosing time", "contraindication due to drug allergy", "wrong patient" or "duplicate prescription", which resulted in the improvement of prescriptions. Drug prescription errors have been identified and analyzed by FMEA methodology, improving the clinical safety of these prescriptions. This tool allows updates of electronic prescribing to be monitored. To avoid such errors would require the mandatory completion of all sections of a prescription. Copyright © 2014 SECA. Published by Elsevier Espana. All rights reserved.

  5. Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs.

    Science.gov (United States)

    Milo, Ron

    2015-04-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

  6. REBAMIPIDE: EFFECTIVE DRUG PREVENTION OF NSAID ENTEROPATHY IS POSSIBLE

    OpenAIRE

    E. V. Moroz; A. E. Karateev

    2016-01-01

    Prevention of gastrointestinal tract (GIT) complications is the most important element for the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin (LDA). Proton pump inhibitors (PPIs) have long been the only medication to prevent these complications. However, PPIs are only effective in preventing and treating upper GIT diseases (NSAID gastropathy) rather than small intestinal injury (NSAID enteropathy). Rebamipide has emerged as a novel agent to protect the gast...

  7. Effect of reporting bias on meta-analyses of drug trials

    DEFF Research Database (Denmark)

    Hart, Beth; Lundh, Andreas; Bero, Lisa

    2012-01-01

    To investigate the effect of including unpublished trial outcome data obtained from the Food and Drug Administration (FDA) on the results of meta-analyses of drug trials.......To investigate the effect of including unpublished trial outcome data obtained from the Food and Drug Administration (FDA) on the results of meta-analyses of drug trials....

  8. Effect of drug law enforcement on drug market violence: a systematic review.

    Science.gov (United States)

    Werb, Dan; Rowell, Greg; Guyatt, Gordon; Kerr, Thomas; Montaner, Julio; Wood, Evan

    2011-03-01

    Violence is amongst the primary concerns of communities around the world and research has demonstrated links between violence and the illicit drug trade, particularly in urban settings. Given the growing emphasis on evidence-based policy-making, and the ongoing severe drug market violence in Mexico and other settings, we conducted a systematic review to examine the impacts of drug law enforcement on drug market violence. We conducted a systematic review using Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Specifically, we undertook a search of English language electronic databases (Academic Search Complete, PubMed, PsycINFO, EMBASE, Web of Science, Sociological Abstracts, Social Service Abstracts, PAIS International and Lexis-Nexis), the Internet (Google, Google Scholar), and article reference lists, from database inception to January 24, 2011. Overall, 15 studies were identified that evaluated the impact of drug law enforcement on drug market violence, including 11 (73%) longitudinal analyses using linear regression, 2 (13%) mathematical drug market models, and 2 (13%) qualitative studies. Fourteen (93%) studies reported an adverse impact of drug law enforcement on levels of violence. Ten of the 11 (91%) studies employing longitudinal qualitative analyses found a significant association between drug law enforcement and drug market violence. Our findings suggest that increasing drug law enforcement is unlikely to reduce drug market violence. Instead, the existing evidence base suggests that gun violence and high homicide rates may be an inevitable consequence of drug prohibition and that disrupting drug markets can paradoxically increase violence. In this context, and since drug prohibition has not meaningfully reduced drug supply, alternative regulatory models will be required if drug supply and drug market violence are to be meaningfully reduced. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. A new method to assess Pavlovian conditioning of psychostimulant drug effects.

    Science.gov (United States)

    Damianopoulos, E N; Carey, R J

    1994-07-01

    Experimental studies of psychoactive drugs by pavlovian drug-conditioning methods, which originally began with investigations of drug-induced responses mediated by the autonomic nervous system, have now been expanded to include drug-induced response effects expressed as modulations of spontaneous motoric behaviors. In the latter application, however, equivalent behavioral response outcomes in post-treatment tests for conditioning can occur following a psychostimulant drug treatment either through drug interference effects on habituation processes, drug-induced stress effects and/or by pavlovian conditioning of the drug-induced motoric activation effect. Current methodologies for the study of pavlovian conditioned drug effects and/or drug sensitization cannot distinguish among these possibilities. This methodological inadequacy was addressed by a modification of the conventional paired-unpaired treatment protocol. In the new protocol, the animal is sequentially placed into two test compartments with the drug treatment administered in conjunction with placement into the second test compartment. This design permits a differentiation of a pavlovian conditioned drug responses from non-conditioned drug effects through continuous measurement of the non-drug behavioral baseline in both the drug and non-drug control treatment groups combined with multiple response measurements and post-treatment tests for conditioning at variable post-conditioning intervals. The present study details the use of the new modified pavlovian protocol with repeated cocaine (10 mg/kg) treatment. A cocaine conditioned response at 1, 7, and 21 days post-conditioning was identified and distinguished from habituation and stress effects.

  10. Does the Drug Facts Label for nonprescription drugs meet its design objectives? A new procedure for assessing label effectiveness

    Directory of Open Access Journals (Sweden)

    Michael P Ryan

    2017-07-01

    Full Text Available We demonstrate an expanded procedure for assessing drug-label comprehension. Innovations include a pretest of drug preconceptions, verbal ability and label attentiveness measures, a label-scanning task, a free-recall test, category-clustering measures, and preconception-change scores. In total, 55 female and 39 male undergraduates read a facsimile Drug Facts Label for aspirin, a Cohesive-Prose Label, or a Scrambled-Prose Label. The Drug Facts Label outperformed the Scrambled-Prose Label, but not the Cohesive-Prose Label, in scanning effectiveness. The Drug Facts Label was no better than the Cohesive-Prose Label or the Scrambled-Prose Label in promoting attentiveness, recall and organization of drug facts, or misconception refutation. Discussion focuses on the need for refutational labels based on a sequence-of-events text schema.

  11. Expectations and satisfaction of pregnant women: unveiling prenatal care in primary care.

    Science.gov (United States)

    Aparecida Maciel Cardelli, Alexandrina; Li Marrero, Tai; Aparecida Pimenta Ferrari, Rosângela; Trevisan Martins, Júlia; Serafim, Deise

    2016-06-01

    To analyze the perception of primiparous women about prenatal care in Basic Health Units in a municipality in southern Brazil. This is a qualitative research from the perspective of Social Representation Theory, from the following question: How has been the pre-natal care for you? Eighteen pregnant women were interviewed. The analysis resulted in three categories: Expectation representation about prenatal care; Rescuing the care offered in prenatal consultation; Unveiling the (dis) satisfaction with prenatal consultation. The prenatal care was apprehended as an essential moment for safe pregnancy, although centered on the doctor's figure and guarantee access to early laboratory and imaging tests. On the other hand, dissatisfaction was revealed from the reception at the entrance to the health unit to the consultations access, although some statements suggest timely satisfaction. Prenatal care did not meet the specific expectations of the study group and unveiled that the nurse did not supply it, as a member of the multidisciplinary team. The organization of the nursing work process in primary care, related to prenatal care, needs to be revisited to promote the effectiveness of its actions.

  12. Expectations and satisfaction of pregnant women: unveiling prenatal care in primary care

    Directory of Open Access Journals (Sweden)

    Alexandrina Aparecida Maciel Cardelli

    Full Text Available Objective.To analyze the perception of primiparous women about prenatal care in Basic Health Units in a municipality in southern Brazil. Methods. This is a qualitative research from the perspective of Social Representation Theory, from the following question: How has been the pre-natal care for you? Eighteen pregnant women were interviewed. Results. The analysis resulted in three categories: Expectation representation about prenatal care; Rescuing the care offered in prenatal consultation; Unveiling the (dis satisfaction with prenatal consultation. The prenatal care was apprehended as an essential moment for safe pregnancy, although centered on the doctor's figure and guarantee access to early laboratory and imaging tests. On the other hand, dissatisfaction was revealed from the reception at the entrance to the health unit to the consultations access, although some statements suggest timely satisfaction. Conclusion. Prenatal care did not meet the specific expectations of the study group and unveiled that the nurse did not supply it, as a member of the multidisciplinary team. The organization of the nursing work process in primary care, related to prenatal care, needs to be revisited to promote the effectiveness of its actions.

  13. Liver Effects of Clinical Drugs Differentiated in Human Liver Slices

    Directory of Open Access Journals (Sweden)

    Alison E. M. Vickers

    2017-03-01

    Full Text Available Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM, diclofenac (DCF, 1 mM and etomoxir (ETM, 100 μM. Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM and cyclosporin A (CSA, 10 μM, while GSH was affected more than ATP by methimazole (MMI, 500 μM, terbinafine (TBF, 100 μM, and carbamazepine (CBZ 100 μM. Oxidative stress genes were affected by TBF (18%, CBZ, APAP, and ETM (12%–11%, and mitochondrial genes were altered by CBZ, APAP, MMI, and ETM (8%–6%. Apoptosis genes were affected by DCF (14%, while apoptosis plus necrosis were altered by APAP and ETM (15%. Activation of oxidative stress, mitochondrial energy, heat shock, ER stress, apoptosis, necrosis, DNA damage, immune and inflammation genes ranked CSA (75%, ETM (66%, DCF, TBF, MMI (61%–60%, APAP, CBZ (57%–56%, and DTL (48%. Gene changes in fatty acid metabolism, cholestasis, immune and inflammation were affected by DTL (51%, CBZ and ETM (44%–43%, APAP and DCF (40%–38%, MMI, TBF and CSA (37%–35%. This model advances multiple dosing in a human ex vivo model, plus functional markers and gene profile markers of drug induced human liver side-effects.

  14. Effect of irradiation of drugs and aiding substances

    International Nuclear Information System (INIS)

    Schnell, R.; Boegl, W.

    1982-01-01

    In this bibliographic study (Part I - VI), the results of more than 300 radiation tested pharmaceuticals are discussed and evaluated. The substances were treated with ionizing radiation in their pure form (solid substance or liquid), as aqueous or alcohol solution, as emulsion or in compound form, almost exclusively with gamma radiation from cobaldt-60 sources. The radiation doses applied amounted from some krd to about 100 Mrd. The results of the original papers analyzed in this Part VI are not summarized separately since the final Part VII of the study on the effects of irradiation of drugs and drug additives will contain a survey for all essential data discussed in Parts I to VI. (orig./MG) [de

  15. Unveiling the Higgs mechanism to students

    International Nuclear Information System (INIS)

    Organtini, Giovanni

    2012-01-01

    In this paper we outline a lecture given to undergraduate students to explain why physicists are so interested in the Higgs boson. The lecture was conceived for students not yet familiar with advanced physics and is suitable for those studying several other disciplines. The Higgs mechanism is introduced through semi-classical arguments mimicking basic field-theory concepts, assuming the validity of a symmetry principle in the expression of the energy of particles in a classical field. The lecture is divided into two parts. The first, suitable even for high-school students, shows how the mass of a particle results from a dynamical effect caused by interaction between a massless particle and a field (as in the Higgs mechanism). The audience for the second, much more technical part consists mainly of teachers and university students from disciplines other than physics. (paper)

  16. Effects of Antidiabetic Drugs on Gut Microbiota Composition

    Directory of Open Access Journals (Sweden)

    Sophie A. Montandon

    2017-09-01

    Full Text Available Gut microbiota forms a catalog of about 1000 bacterial species; which mainly belong to the Firmicutes and Bacteroidetes phyla. Microbial genes are essential for key metabolic processes; such as the biosynthesis of short-chain fatty acids (SCFA; amino acids; bile acids or vitamins. It is becoming clear that gut microbiota is playing a prevalent role in pathologies such as metabolic syndrome; type 2 diabetes (T2D; inflammatory and bowel diseases. Obesity and related diseases; notably type 2 diabetes, induce gut dysbiosis. In this review; we aim to cover the current knowledge about the effects of antidiabetic drugs on gut microbiota diversity and composition as well as the potential beneficial effects mediated by specific taxa. Metformin is the first-line treatment against T2D. In addition to its glucose-lowering and insulin sensitizing effects, metformin promotes SCFA-producing and mucin-degrading bacteria. Other antidiabetic drugs discussed in this review show positive effects on dysbiosis; but without any consensus specifically regarding the Firmicutes to Bacteroidetes ratio. Thus, beneficial effects might be mediated by specific taxa.

  17. Effects of anaesthesia techniques and drugs on pulmonary function

    Directory of Open Access Journals (Sweden)

    Vijay Saraswat

    2015-01-01

    Full Text Available The primary task of the lungs is to maintain oxygenation of the blood and eliminate carbon dioxide through the network of capillaries alongside alveoli. This is maintained by utilising ventilatory reserve capacity and by changes in lung mechanics. Induction of anaesthesia impairs pulmonary functions by the loss of consciousness, depression of reflexes, changes in rib cage and haemodynamics. All drugs used during anaesthesia, including inhalational agents, affect pulmonary functions directly by acting on respiratory system or indirectly through their actions on other systems. Volatile anaesthetic agents have more pronounced effects on pulmonary functions compared to intravenous induction agents, leading to hypercarbia and hypoxia. The posture of the patient also leads to major changes in pulmonary functions. Anticholinergics and neuromuscular blocking agents have little effect. Analgesics and sedatives in combination with volatile anaesthetics and induction agents may exacerbate their effects. Since multiple agents are used during anaesthesia, ultimate effect may be different from when used in isolation. Literature search was done using MeSH key words 'anesthesia', 'pulmonary function', 'respiratory system' and 'anesthesia drugs and lungs' in combination in PubMed, Science Direct and Google Scholar filtered by review and research articles sorted by relevance.

  18. Effects of the great recession on drugs consumption in Spain.

    Science.gov (United States)

    Martin Bassols, Nicolau; Vall Castelló, Judit

    2016-09-01

    This paper presents evidence on how the consumption of legal and illegal drugs has changed in response to the Great Recession in Spain. We use a large scale survey from 2005 to 2011 to analyze the association between changes in local economic conditions and drug consumption among individuals aged 15-64. Although Spain was one of the countries hardest hit by the economic downturn, the crisis was unevenly felt across the country. Therefore, we exploit this difference in unemployment rates across provinces to identify the effects of business cycle variations on the consumption of legal and illegal drugs. To the best of our knowledge, this is the first study to find a relation between the deterioration of local economic conditions and a strong increase in the consumption of marihuana and cocaine. We also report a decrease in alcohol consumption but a significant escalation in abusive smoking behavior (smoking every day). We believe that these findings are important not only for the potential negative implications at the individual level but also for the costs to society as a whole. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. A unified frame of predicting side effects of drugs by using linear neighborhood similarity.

    Science.gov (United States)

    Zhang, Wen; Yue, Xiang; Liu, Feng; Chen, Yanlin; Tu, Shikui; Zhang, Xining

    2017-12-14

    Drug side effects are one of main concerns in the drug discovery, which gains wide attentions. Investigating drug side effects is of great importance, and the computational prediction can help to guide wet experiments. As far as we known, a great number of computational methods have been proposed for the side effect predictions. The assumption that similar drugs may induce same side effects is usually employed for modeling, and how to calculate the drug-drug similarity is critical in the side effect predictions. In this paper, we present a novel measure of drug-drug similarity named "linear neighborhood similarity", which is calculated in a drug feature space by exploring linear neighborhood relationship. Then, we transfer the similarity from the feature space into the side effect space, and predict drug side effects by propagating known side effect information through a similarity-based graph. Under a unified frame based on the linear neighborhood similarity, we propose method "LNSM" and its extension "LNSM-SMI" to predict side effects of new drugs, and propose the method "LNSM-MSE" to predict unobserved side effect of approved drugs. We evaluate the performances of LNSM and LNSM-SMI in predicting side effects of new drugs, and evaluate the performances of LNSM-MSE in predicting missing side effects of approved drugs. The results demonstrate that the linear neighborhood similarity can improve the performances of side effect prediction, and the linear neighborhood similarity-based methods can outperform existing side effect prediction methods. More importantly, the proposed methods can predict side effects of new drugs as well as unobserved side effects of approved drugs under a unified frame.

  20. Observational Pharmacoepidemiology in the Drug Safety and Effectiveness Evaluation

    Directory of Open Access Journals (Sweden)

    José Cabrita

    2017-04-01

    Full Text Available Observational epidemiological studies have been used in the medicines context for more than 40 years, contributing to characterize drug use patterns and safety, efficacy and effectiveness profiles. Its use has been increased in recognition of the clinical trials limitations to assess the therapeutic and iatrogenic potential of the medicines after its commercialization. The evolution of the regulatory framework for pharmacovigilance, requiring post-marketing studies, post-authorization safety studies (PASS and the post-authorization efficacy studies (PAES to approve certain drugs, reinforced the importance of observational pharmacoepidemiology for the characterization of the medicines safety and effectiveness profiles. Pharmacoepidemiological research can be carried out from field studies designed to obtain the necessary information or in databases with health records of population samples that already contain the information. This 2nd option is more efficient and more and more frequent. Although, observational research from field studies continues to have its space, the increasing availability of databases allowed a new development to observational pharmacoepidemiology. Indeed, access to automated records databases with up-to-date information on medical prescriptions and global health care to representative population samples with long follow-up periods is a valuable tool for the study of drug use patterns and therapeutic and iatrogenic potential in routine clinical practice. In this context, observational pharmacoepidemiology reinforces its role as a scientific area particularly suitable for evaluating the safety and the effectiveness of the medicines in the “real world”, making a relevant contribution to overcome the gap in translating the evidence from the clinical trials for clinical practice.

  1. Cardiovascular effects of current and future anti-obesity drugs

    DEFF Research Database (Denmark)

    Comerma Steffensen, Simon Gabriel; Grann, Martin; Andersen, Charlotte U

    2014-01-01

    cardiovascular risk, while an inverse agonist at cannabinoid type 1 (CB1) receptors, rimonobant was withdrawn due to serious psychiatric problems. At present there are only few treatments available including orlistat and, phentermine alone or in combination with topiramate and lorcaserin, although cardiovascular...... side effects need to be clarified regarding phentermine and lorcaserin. Drugs approved for type 2 diabetes including glucagon like peptide (GLP-1) analogues and metformin also cause moderate weight losses and have a favourable cardiovascular profile, while the anti-obesity potential of nebivolol...

  2. Effect of Antiretroviral Drug (arved) on the Kidney in Albino Rat ...

    African Journals Online (AJOL)

    African studies on effect of antiretroviral drugs on the kidney are limited resulting to scanty information on the safety of these drugs. This study was therefore designed to evaluate the effects of antiretroviral drugs arved®, on creatinine, urea, potassium and sodium ions as well as histological effect on the kidney. A total of fifty ...

  3. Functionality Effect of Pressure Sensitive Adhesives on In Vitro Drug Release Behavior of Fentanyl Drug in an Adhesive Patch

    Directory of Open Access Journals (Sweden)

    S.M. Taghizadeh

    2009-12-01

    Full Text Available Some formulations of drug in adhesive transdermal drug delivery systems (TDDSs( with different functional and non-functional acrylic pressure sensitive adhesives PSAs( were prepared. For this purpose fentanyl was used as a drug component. The effects of PSAs type on skin permeation and in vitro drug release from devices were evaluated using hydrodynamically well-characterized Chien permeation system fitted with excised rat abdominal skin. The adhesion properties of devices (peel strength and tack values( were obtained. It was found that TDDS with –COOH functional PSA had the lowest steady state flux. Drug release was followed by Higuchi's kinetic model. Adhesion properties of the samples were improved by addition of functional PSA in the formulations.

  4. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  5. Drug Facts

    Medline Plus

    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  6. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  7. Expression of Genes for Drug Transporters in the Human Female Genital Tract and Modulatory Effect of Antiretroviral Drugs.

    Directory of Open Access Journals (Sweden)

    Karolin Hijazi

    Full Text Available Anti-retroviral (ARV -based microbicides are one of the strategies pursued to prevent HIV-1 transmission. Delivery of ARV drugs to subepithelial CD4+ T cells at concentrations for protection is likely determined by drug transporters expressed in the cervicovaginal epithelium. To define the role of drug transporters in mucosal disposition of topically applied ARV-based microbicides, these must be tested in epithelial cell line-based biopharmaceutical assays factoring the effect of relevant drug transporters. We have characterised gene expression of influx and efflux drug transporters in a panel of cervicovaginal cell lines and compared this to expression in cervicovaginal tissue. We also investigated the effect of dapivirine, darunavir and tenofovir, currently at advanced stages of microbicides development, on expression of drug transporters in cell lines. Expression of efflux ABC transporters in cervical tissue was best represented in HeLa, Ect1/E6E7 and End1/E6E7 cell lines. Expression of influx OCT and ENT transporters in ectocervix matched expression in Hela while expression of influx SLCO transporters in vagina was best reflected in VK2/E6E7 cell line. Stimulation with darunavir and dapivirine upregulated MRP transporters, including MRP5 involved in transport of tenofovir. Dapivirine also significantly downregulated tenofovir substrate MRP4 in cervical cell lines. Treatment with darunavir and dapivirine showed no significant effect on expression of BCRP, MRP2 and P-glycoprotein implicated in efflux of different ARV drugs. Darunavir strongly induced expression in most cell lines of CNT3 involved in cell uptake of nucleotide/nucleoside analogue reverse transcriptase inhibitors and SLCO drug transporters involved in cell uptake of protease inhibitors. This study provides insight into the suitability of cervicovaginal cell lines for assessment of ARV drugs in transport kinetics studies. The modulatory effect of darunavir and dapivirine on

  8. The effects of antiepileptic drugs on the growth of glioblastoma cell lines

    OpenAIRE

    Lee, Ching-Yi; Lai, Hung-Yi; Chiu, Angela; Chan, She-Hung; Hsiao, Ling-Ping; Lee, Shih-Tseng

    2016-01-01

    To determine the effects of antiepileptic drug compounds on glioblastoma cellular growth, we exposed glioblastoma cell lines to select antiepileptic drugs. The effects of selected antiepileptic drugs on glioblastoma cells were measured by MTT assay. For compounds showing significant inhibition, cell cycle analysis was performed. Statistical analysis was performed using SPSS. The antiepileptic compounds selected for screening included carbamazepine, ethosuximide, gabapentin, lamotrigine, levet...

  9. 49 CFR 40.207 - What is the effect of a cancelled drug test?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false What is the effect of a cancelled drug test? 40.207 Section 40.207 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Problems in Drug Tests § 40.207 What is the effect of...

  10. The effect of activated charcoal on drug exposure in healthy volunteers: a meta-analysis

    DEFF Research Database (Denmark)

    Jürgens, G; Hoegberg, L C Groth; Graudal, N A

    2009-01-01

    The objective of the study was to estimate the effect of activated charcoal (AC) administered during the first 6 h after drug intake and the effect of drug properties on drug exposure. Sixty-four controlled studies were integrated in a meta-analysis. AC administered 0-5 min after administration...

  11. Effect of Anionic Polymers on Drug Loading and Release from ...

    African Journals Online (AJOL)

    Purpose: To develop and characterize solid lipid nanoparticle (SLN) systems containing dextran sulfate or sodium ... SLNs. Drug release from SLNs is also dependent on the polymer type. ..... nanoparticles for parenteral drug delivery. Adv.

  12. Effects of pathological conditions on ocular pharmacokinetics of antimicrobial drugs.

    Science.gov (United States)

    Ueda, Kayoko; Ohtori, Akira; Tojo, Kakuji

    2010-10-01

    A diffusion model of ocular pharmacokinetics was used to estimate the effects of pathological conditions on ocular pharmacokinetics. In vivo rabbit data after topical instillation of ciprofloxacin and ofloxacin were compared with the simulated concentrations in the aqueous and vitreous humors. The barrier capacity of the surrounding membranes such as the retina/choroid/sclera (RCS) membrane and the cornea was characterized by dimensionless Sherwood number derived by the pseudo-steady state approach (PSSA). We assumed the barrier capacity decreased by inflammation; when the barrier capacity of the RCS membrane and the cornea was assumed to be one-tenth for the RCS membrane and a half for the cornea respectively, the in vivo data agreed with the simulated profile without contradiction. The drug concentration gradient simulated in the vitreous body near the RCS membrane was more significant in the inflamed eyes than in the normal eyes, suggesting that the elimination of the drugs from the RCS membrane was enhanced by inflammation. The present diffusion model can better describe the ocular pharmacokinetics in both normal and diseased conditions.

  13. Fear Conditioning Effects on Sensitivity to Drug Reward

    Science.gov (United States)

    2010-06-01

    motivational responses and self-administration behaviors (Robbins et al., 2008). Pavlovian conditioning mechanisms link unconditioned drug responses...model. Induction of fear conditioning is followed by measurement of sensitivity to drug reward using a conditioned place preference (CPP) model to...morphine. Conditioned drug reward is a relevant model in addiction because environmental cues (e.g. a barroom) induce craving and persistent

  14. Potentiation of Anticancer Drugs: Effects of Pentoxifylline on Neoplastic Cells

    Directory of Open Access Journals (Sweden)

    Miroslav Barancik

    2011-12-01

    Full Text Available The drug efflux activity of P-glycoprotein (P-gp, a product of the mdr1 gene, ABCB1 member of ABC transporter family represents a mechanism by which tumor cells escape death induced by chemotherapeutics. In this study, we investigated the mechanisms involved in the effects of pentoxifylline (PTX on P-gp-mediated multidrug resistance (MDR in mouse leukemia L1210/VCR cells. Parental sensitive mouse leukemia cells L1210, and multidrug-resistant cells, L1210/VCR, which are characterized by the overexpression of P-gp, were used as experimental models. The cells were exposed to 100 μmol/L PTX in the presence or absence of 1.2 μmol/L vincristine (VCR. Western blot analysis indicated a downregulation of P-gp protein expression when multidrug-resistant L1210/VCR cells were exposed to PTX. The effects of PTX on the sensitization of L1210/VCR cells to VCR correlate with the stimulation of apoptosis detected by Annexin V/propidium iodide apoptosis necrosis kit and proteolytic activation of both caspase-3 and caspase-9 monitored by Western blot analysis. Higher release of matrix metalloproteinases (MMPs, especially MMP-2, which could be attenuated by PTX, was found in L1210/VCR than in L1210 cells by gelatin zymography in electrophoretic gel. Exposure of resistant cells to PTX increased the content of phosphorylated Akt kinase. In contrast, the presence of VCR eliminated the effects of PTX on Akt kinase phosphorylation. Taken together, we conclude that PTX induces the sensitization of multidrug-resistant cells to VCR via downregulation of P-gp, stimulation of apoptosis and reduction of MMPs released from drug-resistant L1210/VCR cells. These facts bring new insights into the mechanisms of PTX action on cancer cells.

  15. CAN MELATONIN BE EFFECTIVELY USED TO DIMINISH SIDE EFFECTS OF VARIOUS PSYCHOTROPIC DRUGS AND ELECTROCONVULSIVE THERAPY?

    Directory of Open Access Journals (Sweden)

    Roman Aleksandrovich Bekker

    2017-10-01

    Full Text Available Purpose. To study and summarize the existing evidence base for the use of melatonin as a mean to counteract or diminish the side effects of various psychotropic drugs and electroconvulsive therapy, and to provide the reader with relevant conclusions. Methodology. The authors have searched for the scientific literature regarding the use of melatonin as a mean to counteract or diminish the side effects of various psychotropic drugs and electroconvulsive therapy, using the PubMed and Google Scholar as a search tool. Then the authors thoroughly reviewed the data they found. The resulting review is presented in this article. Results. The data we have obtained from this review of the literature indicate that melatonin can be effectively used both in monotherapy and in combination with other therapeutic means in order to reduce several different side effects of psychotropic drugs and electroconvulsive therapy. Melatonin also deserves further study in this regard. The evidence base for its use in this manner is very variable in quality for different side effects. For now, the greatest evidence base exists regarding the potential effectiveness of melatonin in the prevention and treatment of drug-induced insomnia, memory and cognitive impairment, akathisia, tardive dyskinesias, and metabolic syndrome. Practical implications. The results we have obtained can be widely applied in psychiatry, neurology and addiction medicine, as well as in all those areas of general medicine, which make use of psychotropic drugs.

  16. Prediction of Effective Drug Combinations by an Improved Naïve Bayesian Algorithm.

    Science.gov (United States)

    Bai, Li-Yue; Dai, Hao; Xu, Qin; Junaid, Muhammad; Peng, Shao-Liang; Zhu, Xiaolei; Xiong, Yi; Wei, Dong-Qing

    2018-02-05

    Drug combinatorial therapy is a promising strategy for combating complex diseases due to its fewer side effects, lower toxicity and better efficacy. However, it is not feasible to determine all the effective drug combinations in the vast space of possible combinations given the increasing number of approved drugs in the market, since the experimental methods for identification of effective drug combinations are both labor- and time-consuming. In this study, we conducted systematic analysis of various types of features to characterize pairs of drugs. These features included information about the targets of the drugs, the pathway in which the target protein of a drug was involved in, side effects of drugs, metabolic enzymes of the drugs, and drug transporters. The latter two features (metabolic enzymes and drug transporters) were related to the metabolism and transportation properties of drugs, which were not analyzed or used in previous studies. Then, we devised a novel improved naïve Bayesian algorithm to construct classification models to predict effective drug combinations by using the individual types of features mentioned above. Our results indicated that the performance of our proposed method was indeed better than the naïve Bayesian algorithm and other conventional classification algorithms such as support vector machine and K-nearest neighbor.

  17. Prediction of Effective Drug Combinations by an Improved Naïve Bayesian Algorithm

    Directory of Open Access Journals (Sweden)

    Li-Yue Bai

    2018-02-01

    Full Text Available Drug combinatorial therapy is a promising strategy for combating complex diseases due to its fewer side effects, lower toxicity and better efficacy. However, it is not feasible to determine all the effective drug combinations in the vast space of possible combinations given the increasing number of approved drugs in the market, since the experimental methods for identification of effective drug combinations are both labor- and time-consuming. In this study, we conducted systematic analysis of various types of features to characterize pairs of drugs. These features included information about the targets of the drugs, the pathway in which the target protein of a drug was involved in, side effects of drugs, metabolic enzymes of the drugs, and drug transporters. The latter two features (metabolic enzymes and drug transporters were related to the metabolism and transportation properties of drugs, which were not analyzed or used in previous studies. Then, we devised a novel improved naïve Bayesian algorithm to construct classification models to predict effective drug combinations by using the individual types of features mentioned above. Our results indicated that the performance of our proposed method was indeed better than the naïve Bayesian algorithm and other conventional classification algorithms such as support vector machine and K-nearest neighbor.

  18. Microbiological aspects of the effectiveness of antimicrobial drugs

    Directory of Open Access Journals (Sweden)

    Oleksandr Nazarchuk

    2015-06-01

      Abstract Introduction. It is well known, that patients with deep burns belong to the category of critically ill ones. According to the data of National Nosocomial Infections Surveillance (2004, Staphylococcus spp. are among leading opportunistic pathogens of infectious complications in such patients. Nowadays much attention is given to the problem of antibiotic resistance of Staphylococcus clinical strains. More often antiseptics are used in treatment of infectious complications, caused by antibiotic resistant miсroorganisms. The aim of the research was to study microbiological aspects of the effectiveness of antimicrobial drugs. Materials and methods. There were examined 372 critically ill patients with burns, having infectious complications. In all patients microbiological examinations were carried out during the first 7 days after burn trauma. There were isolated 115 clinical strains of Staphylococcus spp.. Their morphological, cultural, biochemical qualities and sensitivity to antibiotics, antiseptics were studied. Rresults of the study. We found, that clinical strains of S. aureus, S. epidermidis were highly resistant to oxacillin (46,9; 59,1 % respectively; were insensitive to clavulanate and sulbactam potentiated beta-lactams; ceftriaxone; meropenem, imipenem; ciprofloxacin. Sensitivity of Staphylococcus to amikacin, linezolid, vancomycin was found. There was shown the sensitivity of antibiotic resistant strains of Staphylococcus to decamethoxin, its polymer composition, chlorhexidine digluconate. In the research there was proved the decreasing of the effectiveness of chlorhexidine digluconate against Staphylococcus in conditions of increasing microbial load to 109 CFU/ml in 6,6 times comparably to decamethoxin drugs (p<0,001. Conclusions Resistant to the majority of antibiotics strains of Staphylococcus spp. store their high sensitivity to antiseptic decamethoxin and its polymeric composition, chlorhexidine digluconate. Microbial load increase up to 109

  19. Integrative relational machine-learning for understanding drug side-effect profiles.

    Science.gov (United States)

    Bresso, Emmanuel; Grisoni, Renaud; Marchetti, Gino; Karaboga, Arnaud Sinan; Souchet, Michel; Devignes, Marie-Dominique; Smaïl-Tabbone, Malika

    2013-06-26

    Drug side effects represent a common reason for stopping drug development during clinical trials. Improving our ability to understand drug side effects is necessary to reduce attrition rates during drug development as well as the risk of discovering novel side effects in available drugs. Today, most investigations deal with isolated side effects and overlook possible redundancy and their frequent co-occurrence. In this work, drug annotations are collected from SIDER and DrugBank databases. Terms describing individual side effects reported in SIDER are clustered with a semantic similarity measure into term clusters (TCs). Maximal frequent itemsets are extracted from the resulting drug x TC binary table, leading to the identification of what we call side-effect profiles (SEPs). A SEP is defined as the longest combination of TCs which are shared by a significant number of drugs. Frequent SEPs are explored on the basis of integrated drug and target descriptors using two machine learning methods: decision-trees and inductive-logic programming. Although both methods yield explicit models, inductive-logic programming method performs relational learning and is able to exploit not only drug properties but also background knowledge. Learning efficiency is evaluated by cross-validation and direct testing with new molecules. Comparison of the two machine-learning methods shows that the inductive-logic-programming method displays a greater sensitivity than decision trees and successfully exploit background knowledge such as functional annotations and pathways of drug targets, thereby producing rich and expressive rules. All models and theories are available on a dedicated web site. Side effect profiles covering significant number of drugs have been extracted from a drug ×side-effect association table. Integration of background knowledge concerning both chemical and biological spaces has been combined with a relational learning method for discovering rules which explicitly

  20. Methodological challenges to control for immortal time bias in addressing drug effects in type 2 diabetes

    OpenAIRE

    Yang, Xi-Lin; Huo, Xiao-Xu; Chan, Juliana CN

    2015-01-01

    There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system (RAS) inhibitors and statins as reference drugs with proven efficacies in randomized clinical trials (RCTs) and examined their effectiveness in the prospective Hong Kong Diabetes Registry using adjustment methods proposed in the literature. Using time-dependent exposures to drug treatments yielded gr...

  1. Effects of antidepressant drugs on different receptors in the brain

    International Nuclear Information System (INIS)

    Hall, H.; Oegren, S.-O.

    1981-01-01

    Radioligand receptor binding techniques were used to characterize the effects of different structural types of antidepressant drugs on neurotransmitter receptors. The tricyclic antidepressants more or less potently inhibited the binding to rat brain preparations of several different radiolabelled ligands ([ 3 H]WB4101, [ 3 H]QNB, [ 3 H]d-LSD, [ 3 H]mepyramine). The potency of the nontricyclic antidepressants varied greatly. Mianserin, potently displaced [ 3 H]mepyramine, [ 3 H]d-LSD and [ 3 H]WB4101 while it was very weak on [ 3 H]QNB-binding. Nomifensine and the specific 5-HT uptake inhibitors zimelidine and alaproclate had very low affinity for these receptors. All the antidepressants tested were practically devoid of activity on [ 3 H]DHA binding, [ 3 H]spiroperidol binding, [ 3 H]flunitrazepam binding, [ 3 H]muscimol binding and [ 3 H]naloxone binding. The implications of these findings for biogenic amine theories of affective disorders are discussed. (Auth.)

  2. Production of drug nanosuspensions: effect of drug physical properties on nanosizing efficiency.

    Science.gov (United States)

    Liu, Tao; Müller, Rainer H; Möschwitzer, Jan P

    2018-02-01

    Drug nanosuspension is one of the established methods to improve the bioavailability of poorly soluble drugs. Drug physical properties aspect (morphology, solid state, starting size et al) is a critical parameter determining the production efficiency. Some drug modification approaches such as spray-drying were proved to improve the millability of drug powders. However, the mechanism behind those improved performances is unclear. This study is to systematically investigate the influence of those physical properties. Five different APIs (active pharmaceutical ingredients) with different millabilities, i.e. resveratrol, hesperetin, glibenclamide, rutin, and quercetin, were processed by standard high pressure homogenization (HPH), wet bead milling (WBM), and a combinative method of spray-drying and HPH. Smaller starting sizes of certain APIs could accelerate the particle size reduction velocity during both HPH and WBM processes. Spherical particles were observed for almost all spray-dried powders (except spray-dried hesperetin) after spray-drying. The crystallinity of some spray-dried samples such as rutin and glibenclamide became much lower than their corresponding unmodified powders. Almost all spray-dried drug powders after HPH processes could lead to smaller nanocrystal particle size than unmodified APIs. The modified microstructure instead of solid state after spray-drying explained the potential reason for improved nanosizing efficiency. In addition, the contribution of starting size on the production efficiency was also critical according to both HPH and WBM results.

  3. 'THE UNVEILED HEART' a teaching program in cardiovascular nuclear medicine

    International Nuclear Information System (INIS)

    Itti, Roland; Merabet, Yasmina; Roca, Ramona; Bontemps, Laurence; Itti, Emmanuel

    2004-01-01

    The functional investigation of cardiac diseases using nuclear techniques involves several variables, such as myocardial perfusion, cellular viability or mechanical contraction. The combined, topographical and quantitative assessment of these variables can characterize the functional state of the heart in terms of normal myocardium, ischemia, hibernation or necrosis. The teaching program, 'The Unveiled Heart', has been designed in order to help nuclear physicians or cardiologists approaching these concepts and their implications for diagnosis of coronary artery disease, optimization of therapeutic strategies and prognosis evaluation. Anatomical correlations with coronary angiographic results obtained during balloon occlusion at the time of coronary angioplasty demonstrate the complementary role of imaging techniques and highlight the patient to patient variability of risk areas. A sectorial model derived from a polar projection of the myocardium presents for each sector the probability of involvement of a given coronary artery

  4. Photonic integrated circuits unveil crisis-induced intermittency.

    Science.gov (United States)

    Karsaklian Dal Bosco, Andreas; Akizawa, Yasuhiro; Kanno, Kazutaka; Uchida, Atsushi; Harayama, Takahisa; Yoshimura, Kazuyuki

    2016-09-19

    We experimentally investigate an intermittent route to chaos in a photonic integrated circuit consisting of a semiconductor laser with time-delayed optical feedback from a short external cavity. The transition from a period-doubling dynamics to a fully-developed chaos reveals a stage intermittently exhibiting these two dynamics. We unveil the bifurcation mechanism underlying this route to chaos by using the Lang-Kobayashi model and demonstrate that the process is based on a phenomenon of attractor expansion initiated by a particular distribution of the local Lyapunov exponents. We emphasize on the crucial importance of the distribution of the steady-state solutions introduced by the time-delayed feedback on the existence of this intermittent dynamics.

  5. Withanolide D Exhibits Similar Cytostatic Effect in Drug-Resistant and Drug-Sensitive Multiple Myeloma Cells

    Directory of Open Access Journals (Sweden)

    Mark E. Issa

    2017-09-01

    Full Text Available In spite of recent therapeutic advances, multiple myeloma (MM remains a malignancy with very low curability. This has been partly attributed to the existence of a drug-resistant subpopulation known as cancer stem cells (CSCs. MM-CSCs are equipped with the necessary tools that render them highly resistant to virtually all conventional therapies. In this study, the growth inhibitory effects of withanolide D (WND, a steroidal lactone isolated from Withania somnifera, on drug-sensitive tumoral plasma cells and drug-resistant MM cells have been investigated. In MTT/XTT assays, WND exhibited similar cytostatic effects between drug-resistant and drug-sensitive cell lines in the nM range. WND also induced cell death and apoptosis in MM-CSCs and RPMI 8226 cells, as examined by the calcein/ethidium homodimer and annexin V/propidium iodide stainings, respectively. To determine whether P-glycoprotein (P-gp efflux affected the cytostatic activity of WND, P-gp was inhibited with verapamil and results indicated that the WND cytostatic effect in MM-CSCs was independent of P-gp efflux. Furthermore, WND did not increase the accumulation of the fluorescent P-gp substrate rhodamine 123 in MM-CSCs, suggesting that WND may not inhibit P-gp at the tested relevant doses. Therefore, the WND-induced cytostatic effect may be independent of P-gp efflux. These findings warrant further investigation of WND in MM-CSC animal models.

  6. The health and economic effects of counterfeit drugs.

    Science.gov (United States)

    Blackstone, Erwin A; Fuhr, Joseph P; Pociask, Steve

    2014-06-01

    Counterfeit drugs comprise an increasing percentage of the US drug market and even a larger percentage in less developed countries. Counterfeit drugs involve both lifesaving and lifestyle drugs. To review the health and economic consequences of counterfeit drugs on the US public and on the healthcare system as a whole. This comprehensive review of the literature encompassed a search of MEDLINE/PubMed, Google Scholar, and ProQuest using the keywords "counterfeit drugs," "counterfeit medicines," "fake drugs," and "fake medicines." A search of the various FiercePharma daily newsletter series on the healthcare market was also conducted. In addition, the US Food and Drug Administration and the World Health Organization websites were reviewed for additional information. The issue of counterfeit drugs has been growing in importance in the United States, with the supply of these counterfeit drugs coming from all over the world. Innovation is important to economic growth and US competitiveness in the global marketplace, and intellectual property protections provide the ability for society to prosper from innovation. Especially important in terms of innovation in healthcare are the pharmaceutical and biopharmaceutical industries. In addition to taking income from consumers and drug companies, counterfeit drugs also pose health hazards to patients, including death. The case of bevacizumab (Avastin) is presented as one recent example. Internet pharmacies, which are often the source of counterfeit drugs, often falsely portray themselves as Canadian, to enhance their consumer acceptance. Adding to the problems are drug shortages, which facilitate access for counterfeits. A long and convoluted supply chain also facilitates counterfeits. In addition, the wholesale market involving numerous firms is a convenient target for counterfeit drugs. Trafficking in counterfeits can be extremely profitable; detection of counterfeits is difficult, and the penalties are modest. Counterfeit

  7. Solubility of drugs in aqueous polymeric solution: effect of ovalbumin on microencapsulation process.

    Science.gov (United States)

    Aziz, Hesham Abdul; Tan, Yvonne Tze Fung; Peh, Kok Khiang

    2012-03-01

    Microencapsulation of water-soluble drugs using coacervation-phase separation method is very challenging, as these drugs partitioned into the aqueous polymeric solution, resulting in poor drug entrapment. For evaluating the effect of ovalbumin on the microencapsulation of drugs with different solubility, pseudoephedrine HCl, verapamil HCl, propranolol HCl, paracetamol, and curcuminoid were used. In addition, drug mixtures comprising of paracetamol and pseudoephedrine HCl were also studied. The morphology, encapsulation efficiency, particle size, and in vitro release profile were investigated. The results showed that the solubility of the drug determined the ratio of ovalbumin to be used for successful microencapsulation. The optimum ratios of drug, ovalbumin, and gelatin for water-soluble (pseudoephedrine HCl, verapamil HCl, and propranolol HCl), sparingly water-soluble (paracetamol), and water-insoluble (curcuminoid) drugs were found to be 1:1:2, 2:3:5, and 1:3:4. As for the drug mixture, the optimum ratio of drug, ovalbumin, and gelatin was 2:3:5. Encapsulated particles prepared at the optimum ratios showed high yield, drug loading, entrapment efficiency, and sustained release profiles. The solubility of drug affected the particle size of the encapsulated particle. Highly soluble drugs resulted in smaller particle size. In conclusion, addition of ovalbumin circumvented the partitioning effect, leading to the successful microencapsulation of water-soluble drugs.

  8. 76 FR 72422 - Draft Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food...

    Science.gov (United States)

    2011-11-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0784] Draft Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food-Producing Animals; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

  9. Persuader Sex Differences and Peer Pressure Effects on Attitudes Toward Drug Abuse.

    Science.gov (United States)

    Stone, Christopher I.; Shute, Robert E.

    This experiment was performed to assess the effects of the experimental confederates' sex and contrived group peer pressure on the drug attitudes of male college students. Subjects were exposed to all male or all female groups of experimental confederates (persuaders) who expressed either extremely pro-drug or anti-drug sentiments in a guided…

  10. The effects of cyclodextrins on drug release from fatty suppository bases : II. In vivo observations

    NARCIS (Netherlands)

    Frijlink, H.W.; Eissens, Anko; Schoonen, Adelbert; Lerk, C.F.

    The effects of cyclodextrin complexation on the absorption of drugs from fatty suppositories was evaluated in human volunteers. Three model drugs: diazepam, ibuprofen and prednisolone were used. When diazepam was complexed with γ-cyclcodextrin the drug release from the fatty suppositories was

  11. Effect of Drug and Alcohol Education on Attitudes of High School Students.

    Science.gov (United States)

    Lignell, Constance; Davidhizar, Ruth

    1991-01-01

    Examined effects of 3-week alcohol and drug education course on attitudes about alcohol and drugs in ninth grade students (n=180). Results showed mean attitude score changed in desired direction after education indicating negative feelings toward drugs and alcohol use and abuse, polydrug use, dependency, social pressure, and media pressure and…

  12. The "War on drugs" in Nigeria: How effective and beneficial is it in ...

    African Journals Online (AJOL)

    Since drugs became both a public and social issue in Nigeria, fear about both the real ... research literature, published documents and media reports on drug policy matters. ... The shift will provide far more cost-effective drug control results and ...

  13. Salt Effect on the Cloud Point Phenomenon of Amphiphilic Drug-Hydroxypropylmethyl Cellulose System

    Directory of Open Access Journals (Sweden)

    Mohd. Sajid Ali

    2014-01-01

    Full Text Available Effect of two amphiphilic drugs (tricyclic antidepressant, nortriptyline hydrochloride (NORT, and nonsteroidal anti-inflammatory drug, sodium salt of ibuprofen (IBF on the cloud point of biopolymer hydroxypropylmethyl cellulose (HPMC was studied. Effect of NaCl was also seen on the CP of HPMC-drug system. CP of HPMC increases uniformly on increasing the (drug. Both drugs, though one being anionic (IBF and other cationic (NORT, affect the CP in almost the same manner but with different extent implying the role of hydrophobicity in the interaction between drug and polymer. Salt affects the CP of the drug in a dramatic way as low concentration of salt was only able to increase the value of the CP, though not affecting the pattern. However, in presence of high concentration of salts, minimum was observed on CP versus (drug plots. Various thermodynamic parameters were evaluated and discussed on the basis of the observed results.

  14. Potential Effects of a Ban on Direct-to-Consumer Advertising of New Prescription Drugs

    OpenAIRE

    Congressional Budget Office

    2011-01-01

    Concerns about direct-to-consumer advertising of prescription drugs have spurred recent proposals for a moratorium on advertising brand-name prescription drugs to consumers during the first two years following a drug's approval by the Food and Drug Administration. This Congressional Budget Office brief examines some of the effects of such a moratorium, drawing on data documenting direct-to-consumer advertising and other promotional activities used by pharmaceutical producers as well as academ...

  15. Effect of ingested lipids on drug dissolution and release with concurrent digestion: a modeling approach

    Science.gov (United States)

    Buyukozturk, Fulden; Di Maio, Selena; Budil, David E.; Carrier, Rebecca L.

    2014-01-01

    Purpose To mechanistically study and model the effect of lipids, either from food or self-emulsifying drug delivery systems (SEDDS), on drug transport in the intestinal lumen. Methods Simultaneous lipid digestion, dissolution/release, and drug partitioning were experimentally studied and modeled for two dosing scenarios: solid drug with a food-associated lipid (soybean oil) and drug solubilized in a model SEDDS (soybean oil and Tween 80 at 1:1 ratio). Rate constants for digestion, permeability of emulsion droplets, and partition coefficients in micellar and oil phases were measured, and used to numerically solve the developed model. Results Strong influence of lipid digestion on drug release from SEDDS and solid drug dissolution into food-associated lipid emulsion were observed and predicted by the developed model. 90 minutes after introduction of SEDDS, there was 9% and 70% drug release in the absence and presence of digestion, respectively. However, overall drug dissolution in the presence of food-associated lipids occurred over a longer period than without digestion. Conclusion A systems-based mechanistic model incorporating simultaneous dynamic processes occurring upon dosing of drug with lipids enabled prediction of aqueous drug concentration profile. This model, once incorporated with a pharmacokinetic model considering processes of drug absorption and drug lymphatic transport in the presence of lipids, could be highly useful for quantitative prediction of impact of lipids on bioavailability of drugs. PMID:24234918

  16. Acanthamoeba: epidimiology, pathogenicity and evaluation of effectiveness of recent drugs

    International Nuclear Information System (INIS)

    Issa, R.M.

    2007-01-01

    To study the epidimiology of Acanthamoeba and to evaluate the effectiveness of some recent drugs against parasite. The study was carried out from March to May 2005 at the ophthalmic clinic of King Fahad Hospital, Saudi Arabia. Samples of rinsing solutions and saline of contact lens, tap water, Swimming pool water and Soil from Hufof city Saudi Arabia were tested. Mice were used to infect them via intranasal inoculation from isolated culture strain for confirming pathogenicity. Rokitamycin, polymixin B, suramin and chloropromazin were used to study their effects on Acanthamoeba growth in vitro. Acanthamoeba were detected in 20% of solution of contact lens, 20% of tap water, 50% of swimming pool samples and 40% of soil samples. All animals died or were sacrificed and had Acanthamoeba isolated from their organs. Higher percentage of growth inhibition of Acanthamoeba cultured was shown by chloropromazine and rokitamycin after 21 days (100%), while Polymyin B and Suramin showed 83% and 64% inhibition respectively. Acanthamoeba isolated in significant percent of environmental sources. Pathogenicity of organism was confirmed in mice. Contact lens wearers should be aware of the risks associated with Acanthamoeba. Rokitamycin and chlorpromazine showed good inhibition in vitro. (author)

  17. Leveraging 3D chemical similarity, target and phenotypic data in the identification of drug-protein and drug-adverse effect associations.

    Science.gov (United States)

    Vilar, Santiago; Hripcsak, George

    2016-01-01

    Drug-target identification is crucial to discover novel applications for existing drugs and provide more insights about mechanisms of biological actions, such as adverse drug effects (ADEs). Computational methods along with the integration of current big data sources provide a useful framework for drug-target and drug-adverse effect discovery. In this article, we propose a method based on the integration of 3D chemical similarity, target and adverse effect data to generate a drug-target-adverse effect predictor along with a simple leveraging system to improve identification of drug-targets and drug-adverse effects. In the first step, we generated a system for multiple drug-target identification based on the application of 3D drug similarity into a large target dataset extracted from the ChEMBL. Next, we developed a target-adverse effect predictor combining targets from ChEMBL with phenotypic information provided by SIDER data source. Both modules were linked to generate a final predictor that establishes hypothesis about new drug-target-adverse effect candidates. Additionally, we showed that leveraging drug-target candidates with phenotypic data is very useful to improve the identification of drug-targets. The integration of phenotypic data into drug-target candidates yielded up to twofold precision improvement. In the opposite direction, leveraging drug-phenotype candidates with target data also yielded a significant enhancement in the performance. The modeling described in the current study is simple and efficient and has applications at large scale in drug repurposing and drug safety through the identification of mechanism of action of biological effects.

