Expectancies for cigarettes, e-cigarettes, and nicotine replacement therapies among e-cigarette users (aka vapers).

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Harrell, Paul T; Marquinez, Nicole S; Correa, John B; Meltzer, Lauren R; Unrod, Marina; Sutton, Steven K; Simmons, Vani N; Brandon, Thomas H

2015-02-01

Use of e-cigarettes has been increasing exponentially, with the primary motivation reported as smoking cessation. To understand why smokers choose e-cigarettes as an alternative to cigarettes, as well as to US Food and Drug Administration (FDA)--approved nicotine replacement therapies (NRT), we compared outcome expectancies (beliefs about the results of drug use) for the three nicotine delivery systems among vapers, i.e., e-cigarette users, who were former smokers. Vapers (N = 1,434) completed an online survey assessing 14 expectancy domains as well as perceived cost and convenience. We focused on comparisons between e-cigarettes and cigarettes to determine the attraction of e-cigarettes as a smoking alternative and between e-cigarettes and NRT to determine perceived advantages of e-cigarettes over FDA-approved pharmacotherapy. Participants believed that e-cigarettes, in comparison to conventional cigarettes, had fewer health risks; caused less craving, withdrawal, addiction, and negative physical feelings; tasted better; and were more satisfying. In contrast, conventional cigarettes were perceived as better than e-cigarettes for reducing negative affect, controlling weight, providing stimulation, and reducing stress. E-cigarettes, compared to NRT, were perceived to be less risky, cost less, cause fewer negative physical feelings, taste better, provide more satisfaction, and be better at reducing craving, negative affect, and stress. Moderator analyses indicated history with ad libitum forms of NRT was associated with less positive NRT expectancies. The degree to which expectancies for e-cigarettes differed from expectancies for either tobacco cigarettes or NRT offers insight into the motivation of e-cigarette users and provides guidance for public health and clinical interventions to encourage smoking-related behavior change. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved

Smokers making a quit attempt using e-cigarettes with or without nicotine or prescription nicotine replacement therapy: Impact on cardiovascular function (ISME-NRT) - a study protocol.

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Klonizakis, Markos; Crank, Helen; Gumber, Anil; Brose, Leonie S

2017-04-04

The estimated number of cigarette smokers in the world is 1.3 billion, expected to rise to 1.7 billion by 2025, with 10 million smokers living in the U.K. Smoking is the leading, preventable death-cause worldwide, being responsible for almost 650,000 deaths in the E.U. annually. A combination of pharmacological interventions, including nicotine replacement therapy, bupropion and varenicline, and behavioural support is the most effective approach to smoking cessation. However, even the best methods have high relapse rates of approximately 75% within 6 months. Electronic (or "e-") cigarettes use battery power to disperse a solution that usually contains propylene glycol or glycerine, water, flavouring and nicotine. E-cigarettes have become the most popular smoking cessation aid in England, however, information on their effects on cardiovascular function is limited and contradictory. As e-cigarettes are not solely nicotine-based products, existing research exploring the effects of nicotine on the cardio-vasculature provides only limited information, while their extensive uptake urges the need of evidence to inform the general public, smokers and policy-makers. This is a pragmatic, 3-group, randomised, assessor-blinded, single-centre trial exploring the cardiovascular physiological effects of the use of e-cigarettes (nicotine-free and nicotine-inclusive, assessed separately) combined with behavioural support as a smoking cessation method in comparison to the combination of NRT and behavioural support. The primary outcome will be macro-vascular function, determined by a Flow Mediated Dilatation ultrasound assessment, 6 months following participants' "quit date". Participants will be assessed at baseline, 3 days following their self-determined "quit date", at intervention end (3 months) and 6 months following their "quite date". Findings are expected to give an indication of the cardiovascular effects of e-cigarettes both in the short- and in the medium-term period

How do consumers perceive differences in risk across nicotine products? A review of relative risk perceptions across smokeless tobacco, e-cigarettes, nicotine replacement therapy and combustible cigarettes.