  18. The effect of an interactive e-drug calculations package on nursing students' drug calculation ability and self-efficacy.

    Science.gov (United States)

    McMullan, Miriam; Jones, Ray; Lea, Susan

    2011-06-01

    Nurses need to be competent and confident in performing drug calculations to ensure patient safety. The purpose of this study is to compare an interactive e-drug calculations package, developed using Cognitive Load Theory as its theoretical framework, with traditional handout learning support on nursing students' drug calculation ability, self-efficacy and support material satisfaction. A cluster randomised controlled trial comparing the e-package with traditional handout learning support was conducted with a September cohort (n=137) and a February cohort (n=92) of second year diploma nursing students. Students from each cohort were geographically dispersed over 3 or 4 independent sites. Students from each cohort were invited to participate, halfway through their second year, before and after a 12 week clinical practice placement. During their placement the intervention group received the e-drug calculations package while the control group received traditional 'handout' support material. Drug calculation ability and self-efficacy tests were given to the participants pre- and post-intervention. Participants were given the support material satisfaction scale post-intervention. Students in both cohorts randomised to e-learning were more able to perform drug calculations than those receiving the handout (September: mean 48.4% versus 34.7%, p=0.027; February: mean 47.6% versus 38.3%, p=0.024). February cohort students using the e-package were more confident in performing drug calculations than those students using handouts (self-efficacy mean 56.7% versus 45.8%, p=0.022). There was no difference in improved self-efficacy between intervention and control for students in the September cohort. Students who used the package were more satisfied with its use than the students who used the handout (mean 29.6 versus 26.5, p=0.001), particularly with regard to the package enhancing their learning (p=0.023), being an effective way to learn (p=0.005), providing practice and

  19. Dissolution Enhancement of Drugs. Part II: Effect of Carriers ...

    African Journals Online (AJOL)

    Recent high throughput screening and combinatorial and parallel synthesis are increasing the number of drug molecules which are highly lipophilic. The oral route is the most preferred route of drug administration due to its convenience, good patient compliance and low medicine production costs. The challenges to ...

  20. Systematic review: ursodeoxycholic acid--adverse effects and drug interactions

    NARCIS (Netherlands)

    Hempfling, W.; Dilger, K.; Beuers, U.

    2003-01-01

    BACKGROUND: Ursodeoxycholic acid is increasingly being used for the treatment of chronic cholestatic liver diseases. It appears to be generally well tolerated, but a systematic review on drug safety is lacking. AIM: As experimental data suggest a role of bile acids in the regulation of hepatic drug

  1. Mixing pleasures: review of the effects of drugs on sex behavior in humans and animal models.

    Science.gov (United States)

    Frohmader, Karla S; Pitchers, Kyle K; Balfour, Margaret E; Coolen, Lique M

    2010-06-01

    Drugs of abuse act on the brain circuits mediating motivation and reward associated with natural behaviors. There is ample evidence that drugs of abuse impact male and female sexual behavior. First, the current review discusses the effect of drugs of abuse on sexual motivation and performance in male and female humans. In particular, we discuss the effects of commonly abused drugs including psychostimulants, opiates, marijuana/THC, and alcohol. In general, drug use affects sexual motivation, arousal, and performance and is commonly associated with increased sexual risk behaviors. Second, studies on effects of systemic administration of drugs of abuse on sexual behavior in animals are reviewed. These studies analyze the effects on sexual performance and motivation but do not investigate the effects of drugs on risk-taking behavior, creating a disconnect between human and animal studies. For this reason, we discuss two studies that focus on the effects of alcohol and methamphetamine on inhibition of maladaptive sex-seeking behaviors in rodents. Third, this review discusses potential brain areas where drugs of abuse may be exerting their effect on sexual behavior with a focus on the mesolimbic system as the site of action. Finally, we discuss recent studies that have brought to light that sexual experience in turn can affect drug responsiveness, including a sensitized locomotor response to amphetamine in female and male rodents as well as enhanced drug reward in male rats. Copyright 2009 Elsevier Inc. All rights reserved.

  2. [Detoxification effects of two drugs in thallium -poisoned mice].

    Science.gov (United States)

    Wang, Ying; He, Yue-zhong; Zhang, Xi-gang

    2012-06-01

    To observe the thallium eliminating effect of prussian blue, pentetate zinc trisodium (Zn-DTPA), and their combined use in the treatment of acute thallium poisoning in mice. Thallium poisoned mice were reproduced by oral administration of 0.2 ml thallous nitrate (3 mg/ml). They were assigned randomly to four groups according to the random number table method, namely, model group, prussian blue group, Zn-DTPA group and the combination therapy group, with 10 mice in each group. Prussian blue was administered orally [4.52 g×kg(-1)×d(-1), total four times], and Zn-DTPA was injected intraperitoneally [500 mg×kg(-1)×d(-1), one time]4 hours after giving thallium. The dosage of both drugs in combination treatment was as the same as described above. After treatment for 5 days, all the animals were sacrificed. Brain, intestine, kidney and liver of 1 mouse from each group were collected for pathological examination to observe the necrosis. Thallium contents of blood, brain, urine and feces from the other mice were determined. Pathological examination showed that the damage to intestine, kidney and liver was less obvious in treatment group compared with those of the model group. The effect was most obvious in the combination treatment group. However, brain damage was slightly improved. Thallium content in blood (mg/ml) of prussian blue group and the combination treatment group decreased obviously compared with the model group, and the decrease was more obvious in the combination treatment group (0.05 ± 0.01 vs. 0.18 ± 0.02). Thallium content in urine (mg/ml) and feces (mg/kg) was significantly increased after treatment, and the thallium elimination was most significant in the combined treatment group (urine: 11.34 ± 0.81 vs. 0.02 ± 0.01, feces: 13.11 ± 1.84 vs. 0.21 ± 0.07, both P Thallium content in brain was similar among all the groups. The single and combined use of prussian blue and Zn-DTPA could reduce the damage in intestine, kidney and liver. Combined use of

  3. Effect of radioimmunoassay procedures on therapeutic drug monitoring

    International Nuclear Information System (INIS)

    Kampa, I.S.

    1985-01-01

    Methods for the measurement of therapeutic drugs have covered every aspect of analysis from extraction to derivatization. In general, published methods were modified to shorten drug extractions and overall analysis time. The use of different standards, as well as the frequent omission of internal standards, often produced large and clinically unacceptable analytical variations. As a result, physicians would adjust drug dosages according to the physiological response to a standard dose. The introduction of radioimmunoassay techniques for the quantitation of therapeutic drugs have made a significant impact on the clinical chemistry laboratory. The similarities of the various assay methods and the technologists' familiarity with the assay protocols have produced clinically relevant results. Clinical laboratories are now able to frequently analyze a large number of samples with acceptable accuracy and precision. The esoteric test once performed infrequently is today a routine analytical assay often performed STAT. Therapeutic drug monitoring has become a major activity in many clinical laboratories

  4. Effect of Na2SO3 concentration to drug loading and drug release of ascorbic acid in chitosan edible film as drug delivery system membrane

    Directory of Open Access Journals (Sweden)

    Kistriyani Lilis

    2018-01-01

    Full Text Available Chitosan is a type of carbohydrate compounds produced from waste marine products, in particular the class of shrimp, crabs and clams. Chitosan is often process into edible films and utilized for food packaging also has potential as a membrane for drug delivery system. Drug loading and drug release can be controlled by improve the characteristics of the membrane by adding crosslinker. The purpose of this research is to study the effect of addition of crosslinker to the rate of loading and release of ascorbic acid in the chitosan edible film. Na2SO3 was used as crosslinker. Two grams of chitosan was dissolved into 100 ml of distilled water. Acetic acid and plasticizer were added in the solution then heated at 50°C. Na2SO3 solution with mass various of Na2SO3 dissolved, 01026 0.3; and 0.5 grams were added about 30 mL to make edible film. The analysis include of drug loading, drug release and tensile strength. The result showed that the loading of edible film with crosslinker 0.15 g; 0.3 g; and 0.5 g respectively were 60.98 ppm; 52.53 ppm; and 40.88 ppm, meanwhile for the release with crosslinker 0.15 g; 0.3 g; and 0.5 g respectively were 3.78 ppm; 5.72 ppm; and 5.97 ppm.

  5. Effect of radiation decontamination on drug-resistant bacteria

    International Nuclear Information System (INIS)

    Ito, Hitoshi

    2006-01-01

    More than 80% of food poisoning bacteria such as Salmonella are reported as antibiotic-resistant to at least one type antibiotic, and more than 50% as resistant to two or more. For the decontamination of food poisoning bacteria in foods, radiation resistibility on drug-resistant bacteria were investigated compared with drug-sensitive bacteria. Possibility on induction of drug-resistant mutation by radiation treatment was also investigated. For these studies, type strains of Escherichia coli S2, Salmonella enteritidis YK-2 and Staphylococcus aureus H12 were used to induce drug-resistant strains with penicillin G. From the study of radiation sensitivity on the drug-resistant strain induced from E. coli S2, D 10 value was obtained to be 0.20 kGy compared with 0.25 kGy at parent strain. On S. enteritidis YK-2, D 10 value was obtained to be 0.14 kGy at drug-resistant strain compared with 0.16 kGy at parent strain. D 10 value was also obtained to be 0.15 kGy at drug-resistant strain compared with 0.21 kGy at parent strain of St. aureus H12. Many isolates of E. coli 157:H7 or other type of E. coli from meats such as beef were resistant to penicillin G, and looked to be no relationship on radiation resistivities between drug-resistant strains and sensitive strains. On the study of radiation sensitivity on E. coli S2 at plate agars containing antibiotics, higher survival fractions were obtained at higher doses compared with normal plate agar. The reason of higher survival fractions at higher doses on plate agar containing antibiotics should be recovery of high rate of injured cells by the relay of cell division, and drug-resistant strains by mutation are hardly induced by irradiation. (author)

  6. A qualitative examination of the effects of international counter-drug interdictions.

    Science.gov (United States)

    Toth, Alexander G; Mitchell, Ojmarrh

    2018-05-01

    The purpose of this study is to utilize unique qualitative data to determine the effects of sporadic international drug interdictions on drug trafficking, and to assess whether the responses of drug traffickers align with rational choice theory. Qualitative data obtained from 23 high-level United States Drug Enforcement Administration (DEA) informants, who are embedded in international drug trafficking groups, are examined to identify common responses to drug interdiction operations. The findings indicate that sporadic counter-drug interdictions do not a have permanent deterrent effect on transnational drug smuggling operations. However, these types of law enforcement operations produce temporary alterations in drug trafficking, as traffickers adopted a variety of methods to thwart the efforts of law enforcement-often by relying on information acquired from corrupt local law enforcement. The results also indicate that while interdiction operations displaced trafficking activities (temporally, spatially, and methodological), there is little evidence that drug traffickers responded to such operations by moving into new areas (i.e., malign spatial displacement). Sporadic international drug interdiction programs do little to deter drug trafficking organizations (DTOs) from engaging in their illicit trade. Instead, DTOs adjust in a calculating manner to these operations to ensure that their illegal products reach consumer marketplaces, which is congruent with the rational choice theoretical perspective. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Lack of effect of spinal anesthesia on drug metabolism

    International Nuclear Information System (INIS)

    Whelan, E.; Wood, A.J.; Shay, S.; Wood, M.

    1989-01-01

    The effect of spinal anesthesia on drug disposition was determined in six dogs with chronically implanted vascular catheters using propranolol as a model compound. On the first study day, 40 mg of unlabeled propranolol and 200 microCi of [3H]propranolol were injected into the portal and femoral veins respectively. Arterial blood samples were taken for 4 hr for measurement of plasma concentrations of labeled and unlabeled propranolol by high-pressure liquid chromatography (HPLC) and of [3H]propranolol by liquid scintillation counting of the HPLC eluant corresponding to each propranolol peak. Twenty-four hr later, spinal anesthesia was induced with tetracaine (mean dose 20.7 +/- 0.6 mg) with low sacral to midthoracic levels and the propranolol infusions and sampling were then repeated. Spinal anesthesia had no significant effect on either the intrinsic clearance of propranolol (2.01 +/- 0.75 L/min before and 1.9 +/- 0.7 L/min during spinal anesthesia), or on mean hepatic plasma flow (2.01 +/- 0.5 L/min before and 1.93 +/- 0.5 L/min during spinal anesthesia). The systemic clearance and elimination half-life of propranolol were also unchanged by spinal anesthesia (0.9 +/- 0.23 L/min on the first day, 0.7 +/- 0.1 L/min during spinal anesthesia; and 101 +/- 21 min on the first day, 115 +/- 16 min during spinal anesthesia, respectively). The volume of distribution (Vd) of propranolol was similarly unaffected by spinal anesthesia

  8. Stigma, discrimination, treatment effectiveness, and policy: public views about drug addiction and mental illness.

    Science.gov (United States)

    Barry, Colleen L; McGinty, Emma E; Pescosolido, Bernice A; Goldman, Howard H

    2014-10-01

    Public attitudes about drug addiction and mental illness were compared. A Web-based national survey (N=709) was conducted to compare attitudes about stigma, discrimination, treatment effectiveness, and policy support in regard to drug addiction and mental illness. Respondents held significantly more negative views toward persons with drug addiction. More respondents were unwilling to have a person with drug addiction marry into their family or work closely with them. Respondents were more willing to accept discriminatory practices against persons with drug addiction, more skeptical about the effectiveness of treatments, and more likely to oppose policies aimed at helping them. Drug addiction is often treated as a subcategory of mental illness, and insurance plans group them together under the rubric of "behavioral health." Given starkly different public views about drug addiction and mental illness, advocates may need to adopt differing approaches to reducing stigma and advancing public policy.

  9. The effect of qualifying language on perceptions of drug appeal, drug experience, and estimates of side-effect incidence in DTC advertising.

    Science.gov (United States)

    Davis, Joel

    2007-01-01

    This study examined how the use of qualifying language in direct-to-consumer (DTC) pharmaceutical advertising affects consumers' perceptions of drug appeal, anticipated pleasantness of drug usage, and the expected incidence of side-effect occurrence. A sample of 669 individuals participated in a 2 x 8 complete factorial design. The design manipulated the number of side effects associated with drug use and the type of qualifying language used to describe the side effects. The eight experimental qualifying language cells represented one control condition (no qualifying language), three cells where each of three types of qualifying language were presented individually, and four cells where qualifying language was combined. The results indicate that qualifying language has a profound effect on drug perceptions, especially when used in combination. Drug appeal and the anticipated drug-using experience almost always were more positive in the presence of qualifying language. Qualifying language appears to exert its influence by causing individuals to reduce their estimate of the likelihood of experiencing individual side effects. Policy implications of the research, particularly for evaluation of "fair balance" and the reporting of side effects, are presented.

  10. Nonsteroidal anti-inflammatory drugs: adverse effects and their prevention.

    NARCIS (Netherlands)

    Vonkeman, Harald Erwin; van de Laar, Mart A F J

    2010-01-01

    Objectives: To discuss nonsteroidal anti-inflammatory drugs (NSAIDs), their history, development, mode of action, toxicities, strategies for the prevention of toxicity, and future developments. - Methods: Medline search for articles published up to 2007, using the keywords acetylsalicylic acid,

  11. Drugs with anticholinergic side‑effects in primary care

    African Journals Online (AJOL)

    2014-05-31

    May 31, 2014 ... retention or hesitancy, visual impairment, falls, confusion, drowsiness ... updated in 2012; as drugs, which may cause dementia and cognitive ... Two questions were asked to determine physicians' attention ... Even if selective.

  12. Adverse effects of sympathomimetic drugs in a group of adolescents

    OpenAIRE

    Jerí, F. Raúl; Carbajal, Carlos; Sánchez M., César

    2014-01-01

    Clinical observations of 35 youths who used hallucinogenic drugs for two to four years are mostly present . The proportion of males was three times compared to women , almost all households were from well integrated and belonged to a higher socio- economic level or medium . The drugs used were marijuana , LSD , barbiturates , mescaline , afetamina , methaqualone and alcohol, in various combinations . All of these young people showed signs of psychological disturbance , personality disorders g...

  13. The Effective Business Practices of Mexican Drug Trafficking Organizations (DTOs)

    Science.gov (United States)

    2013-06-01

    today, customers have easy access to information, products, and services from numerous companies simply by using the Internet or a smartphone , so...customers in the smartphone 81 Campbell, Drug War Zone, 245. 82 Paul Gootenberg, “Talking About The...Drug addictions bring people back once they become hooked. Cartels have been known to allow contractors to use the “bait and hook” technique, a method

  14. Drug Facts

    Medline Plus

    Full Text Available ... Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen ... to prescription drugs. The addiction slowly took over his life. I need different people around me. To ...

  15. Traditional Islamic cities unveiled: the quest for urban design regularity

    Directory of Open Access Journals (Sweden)

    Jorge Correia

    2015-08-01

    Full Text Available Traditional Islamic cities have generally gathered orientalized gazes and perspectives, picking up from misconceptions and stereotypes that during the second half af the 19th century andwere perpectuated by colonialism. More recent scholarship has shed light on the urban organizationand composition of such tissues; most of them confined to old quarters or historical centres ofthriving contemporary cities within the Arab-Muslim world. In fact, one of the most striking featureshas been the unveiling of layered urban assemblages where exterior agents have somehowlaunched or interrupted an apparent islamicized continuum. Primarly, this paper wishes to search forexternal political factors that have designed regularly geometrized patterns in medium-sized Arabtowns. For that, two case studies from different geographies - Maghreb and the Near East - will bemorphologically analysed through updated urban surveys. Whereas Nablus (Palestine ows the urbanmatrix of its old town to its Roman past, in Azemmour’s medina (Morocco it is still possible to trackthe thin European early-modern colonial stratum. However, both cases show how regularity patternschallenge Western concepts of geometrical design to embrace levels of rationality related to tradionalIslamic urban forms, societal configurations and built environment. Urban morphology becomes afundamental tool for articulating the history with me processes of sedimentation and evolution in orderto read current urban prints and dynamics. Thus, the paper will also interpret alternative logics ofrational urban display in Azemmour and Nablus, linked to ways of living within the Islamic sphere.

  16. Tempo and mode of genomic mutations unveil human evolutionary history.

    Science.gov (United States)

    Hara, Yuichiro

    2015-01-01

    Mutations that have occurred in human genomes provide insight into various aspects of evolutionary history such as speciation events and degrees of natural selection. Comparing genome sequences between human and great apes or among humans is a feasible approach for inferring human evolutionary history. Recent advances in high-throughput or so-called 'next-generation' DNA sequencing technologies have enabled the sequencing of thousands of individual human genomes, as well as a variety of reference genomes of hominids, many of which are publicly available. These sequence data can help to unveil the detailed demographic history of the lineage leading to humans as well as the explosion of modern human population size in the last several thousand years. In addition, high-throughput sequencing illustrates the tempo and mode of de novo mutations, which are producing human genetic variation at this moment. Pedigree-based human genome sequencing has shown that mutation rates vary significantly across the human genome. These studies have also provided an improved timescale of human evolution, because the mutation rate estimated from pedigree analysis is half that estimated from traditional analyses based on molecular phylogeny. Because of the dramatic reduction in sequencing cost, sequencing on-demand samples designed for specific studies is now also becoming popular. To produce data of sufficient quality to meet the requirements of the study, it is necessary to set an explicit sequencing plan that includes the choice of sample collection methods, sequencing platforms, and number of sequence reads.

  17. Hidden temporal order unveiled in stock market volatility variance

    Directory of Open Access Journals (Sweden)

    Y. Shapira

    2011-06-01

    Full Text Available When analyzed by standard statistical methods, the time series of the daily return of financial indices appear to behave as Markov random series with no apparent temporal order or memory. This empirical result seems to be counter intuitive since investor are influenced by both short and long term past market behaviors. Consequently much effort has been devoted to unveil hidden temporal order in the market dynamics. Here we show that temporal order is hidden in the series of the variance of the stocks volatility. First we show that the correlation between the variances of the daily returns and means of segments of these time series is very large and thus cannot be the output of random series, unless it has some temporal order in it. Next we show that while the temporal order does not show in the series of the daily return, rather in the variation of the corresponding volatility series. More specifically, we found that the behavior of the shuffled time series is equivalent to that of a random time series, while that of the original time series have large deviations from the expected random behavior, which is the result of temporal structure. We found the same generic behavior in 10 different stock markets from 7 different countries. We also present analysis of specially constructed sequences in order to better understand the origin of the observed temporal order in the market sequences. Each sequence was constructed from segments with equal number of elements taken from algebraic distributions of three different slopes.

  18. Evaluation of Anti-Inflammatory Drug-Conjugated Silicon Quantum Dots: Their Cytotoxicity and Biological Effect

    Directory of Open Access Journals (Sweden)

    Kenji Yamamoto

    2013-01-01

    Full Text Available Silicon quantum dots (Si-QDs have great potential for biomedical applications, including their use as biological fluorescent markers and carriers for drug delivery systems. Biologically inert Si-QDs are less toxic than conventional cadmium-based QDs, and can modify the surface of the Si-QD with covalent bond. We synthesized water-soluble alminoprofen-conjugated Si-QDs (Ap-Si. Alminoprofen is a non-steroid anti-inflammatory drug (NSAID used as an analgesic for rheumatism. Our results showed that the “silicon drug” is less toxic than the control Si-QD and the original drug. These phenomena indicate that the condensed surface integration of ligand/receptor-type drugs might reduce the adverse interaction between the cells and drug molecules. In addition, the medicinal effect of the Si-QDs (i.e., the inhibition of COX-2 enzyme was maintained compared to that of the original drug. The same drug effect is related to the integration ratio of original drugs, which might control the binding interaction between COX-2 and the silicon drug. We conclude that drug conjugation with biocompatible Si-QDs is a potential method for functional pharmaceutical drug development.

  19. The Effects of Students' Perception of a Speaker's Role on Their Recall of Drug Facts and Their Opinions and Attitudes About Drugs

    Science.gov (United States)

    McCleaf, James E.; Colby, Margaret A.

    1975-01-01

    The ascribed social role of a speaker and his ascribed experience with drugs contributed to significant differences in student recall of drug information. Sex of the respondent was found to have a significant effect on students' scores on the Drug Opinion and Attitudes Test. (RC)

  20. Drug-drug interaction and doping, part 1: an in vitro study on the effect of non-prohibited drugs on the phase I metabolic profile of toremifene.

    Science.gov (United States)

    Mazzarino, Monica; de la Torre, Xavier; Fiacco, Ilaria; Palermo, Amelia; Botrè, Francesco

    2014-05-01

    The present study was designed to provide preliminary information on the potential impact of metabolic drug-drug interaction on the effectiveness of doping control strategies currently followed by the anti-doping laboratories to detect the intake of banned agents. In vitro assays based on the use of human liver microsomes and recombinant CYP isoforms were designed and performed to characterize the phase I metabolic profile of the prohibited agent toremifene, selected as a prototype drug of the class of selective oestrogen receptor modulators, both in the absence and in the presence of medicaments (fluconazole, ketoconazole, itraconazole, miconazole, cimetidine, ranitidine, fluoxetine, paroxetine, nefazodone) not included in the World Anti-Doping Agency list of prohibited substances and methods and frequently administered to athletes. The results show that the in vitro model developed in this study was adequate to simulate the in vivo metabolism of toremifene, confirming the results obtained in previous studies. Furthermore, our data also show that ketoconazole, itraconazole, miconazole and nefazodone cause a marked modification in the production of the metabolic products (i.e. hydroxylated and carboxylated metabolites) normally selected by the anti-doping laboratories as target analytes to detect toremifene intake; moderate variations were registered in the presence of fluconazole, paroxetine and fluoxetine; while no significant modifications were measured in the presence of ranitidine and cimetidine. This evidence imposes that the potential effect of drug-drug interactions is duly taken into account in anti-doping analysis, also for a broader significance of the analytical results. Copyright © 2014 John Wiley & Sons, Ltd.

  1. Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis

    DEFF Research Database (Denmark)

    Zielinski, Daniel C.; Filipp, F. V.; Bordbar, A.

    2015-01-01

    Drug side effects cause a significant clinical and economic burden. However, mechanisms of drug action underlying side effect pathogenesis remain largely unknown. Here, we integrate pharmacogenomic and clinical data with a human metabolic network and find that non-pharmacokinetic metabolic pathways...

  2. Effect of nonsteroidal antiinflammatory drugs on the C-reactive protein level in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Tarp, Simon; Bartels, Else M.; Bliddal, Henning

    2012-01-01

    To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs.......To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs....

  3. Quiet please! Drug round tabards: are they effective and accepted? A mixed method study

    NARCIS (Netherlands)

    Verweij, Lotte; Smeulers, Marian; Maaskant, Jolanda M.; Vermeulen, Hester

    2014-01-01

    The use of drug round tabards is a widespread intervention that is implemented to reduce the number of interruptions and medication administration errors (MAEs) by nurses; however, evidence for their effectiveness is scarce. Evaluation of the effect of drug round tabards on the frequency and type of

  4. Drug-drug Interactions of Statins Potentially Leading to Muscle-Related Side Effects in Hospitalized Patients.

    Science.gov (United States)

    Bucsa, Camelia; Farcas, Andreea; Leucuta, D; Mogosan, Cristina; Bojita, M; Dumitrascu, D L

    2015-01-01

    The associations of drugs that may interact with the statins resulting in elevated serum concentration of the statins are an important risk factor for statin induced muscle disorders. We aimed to determine the prevalence of these associations in all hospitalized patients that had been prescribed statins before/during hospitalization and to find out how often they are associated with muscle-related side effects. This prospective, non-interventional study performed in two internal medicine departments included patients with statin therapy before/during hospitalization. Data on each patient demographic characteristics, co-morbidities and treatment was collected from medical charts and interviews. We evaluated patients' therapy for the targeted associations using Thomson Micromedex Drug Interactions checker and we ranked the identified drug-drug interactions (DDIs) accordingly. Each patient with statin treatment before admission was additionally interviewed in order to identify muscular symptoms. In 109 patients on statin treatment we found 35 potential (p) DDIs of statins in 30 (27.5%) patients, most of which were in the therapy before admission (27 pDDIs). The pDDIs were moderate (20 pDDIs) and major (15 pDDIs). Of the total number of pDDIs, 24 were targeting the muscular system. The drugs most frequently involved in the statins' pDDIs were amiodarone and fenofibrate. Two of the patients with pDDIs reported muscle pain, both having additional risk factors for statin induced muscular effects. The prevalence of statins' pDDIs was high in our study, mostly in the therapy before admission, with only a small number of pDDIs resulting in clinical outcome.

  5. Effectiveness of HIV prevention social marketing with injecting drug users.

    Science.gov (United States)

    Gibson, David R; Zhang, Guili; Cassady, Diana; Pappas, Les; Mitchell, Joyce; Kegeles, Susan M

    2010-10-01

    Social marketing involves applying marketing principles to promote social goods. In the context of health behavior, it has been used successfully to reduce alcohol-related car crashes, smoking among youths, and malaria transmission, among other goals. Features of social marketing, such as audience segmentation and repeated exposure to prevention messages, distinguish it from traditional health promotion programs. A recent review found 8 of 10 rigorously evaluated social marketing interventions responsible for changes in HIV-related behavior or behavioral intentions. We studied 479 injection drug users to evaluate a community-based social marketing campaign to reduce injection risk behavior among drug users in Sacramento, California. Injecting drugs is associated with HIV infection in more than 130 countries worldwide.

  6. Renal Side Effects of Non-Steroidal Anti-Inflammatory Drugs in Neonates

    Directory of Open Access Journals (Sweden)

    Marc Gewillig

    2010-02-01

    Full Text Available Non-steroidal anti-inflammatory drugs like ibuprofen or indomethacin are commonly prescribed drugs to induce pharmacologic closure of a patent ductus arteriosus in preterm neonates. Based on a recently published Cochrane meta-analysis, both drugs are equally effective to induce closure. Drug choice can therefore be based on differences in side effects or pharmaco-economic arguments. The current review quantifies the negative impact of either ibuprofen or indomethacin on renal function, including diuresis, glomerular filtration rate and renal tubular function. Both ibuprofen and indomethacin have a quantifiable impact on renal function. However, compared to ibuprofen, the negative impact of indomethacin is more pronounced.

  7. [Effects of the new comprehensive system for designating illegal drug components on the abuse of designer drugs and future problems based on an online questionnaire].

    Science.gov (United States)

    Morino, Taichi; Okazaki, Mitsuhiro; Toda, Takaki; Yokoyama, Takashi

    2015-12-01

    Recently, the abuse of designer drugs has become a social problem. Designer drugs are created by modifying part of the chemical structure of drugs that have already been categorized as illegal, thereby creating a different chemical compound in order to evade Pharmaceutical Affairs Law regulations. The new comprehensive system for designating illegal drug components has been in effect since March 2013, and many designer drugs can now be regulated. We conducted an online questionnaire survey of people with a history of designer drug use to elucidate the effects of the new system on the abuse of designer drugs and to identify potential future problems. Over half the subjects obtained designer drugs only before the new system was implemented. Awareness of the system was significantly lower among subjects who obtained designer drugs for the first time after its introduction than those who obtained the drugs only before its implementation. Due to the new system, all methods of acquiring designer drugs saw decreases in activity. However, the ratio of the acquisition of designer drugs via the Internet increased. Since over 50% of the subjects never obtained designer drugs after the new system was introduced, goals that aimed to make drug procurement more difficult were achieved. However, awareness of the new system among subjects who obtained designer drugs after the new system was introduced was significantly low. Therefore, fostering greater public awareness of the new system is necessary. The results of the questionnaire also suggested that acquiring designer drugs through the Internet has hardly been affected by the new system. We strongly hope that there will be a greater push to restrict the sale of designer drugs on the Internet in the near future.

  8. Effects of chronic administration of drugs of abuse on impulsive choice (delay discounting) in animal models.

    Science.gov (United States)

    Setlow, Barry; Mendez, Ian A; Mitchell, Marci R; Simon, Nicholas W

    2009-09-01

    Drug-addicted individuals show high levels of impulsive choice, characterized by preference for small immediate over larger but delayed rewards. Although the causal relationship between chronic drug use and elevated impulsive choice in humans has been unclear, a small but growing body of literature over the past decade has shown that chronic drug administration in animal models can cause increases in impulsive choice, suggesting that a similar causal relationship may exist in human drug users. This article reviews this literature, with a particular focus on the effects of chronic cocaine administration, which have been most thoroughly characterized. The potential mechanisms of these effects are described in terms of drug-induced neural alterations in ventral striatal and prefrontal cortical brain systems. Some implications of this research for pharmacological treatment of drug-induced increases in impulsive choice are discussed, along with suggestions for future research in this area.

  9. A side-effect free method for identifying cancer drug targets.

    Science.gov (United States)

    Ashraf, Md Izhar; Ong, Seng-Kai; Mujawar, Shama; Pawar, Shrikant; More, Pallavi; Paul, Somnath; Lahiri, Chandrajit

    2018-04-27

    Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.

  10. Stem cells as anticancer drug carrier to reduce the chemotherapy side effect

    Science.gov (United States)

    Salehi, Hamideh; Al-Arag, Siham; Middendorp, Elodie; Gergley, Csilla; Cuisinier, Frederic

    2017-02-01

    Chemotherapy used for cancer treatment, due to the lack of specificity of drugs, is associated to various damaging side effects that have severe impact on patients' quality of life. Over the past 30 years, increasing efforts have been placed on optimizing chemotherapy dosing with the main goal of increasing antitumor efficacy while reducing drug-associated toxicity. A novel research shows that stem cells may act as a reservoir for the anticancer agent, which will subsequently release some of the drug's metabolites, or even the drug in its original form, in vicinity of the cancer cells. These cells may play a dual role in controlling drug toxicity depending on their capacity to uptake and release the chemotherapeutic drug. In our study, we show that Dental Pulp Stem Cells DPSCs are able to rapidly uptake Paclitaxel PTX, and to release it in the culture medium in a time-dependent manner. This resulting conditioned culture medium is to be transferred to breast cancer cells, the MCF-7. By applying Confocal Raman Microscopy, the anticancer drug uptake by the MCF-7 was measured. Surprisingly, the cancer cells -without any direct contact with PTX- showed a drug uptake. This proves that the stem cells carried and delivered the anticancer drug without its modification. It could be a revolution in chemotherapy to avoid the drug's side effects and increase its efficacy.

  11. The Paradoxical and Unintended Effects of the War on Drugs

    Science.gov (United States)

    1993-04-01

    of coca leaves; 2) heroin, derived from the opium poppy; and, 3) marijuana and hashish from the cannabis plant. Cocaine and crack come into the U.S...example, is 28 to 43 per cent of its total exports, and generates more money than its major export, coffee . 52 Moreover, the drug business is a major source

  12. Drug combination may be highly effective in recurrent ovarian cancer

    Science.gov (United States)

    Significant improvement with the use of a combination drug therapy for recurrent ovarian cancer was reported at the annual meeting of the American Society of Clinical Oncology meeting in Chicago. The trial compared the activity of a combination of the dru

  13. [Adverse muscle effects of a podofyllotoxin-containing cytotoxic drug product with simvastatin].

    Science.gov (United States)

    Kaipiainen-Seppänen, Oili; Savolainen, Elina; Elfving, Pia; Kononoff, Aulikki

    2009-01-01

    With the ageing population, drug interactions pose an increasing challenge to health professionals. We describe four patients, for whom concurrent administration of a podofyllotoxin-containing cytotoxic drug product and simvastatin caused severe adverse effects on muscles, including muscle pain, soreness or fatigue or weakness, and in some patients also disintegration of muscle tissue, i.e. rhabdomyolysis. The metabolism of both drugs proceeds via the common CYP3A4 enzyme pathway.

  14. Called to respond: The potential of unveiling hiddens

    Directory of Open Access Journals (Sweden)

    Alison L Black

    2014-12-01

    Full Text Available Interested in exploring how personal stories and aesthetic modes of representing experiences can nudge open academic and educational spaces, this article/collection of particles seeks to document our encounters of being affected and called to respond to things the other has written and represented. As a way of engaging with questions about what research and research data might be and become, our attention has been drawn to stories and images from our lives that we have not shaken off – and to how, as we have opened these to the other, making once private moments public, our hiddens have morphed tenderly into a shared knowing and being. As we have acted on the call we have felt to respond we have found ourselves entering spaces of collaboration, communion, contemplation, and conversation – spaces illuminated by what we have not been able to – and cannot – set aside. Using visual and poetic materials we explore heartfelt and heartbroken aspects of our educational worlds and lives, to be present with each other and our (reemerging personal and professional meanings. We see the shared body (of work, of writing, of image that develops from the taking of brave steps and the risky slipping off of academic masks and language, as a manifestation of the trusted and nurturing spaces that can be generated through collaborative opportunities to gather together. These steps towards unveiling hiddens are producing in us and of us a friendship, fluency, and fluidity as we write new ways of becoming. In turn, we hope the uncovering and revealing of our dialogue in the public gathering of this journal might supports readers’ telling of their own life stories through what calls them to respond.

  15. Sirtuins: Novel targets for metabolic disease in drug development

    International Nuclear Information System (INIS)

    Jiang Weijian

    2008-01-01

    Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases such as type 2 diabetes. SIRT1, an NAD + -dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produces beneficial effects on glucose homeostasis and insulin sensitivity. Activation of SIRT1 leads to enhanced activity of multiple proteins, including peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) and FOXO which helps to mediate some of the in vitro and in vivo effects of sirtuins. Resveratrol, a polyphenolic SIRT1 activator, mimics the effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance. In this review, we summarize recent research advances in unveiling the molecular mechanisms that underpin sirtuin as therapeutic candidates and discuss the possibility of using resveratrol as potential drug for treatment of diabetes

  16. Deciphering the clinical effect of drugs through large-scale data integration

    DEFF Research Database (Denmark)

    Kjærulff, Sonny Kim

    . This work demonstrates the power of a strategy that uses clinical data mining in association with chemical biology in order to reduce the search space and aid identification of novel drug actions. The second article described in chapter 3 outlines a high confidence side-effect-drug interaction dataset. We...... demonstrates the importance of using high-confidence drug-side-effect data in deciphering the effect of small molecules in humans. In summary, this thesis presents computational systems chemical biology approaches that can help identify clinical effects of small molecules through large-scale data integration...

  17. Dilemmas in the (un)veiling of the diagnosis of Alzheimer's disease: walking an ethical and professional tight rope.

    Science.gov (United States)

    Karnieli-Miller, Orit; Werner, Perla; Aharon-Peretz, Judith; Eidelman, Shmuel

    2007-08-01

    To enhance the understanding and effect of physician's difficulties, attitudes and communication styles on the disclosure of the diagnosis of AD in practice. Qualitative, phenomenological study, combining pre-encounter interviews with physicians, observations of actual encounters of diagnosis disclosure of AD, and post-encounter interviews. There were various ways or tactics to (un)veil the bad news that may be perceived as different ways of dulling the impact and avoiding full and therefore problematic statements. In the actual encounters this was accomplished by keeping encounters short, avoiding elaboration, confirmation of comprehension and explicit terminology and using fractured sentences. The present study's findings highlight the difficulties encountered in breaking the news about AD, in the way it is actually done, and the problems that may arise from this way of un/veiling the news. The main problem is that the reluctance to make a candid disclosure of the diagnosis as was demonstrated in this study may violate basic moral and legal rights and may also deprive patients and caregivers of some of the benefits of early disclosure of diagnosis. There is a need for assisting physicians to cope with their personal difficulties, problems and pitfalls in breaking the news.

  18. Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment

    DEFF Research Database (Denmark)

    Phillips, Andrew N; Cambiano, Valentina; Miners, Alec

    2014-01-01

    BACKGROUND: With continued roll-out of antiretroviral therapy (ART) in resource-limited settings, evidence is emerging of increasing levels of transmitted drug-resistant HIV. We aimed to compare the effectiveness and cost-effectiveness of different potential public health responses to substantial...

  19. Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; policies, requirements, and administrative procedures; delay of effective date; reopening of administrative record. Food and Drug Administration, HHS. Final rule; delay of effective date; reopening of administrative record.

    Science.gov (United States)

    2000-05-03

    The Food and Drug Administration (FDA) is delaying until October 1, 2001, the effective date and reopening the administrative record to receive additional comments regarding certain requirements of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720). The other provisions of the final rule become effective on December 4, 2000. The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA) and the FDA Modernization Act of 1997 (the Modernization Act). FDA is delaying the effective date for certain requirements relating to wholesale distribution of prescription drugs by distributors that are not authorized distributors of record. FDA is also delaying the effective date of another requirement that would prohibit blood centers functioning as "health care entities" to act as wholesale distributors of blood derivatives. The agency is taking this action to address numerous concerns about the provisions raised by affected parties.

  20. Impact of Maine's Medicaid drug formulary change on non-Medicaid markets: spillover effects of a restrictive drug formulary.

    Science.gov (United States)

    Wang, Y Richard; Pauly, Mark V; Lin, Y Aileen

    2003-10-01

    Market penetration of HMOs affect physician practice styles for non-HMO patients. To study the impact of a restrictive Medicaid drug formulary on prescribing patterns for other patients, ie, so-called spillover effects. A before-and-after, 3-state comparison study. On January 1, 2001, Maine's Medicaid program implemented a restrictive drug formulary for the proton pump inhibitor class, with pantoprazole as the only preferred drug. The Medicaid and non-Medicaid market shares of pantoprazole in Maine (vs New Hampshire and Vermont and among Maine physicians with different Medicaid share of practice. After 3 months, the market share of pantoprazole in Maine (vs 2 control states) increased 79% among Medicaid prescriptions (vs 1%-2%), 10% among cash prescriptions (vs 3%), and 7% among other third-party payer prescriptions (vs 1%). The market shares increased more among Maine physicians with a higher Medicaid share of practice (high vs middle vs low [market]: 16% vs 8% vs 5% [cash]; 11% vs 5% vs 4% [other third-party payers]). Linear regression results indicate that practicing medicine in Maine leads to a 72% increase in pantoprazole share among Medicaid prescriptions (P markets, with somewhat stronger effects in the cash market.

  1. Effects of acute doses of prosocial drugs methamphetamine and alcohol on plasma oxytocin levels.

    Science.gov (United States)

    Bershad, Anya K; Kirkpatrick, Matthew G; Seiden, Jacob A; de Wit, Harriet

    2015-06-01

    Many drugs, including alcohol and stimulants, demonstrably increase sociability and verbal interaction and are recreationally consumed in social settings. One drug, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), seems to produce its prosocial effects by increasing plasma oxytocin levels, and the oxytocin system has been implicated in responses to several other drugs of abuse. Here, we sought to investigate the effects of 2 other "social" drugs on plasma oxytocin levels--methamphetamine and alcohol. Based on their shared capacity to enhance sociability, we hypothesized that both methamphetamine and alcohol would increase plasma oxytocin levels. In study 1, 11 healthy adult volunteers attended 3 sessions during which they received methamphetamine (10 mg or 20 mg) or placebo under double-blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin levels were measured at regular intervals throughout the sessions. In study 2, 8 healthy adult volunteers attended a single session during which they received 1 beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin levels were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither of these drugs increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified.

  2. Cost-effectiveness analysis of microdose clinical trials in drug development.

    Science.gov (United States)

    Yamane, Naoe; Igarashi, Ataru; Kusama, Makiko; Maeda, Kazuya; Ikeda, Toshihiko; Sugiyama, Yuichi

    2013-01-01

    Microdose (MD) clinical trials have been introduced to obtain human pharmacokinetic data early in drug development. Here we assessed the cost-effectiveness of microdose integrated drug development in a hypothetical model, as there was no such quantitative research that weighed the additional effectiveness against the additional time and/or cost. First, we calculated the cost and effectiveness (i.e., success rate) of 3 types of MD integrated drug development strategies: liquid chromatography-tandem mass spectrometry, accelerator mass spectrometry, and positron emission tomography. Then, we analyzed the cost-effectiveness of 9 hypothetical scenarios where 100 drug candidates entering into a non-clinical toxicity study were selected by different methods as the conventional scenario without MD. In the base-case, where 70 drug candidates were selected without MD and 30 selected evenly by one of the three MD methods, incremental cost-effectiveness ratio per one additional drug approved was JPY 12.7 billion (US$ 0.159 billion), whereas the average cost-effectiveness ratio of the conventional strategy was JPY 24.4 billion, which we set as a threshold. Integrating MD in the conventional drug development was cost-effective in this model. This quantitative analytical model which allows various modifications according to each company's conditions, would be helpful for guiding decisions early in clinical development.

  3. Metabolic and Endocrine Side Effects of Atypical Antipsychotic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Aysegul Tahiroglu

    2011-03-01

    Full Text Available omorbid psychiatric disorders, frequent hospitalization, multiple outpatient treatment, prior history of hypertension, obesity and lipid dysregulation are associated with higher risk of metabolic syndrome in children. Side effects of antipsychotic drugs and their management have recently become a major subject of research due to enhanced antipsychotic drug usage in child and adolescents. Prevention strategies are usually preferred to secondary or tertiary strategies in the management of metabolic syndrome associated with antipsychotic drugs. Clinicians should present multidisciplinary approach to endocrine and metabolic side effects due to antipsychotic use in pediatric patient groups and avoid multiple drug use in such patients. In this paper, we briefly reviewed metabolic side effects of second generation antipsychotic drugs in child and adolescent population, possible mechanisms of susceptibility to metabolic syndrome and pharmacological and non pharmacological treatment approach to prevention of weight gain.

  4. Effect of some radiosensitising drugs on human erythrocyte membrane - - spin label study

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, K P [Bhabha Atomic Research Centre, Bombay (India). Biology and Agriculture Div.

    1982-02-01

    Electron spin resonance and spin label techniques have been employed to study the effects of local anaesthetic drugs, procaine and tetracaine, on human erythrocyte membrane. Both the drugs altered the protein and lipid arrangements in the membrane and these changes were reversible. Procaine had greater effect on the labels attached to proteins while tetracaine fluidized interior of lipid bilayer to a greater extent. The differential effects of these drugs on the protein and lipid labels have been interpreted in terms of their relative penetrability in the membrane. Present results have explained that radiation induced enhanced killing of cells in the presence of these drugs might be due to the alterations in membrane, particularly proteins both structural and enzymatic. In addition, these results indicate a possible relationship between drug-induced structural changes in membrane and their anaesthetic potency.

  5. The effect of network biology on drug toxicology

    DEFF Research Database (Denmark)

    Gautier, Laurent; Taboureau, Olivier; Audouze, Karine Marie Laure

    2013-01-01

    Introduction: The high failure rate of drug candidates due to toxicity, during clinical trials, is a critical issue in drug discovery. Network biology has become a promising approach, in this regard, using the increasingly large amount of biological and chemical data available and combining...... it with bioinformatics. With this approach, the assessment of chemical safety can be done across multiple scales of complexity from molecular to cellular and system levels in human health. Network biology can be used at several levels of complexity. Areas covered: This review describes the strengths and limitations...... of network biology. The authors specifically assess this approach across different biological scales when it is applied to toxicity. Expert opinion: There has been much progress made with the amount of data that is generated by various omics technologies. With this large amount of useful data, network...

  6. The effect of anticholinergic drugs on 123I-IMP SPECT in Parkinson's disease

    International Nuclear Information System (INIS)

    Mizuno, Tomoyuki; Nishiyama, Kazutoshi; Hitoshi, Seiji; Takeda, Koichi; Sakuta, Manabu

    1992-01-01

    Anticholinergic drugs may be responsible for mental deterioration in Parkinson's disease (PD). This study was thus performed to examine effects of anticholinergic drugs on the brain by using N-isopropyl-p-[I-123] iodoamphetamine SPECT. The purpose of the study was twofold: (I) to compare regional cerebral uptake of tracer during treatment with anticholinergic drugs and one month after the discontinuation of the drugs in 7 PD patients given them for 6 months or more; and (II) to compare tracer uptake in 11 PD patients administered anticholinergic drugs and 25 PD patients not administered them. Each 16 regions in the bilateral cerebral cortexes and each one region in the bilateral basal ganglia, thalamus, and cerebellum were assigned as regions of interest (ROI). The count ratio of each ROI in the cerebrum to ROI in the cerebellum was designated as regional cerebral uptake ratio (rCUR). A mean rCUR was lower during administration of anticholinergic drugs in all ROIs, except for two in Group I and one in Group II, than during the period not administered the drugs. The administration of anticholinergic drugs was sigificantly associated with decreased rCUR in 10 ROIs in Group I, and in 15 ROIs in Group II. The rCUR in the occipital, basal ganglia, and thalamus was independent of the administration of anticholinergic drugs. These results suggest that anticholinergic drugs may inhibit the cortical cholinergic system in PD patients. (N.K.)

  7. The effect of anticholinergic drugs on [sup 123]I-IMP SPECT in Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Mizuno, Tomoyuki; Nishiyama, Kazutoshi; Hitoshi, Seiji; Takeda, Koichi; Sakuta, Manabu [Japan Red Cross Central Hospital, Tokyo (Japan)

    1992-04-01

    Anticholinergic drugs may be responsible for mental deterioration in Parkinson's disease (PD). This study was thus performed to examine effects of anticholinergic drugs on the brain by using N-isopropyl-p-[I-123] iodoamphetamine SPECT. The purpose of the study was twofold: (I) to compare regional cerebral uptake of tracer during treatment with anticholinergic drugs and one month after the discontinuation of the drugs in 7 PD patients given them for 6 months or more; and (II) to compare tracer uptake in 11 PD patients administered anticholinergic drugs and 25 PD patients not administered them. Each 16 regions in the bilateral cerebral cortexes and each one region in the bilateral basal ganglia, thalamus, and cerebellum were assigned as regions of interest (ROI). The count ratio of each ROI in the cerebrum to ROI in the cerebellum was designated as regional cerebral uptake ratio (rCUR). A mean rCUR was lower during administration of anticholinergic drugs in all ROIs, except for two in Group I and one in Group II, than during the period not administered the drugs. The administration of anticholinergic drugs was sigificantly associated with decreased rCUR in 10 ROIs in Group I, and in 15 ROIs in Group II. The rCUR in the occipital, basal ganglia, and thalamus was independent of the administration of anticholinergic drugs. These results suggest that anticholinergic drugs may inhibit the cortical cholinergic system in PD patients. (N.K.).

  8. Effects of image congruency on persuasiveness and recall in direct-to-consumer prescription drug advertising.

    Science.gov (United States)

    Kiernicki, Kristen; Helme, Donald W

    2017-01-01

    Although direct-to-consumer (DTC) prescription drug advertising is regulated by the U.S. Food and Drug Administration, content analyses suggest advertisers may not disclose drug risks in the same way they describe drug benefits. This study tests the relationship between image congruency in televised DTC advertisements, recall of risks/benefits, and perceived persuasiveness. Advertisements for Nasonex, Advair, and Lunesta were shown to college students in either their original (image incongruent) or modified (image neutral) form. Risks were easier to recall with image-neutral advertisements. Gender also had a significant interaction effect, suggesting that males and females process DTC advertisement differently.

  9. Consumers' reports on the health effects of direct-to-consumer drug advertising.

    Science.gov (United States)

    Weissman, Joel S; Blumenthal, David; Silk, Alvin J; Zapert, Kinga; Newman, Michael; Leitman, Robert

    2003-01-01

    We conducted a national telephone survey about health care experiences associated with direct-to-consumer advertising (DTCA) of prescription drugs. Among the 35 percent of our sample who had a physician visit during which DTCA was discussed, 25 percent received a new diagnosis, of which 43 percent were considered high priority according to authoritative sources. More than half also reported actions taken by their physician other than prescribing the advertised drug. Despite concerns about DTCA's negative consequences, we found no differences in health effects between patients who took advertised drugs and those who took other prescription drugs.

  10. Inhibitory effects of drugs on the metabolic activity of mouse and human aldehyde oxidases and influence on drug-drug interactions.

    Science.gov (United States)

    Takaoka, Naoki; Sanoh, Seigo; Okuda, Katsuhiro; Kotake, Yaichiro; Sugahara, Go; Yanagi, Ami; Ishida, Yuji; Tateno, Chise; Tayama, Yoshitaka; Sugihara, Kazumi; Kitamura, Shigeyuki; Kurosaki, Mami; Terao, Mineko; Garattini, Enrico; Ohta, Shigeru

    2018-04-17

    As aldehyde oxidase (AOX) plays an emerging role in drug metabolism, understanding its significance for drug-drug interactions (DDI) is important. Therefore, we tested 10 compounds for species-specific and substrate-dependent differences in the inhibitory effect of AOX activity using genetically engineered HEK293 cells over-expressing human AOX1, mouse AOX1 or mouse AOX3. The IC 50 values of 10 potential inhibitors of the three AOX enzymes were determined using phthalazine and O 6 -benzylguanine as substrates. 17β-Estradiol, menadione, norharmane and raloxifene exhibited marked differences in inhibitory effects between the human and mouse AOX isoforms when the phthalazine substrate was used. Some of the compounds tested exhibited substrate-dependent differences in their inhibitory effects. Docking simulations with human AOX1 and mouse AOX3 were conducted for six representative inhibitors. The rank order of the minimum binding energy reflected the order of the corresponding IC 50 values. We also evaluated the potential DDI between an AOX substrate (O 6 -benzylguanine) and an inhibitor (hydralazine) using chimeric mice with humanized livers. Pretreatment of hydralazine increased the maximum plasma concentration (C max ) and the area under the plasma concentration-time curve (AUC 0-24 ) of O 6 -benzylguanine compared to single administration. Our in vitro data indicate species-specific and substrate-dependent differences in the inhibitory effects on AOX activity. Our in vivo data demonstrate the existence of a DDI which may be of relevance in the clinical context. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Effect of Zeta Potential on the Properties of Nano-Drug Delivery ...

    African Journals Online (AJOL)

    Zeta potential is a scientific term for electrokinetic potential in colloidal systems which has a major effect on the various properties of nano-drug delivery systems. Presently, colloidal nano-carriers are growing at a remarkable rate owing to their strong potential for overcoming old challenges such as poor drug solubility and ...

  12. Money Matters: Cost-Effectiveness of Juvenile Drug Court with and without Evidence-Based Treatments

    Science.gov (United States)

    Sheidow, Ashli J.; Jayawardhana, Jayani; Bradford, W. David; Henggeler, Scott W.; Shapiro, Steven B.

    2012-01-01

    The 12-month cost-effectiveness of juvenile drug court and evidence-based treatments within court were compared with traditional Family Court for 128 substance-abusing/dependent juvenile offenders participating in a 4-condition randomized trial. Intervention conditions included Family Court with community services (FC), Drug Court with community…

  13. What Will Happen if . . . A Programmed Instruction Course on Drugs and Their Effects.

    Science.gov (United States)

    Health Services and Mental Health Administration (DHEW), Bethesda, MD.

    Developed by the National Institute of Mental Health, this booklet offers a programed instruction course on drugs and their effects. The purpose of the text is to learn about specific drugs which are currently being used and abused by a large group of people in our society. Narcotics, stimulants, depressants, hallucinogens, and marihuana are…

  14. Prediction of Effective Drug Combinations by Chemical Interaction, Protein Interaction and Target Enrichment of KEGG Pathways

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2013-01-01

    Full Text Available Drug combinatorial therapy could be more effective in treating some complex diseases than single agents due to better efficacy and reduced side effects. Although some drug combinations are being used, their underlying molecular mechanisms are still poorly understood. Therefore, it is of great interest to deduce a novel drug combination by their molecular mechanisms in a robust and rigorous way. This paper attempts to predict effective drug combinations by a combined consideration of: (1 chemical interaction between drugs, (2 protein interactions between drugs’ targets, and (3 target enrichment of KEGG pathways. A benchmark dataset was constructed, consisting of 121 confirmed effective combinations and 605 random combinations. Each drug combination was represented by 465 features derived from the aforementioned three properties. Some feature selection techniques, including Minimum Redundancy Maximum Relevance and Incremental Feature Selection, were adopted to extract the key features. Random forest model was built with its performance evaluated by 5-fold cross-validation. As a result, 55 key features providing the best prediction result were selected. These important features may help to gain insights into the mechanisms of drug combinations, and the proposed prediction model could become a useful tool for screening possible drug combinations.

  15. The effects of cyclodextrins on drug release from fatty suppository bases : I. In vitro observations

    NARCIS (Netherlands)

    Frijlink, H.W.; Eissens, Anko; Schoonen, Adelbert; Lerk, C.F.

    The effect of cyclodextrins on suppository drug release was investigated. Complexes of several lipophilic drugs with β- and/or γ-cyclodextrin were prepared using the coprecipitation method. The formation of true complexes was confirmed by DSC and an 'ether-wash' method. Witepsol H15 suppositories

  16. Meta-analysis of recent studies on patients admitted to hospital due to adverse drug effects

    NARCIS (Netherlands)

    Atiqi, R.; Cleophas, T. J.; van Bommel, E.; Zwinderman, A. H.

    2009-01-01

    The use of drugs has expanded during the previous decade. However, earlier studies oil patients admitted for adverse drugs effects (ADEs) have been heterogeneous. The objectives of this Study were to assess the number of recent admissions to hospital Clue to ADEs and to assess the degree of

  17. Effect of the surfactant on the availability of piroxicam as a poorly hydrosoluble drug from suppositories.

    Science.gov (United States)

    Dal Zorro, M; Franceschinis, E; Punchina, A; Realdon, N

    2012-01-01

    The use of surfactants in suppository formulations has been suggested to improve availability of poorly soluble drugs. In the present study, different kinds of surfactants have been investigated to clarify the influence on piroxicam release from suppositories formulated with both lipophilic and hydrophilic bases. Two hydrophilic glucose-derivate surfactants, and a polyoxylglyceride amphiphilic surfactant, all with high HLB values, were investigated for their use in improving drug availability. The two glucose derivate surfactants reduced drug availability from both lipophilic suppositories and hydrophilic formulations, according to longer disintegration times and drug micellization. The more complex surfactant, a lauroyl macrogolglyceride, showed an increase in piroxicam availability from lipophilic suppositories at the higher tested concentrations (15% and 20%). Otherwise, when used in hydrophilic formulations, it was less effective in promoting drug release and even reduced drug availability.

  18. Drug-releasing shape-memory polymers - the role of morphology, processing effects, and matrix degradation.

    Science.gov (United States)

    Wischke, Christian; Behl, Marc; Lendlein, Andreas

    2013-09-01

    Shape-memory polymers (SMPs) have gained interest for temporary drug-release systems that should be anchored in the body by self-sufficient active movements of the polymeric matrix. Based on the so far published scientific literature, this review highlights three aspects that require particular attention when combining SMPs with drug molecules: i) the defined polymer morphology as required for the shape-memory function, ii) the strong effects that processing conditions such as drug-loading methodologies can have on the drug-release pattern from SMPs, and iii) the independent control of drug release and degradation by their timely separation. The combination of SMPs with a drug-release functionality leads to multifunctional carriers that are an interesting technology for pharmaceutical sciences and can be further expanded by new materials such as thermoplastic SMPs or temperature-memory polymers. Experimental studies should include relevant molecules as (model) drugs and provide a thermomechanical characterization also in an aqueous environment, report on the potential effect of drug type and loading levels on the shape-memory functionality, and explore the potential correlation of polymer degradation and drug release.

  19. Metabolomics to unveil and understand phenotypic diversity between pathogen populations.

    Directory of Open Access Journals (Sweden)

    Ruben t'Kindt

    Full Text Available Leishmaniasis is a debilitating disease caused by the parasite Leishmania. There is extensive clinical polymorphism, including variable responsiveness to treatment. We study Leishmania donovani parasites isolated from visceral leishmaniasis patients in Nepal that responded differently to antimonial treatment due to differing intrinsic drug sensitivity of the parasites. Here, we present a proof-of-principle study in which we applied a metabolomics pipeline specifically developed for L. donovani to characterize the global metabolic differences between antimonial-sensitive and antimonial-resistant L. donovani isolates. Clones of drug-sensitive and drug-resistant parasite isolates from clinical samples were cultured in vitro and harvested for metabolomics analysis. The relative abundance of 340 metabolites was determined by ZIC-HILIC chromatography coupled to LTQ-Orbitrap mass spectrometry. Our measurements cover approximately 20% of the predicted core metabolome of Leishmania and additionally detected a large number of lipids. Drug-sensitive and drug-resistant parasites showed distinct metabolic profiles, and unsupervised clustering and principal component analysis clearly distinguished the two phenotypes. For 100 metabolites, the detected intensity differed more than three-fold between the 2 phenotypes. Many of these were in specific areas of lipid metabolism, suggesting that the membrane composition of the drug-resistant parasites is extensively modified. Untargeted metabolomics has been applied on clinical Leishmania isolates to uncover major metabolic differences between drug-sensitive and drug-resistant isolates. The identified major differences provide novel insights into the mechanisms involved in resistance to antimonial drugs, and facilitate investigations using targeted approaches to unravel the key changes mediating drug resistance.

  20. TERATOGENIC EFFECTS OF DRUGS ON THE ORGANISM OF A FUTURE CHILD DURING FETAL STAGE OF DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    S.A. Sher

    2011-01-01

    Full Text Available Article assesses the impact of adverse factors on intrauterine development of the child, first of all, drugs. The author stresses that the importance of drug safety (D is due to the large number of unintended pregnancies worldwide. A list of the D, providing proven teratogenic effects on a child organism is presenting. It is shown that the D teratogenic effect in humans can not be assessed on the basis of experimental data obtained in animals due to the difference between metabolic and detoxification processes in a different mammals and individuals. Key words: drugs, safety, teratogenic effects, fetal development, the unborn child. (Pediatric pharmacology. — 2011; 8 (6: 57–60.

  1. The Effect of Digestion and Drug Load on Halofantrine Absorption from Self-nanoemulsifying Drug Delivery System (SNEDDS)

    DEFF Research Database (Denmark)

    Michaelsen, Maria Hotoft; Wasan, Kishor M.; Sivak, Olena

    2016-01-01

    A super-saturated self-nanoemulsifying drug delivery system (super-SNEDDS), containing the poorly water-soluble drug halofantrine (Hf) at 150% of equilibrium solubility (Seq), was compared in vitro and in vivo with a conventional SNEDDS (75% of Seq) with respect to bioavailability and digestibility....... Further, the effect of digestion on oral absorption of Hf from SNEDDS and super-SNEDDS was assessed by incorporation of the lipase inhibitor tetrahydrolipstatin (orlistat) into the SNEDDS. The SNEDDS contained soybean oil/Maisine 34-I (1:1), Kolliphor RH40, and ethanol at a ratio of 55:35:10, w/w percent....... For the dynamic in vitro lipolysis, the precipitation of Hf at 60 min was significantly larger for the super-SNEDDS (66.8 ± 16.4%) than for the SNEDDS (18.5 ± 9.2%). The inhibition of the in vitro digestion by orlistat (1% (w/w)) lowered drug precipitation significantly for both the super-SNEDDS (36.8 ± 1...

  2. Reduced Effectiveness of Interruptive Drug-Drug Interaction Alerts after Conversion to a Commercial Electronic Health Record.

    Science.gov (United States)

    Wright, Adam; Aaron, Skye; Seger, Diane L; Samal, Lipika; Schiff, Gordon D; Bates, David W

    2018-05-15

    Drug-drug interaction (DDI) alerts in electronic health records (EHRs) can help prevent adverse drug events, but such alerts are frequently overridden, raising concerns about their clinical usefulness and contribution to alert fatigue. To study the effect of conversion to a commercial EHR on DDI alert and acceptance rates. Two before-and-after studies. 3277 clinicians who received a DDI alert in the outpatient setting. Introduction of a new, commercial EHR and subsequent adjustment of DDI alerting criteria. Alert burden and proportion of alerts accepted. Overall interruptive DDI alert burden increased by a factor of 6 from the legacy EHR to the commercial EHR. The acceptance rate for the most severe alerts fell from 100 to 8.4%, and from 29.3 to 7.5% for medium severity alerts (P fell by 50.5%, and acceptance of Tier 1 alerts rose from 9.1 to 12.7% (P < 0.01). Changing from a highly tailored DDI alerting system to a more general one as part of an EHR conversion decreased acceptance of DDI alerts and increased alert burden on users. The decrease in acceptance rates cannot be fully explained by differences in the clinical knowledge base, nor can it be fully explained by alert fatigue associated with increased alert burden. Instead, workflow factors probably predominate, including timing of alerts in the prescribing process, lack of differentiation of more and less severe alerts, and features of how users interact with alerts.

  3. Evidence behind FDA alerts for drugs with adverse cardiovascular effects: implications for clinical practice.

    Science.gov (United States)

    Rackham, Daniel M; C Herink, Megan; Stevens, Ian G; Cardoza, Natalie M; Singh, Harleen

    2014-01-01

    The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety Communications and Drug Alerts notifying health care practitioners and the general public of important information regarding drug therapies following FDA approval. These alerts can result in both positive and negative effects on patient care. Most clinical trials are not designed to detect long-term safety end points, and postmarketing surveillance along with patient reported events are often instrumental in signaling the potential harmful effect of a drug. Recently, many cardiovascular (CV) safety announcements have been released for FDA-approved drugs. Because a premature warning could discourage a much needed treatment or prompt a sudden discontinuation, it is essential to evaluate the evidence supporting these FDA alerts to provide effective patient care and to avoid unwarranted changes in therapy. Conversely, paying attention to these warnings in cases involving high-risk patients can prevent adverse effects and litigation. This article reviews the evidence behind recent FDA alerts for drugs with adverse CV effects and discusses the clinical practice implications. © 2013 Pharmacotherapy Publications, Inc.

  4. Off-target effects of psychoactive drugs revealed by genome-wide assays in yeast.

    Directory of Open Access Journals (Sweden)

    Elke Ericson

    2008-08-01

    Full Text Available To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system. Because the known human targets of these drugs do not exist in yeast, we could employ the yeast gene deletion collections and parallel fitness profiling to explore potential off-target effects in a genome-wide manner. Among 214 tested, documented psychoactive drugs, we identified 81 compounds that inhibited wild-type yeast growth and were thus selected for genome-wide fitness profiling. Many of these drugs had a propensity to affect multiple cellular functions. The sensitivity profiles of half of the analyzed drugs were enriched for core cellular processes such as secretion, protein folding, RNA processing, and chromatin structure. Interestingly, fluoxetine (Prozac interfered with establishment of cell polarity, cyproheptadine (Periactin targeted essential genes with chromatin-remodeling roles, while paroxetine (Paxil interfered with essential RNA metabolism genes, suggesting potential secondary drug targets. We also found that the more recently developed atypical antipsychotic clozapine (Clozaril had no fewer off-target effects in yeast than the typical antipsychotics haloperidol (Haldol and pimozide (Orap. Our results suggest that model organism pharmacogenetic studies provide a rational foundation for understanding the off-target effects of clinically important psychoactive agents and suggest a rational means both for devising compound derivatives with fewer side effects and for tailoring drug treatment to individual patient genotypes.

  5. Cost-effectiveness analysis of introducing malaria diagnostic testing in drug shops

    DEFF Research Database (Denmark)

    Hansen, Kristian Schultz; Clarke, Siân E.; Lal, Sham

    2017-01-01

    Background Private sector drug shops are an important source of malaria treatment in Africa, yet diagnosis without parasitological testing is common among these providers. Accurate rapid diagnostic tests for malaria (mRDTs) require limited training and present an opportunity to increase access...... to correct diagnosis. The present study was a cost-effectiveness analysis of the introduction of mRDTs in Ugandan drug shops. Methods Drug shop vendors were trained to perform and sell subsidised mRDTs and artemisinin-based combination therapies (ACTs) in the intervention arm while vendors offered ACTs...... following presumptive diagnosis of malaria in the control arm. The effect on the proportion of customers with fever ‘appropriately treated of malaria with ACT’ was captured during a randomised trial in drug shops in Mukono District, Uganda. Health sector costs included: training of drug shop vendors...

  6. Unveiling the development of intracranial injury using dynamic brain EIT: an evaluation of current reconstruction algorithms.

    Science.gov (United States)

    Li, Haoting; Chen, Rongqing; Xu, Canhua; Liu, Benyuan; Tang, Mengxing; Yang, Lin; Dong, Xiuzhen; Fu, Feng

    2017-08-21

    Dynamic brain electrical impedance tomography (EIT) is a promising technique for continuously monitoring the development of cerebral injury. While there are many reconstruction algorithms available for brain EIT, there is still a lack of study to compare their performance in the context of dynamic brain monitoring. To address this problem, we develop a framework for evaluating different current algorithms with their ability to correctly identify small intracranial conductivity changes. Firstly, a simulation 3D head phantom with realistic layered structure and impedance distribution is developed. Next several reconstructing algorithms, such as back projection (BP), damped least-square (DLS), Bayesian, split Bregman (SB) and GREIT are introduced. We investigate their temporal response, noise performance, location and shape error with respect to different noise levels on the simulation phantom. The results show that the SB algorithm demonstrates superior performance in reducing image error. To further improve the location accuracy, we optimize SB by incorporating the brain structure-based conductivity distribution priors, in which differences of the conductivities between different brain tissues and the inhomogeneous conductivity distribution of the skull are considered. We compare this novel algorithm (called SB-IBCD) with SB and DLS using anatomically correct head shaped phantoms with spatial varying skull conductivity. Main results and Significance: The results showed that SB-IBCD is the most effective in unveiling small intracranial conductivity changes, where it can reduce the image error by an average of 30.0% compared to DLS.

  7. Mechanistic models enable the rational use of in vitro drug-target binding kinetics for better drug effects in patients.

    NARCIS (Netherlands)

    Witte, W.E.; Wong, Y.C.; Nederpelt, I.; Heitman, L.H.; Danhof, M.; Graaf, van der P.H.; Gilissen, R.A.; de, Lange E.C.

    2016-01-01

    INTRODUCTION Drug-target binding kinetics are major determinants of the time course of drug action for several drugs, as clearly described for the irreversible binders omeprazole and aspirin. This supports the increasing interest to incorporate newly developed high-throughput assays for drug-target

  8. Elite athletes' estimates of the prevalence of illicit drug use: evidence for the false consensus effect.

    Science.gov (United States)

    Dunn, Matthew; Thomas, Johanna O; Swift, Wendy; Burns, Lucinda

    2012-01-01

    The false consensus effect (FCE) is the tendency for people to assume that others share their attitudes and behaviours to a greater extent than they actually do. The FCE has been demonstrated for a range of health behaviours, including substance use. The study aimed to explore the relationship between elite athlete's engagement in recreational drug use and their consensus estimates (the FCE) and to determine whether those who engage in the behaviour overestimate the use of others around them. The FCE was investigated among 974 elite Australian athletes who were classified according to their drug use history. Participants tended to report that there was a higher prevalence of drug use among athletes in general compared with athletes in their sport, and these estimates appeared to be influenced by participants' drug use history. While overestimation of drug use by participants was not common, this overestimation also appeared to be influenced by athletes' drug use history. The results suggest that athletes who have a history of illicit drug use overestimate the prevalence of drug use among athletes. These findings may be helpful in the formulation of normative education initiatives. © 2011 Australasian Professional Society on Alcohol and other Drugs.

  9. Psychomotor developmental effects of prenatal exposure to psychotropic drugs: a study in EFEMERIS database.

    Science.gov (United States)

    Hurault-Delarue, Caroline; Damase-Michel, Christine; Finotto, Laurent; Guitard, Claudine; Vayssière, Christophe; Montastruc, Jean-Louis; Montastruc, François; Lacroix, Isabelle

    2016-10-01

    Little is known about neurodevelopment of children exposed to psychotropic drugs during pregnancy. The purpose of this study was to evaluate the effects of prenatal exposure to psychotropic drugs on psychomotor development in children. This observational study used the EFEMERIS database. The database records the drugs prescribed and delivered during pregnancy and the resulting outcomes. Neurodevelopment at nine and 24 months of children born to women exposed to psychotropic drugs (anxiolytics, antidepressants, neuroleptics and anti-epileptics) during the second and/or third trimesters of pregnancy was compared to children who were not exposed to these drugs. Psychomotor development of 493 children (1.5%) exposed to psychotropic drugs during pregnancy was compared to 32 303 unexposed children. Exposure to psychotropic drugs during pregnancy was associated with an increased risk of abnormal motor development at 9 months (OR = 1.3 [1.1-2.2]) and abnormal motor and mental development at 24 months (OR = 4.8 [2.1-11.0] and OR = 2.3 [1.05-4.9]). Increased risk was observed in children born to women exposed to anti-epileptic drugs, neuroleptics or antidepressants during pregnancy. This study found a higher rate of deviation from the normal developmental milestones in children born to women exposed to psychotropic drugs during pregnancy and more particularly antidepressants, neuroleptics and anti-epileptics. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  10. Predictive tools for the evaluation of microbial effects on drugs during gastrointestinal passage.

    Science.gov (United States)

    Pieper, Ines A; Bertau, Martin

    2010-06-01

    Predicting drug metabolism after oral administration is highly complex, yet indispensable. Hitherto, drug metabolism mainly focuses on hepatic processes. In the intestine, drug molecules encounter the metabolic activity of microorganisms prior to absorption through the gut wall. Drug biotransformation through the gastrointestinal microflora has the potential to evoke serious problems because the metabolites formed may cause unexpected and undesired side effects in patients. Hence, in the course of drug development, the question has to be addressed if microbially formed metabolites are physiologically active, pharmaceutically active or even toxic. In order to provide answers to these questions and to keep the number of laboratory tests needed low, predictive tools - in vivo as well as in silico - are invaluable. This review gives an outline of the current state of the art in the field of predicting the drug biotransformation through the gastrointestinal microflora on several levels of modelling. A comprehensive review of the literature with a thorough discussion on assets and drawbacks of the different modelling approaches. The impact of the gastrointestinal drug biotransformation on patients' health will grow with increasing complexity of drug entities. Predicting metabolic fates of drugs by combining in vitro and in silico models provides invaluable information which will be suitable to particularly reduce in vivo studies.

  11. Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects

    International Nuclear Information System (INIS)

    Florea, Ana-Maria; Büsselberg, Dietrich

    2011-01-01

    Platinum complexes are clinically used as adjuvant therapy of cancers aiming to induce tumor cell death. Depending on cell type and concentration, cisplatin induces cytotoxicity, e.g., by interference with transcription and/or DNA replication mechanisms. Additionally, cisplatin damages tumors via induction of apoptosis, mediated by the activation of various signal transduction pathways, including calcium signaling, death receptor signaling, and the activation of mitochondrial pathways. Unfortunately, neither cytotoxicity nor apoptosis are exclusively induced in cancer cells, thus, cisplatin might also lead to diverse side-effects such as neuro- and/or renal-toxicity or bone marrow-suppression. Moreover, the binding of cisplatin to proteins and enzymes may modulate its biochemical mechanism of action. While a combination-chemotherapy with cisplatin is a cornerstone for the treatment of multiple cancers, the challenge is that cancer cells could become cisplatin-resistant. Numerous mechanisms of cisplatin resistance were described including changes in cellular uptake, drug efflux, increased detoxification, inhibition of apoptosis and increased DNA repair. To minimize cisplatin resistance, combinatorial therapies were developed and have proven more effective to defeat cancers. Thus, understanding of the biochemical mechanisms triggered by cisplatin in tumor cells may lead to the design of more efficient platinum derivates (or other drugs) and might provide new therapeutic strategies and reduce side effects

  12. Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects

    Energy Technology Data Exchange (ETDEWEB)

    Florea, Ana-Maria [Department of Neuropathology, Heinrich-Heine University, Düsseldorf (Germany); Büsselberg, Dietrich, E-mail: dib2015@qatar-med.cornell.edu [Weil Cornell Medical College in Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha (Qatar)

    2011-03-15

    Platinum complexes are clinically used as adjuvant therapy of cancers aiming to induce tumor cell death. Depending on cell type and concentration, cisplatin induces cytotoxicity, e.g., by interference with transcription and/or DNA replication mechanisms. Additionally, cisplatin damages tumors via induction of apoptosis, mediated by the activation of various signal transduction pathways, including calcium signaling, death receptor signaling, and the activation of mitochondrial pathways. Unfortunately, neither cytotoxicity nor apoptosis are exclusively induced in cancer cells, thus, cisplatin might also lead to diverse side-effects such as neuro- and/or renal-toxicity or bone marrow-suppression. Moreover, the binding of cisplatin to proteins and enzymes may modulate its biochemical mechanism of action. While a combination-chemotherapy with cisplatin is a cornerstone for the treatment of multiple cancers, the challenge is that cancer cells could become cisplatin-resistant. Numerous mechanisms of cisplatin resistance were described including changes in cellular uptake, drug efflux, increased detoxification, inhibition of apoptosis and increased DNA repair. To minimize cisplatin resistance, combinatorial therapies were developed and have proven more effective to defeat cancers. Thus, understanding of the biochemical mechanisms triggered by cisplatin in tumor cells may lead to the design of more efficient platinum derivates (or other drugs) and might provide new therapeutic strategies and reduce side effects.

  13. The cost-effectiveness of direct-to-consumer advertising for prescription drugs.

    Science.gov (United States)

    Atherly, Adam; Rubin, Paul H

    2009-12-01

    In this paper we use published information to analyze the economic value of Direct to Consumer Advertising (DTCA). The reviewed research finds that DTCA leads to increased demand for the advertised drug and that the effect of the drug tends to be class-wide rather than product specific. There is weak evidence that DTCA may increase compliance and improve clinical outcomes. However, there is little research on the effect of DTCA on inappropriate prescribing or on the characteristics of patients who respond to treatment. On net, if the advertised drugs are cost effective on average and the patients using the drugs in response to the advertisement are similar to other users, DTCA is likely cost effective. Overall, the literature to date is consistent with the idea that DTCA is beneficial, but further research is needed before definitive conclusions can be drawn.

  14. Australian governments' spending on preventing and responding to drug abuse should target the main sources of drug-related harm and the most cost-effective interventions.

    Science.gov (United States)

    McDonald, David

    2011-01-01

    A notable feature of Australian drug policy is the limited public and professional attention given to the financial costs of drug abuse and to the levels and patterns of government expenditures incurred in preventing and responding to this. Since 1991, Collins and Lapsley have published scholarly reports documenting the social costs of drug abuse in Australia and their reports also contain estimates of governments' drug budgets: revenue and expenditures. They show that, in 2004-2005, Australian governments expended at least $5288 million on drug abuse, with 50% of the expenditure directed to preventing and dealing with alcohol-related problems, 45% to illicit drugs and just 5% to tobacco. Some 60% of the expenditure was directed at drug crime and 37% at health interventions. This pattern of resource allocation does not adequately reflect an evidence-informed policy orientation in that it largely fails to focus on the drug types that are the sources of the most harm (tobacco and alcohol rather than illicit drugs), and the sectors for which we have the strongest evidence of the cost-effectiveness of the available interventions (treatment and harm reduction rather than legislation and law enforcement). The 2010-2014 phase of Australia's National Drug Strategy should include incremental changes to the resource allocation mix, and not simply maintain the historical resource allocation formulae. © 2010 Australasian Professional Society on Alcohol and other Drugs.

  15. Effectiveness of mindfulness-based stress reduction in drug relapse prevention

    Directory of Open Access Journals (Sweden)

    Ali Hamedi

    2014-02-01

    Full Text Available Objective: The present study was designed to investigate the effectiveness of mindfulness in the prevention of relapse in drug abusers. Method: Using a quasi experimental design, 90 male drug abusers who had undergone detoxification were selected from among all detoxified individuals referred to drug rehabilitation centers in the City of Tehran. Patients were placed randomly in three groups: Mindfulness training intervention, behavioral drug reduction counseling and a control group in which no intervention was applied. Diagnosis of drug abuse was made using structured clinical interview for diagnosing axis I disorders on DSMIV (SCID-I as well as tests to measure morphine levels in the blood. Fisher test was used to compare groups. Patients were assessed two weeks and two months after the intervention as follow up measure. Findings: Results show that both intervention groups were effective in preventing relapse as compared to the control group. Furthermore, the effectiveness of mindfulness training and BDRC was about the same. There were no significant differences between patients with and without experience of drug abuse and married and single patients. Conclusion: Both mindfulness training and BDRC may be considered effective practical methods in reducing the risk of relapse in male drug abusers.

  16. Effect of heterogeneous microvasculature distribution on drug delivery to solid tumour

    International Nuclear Information System (INIS)

    Zhan, Wenbo; Xu, Xiao Yun; Gedroyc, Wladyslaw

    2014-01-01

    Most of the computational models of drug transport in vascular tumours assume a uniform distribution of blood vessels through which anti-cancer drugs are delivered. However, it is well known that solid tumours are characterized by dilated microvasculature with non-uniform diameters and irregular branching patterns. In this study, the effect of heterogeneous vasculature on drug transport and uptake is investigated by means of mathematical modelling of the key physical and biochemical processes in drug delivery. An anatomically realistic tumour model accounting for heterogeneous distribution of blood vessels is reconstructed based on magnetic resonance images of a liver tumour. Numerical simulations are performed for different drug delivery modes, including direct continuous infusion and thermosensitive liposome-mediated delivery, and the anti-cancer effectiveness is evaluated through changes in tumour cell density based on predicted intracellular concentrations. Comparisons are made between regions of different vascular density, and between the two drug delivery modes. Our numerical results show that both extra- and intra-cellular concentrations in the liver tumour are non-uniform owing to the heterogeneous distribution of tumour vasculature. Drugs accumulate faster in well-vascularized regions, where they are also cleared out more quickly, resulting in less effective tumour cell killing in these regions. Compared with direct continuous infusion, the influence of heterogeneous vasculature on anti-cancer effectiveness is more pronounced for thermosensitive liposome-mediated delivery. (paper)

  17. Effect of wide spectrum anti-helminthic drugs upon Schistosoma mansoni experimentally infected mice

    Directory of Open Access Journals (Sweden)

    PANCERA Christiane Finardi

    1997-01-01

    Full Text Available Mebendazole, albendazole, levamisole and thiabendazole are well known as active drugs against several nematode species, and against cestodes as well, when the first two drugs are considered. None of the drugs have proven activity, however, against trematodes. We tested the effect of these drugs on the fecal shedding of schistosome eggs and the recovering of adult schistosomes, after portal perfusion in Schistosoma mansoni experimentally infected mice. Balb/c mice infected with 80 S. mansoni cercariae were divided into three groups, each in turn subdivided into four other groups, for each tested drug. The first group was treated with each one of the studied drugs 25 days after S. mansoni infection; the second group was submitted to treatment with each one of the drugs 60 days after infection. Finally, the third group, considered as control, received no treatment. No effect upon fecal shedding of S. mansoni eggs and recovering of schistosomes after portal perfusion was observed when mice were treated with either mebendazole or albendazole. Mice treated with either levamisole or thiabendazole, on the other hand, showed a significant reduction in the recovering of adult schistosomes after portal perfusion, mainly when both drugs were given during the schistosomula evolution period, i.e., 25 days after cercariae penetration, probably due to unspecific immunomodulation

  18. A review of illicit psychoactive drug use in elective surgery patients: Detection, effects, and policy.

    Science.gov (United States)

    Selvaggi, Gennaro; Spagnolo, Antonio G; Elander, Anna

    2017-12-01

    Limited information is present in literature regarding detection of illicit drug users visiting physicians when planning elective surgery; also, there is no update manuscript that is illustrating the effects of illicit drugs use that require reconstructive surgery interventions. Aims of this manuscript are: 1) to summarize existing knowledge, and give surgeons information how to detect patients who might possible use illicit drugs; 2) to review the effects of illicit drug use that specifically require reconstructive surgery interventions; 3) to assess on existing policies on asymptomatic illicit drug users when planning elective surgery. Studies were identified by searching systematically in the electronic databases PubMed, Medline, The Cochrane Library and SveMed+. Because of the nature of research questions to be investigated (drug policy and surgery), a "systematic review" was not possible. In spite of some existing policies to detect illicit drug use in specific situations such as workplaces or acute trauma patients, there is a lack of data and lack of information, and subsequently no policy has ever been made, for detection and management of illicit drug use asymptomatic patients requesting or referred for plastic surgery interventions. This manuscript poses questions for further ethical evaluations and future policy. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  19. Effect of electron beam irradiation on bacterial cellulose membranes used as transdermal drug delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Stoica-Guzun, Anicuta [Department of Chemical Engineering, ' Politehnica' University Bucharest, 313 Splaiul Independentei, 060042 Bucharest (Romania)], E-mail: astoica@mt.pub.ro; Stroescu, Marta; Tache, Florin [Department of Chemical Engineering, ' Politehnica' University Bucharest, 313 Splaiul Independentei, 060042 Bucharest (Romania); Zaharescu, Traian [Advanced Research Institute for Electrical Engineering, 313 Splaiul Unirii, 030138 Bucharest (Romania)], E-mail: zaharescut@icpe-ca.ro; Grosu, Elena [Department of Chemical Engineering, ' Politehnica' University Bucharest, 313 Splaiul Independentei, 060042 Bucharest (Romania)

    2007-12-15

    Ionizing radiation is an effective energetic source for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. In this work, gamma rays have been applied to induce changes in bacterial cellulose membranes. Permeation of drug (tetracycline) was theoretically and experimentally investigated starting from the effect of {gamma}-irradiation on membranes permeability. Release and permeation of drug from irradiated and non-irradiated membranes have been performed using a diffusion cell.

  20. Effect of electron beam irradiation on bacterial cellulose membranes used as transdermal drug delivery systems

    International Nuclear Information System (INIS)

    Stoica-Guzun, Anicuta; Stroescu, Marta; Tache, Florin; Zaharescu, Traian; Grosu, Elena

    2007-01-01

    Ionizing radiation is an effective energetic source for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. In this work, gamma rays have been applied to induce changes in bacterial cellulose membranes. Permeation of drug (tetracycline) was theoretically and experimentally investigated starting from the effect of γ-irradiation on membranes permeability. Release and permeation of drug from irradiated and non-irradiated membranes have been performed using a diffusion cell

  1. Effect of electron beam irradiation on bacterial cellulose membranes used as transdermal drug delivery systems

    Science.gov (United States)

    Stoica-Guzun, Anicuta; Stroescu, Marta; Tache, Florin; Zaharescu, Traian; Grosu, Elena

    2007-12-01

    Ionizing radiation is an effective energetic source for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. In this work, gamma rays have been applied to induce changes in bacterial cellulose membranes. Permeation of drug (tetracycline) was theoretically and experimentally investigated starting from the effect of γ-irradiation on membranes permeability. Release and permeation of drug from irradiated and non-irradiated membranes have been performed using a diffusion cell.

  2. Using a 3-d model system to screen for drugs effective on solid tumors

    OpenAIRE

    Fayad, Walid

    2011-01-01

    There is a large medical need for the development of effective anticancer agents with minimal side effects. The present thesis represents an attempt to identify potent drugs for treatment of solid tumors. We used a strategy where 3-D multicellular tumor spheroids (cancer cells grown in three dimensional culture) were utilized as in vitro models for solid tumors. Drug libraries were screened using spheroids as targets and using apoptosis induction and loss of cell viability as endpoints. The h...

  3. Drug side effect extraction from clinical narratives of psychiatry and psychology patients.

    Science.gov (United States)

    Sohn, Sunghwan; Kocher, Jean-Pierre A; Chute, Christopher G; Savova, Guergana K

    2011-12-01

    To extract physician-asserted drug side effects from electronic medical record clinical narratives. Pattern matching rules were manually developed through examining keywords and expression patterns of side effects to discover an individual side effect and causative drug relationship. A combination of machine learning (C4.5) using side effect keyword features and pattern matching rules was used to extract sentences that contain side effect and causative drug pairs, enabling the system to discover most side effect occurrences. Our system was implemented as a module within the clinical Text Analysis and Knowledge Extraction System. The system was tested in the domain of psychiatry and psychology. The rule-based system extracting side effects and causative drugs produced an F score of 0.80 (0.55 excluding allergy section). The hybrid system identifying side effect sentences had an F score of 0.75 (0.56 excluding allergy section) but covered more side effect and causative drug pairs than individual side effect extraction. The rule-based system was able to identify most side effects expressed by clear indication words. More sophisticated semantic processing is required to handle complex side effect descriptions in the narrative. We demonstrated that our system can be trained to identify sentences with complex side effect descriptions that can be submitted to a human expert for further abstraction. Our system was able to extract most physician-asserted drug side effects. It can be used in either an automated mode for side effect extraction or semi-automated mode to identify side effect sentences that can significantly simplify abstraction by a human expert.

  4. Combining automatic table classification and relationship extraction in extracting anticancer drug-side effect pairs from full-text articles.

    Science.gov (United States)

    Xu, Rong; Wang, QuanQiu

    2015-02-01

    Anticancer drug-associated side effect knowledge often exists in multiple heterogeneous and complementary data sources. A comprehensive anticancer drug-side effect (drug-SE) relationship knowledge base is important for computation-based drug target discovery, drug toxicity predication and drug repositioning. In this study, we present a two-step approach by combining table classification and relationship extraction to extract drug-SE pairs from a large number of high-profile oncological full-text articles. The data consists of 31,255 tables downloaded from the Journal of Oncology (JCO). We first trained a statistical classifier to classify tables into SE-related and -unrelated categories. We then extracted drug-SE pairs from SE-related tables. We compared drug side effect knowledge extracted from JCO tables to that derived from FDA drug labels. Finally, we systematically analyzed relationships between anti-cancer drug-associated side effects and drug-associated gene targets, metabolism genes, and disease indications. The statistical table classifier is effective in classifying tables into SE-related and -unrelated (precision: 0.711; recall: 0.941; F1: 0.810). We extracted a total of 26,918 drug-SE pairs from SE-related tables with a precision of 0.605, a recall of 0.460, and a F1 of 0.520. Drug-SE pairs extracted from JCO tables is largely complementary to those derived from FDA drug labels; as many as 84.7% of the pairs extracted from JCO tables have not been included a side effect database constructed from FDA drug labels. Side effects associated with anticancer drugs positively correlate with drug target genes, drug metabolism genes, and disease indications. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. “On-Target” Cardiac Effects of Anticancer Drugs

    Science.gov (United States)

    Simons, Michael; Eichmann, Anne

    2014-01-01

    The development of new biological therapeutics such as neutralizing antibodies and small molecule inhibitors of receptors signaling is revolutionizing many fields of medicine—and creating new insights into normal biology. In particular, inhibition of blood vessel growth has been vigorously pursued in a number of fields, including oncology and ophthalmology. To date, most experience with this class of drugs centers on anti-vascular endothelial growth factor (VEGF) agents such as a neutralizing antibody bevacizumab and small molecule inhibitors of VEGF receptor-2 (VEGFR2). Anti-VEGF therapies have been spectacularly successful for treatment of macular degeneration, and somewhat less so in the treatment of cancer. Hand in hand with these advances is the emergence of new cardiac illnesses directly related to the activity of these agents. PMID:22703925

  6. Legal Drugs Are Good Drugs and Illegal Drugs Are Bad Drugs

    OpenAIRE

    Indrati, Dina; Prasetyo, Herry

    2011-01-01

    ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing s...

  7. Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; policies, requirements, and administrative procedures; delay of effective date. Final rule; delay of effective date.

    Science.gov (United States)

    2004-02-23

    The Food and Drug Administration (FDA) is further delaying, until December 1, 2006, the effective date of certain requirements of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720). In the Federal Register of May 3, 2000 (65 FR 25639), the agency delayed until October 1, 2001, the effective date of certain requirements in the final rule relating to wholesale distribution of prescription drugs by distributors that are not authorized distributors of record, and distribution of blood derivatives by entities that meet the definition of a "health care entity" in the final rule. The agency further delayed the effective date of these requirements in three subsequent Federal Register notices. Most recently, in the Federal Register of January 31, 2003 (68 FR 4912), FDA delayed the effective date until April 1, 2004. This action further delays the effective date of these requirements until December 1, 2006. The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA), and the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). The agency is taking this action to address concerns about the requirements in the final rule raised by affected parties. As explained in the SUPPLEMENTARY INFORMATION section, FDA is working with stakeholders through its counterfeit drug initiative to facilitate widespread, voluntary adoption of track and trace technologies that will generate a de facto electronic pedigree, including prior transaction history back to the original manufacturer, as a routine course of business. If this technology is widely adopted, it is expected to help fulfill the pedigree requirements of the PDMA and obviate or resolve many of the concerns that have been raised with respect to the final rule by ensuring that an electronic pedigree travels with a drug product at all times. Therefore, it is necessary to delay the effective date of Sec

  8. Drug repurposing based on drug-drug interaction.

    Science.gov (United States)

    Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

    2015-02-01

    Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

  9. Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis.

    Directory of Open Access Journals (Sweden)

    Kuang-Lin Lin

    Full Text Available Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy.Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed.During the study period, 1038 patients (450 girls, 588 boys were enrolled. Among them, 44.6% (463 had seizures in the acute phase, 33% had status epilepticus, and 26% (251 developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects.Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy.

  10. The effect of depression and side effects of antiepileptic drugs on injuries in patients with epilepsy.

    Science.gov (United States)

    Gur-Ozmen, S; Mula, M; Agrawal, N; Cock, H R; Lozsadi, D; von Oertzen, T J

    2017-09-01

    People with epilepsy are at increased risk of accidents and injuries but, despite several studies on this subject, data regarding preventable causes are still contradictory. The aim of this study was to investigate the relationship between injuries, side effects of antiepileptic drugs (AEDs) and depression. Data from a consecutive sample of adult patients with epilepsy attending the outpatient clinics at St George's University Hospital in London were included. All patients were asked if they had had any injury since the last clinic appointment and completed the Liverpool Adverse Event Profile (LAEP) and Neurological Disorders Depression Inventory for Epilepsy. Among 407 patients (243 females, mean age 43.1 years), 71 (17.4%) reported injuries since the last appointment. A two-step cluster analysis revealed two clusters with the major cluster (53.5% of the injured group) showing a total score for LAEP ≥45, a positive Neurological Disorders Depression Inventory for Epilepsy screening and presence of AED polytherapy. A total score for LAEP ≥45 was the most important predictor. Antiepileptic drug treatment should be reviewed in patients reporting injuries in order to evaluate the potential contribution and burden of AED side effects. © 2017 EAN.

  11. ADVERPred-Web Service for Prediction of Adverse Effects of Drugs.

    Science.gov (United States)

    Ivanov, Sergey M; Lagunin, Alexey A; Rudik, Anastasia V; Filimonov, Dmitry A; Poroikov, Vladimir V

    2018-01-22

    Application of structure-activity relationships (SARs) for the prediction of adverse effects of drugs (ADEs) has been reported in many published studies. Training sets for the creation of SAR models are usually based on drug label information which allows for the generation of data sets for many hundreds of drugs. Since many ADEs may not be related to drug consumption, one of the main problems in such studies is the quality of data on drug-ADE pairs obtained from labels. The information on ADEs may be included in three sections of the drug labels: "Boxed warning," "Warnings and Precautions," and "Adverse reactions." The first two sections, especially Boxed warning, usually contain the most frequent and severe ADEs that have either known or probable relationships to drug consumption. Using this information, we have created manually curated data sets for the five most frequent and severe ADEs: myocardial infarction, arrhythmia, cardiac failure, severe hepatotoxicity, and nephrotoxicity, with more than 850 drugs on average for each effect. The corresponding SARs were built with PASS (Prediction of Activity Spectra for Substances) software and had balanced accuracy values of 0.74, 0.7, 0.77, 0.67, and 0.75, respectively. They were implemented in a freely available ADVERPred web service ( http://www.way2drug.com/adverpred/ ), which enables a user to predict five ADEs based on the structural formula of compound. This web service can be applied for estimation of the corresponding ADEs for hits and lead compounds at the early stages of drug discovery.

  12. Drug research methodology. Volume 5, Experimentation in drugs and highway safety : the study of drug effects on skills related to driving

    Science.gov (United States)

    1980-06-01

    This report presents the findings of a workshop on experimental research in the area of drugs and highway safety. Complementing studies of drug use in different driving populations, experimentation here refers to studies performed under controlled co...

  13. Effect of temperature and ph on the drug release rate from a polymer conjugate system

    International Nuclear Information System (INIS)

    Kenawy, E.; Abdel-Hay, F.I.; El-Newehy, M.H.; Ottenbrite, R.M.

    2005-01-01

    Hydroximide and A-methylhydroxamic acid of poly(ethylene-altmaleic anhydride) (average MW 100-500 k) were used as a carrier for a new drug delivery system. The synthesis of the hydroximide and N methylhydroxamic acid of poly(ethylene-alt-maleic anhydride) were carried out by chemical modification of poly(ethylene-alt-maleic anhydride) with hydroxylamine and N-methyl hydroxylamine, respectively, in N,N- dimethylformamide at room temperature to yield water soluble copolymer. Ketoprofen was reacted with hydroximide and N-methylhydroxamic acid derivatives of poly(ethylene-alt-maleic anhydride) using dicyclohexylcarbodiimide as condensation agent at -5 degree C to yield water insoluble ketoprofen conjugates. All products were characterized by elemental analysis, FTIR and 1HNMR spectra. The in-vitro ketoprofen release was carried out by UV spectrophotometer at max =260 nm. The results demonstrated the effectiveness of hydroximide and N-methylhydroxamic acid of polyethylene-alt-maleic anhydride) as a drug delivery system. The release rates were studied at various ph and temperatures. The copolymer-drug adducts released the drug very slowly at the low ph found in the stomach thus protecting the drug from the action of high concentrations of digestive acids. These results showed the usefulness of hydroxamic acid polymer-drug conjugates as a new drug delivery system for drugs to be targeted to sites in the GI system

  14. The Effect of Muscle Dysmorphia and Social Physique Anxiety on the Use of Supplements and Drugs

    Directory of Open Access Journals (Sweden)

    Yadollah Khorramabady

    2017-09-01

    Full Text Available Background The use of dietary supplements and drugs to improve performance and physical appearance has recently increased among professional and recreational ‎athletes. Literature shows that bodybuilders, more than other athletes use supplements and drugs. Objectives This study aims to predict the use of supplements and drugs by muscle dysmorphia and social physique anxiety variables among Hamedan bodybuilders. Methods This cross-sectional investigation was conducted with 438 bodybuilders in Hamedan province. For collecting data, we used a demographic questionnaire, muscle dysmorphia scale, and social ‎physique anxiety scale. Results The results showed that 79.2% of the subjects used supplements, and vitamins (22.1% and protein powders (21.9% had the highest rates of use among supplements. Moreover, 145 subjects (33.1% used drugs, and steroid derivatives (16.2% and peptide hormones and growth factors (12.6% had the highest rates of use among drugs. The results of t-test showed that muscle dysmorphia and social physique anxiety were significantly higher in the subjects who used supplements and drugs than those who did not. Additionally, the results of logistic regression indicated that muscle dysmorphia and social physique anxiety can predict the likelihood of drug abuse. Conclusions The present study provides novel findings of the effect of social physique anxiety and muscle ‎dysmorphia on nutritional supplement and drugs use among bodybuilders. ‎

  15. Nasa Unveils Cosmic Images Book in Braille for Blind Readers

    Science.gov (United States)

    2008-01-01

    BALTIMORE - At a Tuesday ceremony at the National Federation of the Blind, NASA unveiled a new book that brings majestic images taken by its Great Observatories to the fingertips of the blind. "Touch the Invisible Sky" is a 60-page book with color images of nebulae, stars, galaxies and some of the telescopes that captured the original pictures. Each image is embossed with lines, bumps and other textures. These raised patterns translate colors, shapes and other intricate details of the cosmic objects, allowing visually impaired people to experience them. Braille and large-print descriptions accompany each of the book's 28 photographs, making the book's design accessible to readers of all visual abilities. Sample page Sample page The book contains spectacular images from the Hubble Space Telescope, Chandra X-ray Observatory, Spitzer Space Telescope and powerful ground-based telescopes. The celestial objects are presented as they appear through visible-light telescopes and different spectral regions invisible to the naked eye, from radio to infrared, visible, ultraviolet and X-ray light. The book introduces the concept of light and the spectrum and explains how the different observatories complement each others' findings. Readers take a cosmic journey beginning with images of the sun, and travel out into the galaxy to visit relics of exploding and dying stars, as well as the Whirlpool galaxy and colliding Antennae galaxies. People Who Read This Also Read... Chandra Data Reveal Rapidly Whirling Black Holes Jet Power and Black Hole Assortment Revealed in New Chandra Image Action Replay of Powerful Stellar Explosion Black Holes Are The Rhythm at The Heart of Galaxies "Touch the Invisible Sky" was written by astronomy educator and accessibility specialist Noreen Grice of You Can Do Astronomy LLC and the Museum of Science, Boston, with authors Simon Steel, an astronomer with the Harvard-Smithsonian Center for Astrophysics in Cambridge, Mass., and Doris Daou, an astronomer

  16. The role of the seven crude drug components in the sleep-promoting effect of Yokukansan.

    Science.gov (United States)

    Ogawa, Yuko; Fujii, Yuuko; Sugiyama, Reina; Konishi, Tenji

    2016-01-11

    Yokukansan is a traditional Japanese "Kampo" medicine derived from Yi-Gan San in traditional Chinese medicine. Many studies have been published on its effects and mechanisms. In this study, we focused on the sleep-promoting effects of Yokukansan. Yokukansan composes of seven crude drugs: Uncaria Hook, Bupleurm Root, Cnidium Rhizome, Japanese Angelica Root, Poria Sclerotium, Atractylodes Lancea Rhizome, and Glycyrrhiza. Although each has distinctive effects in isolation, they combine to work as a sleep aid in the Yokukansan formula. We examined the roles of the seven crude drug components in the sleep-promoting effect of Yokukansan. In this study, we used an easy in vivo assay method which we developed previously to screen sleeping substances using thermography. This assay method focuses on the decrease in skin temperature of mice during sleep inducement. By administering the crude drug components of Yokukansan one at a time, it was possible to separate them into two groups: those that caused a decrease in body temperature (Uncaria Hook, Bupleurm Root, Cnidium rhizome, and Japanese Angelica root) and those that did not (Poria Sclerotium, Atractylodes Lancea Rhizome, and Glycyrrhiza). Accordingly, it was thought that the crude drugs causing a drop in body temperature were responsible for promoting sleep, while those in the other group would have no such effect in isolation. To investigate whether the crude drugs that did not cause a decrease in body temperature might be unnecessary for the sleep-promoting effect of Yokukansan, a number of decoctions were prepared using only six of the seven crude drug components, excluding a different crude drug in each case. Results showed that when any of the three components (Poria Sclerotium, Atractylodes Lancea Rhizome, or Glycyrrhiza) of Yokukansan that had no effect on body temperature in isolation were removed from Yokukansan, the resulting extract no longer had any of Yokukansan's sleep-promoting effects. This result

  17. Protein microarray: sensitive and effective immunodetection for drug residues

    Directory of Open Access Journals (Sweden)

    Zer Cindy

    2010-02-01

    Full Text Available Abstract Background Veterinary drugs such as clenbuterol (CL and sulfamethazine (SM2 are low molecular weight ( Results The artificial antigens were spotted on microarray slides. Standard concentrations of the compounds were added to compete with the spotted antigens for binding to the antisera to determine the IC50. Our microarray assay showed the IC50 were 39.6 ng/ml for CL and 48.8 ng/ml for SM2, while the traditional competitive indirect-ELISA (ci-ELISA showed the IC50 were 190.7 ng/ml for CL and 156.7 ng/ml for SM2. We further validated the two methods with CL fortified chicken muscle tissues, and the protein microarray assay showed 90% recovery while the ci-ELISA had 76% recovery rate. When tested with CL-fed chicken muscle tissues, the protein microarray assay had higher sensitivity (0.9 ng/g than the ci-ELISA (0.1 ng/g for detection of CL residues. Conclusions The protein microarrays showed 4.5 and 3.5 times lower IC50 than the ci-ELISA detection for CL and SM2, respectively, suggesting that immunodetection of small molecules with protein microarray is a better approach than the traditional ELISA technique.