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Czoli, Christine D; Fong, Geoffrey T; Mays, Darren; Hammond, David

2017-03-01

To systematically review the literature regarding relative risk perceptions (RRPs) across non-combustible nicotine products. MEDLINE and PsycINFO databases were searched for articles published up to October 2014. Of the 5266 records identified, articles not published in English that did not quantitatively assess RRPs across categories of non-combustible nicotine products were excluded, yielding 55 records. One reviewer extracted measures and findings of RRPs for product comparisons of smokeless tobacco (SLT), e-cigarettes (ECs) and nicotine replacement therapy (NRT) to one another, and to combustible cigarettes (CCs). A total of 157 samples from 54 studies were included in the analyses. The accuracy of RRPs differed based on the products being compared: although the accuracy of RRPs was variable across studies, substantial proportions of respondents reported inaccurate beliefs about the relative harmfulness of SLT versus CCs, as well as of ECs versus NRT. In addition, in most studies, respondents did not know the relative harmfulness of SLT versus NRT. In contrast, respondents in many studies correctly perceived NRT and ECs as less harmful than CCs. Cigarette smokers and users of non-combustible nicotine products tended to correctly perceive the relative harmfulness of products more often than non-users. Measures used to assess RRPs varied across studies, with different approaches characterised by certain strengths and limitations. The highly variable and context-specific nature of non-combustible nicotine product RRPs have direct implications for researchers and present several challenges for policymakers working with modified risk products, including issues of measurement, health risk communication and behaviour change. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Long-term effectiveness of mailed nicotine replacement therapy: study protocol of a randomized controlled trial 5-year follow-up.

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Kushnir, Vladyslav; Selby, Peter; Zawertailo, Laurie; Tyndale, Rachel F; Leatherdale, Scott T; Cunningham, John A

2017-07-18

Our group recently completed a randomized controlled trial, evaluating the efficacy of providing 5 weeks of free nicotine replacement therapy (NRT; in the form of the nicotine patch) by expedited postal mail without behavioral assistance to regular adult smokers interested in receiving it. The findings revealed that mailed provision of nicotine patches resulted in more than a doubling of quit rates at a six-month follow-up compared to a no intervention control group. While this trial provided evidence for the effectiveness of mailed nicotine patches in promoting cessation, the findings speak only to the short term effectiveness of this approach. As relapse to smoking is known to occur beyond the 6 month period, it is important to evaluate whether the net benefit of NRT in naturalistic settings can be maintained long-term. The present study aims to perform a 5-year follow-up survey of participants in the original trial to evaluate the long-term effectiveness of mailed NRT. Trained interviewers will contact participants in the randomized controlled trial 5 years post-enrollment. A total of 924 participants will be eligible to be contacted. Interviewers will first assess participants' smoking status and their level of nicotine dependence. Participants reporting not currently smoking will be asked whether they have smoked tobacco, even a puff, in the last 30 days (primary outcome measure: 30-day point prevalence abstinence), past 6 months (secondary outcome measure: prolonged 6-month abstinence), and since the 8-week follow-up survey (secondary outcome measure: > 4 year continuous abstinence). Interviewers will be blind to experimental condition at the time the primary outcome measure will be assessed. It is hypothesized that participants who received nicotine patches at baseline will display significantly higher quit rates at the 5-year follow-up as compared to participants who did not receive nicotine patches at baseline. If the study finds that the mailed

Smokers making a quit attempt using e-cigarettes with or without nicotine or prescription nicotine replacement therapy: Impact on cardiovascular function (ISME-NRT - a study protocol