  18. Dopaminergic Drug Effects on Probability Weighting during Risky Decision Making.

    Science.gov (United States)

    Ojala, Karita E; Janssen, Lieneke K; Hashemi, Mahur M; Timmer, Monique H M; Geurts, Dirk E M; Ter Huurne, Niels P; Cools, Roshan; Sescousse, Guillaume

    2018-01-01

    Dopamine has been associated with risky decision-making, as well as with pathological gambling, a behavioral addiction characterized by excessive risk-taking behavior. However, the specific mechanisms through which dopamine might act to foster risk-taking and pathological gambling remain elusive. Here we test the hypothesis that this might be achieved, in part, via modulation of subjective probability weighting during decision making. Human healthy controls ( n = 21) and pathological gamblers ( n = 16) played a decision-making task involving choices between sure monetary options and risky gambles both in the gain and loss domains. Each participant played the task twice, either under placebo or the dopamine D 2 /D 3 receptor antagonist sulpiride, in a double-blind counterbalanced design. A prospect theory modelling approach was used to estimate subjective probability weighting and sensitivity to monetary outcomes. Consistent with prospect theory, we found that participants presented a distortion in the subjective weighting of probabilities, i.e., they overweighted low probabilities and underweighted moderate to high probabilities, both in the gain and loss domains. Compared with placebo, sulpiride attenuated this distortion in the gain domain. Across drugs, the groups did not differ in their probability weighting, although gamblers consistently underweighted losing probabilities in the placebo condition. Overall, our results reveal that dopamine D 2 /D 3 receptor antagonism modulates the subjective weighting of probabilities in the gain domain, in the direction of more objective, economically rational decision making.

  19. Dopaminergic Drug Effects on Probability Weighting during Risky Decision Making

    Science.gov (United States)

    Timmer, Monique H. M.; ter Huurne, Niels P.

    2018-01-01

    Abstract Dopamine has been associated with risky decision-making, as well as with pathological gambling, a behavioral addiction characterized by excessive risk-taking behavior. However, the specific mechanisms through which dopamine might act to foster risk-taking and pathological gambling remain elusive. Here we test the hypothesis that this might be achieved, in part, via modulation of subjective probability weighting during decision making. Human healthy controls (n = 21) and pathological gamblers (n = 16) played a decision-making task involving choices between sure monetary options and risky gambles both in the gain and loss domains. Each participant played the task twice, either under placebo or the dopamine D2/D3 receptor antagonist sulpiride, in a double-blind counterbalanced design. A prospect theory modelling approach was used to estimate subjective probability weighting and sensitivity to monetary outcomes. Consistent with prospect theory, we found that participants presented a distortion in the subjective weighting of probabilities, i.e., they overweighted low probabilities and underweighted moderate to high probabilities, both in the gain and loss domains. Compared with placebo, sulpiride attenuated this distortion in the gain domain. Across drugs, the groups did not differ in their probability weighting, although gamblers consistently underweighted losing probabilities in the placebo condition. Overall, our results reveal that dopamine D2/D3 receptor antagonism modulates the subjective weighting of probabilities in the gain domain, in the direction of more objective, economically rational decision making. PMID:29632870

  20. Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Soni, Parth; Kaur, Jasmine; Tikoo, Kulbhushan, E-mail: tikoo.k@gmail.com [National Institute of Pharmaceutical Education and Research (NIPER), Laboratory of Epigenetics and Diseases, Department of Pharmacology and Toxicology (India)

    2015-01-15

    The present study highlights the beneficial synergistic blend of anticancer drug paclitaxel (PTX) and thymoquinone (TQ) in MCF-7 breast cancer cells. We aimed to augment the therapeutic index of PTX using a polymeric nanoparticle system loaded with PTX and TQ. PLGA nanoparticles encapsulating the two drugs, individually or in combination, were prepared by single emulsion solvent evaporation method. The formulated nanoparticles were homogenous with an overall negative charge and their size ranging between 200 and 300 nm. Entrapment efficiency of PTX and TQ in the dual drug-loaded nanoparticles was found to be 82.4 ± 2.18 and 65.8 ± 0.45 %, respectively. The release kinetics of PTX and TQ from the nanoparticles exhibited a biphasic pattern characterised by an initial burst, followed by a gradual and continuous release. The anticancer activity of nanoparticles encapsulating both the drugs was higher as compared to the free drugs in MCF-7 breast cancer cells. The combination index for the dual drug-loaded NPs was found to be 0.688 which is indicative of synergistic interaction. Thus, here, we propose the synthesis and use of dual drug-loaded TQ and PTX NPs which exhibits enhanced anticancer activity and can additionally help to alleviate the toxic effects of PTX by lowering its effective dose.

  1. Fractured families: parental perspectives of the effects of adolescent drug abuse on family life.

    Science.gov (United States)

    Jackson, Debra; Usher, Kim; O'Brien, Louise

    Drug use in young people has serious ramifications for health and well-being of young people and their families and continues to be an area of major concern for health workers. Though the task of dealing with drug-related problems falls on families, particularly parents, very little literature has explored parental experiences of managing drug use within the context of family life. Eighteen parents of drug-abusing young people were recruited into this qualitative study that aimed to develop understandings into the effects of adolescent drug use on family life. Findings revealed that the experience of having a drug-abusing adolescent family member had a profound effect on other members of the immediate family. Family relationships were fractured and split as a result of the on-going destructive and damaging behaviour of the drug-abusing young person. Five themes were identified that captured the concept of fractured families. These are: betrayal and loss of trust: 'You had to have the doors locked'; abuse, threats and violence: 'there were holes in the wall'; sibling anger and resentment: 'Better off now with him gone'; isolated, disgraced and humiliated: 'You are on your own with it'; and, feeling blamed: 'You are not a good parent'. Implications for practice and further research are drawn from the findings of this paper.

  2. Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy

    International Nuclear Information System (INIS)

    Soni, Parth; Kaur, Jasmine; Tikoo, Kulbhushan

    2015-01-01

    The present study highlights the beneficial synergistic blend of anticancer drug paclitaxel (PTX) and thymoquinone (TQ) in MCF-7 breast cancer cells. We aimed to augment the therapeutic index of PTX using a polymeric nanoparticle system loaded with PTX and TQ. PLGA nanoparticles encapsulating the two drugs, individually or in combination, were prepared by single emulsion solvent evaporation method. The formulated nanoparticles were homogenous with an overall negative charge and their size ranging between 200 and 300 nm. Entrapment efficiency of PTX and TQ in the dual drug-loaded nanoparticles was found to be 82.4 ± 2.18 and 65.8 ± 0.45 %, respectively. The release kinetics of PTX and TQ from the nanoparticles exhibited a biphasic pattern characterised by an initial burst, followed by a gradual and continuous release. The anticancer activity of nanoparticles encapsulating both the drugs was higher as compared to the free drugs in MCF-7 breast cancer cells. The combination index for the dual drug-loaded NPs was found to be 0.688 which is indicative of synergistic interaction. Thus, here, we propose the synthesis and use of dual drug-loaded TQ and PTX NPs which exhibits enhanced anticancer activity and can additionally help to alleviate the toxic effects of PTX by lowering its effective dose

  3. Machine learning-based prediction of adverse drug effects: An example of seizure-inducing compounds

    Directory of Open Access Journals (Sweden)

    Mengxuan Gao

    2017-02-01

    Full Text Available Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs that induced seizure-like events and identified diphenhydramine, enoxacin, strychnine and theophylline as “seizure-inducing” drugs, which indeed were reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to detect the seizure-inducing side effects of preclinical drugs.

  4. EFFECTS OF PSYCHOTROPIC DRUGS AS BACTERIAL EFFLUX PUMP INHIBITORS ON QUORUM SENSING REGULATED BEHAVIORS

    Directory of Open Access Journals (Sweden)

    Aynur Aybey

    2014-10-01

    Full Text Available Psychotropic drugs are known to have antimicrobial activity against several groups of microorganisms. The antidepressant agents such as duloxetine, paroxetine, hydroxyzine and venlafaxine are shown to act as efflux pump inhibitors in bacterial cells. In order to the investigation of the effects of psychotropic drugs were determined for clinically significant pathogens by using standart broth microdillusion method. The anti-quorum sensing (anti-QS activity of psychotropic drugs was tested against four test pathogens using the agar well diffusion method. All drugs showed strong inhibitory effect on the growth of S. typhimurium. Additionally, quorum sensing-regulated behaviors of Pseudomonas aeruginosa, including swarming, swimming and twitching motility and alkaline protease production were investigated. Most effective drugs on swarming, swimming and twitching motility and alkaline protease production, respectively, were paroxetine and duloxetine; duloxetine; hydroxyzine and venlafaxine; paroxetine and venlafaxine; venlafaxine. Accordingly, psychotropic drugs were shown strongly anti-QS activity by acting as bacterial efflux pump inhibitors and effection on motility and alkaline protease production of P. aeruginosa.

  5. Biological therapies (immunomodulatory drugs), worsening of psoriasis and rebound effect: new evidence of similitude.

    Science.gov (United States)

    Teixeira, Marcus Zulian

    2016-11-01

    Employing the secondary action or adaptative reaction of the organism as therapeutic response, homeopathy uses the treatment by similitude (similia similibus curentur) administering to sick individuals the medicines that caused similar symptoms in healthy individuals. Such homeostatic or paradoxical reaction of the organism is scientifically explained through the rebound effect of drugs, which cause worsening of symptoms after withdrawal of several palliative treatments. Despite promoting an improvement in psoriasis at the beginning of the treatment, modern biological therapies provoke worsening of the psoriasis (rebound psoriasis) after discontinuation of drugs. Exploratory qualitative review of the literature on the occurrence of the rebound effect with the use of immunomodulatory drugs [T-cell modulating agents and tumor necrosis factor (TNF) inhibitors drugs] in the treatment of psoriasis. Several researches indicate the rebound effect as the mechanism of worsening of psoriasis with the use of efalizumab causing the suspension of its marketing authorization in 2009, in view of some severe cases. Other studies also have demonstrated the occurrence of rebound psoriasis with the use of alefacept, etanercept and infliximab. As well as studied in other classes of drugs, the rebound effect of biologic agents supports the principle of similitude (primary action of the drugs followed by secondary action and opposite of the organism). Copyright © 2016 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  6. "It Ruined My Life": The effects of the War on Drugs on people who inject drugs (PWID) in rural Puerto Rico.

    Science.gov (United States)

    Abadie, R; Gelpi-Acosta, C; Davila, C; Rivera, A; Welch-Lazoritz, M; Dombrowski, K

    2018-01-01

    The War on Drugs has raised the incarceration rates of racial minorities for non-violent drug-related crimes, profoundly stigmatized drug users, and redirected resources from drug prevention and treatment to militarizing federal and local law enforcement. Yet, while some states consider shifting their punitive approach to drug use, to one based on drug treatment and rehabilitation, nothing suggests that these policy shifts are being replicated in Puerto Rico. This paper utilizes data from 360 PWID residing in four rural towns in the mountainous area of central Puerto Rico. We initially recruited 315 PWID using respondent-driven sampling (RDS) and collected data about risk practices and conducted HIV and HCV testing. During a second phase, we conducted 34 micro-ethnographic assays, in which we randomly recruited 34 participants from the first phase and included their ego networks in this phase. Our ethnographic inquiry produced significant data regarding the effects of the war on drugs on the local drug trade, drug availability, and injectors' social networks. Findings suggest that repressive policing has been ineffective in preventing drug distribution and use among those in our study. This type of law enforcement approach has resulted in the disproportionate incarceration of poor drug users in rural Puerto Rico, and mainly for nonviolent drug-related crimes. In addition, incarceration exposes PWID to a form of a cruel and unusual punishment: having to quit heroin "cold turkey" while the prison environment also represents a HIV/HCV risk. In turn, the war on drugs not only diverts resources from treatment but also shapes treatment ideologies, punishing non-compliant patients. Shifting the emphasis from repression to treatment and rehabilitation is likely to have a positive impact on the health and overall quality of life of PWID and their communities. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Cost-effectiveness of antiplatelet drugs after percutaneous coronary intervention.

    Science.gov (United States)

    Wisløff, Torbjørn; Atar, Dan

    2016-01-01

    Clopidogrel has, for long time, been accepted as the standard treatment for patients who have undergone a percutaneous coronary intervention (PCI). The introduction of prasugrel-and more recently, ticagrelor-has introduced a decision-making problem for clinicians and governments worldwide: to use the cheaper clopidogrel or the more effective, and also more expensive prasugrel or ticagrelor. We aim to give helpful contributions to this debate by analysing the cost-effectiveness of clopidogrel, prasugrel, and ticagrelor compared with each other. We modified a previously developed Markov model of cardiac disease progression. In the model, we followed up cohorts of patients who have recently had a PCI until 100 years or death. Possible events are revascularization, bleeding, acute myocardial infarction, and death. Our analysis shows that ticagrelor is cost-effective in 77% of simulations at an incremental cost-effectiveness ratio of €7700 compared with clopidogrel. Ticagrelor was also cost-effective against prasugrel at a cost-effectiveness ratio of €7800. Given a Norwegian cost-effectiveness threshold of €70 000, both comparisons appear to be clearly cost-effective in favour of ticagrelor. Ticagrelor is cost-effective compared with both clopidogrel and prasugrel for patients who have undergone a PCI.

  8. Effects of drugs on beta-endorphin and cortisol in smokers

    International Nuclear Information System (INIS)

    Du Tongxin; Wang Zizheng; Wang Shukui

    2001-01-01

    The authors observed the effects of drugs on beta-endorphin and cortisol in smokers and their correlation. The levels of plasma beta-endorphin and cortisol of smokers before and after cigarette withdrawal were detected by radioimmunoassay (RIA). The Levels of plasma beta-endorphin and cortisol in smokers is significantly higher than in controls. After natural withdrawal, the levels of plasma cortisol increased significantly, while beta-endorphin decreased significantly. After drug treatment, the levels of beta-endorphin and cortisol balanced. The drugs may play the role of cigarette withdrawal by improving the secretion of endogenous opium and the axis of hypothalamus-pituitary adrenal

  9. Oral adverse effects of gastrointestinal drugs and considerations for dental management in patients with gastrointestinal disorders

    Directory of Open Access Journals (Sweden)

    Ramya Karthik

    2012-01-01

    Full Text Available Gastrointestinal disease is associated with alterations in the mouth or influence the course of the dental diseases, and the dental health care workers are expected to recognize, diagnose, and treat oral conditions associated with gastrointestinal diseases and also provide safe and appropriate dental care for afflicted individuals. Drugs used in the management of these diseases result in oral adverse effects and also are known to interact with those prescribed during dental care. Hence, this article has reviewed the drug considerations and guidelines for drug use during dental management of patients with gastrointestinal diseases.

  10. The persuasion network is modulated by drug-use risk and predicts anti-drug message effectiveness

    Science.gov (United States)

    Mangus, J Michael; Turner, Benjamin O

    2017-01-01

    Abstract While a persuasion network has been proposed, little is known about how network connections between brain regions contribute to attitude change. Two possible mechanisms have been advanced. One hypothesis predicts that attitude change results from increased connectivity between structures implicated in affective and executive processing in response to increases in argument strength. A second functional perspective suggests that highly arousing messages reduce connectivity between structures implicated in the encoding of sensory information, which disrupts message processing and thereby inhibits attitude change. However, persuasion is a multi-determined construct that results from both message features and audience characteristics. Therefore, persuasive messages should lead to specific functional connectivity patterns among a priori defined structures within the persuasion network. The present study exposed 28 subjects to anti-drug public service announcements where arousal, argument strength, and subject drug-use risk were systematically varied. Psychophysiological interaction analyses provide support for the affective-executive hypothesis but not for the encoding-disruption hypothesis. Secondary analyses show that video-level connectivity patterns among structures within the persuasion network predict audience responses in independent samples (one college-aged, one nationally representative). We propose that persuasion neuroscience research is best advanced by considering network-level effects while accounting for interactions between message features and target audience characteristics. PMID:29140500

  11. The persuasion network is modulated by drug-use risk and predicts anti-drug message effectiveness.

    Science.gov (United States)

    Huskey, Richard; Mangus, J Michael; Turner, Benjamin O; Weber, René

    2017-12-01

    While a persuasion network has been proposed, little is known about how network connections between brain regions contribute to attitude change. Two possible mechanisms have been advanced. One hypothesis predicts that attitude change results from increased connectivity between structures implicated in affective and executive processing in response to increases in argument strength. A second functional perspective suggests that highly arousing messages reduce connectivity between structures implicated in the encoding of sensory information, which disrupts message processing and thereby inhibits attitude change. However, persuasion is a multi-determined construct that results from both message features and audience characteristics. Therefore, persuasive messages should lead to specific functional connectivity patterns among a priori defined structures within the persuasion network. The present study exposed 28 subjects to anti-drug public service announcements where arousal, argument strength, and subject drug-use risk were systematically varied. Psychophysiological interaction analyses provide support for the affective-executive hypothesis but not for the encoding-disruption hypothesis. Secondary analyses show that video-level connectivity patterns among structures within the persuasion network predict audience responses in independent samples (one college-aged, one nationally representative). We propose that persuasion neuroscience research is best advanced by considering network-level effects while accounting for interactions between message features and target audience characteristics. © The Author (2017). Published by Oxford University Press.

  12. 77 FR 69634 - Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food-Producing...

    Science.gov (United States)

    2012-11-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0784] Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food-Producing Animals... Effectiveness of Anticoccidial Drugs in Food-Producing Animals.'' The guidance provides guidance to industry for...

  13. Simulated food effects on drug release from ethylcellulose: PVA-PEG graft copolymer-coated pellets.

    Science.gov (United States)

    Muschert, Susanne; Siepmann, Florence; Leclercq, Bruno; Carlin, Brian; Siepmann, Juergen

    2010-02-01

    Food effects might substantially alter drug release from oral controlled release dosage forms in vivo. The robustness of a novel type of controlled release film coating was investigated using various types of release media and two types of release apparatii. Importantly, none of the investigated conditions had a noteworthy impact on the release of freely water-soluble diltiazem HCl or slightly water-soluble theophylline from pellets coated with ethylcellulose containing small amounts of PVA-PEG graft copolymer. In particular, the presence of significant amounts of fats, carbohydrates, surfactants, bile salts, and calcium ions in the release medium did not alter drug release. Furthermore, changes in the pH and differences in the mechanical stress the dosage forms were exposed to did not affect drug release from the pellets. The investigated film coatings allowing for oral controlled drug delivery are highly robust in vitro and likely to be poorly sensitive to classical food effects in vivo.

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

    African Journals Online (AJOL)

    In 2005 children in Mwea schools were treated with albendazole 400mg and praziquantel. 40mg/kg body ... treatment to three hundred children in one day, which makes the approach cost effective and should be ... sex, and whether they had had headache, fever, cough, .... incase of severe side effects their efficacy may not.

  15. Manual control analysis of drug effects on driving performance

    Science.gov (United States)

    Smiley, A.; Ziedman, K.; Moskowitz, H.

    1981-01-01

    The effects of secobarbital, diazepam, alcohol, and marihuana on car-driver transfer functions obtained using a driving simulator were studied. The first three substances, all CNS depressants, reduced gain, crossover frequency, and coherence which resulted in poorer tracking performance. Marihuana also impaired tracking performance but the only effect on the transfer function parameters was to reduce coherence.

  16. Pharmacodynamic drug interaction study: effect of sertraline on the ...

    African Journals Online (AJOL)

    The effect of sertraline on glibenclamide control of blood sugar level was determined in normoglycemic and alloxanised rats. Sertraline enhance the hypoglycaemic action in a non-dose dependent fashion in the normoglycaemic and alloxanised rats. Sertraline (40mg/Kg body weight) was more effective in the enhancement ...

  17. The cytogenetic effect of the new asthma and allergy drug ...

    African Journals Online (AJOL)

    Montelukast or Singulair has recently been introduced to treat asthma. Because it is apparently free of serious side-effects, the present work aimed to investigate its effects on chromosomes of bone marrow cells of mice. The percentage of structural chromosomal aberrations was highly elevated due to treatment with ...

  18. A strategy to reduce illicit drug use is effective in elite Australian football.

    Science.gov (United States)

    Harcourt, Peter R; Unglik, Harry; Cook, Jill L

    2012-10-01

    The World Anti-Doping Agency (WADA) prescribes that drug testing is conducted in sports competitions to detect drug use in athletes. This testing includes performance-enhancing drugs as well as illicit substances such as marijuana, amphetamines and cocaine. Illicit drugs are tested for on match days but not on non-match days. Some athletes are known to use illicit substances for recreational purposes, away from competition times and this poses a serious health and welfare issue not addressed by the usual sport drug testing regimes. This paper reports the results of the first 7 years of an illicit drug-testing programme that included non-match day testing in the elite Australian Football competition, the Australian Football League (AFL). Players in the AFL were tested for illicit drugs both in-competition and out-of-competition. Players were selected for illicit substance tests either randomly or targeted based on previous test history or time since previous test. The number of tests conducted was increased each year from 2005 to 2011 and testing was focused on high-risk times during non-competition periods. There were no positive match day tests. There was a significant reduction in positive tests (19-6) for illicit drugs during non-competition periods over the 7 years (p<0.0001). The reduction in positive tests may be related to player education, the greater number of tests conducted and the harm minimisation approach of the illicit drug policy. An illicit drugs programme using a harm minimisation strategy can work effectively alongside a sport's WADA compliant Anti-Doping Code.

  19. Effects of maternal psychotropic drug dosage on birth outcomes

    Directory of Open Access Journals (Sweden)

    Michielsen LA

    2013-12-01

    Full Text Available Laura A Michielsen,1 Frank MMA van der Heijden,1 Paddy KC Janssen,2 Harold JH Kuijpers11Vincent van Gogh Institute for Psychiatry, Venlo, the Netherlands; 2Department of Pharmacy, VieCuri Medical Centre, Venlo, the NetherlandsBackground: The aim of this retrospective study was to explore the relationship between psychotropic medication dosage and birth outcomes.Methods: A total of 136 women were enrolled, who had an active mental disorder, were taking medication to prevent a relapse, or had a history of postpartum depression or psychosis. Medication use was evaluated for the three trimesters and during labor. Based on the defined daily dose, medication use was classified into three groups. Primary outcome variables included the infant gestational age at birth, birth weight, and Apgar scores at one and 5 minutes.Results: Our study showed a significantly higher incidence of Apgar score ≤7 at 5 minutes in women taking psychotropic drugs as compared with the group taking no medication, respectively (16.3% versus 0.0%, P=0.01. There was no significant difference between the two groups in Apgar score at one minute or in gestational age and birth weight. The results showed no significant differences in gestational age, birth weight, or Apgar scores for a low–intermediate or high dose of a selective serotonin reuptake inhibitor and for a low or intermediate dose of an antipsychotic.Conclusion: This study does not indicate a relationship between doses of selective serotonin reuptake inhibitors and antipsychotics and adverse neonatal outcomes.Keywords: pregnancy, psychotropic medication, dosage, birth outcomes

  20. Effect of lipid-lowering and anti-hypertensive drugs on plasma homocysteine levels

    Directory of Open Access Journals (Sweden)

    Jutta Dierkes

    2007-03-01

    Full Text Available Jutta Dierkes, Claus Luley, Sabine WestphalInstitute of Clinical Chemistry and Biochemistry, University Hospital Magdeburg, Germany Abstract: Elevated plasma concentrations of homocysteine, a sulfur-containing amino acid, are a risk factor for coronary, cerebral and peripheral artery disease. Next to other factors, drugs used for the prevention or treatment of cardiovascular disease may modulate plasma homocysteine levels. Thus, a drug induced homocysteine increase may counteract the desired cardioprotective effect. The aim is to summarize the current knowledge on the effect of two important classes of drugs, lipid-lowering drugs and anti-hypertensive drugs, on homocysteine metabolism. Among the lipid-lowering drugs, especially the fibric acid derivatives, which are used for treatment of hypertriglyceridemia and low HDL-cholesterol, are associated with an increase of homocysteine by 20%–50%. This increase can be reduced, but not totally avoided by the addition of folic acid, vitamin B12 and B6 to fibrates. HMG-CoA reductase inhibitors (statins do not influence homocysteine concentrations substantially. The effects of nicotinic acid and n3-fatty acids on the homocysteine concentrations are less clear, more studies are necessary to clarify their influence on homocysteine. Antihypertensive drugs have also been studied with respect to homocysteine metabolism. A homocysteine increase has been shown after treatment with hydrochlorothiazide, a lowering was observed after treatment with ß-blockers, but no effect with ACE-inhibitors. The clinical significance of the homocysteine elevation by fibrates and thiazides is not clear. However, individual patients use these drugs for long time, indicating that even moderate increases may be important.Keywords: homocysteine, fibrates, diuretics, cardiovascular disease

  1. Effectiveness of an educational feedback intervention on drug prescribing in dental practice.

    Science.gov (United States)

    Rauniar, G P; Das, B P; Manandhar, T R; Bhattacharya, S K

    2012-01-01

    Irrational use of drugs as well as inappropriate and over drug prescribing leads to unnecessary expenditures and emergence of resistant bacterial strains. Feedback intervention on drug prescribing habits and face to face educational intervention of prescription audit would be effective in rationalizing prescribing practices. To measure the impact of educational feedback intervention on the prescribing behavior of dental surgeons. Prospective audit of twelve hundred outpatients prescriptions in dental OPD at BPKIHS of those dental surgeon who attended the educational intervention session was collected randomly by trained persons on customized data collection sheet before and after educational intervention. A total 1200 prescription were collected, 300 before and 300 after intervention period at the internal of one month, three months and six months. Majority of the prescriptions (39.33%) contained four drugs but after intervention, prescriptions contained mostly one drug, 73% in first month, 78.67% in third month and 65.34% in six month. Mean number of drugs per prescription after intervention were decreased. There was increased number of generic names of drugs after intervention. Amoxicillin, Metronidazole, Chlorhexidine, Povidone iodine gargle, Nimesulide, Ibuprofen, Ibuprofen + paracetamol, and Paracetamol were most commonly prescribed by dental prescribers before and after intervention. Selection of antimicrobial was done on empirical basis which was correct because Amoxicillin concentration reaches effectively in gingival crevicular fluid and Metronidazole covered effectively against anaerobic bacteria were found in orodental infection. The uses of topical anti-infective preparation as irrigants of choice that can kill majority of micro-organisms found is root canal and dental tubules and minimize systemic use of antimicrobials. Nimesulide prescribing needs to be rationalized. Feedback educational intervention of prescription audit is effective to improve their

  2. Predicting Adverse Drug Effects from Literature- and Database-Mined Assertions.

    Science.gov (United States)

    La, Mary K; Sedykh, Alexander; Fourches, Denis; Muratov, Eugene; Tropsha, Alexander

    2018-06-06

    Given that adverse drug effects (ADEs) have led to post-market patient harm and subsequent drug withdrawal, failure of candidate agents in the drug development process, and other negative outcomes, it is essential to attempt to forecast ADEs and other relevant drug-target-effect relationships as early as possible. Current pharmacologic data sources, providing multiple complementary perspectives on the drug-target-effect paradigm, can be integrated to facilitate the inference of relationships between these entities. This study aims to identify both existing and unknown relationships between chemicals (C), protein targets (T), and ADEs (E) based on evidence in the literature. Cheminformatics and data mining approaches were employed to integrate and analyze publicly available clinical pharmacology data and literature assertions interrelating drugs, targets, and ADEs. Based on these assertions, a C-T-E relationship knowledge base was developed. Known pairwise relationships between chemicals, targets, and ADEs were collected from several pharmacological and biomedical data sources. These relationships were curated and integrated according to Swanson's paradigm to form C-T-E triangles. Missing C-E edges were then inferred as C-E relationships. Unreported associations between drugs, targets, and ADEs were inferred, and inferences were prioritized as testable hypotheses. Several C-E inferences, including testosterone → myocardial infarction, were identified using inferences based on the literature sources published prior to confirmatory case reports. Timestamping approaches confirmed the predictive ability of this inference strategy on a larger scale. The presented workflow, based on free-access databases and an association-based inference scheme, provided novel C-E relationships that have been validated post hoc in case reports. With refinement of prioritization schemes for the generated C-E inferences, this workflow may provide an effective computational method for

  3. Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

    OpenAIRE

    Wiltschko, Alexander B; Pettibone, Jeffrey R; Berke, Joshua D

    2010-01-01

    Psychomotor stimulants and typical antipsychotic drugs have powerful but opposite effects on mood and behavior, largely through alterations in striatal dopamine signaling. Exactly how these drug actions lead to behavioral change is not well understood, as previous electrophysiological studies have found highly heterogeneous changes in striatal neuron firing. In this study, we examined whether part of this heterogeneity reflects the mixture of distinct cell types present in the striatum, by di...

  4. Old Wine in New Wine Skins: Tombstone Unveiling as a Case of ...

    African Journals Online (AJOL)

    This article reflects on the practice of Tombstone Unveiling, a recent phenomenon among Shona Christians in Zimbabwe, as a case of religious change. Historically, many church doctrines and practices have been negative towards African Traditional Religions (ATRs). Shona Christians have reacted by trying to ...

  5. Atomic Force Microscopy - A Tool to Unveil the Mystery of Biological ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 15; Issue 7. Atomic Force Microscopy - A Tool to Unveil the Mystery of Biological Systems ... Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560 ...

  6. Rotifer neuropharmacology--III. Adrenergic drug effects on Brachionus plicatilis.

    Science.gov (United States)

    Keshmirian, J; Nogrady, T

    1987-01-01

    Norepinephrine (NE) induces three pharmacological effects in Brachionus plicatilis. As a result of excitation the rate of ciliary motion and swimming increases, and the animals flip their foot constantly at a rapid rate. This rapid foot flipping was used as a specific model to measure adrenergic effects in B. plicatilis. Phenylephrine induces the same effect at identical efficacy, while isoproterenol and salbutamol, two beta-agonists, show one-half and one-tenth NE efficacy. The beta blocker propranolol and the alpha blocker tolazoline both antagonize foot flipping induced by NE. However, propranolol shows antagonism because it causes foot paralysis by itself. Timolol, another beta blocker but without the membrane effect of propranolol, does not antagonize the alpha receptor mediated NE effect, nor does it cause foot paralysis. Propranolol, timolol and tolazoline also show agonist activity, inducing foot flipping. NE does not antagonize the foot paralysis induced by propranolol, only its anesthetic effect by delaying its onset. These results indicate that the foot flipping induced by NE is a receptor-mediated alpha adrenergic effect, while the foot paralysis is caused by membrane phenomena.

  7. [Effects of sub-micro emulsion composition on cellular disposition of incorporated lipophilic drug].

    Science.gov (United States)

    Sun, Xiao-Yi; Xiang, Zhi-Qiang; Wu, Shuo; Lv, Yuan-Yuan; Liang, Wen-Quan

    2013-09-01

    To investigate the effects of sub-micro emulsion composition on cellular uptake and disposition of incorporated lipophilic drug. Sub-micro emulsions containing 10 % oil, 1.2 % lecithin and 2.25 % glycerol were prepared, and the fluorescent agent coumarin 6 was used as a model drug. The effects of oil types, co-surfactants and cationic lipid on uptake and elimination kinetics of 6-coumarin in HeLa cells were studied. The uptake mechanism of sub-micro emulsions was further investigated. Oil type and Tweens had no influence on the cellular uptake. Modifications of surfactants with Span series increased the cellular influx, among which Span 20 with hydrophilic-lipophilic balance (HLB) value of 8.6 was the best enhancer. The intracellular drug level reached up to (46.09 ± 1.98)ng/μg protein which had significant difference with control group [(38.54 ± 0.34)ng/μg protein]. The positively charged emulsions significantly increased the uptake rate constant and elimination rate constant which were 4 times and 1.5 times of those in anionic groups, respectively. The uptake enhancement was also observed in cationic emulsions, cellular concentrations at plateau were (42.73 ± 0.84)ng/μg protein, which was about 3 times of that in anionic emulsions [(15.71 ± 0.74)ng/μg protein], when extracellular drug concentration kept at 100 ng/ml. Cationic emulsions delivered the payload mainly by direct drug transfer to contacted cells, while the negative ones depended on both drug passive diffusion and clathrin-mediated endocytosis of drug containing oil droplets which accounted for 20% of the intracellular drug. Interfacial characteristic of sub-micro emulsions such as co-surfactants HLB as well as zeta potentials can influence lipophilic drug both in cellular uptake and elimination.

  8. Effect of cell culture medium components on color of formulated monoclonal antibody drug substance.

    Science.gov (United States)

    Vijayasankaran, Natarajan; Varma, Sharat; Yang, Yi; Mun, Melissa; Arevalo, Silvana; Gawlitzek, Martin; Swartz, Trevor; Lim, Amy; Li, Feng; Zhang, Boyan; Meier, Steve; Kiss, Robert

    2013-01-01

    As the industry moves toward subcutaneous delivery as a preferred route of drug administration, high drug substance concentrations are becoming the norm for monoclonal antibodies. At such high concentrations, the drug substance may display a more intense color than at the historically lower concentrations. The effect of process conditions and/or changes on color is more readily observed in the higher color, high concentration formulations. Since color is a product quality attribute that needs to be controlled, it is useful to study the impact of process conditions and/or modifications on color. This manuscript summarizes cell culture experiments and reports on findings regarding the effect of various media components that contribute to drug substance color for a specific monoclonal antibody. In this work, lower drug substance color was achieved via optimization of the cell culture medium. Specifically, lowering the concentrations of B-vitamins in the cell culture medium has the effect of reducing color intensity by as much as 25%. In addition, decreasing concentration of iron was also directly correlated color intensity decrease of as much as 37%. It was also shown that the color of the drug substance directly correlates with increased acidic variants, especially when increased iron levels cause increased color. Potential mechanisms that could lead to antibody coloration are briefly discussed. © 2013 American Institute of Chemical Engineers.

  9. A systems-based mathematical modelling framework for investigating the effect of drugs on solid tumours

    Directory of Open Access Journals (Sweden)

    Liu Cong

    2011-12-01

    Full Text Available Abstract Background Elucidating the effects of drugs on solid tumours is a highly challenging multi-level problem, since this involves many complexities associated with transport and cellular response, which in turn is characterized by highly non-linear chemical signal transduction. Appropriate systems frameworks are needed to seriously address the sources of these complexities, especially from the cellular side. Results We develop a skeletal modelling framework incorporating interstitial drug transport, intracellular signal processing and cell population descriptions. The descriptions aim to appropriately capture the nature of information flow. The model is deliberately formulated to start with simple intracellular descriptions so that additional features can be incorporated in a modular fashion. Two kinds of intracellular signalling modules which describe the drug effect were considered, one a monostable switch and the other a bistable switch. Analysis of our model revealed how different drug stimuli can lead to cell killing in the tumour. Interestingly both modules considered exhibited similar trends. The effects of important parameters were also studied. Conclusions We have created a predictive systems platform integrating drug transport and cellular response which can be systematically augmented to include additional layers of cellular complexity. Our results indicate that intracellular signalling models which are qualitatively different can give rise to similar behaviour to simple (and typical stimuli, and that validating intracellular descriptions must be performed with care by considering a variety of drug stimuli.

  10. A review of ecological effects and environmental fate of illicit drugs in aquatic ecosystems.

    Science.gov (United States)

    Rosi-Marshall, E J; Snow, D; Bartelt-Hunt, S L; Paspalof, A; Tank, J L

    2015-01-23

    Although illicit drugs are detected in surface waters throughout the world, their environmental fate and ecological effects are not well understood. Many illicit drugs and their breakdown products have been detected in surface waters and temporal and spatial variability in use translates into "hot spots and hot moments" of occurrence. Illicit drug occurrence in regions of production and use and areas with insufficient wastewater treatment are not well studied and should be targeted for further study. Evidence suggests that illicit drugs may not be persistent, as their half-lives are relatively short, but may exhibit "pseudo-persistence" wherein continual use results in persistent occurrence. We reviewed the literature on the ecological effects of these compounds on aquatic organisms and although research is limited, a wide array of aquatic organisms, including bacteria, algae, invertebrates, and fishes, have receptors that make them potentially sensitive to these compounds. In summary, illicit drugs occur in surface waters and aquatic organisms may be affected by these compounds; research is needed that focuses on concentrations of illicit drugs in areas of production and high use, environmental fate of these compounds, and effects of these compounds on aquatic ecosystems at the concentrations that typically occur in the environment. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. [PHARMACOLOGICAL TREATMENT IN PALLIATIVE CARE. DRUG ADMINISTRATION ROUTE, CONTINUOUS SUBCUTANEOUS INFUSION, ADVERSE SIDE EFFECTS, SYMPTOM MANAGEMENT].

    Science.gov (United States)

    Dominguez Álvarez, Rocío; Calderón Carrasco, Justo; García Colchero, Francisco; Postigo Mota, Salvador; Alburquerque Medina, Eulalia

    2015-01-01

    To achieve well-being in patients in Palliative Care is required to know which are the most common symptoms, which are the drugs used for relief, which are the routes of administration of drugs that are suitable, how effective the drugs are and what incompatibilities, interactions and adverse effects occur. The aim of this article is to review the relevant issues in the management of the drugs commonly used by nursing in Palliative Care and presenting recommendations to clinical practice. Management interventions drugs for nurses in Palliative Care recommended by the scientific literature after a search of Scopus, CINAHL, Medline, PubMed, UpToDate and Google Scholar are selected. The oral route is the choice for patients in palliative situation and subcutaneous route when the first is not available. The symptoms, complex, intense and moody, should be systematically reevaluated by the nurse, to predict when a possible decompensation of it needing extra dose of medication. Nurses must be able to recognize the imbalance of well-being and act quickly and effectively, to get relief to some unpleasant situations for the patient as the pain symptoms, dyspnea or delirium. For the proper administration of rescue medication, the nurse should know the methods of symptomatic evaluation, pharmacokinetics and pharmacodynamics of drugs, the time intervals to elapse between different rescues and nccocc rocnnnco t thocm

  12. Adverse effects and Drug Interactions Associated with Inhaled Recreational and Medical Marijuana

    Directory of Open Access Journals (Sweden)

    Maisha Kelly Freeman

    2016-06-01

    Full Text Available Objectives: To provide an overview of the addiction potential; adverse effects (e.g., cardiovascular, immune dysfunction, respiratory system, mental health disorders; drug interactions; effects of accidental exposure; crime statistics; and pharmacist’s considerations for the use of inhaled medical marijuana. Methods: A PubMed search was conducted from 1966 to March 2016 to identify articles in which the safety of inhaled medical marijuana was assessed. Key MeSH search terms included medical marijuana with a subheading for adverse effect. Only articles in adult patients were considered. In addition, medical marijuana or cannabis plus one of the following search terms were searched: drug interactions, herb-drug interactions, drug-related side effects and adverse drug reactions, substance-related disorders, addiction, and abuse. A free-text search was also conducted to identify articles not included in the MeSH term search. A bibliographic search was also conducted. Articles were included if they addressed adverse effects of medical marijuana for the treatment of a condition. Meta-analyses, randomized controlled clinical trials, and case reports were included in the review if the primary focus of the article related to the adverse effect profile of inhaled medical marijuana. Medical marijuana efficacy studies were not assessed. In the absence of this information, case reports or reports of inhaled recreational marijuana use was used. Studies were excluded if published in languages other than English. In addition, studies highlighting mechanisms of action, studies of pharmacodynamics or pharmacokinetic effects were excluded, unless these effects were due to drug-drug interactions. Prescription products containing marijuana or derivatives were excluded from evaluation. An Internet search was conducted to locate the most up-to-date information on the laws concerning medical marijuana. Key findings: A PubMed search revealed 58 articles and 28 of

  13. Study on Ca2+ antagonistic effect and mechanism of Chinese herbal drugs using 45Ca

    International Nuclear Information System (INIS)

    Yang Yuanyou; Liu Ning; Mo Shangwu; Qiu Mingfeng; Jin Jiannan; Liao Jiali

    2002-01-01

    The Ca 2+ antagonistic effect and mechanism of Chinese herbal drugs are studied by using 45 Ca. The results indicate that potential-dependent Ca 2+ channel (PDC) and receptor-operated Ca 2+ channel (ROC) in cell membranes of smooth muscle can be blocked by several Chinese herbal drugs, including as Crocus sativus L., Carthamus L., Di-ao-xin-xue-kang (DAXXG) and Ginkgo biloba L. leaves. Among them Crocus sativus L. has the strongest antagonistic effect on Ca 2+ channel, while Ginkgo biloba L. leaves has no obvious effect. The whole prescription and the other functional drugs have significant effect on ROC and PDC. The compositions extracted by hexane have the strongest antagonistic. The wrinkled giant hyssop have five active compositions and Pei-lan have two active compositions

  14. Anti-Obesity Drugs: A Review about Their Effects and Safety

    Directory of Open Access Journals (Sweden)

    Jun Goo Kang

    2012-02-01

    Full Text Available The current recommendations for the treatment of obese people include increased physical activity and reduced calories intake. When the behavioral approach is not sufficient, a pharmacologic treatment is recommended. In past years, numerous drugs have been approved for the treatment of obesity; however, most of them have been withdrawn from the market because of their adverse effects. In fact, amphetamine, rimonabant and sibutramine licenses have been withdrawn due to an increased risk of psychiatric disorders and non-fatal myocardial infarction or stroke. Even if orlistat is not as effective as other drugs in reducing body weight, orlistat is presently the only available choice for the treatment of obesity because of its safety for cardiovascular events and positive effects on diabetic control. Hopefully, more effective and better tolerated anti-obesity drugs will be developed through an improved understanding of the multiple mechanisms and complex physiological systems targeting appetite.

  15. Institutional corruption of pharmaceuticals and the myth of safe and effective drugs.

    Science.gov (United States)

    Light, Donald W; Lexchin, Joel; Darrow, Jonathan J

    2013-01-01

    Over the past 35 years, patients have suffered from a largely hidden epidemic of side effects from drugs that usually have few offsetting benefits. The pharmaceutical industry has corrupted the practice of medicine through its influence over what drugs are developed, how they are tested, and how medical knowledge is created. Since 1906, heavy commercial influence has compromised congressional legislation to protect the public from unsafe drugs. The authorization of user fees in 1992 has turned drug companies into the FDA's prime clients, deepening the regulatory and cultural capture of the agency. Industry has demanded shorter average review times and, with less time to thoroughly review evidence, increased hospitalizations and deaths have resulted. Meeting the needs of the drug companies has taken priority over meeting the needs of patients. Unless this corruption of regulatory intent is reversed, the situation will continue to deteriorate. We offer practical suggestions including: separating the funding of clinical trials from their conduct, analysis, and publication; independent FDA leadership; full public funding for all FDA activities; measures to discourage R&D on drugs with few, if any, new clinical benefits; and the creation of a National Drug Safety Board. © 2013 American Society of Law, Medicine & Ethics, Inc.

  16. Premature drug release of polymeric micelles and its effects on tumor targeting.

    Science.gov (United States)

    Miller, Tobias; Breyer, Sandra; van Colen, Gwenaelle; Mier, Walter; Haberkorn, Uwe; Geissler, Simon; Voss, Senta; Weigandt, Markus; Goepferich, Achim

    2013-03-10

    Based on the enhanced permeability and retention (EPR) effect, nanoparticles are believed to accumulate in tumors. In this conjunction, the stability of drug encapsulation is assumed to be sufficient. For clarification purposes, PEGylated poly-(D,L-lactic acid) (PEG-PDLLA) micelles which incorporated the hydrophobic model drug dechloro-4-iodo-fenofibrate (IFF) were investigated. H2N-PEG-PDLLA was synthesized, coupled to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and labeled with 111-indium. From this polymeric species, mixed micelles with H3CO-PEG-PDLLA were prepared which encapsulated the 125-iodine or 131-iodine labeled drug IFF. Bioimaging and biodistribution experiments in healthy and AR42J-tumor bearing mice were carried out to quantify the uptake of the drug and its carrier in single organs. As a result, upon injection of this system, a rapid dissociation of the polymeric carrier and the incorporated drug (system allowed for successful solubilization of the hydrophobic drug by physical incorporation into micelles whereas the tumor targeting properties of the drug delivery system could not be sufficiently shown. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Considerations for a business model for the effective integration of novel biomarkers into drug development.

    Science.gov (United States)

    Frueh, Felix W

    2008-11-01

    It is 10 years since the introduction of trastuzumab into the US market, and we are still waiting for a validation of the business case for biomarker-driven drug development. While many reasons for the lack of duplication of this model may exist, the need for accelerated innovation in drug development paired with the opportunity of integrating biomarker-driven research into drug development programs may lead to new and creative ways of fostering the cooperation between drug developers and test manufacturers. The rapid increase in knowledge about biomarkers and our understanding of disease and disease mechanisms open unprecedented prospects to make not only better, more informed decisions regarding patient care, but also strategic decisions during drug development. This requires that a biomarker strategy becomes an integral part of (early) drug development and that new, innovative paths are tried towards a model that combines the scientific approach with an economically feasible implementation strategy. Collaborative research, the use of new communication tools, the exploration of alternative ways to position a product in the market, and other considerations are part of such a strategy. This perspective article illustrates the current landscape and takes a look at some of these new ways for more effectively integrating biomarkers into drug development.

  18. Psychotropic drug effects contributing to psychiatric hospitalization of children: a preliminary study.

    Science.gov (United States)

    Fialkov, M J; Hasley, S

    1984-12-01

    Over an 11-month period on a Children's Psychiatric Unit 5% of 60 first admissions for hospitalization were apparently associated with adverse effects of psychotropic medication. Forty (66%) of the first admissions had used, prior to hospitalization, a wide variety of drugs including stimulants, major and minor tranquilizers, anticonvulsants, antidepressants and over-the-counter drugs containing antihistamines and analgesics. It is suggested that inappropriate and injudicious use of psychotropic medications may be associated with unanticipated adverse behavioral effects, which can result in deterioration of a child's functioning to the point of necessitating psychiatric hospitalization. Early identification of these unwanted psychotropic effects has diagnostic, prognostic, economic, and legal implications.

  19. A prominent anchoring effect on the kinetic control of drug release from mesoporous silica nanoparticles (MSNs).

    Science.gov (United States)

    Tran, Vy Anh; Lee, Sang-Wha

    2018-01-15

    This work demonstrated kinetically controlled release of model drugs (ibuprofen, FITC) from well-tailored mesoporous silica nanoparticles (MSNs) depending on the surface charges and molecular sizes of the drugs. The molecular interactions between entrapped drugs and the pore walls of MSNs controlled the release of the drugs through the pore channels of MSNs. Also, polydopamine (PDA) layer-coated MSNs (MSNs@PDA) was quite effective to retard the release of large FITC, in contrast to a slight retardation effect on relatively small Ibuprofen. Of all things, FITC (Fluorescein isothiocyanate)-labeled APTMS (3-aminopropyltrimethoxysilane) (APTMS-FITC conjugates) grafted onto the MSNs generate a pinch-effect on the pore channel (so-called a prominent anchoring effect), which was highly effective in trapping (or blocking) drug molecules at the pore mouth of the MSNs. The anchored APTMS-FITC conjugates provided not only tortuous pathways to the diffusing molecules, but also sustained release of the ibuprofen over a long period of time (∼7days). The fast release kinetics was predicted by an exponential equation based on Fick's law, while the slow release kinetics was predicted by Higuchi model. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. [The effect of food intake on drug action].

    Science.gov (United States)

    Pletscher, W; Peretti, E

    1990-01-01

    Interactions between medicaments and food are only incompletely documented--despite their frequent occurrence. Food can influence the effect of medicaments in a variety of ways: the effect of the medicament can be delayed or weakened; in some cases the effect may also be increased. The interactions between the kinetics of medicaments and food are described in the present survey. The absorption conditions in the stomach and small intestine are influenced physiologically and chemically by food. In very rare cases the elimination of active ingredients too can be modified by the quality and quantity of the food. Detailed knowledge about the physical-chemical properties of the medicaments used help to optimize the pharmacotherapy in the individual case. For the patient, the easiest suggestion to follow would be to take the medicaments with plenty of water and always at the same time.

  1. The cytogenetic effect of the new asthma and allergy drug ...

    African Journals Online (AJOL)

    Black Code

    The most common adverse effects of Montelukast in pediatric studies were headache, asthma, and ... chromosomal gaps and centric fusion represent the most predominant types of aberrations. The highest readings ... At the 10mg/d treatment, it is obvious that the most frequent types of aberrations are deletions and centric ...

  2. Cost effectiveness of withdrawal of fall-risk-increasing drugs in geriatric outpatients

    NARCIS (Netherlands)

    van der Velde, Nathalie; Meerding, Willen Jan; Looman, Caspar W.; Pols, Huibert A. P.; van der Cammen, Tischa J. M.

    2008-01-01

    BACKGROUND: Withdrawal of fall-risk-increasing drugs has been proven to be effective in older persons. However, given the enormous rise in healthcare costs in recent decades, the effect of such withdrawals on healthcare costs also needs to be considered. METHOD: Within a common geriatric outpatient

  3. The effects of Psychotropic drugs On Developing brain (ePOD) study : methods and design

    NARCIS (Netherlands)

    Bottelier, Marco A; Schouw, Marieke L J; Klomp, Anne; Tamminga, Hyke G H; Schrantee, Anouk G M; Bouziane, Cheima; de Ruiter, Michiel B; Boer, Frits; Ruhé, Henricus G; Denys, D.; Rijsman, Roselyne; Lindauer, Ramon J L; Reitsma, Hans B; Geurts, Hilde M; Reneman, Liesbeth

    2014-01-01

    BACKGROUND: Animal studies have shown that methylphenidate (MPH) and fluoxetine (FLX) have different effects on dopaminergic and serotonergic system in the developing brain compared to the developed brain. The effects of Psychotropic drugs On the Developing brain (ePOD) study is a combination of

  4. The effects of psychotropic drugs on developing brain (ePOD) study: methods and design

    NARCIS (Netherlands)

    Bottelier, M.A.; Schouw, M.L.J.; Klomp, A.; Tamminga, G.H.; Schrantee, A.G.M.; Bouziane, C.; de Ruiter, M.B.; Boer, F.; Ruhé, H.G.; Denys, D.; Rijsman, R.; Lindauer, R.J.L.; Reitsma, H.B.; Geurts, H.M.; Reneman, L.

    2014-01-01

    Background: Animal studies have shown that methylphenidate (MPH) and fluoxetine (FLX) have different effects on dopaminergic and serotonergic system in the developing brain compared to the developed brain. The effects of Psychotropic drugs On the Developing brain (ePOD) study is a combination of

  5. The effects of Psychotropic drugs On Developing brain (ePOD) study : methods and design

    NARCIS (Netherlands)

    Bottelier, Marco A.; Schouw, Marieke L. J.; Klomp, Anne; Tamminga, Hyke G. H.; Schrantee, Anouk G. M.; Bouziane, Cheima; de Ruiter, Michiel B.; Boer, Frits; Ruhe, Henricus G.; Denys, Damiaan; Rijsman, Roselyne; Lindauer, Ramon J. L.; Reitsma, Hans B.; Geurts, Hilde M.; Reneman, Liesbeth

    2014-01-01

    Background: Animal studies have shown that methylphenidate (MPH) and fluoxetine (FLX) have different effects on dopaminergic and serotonergic system in the developing brain compared to the developed brain. The effects of Psychotropic drugs On the Developing brain (ePOD) study is a combination of

  6. The effects of Psychotropic drugs On Developing brain (ePOD) study: methods and design

    NARCIS (Netherlands)

    Bottelier, Marco A.; Schouw, Marieke L. J.; Klomp, Anne; Tamminga, Hyke G. H.; Schrantee, Anouk G. M.; Bouziane, Cheima; de Ruiter, Michiel B.; Boer, Frits; Ruhé, Henricus G.; Denys, Damiaan; Rijsman, Roselyne; Lindauer, Ramon J. L.; Reitsma, Hans B.; Geurts, Hilde M.; Reneman, Liesbeth

    2014-01-01

    Animal studies have shown that methylphenidate (MPH) and fluoxetine (FLX) have different effects on dopaminergic and serotonergic system in the developing brain compared to the developed brain. The effects of Psychotropic drugs On the Developing brain (ePOD) study is a combination of different

  7. Novel sample preparation method for surfactant containing suppositories: effect of micelle formation on drug recovery.

    Science.gov (United States)

    Kalmár, Éva; Ueno, Konomi; Forgó, Péter; Szakonyi, Gerda; Dombi, György

    2013-09-01

    Rectal drug delivery is currently at the focus of attention. Surfactants promote drug release from the suppository bases and enhance the formulation properties. The aim of our work was to develop a sample preparation method for HPLC analysis for a suppository base containing 95% hard fat, 2.5% Tween 20 and 2.5% Tween 60. A conventional sample preparation method did not provide successful results as the recovery of the drug failed to fulfil the validation criterion 95-105%. This was caused by the non-ionic surfactants in the suppository base incorporating some of the drug, preventing its release. As guidance for the formulation from an analytical aspect, we suggest a well defined surfactant content based on the turbidimetric determination of the CMC (critical micelle formation concentration) in the applied methanol-water solvent. Our CMC data correlate well with the results of previous studies. As regards the sample preparation procedure, a study was performed of the effects of ionic strength and pH on the drug recovery with the avoidance of degradation of the drug during the procedure. Aminophenazone and paracetamol were used as model drugs. The optimum conditions for drug release from the molten suppository base were found to be 100 mM NaCl, 20-40 mM NaOH and a 30 min ultrasonic treatment of the final sample solution. As these conditions could cause the degradation of the drugs in the solution, this was followed by NMR spectroscopy, and the results indicated that degradation did not take place. The determined CMCs were 0.08 mM for Tween 20, 0.06 mM for Tween 60 and 0.04 mM for a combined Tween 20, Tween 60 system. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Stigma, Discrimination, Treatment Effectiveness and Policy Support: Comparing Public Views about Drug Addiction with Mental Illness

    Science.gov (United States)

    Barry, Colleen L; McGinty, Emma Elizabeth; Pescosolido, Bernice; Goldman, Howard H.

    2014-01-01

    Objective This study compares current public attitudes about drug addiction with attitudes about mental illness. Methods A web-based national public opinion survey (N=709) was conducted to compare attitudes about stigma, discrimination, treatment effectiveness, and policy support. Results Respondents hold significantly more negative views toward persons with drug addiction compared to those with mental illness. More respondents were unwilling to have a person with drug addiction marry into their family or work closely with them on a job. Respondents were more willing to accept discriminatory practices, more skeptical about the effectiveness of available treatments, and more likely to oppose public policies aimed at helping persons with drug addiction. Conclusions Drug addiction is often treated as a sub-category of mental illness, and health insurance benefits group these conditions together under the rubric of behavioral health. Given starkly different public views about drug addiction and mental illness, advocates may need to adopt differing approaches for advancing stigma reduction and public policy. PMID:25270497

  9. Effect of combinations of marketed human anthelmintic drugs against Trichuris muris in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Keiser Jennifer

    2012-12-01

    Full Text Available Abstract Background Soil-transmitted helminth (STH infections are responsible for a huge public health burden, however treatment options are limited. The discovery and development of novel efficacious drugs or drug combinations for the treatment of STH infections therefore has a high research priority. Methods We studied drug combination effects using the main standard anthelmintics, albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin in the Trichuris muris model. Drug combinations were first tested in vitro and additive and synergistic combinations investigated further in vivo in female mice using ratios based on the ED50 of the respective drugs. Results In vitro all 10 combinations of the standard anthelmintics tested against T. muris revealed synergistic behavior. We identified three drug combinations in vivo as strongly synergistic, namely mebendazole-ivermectin (Combination index (CI=0.16, mebendazole-levamisole (CI=0.17 and albendazole-mebendazole (CI=0.23. For albendazole-ivermectin, moderate synergism was observed (CI=0.81 and for albendazole-levamisole a nearly additive effect was documented (CI=0.93 in vivo. Five combinations (albendazole-pyrantel pamoate, mebendazole-pyrantel pamoate, levamisole-pyrantel pamoate, levamisole-ivermectin and pyrantel pamoate-ivermectin were antagonistic in vivo. Conclusion Our results strengthen the evidence that combination chemotherapy might play a role in the treatment of Trichuris infections. Albendazole-mebendazole should be studied in greater detail in preclinical studies.

  10. Effects of opioid drugs on dopamine mediated locomotor activity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Leathern, L L

    1986-01-01

    Opioid drugs influence various behavioural parameters including locomotor activity in experimental animals. The interaction between the opioid and dopaminergic systems is one possible explanation for the effect of opioid drugs on locomotor activity. In this study behavioural and biochemical assays were done to investigate the interaction between the opioid and dopaminergic systems. Behavioural studies were done by measurement of locomotor activity (LA) of rats after acute or chronic pretreatment with opioid andor dopaminergic drugs. Biochemical studies were in the form of radioligand binding assays, the effect on the number (Bmax) and affinity (K/sub D/) of receptors was measured after chronic pretreatment with opioid andor dopaminergic drugs. The opioid drugs used are morphine, nalbuphine and naloxone. Dopaminergic drugs used included: agonists-apomorphine and piribedil; antagonists-pimozide, haloperidol, chlorpromazine. In the acute situation increased LA was obtained with morphine and the DA agonists. A correlation between the behavioural and biochemical assays was found. Chronic pretreatment with morphine enhanced apomorphine induced LA, this supersensitivity was also measured as an increased receptor density (Bmax) of D2 receptors in the striatum. Chronic morphine pretreatment caused a decrease in morphine induced LA, while this subsensitivity was not apparent in the ligand binding assays - where no change in receptor number was observed. Chronic naloxone pretreatment enhanced morphine induced LA, as well as increased the Bmax of opioid receptors in the whole brain. It is concluded that an interaction between the opioid and dopaminergic systems does exist, and may account for the mechanism of action of the opioids.

  11. Effect of herb drug medicine Treatment for Functional Dyspepsia:Controlled Trial

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    Lee Jae-Jin

    2009-06-01

    Full Text Available Obejective : Functional dyspepsia is a prevalent disease. It impedes subjective quality of life. The purpose of this research is to examine the equivalent effect of herb drug medicine treatment(H-Dand Over the Counter(OTC for functional dyspepsia. Method : In this controlled study, we compared herb drug medicine(H-D with Over the Counter(OTC of functional dyspepsia. 30 volunteers who satisfied the requirements were enrolled in study. Severity of dyspepsia was measured by Nepean Dyspepsia Index(NDI-K before and after treatments. Result : The results are summarized as follows. 1. In Herb drug medicine and Over the Counter groups, total key symptoms score of after treatment were significantly decreased and improve rate of key symptoms was higher than before treatment, but there were no statistical significance between two groups. 2. In Herb drug medicine and Over the Counter groups, each symptoms score of after treatment were significantly decreased and improve rate of key symptoms was higher than before treatment, but there were no statistical significance between two groups. 3. In Herb drug medicine and Over the Counter groups, quality of life score of after treatment were significantly decreased and improve rate of key symptoms was higher than before treatment, but there were no statistical significance between two groups. Conclusion : Herb drug medicine treatment(H-D is effective to improve the symptoms and quality of life in patients with functional dyspepsia.

  12. Multilayered pyramidal dissolving microneedle patches with flexible pedestals for improving effective drug delivery.

    Science.gov (United States)

    Lau, Shinying; Fei, Jie; Liu, Haoran; Chen, Weixing; Liu, Ran

    2017-11-10

    Dissolving microneedles have been employed as a safe and convenient transdermal delivery system for drugs and vaccines. To improve effective drug delivery, a multilayered pyramidal dissolving microneedle patch, composed of silk fibroin tips with the ability of robust mechanical strength, rapid dissolution and drug release supported on a flexible polyvinyl alcohol (PVA) pedestal is reported. To show the utility of this approach the ability of the fabricated microneedles to deliver insulin is demonstrated. The dissolving microneedles have sufficient mechanical strength to be inserted into abdomen skin of mice to a depth of approximately 150μm, and release their encapsulated insulin into the skin to cause a hypoglycemic effect. The fabrication of microneedles avoids high temperature which benefits storage stability at room temperature for 20d. This result indicates >99.4% of insulin remained in the microneedles. In comparison to traditional needle-based administration, the proposed multilayered pyramidal dissolving microneedle patches enable self-administration, miniaturization, pain-free administration, drug delivery and drug stability, all being important features in needle free drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Nonlinear dynamics of the patient’s response to drug effect during general anesthesia

    Science.gov (United States)

    Ionescu, Clara; Tenreiro Machado, Jose; De Keyser, Robin; Decruyenaere, Johan; Struys, Michel M. R. F.

    2015-03-01

    In today's healthcare paradigm, optimal sedation during anesthesia plays an important role both in patient welfare and in the socio-economic context. For the closed-loop control of general anesthesia, two drugs have proven to have stable, rapid onset times: propofol and remifentanil. These drugs are related to their effect in the bispectral index, a measure of EEG signal. In this paper wavelet time-frequency analysis is used to extract useful information from the clinical signals, since they are time-varying and mark important changes in patient's response to drug dose. Model based predictive control algorithms are employed to regulate the depth of sedation by manipulating these two drugs. The results of identification from real data and the simulation of the closed loop control performance suggest that the proposed approach can bring an improvement of 9% in overall robustness and may be suitable for clinical practice.

  14. [Effects of antimicrobial drugs on soil microbial respiration].

    Science.gov (United States)

    Liu, Feng; Ying, Guang-Guo; Zhou, Qi-Xing; Tao, Ran; Su, Hao-Chang; Li, Xu

    2009-05-15

    The effects on soil microbial respiration of sulfonamides, tetracyclines, macrolides and so on were studied using the direct absorption method. The results show sulfamethazine, sulfamethoxazole, chlortetracycline, tetracycline, tylosin and trimethoprim inhibit soil respiration 34.33%, 34.43%, 2.71%, 3.08%, 7.13%, 38.08% respectively. Sulfamethoxazole and trimethoprim have the highest inhibition rates among all the antibiotics. In early incubation period (0-2 d), the concentrations above 10 mg x kg(-1) of sulfamethazine, sulfamethoxazole and trimethoprim remarkably decrease soil CO2 emission. The effects of these antibiotics vary with their concentrations too. Sulfamethoxazole and trimethoprim show good dose-response relationships. According to the standard of pesticide safety evaluation protocol, the six antibiotics pose a little risk to soil microbial environment.

  15. Wukong Sharpens Its Eyes and Unveils the Nature of Dark Matter

    Science.gov (United States)

    Cong, Kun-Lin

    2016-07-01

    Dark matter does not emit light or reflect electromagnetic radiation, but its existence can be inferred from the effects of measurements such as gravity and mass. Unveiling the nature of dark matter is one of the biggest mysteries of modern science. Exploration of dark matter could give scientists a clearer understanding of the past and future of galaxies and the universe. Chinese scientists have been engaged actively in dark matter research in recent years, and made some significant achievements in theoretical studies, numerical simulations, and experimental investigation. The Dark Matter Particles Explorer Satellite (DAMPE) was launched by LM launch vehicle on 17th December 2015. It was constructed as a scientific satellite that has four major parts - a plastic scintillator array detector, a silicon array detector, a BGO calorimeter and a neutron detector - together comprising about 76,000 minor detectors. The main scientific purpose of DAMPE is to investigate dark matter particle from deep space, via high resolution observation of gamma-rays and electrons spectra, and its space distribution. It will also help scientists study the transportation and acceleration of cosmic rays in the galaxy by measuring the energy spectra of heavy ions. DAMPE was dubbed Wukong after the Monkey King character from the Chinese classic legend Journey to the West. "Wu" means becoming aware of through the senses, and "Kong" refers to the space. The figurative meaning of "Wukong" is to know and comprehend the nature of the space. DAMPE is the most sensitive and accurate detectors designed for dark matter with the highest performance among the similar explorers. It will find the evidence that can certify the existence of dark matter.

  16. Unveiled Risks in a Telecoupled Arena Dependent on Agricultural Commodity Trade

    Science.gov (United States)

    Batistella, M.; Silva, R. F. B. D.; Liu, J.; Moran, E. F.; Torres, S.; Dou, Y.

    2017-12-01

    In less than five years, a new field of interdisciplinary research has been widely developed within the coupled human-natural systems (CHANS) community. Based on well-known concepts acting over long distances, such as teleconnections for biophysical sciences and globalization for human sciences, the telecoupling framework states that long distant CHANS may be integrated through flows of capital, information, and matter, shaping environmental and socioeconomic changes within local systems. An international project including researchers from Brazil, China, United Kingdom (UK), and United States of America (USA) is using such a framework to study the flows of agricultural commodities between sending systems such as Brazil and the USA, and receiving systems such as China with soybean trade as a case in point. Many findings have already shown that these dynamics are intrinsically connected and changes in environmental conditions in one system may affect economic conditions in other systems. In the case of the double-crop practice (i.e., soybean followed by maize, two crops year round) used in some regions of Brazil, maize production is strongly connected with soybean production through the supply chain, logistics, producer regions, and farmers. Consequently, maize has been displaced to second-crop status, making it more vulnerable to rain shortfalls. The use of the telecoupling framework has also unveiled a possible threat for soybean production in the long run if it only relies on international demand and inputs. The telecoupled soybean production system has put some Brazilian farmers at economic risk, and is pushing them towards diversification and alternative production practices (e.g., non-GMO crops, biological control, in-farm seed production) to reduce their risk. This, in turn, may affect the demand-consumption relationship among traditional trading partners. With this paper, we also highlight the role of cascading effects and spillover systems of telecoupling in

  17. Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

    Directory of Open Access Journals (Sweden)

    Frederickson Martyn

    2010-01-01

    Full Text Available Abstract Background Targeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior. Results We developed chemical synthesis methodologies for assembling these tripartite complexes using a variety of axonal transport facilitators including nerve growth factor, wheat germ agglutinin, and synthetic facilitators derived from phage display work. Loading of up to 100 drug molecules per complex was achieved. Conjugation methods were used that allowed the drugs to be released in active form inside the cell body after transport. Intramuscular and intradermal injection proved effective for introducing pharmacologically effective doses into selected populations of CNS neurons. Pharmacological efficacy with gabapentin in a paw withdrawal latency model revealed a ten fold increase in half life and a 300 fold decrease in necessary dose relative to systemic administration for gabapentin when the drug was delivered by axonal transport using the tripartite vehicle. Conclusion Specific targeting of selected subpopulations of CNS neurons for drug delivery by axonal

  18. MRP- and BCL-2-mediated drug resistance in human SCLC: effects of apoptotic sphingolipids in vitro.

    Science.gov (United States)

    Khodadadian, M; Leroux, M E; Auzenne, E; Ghosh, S C; Farquhar, D; Evans, R; Spohn, W; Zou, Y; Klostergaard, J

    2009-10-01

    Multidrug-resistance-associated protein (MRP) and BCL-2 contribute to drug resistance expressed in SCLC. To establish whether MRP-mediated drug resistance affects sphingolipid (SL)-induced apoptosis in SCLC, we first examined the human SCLC cell line, UMCC-1, and its MRP over-expressing, drug-resistant subline, UMCC-1/VP. Despite significantly decreased sensitivity to doxorubicin (Dox) and to the etoposide, VP-16, the drug-selected line was essentially equally as sensitive to treatment with exogenous ceramide (Cer), sphingosine (Sp) or dimethyl-sphingosine (DMSP) as the parental line. Next, we observed that high BCL-2-expressing human H69 SCLC cells, that were approximately 160-fold more sensitive to Dox than their combined BCL-2 and MRP-over-expressing (H69AR) counterparts, were only approximately 5-fold more resistant to DMSP. Time-lapse fluorescence microscopy of either UMCC cell line treated with DMSP-Coumarin revealed comparable extents and kinetics of SL uptake, further ruling out MRP-mediated effects on drug uptake. DMSP potentiated the cytotoxic activity of VP-16 and Taxol, but not Dox, in drug-resistant UMCC-1/VP cells. However, this sensitization did not appear to involve DMSP-mediated effects on the function of MRP in drug export; nor did DMSP strongly shift the balance of pro-apoptotic Sps and anti-apoptotic Sp-1-Ps in these cells. We conclude that SL-induced apoptosis markedly overcomes or bypasses MRP-mediated drug resistance relevant to SCLC and may suggest a novel therapeutic approach to chemotherapy for these tumors.

  19. Effect of drugs of abuse on social behaviour: a review of animal models.

    Science.gov (United States)

    Blanco-Gandía, Maria C; Mateos-García, Ana; García-Pardo, Maria P; Montagud-Romero, Sandra; Rodríguez-Arias, Marta; Miñarro, José; Aguilar, María A

    2015-09-01

    Social behaviour is disturbed in many substance abuse and psychiatric disorders. Given the consensus that social behaviours of lower mammals may help to understand some human emotional reactions, the aim of the present work was to provide an up-to-date review of studies on the changes in social behaviour induced by drugs of abuse. Various animal models have been used to study the relationship between drugs of abuse and social behaviour. Herein, we describe the effects of different substances of abuse on the three most commonly used animal models of social behaviour: the social play test, the social interaction test and the resident-intruder paradigm. The first is the most widely used test to assess adolescent behaviour in rodents, the second is generally used to evaluate a wide repertoire of behaviours in adulthood and the latter is specific to aggressive behaviour. Throughout the review we will explore the most relevant studies carried out to date to evaluate the effects of alcohol, cocaine, opioids, 3,4-methylenedioxymethamphetamine (MDMA), cannabinoids, nicotine and other drugs of abuse on these three paradigms, taking into account the influence of different variables, such as social history, age and type of exposure. Drugs of diverse pharmacological classes induce alterations in social behaviour, although they can be contrasting depending on several factors (drug, individual differences and environmental conditions). Ethanol and nicotine increase social interaction at low doses but reduce it at high doses. Psychostimulants, MDMA and cannabinoids reduce social interaction, whereas opiates increase it. Ethanol and psychostimulants enhance aggression, whereas MDMA, opiates, cannabinoids and nicotine reduce it. Prenatal drug exposure alters social behaviour, whereas drug withdrawal decreases sociability and enhances aggression. As a whole, this evidence has improved our understanding of the social dimension of drug addiction.

  20. Walnut kernel-like mesoporous silica nanoparticles as effective drug carrier for cancer therapy in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Kun; Ren, Huihui; Sun, Wentong [Hebei University, Key Laboratory of Chemical Biology of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry & Environmental Science (China); Zhao, Qi [Hebei University, College of Clinical Science (China); Jia, Guang [Hebei University, Key Laboratory of Chemical Biology of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry & Environmental Science (China); Zang, Aimin [Affiliated Hospital of Hebei University (China); Zhang, Cuimiao, E-mail: cmzhanghbu@163.com; Zhang, Jinchao, E-mail: jczhang6970@163.com [Hebei University, Key Laboratory of Chemical Biology of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry & Environmental Science (China)

    2016-03-15

    In drug delivery systems, nanocarriers could reduce the degradation and renal clearance of drugs, increase the half-life in the bloodstream and payload of drugs, control the release patterns, and improve the solubility of some insoluble drugs. In particular, mesoporous silica nanoparticles (MSNs) are considered to be attractive nanocarriers for application of delivery systems because of their large surface areas, large pore volume, tunable pore sizes, good biocompatibility, and the ease of surface functionalization. However, the large-scale synthesis of monodisperse MSNs that are smaller than 200 nm remains a challenge. In this study, monodisperse walnut kernel-like MSNs with diameters of approximately 100 nm were synthesized by a sol–gel route on a large scale. The morphology and structure of MSNs were characterized by scanning electron microscope, and transmission electron microscopy, N{sub 2} adsorption–desorption isotherms, Zeta potentials, and dynamic light scattering. Drug loading and release profile, cellular uptake, subcellular localization, and anticancer effect in vitro were further investigated. The results indicated that the loading efficiency of doxorubicinhydrochloride (DOX) into the MSNs was 57 %. The MSNs–DOX delivery system exhibited a drug-pronounced initial burst release within 12 h, followed by the slow sustained release of DOX molecules; moreover, MSNs could improve DOX release efficiency in acidic medium. Most free DOX was localized in the cytoplasm, whereas the MSNs–DOX was primarily distributed in lysosome. MSNs–DOX exhibited a potential anticancer effect against MCF-7, HeLa, and A549 cells in dose- and time-dependent manners. In summary, the as-synthesized MSNs may have well function as a promising drug carrier in drug delivery fields.Graphical Abstract.

  1. Effects of Neuroactive Drugs in the Discharge Patterns of Microsternarchus (Hypopomidae: Gymnotiformes) Electric Organ.

    Science.gov (United States)

    de Jesus, Isac Silva; Ferreira, Milena; Silva-Júnior, Urbano Lopes; Alves-Gomes, José Antônio

    2017-12-01

    Considering the conserved nature of synaptic physiology among vertebrates, we tested the effects of three psychotropics (diazepam, doxapram, and nicotine) on Microsternarchus cf. bilineatus, measuring 10 parameters associated to the electric organ discharges rhythm and waveform before and after the administration of each drug and a control group. There were statistically significant differences (p electric organ's (EO) firing rate, regardless of the expected stimulant or depressor effect of the drugs on the central nervous system (CNS). The intensity of the response changed with the treatment. The observed changes in the fishes' behavior may be a result of the drugs' direct action on the CNS or a combination of this with systemic effects of each substance tested, also in the EO.

  2. How strong is the edge effect in the adsorption of anticancer drugs on a graphene cluster?

    Science.gov (United States)

    Rungnim, Chompoonut; Chanajaree, Rungroj; Rungrotmongkol, Thanyada; Hannongbua, Supot; Kungwan, Nawee; Wolschann, Peter; Karpfen, Alfred; Parasuk, Vudhichai

    2016-04-01

    The adsorption of nucleobase-analog anticancer drugs (fluorouracil, thioguanine, and mercaptopurine) on a graphene flake (C54H18) was investigated by shifting the site at which adsorption occurs from one end of the sheet to the other end. The counterpoise-corrected M06-2X/cc-pVDZ binding energies revealed that the binding stability decreases in the sequence thioguanine > mercaptopurine > fluorouracil. We found that adsorption near the middle of the sheet is more favorable than adsorption near the edge due to the edge effect. This edge effect is stronger for the adsorption of thioguanine or mercaptopurine than for fluorouracil adsorption. However, the edge effect reduces the binding energy of the drug to the flake by only a small amount, <5 kcal/mol, depending on the adsorption site and the alignment of the drug at this site.

  3. THE EFFECT OF DIFFERENT TB DRUGS AND ANTIMICROBIAL AGENTS ON THE EFFICIENCY OF TREATMENT OF TUBERCULOSIS PATIENTS WITH MULTIPLE DRUG RESISTANCE

    Directory of Open Access Journals (Sweden)

    I. A. Vasilyeva

    2017-01-01

    Full Text Available Objective of the study: to study the effect of specific TB drugs and antimicrobial agents constituting chemotherapy regimens on the efficiency of treatment of tuberculosis patients with various patterns of multiple drug resistance.Subjects and Methods. 412 pulmonary tuberculosis patients with bacillary excretion and various patterns of multiple drug resistance were enrolled into the study (117 patients with MDR TB (non pre-XDR and non-XDR; 120 patients with pre-XDR TB and 175 with XDR TB. Patients in the subgroups were compatible regarding sex and age. The patients were prescribed regimens including 5-6 drugs in accordance with their drug resistance pattern. The time of sputum conversion (by culture versus the year of treatment was selected as a surrogate endpoint. The effect of specific TB drugs and antimicrobial agents on treatment efficiency was assessed through calculation of odds ratio (OR of achieving a surrogate endpoint in the patients receiving and not receiving a certain drug.Results. In the subgroup of pre-XDR TB, the following drugs demonstrated the valid increase of odds of sputum conversion: ethambutol (OR 11.8, pyrazinamide (OR 10.2, moxifloxacin (OR 7.8, capreomicin (OR 4.41. Sputum conversion was achieved in all 11 patients treated with bedaquiline.In the subgroup of XDR TB, the following drugs provided a positive effect on the achievement of sputum conversion: bedaquiline (OR 9.62, linezolid (OR 8.15, cycloserine (OR 7.88, pyrazinamide (OR 7.29, moxifloxacin (OR 7.08, and ethambutol (OR 6.69. Ofloxacin demonstrated a confident negative effect on achieving sputum conversion (95% CI 0.06-0.32. 

  4. The effect of direct-to-consumer advertising on prescription drug use by older adults.

    Science.gov (United States)

    Datti, Balaji; Carter, Mary W

    2006-01-01

    Although older adults are frequent consumers of prescription drugs and increasingly the intended audience of direct-to-consumer advertising (DTCA) marketing efforts, little is known about the effect of DTCA on older adults' prescription drug-seeking behaviour. In response, the objective of this study is to examine factors associated with requesting a prescription drug from a physician following exposure to DTCA among older adults, and whether the drug or other medical treatment was prescribed during the encounter. A secondary data analysis of the "Public Health Impact of Direct-to-Consumer Advertising of Prescription Drugs", a data set publicly available through the Inter-university Consortium for Political and Social Research (ICPSR 3687), was conducted. For the purposes of this study, only those respondents who indicated that they had been exposed to DTCA (n = 2601) were included in the study sample. Using a two-step weighted logistic regression approach, separate models were estimated to examine first, whether a request for the advertised drug was made following exposure to DTCA and secondly, the outcomes of any patient-physician encounters that occurred following exposure to DTCA. Descriptive analysis of the outcome variables revealed that, among respondents exposed to DTCA, 31% (n = 801) requested a prescription drug from their physician. Approximately 5% of those who made a request were > or =75 years of age. Among respondents requesting a prescription drug, 69% (n = 556) received a prescription in response to their request, of whom, approximately 5% were > or =75 years of age. Multivariate findings suggest that although adults > or =75 years of age are less likely to request a prescription drug following exposure to DTCA (odds ratio [OR] = 0.58; p = 0.032), when they do approach their physicians, they are more likely to receive recommendations for further treatment, with ORs indicating a 250% (OR = 3.507; p = 0.002) increase in the odds of further referral

  5. Autism and Obesity: Co-Occurring Conditions or Drug Side Effects

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0374 TITLE: Autism and Obesity: Co-Occurring Conditions or Drug Side Effects? PRINCIPAL INVESTIGATOR: Zohreh...SUBTITLE Autism and Obesity: Co-Occurring Conditions or Drug Side Effects? 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0374 5c. PROGRAM ELEMENT...project is to better understand the relationship between autism and obesity. It is not clear if obesity is co-occurring with autism or is related to

  6. Is More Better? Outcome and Dose of a Universal Drug Prevention Effectiveness Trial

    Science.gov (United States)

    Ferrer-Wreder, Laura; Cadely, Hans Saint-Eloi; Domitrovich, Celene E.; Small, Meg L.; Caldwell, Linda L.; Cleveland, Michael J.

    2014-01-01

    Two evidence-based interventions, Life Skills Training and TimeWise, were combined in an effectiveness trial. Participants were predominately African American youth (N = 715; Mage = 12). The study authors provide an empirical demonstration of the implications of incorporating dosage information in intervention outcome analyses. Study results showed no program-related benefits for drug use. Results indicated intervention-related benefits for assertiveness and anxiety management skills and drug use intentions as well as a reduction in detrimental leisure motivations. High program exposure and lesson coverage tended to be connected to intervention benefits. Study findings also documented ways that dosage information provides insight into interventions and their effects. PMID:21053080

  7. The effects of estrus cycle on drug metabolism in the rat.

    Science.gov (United States)

    Brandstetter, Y; Kaplanski, J; Leibson, V; Ben-Zvi, Z

    1986-01-01

    The effect of the female rat estral cycle on microsomal drug metabolism in-vivo and in-vitro has been studied. Two microsomal enzymes, aminopyrine-N-demethylase and aniline hydroxylase showed a greater specific activity (p less than 0.01) in the diestrus phase of the estral cycle while the oxidative enzyme aryl hydrocarbon hydroxylase and the conjugative enzyme, glucuronyl transferase, were not affected. In vivo studies which included theophylline and antipyrine metabolism, and hexobarbital sleeping times showed no difference between the different phases of the estral cycle. Conflicting evidence about the effect of steroid sex hormones on hepatic drug metabolism is discussed.

  8. Excitant and depressant drugs modulate effects of environment on brain weight and cholinesterases

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, E.L.; Rosenzweig, M.R.; Wu, S.Y.C.

    1973-01-01

    Certain excitant drugs can enhance the effects of enriched experience on weights of brain sections and on the activities of acetylcholinesterase and cholinesterase in the brain, and certain depressants can lessen the brain weight effects. Most experiments were performed with prepubertal male rats. Some rats were exposed in groups of 12 to an enriched environmental condition (EC), usually for 2 h per day and over a 30-day period; others remained in their individual home cages (HC) throughout. Some received a drug injection and others received a saline injection before the daily EC period; HC controls received similar injections. The drug injections had no significant effects on brain values of HC rats, but they altered effects of EC, probably by influencing the animals' reactions to the environment. Methamphetamine and d-amphetamine enhanced the EC effects; metrazol had small positive effects; and strychnine was without effects. Phenobarbital depressed the brain weight effects but increased the enzymatic effects. Use of methamphetamine made it possible to find EC effects with short daily periods (30 min) or with a shortened experimental duration (15 days). In experiments with adult rats, methamphetamine did not modulate the brain weight effects. The results of this study may bear on the use of stimulants to promote recovery from brain damage.

  9. Regulatory volume decrease in Leishmania mexicana: effect of anti-microtubule drugs

    Directory of Open Access Journals (Sweden)

    Francehuli Dagger

    2013-02-01

    Full Text Available The trypanosomatid cytoskeleton is responsible for the parasite's shape and it is modulated throughout the different stages of the parasite's life cycle. When parasites are exposed to media with reduced osmolarity, they initially swell, but subsequently undergo compensatory shrinking referred to as regulatory volume decrease (RVD. We studied the effects of anti-microtubule (Mt drugs on the proliferation of Leishmania mexicana promastigotes and their capacity to undergo RVD. All of the drugs tested exerted antiproliferative effects of varying magnitudes [ansamitocin P3 (AP3> trifluoperazine > taxol > rhizoxin > chlorpromazine]. No direct relationship was found between antiproliferative drug treatment and RVD. Similarly, Mt stability was not affected by drug treatment. Ansamitocin P3, which is effective at nanomolar concentrations, blocked amastigote-promastigote differentiation and was the only drug that impeded RVD, as measured by light dispersion. AP3 induced 2 kinetoplasts (Kt 1 nucleus cells that had numerous flagella-associated Kts throughout the cell. These results suggest that the dramatic morphological changes induced by AP3 alter the spatial organisation and directionality of the Mts that are necessary for the parasite's hypotonic stress-induced shape change, as well as its recovery.

  10. The Potential Return on Public Investment in Detecting Adverse Drug Effects.

    Science.gov (United States)

    Huybrechts, Krista F; Desai, Rishi J; Park, Moa; Gagne, Joshua J; Najafzadeh, Mehdi; Avorn, Jerry

    2017-06-01

    Many countries lack fully functional pharmacovigilance programs, and public budgets allocated to pharmacovigilance in industrialized countries remain low due to resource constraints and competing priorities. Using 3 case examples, we sought to estimate the public health and economic benefits resulting from public investment in active pharmacovigilance programs to detect adverse drug effects. We assessed 3 examples in which early signals of safety hazards were not adequately recognized, resulting in continued exposure of a large number of patients to these drugs when safer and effective alternative treatments were available. The drug examples studied were rofecoxib, cerivastatin, and troglitazone. Using an individual patient simulation model and the health care system perspective, we estimated the potential costs that could have been averted by early systematic detection of safety hazards through the implementation of active surveillance programs. We found that earlier drug withdrawal made possible by active safety surveillance would most likely have resulted in savings in direct medical costs of $773-$884 million for rofecoxib, $3-$10 million for cerivastatin, and $38-$63 million for troglitazone in the United States through the prevention of adverse events. By contrast, the yearly public investment in Food and Drug Administration initiated population-based pharmacovigilance activities in the United States is about $42.5 million at present. These examples illustrate a critical and economically justifiable role for active adverse effect surveillance in protecting the health of the public.

  11. Privacy effects on self-reported drug use: interactions with survey mode and respondent characteristics.

    Science.gov (United States)

    Aquilino, W S

    1997-01-01

    This chapter examines the impact of interview privacy on self-reported illicit drug use. In 1991, interviews were completed with an urban-suburban sample of 2,417 adults aged 18 to 45. Results show that the presence of third parties during the interview significantly influences respondents' willingness to reveal illicit drug use. Among married respondents, presence of a spouse resulted in higher reporting of illicit drug use, while the presence of adults other than the spouse had a consistent negative effect on drug use reports. A parent's presence during the interview significantly reduced respondents' willingness to report illicit drug use. The pattern of findings suggests that the direction of effects due to third party presence is linked to two factors: the extent of the third party's knowledge of the information requested, and the degree of personal stake the third party may have in the respondent's answers. The differential impact of privacy by interview mode was also examined. Tests of interactions between privacy and interview mode failed to support the hypothesis that the use of self-administered answer sheets reduces privacy effects compared with interviewer-administered interviews.

  12. Retail price as an outcome measure for the effectiveness of drug law enforcement.

    Science.gov (United States)

    Bright, David A; Ritter, Alison

    2010-09-01

    One outcome measure of law enforcement effectiveness is the reduction in drug consumption which occurs as a result of law enforcement interventions. A theoretical relationship between drug consumption and retail price has promoted the use of retail price as a surrogate measure for consumption. In the current article, retail price is examined as a potential outcome measure for the effectiveness of law enforcement. The predictions regarding the relationship between law enforcement intensity and price are only partially supported by research. Explanations for the disconnect between the drug law enforcement activity and retail price include: rapid adaptation by market players, enforcement swamping, assumptions of rational actors, short-run versus long-run effects, structure of the illicit market, simultaneous changes that affect price in perverse ways, the role of violence in markets, and data limitations. Researchers who use retail price as an outcome measure need to take into account the complex relationship between drug law enforcement interventions and the retail price of illicit drugs. Viable outcome measures which can be used as complements to retail price are worth investigation. Copyright 2009 Elsevier B.V. All rights reserved.

  13. Effects of cancer, radiotherapy and cytotoxic drugs on intestinal structure and function

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, M T; Spector, M H; Ladman, A J [New Mexico Univ., Albuquerque (USA)

    1979-09-01

    Intestinal malabsorption and the structural changes in the small intestine in relation to cancer, radiotherapy and cytotoxic drugs are reviewed. Primary intestinal malignancies are often associated with malabsorption; further studies have shown that tumours outside the gastrointestinal tract may also be accompanied by changes in intestinal structure resulting in malabsorption. Abdominal radiotherapy of cancer patients has been shown to result in ultrastructural changes in the small intestine, a decrease in intestinal enzyme activity and malabsorption of nutrients. The effects of cytotoxic drugs on the small intestinal structure and function are reviewed in more detail. The drugs discussed include the alkylating agents such as nitrogen mustard, cyclophosphamide, iphosphamide, 1,3-bis (2-chloroethyl)-1-nitrosourea and 1(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea. The effects of antimetabolites such as aminopterin, methotrexate, 5-fluoracil, cytosine arabinoside and 6-mercaptorpurine are also reviewed. Other drugs discussed were adriamycin, vincrinstine sulfate, vinblastine and hydroxyurea. Studies of the effects of combination chemotherapy on small intestinal structure and function are also described. It is concluded that chemotherapeutic drugs and radiation therapy may aggravate a malabsorptive state in view of their toxicity to the small intestinal cell, or may by themselves be responsible for malabsorption with resultant increase in cachexia and weight loss.

  14. Effects of cancer, radiotherapy and cytotoxic drugs on intestinal structure and function

    International Nuclear Information System (INIS)

    Shaw, M.T.; Spector, M.H.; Ladman, A.J.

    1979-01-01

    Intestinal malabsorption and the structural changes in the small intestine in relation to cancer, radiotherapy and cytotoxic drugs are reviewed. Primary intestinal malignancies are often associated with malabsorption; further studies have shown that tumours outside the gastrointestinal tract may also be accompanied by changes in intestinal structure resulting in malabsorption. Abdominal radiotherapy of cancer patients has been shown to result in ultrastructural changes in the small intestine, a decrease in intestinal enzyme activity and malabsorption of nutrients. The effects of cytotoxic drugs on the small intestinal structure and function are reviewed in more detail. The drugs discussed include the alkylating agents such as nitrogen mustard, cyclophosphamide, iphosphamide, 1,3-bis (2-chloroethyl)-1-nitrosourea and 1(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea. The effects of antimetabolites such as aminopterin, methotrexate, 5-fluoracil, cytosine arabinoside and 6-mercaptorpurine are also reviewed. Other drugs discussed were adriamycin, vincrinstine sulfate, vinblastine and hydroxyurea. Studies of the effects of combination chemotherapy on small intestinal structure and function are also described. It is concluded that chemotherapeutic drugs and radiation therapy may aggravate a malabsorptive state in view of their toxicity to the small intestinal cell, or may by themselves be responsible for malabsorption with resultant increase in cachexia and weight loss. (UK)

  15. Neuroprotective effects of the antiparkinson drug Mucuna pruriens.

    Science.gov (United States)

    Manyam, Bala V; Dhanasekaran, Muralikrishnan; Hare, Theodore A

    2004-09-01

    Mucuna pruriens possesses significantly higher antiparkinson activity compared with levodopa in the 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease. The present study evaluated the neurorestorative effect of Mucuna pruriens cotyledon powder on the nigrostriatal tract of 6-OHDA lesioned rats. Mucuna pruriens cotyledon powder significantly increased the brain mitochondrial complex-I activity but did not affect the total monoamine oxidase activity (in vitro). Unlike synthetic levodopa treatment, Mucuna pruriens cotyledon powder treatment significantly restored the endogenous levodopa, dopamine, norepinephrine and serotonin content in the substantia nigra. Nicotine adenine dinucleotide (NADH) and coenzyme Q-10, that are shown to have a therapeutic benefit in Parkinson's disease, were present in the Mucuna pruriens cotyledon powder. Earlier studies showed that Mucuna pruriens treatment controls the symptoms of Parkinson's disease. This additional finding of a neurorestorative benefit by Mucuna pruriens cotyledon powder on the degenerating dopaminergic neurons in the substantia nigra may be due to increased complex-I activity and the presence of NADH and coenzyme Q-10. Copyright (c) 2004 John Wiley & Sons, Ltd.

  16. Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease

    Directory of Open Access Journals (Sweden)

    Edward C. Lauterbach

    2013-11-01

    Full Text Available Psychotropics (antipsychotics, mood stabilizers, antidepressants, anxiolytics, etc. are commonly prescribed to treat Huntington’s disease (HD. In HD preclinical models, while no psychotropic has convincingly affected huntingtin gene, HD modifying gene, or huntingtin protein expression, psychotropic neuroprotective effects include upregulated huntingtin autophagy (lithium, histone acetylation (lithium, valproate, lamotrigine, miR-222 (lithium-plus-valproate, mitochondrial protection (haloperidol, trifluoperazine, imipramine, desipramine, nortriptyline, maprotiline, trazodone, sertraline, venlafaxine, melatonin, neurogenesis (lithium, valproate, fluoxetine, sertraline, and BDNF (lithium, valproate, sertraline and downregulated AP-1 DNA binding (lithium, p53 (lithium, huntingtin aggregation (antipsychotics, lithium, and apoptosis (trifluoperazine, loxapine, lithium, desipramine, nortriptyline, maprotiline, cyproheptadine, melatonin. In HD live mouse models, delayed disease onset (nortriptyline, melatonin, striatal preservation (haloperidol, tetrabenazine, lithium, sertraline, memory preservation (imipramine, trazodone, fluoxetine, sertraline, venlafaxine, motor improvement (tetrabenazine, lithium, valproate, imipramine, nortriptyline, trazodone, sertraline, venlafaxine, and extended survival (lithium, valproate, sertraline, melatonin have been documented. Upregulated CREB binding protein (CBP; valproate, dextromethorphan and downregulated histone deacetylase (HDAC; valproate await demonstration in HD models. Most preclinical findings await replication and their limitations are reviewed. The most promising findings involve replicated striatal neuroprotection and phenotypic disease modification in transgenic mice for tetrabenazine and for sertraline. Clinical data consist of an uncontrolled lithium case series (n = 3 suggesting non-progression and a primarily negative double-blind, placebo-controlled clinical trial of lamotrigine.

  17. IONP-doped nanoparticles for highly effective NIR-controlled drug release and combination tumor therapy

    Directory of Open Access Journals (Sweden)

    Fu X

    2017-05-01

    Full Text Available Xudong Fu,1 Xinjun Wang,1 Shaolong Zhou,1 Yanyan Zhang2 1The Fifth Affiliated Hospital of Zhengzhou University, 2School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China Abstract: Despite advances in controlled drug delivery, drug delivery systems (DDSs with controlled activated drug release and high spatial and temporal resolution are still required. Theranostic nanomedicine is capable of diagnosis, therapy, and monitoring the delivery and distribution of drug molecules and has received growing interest. In this study, a near-infrared light-controlled “off–on” DDS with magnetic resonance imaging and magnetic targeting properties was developed using a hybrid nanoplatform (carbon nanotubes [CNTs]-iron oxide nanoparticle. Doxorubicin (DOX and distearoyl-sn-glycero-3-phosphoethanolamine-PEG were adsorbed onto CNTs-iron oxide nanoparticle, and then to avoid the unexpected drug release during circulation, 1-myristyl alcohol was used to encapsulate the CNTs–drug complex. Herein, multifunctional DOX-loaded nanoparticles (NPs with “off–on” state were developed. DOX-NPs showed an obvious “off–on” effect (temperature increase, drug release controlled by near-infrared light in vitro and in vivo. In the in vivo and in vitro studies, DOX-NPs exhibited excellent magnetic resonance imaging ability, magnetic targeting property, high biosafety, and high antitumor combined therapeutic efficacy (hyperthermia combined with chemotherapy. These results highlight the great potential of DOX-NPs in the treatment of cancer. Keywords: controlled drug release, magnetic targeting, MRI, combination therapy

  18. Patient centric drug product design in modern drug delivery as an opportunity to increase safety and effectiveness.

    Science.gov (United States)

    Stegemann, Sven

    2018-06-01

    The advances in drug delivery technologies have enabled pharmaceutical scientists to deliver a drug through various administration routes and optimize the drug release and absorption. The wide range of drug delivery systems and dosage forms represent a toolbox of technology for the development of pharmaceutical drug products but might also be a source of medication errors and nonadherence. Patient centric drug product development is being suggested as an important factor to increase therapeutic outcomes. Areas covered: Patients have impaired health and potentially disabilities and they are not medical or pharmaceutical experts but are requested to manage complex therapeutic regimens. As such the application of technology should also serve to reduce complexity, build on patients' intuition and ease of use. Patients form distinct populations based on the targeted disease, disease cluster or age group with specific characteristics or therapeutic contexts. Expert opinion: Establishing a target product and patient profile is essential to guide drug product design development. Including the targeted patient populations in the process is a prerequisite to achieve patient-centric pharmaceutical drug product design. Addressing the needs early on in the product design process, will create more universal design, avoiding the necessity for multiple product presentations to cover the different patient populations.

  19. Legal Drugs Are Good Drugs And Illegal Drugs Are Bad Drugs

    Directory of Open Access Journals (Sweden)

    Dina Indrati

    2011-07-01

    Full Text Available ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing setting and dual diagnosis.Key words: Legal, good drugs, illegal, bad drugs.

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

    Science.gov (United States)

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

    2008-01-01

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

  1. Therapeutic use of the rebound effect of modern drugs: "New homeopathic medicines"

    Directory of Open Access Journals (Sweden)

    Marcus Zulian Teixeira

    Full Text Available Summary The homeopathic treatment is based on the principle of therapeutic similitude, employing medicines that cause certain disorders to treat similar manifestations, stimulating a reaction of the organism against its own ailments. The occurrence of this secondary reaction of the organism, opposite in nature to the primary action of the medicines, is evidenced in the study of the rebound (paradoxical effect of several classes of modern drugs. In this work, in addition to substantiate the principle of similitude before the experimental and clinical pharmacology, we suggest a proposal to employ hundreds of conventional drugs according to homeopathic method, applying the therapeutic similitude between the adverse events of medicines and the clinical manifestations of patients. Describing existing lines of research and a specific method for the therapeutic use of the rebound effect of modern drugs (http://www.newhomeopathicmedicines.com, we hope to minimize prejudices related to the homeopathy and contribute to a broadening of the healing art.

  2. Use of comparative effectiveness research in drug coverage and pricing decisions: a six-country comparison.

    Science.gov (United States)

    Sorenson, Corinna

    2010-07-01

    Comparative effectiveness research (CER) has assumed an increasing role in drug coverage and, in some cases, pricing decisions in Europe, as decision-makers seek to obtain better value for money. This issue brief comparatively examines the use of CER across six countries--Denmark, England, France, Germany, the Netherlands, and Sweden. With CER gaining traction in the United States, these international experiences offer insights and potential lessons. Investing in CER can help address the current gap in publicly available, credible, up-to-date, and scientifically based comparative information on the effectiveness of drugs and other health interventions. This information can be used to base coverage and pricing decisions on evidence of value, thereby facilitating access to and public and private investment in the most beneficial new drugs and technologies. In turn, use of CER creates incentives for more efficient, high-quality health care and encourages development of innovative products that offer measurable value to patients.

  3. Is Neural Processing of Negative Stimuli Altered in Addiction Independent of Drug Effects? Findings From Drug-Naïve Youth with Internet Gaming Disorder.

    Science.gov (United States)

    Yip, Sarah W; Gross, James J; Chawla, Megha; Ma, Shan-Shan; Shi, Xing-Hui; Liu, Lu; Yao, Yuan-Wei; Zhu, Lei; Worhunsky, Patrick D; Zhang, Jintao

    2018-05-01

    Difficulties in emotion regulation are commonly reported among individuals with alcohol and drug addictions and contribute to the acquisition and maintenance of addictive behaviors. Alterations in neural processing of negative affective stimuli have further been demonstrated among individuals with addictions. However, it is unclear whether these alterations are a general feature of addictions or are a result of prolonged exposure to drugs of abuse. To test the hypothesis of altered negative affect processing independent of drug effects, this study assessed neural function among drug-naïve youth with a behavioral addiction-Internet gaming disorder (IGD). Fifty-six young adults (28 with IGD, 28 matched controls) participated in fMRI scanning during performance of a well-validated emotion regulation task. Between-group differences in neural activity during task performance were assessed using a whole-brain, mixed-effects ANOVA with correction for multiple comparisons at currently recommended thresholds (voxel-level peffects.

  4. Optimal Anti-cancer Drug Profiles for Effective Penetration of the Anti-cancer Drug Market by Generic Drugs in Japan.

    Science.gov (United States)

    Shibata, Shoyo; Matsushita, Maiko; Saito, Yoshimasa; Suzuki, Takeshi

    2017-01-01

    The increased use of generic drugs is a good indicator of the need to reduce the increasing costs of prescription drugs. Since there are more expensive drugs compared with other therapeutic areas, "oncology" is an important one for generic drugs. The primary objective of this article was to quantify the extent to which generic drugs in Japan occupy each level of the Anatomical Therapeutic Chemical (ATC) classification system. The dataset used in this study was created from publicly available information obtained from the IMS Japan Pharmaceutical Market database. Data on the total amount of sales and number of prescriptions for anti-cancer drugs between 2010 and 2016 in Japan were selected. The data were categorized according to the third level of the ATC classification system. All categories of the ATC classification system had increased market shares in Japan between 2010 and 2016. The barriers to market entry were relatively low in L01F (platinum anti-neoplastics), L01C (plant-based neoplastics), L02B (cytostatic hormone antagonists), and L01D (anti-neoplastic antibiotics) but were high in L02A (cytostatic hormones), L01H (protein kinase inhibitors), and L01B (anti-metabolites). Generic cancer drugs could bring savings to Japanese health care systems. Therefore, their development should be directed toward niche markets, such as L02A, L01H, and L01B, and not competitive markets.

  5. Clinical effectiveness of multiple-drug injection treatment in unruptured ectopic pregnancies: a retrospective study.

    Science.gov (United States)

    Dai, Quan; Wang, Lu-Lu; Shao, Xiao-Hui; Wang, Si-Ming; Dong, Xiao-Qiu

    2012-10-01

    To study the effect of local interventional treatment of unruptured ectopic pregnancies with multiple-drug injection guided by color Doppler sonography. In this retrospective analysis, 49 patients with an unruptured ectopic pregnancy were treated with two different local injection methods administered under sonographic guidance. The patients were divided into single-drug (n = 23) and multiple-drug (n = 26) injection groups, and they received a locally administered injection of methotrexate alone or a combination including methotrexate, hemocoagulase, antibiotics, and anti-inflammatory drugs, respectively. Overall, local injection treatment was successful in 44 patients. The 5 patients with failed treatment underwent laparotomy about 1 week after single-drug injection. Serum β-human chorionic gonadotropin (β-hCG ) levels, ectopic pregnancy mass sizes, blood flow at various points after treatment, the incidence of pelvic bleeding, and the time for serum β-hCG levels to return to normal and the mass to resolve were analyzed in the remaining 44 patients. Single-drug treatment was successful in 18 patients; 10 of 23 had low to moderate pelvic bleeding after treatment, and 5 were referred for surgery. All 26 patients were successfully treated by multiple-drug injection. Only 2 patients had a small amount of pelvic bleeding. Differences between groups were statistically significant (P injection under color Doppler guidance is a new, safe, and effective method for treating unruptured ectopic pregnancies. It accelerates the serum β-hCG decline and facilitates mass resolution. This regimen is associated with a very low rate of pelvic bleeding, improves the success rate of conservative treatment, and, therefore, has value as an important clinical application.

  6. Effects of drugs of abuse on putative rostromedial tegmental neurons, inhibitory afferents to midbrain dopamine cells.

    Science.gov (United States)

    Lecca, Salvatore; Melis, Miriam; Luchicchi, Antonio; Ennas, Maria Grazia; Castelli, Maria Paola; Muntoni, Anna Lisa; Pistis, Marco

    2011-02-01

    Recent findings have underlined the rostromedial tegmental nucleus (RMTg), a structure located caudally to the ventral tegmental area, as an important site involved in the mechanisms of aversion. RMTg contains γ-aminobutyric acid neurons responding to noxious stimuli, densely innervated by the lateral habenula and providing a major inhibitory projection to reward-encoding midbrain dopamine (DA) neurons. One of the key features of drug addiction is the perseverance of drug seeking in spite of negative and unpleasant consequences, likely mediated by response suppression within neural pathways mediating aversion. To investigate whether the RMTg has a function in the mechanisms of addicting drugs, we studied acute effects of morphine, cocaine, the cannabinoid agonist WIN55212-2 (WIN), and nicotine on putative RMTg neurons. We utilized single unit extracellular recordings in anesthetized rats and whole-cell patch-clamp recordings in brain slices to identify and characterize putative RMTg neurons and their responses to drugs of abuse. Morphine and WIN inhibited both firing rate in vivo and excitatory postsynaptic currents (EPSCs) evoked by stimulation of rostral afferents in vitro, whereas cocaine inhibited discharge activity without affecting EPSC amplitude. Conversely, nicotine robustly excited putative RMTg neurons and enhanced EPSCs, an effect mediated by α7-containing nicotinic acetylcholine receptors. Our results suggest that activity of RMTg neurons is profoundly influenced by drugs of abuse and, as important inhibitory afferents to midbrain DA neurons, they might take place in the complex interplay between the neural circuits mediating aversion and reward.

  7. Effects of Music Therapy on Drug Therapy of Adult Psychiatric Outpatients: A Pilot Randomized Controlled Study

    Science.gov (United States)

    Degli Stefani, Mario; Biasutti, Michele

    2016-01-01

    Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in addition to other non-expressive group activities in the treatment of psychiatric outpatients. Method: Participants (n = 27) with ICD-10 diagnoses of F20 (schizophrenia), F25 (schizoaffective disorders), F31 (bipolar affective disorder), F32 (depressive episode), and F60 (specific personality disorders) were randomized to receive group music therapy plus standard care (48 weekly sessions of 2 h) or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilizers, and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage with respect to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilizers did not show any significant change in either group. Conclusion: Group music therapy combined with standard drug care was effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discussed the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centered perspective were also discussed. PMID:27774073

  8. Effects of music therapy on drug therapy of adult psychiatric outpatients: A pilot randomised controlled study

    Directory of Open Access Journals (Sweden)

    Mario Degli Stefani

    2016-10-01

    Full Text Available Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in the treatment of psychiatric outpatients. Method: Participants (n = 27 with ICD-10 diagnoses of F20 (schizophrenia, F25 (schizoaffective disorders, F31 (bipolar affective disorder, F32 (depressive episode and F60 (specific personality disorders were randomised to receive group music therapy plus standard care (48 weekly sessions of two hours or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilisers and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage relative to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilisers did not show any significant change in either group. Conclusions: Group music therapy combined with standard drug care is effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discuss the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centred perspective were also discussed.

  9. Effects of regulation on drug launch and pricing in interdependent markets.

    Science.gov (United States)

    Danzon, Patricia M; Epstein, Andrew J

    2012-01-01

    This study examines the effect of price regulation and competition on launch timing and pricing of new drugs. Our data cover launch experience in 15 countries from 1992 to 2003 for drugs in 12 major therapeutic classes. We estimate a two-equation model of launch hazard and launch price of new drugs. We find that launch timing and prices of new drugs are related to a country's average prices of established products in a class. Thus to the extent that price regulation reduces price levels, such regulation directly contributes to launch delay in the regulating country. Regulation by external referencing, whereby high-price countries reference low-price countries, also has indirect or spillover effects, contributing to launch delay and higher launch prices in low-price referenced countries. Referencing policies adopted in high-price countries indirectly impose welfare loss on low-price countries. These findings have implications for US proposals to constrain pharmaceutical prices through external referencing and drug importation.

  10. Amazing structure of respirasome: unveiling the secrets of cell respiration.

    Science.gov (United States)

    Guo, Runyu; Gu, Jinke; Wu, Meng; Yang, Maojun

    2016-12-01

    Respirasome, a huge molecular machine that carries out cellular respiration, has gained growing attention since its discovery, because respiration is the most indispensable biological process in almost all living creatures. The concept of respirasome has renewed our understanding of the respiratory chain organization, and most recently, the structure of respirasome solved by Yang's group from Tsinghua University (Gu et al. Nature 237(7622):639-643, 2016) firstly presented the detailed interactions within this huge molecular machine, and provided important information for drug design and screening. However, the study of cellular respiration went through a long history. Here, we briefly showed the detoured history of respiratory chain investigation, and then described the amazing structure of respirasome.

  11. Pharmacotherapy in pregnancy; effect of ABC and SLC transporters on drug transport across the placenta and fetal drug exposure.

    Science.gov (United States)

    Staud, Frantisek; Cerveny, Lukas; Ceckova, Martina

    2012-11-01

    Pharmacotherapy during pregnancy is often inevitable for medical treatment of the mother, the fetus or both. The knowledge of drug transport across placenta is, therefore, an important topic to bear in mind when deciding treatment in pregnant women. Several drug transporters of the ABC and SLC families have been discovered in the placenta, such as P-glycoprotein, breast cancer resistance protein, or organic anion/cation transporters. It is thus evident that the passage of drugs across the placenta can no longer be predicted simply on the basis of their physical-chemical properties. Functional expression of placental drug transporters in the trophoblast and the possibility of drug-drug interactions must be considered to optimize pharmacotherapy during pregnancy. In this review we summarize current knowledge on the expression and function of ABC and SLC transporters in the trophoblast. Furthermore, we put this data into context with medical conditions that require maternal and/or fetal treatment during pregnancy, such as gestational diabetes, HIV infection, fetal arrhythmias and epilepsy. Proper understanding of the role of placental transporters should be of great interest not only to clinicians but also to pharmaceutical industry for future drug design and development to control the degree of fetal exposure.

  12. Some remarks on the effects of drugs, lack of sleep and loud noise on human performance.

    NARCIS (Netherlands)

    Sanders, A.F. & A.A. Bunt.

    1971-01-01

    Some literature is reviewed on the effect of some drugs, (amphetamine, hypnotics, alcohol), loud noise and sleep loss in test of time estimation, decision making, long term performance and short term memory. Results are most clear with respect to amphetamine, hypnotics and lack of sleep, in that

  13. Is Chronic Dialysis the Right Hard Renal End Point To Evaluate Renoprotective Drug Effects?

    NARCIS (Netherlands)

    Weldegiorgis, Misghina; de Zeeuw, Dick; Dwyer, Jamie P.; Mol, Peter; Heerspink, Hiddo J. L.

    2017-01-01

    Background and objectives: RRT and doubling of serum creatinine are considered the objective hard end points in nephrology intervention trials. Because both are assumed to reflect changes in the filtration capacity of the kidney, drug effects, if present, are attributed to kidney protection.

  14. Ankle sprain: the effects of non-steroidal anti-inflammatory drugs

    NARCIS (Netherlands)

    Struijs, Peter A. A.; Kerkhoffs, Gino M. M. J.

    2015-01-01

    Injury of the lateral ligament complex of the ankle joint occurs in about one in 10,000 people per day, accounting for a quarter of all sports injuries. We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of non-steroidal anti-inflammatory drugs

  15. Effect of Zeta Potential on the Properties of Nano-Drug Delivery ...

    African Journals Online (AJOL)

    The zeta potential (ZP) of colloidal systems and nano-medicines, as well as their particle size exert a major effect on the various properties of nano-drug delivery systems. Not only the stability of dosage forms and their release rate are affected but also their circulation in the blood stream and absorption into body membranes ...

  16. Effectiveness of various non-steroidal anti-inflammatory drugs in ...

    African Journals Online (AJOL)

    Purpose: To study the effectiveness of various nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with vertebral fractures. Methods: A total of 78 patients (17 males and 61 females) with a mean age of 69.5 years were included. The major inclusion criterion was an osteoporotic vertebral fracture between T7 and L3.

  17. Effects of dietary anticarcinogens and nonsteroidal anti-inflammatory drugs on rat gastrointestinal UDP-glucuronosyltransferases.

    NARCIS (Netherlands)

    Logt, E.M.J. van der; Roelofs, H.M.J.; Lieshout, E.M.M. van; Nagengast, F.M.; Peters, W.H.M.

    2004-01-01

    BACKGROUND: Dietary compounds or nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce cancer rates. Elevation of phase II detoxification enzymes might be one of the mechanisms leading to cancer prevention. We investigated the effects of dietary anticarcinogens and NSAIDs on rat gastrointestinal

  18. Synergistic effects of plasma-activated medium and chemotherapeutic drugs in cancer treatment

    Science.gov (United States)

    Chen, Chao-Yu; Cheng, Yun-Chien; Cheng, Yi-Jing

    2018-04-01

    Chemotherapy is an important treatment method for metastatic cancer, but the drug-uptake efficiency of cancer cells needs to be enhanced in order to diminish the side effects of chemotherapeutic drugs and improve survival. The use of a nonequilibrium low-temperature atmospheric-pressure plasma jet (APPJ) has been demonstrated to exert selective effects in cancer therapy and to be able to enhance the uptake of molecules by cells, which makes an APPJ a good candidate adjuvant in combination chemotherapy. This study estimated the effects of direct helium-based APPJ (He-APPJ) exposure (DE) and He-APPJ-activated RPMI medium (PAM) on cell viability and migration. Both of these treatments decreased cell viability and inhibited cell migration, but to different degrees in different cell types. The use of PAM as a culture medium resulted in the dialkylcarbocyanine (DiI) fluorescent dye entering the cells more efficiently. PAM was combined with the anticancer drug doxorubicin (Doxo) to treat human heptocellular carcinoma HepG2 cells and human adenocarcinomic alveolar basal epithelial A549 cells. The results showed that the synergistic effects of combined PAM and Doxo treatment resulted in stronger lethality in cancer cells than did PAM or Doxo treatment alone. To sum up, PAM has potential as an adjuvant in combination with other drugs to improve curative cancer therapies.

  19. Adolescent Drug Use and the Deterrent Effect of School-Imposed Penalties

    Science.gov (United States)

    Waddell, G. R.

    2012-01-01

    Estimates of the effect of school-imposed penalties for drug use on a student's consumption of marijuana are biased if both are determined by unobservable school or individual attributes. Reverse causality is also a potential challenge to retrieving estimates of the causal relationship, as the severity of school sanctions may simply reflect the…

  20. Effects of Program and Patient Characteristics on Retention of Drug Treatment Patients.

    Science.gov (United States)

    Hser, Yih-Ing; Joshi, Vandana; Maglione, Margaret; Chou, Chih Ping; Anglin, M. Douglas

    2001-01-01

    Studied the effects of program and patient characteristics on patient retention in residential, out-patient, and methadone maintenance drug treatment programs. Data for 26,047 patients in 87 programs show that threshold retention rates were generally low for all 3 program types, although program practice and service provision played important…

  1. Effectiveness of recommended drug classes in secondary prevention of acute coronary syndrome in France

    NARCIS (Netherlands)

    Bezin, Julien; Groenwold, Rolf; Ali, Sanni; Lassalle, Régis; De Boer, Anthonius; Moore, Nicholas; Klungel, Olaf; Pariente, Antoine

    Background: Guidelines for cardiovascular secondary prevention are based on evidence from relatively old clinical trials and need to be evaluated in daily clinical practice. Objectives: To evaluate effectiveness of the recommended drug classes after an acute coronary syndrome (ACS) for secondary

  2. Effectiveness of Drug Education Components: Knowledge, Attitudes, Decision Making, Motivations, and Self-Esteem.

    Science.gov (United States)

    Roberts, Scott W.

    1995-01-01

    This study examined the effectiveness of school-based drug education in affecting knowledge, attitudes, decision making, motivation, and self-esteem. Pre- and postintervention surveys of fourth through eighth graders indicated that self-esteem did not improve significantly. Knowledge and attitude scores improved significantly, with a positive…

  3. Effect of antiretroviral drug (arved) on hepatic enzymes in albino rats ...

    African Journals Online (AJOL)

    ... with very little or no laboratory monitory, limited attention has been given to side effects ... A total of fifty two (52) albino rats were randomly divided into four groups ... The mean value of ALT activity for the drug in dose dependent manner was ...

  4. School-Based Drug Prevention among At-Risk Adolescents: Effects of ALERT Plus

    Science.gov (United States)

    Longshore, Douglas; Ellickson, Phyllis L.; McCaffrey, Daniel F.; St. Clair, Patricia A.

    2007-01-01

    In a recent randomized field trial, Ellickson et al. found the Project ALERT drug prevention curriculum curbed alcohol misuse and tobacco and marijuana use among eighth-grade adolescents. This article reports effects among ninth-grade at-risk adolescents. Comparisons between at-risk girls in ALERT Plus schools (basic curriculum extended to ninth…

  5. Suicide Risk in College Students: The Effects of Internet Addiction and Drug Use

    Science.gov (United States)

    Genctanirim Kurt, Dilek

    2015-01-01

    This study aims to identify the factors in suicide risk among college students by examining the direct and indirect effects of drug use, internet addiction, gender, and alcohol use on suicide risk. The sample of the study is composed of 975 students studying at different faculties of Ahi Evran University during the academic year 2011-2012. They…

  6. Methods to assess intended effects of drug treatment in observational studies are reviewed

    NARCIS (Netherlands)

    Klungel, Olaf H|info:eu-repo/dai/nl/181447649; Martens, Edwin P|info:eu-repo/dai/nl/088859010; Psaty, Bruce M; Grobbee, Diederik E; Sullivan, Sean D; Stricker, Bruno H Ch; Leufkens, Hubert G M|info:eu-repo/dai/nl/075255049; de Boer, A|info:eu-repo/dai/nl/075097346

    2004-01-01

    BACKGROUND AND OBJECTIVE: To review methods that seek to adjust for confounding in observational studies when assessing intended drug effects. METHODS: We reviewed the statistical, economical and medical literature on the development, comparison and use of methods adjusting for confounding. RESULTS:

  7. The effects of drugs on nutrition | Van Zyl | South African Journal of ...

    African Journals Online (AJOL)

    South African Journal of Clinical Nutrition. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 24, No 3 (2011) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. The effects of drugs on nutrition. M Van Zyl ...

  8. Effectiveness of a Clinical Skills Workshop for drug-dosage calculation in a nursing program.

    Science.gov (United States)

    Grugnetti, Anna Maria; Bagnasco, Annamaria; Rosa, Francesca; Sasso, Loredana

    2014-04-01

    Mathematical and calculation skills are widely acknowledged as being key nursing competences if patients are to receive care that is both effective and safe. Indeed, weaknesses in mathematical competence may lead to the administration of miscalculated drug doses, which in turn may harm or endanger patients' lives. However, little attention has been given to identifying appropriate teaching and learning strategies that will effectively facilitate the development of these skills in nurses. One such approach may be simulation. To evaluate the effectiveness of a Clinical Skills Workshop on drug administration that focused on improving the drug-dosage calculation skills of second-year nursing students, with a view to promoting safety in drugs administration. A descriptive pre-post test design. Educational. Simulation center. The sample population included 77 nursing students from a Northern Italian University who attended a 30-hour Clinical Skills Workshop over a period of two weeks. The workshop covered integrated teaching strategies and innovative drug-calculation methodologies which have been described to improve psychomotor skills and build cognitive abilities through a greater understanding of mathematics linked to clinical practice. Study results showed a significant improvement between the pre- and the post-test phases, after the intervention. Pre-test scores ranged between 0 and 25 out of a maximum of 30 points, with a mean score of 15.96 (SD 4.85), and a median score of 17. Post-test scores ranged between 15 and 30 out of 30, with a mean score of 25.2 (SD 3.63) and a median score of 26 (pstudy shows that Clinical Skills Workshops may be tailored to include teaching techniques that encourage the development of drug-dosage calculation skills, and that training strategies implemented during a Clinical skills Workshop can enhance students' comprehension of mathematical calculations. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Well-Defined Poly(Ortho Ester Amides) for Potential Drug Carriers: Probing the Effect of Extra- and Intracellular Drug Release on Chemotherapeutic Efficacy.

    Science.gov (United States)

    Yan, Guoqing; Wang, Jun; Qin, Jiejie; Hu, Liefeng; Zhang, Panpan; Wang, Xin; Tang, Rupei

    2017-07-01

    To compare the chemotherapeutic efficacy determined by extra- and intracellular drug release strategies, poly(ortho ester amide)-based drug carriers (POEAd-C) with well-defined main-chain lengths, are successfully constructed by a facile method. POEAd-C3-doxorubicin (DOX) can be rapidly dissolved to release drug at tumoral extracellular pH (6.5-7.2), while POEAd-C6-DOX can rapidly release drug following gradual swelling at intracellular pH (5.0-6.0). In vitro cytotoxicity shows that POEAd-C3-DOX exhibits more toxic effect on tumor cells than POEAd-C6-DOX at extracellular pH, but POEAd-C6-DOX has stronger tumor penetration and inhibition in vitro and in vivo tumor models. So, POEAd-C6-DOX with the intracellular drug release strategy has stronger overall chemotherapeutic efficacy than POEAd-C3-DOX with extracellular drug release strategy. It is envisioned that these poly(ortho ester amides) can have great potential as drug carriers for efficient chemotherapy with further optimization. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Non-invasive assessment of the effects of drugs on acute myocardial infarct size in man

    Energy Technology Data Exchange (ETDEWEB)

    Maclean, D [Ninewells Hospital and Medical School, Dundee (UK)

    1979-06-01

    The amount of necrotic myocardium following acute coronary artery occlusion influences both the early and long-term consequences of myocardial infarction. Experiments, however, indicate that several drugs given early after the occlusion can substantially alter final infarct size. Clinical assessment of the effects of these drugs poses difficulties and an awareness of the limitations of existing methods is essential for their successful application. This discussion is restricted largely to the advantages and disadvantages of the three main methods currently used for assessing acute myocardial infarct size:-praecordial electrocardiographic mapping, serial estimates of serum creatine kinase activity, and radionuclide scintigraphy.

  11. Effect of buspirone: An anxiolytic drug on blood glucose in humans

    OpenAIRE

    Ojha, S. K.; Nandave, M.; Sharma, C.

    2006-01-01

    The present study investigated the effect of an antianxiety drug, buspirone on blood glucose and plasma insulin level concerning the role of 5-HT1A receptors in blood glucose regulation in healthy humans. Twelve healthy male volunteers were administered single oral doses of buspirone (10 mg) or placebo, in a randomized, crossover way, followed by oral glucose load (75 gm in 200 ml) at reported Tmax i.e. the time of peak plasma concentration of the respective administered drug. The blood sampl...

  12. Effects of pay resets following drug use on attendance and hours worked in a therapeutic workplace.

    Science.gov (United States)

    Holtyn, August F; Silverman, Kenneth

    2016-06-01

    This secondary data analysis examined effects of an abstinence contingency on participation in a therapeutic workplace. Participants exposed to a pay reset after drug use did not differ in overall attendance from participants who were not exposed to a pay reset after drug use; however, they initially worked less after a pay reset than participants who did not receive a pay reset, and their attendance increased as their pay increased. Overall participation was not influenced by the abstinence contingency, but transient decreases in attendance occurred. © 2016 Society for the Experimental Analysis of Behavior.

  13. Effect of ''pasteurizing'' doses of ionizing radiations on drug sensitivity of microbes isolated at pharmacentical factory

    International Nuclear Information System (INIS)

    Pavlov, E.P.; Shcheglova, S.G.; Sedov, V.V.

    1978-01-01

    The effect of ionizing radiations on drug sensitivity of microorganisms has been investigated, particularly, the influence of pasteurizing'' doses of ionizing radia''ons on the drug sensitivity of microorganisms isolated at a Moscow pharmaceutical factory to a number of widely used antibiotics. 250 krad single irradiation of dry microbial culture resulted in a change of the antibiotic sensitivity in 0.5% of 686 strains studied. All changes were toward the appearance of sensitivity to one or several antibiotics. When cultures were irradiated 3 times, this value increased up to 9%. In no case the appearance of resistance to antibiotics was observed

  14. The crystal structures of the tryparedoxin-tryparedoxin peroxidase couple unveil the structural determinants of Leishmania detoxification pathway.

    Directory of Open Access Journals (Sweden)

    Annarita Fiorillo

    Full Text Available Leishmaniasis is a neglected disease caused by Leishmania, an intracellular protozoan parasite which possesses a unique thiol metabolism based on trypanothione. Trypanothione is used as a source of electrons by the tryparedoxin/tryparedoxin peroxidase system (TXN/TXNPx to reduce the hydroperoxides produced by macrophages during infection. This detoxification pathway is not only unique to the parasite but is also essential for its survival; therefore, it constitutes a most attractive drug target. Several forms of TXNPx, with very high sequence identity to one another, have been found in Leishmania strains, one of which has been used as a component of a potential anti-leishmanial polyprotein vaccine. The structures of cytosolic TXN and TXNPx from L. major (LmTXN and LmTXNPx offer a unique opportunity to study peroxide reduction in Leishmania parasites at a molecular level, and may provide new tools for multienzyme inhibition-based drug discovery. Structural analyses bring out key structural features to elucidate LmTXN and LmTXNPx function. LmTXN displays an unusual N-terminal α-helix which allows the formation of a stable domain-swapped dimer. In LmTXNPx, crystallized in reducing condition, both the locally unfolded (LU and fully folded (FF conformations, typical of the oxidized and reduced protein respectively, are populated. The structural analysis presented here points to a high flexibility of the loop that includes the peroxidatic cysteine which facilitates Cys52 to form an inter-chain disulfide bond with the resolving cysteine (Cys173, thereby preventing over-oxidation which would inactivate the enzyme. Analysis of the electrostatic surface potentials of both LmTXN and LmTXNPx unveils the structural elements at the basis of functionally relevant interaction between the two proteins. Finally, the structural analysis of TXNPx allows us to identify the position of the epitopes that make the protein antigenic and therefore potentially suitable

  15. Central and peripheral haemodynamic effects of non-steroidal anti-inflammatory drugs in man.

    Science.gov (United States)

    Wennmalm, A; Carlsson, I; Edlund, A; Eriksson, S; Kaijser, L; Nowak, J

    1984-01-01

    The haemodynamic effects of non-steroidal anti-inflammatory (NSAI) drugs can be attributed either to their common property of inhibiting the formation of prostaglandins (PG) in the cardiovascular system, or to direct actions on the tone and sensitivity of the resistance vessels in various regions. Indomethacin (IND) is the most frequently studied NSAI drug, in animals and in man. Its cardiovascular effects differ somewhat from those of other NSAI, due to the fact that, besides inhibiting PG formation, IND acts as a direct vasoconstrictor. The stimulatory effect of IND in vascular smooth muscle results in an increased systemic vascular resistance which, although partially compensated by a decreased cardiac output, gives rise to a moderate increase in systemic blood pressure. The vasoconstrictor effect of IND is of particular interest in patients with ischemic heart disease, since it lowers their already decreased coronary flow, and may thereby accentuate the risk of myocardial infarction. Administration of IND also leads to a decreased blood flow in the splanchnic region, the kidneys, and the brain. The cerebral blood flow is lowered by 25-35%; in addition, IND almost entirely erases the hyperemic flow response to hypercapnia. Of other NSAI drugs, at least aspirin and naproxen are completely devoid of such actions on the cerebral circulation. A common vascular effect of all NSAI drugs is a diminution of reactive hyperemia, the local hyperemia that develops in a tissue subjected to a short period of arterial occlusion. Part of this hyperemic response is dependent on an intact vascular PG formation and consequently it is inhibited when PG formation is blocked. In contrast, NSAI drugs do not affect the functional increase in the blood flow in working skeletal muscle.

  16. Studying the factors in dependency to substances changing the mood and behavior and effective methods in drug addiction counseling

    Directory of Open Access Journals (Sweden)

    2004-05-01

    Full Text Available Addicts to alcohol and other substances changing the mood and behavior attempt to stop their addiction and avoid its relapse because they suffer mental and physical problems, they are under the pressure of family members, employer and other individuals who influence over their life as well as negative effects of drug addiction on their performance in family, work and social relations. Since drug addicts experience physical pain when they are not using drugs, they refer, at first, to physicians and then to psychiatrists. Although emerging and applying non-medical and non-pharmaceutical approaches models is not too old, arising various addictive drugs and increasing the number of drug addicts as well as individual/social destructive consequences of drug addiction have caused that psychiatrists, psychologists and social workers to represent various non-pharmaceutical theories, models, methods and guidelines based on the conditions of their clients and their clinical experiences. The present article attempts to identify the reasons of drug addiction tendency, consumption patterns, models, theories of addiction to substances changing the mood and behavior, various methods of drug treatment, effective methods in drug addiction counseling and non-medical and non-pharmaceutical methods to give up drug addiction by using recent research findings. On this basis, the most effective methods to help those who suffer from alcohol and other drugs abuse and dependency are studied.

  17. Study on the effects of radiation on microbial; contamination of crude drugs

    International Nuclear Information System (INIS)

    Satake, Motoyoshi; Sekita, Setsuko; Kamakura, Hiroyuki

    1999-01-01

    The effects of radiation on five kinds of crude drugs (fennel, cinnamon bark, rhubarb, senna leaf and peony root) from various countries were studied by 6, 12, 24, 30 and 60 KGy 60 Co-gamma-ray. Number of fungus and bacteria in these crude drugs were changed by radiation and decreased to 10 1 by 12 KGy. But a part of them needed 30 KGy. Contents of components such as PGG and paeonifrolin in peony root and aloe-emodin, rhein, aloe-emodin 8-Glc, rhein 8-Glc, sennoside A and sennoside B in senna leaf were not changed by radiation. Accordingly, the components of crude drugs were not affected by 60 KGy-gamma-ray. (S.Y.)

  18. Suspected Lonely Mouse Syndrome as a Cage Effect in a Drug Safety Study.

    Science.gov (United States)

    Ye, Xiaobu; Itzoe, MariaLisa; Sarabia-Estrada, Rachel; DeTolla, Louis; Tyler, Betty M; Guarnieri, Michael

    2018-01-01

    Studies have demonstrated that buprenorphine, a front line drug for veterinary analgesia, may alleviate symptoms of chronic pain. A cage side observation protocol was used to record behavioral signs in a mouse clinical trial of extended release buprenorphine. A retrospective review of the observations for signs of pain and stress revealed that mice given a fivefold overdose of buprenorphine (16.25 mg/kg) showed lethargy and facial signs associated with stress. However, similar signs were observed in the drug-free control mice as early as Day 3 of single-cage housing. This appears to be the first report of cage effects in a clinical trial for a veterinary drug.

  19. Suspected Lonely Mouse Syndrome as a Cage Effect in a Drug Safety Study

    Directory of Open Access Journals (Sweden)

    Xiaobu Ye

    2018-01-01

    Full Text Available Studies have demonstrated that buprenorphine, a front line drug for veterinary analgesia, may alleviate symptoms of chronic pain. A cage side observation protocol was used to record behavioral signs in a mouse clinical trial of extended release buprenorphine. A retrospective review of the observations for signs of pain and stress revealed that mice given a fivefold overdose of buprenorphine (16.25 mg/kg showed lethargy and facial signs associated with stress. However, similar signs were observed in the drug-free control mice as early as Day 3 of single-cage housing. This appears to be the first report of cage effects in a clinical trial for a veterinary drug.

  20. Effects of psychotropic drugs and psychiatric illness on vocational aptitude and interest assessment.

    Science.gov (United States)

    Helmes, E; Fekken, G C

    1986-07-01

    This study examined the vocational aptitude and interest scores of 326 inpatients at a large urban psychiatric hospital. The inpatient group performed significantly below the adult normative mean on eight of nine General Aptitude Test Battery (GATB) aptitude measures; the single exception was Verbal Aptitude. Further, GATB aptitude scores (adjusted for age and education) were significantly lower for patients who were receiving (N = 210) psychotropic medication than for patients who were not receiving (N = 114) psychotropic medication, again with the exception of Verbal Aptitude. Differentiation of patients into subsamples who were receiving particular drugs or drug combinations indicated that phenothiazines in combination with Anti-Parkinsonians were associated with the poorest GATB performances. Interestingly, self-reported vocational interests were not related in any systematic fashion to receiving medication. A variety of explanations that may account for these findings, including drug side-effects and severity or type of psychiatric disorder, were investigated. Implications for vocational counselors were discussed.

  1. Effect of a Modest Weight Loss in Normalizing Blood Pressure in Obese Subjects on Antihypertensive Drugs

    Directory of Open Access Journals (Sweden)

    Luisa Gilardini

    2016-07-01

    Full Text Available Objective: To assess the effect of a lifestyle intervention in lowering/normalizing blood pressure (BP levels in hypertensive (controlled or not obese patients. Methods: In this prospective observational study, 490 obese hypertensive patients, 389 controlled (BP Results: 18.9% of CH and 20.0% of UH were on ≥ 3 antihypertensive drugs. Weight change (average -4.9 ± 2.7% was independent of the antihypertensive drugs employed. Systolic BP (SBP decreased by 23 mm Hg and diastolic BP (DBP by 9 mm Hg, in patients with UH most of whom (89% normalized BP levels (in 49% after a weight loss Conclusion: Lifestyle interventions are useful for all obese hypertensive patients in most of whom a modest weight loss is sufficient to normalize BP levels avoiding the aggressive use of multiple antihypertensive drugs.

  2. Magnetocaloric effect in magnetothermally-responsive nanocarriers for hyperthermia-triggered drug release

    International Nuclear Information System (INIS)

    Li Jianbo; Qu Yang; Ren Jie; Yuan Weizhong; Shi Donglu

    2012-01-01

    The magnetocaloric effects and lower critical solution temperature (LCST) were investigated in a magnetothermally-responsive nanocarrier for magnetothermal drug release under alternating magnetic field (AMF). The Mn 0.2 Zn 0.8 Fe 2 O 4 nanoparticles with low T c were dispersed in a polymeric matrix consisting of N-Isopropyl acrylamide (NIPAAm) and N-hydroxymethyl acrylamide (HMAAm). The magnetocaloric effects and LCST of the nanocarriers were characterized by using high-resolution electron transmission microscopy, thermogravimetric analyses, and vibrating sample magnetometer. The maximum self-heating temperature of 42.9 °C was achieved by optimizing the Mn 0.2 Zn 0.8 Fe 2 O 4 concentration in the polymer matrix. By adjusting the NIPAAm to HMAAm ratio, the LCST was controlled at an ideal level of 40.1 °C for efficient thermosensitive drug delivery. Magnetothermally responsive drug release of Doxorubicin, an anticancer drug, was significantly enhanced by application of an external AMF on the nanocarriers. The cytotoxicity experimental results in vitro show good biocompatibility and efficient therapeutic effects in cancer treatment. (paper)

  3. Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy.

    Science.gov (United States)

    Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

    2016-05-26

    The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery.

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

    Directory of Open Access Journals (Sweden)

    Herxheimer Andrew

    2002-03-01

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

  5. Long-term effects of ovulation-stimulating drugs on cancer risk.

    Science.gov (United States)

    Brinton, Louise

    2007-07-01

    Although nulliparity has been extensively related to the risk of ovarian, breast and endometrial cancers, with many studies showing the relationship largely attributable to infertility, treatment effects on cancer risk are poorly understood. Two early studies raised substantial concern when ovulation-stimulating drugs were linked with large increases in ovarian cancer, supporting the notion of an important aetiological role of incessant ovulation. Subsequent studies have been mainly reassuring, although some have suggested possible risk increases among nulligravid women, those with extensive follow-up, and those developing borderline tumours. Results regarding effects of fertility drugs on breast cancer risk are conflicting, with some showing no associations and others demonstrating possible risk increases, although for varying subgroups. In contrast, endometrial cancer results are more consistent, with two recent studies showing increased risks related to clomiphene usage. This is of interest given that clomiphene is structurally similar to tamoxifen, a drug extensively linked with this cancer. Given the recent marketing of fertility drugs and the fact that exposed women are only beginning to reach the cancer age range, further follow-up is necessary. This will also be important to fully resolve effects of exposures such as gonadotrophins, used more recently in conjunction with IVF.

  6. Effects of gender and level of parental involvement among parents in drug treatment.

    Science.gov (United States)

    Collins, Cyleste C; Grella, Christine E; Hser, Yih-Ing

    2003-05-01

    Most studies of parents in drug treatment have focused exclusively on mothers, and few studies have examined the effects of parents' level of involvement with their children on the parents' drug use and psychological functioning, either before or after treatment. This study examined mothers and fathers (n = 331) who were parents of children under the age of 18; participants were sampled from 19 drug treatment programs across four types of treatment modalities in Los Angeles County. A majority of each group (57% of 214 mothers and 51% of 117 fathers) were classified as being highly involved with their children. At the baseline assessment, higher parental involvement was related to lower levels of addiction severity, psychological severity, and symptoms of psychological distress, and to higher levels of self-esteem and perception of parenting skills. In general, fathers had higher levels of alcohol and drug-use severity than did mothers, but fathers who were more involved with their children showed lower levels of addiction severity than fathers who were less involved. Parental involvement at baseline was unrelated to drug use at the 12-month follow-up, although parents who were less involved with their children reported experiencing more stressors. Given the association of parental involvement with lower levels of addiction severity and psychological distress at baseline, treatment protocols should build upon the positive relationships of parents with their children, and seek to improve those of less-involved parents.

  7. Adverse effects and Drug Interactions Associated with Inhaled Recreational and Medical Marijuana

    OpenAIRE

    Maisha Kelly Freeman; Pilar Z Murphy

    2016-01-01

    Objectives: To provide an overview of the addiction potential; adverse effects (e.g., cardiovascular, immune dysfunction, respiratory system, mental health disorders); drug interactions; effects of accidental exposure; crime statistics; and pharmacist’s considerations for the use of inhaled medical marijuana. Methods: A PubMed search was conducted from 1966 to March 2016 to identify articles in which the safety of inhaled medical marijuana was assessed. Key MeSH search terms included med...

  8. A hepatitis C virus infection model with time-varying drug effectiveness: solution and analysis.

    Directory of Open Access Journals (Sweden)

    Jessica M Conway

    2014-08-01

    Full Text Available Simple models of therapy for viral diseases such as hepatitis C virus (HCV or human immunodeficiency virus assume that, once therapy is started, the drug has a constant effectiveness. More realistic models have assumed either that the drug effectiveness depends on the drug concentration or that the effectiveness varies over time. Here a previously introduced varying-effectiveness (VE model is studied mathematically in the context of HCV infection. We show that while the model is linear, it has no closed-form solution due to the time-varying nature of the effectiveness. We then show that the model can be transformed into a Bessel equation and derive an analytic solution in terms of modified Bessel functions, which are defined as infinite series, with time-varying arguments. Fitting the solution to data from HCV infected patients under therapy has yielded values for the parameters in the model. We show that for biologically realistic parameters, the predicted viral decay on therapy is generally biphasic and resembles that predicted by constant-effectiveness (CE models. We introduce a general method for determining the time at which the transition between decay phases occurs based on calculating the point of maximum curvature of the viral decay curve. For the parameter regimes of interest, we also find approximate solutions for the VE model and establish the asymptotic behavior of the system. We show that the rate of second phase decay is determined by the death rate of infected cells multiplied by the maximum effectiveness of therapy, whereas the rate of first phase decline depends on multiple parameters including the rate of increase of drug effectiveness with time.

  9. Effect of surfactant chain length on drug release kinetics from microemulsion-laden contact lenses.

    Science.gov (United States)

    Maulvi, Furqan A; Desai, Ankita R; Choksi, Harsh H; Patil, Rahul J; Ranch, Ketan M; Vyas, Bhavin A; Shah, Dinesh O

    2017-05-30

    The effect of surfactant chain lengths [sodium caprylate (C 8 ), Tween 20 (C 12 ), Tween 80 (C 18 )] and the molecular weight of block copolymers [Pluronic F68 and Pluronic F 127] were studied to determine the stability of the microemulsion and its effect on release kinetics from cyclosporine-loaded microemulsion-laden hydrogel contact lenses in this work. Globule size and dilution tests (transmittance) suggested that the stability of the microemulsion increases with increase in the carbon chain lengths of surfactants and the molecular weight of pluronics. The optical transmittance of direct drug-laden contact lenses [DL-100] was low due to the precipitation of hydrophobic drugs in the lenses, while in microemulsion-laden lenses, the transmittance was improved when stability of the microemulsion was achieved. The results of in vitro release kinetics revealed that drug release was sustained to a greater extent as the stability of microemulsion was improved as well. This was evident in batch PF127-T80, which showed sustained release for 15days in comparison to batch DL-100, which showed release up to 7days. An in vivo drug release study in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC) with PF-127-T80 lenses (stable microemulsion) in comparison to PF-68-SC lenses (unstable microemulsion) and DL-100 lenses. This study revealed the correlation between the stability of microemulsion and the release kinetics of drugs from contact lenses. Thus, it was inferred that the stable microemulsion batches sustained the release of hydrophobic drugs, such as cyclosporine from contact lenses for an extended period of time without altering critical lens properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Radiotherapy and 'new' drugs-new side effects?

    International Nuclear Information System (INIS)

    Niyazi, Maximilian; Maihoefer, Cornelius; Krause, Mechthild; Rödel, Claus; Budach, Wilfried; Belka, Claus

    2011-01-01

    Targeted drugs have augmented the cancer treatment armamentarium. Based on the molecular specificity, it was initially believed that these drugs had significantly less side effects. However, currently it is accepted that all of these agents have their specific side effects. Based on the given multimodal approach, special emphasis has to be placed on putative interactions of conventional cytostatic drugs, targeted agents and other modalities. The interaction of targeted drugs with radiation harbours special risks, since the awareness for interactions and even synergistic toxicities is lacking. At present, only limited is data available regarding combinations of targeted drugs and radiotherapy. This review gives an overview on the current knowledge on such combined treatments. Using the following MESH headings and combinations of these terms pubmed database was searched: Radiotherapy AND cetuximab/trastuzumab/panitumumab/nimotuzumab, bevacizumab, sunitinib/sorafenib/lapatinib/gefitinib/erlotinib/sirolimus, thalidomide/lenalidomide as well as erythropoietin. For citation crosscheck the ISI web of science database was used employing the same search terms. Several classes of targeted substances may be distinguished: Small molecules including kinase inhibitors and specific inhibitors, antibodies, and anti-angiogenic agents. Combination of these agents with radiotherapy may lead to specific toxicities or negatively influence the efficacy of RT. Though there is only little information on the interaction of molecular targeted radiation and radiotherapy in clinical settings, several critical incidents are reported. The addition of molecular targeted drugs to conventional radiotherapy outside of approved regimens or clinical trials warrants a careful consideration especially when used in conjunction in hypo-fractionated regimens. Clinical trials are urgently needed in order to address the open question in regard to efficacy, early and late toxicity

  11. The effects of opioid drugs on dopamine mediated locomotor activity in rats

    International Nuclear Information System (INIS)

    Leathern, L.L.

    1986-12-01

    Opioid drugs influence various behavioural parameters including locomotor activity in experimental animals. The interaction between the opioid and dopaminergic systems is one possible explanation for the effect of opioid drugs on locomotor activity. In this study behavioural and biochemical assays were done to investigate the interaction between the opioid and dopaminergic systems. Behavioural studies were done by measurement of locomotor activity (LA) of rats after acute or chronic pretreatment with opioid and/or dopaminergic drugs. Biochemical studies were in the form of radioligand binding assays, the effect on the number (Bmax) and affinity (K D ) of receptors was measured after chronic pretreatment with opioid and/or dopaminergic drugs. The opioid drugs used are morphine, nalbuphine and naloxone. Dopaminergic drugs used included: agonists-apomorphine and piribedil; antagonists-pimozide, haloperidol, chlorpromazine. In the acute situation increased LA was obtained with morphine and the DA agonists. A correlation between the behavioural and biochemical assays was found. Chronic pretreatment with morphine enhanced apomorphine induced LA, this supersensitivity was also measured as an increased receptor density (Bmax) of D2 receptors in the striatum. Chronic morphine pretreatment caused a decrease in morphine induced LA, while this subsensitivity was not apparent in the ligand binding assays - where no change in receptor number was observed. Chronic naloxone pretreatment enhanced morphine induced LA, as well as increased the Bmax of opioid receptors in the whole brain. It is concluded that an interaction between the opioid and dopaminergic systems does exist, and may account for the mechanism of action of the opioids

  12. Large-scale automatic extraction of side effects associated with targeted anticancer drugs from full-text oncological articles.

    Science.gov (United States)

    Xu, Rong; Wang, QuanQiu

    2015-06-01

    Targeted anticancer drugs such as imatinib, trastuzumab and erlotinib dramatically improved treatment outcomes in cancer patients, however, these innovative agents are often associated with unexpected side effects. The pathophysiological mechanisms underlying these side effects are not well understood. The availability of a comprehensive knowledge base of side effects associated with targeted anticancer drugs has the potential to illuminate complex pathways underlying toxicities induced by these innovative drugs. While side effect association knowledge for targeted drugs exists in multiple heterogeneous data sources, published full-text oncological articles represent an important source of pivotal, investigational, and even failed trials in a variety of patient populations. In this study, we present an automatic process to extract targeted anticancer drug-associated side effects (drug-SE pairs) from a large number of high profile full-text oncological articles. We downloaded 13,855 full-text articles from the Journal of Oncology (JCO) published between 1983 and 2013. We developed text classification, relationship extraction, signaling filtering, and signal prioritization algorithms to extract drug-SE pairs from downloaded articles. We extracted a total of 26,264 drug-SE pairs with an average precision of 0.405, a recall of 0.899, and an F1 score of 0.465. We show that side effect knowledge from JCO articles is largely complementary to that from the US Food and Drug Administration (FDA) drug labels. Through integrative correlation analysis, we show that targeted drug-associated side effects positively correlate with their gene targets and disease indications. In conclusion, this unique database that we built from a large number of high-profile oncological articles could facilitate the development of computational models to understand toxic effects associated with targeted anticancer drugs. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Synergistic anti-glioma effect of a coloaded nano-drug delivery system

    Directory of Open Access Journals (Sweden)

    Xu H

    2016-12-01

    Full Text Available Huae Xu,1,* Feng Jia,2,* Pankaj Kumar Singh,3 Shu Ruan,4 Hao Zhang,5,* Xiaolin Li5 1Department of Pharmacy, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 2Department of Neurosurgery, Yancheng City No 1 People’s Hospital, The Fourth Affiliated Hospital of Nantong Medical College, Yancheng, People’s Republic of China; 3Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4Department of Endocrinology, Yancheng Third Hospital, The Affiliated Hospital of Southeast University Medical College, Yancheng, 5Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: The anti-glioma effect of temozolomide (Tem is sometimes undermined by the emerging resistance. Recently, resveratrol (Res, herbal medicine extracted from grape seeds, has been demonstrated for its potential use in chemosensitization. In the current study, both these drugs were loaded simultaneously into nanoparticles with methoxy poly(ethylene glycol-poly epsilon caprolactone (mPEG-PCL as drug carriers in order to achieve better antitumor efficiency. Tem/Res-coloaded mPEG-PCL nanoparticles were constructed, characterized, and tested for antitumor effect on glioma cells by using in vitro and xenograft model system. The nanoparticle constructs were satisfactory with drug loading content (Res =~12.4%; Tem =~9.3% and encapsulation capacity of >85% for both the drugs. In addition, the coencapsulation led to better in vitro stability of the nanoparticles than Tem-loaded nanoparticles. An in vitro uptake study demonstrated a high uptake efficiency of the nanoparticles by glioma cells. The synergistic antitumor effect against glioma cells was observed in the combinational treatment of Res and Tem. Tem/Res-coloaded nanoparticles induced higher apoptosis in U87 glioma cells as

  14. Genomic and post-genomic effects of anti-glaucoma drugs preservatives in trabecular meshwork

    Energy Technology Data Exchange (ETDEWEB)

    Izzotti, Alberto, E-mail: izzotti@unige.it [Mutagenesis Unit, IRCCS AOU San Martino – IST, Genova (Italy); Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa (Italy); La Maestra, Sebastiano; Micale, Rosanna Tindara; Longobardi, Maria Grazia [Department of Health Sciences, University of Genoa, Via A. Pastore 1, 16132 Genoa (Italy); Saccà, Sergio Claudio [Ophthalmology Unit, IRCCS AOU San Martino-IST, Genova (Italy)

    2015-02-15

    Highlights: • Glaucoma drug preservatives induce DNA damage in trabecular meshwork cells. • Cellular alteration is related with the occurrence of activation of apoptosis through the intrinsic pathway. • Drug preservatives unable to induce cell damage are ineffective in killing bacteria. • Anti glaucoma drugs should be formulated as single-dose usage devoid of genotoxic preservatives. - Abstract: Oxidative stress plays an important role in glaucoma. Some preservatives of anti-glaucoma drugs, commonly used in glaucoma therapy, can prevent or induce oxidative stress in the trabecular meshwork. The aim of this study is to evaluate cellular and molecular damage induced in trabecular meshwork by preservatives contained in anti-glaucoma drugs. Cell viability (MTT test), DNA fragmentation (Comet test), oxidative DNA damage (8-oxo-dG), and gene expression (cDNA microarray) have been evaluated in trabecular meshwork specimens and in human trabecular meshwork cells treated with benzalkonium chloride, polyQuad, purite, and sofzia-like mixture. Moreover, antimicrobial effectiveness and safety of preservative contents in drugs was tested. In ex vivo experiments, benzalkonium chloride and polyQuad induced high level of DNA damage in trabecular meshwork specimens, while the effect of purite and sofzia were more attenuated. The level of DNA fragmentation induced by benzalkonium chloride was 2.4-fold higher in subjects older than 50 years than in younger subjects. Benzalkonium chloride, and polyQuad significantly increased oxidative DNA damage as compared to sham-treated specimens. Gene expression was altered by benzalkonium chloride, polyQuad, and purite but not by sofzia. In in vitro experiments, benzalkonium chloride and polyQuad dramatically decreased trabecular meshwork cell viability, increased DNA fragmentation, and altered gene expression. A lesser effect was also exerted by purite and sofzia. Genes targeted by these alterations included Fas and effector caspase-3

  15. Electrospun fibers of layered double hydroxide/biopolymer nanocomposites as effective drug delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Yue-E.; Zhu Hong; Chen Dan; Wang Ruiyu [State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433 (China); Tjiu, Weng Weei [Institute of Materials Research and Engineering, A-STAR (Agency for Science, Technology and Research), 3 Research Link, Singapore 117602 (Singapore); Liu Tianxi, E-mail: txliu@fudan.edu.cn [State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433 (China)

    2012-06-15

    Ibuprofen intercalated layered double hydroxide (LDH-IBU)/polycaprolactone (PCL) and LDH-IBU/polylactide (PLA) nanocomposite fibers are electrospun based on a combination of LDH-IBU with two kinds of biopolymers (i.e. PCL and PLA), to act as effective drug delivery systems. Ibuprofen (IBU) is chosen as a model drug, which is intercalated in MgAl-LDH by coprecipitation. Poly(oxyethylene-b-oxypropylene-b-oxyethylene) (Pluronic) is also added into PLA-based fibers as hydrophilicity enhancer and release modulator. LDH-IBU nanoparticles are uniformly dispersed throughout the nanocomposite fibers, as evidenced by transmission electron microscopy (TEM) observations. In vitro drug release studies show that initial IBU liberation from LDH-IBU/PCL composite fibers is remarkably slower than that from IBU/PCL fibers due to the sustained release property of LDH-IBU and heterogeneous nucleation effect of LDH-IBU on PCL chain segments. Surprisingly, the initial IBU release from LDH-IBU/PLA and LDH-IBU/PLA/Pluronic composite fibers is faster than that from the corresponding IBU/PLA and IBU/PLA/Pluronic fibers. This effect can be attributed to the strong interaction between alkyl groups in IBU molecules and methyl substituent groups of PLA as well as the hydrophilicity of LDH-IBU, which lead to an easier diffusion of water with a faster release of IBU from LDH-IBU/PLA and LDH-IBU/PLA/Pluronic composite fibers. - Graphical abstract: Ibuprofen intercalated layered double hydroxide (LDH-IBU)/polycaprolactone (PCL) and LDH-IBU/polylactide (PLA) nanocomposite fibers are electrospun based on the combination of LDHs with two kinds of biopolymers (i.e. PCL and PLA). LDH-IBU nanoparticles are uniformly dispersed throughout all the electrospun nanocomposite fibers even at a high loading level of 5 wt%. By combining the tunable drug release property of LDHs and electrospinning technique, the new drug delivery system is anticipated for effective loading and sustained release of drugs

  16. Electrospun fibers of layered double hydroxide/biopolymer nanocomposites as effective drug delivery systems

    International Nuclear Information System (INIS)

    Miao, Yue-E.; Zhu Hong; Chen Dan; Wang Ruiyu; Tjiu, Weng Weei; Liu Tianxi

    2012-01-01

    Ibuprofen intercalated layered double hydroxide (LDH-IBU)/polycaprolactone (PCL) and LDH-IBU/polylactide (PLA) nanocomposite fibers are electrospun based on a combination of LDH-IBU with two kinds of biopolymers (i.e. PCL and PLA), to act as effective drug delivery systems. Ibuprofen (IBU) is chosen as a model drug, which is intercalated in MgAl-LDH by coprecipitation. Poly(oxyethylene-b-oxypropylene-b-oxyethylene) (Pluronic) is also added into PLA-based fibers as hydrophilicity enhancer and release modulator. LDH-IBU nanoparticles are uniformly dispersed throughout the nanocomposite fibers, as evidenced by transmission electron microscopy (TEM) observations. In vitro drug release studies show that initial IBU liberation from LDH-IBU/PCL composite fibers is remarkably slower than that from IBU/PCL fibers due to the sustained release property of LDH-IBU and heterogeneous nucleation effect of LDH-IBU on PCL chain segments. Surprisingly, the initial IBU release from LDH-IBU/PLA and LDH-IBU/PLA/Pluronic composite fibers is faster than that from the corresponding IBU/PLA and IBU/PLA/Pluronic fibers. This effect can be attributed to the strong interaction between alkyl groups in IBU molecules and methyl substituent groups of PLA as well as the hydrophilicity of LDH-IBU, which lead to an easier diffusion of water with a faster release of IBU from LDH-IBU/PLA and LDH-IBU/PLA/Pluronic composite fibers. - Graphical abstract: Ibuprofen intercalated layered double hydroxide (LDH-IBU)/polycaprolactone (PCL) and LDH-IBU/polylactide (PLA) nanocomposite fibers are electrospun based on the combination of LDHs with two kinds of biopolymers (i.e. PCL and PLA). LDH-IBU nanoparticles are uniformly dispersed throughout all the electrospun nanocomposite fibers even at a high loading level of 5 wt%. By combining the tunable drug release property of LDHs and electrospinning technique, the new drug delivery system is anticipated for effective loading and sustained release of drugs

  17. [Effect of psychotropic drugs on activity of anticonvulsants in maximal electroshock test].

    Science.gov (United States)

    Alikina, N A; Tregubov, A L; Kotegov, V P

    2010-08-01

    The effect ofpsychotropic drugs on the pharmacological properties of anticonvulsants was studied on white mice under maximal electroshock (ME) test conditions. Changes in the anticonvulsant effect of phenobarbital, diphenin, carbamazepine, hexamidine were traced upon their joint administration with psychotropic drugs, including piracetam, aminalon, amitriptyline, imizine, levomepromazine, and lithium oxybutyrate. An important result of research is the fact, that in no one of combinations the basic pharmacological effect of anticonvulsants was decreased. Based on the results of experiments, the most rational combinations of anticonvulsants with psychotropic preparations were revealed as manifested in the ME test. As criterion of rational combination was the increase in the activity of anticonvulsants and reduction of their toxicity in combination or at least invariance of this parameter. Rational combinations include (i) phenobarbital with piracetam, amitriptyline, levomepromazine, and lithium oxybutyrate; (ii) carbamazepine with piracetam; and (iii) hexamidine with amitriptyline, levomepromazine and imizine.

  18. Effect of the antiparasitic drugs fenbendazole and ivermectin on the soil nematode Pristionchus maupasi.

    Science.gov (United States)

    Grønvold, Jørn; Svendsen, Tina Stendal; Kraglund, Hans-Ole; Bresciani, José; Monrad, Jesper

    2004-09-20

    Pristionchus maupasi, a soil nematode, was used to elucidate the potential ecotoxic effect of the two anthelmintics fenbendazole and ivermectin in cattle dung. The population growth of P. maupasi was greater in faeces from cattle harbouring active Panacur- or Ivomec-boli, which are releasing fenbendazole and ivermectin to the rumen, respectively, compared to the growth in control faeces. In dose-response experiments it could be shown that the pure chemical compound of fenbendazole was increasingly nematocidal to P. maupasi in concentrations from 10 to 20 microg/g faeces (ww, i.e. wet weight) and the pure compound of ivermectin was effective above 3 microg/g faeces (ww). The results indicate that neither fenbendazole nor ivermectin have any acute toxic effect on P. maupasi in naturally excreted concentrations of the pure drugs, together with their metabolites in faeces from bolus-treated cattle. Both drugs are excreted in concentrations that are non-toxic to P. maupasi.

  19. Effect of goat milk on hepatotoxicity induced by antitubercular drugs in rats

    Directory of Open Access Journals (Sweden)

    Sonam Miglani

    2016-10-01

    Full Text Available Aim of the present study was to assess the hepatoprotective activity of goat milk on antitubercular drug-induced hepatotoxicity in rats. Hepatotoxicity was induced in rats using a combination of isoniazid, rifampicin, and pyrazinamide given orally as a suspension for 30 days. Treatment groups received goat milk along with antitubercular drugs. Liver damage was assessed using biochemical and histological parameters. Administration of goat milk (20 mL/kg along with antitubercular drugs (Group III reversed the levels of serum alanine aminotransferase (82 ± 25.1 vs. 128.8 ± 8.9 units/L and aspartate aminotransferase (174.7 ± 31.5 vs. 296.4 ± 56.4 units/L, p<0.01 compared with antitubercular drug treatment Group II. There was a significant decrease in serum alanine aminotransferase (41.8 ± 4.1 vs. 128.8 ± 8.9 ​ units/L, p<0.01 and aspartate aminotransferase (128.8 ± 8.54 vs. 296.4 ± 56.4 units/L, p<0.001 levels in Group IV (goat milk 40 mL/kg compared with antitubercular drug treatment Group II. Goat milk (20 mL/kg and 40 mL/kg was effective in reversing the rise in malondialdehyde level compared with the antitubercular drug suspension groups (58.5 ± 2 vs. 89.88 ± 2.42 μmol/mL of tissue homogenate, p<0.001 and 69.7 ± 0.78 vs. 89.88 ± 2.42 μmol/mL of tissue homogenate, p<0.001, respectively. Similarly, both doses of milk significantly prevented a fall in superoxide dismutase level (6.23 ± 0.29 vs. 3.1 ± 0.288 units/mL, p<0.001 and 7.8 ± 0.392 vs. 3.1 ± 0.288 units/mL, p<0.001 compared with the group receiving antitubercular drugs alone. Histological examination indicated that goat milk reduced inflammation and necrotic changes in hepatocytes in the treatment groups. The results indicated that goat milk prevented the antitubercular drug-induced hepatotoxicity and is an effective hepatoprotective agent.

  20. THE UNVEILING OF LIFE : LITURGY AND THE LURE OF KITSCH

    African Journals Online (AJOL)

    2010-09-01

    Sep 1, 2010 ... To reach an understanding of theological aesthetics proves to be an even more difficult task, given its ..... something. The performance (graceful effect) of the Gospel then .... revelations that lift us up and above the mundane.

  1. Cost effectiveness of withdrawal of fall-risk-increasing drugs in geriatric outpatients.

    Science.gov (United States)

    van der Velde, Nathalie; Meerding, Willen Jan; Looman, Caspar W; Pols, Huibert A P; van der Cammen, Tischa J M

    2008-01-01

    Withdrawal of fall-risk-increasing drugs has been proven to be effective in older persons. However, given the enormous rise in healthcare costs in recent decades, the effect of such withdrawals on healthcare costs also needs to be considered. Within a common geriatric outpatient population, patients with a history of falls were assessed for falls risk (n = 139). Fall-risk-increasing drugs were withdrawn when appropriate (n = 75). All participants had a 2-month follow-up for fall incidents. The number of prevented falls was calculated using a loglinear regression model. The savings on health expenditures as a result of prevented injuries (estimated from a literature review) and reduced consumption of pharmaceuticals were compared with the intervention costs. After adjustment for confounders, drug withdrawal resulted in a falls risk reduction of 0.89 (95% CI 0.33, 0.98) per patient compared with the non-withdrawal group. Net cost savings were euro1691 (95% CI 662, 2181) per patient in the cohort. This resulted in a cost saving of euro491 (95% CI 465, 497) per prevented fall. Withdrawal of fall-risk-increasing drugs generates significant cost savings. Extrapolation of these findings to a national scale results in an estimated reduction of euro60 million in healthcare expenditures, that is, 15% of fall-related health costs.

  2. Stressed lungs: unveiling the role of circulating stress ...

    Science.gov (United States)

    Ozone, a major component of smog generated through the interaction of light and anthropogenic emissions, induces adverse pulmonary, cardiovascular, and systemic health effects upon inhalation. It is generally accepted that ozone-induced lung injury is mediated by its interaction with lung lining components causing local oxidative changes, which then leads to cell damage and recruitment of inflammatory cells. It is postulated that the spillover of reactive intermediates and pro-inflammatory molecules from lung to systemic circulation mediates extra-pulmonary effects. However, recent work from our laboratory supports an alternative hypothesis that circulating stress hormones, such as epinephrine and corticosterone/cortisol, are involved in mediating ozone pulmonary effects. We have shown in rats and humans that ozone increases the levels of circulating stress hormones through activation of the hypothalamus- pituitary-adrenal (HPA) axis before any measurable effects are observed in the lung. The surgical removal of adrenals diminishes circulating stress hormones and at the same time, the pulmonary effects of ozone suggesting a significant contribution of these hormones in ozone-induced lung injury and inflammation. While ozone effects in the lung have been extensively studied, the contribution of central nervous system -mediated hormonal stress response has not been examined. In order to understand the signaling pathways that might be involved in ozone-induced lun

  3. A critical examination of the definition of 'psychoactive effect' in Australian drug legislation.

    Science.gov (United States)

    Barratt, Monica J; Seear, Kate; Lancaster, Kari

    2017-02-01

    As the number of new 'psychoactive substances' detected globally has risen exponentially, the policy response of assessing and prohibiting each new substance individually has become increasingly unworkable. In an attempt to disrupt the availability of new as-yet-unscheduled substances, Ireland (2010), Poland (2011), Romania (2012), New Zealand (2013), Australia (2015) and the United Kingdom (2016) have enacted generic or blanket ban legislation that prohibits all 'psychoactive substances' that are not already regulated or belong to exempt categories. How such generic legislation defines 'psychoactive substance' is therefore crucial. While there is a growing critical literature relating to blanket bans of 'psychoactive substances', the Australian legislation is yet to be described or critically analysed. In this commentary, we aim to draw the attention of local and international drug policy scholars to Australia's newest legislative approach to 'psychoactive substances'. Using the Australian experience as a case study, we first describe and trace the origins of this generic banning approach, especially focusing on how 'psychoactive effect' came to be defined. Then, we critically examine the assumptions underpinning this definition and the possibilities silenced by it, drawing on the work of poststructuralist and critical scholars. In doing so, we explore and raise a series of questions about how this legislation works to stabilise drugs, drug harms and drug effects, as well as addiction realities; how the category of 'psychoactive substances' is produced through this legislation; and some of the material-discursive effects which accompany this rendering of the 'problem'. We offer this commentary not as a comprehensive discussion of each of these elements but rather as a starting-point to promote further discussion and debate within the drug policy field. To this end, we conclude with a suggested research agenda that may help guide such future work. Copyright © 2016

  4. Effect of Pressurized Metered Dose Inhaler Spray Characteristics and Particle Size Distribution on Drug Delivery Efficiency.

    Science.gov (United States)

    Yousefi, Morteza; Inthavong, Kiao; Tu, Jiyuan

    2017-10-01

    A key issue in pulmonary drug delivery is improvement of the delivery device for effective and targeted treatment. Pressurized metered dose inhalers (pMDIs) are the most popular aerosol therapy device for treating lung diseases. This article studies the effect of spray characteristics: injection velocity, spray cone angle, particle size distribution (PSD), and its mass median aerodynamic diameter (MMAD) on drug delivery. An idealized oral airway geometry, extending from mouth to the main bronchus, was connected to a pMDI device. Inhalation flow rates of 15, 30, and 60 L/min were used and drug particle tracking was a one-way coupled Lagrangian model. The results showed that most particles deposited in the pharynx, where the airway has a reduced cross-sectional area. Particle deposition generally decreased with initial spray velocity and with increased spray cone angle for 30 and 60 L/min flow rates. However, for 15 L/min flow rate, the deposition increased slightly with an increase in the spray velocity and cone angle. The effect of spray cone angle was more significant than the initial spray velocity on particle deposition. When the MMAD of a PSD was reduced, the deposition efficiency also reduces, suggesting greater rates of particle entry into the lung. The deposition rate showed negligible change when the MMAD was more than 8 μm. Spray injection angle and velocity change the drug delivery efficacy; however, the efficiency shows more sensitivity to the injection angle. The 30 L/min airflow rate delivers spray particles to the lung more efficiently than 15 and 60 L/min airflow rate, and reducing MMAD can help increase drug delivery to the lung.

  5. Antiepileptic Drug Behavioral Side Effects in Individuals with Mental Retardation and the Use of Behavioral Measurement Techniques.

    Science.gov (United States)

    Kalachnik, John E.; And Others

    1995-01-01

    Behavioral psychology measurement methods helped assess antiepileptic drug behavioral side effects in five individuals with mental retardation who could not verbally communicate presence of side effects. When the suspected antiepileptic drug was altered, an 81% reduction of maladaptive behaviors occurred. The measurement methods enabled systematic…

  6. In silico prediction of harmful effects triggered by drugs and chemicals

    International Nuclear Information System (INIS)

    Vedani, Angelo; Dobler, Max; Lill, Markus A.

    2005-01-01

    While the computer-assisted discovery and optimization of drug candidates based on the known three-dimensional structure of the macromolecular target (structure-based design) or a binding-site surrogate (receptor modeling) is doubtless one of the more potent approaches in rational drug design, the simulation and quantification of side effects triggered by drugs and chemicals are still in their infancy. Major obstacles include the often not available 3D structure of the molecular target, the low specificity of the involved bioregulators and the identification of the controlling metabolic pathways. In the recent past, our laboratory has explored concepts allowing to simulate receptor-mediated toxic phenomena by developing algorithms, allowing to construct realistic 3D binding-site surrogates of receptors known or assumed triggering adverse effects and validating them against large batches of molecular data. The underlying technology (software Quasar and Raptor, respectively) specifically allows for induced fit, solvation phenomena and entropic effects. It has been applied to various systems both of pharmacological and toxicological interest including the neurokinin-1, chemokine-3, bradykinin B 2 , steroid, 5 HT 2A , aryl hydrocarbon, estrogen and androgen receptor, respectively. In this account, we describe the design of a virtual laboratory allowing for a reliable estimation of harmful effects triggered by drugs, chemicals and their metabolites in silico. In the recent past, the Biographics Laboratory 3R has compiled a 3D database including the surrogates of three major receptor systems known to mediate adverse effects (the aryl hydrocarbon, the estrogen and the androgen receptor, respectively) and validated them against a total of 345 compounds (drugs, chemicals, toxins) using multidimensional QSAR technologies. Within this pilot project, we could demonstrate that our virtual laboratory is able to both recognize toxic compounds substantially different from those

  7. Unveiling the UHE Universe from space: the JEM-EUSO mission

    Energy Technology Data Exchange (ETDEWEB)

    Santangelo, A.; Fenu, F. [Institute of Astronomy and Astrophysics, Kepler Center for Astro and Particle Physics, Eberhard-Karls-Universitaet, Sand 1, 72076, Tuebingen (Germany); RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako 351-0198 (Japan); Ebisuzaki, T.; Shinozaki, K. [RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako 351-0198 (Japan)

    2011-03-15

    The Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO) is an international mission designed to explore the origin and nature of the of ultra high-energy cosmic rays (UHECR), with energies E>5.5x10{sup 19} eV, aiming at an integrated exposure of {approx}10{sup 6} km{sup 2} sr yr at E>10{sup 20} eV. Consisting of a near-UV 2.65 m diameter telescope with a field of view of 60{sup o}, JEM-EUSO looks down from space, monitoring the dark side of the Earth, to detect the fluorescence and Cherenkov light emitted along the linear track generated by a cosmic particle traversing the atmosphere. The energy and the arrival direction of each particle will be measured while the all 4{pi} sky is monitored. The primary science goal of the mission is to identify the sources of the highest energy particles, and to measure their flux and spectrum, to unveil the mechanisms for the production, acceleration, and in situ propagation of these extreme particles. Other exploratory objectives of the mission include the study of the galactic and local extragalactic magnetic field; the detection of high-energy gamma rays and neutrinos, and tests of relativity and quantum gravity effects at extreme energies. Other aspects of fundamental physics that will be studied include the top-down models and the behavior of the neutrino cross sections at extreme energies. JEM-EUSO is also expected to conduct a systematic survey of the not yet well known energetic phenomena of the Earth's atmosphere. The mission is currently in the phase A study by JAXA and has been included in the ELIPS research pool of the European Space Agency. JEM-EUSO will be launched by an H2B rocket in the Japanese fiscal year 2016 and will be transferred to the ISS by an H2 Transfer Vehicle (HTV). It will be attached to the external experiment platform of the Japanese 'KIBO' module of the ISS. In this paper we summarize the science case, the science objectives, the technological and

  8. Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation.

    Science.gov (United States)

    Wilby, J; Kainth, A; Hawkins, N; Epstein, D; McIntosh, H; McDaid, C; Mason, A; Golder, S; O'Meara, S; Sculpher, M; Drummond, M; Forbes, C

    2005-04-01

    To examine the clinical effectiveness, tolerability and cost-effectiveness of gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), tiagabine (TGB), topiramate (TPM) and vigabatrin (VGB) for epilepsy in adults. Electronic databases. Internet resources. Pharmaceutical company submissions. Selected studies were screened and quality assessed. Separate analyses assessed clinical effectiveness, serious, rare and long-term adverse events and cost-effectiveness. An integrated economic analysis incorporating information on costs and effects of newer and older antiepileptic drugs (AEDs) was performed to give direct comparisons of long-term costs and benefits. A total of 212 studies were included in the review. All included systematic reviews were Cochrane reviews and of good quality. The quality of randomised controlled trials (RCTs) was variable. Assessment was hampered by poor reporting of methods of randomisation, allocation concealment and blinding. Few of the non-randomised studies were of good quality. The main weakness of the economic evaluations was inappropriate use of the cost-minimisation design. The included systematic reviews reported that newer AEDs were effective as adjunctive therapy compared to placebo. For newer versus older drugs, data were available for all three monotherapy AEDs, although data for OXC and TPM were limited. There was limited, poor-quality evidence of a significant improvement in cognitive function with LTG and OXC compared with older AEDs. However, there were no consistent statistically significant differences in other clinical outcomes, including proportion of seizure-free patients. No studies assessed effectiveness of AEDs in people with intellectual disabilities or in pregnant women. There was very little evidence to assess the effectiveness of AEDs in the elderly; no significant differences were found between LTG and carbamazepine monotherapy. Sixty-seven RCTs compared adjunctive therapy with placebo, older

  9. Endocrine and Metabolic Adverse Effects of Psychotropic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Evrim Aktepe

    2011-12-01

    Full Text Available ABSTRACT Much as an increase in the use of psychotropic drugs is observed in children and adolescents over the last decade, the endocrine and metabolic side effects of these drugs can limit their use. Atypical antipsychotics can cause many side effects, which are not suitable for the developmental periods of children and adolescents, such as those related with thyroid, blood sugar, level of sex hormones, growth rate and bone metabolism. Children are under a more serious risk regarding the weight increasing effects of atypical antipsychotics and weight gain that is not proportionate with age is especially important due to the association between glucose or lipid abnormalities and cardiovascular mortality. Aripiprazole and ziprasidone are the least risky antipsychotic drugs when it comes to metabolic side affects. The antipsychotic drug that is associated with weight increase and diabetes in children and adolescents most is olanzapine. Even though there are no comparative long-term data concerning children, it is suggested by the currently available information that metabolic side effects including dyslipidemia and impaired glucose tolerance are at an alarming level when it comes to long-term treatment with antipsychotics. The most risky agents in terms of hyperglycemia and glucosuria development are olanzapine and clozapine. Use of risperidone and haloperidol should be undertaken with caution since it may bring about the risk of hyperprolactinemia. Among the antidepressants associated with weight loss and suppression of appetite are selective serotonin reuptake inhibitors, bupropion and venlafaxine. Thyroid functions can be affected by lithium, carbamazepine and valproate treatments. It is reported that the side effect most frequently associated with valproate is weight increase. The relationship between valproate treatment and the development of hyperandrogenism and polycystic ovary syndrome in young women should also be kept in mind. [TAF Prev

  10. Animal Models in Studies of Cardiotoxicity Side Effects from Antiblastic Drugs in Patients and Occupational Exposed Workers

    Directory of Open Access Journals (Sweden)

    Monica Lamberti

    2014-01-01

    Full Text Available Cardiotoxicity is an important side effect of cytotoxic drugs and may be a risk factor of long-term morbidity for both patients during therapy and also for staff exposed during the phases of manipulation of antiblastic drugs. The mechanism of cardiotoxicity studied in vitro and in vivo essentially concerns the formation of free radicals leading to oxidative stress, with apoptosis of cardiac cells or immunologic reactions, but other mechanisms may play a role in antiblastic-induced cardiotoxicity. Actually, some new cytotoxic drugs like trastuzumab and cyclopentenyl cytosine show cardiotoxic effects. In this report we discuss the different mechanisms of cardiotoxicity induced by antiblastic drugs assessed using animal models.

  11. Prediction of Central Nervous System Side Effects Through Drug Permeability to Blood-Brain Barrier and Recommendation Algorithm.

    Science.gov (United States)

    Fan, Jun; Yang, Jing; Jiang, Zhenran

    2018-04-01

    Drug side effects are one of the public health concerns. Using powerful machine-learning methods to predict potential side effects before the drugs reach the clinical stages is of great importance to reduce time consumption and protect the security of patients. Recently, researchers have proved that the central nervous system (CNS) side effects of a drug are closely related to its permeability to the blood-brain barrier (BBB). Inspired by this, we proposed an extended neighborhood-based recommendation method to predict CNS side effects using drug permeability to the BBB and other known features of drug. To the best of our knowledge, this is the first attempt to predict CNS side effects considering drug permeability to the BBB. Computational experiments demonstrated that drug permeability to the BBB is an important factor in CNS side effects prediction. Moreover, we built an ensemble recommendation model and obtained higher AUC score (area under the receiver operating characteristic curve) and AUPR score (area under the precision-recall curve) on the data set of CNS side effects by integrating various features of drug.

  12. Effects of chronic mild stress on the development of drug dependence in rats.

    Science.gov (United States)

    Papp, Mariusz; Gruca, Piotr; Lason-Tyburkiewicz, Magdalena; Litwa, Ewa; Willner, Paul

    2014-09-01

    There is high comorbidity between depression and addiction. Features of addiction relevant to depression have been studied extensively, but less is known about features of depression relevant to addiction. Here, we have studied the effects of chronic mild stress (CMS), a valid animal model of depression, on measures of physical and psychological dependence resulting from subchronic treatment of rats with three drugs of abuse that act through disparate neurobiological mechanisms: morphine, nicotine and diazepam. In animals not treated subchronically with drugs of abuse, CMS increased the withdrawal-like effects of the opiate antagonist naloxone, but not those of the nicotinic antagonist mecamylamine or the benzodiazepine antagonist flumazenil. In animals treated subchronically with drugs of abuse, CMS exacerbated, precipitated and conditioned withdrawal effects associated with all three antagonists. CMS also potentiated withdrawal-induced and cue-induced place aversions associated with all three antagonists. All of the effects of CMS were reversed by chronic treatment with the specific serotonin reuptake inhibitor citalopram. These results suggest that treatment of comorbid depression, although not a primary treatment for addiction, may facilitate other treatments for addiction, by decreasing the severity of withdrawal symptoms and the likelihood of relapse.

  13. The effects of four different drugs administered through catheters on slime production in coagulase negative Staphylococci

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    J. Sedef Göçmen

    2012-12-01

    Full Text Available Objectives: Higher rate of slime production has been found in pathogen bacteria strains. Accordingly, the factors thatcontribute to higher slime production rate increase the infection risk, while the factors that reduce the slime productionrate will reduce the infection risk. The effect of some drugs that are administered through catheters in intensive careunits on slime production with coagulase negative Staphylococci was investigated.Materials and methods: In this study, the effect of four different preparations containing Glyceryl trinitrate (Perlinganit®, Dexmedetomidine (Precedex®, Esmolol (Brevibloc®, and Propofol (Propofol® on slime production of 24Staphylococcus epidermidis strains isolated from blood cultures of patients, and reference strain were investigated. Slimeproduction was determined using ‘the quantitative microdilution plaque test’ described by Christensen.Results: Under controlled medium, eight strains formed slimes, and in the media containing esmolol, glyceryl trinitrate,dexmedetomidine, and propofol slimes were positive for five, 21, 15, and 18 strains, respectively. The rate of slime productionin glyceryl trinitrate, dexmedetomidine, and propofol containing media were higher than that of the controls.Conclusions: In the light of the results of this study, it is concluded that the drugs and/or additives increase the rate ofslime production. The effects of the preparations administered through catheters on slime production should be investigated,and these effects should be kept in mind during their use. J Microbiol Infect Dis 2012; 2(4: 150-154Key words: Slime Production, Coagulase Negative Staphyloccoci, Parenteral drugs

  14. Ex vivo analysis identifies effective HIV-1 latency–reversing drug combinations

    Science.gov (United States)

    Laird, Gregory M.; Bullen, C. Korin; Rosenbloom, Daniel I.S.; Martin, Alyssa R.; Hill, Alison L.; Durand, Christine M.; Siliciano, Janet D.; Siliciano, Robert F.

    2015-01-01

    Reversal of HIV-1 latency by small molecules is a potential cure strategy. This approach will likely require effective drug combinations to achieve high levels of latency reversal. Using resting CD4+ T cells (rCD4s) from infected individuals, we developed an experimental and theoretical framework to identify effective latency-reversing agent (LRA) combinations. Utilizing ex vivo assays for intracellular HIV-1 mRNA and virion production, we compared 2-drug combinations of leading candidate LRAs and identified multiple combinations that effectively reverse latency. We showed that protein kinase C agonists in combination with bromodomain inhibitor JQ1 or histone deacetylase inhibitors robustly induce HIV-1 transcription and virus production when directly compared with maximum reactivation by T cell activation. Using the Bliss independence model to quantitate combined drug effects, we demonstrated that these combinations synergize to induce HIV-1 transcription. This robust latency reversal occurred without release of proinflammatory cytokines by rCD4s. To extend the clinical utility of our findings, we applied a mathematical model that estimates in vivo changes in plasma HIV-1 RNA from ex vivo measurements of virus production. Our study reconciles diverse findings from previous studies, establishes a quantitative experimental approach to evaluate combinatorial LRA efficacy, and presents a model to predict in vivo responses to LRAs. PMID:25822022

  15. Maternal use of drug substrates of placental transporters and the effect of transporter-mediated drug interactions on the risk of congenital anomalies.

    Directory of Open Access Journals (Sweden)

    Aizati N A Daud

    Full Text Available A number of transporter proteins are expressed in the placenta, and they facilitate the placental transfer of drugs. The inhibition of P-glycoprotein (P-gp was previously found to be associated with an increase in the risk of congenital anomalies caused by drug substrates of this transporter. We now explore the role of other placental transporter proteins.A population-based case-referent study was performed using cases with congenital anomalies (N = 5,131 from EUROCAT Northern Netherlands, a registry of congenital anomalies. The referent population (N = 31,055 was selected from the pregnancy IADB.nl, a pharmacy prescription database.Ten placental transporters known to have comparable expression levels in the placenta to that of P-gp, were selected in this study. In total, 147 drugs were identified to be substrates, inhibitors or inducers, of these transporters. Fifty-eight of these drugs were used by at least one mother in our cases or referent population, and 28 were used in both. The highest user rate was observed for the substrates of multidrug resistance-associated protein 1, mainly folic acid (6% of cases, 8% of referents, and breast cancer resistance protein, mainly nitrofurantoin (2.3% of cases, 2.9% of referents. In contrast to P-gp, drug interactions involving substrates of these transporters did not have a significant effect on the risk of congenital anomalies.Some of the drugs which are substrates or inhibitors of placental transporters were commonly used during pregnancy. No significant effect of transporter inhibition was found on fetal drug exposure, possibly due to a limited number of exposures.

  16. Safety and effectiveness of drug therapy for the acutely agitated patient (Part 2

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    Gianluca Airoldi

    2013-04-01

    Full Text Available Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the second in a 2-part series is to review published data on the efficacy and safety of antipsychotic medications currently available for managing situations of this type. Arrhythmias caused by QT-prolonging drugs occur infrequently, and multiple factors are often involved, including concomitant use of other drugs affecting the same pathway (most antipsychotic drugs prolong the QT interval by blocking potassium IKr current in HERG channels of myocardial cells, electrolyte disorders and, possibly, genetic predisposition. Judicious use of typical antipsychotics (mainly haloperidol and benzodiazepines (mainly lorazepam, given intramuscularly alone or in combination, has proved to be safe and effective for controlling acute motor agitation related to psychiatric illness; cocaine, methamphetamine, and ethanol toxicity; ethanol withdrawal; and other factors. They are still widely used and are particularly useful when limited data are available on the patient’s history of cardiovascular disease, current use of medication, and/or the likelihood of illicit drug or alcohol intoxication; when the diagnosis involves medical comorbidity or intoxication; or when there is no specific treatment (e.g., personality disorders, learning disabilities, mental retardation, organic brain damage. If rapid tranquillization is necessary before a formal diagnosis can be made and there are uncertainties regarding the patient’s medical history, lorazepam is often considered the first-line drug of choice. In

  17. Drug Repurposing Screening Identifies Novel Compounds That Effectively Inhibit Toxoplasma gondii Growth

    Science.gov (United States)

    Dittmar, Ashley J.; Drozda, Allison A.

    2016-01-01

    ABSTRACT The urgent need to develop new antimicrobial therapies has spawned the development of repurposing screens in which well-studied drugs and other types of compounds are tested for potential off-label uses. As a proof-of-principle screen to identify compounds effective against Toxoplasma gondii, we screened a collection of 1,120 compounds for the ability to significantly reduce Toxoplasma replication. A total of 94 compounds blocked parasite replication with 50% inhibitory concentrations of parasite invasion and replication but did so independently of inhibition of dopamine or other neurotransmitter receptor signaling. Tamoxifen, which is an established inhibitor of the estrogen receptor, also reduced parasite invasion and replication. Even though Toxoplasma can activate the estrogen receptor, tamoxifen inhibits parasite growth independently of this transcription factor. Tamoxifen is also a potent inducer of autophagy, and we find that the drug stimulates recruitment of the autophagy marker light chain 3-green fluorescent protein onto the membrane of the vacuolar compartment in which the parasite resides and replicates. In contrast to other antiparasitic drugs, including pimozide, tamoxifen treatment of infected cells leads to a time-dependent elimination of intracellular parasites. Taken together, these data suggest that tamoxifen restricts Toxoplasma growth by inducing xenophagy or autophagic destruction of this obligate intracellular parasite. IMPORTANCE There is an urgent need to develop new therapies to treat microbial infections, and the repurposing of well-characterized compounds is emerging as one approach to achieving this goal. Using the protozoan parasite Toxoplasma gondii, we screened a library of 1,120 compounds and identified several compounds with significant antiparasitic activities. Among these were pimozide and tamoxifen, which are well-characterized drugs prescribed to treat patients with psychiatric disorders and breast cancer

  18. 2940-nm Er:YAG fractional laser enhanced the effect of topical drug for psoriasis.

    Science.gov (United States)

    Li, Ruilian; Zhou, Jun; Su, Hui; Wang, Mei; Wang, Yongxian; Xiao, Shengxiang; Ma, Huiqun

    2017-08-01

    We observed the promoting effects of the 2940-nm erbium:YAG (Er:YAG) fractional laser in topical drug delivery for psoriasis. A total of five (four males and one female) recalcitrant psoriasis patients were given laser treatment eight times at 1-week intervals with the following parameters: 5-11% spot density and 100-μm energy depth. The psoriatic skin lesions on the left knee and the corresponding lesions at the right ones of each psoriasis patient were randomly divided into two groups: laser + topical drug group (L) and drug alone group (D). The psoriatic lesions in both groups were treated with the same topical treatment (calcipotriol ointment). The corresponding psoriatic lesions in the L group received extra 2940-nm Er:YAG laser irradiation before topical treatment. The photos of psoriatic lesions were taken before each treatment. The final photos were obtained from the patients at the seventh day after the final treatment. Drug alone or in combination with laser Er:YAG both reduced psoriatic lesions. However, with the increase in the number of treatments, increasing differences were observed between the treatment and the control sides. The therapeutic outcomes in the L groups were better than those in the D groups. Psoriasis area and severity index (PASI) scores for five cases of both groups were decreased. However, the scores in the L groups were lower than those in the D groups. The use of 2940 nm Er:YAG promoted the absorption of topical drugs for psoriasis, improving the therapeutic effect.

  19. What is known about the cost-effectiveness of orphan drugs? Evidence from cost-utility analyses.

    Science.gov (United States)

    Picavet, E; Cassiman, D; Simoens, S

    2015-06-01

    In times of financial and economic hardship, governments are looking to contain pharmaceutical expenditure by focusing on cost-effective drugs. Because of their high prices and difficulties in demonstrating effectiveness in small patient populations, orphan drugs are often perceived as not able to meet traditional reimbursement threshold value for money. The aim of this study was to provide an overview of the available evidence on the cost-effectiveness of orphan drugs. All orphan drugs listed as authorized on the website of the European Medicines Agency on 21 November 2013 were included in the analysis. Cost-utility analyses (CUAs) were identified by searching the Tufts Medical Center Cost-Effectiveness Analysis Registry and Embase. For each CUA, a number of variables were collected. The search identified 23 articles on the Tufts registry and 167 articles on Embase. The final analysis included 45 CUAs and 61 incremental cost-utility ratios (ICURs) for 19 orphan drugs. Of all ICURS, 16·3% were related to dominant drugs (i.e. more effective and less expensive than the comparator), 70·5% were related to drugs that are more effective, but at a higher cost, and 13·1% were related to dominated drugs (i.e. less effective and more expensive than the comparator). The median overall ICUR was €40 242 per quality-adjusted life year (QALY) with a minimum ICUR of €6311/QALY and a maximum ICUR of €974,917/QALY. This study demonstrates that orphan drugs can meet traditional reimbursement thresholds. Considering a threshold of £30,000/QALY, in this study, ten (52·6%) of a total of 19 orphan drugs for which data were available meet the threshold. As much as fifteen orphan drugs (78·9%) are eligible for reimbursement if a threshold of €80,000/QALY is considered. © 2015 John Wiley & Sons Ltd.

  20. Effect of Electron-Beam Irradiation on Bacterial Cellulose Membranes Used as Transdermal Drug Delivery Systems

    International Nuclear Information System (INIS)

    Stoica-Guzun, A.

    2006-01-01

    Multiple methods are used to modify material surfaces. Radiation is an effective tool for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. Bacterial cellulose is a promising biomaterial synthesized by Acetobacter xylinum. It has a distinctive ultrafine reticulated structure that may become a perfect matrix as an optimal wound healing environment. In this work, high energy irradiation (γ rays from 137 C s) was applied to modify bacterial cellulose membranes. The effect of varying irradiation doses on membranes permeability was studied. Tetracycline was involved in the study of diffusivity as model drug. Release and permeation of drug from irradiated and non-irradiated membranes were done using a diffusion cell. The membrane permeability was determined using a psudo-steady state analysis based on Fick's law

  1. Cyclohexane, a potential drug of abuse with pernicious effects for the brain

    Directory of Open Access Journals (Sweden)

    Oscar eGonzalez-Perez

    2016-01-01

    Full Text Available Cyclohexane is a volatile solvent used as a harmless substitute for dangerous organic solvents in several products, such as paint thinners, gasoline and adhesives. Many of these products are used as drugs of abuse and can severely damage neural tissue and impair neurological functions. However, there is very little information on the effects of cyclohexane on the brain. In humans, cyclohexane produces headaches, sleepiness, dizziness, limb weakness, motor changes and verbal memory impairment. Recent studies in mice have demonstrated behavioral alterations, reactive gliosis, microglial reactivity and oxidative stress in the brains of cyclohexane-exposed animals. This indicates that cyclohexane may represent a potential problem for public health. Therefore, studies are needed to clarify the neurobiological effects of this volatile compound, including the cellular and molecular mechanisms of neurotoxicity, and to minimize the human health risk posed by the intentional or accidental inhalation of this potential drug of abuse.

  2. Effect of quality chronic disease management for alcohol and drug dependence on addiction outcomes.

    Science.gov (United States)

    Kim, Theresa W; Saitz, Richard; Cheng, Debbie M; Winter, Michael R; Witas, Julie; Samet, Jeffrey H

    2012-12-01

    We examined the effect of the quality of primary care-based chronic disease management (CDM) for alcohol and/or other drug (AOD) dependence on addiction outcomes. We assessed quality using (1) a visit frequency based measure and (2) a self-reported assessment measuring alignment with the chronic care model. The visit frequency based measure had no significant association with addiction outcomes. The self-reported measure of care-when care was at a CDM clinic-was associated with lower drug addiction severity. The self-reported assessment of care from any healthcare source (CDM clinic or elsewhere) was associated with lower alcohol addiction severity and abstinence. These findings suggest that high quality CDM for AOD dependence may improve addiction outcomes. Quality measures based upon alignment with the chronic care model may better capture features of effective CDM care than a visit frequency measure. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Effect of supercritical fluid density on nanoencapsulated drug particle size using the supercritical antisolvent method.

    Science.gov (United States)

    Kalani, Mahshid; Yunus, Robiah

    2012-01-01

    The reported work demonstrates and discusses the effect of supercritical fluid density (pressure and temperature of supercritical fluid carbon dioxide) on particle size and distribution using the supercritical antisolvent (SAS) method in the purpose of drug encapsulation. In this study, paracetamol was encapsulated inside L-polylactic acid, a semicrystalline polymer, with different process parameters, including pressure and temperature, using the SAS process. The morphology and particle size of the prepared nanoparticles were determined by scanning electron microscopy and transmission electron microscopy. The results revealed that increasing temperature enhanced mean particle size due to the plasticizing effect. Furthermore, increasing pressure enhanced molecular interaction and solubility; thus, particle size was reduced. Transmission electron microscopy images defined the internal structure of nanoparticles. Thermal characteristics of nanoparticles were also investigated via differential scanning calorimetry. Furthermore, X-ray diffraction pattern revealed the changes in crystallinity structure during the SAS process. In vitro drug release analysis determined the sustained release of paracetamol in over 4 weeks.

  4. Effects of anticholinergic drugs on cognitive function in older Australians: results from the AIBL study.

    Science.gov (United States)

    Sittironnarit, Gobhathai; Ames, David; Bush, Ashley I; Faux, Noel; Flicker, Leon; Foster, Jonathan; Hilmer, Sarah; Lautenschlager, Nicola T; Maruff, Paul; Masters, Colin L; Martins, Ralph N; Rowe, Christopher; Szoeke, Cassandra; Ellis, Kathryn A

    2011-01-01

    The nature and extent of adverse cognitive effects due to the prescription of anticholinergic drugs in older people with and without dementia is unclear. We calculated the anticholinergic load (ACL) of medications taken by participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing, a cohort of 211 Alzheimer's disease (AD) patients, 133 mild cognitive impairment (MCI) patients and 768 healthy controls (HC) all aged over 60 years. The association between ACL and cognitive function was examined for each diagnostic group (HC, MCI, AD). A high ACL within the HC group was associated with significantly slower response speeds for the Stroop color and incongruent trials. No other significant relationships between ACL and cognition were noted. In this large cohort, prescribed anticholinergic drugs appeared to have modest effects upon psychomotor speed and executive function, but not on other areas of cognition in healthy older adults. Copyright © 2011 S. Karger AG, Basel.

  5. Effect of medication burden on persistent use of lipid-lowering drugs among patients with hypertension.

    Science.gov (United States)

    Robertson, Teisha A; Cooke, Catherine E; Wang, Jingshu; Shaya, Fadia T; Lee, Helen Y

    2008-11-01

    To determine the effect of medication burden on persistent use of newly added lipid-lowering (LL) drugs among patients with hypertension. This retrospective database study used medical and pharmacy claims from a mid-Atlantic managed care organization. The cohort was obtained from continuous member enrollment in pharmacy and medical benefits from January 1, 2003, to December 31, 2005. Prescription claims were obtained for 18 months following the date of the first filled LL prescription (ie, index date). Patients were stratified into patients who changed LL drug or strength (group 1) and patients who did not change LL drug or strength (group 2). The primary outcome measure was persistence to newly added LL therapy. Persistence was defined by the length of time a member remained on therapy following the index date. The secondary outcome measure was the medication possession ratio (MPR). The MPR was calculated as the ratio of the sum of the days' supply of prescription filled divided by the number of days filled, plus the days' supply for the final prescription fill. Associations between the daily medication burden, defined as the number of unique drug products, and the outcome measures were analyzed. In the cohort of 3058 patients, the mean medication burden was 2.9 medications. Medication burden was positively associated with persistence and MPR through 18 months. Patients who had greater medication burden had longer persistence (P 80%) (P attention should focus on patients who have changes to their LL regimen compared with patients who continue on the same LL prescription.

  6. Therapeutic effects of acetylspiramycin and garlicin on cryptosporidiosis among drug users

    Directory of Open Access Journals (Sweden)

    Min-Zhu Huang

    2015-12-01

    Full Text Available Cryptosporidiosis affects humans of all ages, particularly malnourished children and those with compromised immune systems such as HIV/AIDS. This study investigated the therapeutic effects of acetylspiramycin and garlicin on Cryptosporidium infection in institutionalized male drug users receiving rehabilitative treatment. Examination of stool specimens from 903 drug users via modified acid-fast bacilli staining resulted in 172 positive cases. Among them 151 subjects consented to participate in a randomized trial of acetylspiramycin and garlicin in four groups: acetylspiramycin plus garlicin, acetylspiramycin only, garlicin only, and placebo control. The cryptosporidiosis rate was higher in younger subjects with longer drug use history than subjects who are older with shorter history of drug use. After two segments of treatments, 76.2% of the cases achieved negative test results, with the four groups achieving the rates of 92.1%, 76.7%, 72.2%, and 61.8%, respectively (χ2 = 9.517, P = 0.023. These results indicate clinical potential of garlicin in conjunction with acetylspiramycin in treating cryptosporidiosis.

  7. The Effect of Central Amygdala Nitric Oxide in Expression Of Drug Seeking Behaviors

    Directory of Open Access Journals (Sweden)

    Mahnaz Rahimpour

    2011-11-01

    Full Text Available Introduction: Previous studies shows L-arginin (nitric oxide precursor increases conditioned place preference and drug seeking behaviors whereas LG-nitro-arginine methyl ester L-NAME( as nitric oxide synthase inhibitor decreases this process. In this project, effects of intra-central amygdale bilateral injection of nitric oxide agents on drug-seeking behaviors including rearing, sniffing and compartment entrance were investigated. Method: animals were wistar male rats (200-250 g which allowed to be recovered after they’re being suffered from a surgery by strereotaxis apparatus to be cannulated in coordination of central amygdale nucleus (CeA. CPP was conducted using a five-day schedule of unbiased procedure. Findings: morphine (2.5-10 mg/kg s.c induced significant drug-seeking behaviors. Naloxone (0.1-0.4 mg/kg i.p injection pretesting (after conditioning by morphine 7.5 mg/kg decreased the expression of behaviors. When L-arginine (0.3-3 µgr/rat injected intra–CeA prior to naloxone (0.4 mg/kg, increased behaviors but L-NAME (0.3-3 µgr/rat intra–CeA injections prior to L-arginine (0.3 µgr/rat pretesting, caused significant decreasement of L-arginine response. Conclusion: NO in the CeA may play an important role in the drug seeking behaviors induced of morphine.

  8. Cross-generational effects on gender differences in psychoactive drug abuse and dependence.

    Science.gov (United States)

    Holdcraft, Laura C; Iacono, William G

    2004-05-10

    Studies of patients with cocaine and heroin use disorders have shown gender differences in prevalence, course, and outcome. These differences may be decreasing in successive generations. Less is known about gender differences in course and symptomatology for other illicit drug use disorders, especially in community samples. Participants (1323 men and 1384 women) who were biological or step-parents of twins and born in the 1940-1960s, from the Minnesota Twin-Family Study (MTFS) were divided into two cohorts based on the median birth year. A structured interview was used to assess DSM-III-R cannabis, amphetamine, cocaine and hallucinogen use disorders. There was a higher prevalence of each of these drug disorders and earlier onset of cannabis and amphetamine use disorders in later-born participants. For most drug use disorder categories, men and women were similar with respect to age of onset and severity of disorder but women had a shorter course of drug use disorders. Women with amphetamine disorders were atypical with respect to having a higher frequency of use but similar number of lifetime uses compared to men, and more emotional effects of amphetamine intoxication than men. In addition, women with amphetamine disorders were more likely to have anorexia nervosa than those without amphetamine disorders. These results have several implications for prevention, etiology and treatment.

  9. Erythromycin potentiates PR interval prolonging effect of verapamil in the rat: A pharmacodynamic drug interaction

    International Nuclear Information System (INIS)

    Dakhel, Yaman; Jamali, Fakhreddin

    2006-01-01

    Calcium channel blockers and macrolide antibiotics account for many drug interactions. Anecdotal reports suggest interactions between the two resulting in severe side effects. We studied the interaction between verapamil and erythromycin in the rat to see whether it occurs at the pharmacokinetics or pharmacodynamic level. Adult male Sprague-Dawley rats received doses of 1 mg/kg verapamil or 100 mg/kg erythromycin alone or in combination (n = 6/group). Serial blood samples (0-6 h) were taken for determination of the drug concentrations using HPLC. Electrocardiograms were recorded (0-6 h) through subcutaneously inserted lead II. Binding of the drugs to plasma proteins was studied using spiked plasma. Verapamil prolonged PR but not QT interval. Erythromycin prolonged QT but not PR interval. The combination resulted in a significant increase in PR interval prolongation and AV node blocks but did not further prolong QT interval. Pharmacokinetics and protein binding of neither drug were altered by the other. Our rat data confirm the anecdotal human case reports that combination of erythromycin and verapamil can result in potentiation of the cardiovascular response. The interaction appears to be at the pharmacodynamic rather than pharmacokinetic level hence may be extrapolated to other calcium channel antagonists

  10. Antisolvent crystallization of a cardiotonic drug in ionic liquids: Effect of mixing on the crystal properties

    Science.gov (United States)

    de Azevedo Jacqueline, Resende; Fabienne, Espitalier; Jean-Jacques, Letourneau; Inês, Ré Maria

    2017-08-01

    LASSBio-294 (3,4-methylenedioxybenzoyl-2-thienylhydrazon) is a poorly soluble drug which has been proposed to have major advantages over other cardiotonic drugs. Poorly water soluble drugs present limited bioavailability due to their low solubility and dissolution rate. An antisolvent crystallization processing can improve the dissolution rate by decreasing the crystals particle size. However, LASSBio-294 is also poorly soluble in organic solvents and this operation is limited. In order to open new perspectives to improve dissolution rate, this work has investigated LASSBio-294 in terms of its antisolvent crystallization in 1-ethyl-3-methylimidazolium methyl phosphonate [emim][CH3O(H)PO2] as solvent and water as antisolvent. Two modes of mixing are tested in stirred vessel with different pre-mixers (Roughton or T-mixers) in order to investigate the mixing effect on the crystal properties (crystalline structure, particle size distribution, residual solvent and in vitro dissolution rate). Smaller drug particles with unchanged crystalline structure were obtained. Despite the decrease of the elementary particles size, the recrystallized particles did not achieve a better dissolution profile. However, this study was able to highlight a certain number of findings such as the impact of the hydrodynamic conditions on the crystals formation and the presence of a gel phase limiting the dissolution rate.

  11. Cerebral blood flow autoregulation in hypertension and effects of antihypertensive drugs

    DEFF Research Database (Denmark)

    Barry, David; Lassen, N A

    1984-01-01

    If antihypertensive treatment, especially emergency blood pressure lowering, is always to be safe, more thought should be given to autoregulation of cerebral blood in the hypertensive patient. This topic is reviewed in the present article, in the hypertensive patient. This topic is reviewed...... in the present article, particular emphasis being placed on the resetting of the lower limit of autoregulation to higher pressure in hypertension and the effects of acute administration of anti-hypertensive drugs on CBF and CBF-autoregulation....

  12. Phospholipid complex enriched micelles: A novel drug delivery approach for promoting the antidiabetic effect of repaglinide.

    Science.gov (United States)

    Kassem, Ahmed Alaa; Abd El-Alim, Sameh Hosam; Basha, Mona; Salama, Abeer

    2017-03-01

    To enhance the oral antidiabetic effect of repaglinide (RG), a newly emerging approach, based on the combination of phospholipid complexation and micelle techniques, was employed. Repaglinide-phospholipid complex (RG-PLC) was prepared by the solvent-evaporation method then characterized using Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XPRD). The results revealed obvious disappearance of the characteristic peaks of the prepared RG-PLCs confirming the formation of drug-phospholipid complex. RG-PLC enriched micelles (RG-PLC-Ms) were prepared by the solvent-evaporation technique employing poloxamer 188 as surfactant. The prepared RG-PLC-Ms showed high drug encapsulation efficiencies (93.81-99.38%), with nanometric particle diameters (500.61-665.32nm) of monodisperse distribution and high stability (Zeta potential < -29.8mV). The in vitro release of RG from RG-PLC-Ms was pH-dependant according to the release media. A higher release pattern was reported in pH=1.2 compared to a more retarded release in pH=6.8 owing to two different kinetics of drug release. Oral antidiabetic effect of two optimized RG-PLC-M formulations was evaluated in an alloxan-induced diabetic rat model for 7-day treatment protocol. The two investigated formulations depicted normal blood glucose, serum malondialdehyde and insulin levels as well as an improved lipid profile, at the end of daily oral treatment, in contrast to RG marketed tablets implying enhanced antidiabetic effect of the drug. Hence, phospholipid-complex enriched micelles approach holds a promising potential for promoting the antidiabetic effect of RG. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Micellar Drug Delivery and Proteomics Analysis for Effective Treatment of Resistant Prostate Cancer

    Science.gov (United States)

    2015-12-01

    by a luminometer (Berthold, Bad Wildbad, Germany ). In Vivo Efficacy of Drug Loaded LHRH Conjugated Micelles in Ectopic Tumor Bearing Mice All...and metabolism) as well as the pathogenesis of several human diseases, including prostate cancers.11,12 Deregulated miRNAs are involved in initiation...signaling pathways and therefore can be more effective in treating cancers that are inherently heterogeneous and are resulted from the deregulation of

  14. The Therapeutic Effect of the Antitumor Drug 11 Beta and Related Molecules on Polycystic Kidney Disease

    Science.gov (United States)

    2017-10-01

    models (Somlo, Yale). Preparation work to assemble a collection of probes specific for oxidative stress genes and other PKD specific genes (as part... Worked : 6 Contribution to Project: Performance of experiments including those related to mitochondrial biology in vivo and unfolded protein...1 AWARD NUMBER: W81XWH-15-1-0364 TITLE: THE THERAPEUTIC EFFECT OF THE ANTITUMOR DRUG 11 BETA AND RELATED MOLECULES ON POLYYSTIC KIDNEY DISEASE

  15. The mastermind approach to CNS drug therapy: translational prediction of human brain distribution, target site kinetics, and therapeutic effects

    OpenAIRE

    de Lange, Elizabeth CM

    2013-01-01

    Despite enormous advances in CNS research, CNS disorders remain the world?s leading cause of disability. This accounts for more hospitalizations and prolonged care than almost all other diseases combined, and indicates a high unmet need for good CNS drugs and drug therapies. Following dosing, not only the chemical properties of the drug and blood?brain barrier (BBB) transport, but also many other processes will ultimately determine brain target site kinetics and consequently the CNS effects. ...

  16. Studying the factors in dependency to substances changing the mood and behavior and effective methods in drug addiction counseling

    OpenAIRE

    2004-01-01

    Addicts to alcohol and other substances changing the mood and behavior attempt to stop their addiction and avoid its relapse because they suffer mental and physical problems, they are under the pressure of family members, employer and other individuals who influence over their life as well as negative effects of drug addiction on their performance in family, work and social relations. Since drug addicts experience physical pain when they are not using drugs, they refer, at first, to physician...

  17. Calotropis procera Latex-Induced Inflammatory Hyperalgesia—Effect of Antiinflammatory Drugs

    Directory of Open Access Journals (Sweden)

    Raman Sehgal

    2005-01-01

    Full Text Available The milky white latex of plant Calotropis procera produces inflammation of the skin and mucous membranes on accidental exposure. It produces edema on local administration due to the release of histamine and prostaglandins and is associated with hyperalgesia. In the present study we have evaluated the antiedematous and analgesic activity of antiinflammatory drugs against inflammatory response induced by dried latex (DL of C procera in rat paw edema model. An aqueous extract of DL of C procera was injected into the subplantar surface of the rat paw and the paw volume was measured by a plethysmometer at 0, 1, 2, 6, 12, and 24 hours. Concomitantly the hyperalgesic response was also evaluated by motility test, stair climbing ability test, dorsal flexion pain test, compression test, and observing the grooming behavior. The inhibitory effect of diclofenac and rofecoxib on edema formation and hyperalgesic response was compared with cyproheptadine (CPH. DL-induced edema formation was maximum at 2 hours that was associated with decreased pain threshold, functional impairment, and grooming. Treatment with antiinflammatory drugs and CPH significantly attenuated the edematous response and grooming, increased the pain threshold, and improved functional parameters. Both antiinflammatory and antiserotonergic drugs significantly inhibited the hyperalgesia associated with DL-induced paw edema. Rofecoxib was found to be superior than diclofenac and was as effective as CPH in ameliorating the hyperalgesia. However, it was found to be less effective than CPH in attenuating edema formation.

  18. Effects of drugs inhibiting prostaglandin or leukotriene biosynthesis on postirradiation haematopoiesis in mouse

    International Nuclear Information System (INIS)

    Kozubik, A.; Hofmanova, J.; Pospisil, M.; Netikova, J.; Hola, J.; Lojek, A.

    1994-01-01

    Two non-steroidal anti-inflammatory drugs, i.e. indomethacin (INDO), an inhibitor of prostaglandin production, and esculetin (ESCUL), an inhibitor of leukotriene production, were tested for their ability to modify haematopoiesis in three experimental systems: (a) in vitro clonal proliferation of marrow GM-CFC from the irradiated mouse was found to be augmented by addition of INDO at a low concentration, and inhibited by ESCUL in a dose-dependent manner; (b) in the lethally irradiated and bone marrow-transplanted mice treated with the drugs in the postirradiation period, stimulatory effects of INDO on CFU-S and GM-CFC populations and an inhibitory effect of ESCUL on GM-CFC were observed; and (c) when the drugs were administered i.p. to mice 1 h before 5-Gy irradiation, INDO enhanced the postirradiation recovery of haematopoietic indices such the numbers of CFU-S, GM-CFC, peripheral blood granuloctyes, and nucleated bone marrow cells, while ESCUL had no effect or even inhibited the recovery of these indices. (author)

  19. Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK

    Directory of Open Access Journals (Sweden)

    Taek-In Oh

    2017-12-01

    Full Text Available Fascaplysin, a natural product isolated from marine sponges, is a potential candidate for the development of anti-cancer drugs. However, the mechanism underlying its therapeutic effect of strengthening anti-cancer efficacy of other drugs is poorly understood. Here, we found that fascaplysin increases phosphorylation of protein kinase B (PKB, also known as AKT, and adenosine monophosphate-activated protein kinase (AMPK, which are considered therapeutic targets for cancer treatment due to their anti-apoptotic or pro-survival functions in cancer. A cell viability assay revealed that pharmacological suppression of AKT using LY294002 enhanced the anti-cancer effect of fascaplysin in various cancer cells. Similarly, fascaplysin was observed to have improved anti-cancer effects in combination with compound C, a selective AMPK inhibitor. Another challenge showed that fascaplysin increased the efficacy of methotrexate (MTX-mediated cancer therapy by suppressing genes related to folate and purine metabolism. Overall, these results suggest that fascaplysin may be useful for improving the anti-cancer efficacy of targeted anti-cancer drugs, such as inhibitors of phosphoinositide 3-kinase AKT signaling, and chemotherapeutic agents, such as MTX.

  20. Nivolumab, a new immunomodulatory drug, a new adverse effect; adrenal crisis

    Directory of Open Access Journals (Sweden)

    Funda Karbek Akarca

    2017-12-01

    Full Text Available Owing to the advancements in medicine, new information is obtained regarding cancer, new antineoplastic agents are developed. Frequent use of these new pharmacological agents emergency physicians to be vigilant about their side effects. We present a case of adrenal crisis in a patient with non-small cell lung cancer (NSCLC, caused by an immunomodulatory drug; nivolumab. While adverse events are related to other immunomodulatory drugs have been reported in literature, our case is the first nivolumab-related adrenal failure to be reported. A patient with lung cancer presented to the emergency room(ER with nausea and vomiting. Hyponatremia, hyperkalemia, persistent hypoglycemia led to the diagnosis of adrenal crisis. Having direct effect on the immune system, these drugs were claimed to be highly reliable. However, there is no reliable data on the side effect profile of these agents. It should be kept in mind that life-threatening auto-immune reactions may occur. Keywords: Nivolumab, Immunomodulation, CTLA 4 antigen, Adrenal crisis

  1. Calcium antagonistic effects of Chinese crude drugs: Preliminary investigation and evaluation by 45Ca

    International Nuclear Information System (INIS)

    Liu Ning; Yang Yuanyou; Mo Shangwu; Liao Jiali; Jin Jiannan

    2005-01-01

    Coronary and other diseases in cardiac or brain blood vessels are considered to be due to the excessive influx of Ca 2+ into cytoplasm. If Ca 2+ channels in cell membrane are blocked by medicines or other substances with considerable calcium antagonistic effects, these diseases might be cured or controlled. The influence of some Chinese crude drugs, including Crocus sativus, Carthamus tinctorius, Ginkgo biloba and Bulbus allii macrostemi on Ca 2+ influx in isolated rat aortas was investigated by using 45 Ca as a radioactive tracer, and their calcium antagonistic effects were evaluated. It can be noted that Ca 2+ uptake in isolated rat aorta rings in normal physiological status was not markedly altered by these drugs, whereas the Ca 2+ influxes induced by norepinephrine of 1.2 μmol/L and KCl of 100 mmol/L were significantly inhibited by Crocus, Carthamus and Bulbus in a concentration-dependent manner, but not by Ginkgo. The results show that extracellular Ca 2+ influx through receptor-operated Ca 2+ channels and potential-dependent Ca 2+ channels can be blocked by Crocus, Carthamus and Bulbus. This implies that these Chinese crude drugs have obvious calcium antagonistic effects

  2. Effects of drugs inhibiting prostaglandin or leukotriene biosynthesis on postirradiation haematopoiesis in mouse

    Energy Technology Data Exchange (ETDEWEB)

    Kozubik, A.; Hofmanova, J.; Pospisil, M.; Netikova, J.; Hola, J.; Lojek, A. (Ceskoslovenska Akademie Ved, Brno (Czech Republic). Biofysikalni Ustav)

    1994-03-01

    Two non-steroidal anti-inflammatory drugs, i.e. indomethacin (INDO), an inhibitor of prostaglandin production, and esculetin (ESCUL), an inhibitor of leukotriene production, were tested for their ability to modify haematopoiesis in three experimental systems: (a) in vitro clonal proliferation of marrow GM-CFC from the irradiated mouse was found to be augmented by addition of INDO at a low concentration, and inhibited by ESCUL in a dose-dependent manner; (b) in the lethally irradiated and bone marrow-transplanted mice treated with the drugs in the postirradiation period, stimulatory effects of INDO on CFU-S and GM-CFC populations and an inhibitory effect of ESCUL on GM-CFC were observed; and (c) when the drugs were administered i.p. to mice 1 h before 5-Gy irradiation, INDO enhanced the postirradiation recovery of haematopoietic indices such the numbers of CFU-S, GM-CFC, peripheral blood granuloctyes, and nucleated bone marrow cells, while ESCUL had no effect or even inhibited the recovery of these indices. (author).

  3. Antineoplastic drugs and radiation: comparison of the phenomena determining the effectiveness of fractionated treatments

    International Nuclear Information System (INIS)

    Mauro, F.; Briganti, G.; Nervi, C.

    1983-01-01

    In the last ten years the criteria for effective radiotherapy regimens have been rediscussed by analyzing the dependence of radiation response upon the radiobiological phenomena affecting the results of fractionated treatments. In the original definition of H.R. Withers, these phenomena have been referred to as the four R's of radiotherapy, and today we suspect that their number may be higher than that. By analogy, and in spite of the fact that chemical cytotoxic agents are seldom radiomimetic in the strict sense of the word, a similar general analysis could be used to discuss the effectiveness of fractionated administrations of anti-neoplastic drugs. However, information is only available for the cell-cycle age-dependence of lethal and kinetic effects and the repair from potentially lethal damage induced by these agents. In the present work, an attempt is made to discuss some of the neglected R's of chemotherapy, with the aim of establishing (not exclusively empirical) criteria for drug scheduling and of clarifying some of the observations on interaction between agents. In particular, with regard to antineoplastic drugs, published and unpublished information is available not only for the well-known phenomenon of reassortment, but also for the shape of the survival curve, recovery (or potentiation) between dose fraction, and recruitment. Some advantages (and pitfalls) can be evidenced when applying this kind of radiobiological approach to chemotherapy

  4. Unveiling adaptation using high-resolution lineage tracking

    Science.gov (United States)

    Blundell, Jamie; Levy, Sasha; Fisher, Daniel; Petrov, Dmitri; Sherlock, Gavin

    2013-03-01

    Human diseases such as cancer and microbial infections are adaptive processes inside the human body with enormous population sizes: between 106 -1012 cells. In spite of this our understanding of adaptation in large populations is limited. The key problem is the difficulty in identifying anything more than a handful of rare, large-effect beneficial mutations. The development and use of molecular barcodes allows us to uniquely tag hundreds of thousands of cells and enable us to track tens of thousands of adaptive mutations in large yeast populations. We use this system to test some of the key theories on which our understanding of adaptation in large populations is based. We (i) measure the fitness distribution in an evolving population at different times, (ii) identify when an appreciable fraction of clones in the population have at most a single adaptive mutation and isolate a large number of clones with independent single adaptive mutations, and (iii) use this clone collection to determine the distribution of fitness effects of single beneficial mutations.

  5. A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache.

    Directory of Open Access Journals (Sweden)

    Jeffrey L Jackson

    Full Text Available To compare the effectiveness and side effects of migraine prophylactic medications.We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models.PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014.We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration.Placebo controlled trials included alpha blockers (n = 9, angiotensin converting enzyme inhibitors (n = 3, angiotensin receptor blockers (n = 3, anticonvulsants (n = 32, beta-blockers (n = 39, calcium channel blockers (n = 12, flunarizine (n = 7, serotonin reuptake inhibitors (n = 6, serotonin norepinephrine reuptake inhibitors (n = 1 serotonin agonists (n = 9 and tricyclic antidepressants (n = 11. In addition there were 53 trials comparing different drugs. Drugs with at least 3 trials that were more effective than placebo for episodic migraines included amitriptyline (SMD: -1.2, 95% CI: -1.7 to -0.82, -flunarizine (-1.1 headaches/month (ha/month, 95% CI: -1.6 to -0.67, fluoxetine (SMD: -0.57, 95% CI: -0.97 to -0.17, metoprolol (-0.94 ha/month, 95% CI: -1.4 to -0.46, pizotifen (-0.43 ha/month, 95% CI: -0.6 to -0.21, propranolol (-1.3 ha/month, 95% CI: -2.0 to -0.62, topiramate (-1.1 ha/month, 95% CI: -1.9 to -0.73 and valproate (-1.5 ha/month, 95% CI: -2.1 to -0.8. Several effective drugs with less than 3 trials included: 3 ace inhibitors (enalapril, lisinopril, captopril, two angiotensin receptor blockers (candesartan, telmisartan, two anticonvulsants (lamotrigine, levetiracetam, and several beta-blockers (atenolol, bisoprolol, timolol. Network meta-analysis found amitriptyline to be better than several other medications including candesartan, fluoxetine, propranolol, topiramate and valproate and no different than

  6. A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache

    Science.gov (United States)

    2015-01-01

    Objective To compare the effectiveness and side effects of migraine prophylactic medications. Design We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models. Data Sources PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014. Eligibility Criteria for Selecting Studies We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration. Results Placebo controlled trials included alpha blockers (n = 9), angiotensin converting enzyme inhibitors (n = 3), angiotensin receptor blockers (n = 3), anticonvulsants (n = 32), beta-blockers (n = 39), calcium channel blockers (n = 12), flunarizine (n = 7), serotonin reuptake inhibitors (n = 6), serotonin norepinephrine reuptake inhibitors (n = 1) serotonin agonists (n = 9) and tricyclic antidepressants (n = 11). In addition there were 53 trials comparing different drugs. Drugs with at least 3 trials that were more effective than placebo for episodic migraines included amitriptyline (SMD: -1.2, 95% CI: -1.7 to -0.82), -flunarizine (-1.1 headaches/month (ha/month), 95% CI: -1.6 to -0.67), fluoxetine (SMD: -0.57, 95% CI: -0.97 to -0.17), metoprolol (-0.94 ha/month, 95% CI: -1.4 to -0.46), pizotifen (-0.43 ha/month, 95% CI: -0.6 to -0.21), propranolol (-1.3 ha/month, 95% CI: -2.0 to -0.62), topiramate (-1.1 ha/month, 95% CI: -1.9 to -0.73) and valproate (-1.5 ha/month, 95% CI: -2.1 to -0.8). Several effective drugs with less than 3 trials included: 3 ace inhibitors (enalapril, lisinopril, captopril), two angiotensin receptor blockers (candesartan, telmisartan), two anticonvulsants (lamotrigine, levetiracetam), and several beta-blockers (atenolol, bisoprolol, timolol). Network meta-analysis found amitriptyline to be better than several other medications including

  7. Unveiling Leadership–Employee Performance Links: Perspective of Young Employees

    Directory of Open Access Journals (Sweden)

    Tehmina Fiaz Qazi

    2014-12-01

    Full Text Available This paper presents the impact of leadership style practiced by managers on their subordinates’ job performance. Emotional Intelligence of the employees has been considered as a moderator to the leadership-performance relationship. Self-administered questionnaire survey was conducted from convenient sampled 100 young employees of telecom and banking sector. They were asked to respond about their perception regarding their manager’s leadership style, job performance and their perceived level of emotional intelligence. 77 out of 100 distributed questionnaires were received back completely filled that yield response rate of 77%. Current research concluded that the style of leadership exhibited by a manager is significantly associated with the subordinates’ job performance while emotional intelligence of employees has no moderating effect on this leadership- performance relationship

  8. Hopping in the Crowd to Unveil Network Topology

    Science.gov (United States)

    Asllani, Malbor; Carletti, Timoteo; Di Patti, Francesca; Fanelli, Duccio; Piazza, Francesco

    2018-04-01

    We introduce a nonlinear operator to model diffusion on a complex undirected network under crowded conditions. We show that the asymptotic distribution of diffusing agents is a nonlinear function of the nodes' degree and saturates to a constant value for sufficiently large connectivities, at variance with standard diffusion in the absence of excluded-volume effects. Building on this observation, we define and solve an inverse problem, aimed at reconstructing the a priori unknown connectivity distribution. The method gathers all the necessary information by repeating a limited number of independent measurements of the asymptotic density at a single node, which can be chosen randomly. The technique is successfully tested against both synthetic and real data and is also shown to estimate with great accuracy the total number of nodes.

  9. Magnetic seismology of interstellar gas clouds: Unveiling a hidden dimension.

    Science.gov (United States)

    Tritsis, Aris; Tassis, Konstantinos

    2018-05-11

    Stars and planets are formed inside dense interstellar molecular clouds by processes imprinted on the three-dimensional (3D) morphology of the clouds. Determining the 3D structure of interstellar clouds remains challenging because of projection effects and difficulties measuring the extent of the clouds along the line of sight. We report the detection of normal vibrational modes in the isolated interstellar cloud Musca, allowing determination of the 3D physical dimensions of the cloud. We found that Musca is vibrating globally, with the characteristic modes of a sheet viewed edge on, not the characteristics of a filament as previously supposed. We reconstructed the physical properties of Musca through 3D magnetohydrodynamic simulations, reproducing the observed normal modes and confirming a sheetlike morphology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  10. Controlled breast cancer microarrays for the deconvolution of cellular multilayering and density effects upon drug responses.

    Directory of Open Access Journals (Sweden)

    Maria Håkanson

    Full Text Available Increasing evidence shows that the cancer microenvironment affects both tumorigenesis and the response of cancer to drug treatment. Therefore in vitro models that selectively reflect characteristics of the in vivo environment are greatly needed. Current methods allow us to screen the effect of extrinsic parameters such as matrix composition and to model the complex and three-dimensional (3D cancer environment. However, 3D models that reflect characteristics of the in vivo environment are typically too complex and do not allow the separation of discrete extrinsic parameters.In this study we used a poly(ethylene glycol (PEG hydrogel-based microwell array to model breast cancer cell behavior in multilayer cell clusters that allows a rigorous control of the environment. The innovative array fabrication enables different matrix proteins to be integrated into the bottom surface of microwells. Thereby, extrinsic parameters including dimensionality, type of matrix coating and the extent of cell-cell adhesion could be independently studied. Our results suggest that cell to matrix interactions and increased cell-cell adhesion, at high cell density, induce independent effects on the response to Taxol in multilayer breast cancer cell clusters. In addition, comparing the levels of apoptosis and proliferation revealed that drug resistance mediated by cell-cell adhesion can be related to altered cell cycle regulation. Conversely, the matrix-dependent response to Taxol did not correlate with proliferation changes suggesting that cell death inhibition may be responsible for this effect.The application of the PEG hydrogel platform provided novel insight into the independent role of extrinsic parameters controlling drug response. The presented platform may not only become a useful tool for basic research related to the role of the cancer microenvironment but could also serve as a complementary platform for in vitro drug development.

  11. Doctors commitment and long-term effectiveness for cost containment policies: lesson learned from biosimilar drugs.

    Science.gov (United States)

    Menditto, Enrica; Orlando, Valentina; Coretti, Silvia; Putignano, Daria; Fiorentino, Denise; Ruggeri, Matteo

    2015-01-01

    Agency is a pervasive feature of the health care market, with doctors acting as agents for both patients and the health care system. In a context of scarce resources, doctors are required to take opportunity cost into account when prescribing treatments, while cost containment policies cannot overlook their active role in determining health care resource allocation. This paper addresses this issue, investigating the effects of cost containment measures in the market of biosimilar drugs that represent a viable and cost-saving strategy for the reduction of health care expenditure. The analysis focuses on a particular region in Italy, where several timely policies to incentivize biosimilar prescribing were launched. Drugs were identified by the anatomical therapeutic chemical classification system. Information about biosimilar drugs and their originator biological products was extracted from the IMS Health regional database. Drug consumption was expressed in terms of counting units, while expenditure was evaluated in Euro (€). The market penetration of biosimilars was analyzed by year and quarterly. In the Campania region of Italy, the effects of cost containment policies, launched between 2009 and 2013, showed the prescription of biosimilars strongly increasing in 2010 until prescribing levels reached and exceeded the market share of the reference biological products in 2012. After a slight reduction, a plateau was observed at the beginning of 2013. At the same time, the use of the originator products had been decreasing until the first quarter of 2011. However, after a 1-year plateau, this trend was reversed, with a new increase in the consumption of the originators observed. Results show that the cost containment policies, applied to cut health expenditure "to cure and not to care", did not produce the cultural change necessary to make these policies effective in the long run. Therefore, top-down policies for cost containment are not successful; rather, a bottom

  12. Dextromethorphan: a case study on addressing abuse of a safe and effective drug.

    Science.gov (United States)

    Spangler, David C; Loyd, Catherine M; Skor, Emily E

    2016-06-23

    Dextromethorphan is a safe, effective cough suppressant, available without a prescription in the United States since 1958. Due to a perceived prevalence of abuse of dextromethorphan by teens, in 2007 the Drug Enforcement Administration requested the Food and Drug Administration evaluate whether dextromethorphan should be recommended for scheduling under the Controlled Substances Act. The Food and Drug Administration held an Advisory Committee meeting in 2010 to provide a scientific and medical evaluation of dextromethorphan and its abuse potential. To address reports of abuse, particularly by teens in the United States, the Consumer Healthcare Products Association initiated an abuse mitigation plan in 2010 with specific goals related to awareness of the behavior, perception of risk, social disapproval, and access to the products. In identifying abuse interventions, experts acknowledge that substance abuse among teens is a highly complex behavior and indicate that the best course of action is to address prevention by focusing on the factors that impact teen behavior. It is noteworthy that the annual prevalence of over-the-counter cough medicine abuse has sharply decreased since 2010. While a true cause-and-effect relationship cannot be assured, the Consumer Healthcare Products Association and its member companies believe that the increased awareness of the issue since the 2010 Food and Drug Administration Advisory Committee meeting, and the subsequent implementation of a well-delivered and targeted abuse mitigation plan that addressed the levers influencing teen decisions is contributing to the observed reduction in abuse. During the period of 2010-2015, reported abuse of dextromethorphan by 8(th), 10(th), and 12(th) graders decreased 35 %. The authors believe this reduction supports the view of the Consumer Healthcare Products Association at the outset of the abuse mitigation plan effort and today: Controlled substance scheduling or prescription requirements would

  13. Atomoxetine effects on attentional bias to drug-related cues in cocaine dependent individuals.

    Science.gov (United States)

    Passamonti, Luca; Luijten, M; Ziauddeen, H; Coyle-Gilchrist, I T S; Rittman, T; Brain, S A E; Regenthal, R; Franken, I H A; Sahakian, B J; Bullmore, E T; Robbins, T W; Ersche, K D

    2017-08-01

    Biased attention towards drug-related cues and reduced inhibitory control over the regulation of drug-intake characterize drug addiction. The noradrenaline system has been critically implicated in both attentional and response inhibitory processes and is directly affected by drugs such as cocaine. We examined the potentially beneficial effects of the noradrenaline reuptake inhibitor atomoxetine in improving cognitive control during two tasks that used cocaine- and non-cocaine-related stimuli. A double-blind, placebo-controlled, and cross-over psycho-pharmacological design was employed. A single oral dose of atomoxetine (40 mg) was administered to 28 cocaine-dependent individuals (CDIs) and 28 healthy controls. All participants performed a pictorial attentional bias task involving both cocaine- and non-cocaine-related pictures as well as a verbal go/no-go task composed of cocaine- and food-related words. As expected, CDIs showed attentional bias to cocaine-related cues whilst controls did not. More importantly, however, atomoxetine, relative to placebo, significantly attenuated attentional bias in CDIs (F 26  = 6.73, P = 0.01). During the go/no-go task, there was a treatment × trial × group interaction, although this finding only showed a trend towards statistical significance (F 26  = 3.38, P = 0.07). Our findings suggest that atomoxetine reduces attentional bias to drug-related cues in CDIs. This may result from atomoxetine's modulation of the balance between tonic/phasic activity in the locus coeruleus and the possibly parallel enhancement of noradrenergic neurotransmission within the prefrontal cortex. Studying how cognitive enhancers such as atomoxetine influence key neurocognitive indices in cocaine addiction may help to develop reliable biomarkers for patient stratification in future clinical trials.

  14. Effects of Community Based Educational Prevention Program of Drug Abuse in Reduction of High Risk Behavior

    Directory of Open Access Journals (Sweden)

    H Aranpour

    2010-08-01

    Full Text Available Introduction: Overcoming social problems requires a participatory approach. This study was performed in order to determine the effect of community based educational prevention program of drug abuse in reduction of high risk behavior. Methods: This study was a community based participatory research. According to planned approach to community health model, "the health companion group" was established with participation of public representatives of villages, researchers, and managers of health sectors. Need assessment and priority setting of health problems was done. Drug abuse was selected as the topmost priority of health problems. By interviewing 10 year olds and older members of households, the questionnaires were completed. By conducting workshops, distributing educational pamphlets and face to face training for six months, the educational program was carried out. After this period, the study population was interviewed again. Data was analyzed by SPSS software, X2, and T tests. Results: The mean score of drug abuse related high risk behavior was 26.8 +/- 2.05 before educational program and 25.2 ±2.3 after the program. The mean score of psychological health was 26.2±5.8 before educational program and 26.4±5.7 after the program. The rate of negative drug abusing related behavior decreased and positive behavior increased after the educational program. Conclusion: The community based participatory research with participation of the public can be a proper pattern to prevent drug abuse and related high risk behaviors and as a result reduce costs and complications of this problem.

  15. Financial Effect of a Drug Distribution Model Change on a Health System.

    Science.gov (United States)

    Turingan, Erin M; Mekoba, Bijan C; Eberwein, Samuel M; Roberts, Patricia A; Pappas, Ashley L; Cruz, Jennifer L; Amerine, Lindsey B

    2017-06-01

    Background: Drug manufacturers change distribution models based on patient safety and product integrity needs. These model changes can limit health-system access to medications, and the financial impact on health systems can be significant. Objective: The primary aim of this study was to determine the health-system financial impact of a manufacturer's change from open to limited distribution for bevacizumab (Avastin), rituximab (Rituxan), and trastuzumab (Herceptin). The secondary aim was to identify opportunities to shift administration to outpatient settings to support formulary change. Methods: To assess the financial impact on the health system, the cost minus discount was applied to total drug expenditure during a 1-year period after the distribution model change. The opportunity analysis was conducted for three institutions within the health system through chart review of each inpatient administration. Opportunity cost was the sum of the inpatient administration cost and outpatient administration margin. Results: The total drug expenditure for the study period was $26 427 263. By applying the cost minus discount, the financial effect of the distribution model change was $1 393 606. A total of 387 administrations were determined to be opportunities to be shifted to the outpatient setting. During the study period, the total opportunity cost was $1 766 049. Conclusion: Drug expenditure increased for the health system due to the drug distribution model change and loss of cost minus discount. The opportunity cost of shifting inpatient administrations could offset the increase in expenditure. It is recommended to restrict bevacizumab, rituximab, and trastuzumab through Pharmacy & Therapeutics Committees to outpatient use where clinically appropriate.

  16. Effect of contraindicated drugs for heart failure on hospitalization among seniors with heart failure

    Science.gov (United States)

    Girouard, Catherine; Grégoire, Jean-Pierre; Poirier, Paul; Moisan, Jocelyne

    2017-01-01

    Abstract Little is known about the effect of nonsteroidal anti-inflammatory drugs (NSAIDs), thiazolidinediones (TZDs), nifedipine and nondihydropyridine calcium channel blockers (CCBs) usage on the risk of all-cause hospitalization among seniors with heart failure (HF). We assessed the risk of all-cause hospitalization associated with exposure to each of these drug classes, in a population of seniors with HF. Using the Quebec provincial databases, we conducted a nested case-control study in a population of individuals aged ≥65 with a first HF diagnosis between 2000 and 2009. Patients were considered users of a potentially inappropriate drug class if their date of hospital admission occurred in the interval between the date of the last drug claim and the end date of its days’ supply. The risks of hospitalization were estimated using multivariate conditional logistic regression. Of the 128,853 individuals included in the study population, 101,273 (78.6%) were hospitalized. When compared to nonusers, users of NSAIDs (adjusted odds ratio: 1.16; 95% confidence interval: 1.13–1.20), TZD (1.09; 1.04–1.14), and CCBs (1.03; 1.01–1.05) had an increased risk of all-cause hospitalization, but not the users of nifedipine (1.00; 0.97–1.03). Seniors with HF exposed to a potentially inappropriate drug class are at increased risk of worse health outcomes. Treatment alternatives should be considered, as they are available. PMID:28248890

  17. The Effect of Drug Addiction on Education from University Students’ Point of View

    Directory of Open Access Journals (Sweden)

    Mohammad Afkhami Aqda

    2013-04-01

    Full Text Available Introduction: Higher education system in each country is mainly responsible for training specialists and efficient personnels in different levels of government. Regarding a community approach, if the system uses social factors properly, goals attainment will be facile. On the contrary, if the system is affected by common social traumas and deviations, it will result in dissonant maladroit graduated students who would trouble themselves, their family and their society. Addiction to narcotic drugs is one of the most important social traumas that is quite common in developing countries. Materials and Methods: The current descriptive analytic study has been conducted in community of Yazd University in academic year of 2010 -2011. For this purpose, 406 students of this university were selected via stratified random sampling method who responded to a researcher-made questionnaire that its validity and reliability were confirmed utilizing psychometric standards. Regarding data description, frequency indexes, percent, mean, and standard deviation were applied. Moreover, inferential tests of chi-square test and correlation coefficient of Pearson were utilized. Results: The study results revealed that approximately 21/9 percent of students were suggested the drug abuse whose rate of drug use was 25/9 percent. 34/1 percent of subjects determined their friend's homes as the most propitious place for their use and most important reasons involved respectively release of spiritual stress, inability to say "No" in response to others’ suggestion. Furthermore, students’ point of view revealed the significant effect of narcotic drugs use on education process. Any of students’ demographic variables had significant correlation with drug abuse. conclusion: since one of the most common social traumas associated with youth generation, specially college students, is addiction to narcotic drugs, that in addition to extensive economic loss, it would jeopardize their

  18. Metabolic approaches to enhance transdermal drug delivery. 1. Effect of lipid synthesis inhibitors.

    Science.gov (United States)

    Tsai, J C; Guy, R H; Thornfeldt, C R; Gao, W N; Feingold, K R; Elias, P M

    1996-06-01

    The intercellular domains of the stratum corneum, which contain a mixture of cholesterol, free fatty acids, and ceramides, mediate both the epidermal permeability barrier and the transdermal delivery of both lipophilic and hydrophilic molecules. Prior studies have shown that each of the three key lipid classes is required for normal barrier function. For example, selective inhibition of either cholesterol, fatty acid, or ceramide synthesis in the epidermis delays barrier recovery rates after barrier perturbation of hairless mouse skin in vivo. In this study, we investigated the potential of certain inhibitors of lipid synthesis to enhance the transdermal delivery of lidocaine or caffeine as a result of their capacity to perturb barrier homeostasis. After acetone disruption of the barrier, the extent of lidocaine delivery and the degree of altered barrier function paralleled each other. Moreover, the further alteration in barrier function produced by either the fatty acid synthesis inhibitor 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), the cholesterol synthesis inhibitor fluvastatin (FLU), or cholesterol sulfate (CS) resulted in a further increase in lidocaine absorption. Furthermore, coapplications of TOFA and CS together caused an additive increase in lidocaine uptake. Finally, a comparable increase in drug delivery occurred when the barrier was disrupted initially with DMSO instead of acetone; coapplications of TOFA and FLU together again delayed barrier recovery and increased drug delivery by about 8-fold vs delivery from a standard enhancing vehicle. Whereas these metabolic inhibitors also variably increased the octanol/water partitioning of the drugs studied (perhaps via complexion or pH alterations), physicochemical effects of the inhibitors alone did not alter drug uptake in intact skin; i.e., passive mechanisms alone cannot account for the net increase in drug delivery. Our results show that modulations of epidermal lipid biosynthesis, following

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

    Science.gov (United States)

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

    2014-01-01

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

  20. UNVEILING THE UNIVERSALITY OF I-LOVE-Q RELATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Sham, Y.-H.; Lin, L.-M.; Leung, P. T. [Department of Physics and Institute of Theoretical Physics, The Chinese University of Hong Kong, Hong Kong SAR (China); Chan, T. K., E-mail: yhsham@phy.cuhk.edu.hk, E-mail: chantsangkeung@gmail.com, E-mail: lmlin@phy.cuhk.edu.hk, E-mail: ptleung@phy.cuhk.edu.hk [Present address: Department of Physics, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. (United States)

    2015-01-10

    The recent discovery of the universal I-Love-Q relations connecting the moment of inertia, tidal deformability, and the spin-induced quadrupole moment of compact stars is intriguing and totally unexpected. In this paper, we provide numerical evidence showing that the universality can be attributed to the incompressible limit of the I-Love-Q relations. The fact that modern equations of state are stiff, with an effective adiabatic index larger than about two, above the nuclear density range is the key to establishing the universality for neutron stars and quark stars with typical compactness from about 0.1 to 0.3. On the other hand, the I-Love-Q relations of low-mass neutron stars near the minimum mass limit depend more sensitively on the underlying equation of state because these stars are composed mainly of softer matter at low densities. However, the I-Love-Q relations for low-mass quark stars can still be represented accurately by the incompressible limit. We also study the I-Love relation connecting the moment of inertia and tidal deformability analytically in Newtonian gravity and show why the I-Love-Q relation is weakly dependent on the underlying equation of state and can be attributed to its incompressible limit.

  1. Unveiling the Universality of I-Love-Q Relations

    Science.gov (United States)

    Sham, Y.-H.; Chan, T. K.; Lin, L.-M.; Leung, P. T.

    2015-01-01

    The recent discovery of the universal I-Love-Q relations connecting the moment of inertia, tidal deformability, and the spin-induced quadrupole moment of compact stars is intriguing and totally unexpected. In this paper, we provide numerical evidence showing that the universality can be attributed to the incompressible limit of the I-Love-Q relations. The fact that modern equations of state are stiff, with an effective adiabatic index larger than about two, above the nuclear density range is the key to establishing the universality for neutron stars and quark stars with typical compactness from about 0.1 to 0.3. On the other hand, the I-Love-Q relations of low-mass neutron stars near the minimum mass limit depend more sensitively on the underlying equation of state because these stars are composed mainly of softer matter at low densities. However, the I-Love-Q relations for low-mass quark stars can still be represented accurately by the incompressible limit. We also study the I-Love relation connecting the moment of inertia and tidal deformability analytically in Newtonian gravity and show why the I-Love-Q relation is weakly dependent on the underlying equation of state and can be attributed to its incompressible limit.

  2. Unveiling the Role of Galactic Rotation on Star Formation

    Science.gov (United States)

    Utreras, José; Becerra, Fernando; Escala, Andrés

    2016-12-01

    We study the star formation process at galactic scales and the role of rotation through numerical simulations of spiral and starburst galaxies using the adaptive mesh refinement code Enzo. We focus on the study of three integrated star formation laws found in the literature: the Kennicutt-Schmidt (KS) and Silk-Elmegreen (SE) laws, and the dimensionally homogeneous equation proposed by Escala {{{Σ }}}{SFR}\\propto \\sqrt{G/L}{{{Σ }}}{gas}1.5. We show that using the last we take into account the effects of the integration along the line of sight and find a unique regime of star formation for both types of galaxies, suppressing the observed bi-modality of the KS law. We find that the efficiencies displayed by our simulations are anti-correlated with the angular velocity of the disk Ω for the three laws studied in this work. Finally, we show that the dimensionless efficiency of star formation is well represented by an exponentially decreasing function of -1.9{{Ω }}{t}{ff}{ini}, where {t}{ff}{ini} is the initial free-fall time. This leads to a unique galactic star formation relation which reduces the scatter of the bi-modal KS, SE, and Escala relations by 43%, 43%, and 35%, respectively.

  3. UNVEILING THE UNIVERSALITY OF I-LOVE-Q RELATIONS

    International Nuclear Information System (INIS)

    Sham, Y.-H.; Lin, L.-M.; Leung, P. T.; Chan, T. K.

    2015-01-01

    The recent discovery of the universal I-Love-Q relations connecting the moment of inertia, tidal deformability, and the spin-induced quadrupole moment of compact stars is intriguing and totally unexpected. In this paper, we provide numerical evidence showing that the universality can be attributed to the incompressible limit of the I-Love-Q relations. The fact that modern equations of state are stiff, with an effective adiabatic index larger than about two, above the nuclear density range is the key to establishing the universality for neutron stars and quark stars with typical compactness from about 0.1 to 0.3. On the other hand, the I-Love-Q relations of low-mass neutron stars near the minimum mass limit depend more sensitively on the underlying equation of state because these stars are composed mainly of softer matter at low densities. However, the I-Love-Q relations for low-mass quark stars can still be represented accurately by the incompressible limit. We also study the I-Love relation connecting the moment of inertia and tidal deformability analytically in Newtonian gravity and show why the I-Love-Q relation is weakly dependent on the underlying equation of state and can be attributed to its incompressible limit

  4. Europe Unveils 20-Year Plan for Brilliant Future in Astronomy

    Science.gov (United States)

    2008-11-01

    Astronomy is enjoying a golden age of fundamental, exciting discoveries. Europe is at the forefront, thanks to 50 years of progress in cooperation. To remain ahead over the next two to three decades, Europe must prioritise and coordinate the investment of its financial and human resources even more closely. The ASTRONET network, backed by the entire European scientific community, supported by the European Commission, and coordinated by the CNRS, today presents its Roadmap for a brilliant future for European astronomy. ESO's European Extremely Large Telescope is ranked as one of two top-priority large ground-based projects. Astronet and the E-ELT ESO PR Photo 43a/08 The E-ELT Europe is a leader in astronomy today, with the world's most successful optical observatory, ESO's Very Large Telescope, and cutting-edge facilities in radio astronomy and in space. In an unprecedented effort demonstrating the potential of European scientific cooperation, all of European astronomy is now joining forces to define the scientific challenges for the future and construct a common plan to address them in a cost-effective manner. In 2007, a top-level Science Vision was prepared to assess the most burning scientific questions over the next quarter century, ranging from dark energy to life on other planets. European astronomy now presents its Infrastructure Roadmap, a comprehensive 20-year plan to coordinate national and community investments to meet these challenges in a cost-effective manner. The Roadmap not only prioritises the necessary new frontline research facilities from radio telescopes to planetary probes, in space and on the ground, but also considers such key issues as existing facilities, human resources, ICT infrastructure, education and outreach, and cost -- of operations as well as construction. This bold new initiative -- ASTRONET -- was created by the major European funding agencies with support from the European Commission and is coordinated by the National Institute

  5. Effect of bioceramic functional groups on drug binding and release kinetics

    Science.gov (United States)

    Trujillo, Christopher

    (p < 0.05) in the cumulative and percent of Vanc released from pre-immersed samples P-0 (1.505 +/- .014 mg; 33.59 +/- 1.35 %) to P-331 (1.581 +/- .057 mg; 42.27 +/- 1.51 %) of Vanc, respectively. Furthermore, in the first 4 hours, the deceleration of drug release from sample P-0 to P-331 decreased from -66.92 to -34.07 microg of Vanc/mL /hr 2, for control non immersed Cris and from -72.60 to -46.04 microg of Vanc/mL/hr2, for pre-immersed samples. Furthermore, during the first 4 hours of burst release the percentage of drug released from the total amount of drug loaded for non-immersed samples P-0 was 41 % and for P-331was 26 %. After the 4 hours of Vanc release the amount of Vanc available for release for samples P-0 and P-331 was .898 mg and .945 mg, respectively. The same relationship was found for pre-immersed samples during the first 4 hours of burst release the percentage of drug released from the total amount of drug loaded for samples P-0 was 42 % and for P-331 was 30 %. After the 4 hours of Vanc release the amount of Vanc available for release for samples P-0 and P-331 was .873 mg and 1.106 mg, respectively. These results indicated the effect of phosphate content on decreasing the drug release rate. The drug release kinetics study showed that the release of phosphate ions from the surface of Cris prior to drug loading exposed active silicate functional groups that enhanced drug binding by physisorption which in turn facilitated rapid release kinetics. On the other hand, a slower drug release rate was observed as the phosphate functional groups increased on the material surface due to chemisorption. Results from the present study indicate that it is possible to enhance the burst release stage of a bioceramic drug carrier by increasing the silicate functional groups. The sustained release profile can be engineered by controlling the phosphate content of the bioceramic drug carrier.

  6. Effect of a new drug releasing system on microencapsulated islet transplantation

    Science.gov (United States)

    Lu, Binjie; Gao, Qingkun; Liu, Rui; Ren, Ming; Wu, Yan; Jiang, Zaixing; Zhou, Yi

    2015-01-01

    Objective: This study aimed to develop a novel release system for grafted islets. Materials and methods: A graphene oxide-FTY720 release system was constructed to test the drug loading and releasing capacity. The recipient rats were divided into four groups as following: Experiment group A (EG A) and B (EG B); Control group A (CG A) and B (CG B). In each group, (2000±100) IEQ microencapsulated islets were implanted into the abdominal cavity of the recipients with oral FTY720, local graphene oxide-FTY720 injection, without immunosuppressants, and with graphene oxide-saturated solution respectively. We detected the immunological data, the blood glucose level, and pericapsular overgrowth to show the transplantation effect. Results: 31% of adsorptive FTY720 was released within 6 h, and 82% of FTY720 was released within 48 h. From day 5 to 8, the amount of PBL in EG B was significantly less than those in EG A (PGraphene oxide-FTY720 complex showed a drug releasing effect. Local application of graphene-FTY720 releasing system could decrease the amount of peripheral blood lymphocytes (PBL) and the percentage of CD3 and CD8 T lymphocytes in blood for longer time than oral drug application. This releasing system could achieve a better blood glucose control. PMID:26722425

  7. Antigenotoxic effects of a polyherbal drug septilin against the genotoxicity of cyclophosphamide in mice

    Directory of Open Access Journals (Sweden)

    S. Shruthi

    Full Text Available Septilin (Spt is a polyherbal drug formulation from Himalaya Drug Company, consisting of extracts from different medicinal plants and minerals. In the traditional system of medicine, septilin is being used as immunomodulatory, antioxidant and anti-inflammatory agent. In the present study, the protective effects of septilin against the genotoxicity of cyclophosphamide (CP a widely used alkylating anticancer drug was evaluated by using in vivo micronucleus (MN and sperm shape abnormality assays in Swiss albino mice. CP administered intraperitoneally at a dose of 50 mg/kg b.w. was used as positive mutagen. Different doses of septilin viz., 125, 250 and 500 mg/kg b.w. was orally administered for 5 consecutive days. CP was administered intraperitoneally on 5th day. MN and sperm preparations were made after 24 h and 35 days respectively. CP induced significant MN in both bone marrow and peripheral blood cells and also a high frequency of abnormal sperms. In septilin supplemented animals, no significant induction of MN and abnormal sperms was recorded. In septilin supplemented groups, a dose dependent significant decrease in CP induced clastogenicity was observed. Thus the current in vivo study revealed the antigenotoxic effects of septilin against CP induced damage, in both somatic and germ cells of Swiss albino mice. Keywords: Septilin, Cyclophosphamide, Micronucleus test, Sperm abnormality, Antigenotoxic

  8. Tamoxifen: an FDA approved drug with neuroprotective effects for spinal cord injury recovery

    Directory of Open Access Journals (Sweden)

    Jennifer M Colón

    2016-01-01

    Full Text Available Spinal cord injury (SCI is a condition without a cure, affecting sensory and/or motor functions. The physical trauma to the spinal cord initiates a cascade of molecular and cellular events that generates a non-permissive environment for cell survival and axonal regeneration. Among these complex set of events are damage of the blood-brain barrier, edema formation, inflammation, oxidative stress, demyelination, reactive gliosis and apoptosis. The multiple events activated after SCI require a multi-active drug that could target most of these events and produce a permissive environment for cell survival, regeneration, vascular reorganization and synaptic formation. Tamoxifen, a selective estrogen receptor modulator, is an FDA approved drug with several neuroprotective properties that should be considered for the treatment of this devastating condition. Various investigators using different animal models and injury parameters have demonstrated the beneficial effects of this drug to improve functional locomotor recovery after SCI. Results suggest that the mechanism of action of Tamoxifen administration is to modulate anti-oxidant, anti-inflammatory and anti-gliotic responses. A gap of knowledge exists regarding the sex differences in response to Tamoxifen and the therapeutic window available to administer this treatment. In addition, the effects of Tamoxifen in axonal outgrowth or synapse formation needs to be investigated. This review will address some of the mechanisms activated by Tamoxifen after SCI and the results recently published by investigators in the field.

  9. Effect of piroxicam on lipid membranes: Drug encapsulation and gastric toxicity aspects.

    Science.gov (United States)

    Wilkosz, Natalia; Rissanen, Sami; Cyza, Małgorzata; Szybka, Renata; Nowakowska, Maria; Bunker, Alex; Róg, Tomasz; Kepczynski, Mariusz

    2017-03-30

    Uptake of piroxicam, a non-steroidal anti-inflammatory drug, from the intestines after oral intake is limited due to its low solubility and its wide use is associated with several side effects related to the gastrointestinal tract. In this study, all-atom molecular dynamics (MD) simulations and fluorescent spectroscopy were employed to investigate the interaction of piroxicam in neutral, zwitterionic, and cationic forms with lipid bilayers composed of phosphatidylcholine, cholesterol, and PEGylated lipids. Our study was aimed to assess the potential for encapsulation of piroxicam in liposomal carriers and to shed more light on the process of gastrointestinal tract injury by the drug. Through both the MD simulations and laser scanning confocal microscopy, we have demonstrated that all forms of piroxicam can associate with the lipid bilayers and locate close to the water-membrane interface. Conventional liposomes used in drug delivery are usually stabilized by the addition of cholesterol and have their bloodstream lifetime extended through the inclusion of PEGylated lipids in the formulation to create a protective polymer corona. For this reason, we tested the effect of these two modifications on the behavior of piroxicam in the membrane. When the bilayer was PEGylated, piroxicam localize to the PEG layer and within the lipid headgroup region. This suggests that PEGylated liposomes are capable of carrying a larger quantity of piroxicam than the conventional ones. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Effect of Antimalarial Drugs on Plasmodia Cell-Free Protein Synthesis

    Directory of Open Access Journals (Sweden)

    Ana Ferreras

    2002-04-01

    Full Text Available A cell-free system from Plasmodium falciparum able to translate endogenous mRNA was used to determine the effect of artemisinin, chloroquine and primaquine on the protein synthesis mechanism of the parasite. The antimalarial drugs did not inhibit the incorporation of [³H] methionine into parasite proteins even at concentrations higher than the ones found to strongly inhibit the parasite growth. Results clearly indicate that these compounds do not have a direct effect on protein synthesis activity of P. falciparum coded by endogenous mRNA.

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

    Science.gov (United States)

    Limbu, Yam; Torres, Ivonne M

    2009-01-01

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

  12. Effects of Membrane PEGylation on Entry and Location of Antifungal Drug Itraconazole and Their Pharmacological Implications

    DEFF Research Database (Denmark)

    Dzieciuch-Rojek, Monika; Poojari, Chetan; Bednar, Jan

    2017-01-01

    Itraconazole (ITZ) is an antifungal agent used clinically to treat mycotic infections. However, its therapeutic effects are limited by low solubility in aqueous media. Liposome-based delivery systems (LDS) have been proposed as a delivery mechanism for ITZ to alleviate this problem. Furthermore...... of ITZ incorporation into liposomes both with and without PEGylation because it can provide a potential foundation for the rational design of LDS-based systems for delivery of ITZ, using alternate protective polymers or formulations. Here we have combined atomistic simulations, cryo-TEM, Langmuir film...... balance, and fluorescence quenching experiments to explore how ITZ interacts with both pristine and PEGylated liposomes. We found that the drug can be incorporated into conventional and PEGylated liposomes for drug concentrations up to 15 mol % without phase separation. We observed that, in addition...

  13. The effectiveness of a course of the drug " Alakton " in the preparation of skilled wrestlers

    Directory of Open Access Journals (Sweden)

    V.V. Sazonov

    2013-12-01

    Full Text Available Purpose . The influence of the new domestic preparation on the performance of functional readiness and psychophysiological performance athletes. Material and methods . The study involved 12 qualified wrestlers (age 17-19 years with the written consent. The drug contains chelated magnesium glycinate cocarboxylase and betaine. Course reception - within seven days of shock microcycle. Results . Found that course reception has a positive impact on health and the special recovery processes athletes. Also found a positive effect on physiological indicators. The authentic reduction in travel time distance shuttle run 4 x 9 m, increase in the coefficient of special endurance, increase the number of repetitions in the test. Showed a reduction in the coefficient of restitution and increasing the number of shots (mill in this test. Conclusions . The data obtained suggest appropriate use of the drug in the practice of preparing skilled fighters.

  14. Creation of nano eye-drops and effective drug delivery to the interior of the eye

    Science.gov (United States)

    Ikuta, Yoshikazu; Aoyagi, Shigenobu; Tanaka, Yuji; Sato, Kota; Inada, Satoshi; Koseki, Yoshitaka; Onodera, Tsunenobu; Oikawa, Hidetoshi; Kasai, Hitoshi

    2017-03-01

    Nano eye-drops are a new type of ophthalmic treatment with increased potency and reduced side effects. Compounds in conventional eye-drops barely penetrate into the eye because the cornea, located at the surface of eye, has a strong barrier function for preventing invasion of hydrophilic or large-sized materials from the outside. In this work, we describe the utility of nano eye-drops utilising brinzolamide, a commercially available glaucoma treatment drug, as a target compound. Fabrication of the nanoparticles of brinzolamide prodrug increases the eye penetration rate and results in high drug efficacy, compared with that of commercially available brinzolamide eye-drops formulated as micro-sized structures. In addition, the resulting nano eye-drops were not toxic to the corneal epithelium after repeated administration for 1 week. The nano eye-drops may have applications as a next-generation ophthalmic treatment.

  15. Particle size, magnetic field, and blood velocity effects on particle retention in magnetic drug targeting.

    Science.gov (United States)

    Cherry, Erica M; Maxim, Peter G; Eaton, John K

    2010-01-01

    A physics-based model of a general magnetic drug targeting (MDT) system was developed with the goal of realizing the practical limitations of MDT when electromagnets are the source of the magnetic field. The simulation tracks magnetic particles subject to gravity, drag force, magnetic force, and hydrodynamic lift in specified flow fields and external magnetic field distributions. A model problem was analyzed to determine the effect of drug particle size, blood flow velocity, and magnetic field gradient strength on efficiency in holding particles stationary in a laminar Poiseuille flow modeling blood flow in a medium-sized artery. It was found that particle retention rate increased with increasing particle diameter and magnetic field gradient strength and decreased with increasing bulk flow velocity. The results suggest that MDT systems with electromagnets are unsuitable for use in small arteries because it is difficult to control particles smaller than about 20 microm in diameter.

  16. Effects of Multidimensional Family Therapy (MDFT) on Nonopioid Drug Abuse: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint

    2018-01-01

    Purpose: This review evaluates the evidence of the effects of multidimensional family therapy (MDFT) on drug use reduction in young people for the treatment of nonopioid drug use. Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials. Meta-analytic methods were used to…

  17. The effect of screening for cardio-renal risk factors on drug use in the general population

    NARCIS (Netherlands)

    Atthobari, J.; Gansevoort, R.T.; Visser, S.T.; De Jong, P.E.; de Jong-van den Berg, L.T.

    2007-01-01

    Aims To evaluate the effect of a cardio-renal screening programme on desired and undue drug use. Methods Data from the PREVEND cohort (Prevention of REnal and Vascular ENd-stage Disease) were used. The drug use of screened (randomly) selected subjects (n = 2650) was compared with unscreened

  18. Unveiling EFL and Self-Contained Teachers’ Discourses on Bilingualism Within the Context of Professional Development

    Directory of Open Access Journals (Sweden)

    Jennyfer Paola Camargo Cely

    2018-01-01

    Full Text Available Throughout time, the predominant use of certain languages has allowed some nations to take control over others and assure for them a privileged position. This study unveiled how certain practices and ideologies in regard to bilingualism have influenced teachers’ professional development. Data were collected through discussion group sessions, reflective journals, and protocols from five teachers from a private K-11 school in Bogota. Analysis indicated participants’ discourses drew on hegemonic, colonial, and manipulative ideas. Nevertheless, when dialoguing and peer coaching, a discourse of resistance was constituted. The study suggested further research into teachers’ professional growth, bilingualism, and bilingual education in monolingual contexts as the Colombian one.

  19. The Effects of Fall-Risk-Increasing Drugs on Postural Control : A Literature Review

    NARCIS (Netherlands)

    de Groot, Maartje H.; van Campen, Jos P. C. M.; Moek, Marije A.; Tulner, Linda R.; Beijnen, Jos H.; Lamoth, Claudine J. C.

    Meta-analyses showed that psychotropic drugs (antidepressants, neuroleptics, benzodiazepines, antiepileptic drugs) and some cardiac drugs (digoxin, type IA anti-arrhythmics, diuretics) are associated with increased fall risk. Because balance and gait disorders are the most consistent predictors of

  20. Effect of particle size of drug on conversion of crystals to an amorphous state in a solid dispersion with crospovidone.

    Science.gov (United States)

    Sugamura, Yuka; Fujii, Makiko; Nakanishi, Sayaka; Suzuki, Ayako; Shibata, Yusuke; Koizumi, Naoya; Watanabe, Yoshiteru

    2011-01-01

    The effect of particle size on amorphization of drugs in a solid dispersion (SD) was investigated for two drugs, indomethacin (IM) and nifedipine (NP). The SD of drugs were prepared in a mixture with crospovidone by a variety of mechanical methods, and their properties investigated by particle sizing, thermal analysis, and powder X-ray diffraction. IM, which had an initial particle size of 1 µm and tends to aggregate, was forced through a sieve to break up the particles. NP, which had a large initial particle size, was jet-milled. In both cases, reduction of the particle size of the drugs enabled transition to an amorphous state below the melting point of the drug. The reduction in particle size is considered to enable increased contact between the crospovidone and drug particles, increasing interactions between the two compounds. © 2011 Pharmaceutical Society of Japan