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Markos Klonizakis

2017-04-01

Full Text Available Abstract Background The estimated number of cigarette smokers in the world is 1.3 billion, expected to rise to 1.7 billion by 2025, with 10 million smokers living in the U.K. Smoking is the leading, preventable death-cause worldwide, being responsible for almost 650,000 deaths in the E.U. annually. A combination of pharmacological interventions, including nicotine replacement therapy, bupropion and varenicline, and behavioural support is the most effective approach to smoking cessation. However, even the best methods have high relapse rates of approximately 75% within 6 months. Electronic (or “e-“ cigarettes use battery power to disperse a solution that usually contains propylene glycol or glycerine, water, flavouring and nicotine. E-cigarettes have become the most popular smoking cessation aid in England, however, information on their effects on cardiovascular function is limited and contradictory. As e-cigarettes are not solely nicotine-based products, existing research exploring the effects of nicotine on the cardio-vasculature provides only limited information, while their extensive uptake urges the need of evidence to inform the general public, smokers and policy-makers. Methods This is a pragmatic, 3-group, randomised, assessor-blinded, single-centre trial exploring the cardiovascular physiological effects of the use of e-cigarettes (nicotine-free and nicotine-inclusive, assessed separately combined with behavioural support as a smoking cessation method in comparison to the combination of NRT and behavioural support. The primary outcome will be macro-vascular function, determined by a Flow Mediated Dilatation ultrasound assessment, 6 months following participants’ “quit date”. Discussion Participants will be assessed at baseline, 3 days following their self-determined “quit date”, at intervention end (3 months and 6 months following their “quite date”. Findings are expected to give an indication of the cardiovascular

A systematic review of possible serious adverse health effects of nicotine replacement therapy.

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Lee, Peter N; Fariss, Marc W

2017-04-01

We conducted a systematic literature review to identify and critically evaluate studies of serious adverse health effects (SAHEs) in humans using nicotine replacement therapy (NRT) products. Serious adverse health effects refer to adverse events, leading to substantial disruption of the ability to conduct normal life functions. Strength of evidence evaluations and conclusions were also determined for the identified SAHEs. We evaluated 34 epidemiological studies and clinical trials, relating NRT use to cancer, reproduction/development, CVD, stroke and/or other SAHEs in patients, and four meta-analyses on effects in healthy populations. The overall evidence suffers from many limitations, the most significant being the short-term exposure (≤12 weeks) and follow-up to NRT product use in most of the studies, the common failure to account for changes in smoking behaviour following NRT use, and the sparse information on SAHEs by type of NRT product used. The only SAHE from NRT exposure we identified was an increase in respiratory congenital abnormalities reported in one study. Limited evidence indicated a lack of effect between NRT exposure and SAHEs for CVD and various reproduction/developmental endpoints. For cancer, stroke and other SAHEs, the evidence was inadequate to demonstrate any association with NRT use. Our conclusions agree with recent statements from authoritative bodies.

Use of pharmacy data to evaluate smoking regulations' impact on sales of nicotine replacement therapies in New York City.

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Metzger, Kristina B; Mostashari, Farzad; Kerker, Bonnie D

2005-06-01

Recently, New York City and New York State increased cigarette excise taxes and New York City implemented a smoke-free workplace law. To assess the impact of these policies on smoking cessation in New York City, we examined over-the-counter sales of nicotine replacement therapy (NRT) products. Pharmacy sales data were collected in real time as part of nontraditional surveillance activities. We used Poisson generalized estimating equations to analyze the effect of smoking-related policies on pharmacy-specific weekly sales of nicotine patches and gum. We assessed effect modification by pharmacy location. We observed increases in NRT product sales during the weeks of the cigarette tax increases and the smoke-free workplace law. Pharmacies in low-income areas generally had larger and more persistent increases in response to tax increases than those in higher-income areas. Real-time monitoring of existing nontraditional surveillance data, such as pharmacy sales of NRT products, can help assess the effects of public policies on cessation attempts. Cigarette tax increases and smoke-free workplace regulations were associated with increased smoking cessation attempts in New York City, particularly in low-income areas.

Cardiovascular risks in smokers treated with nicotine replacement therapy: a historical cohort study

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Dollerup J

2017-04-01

Full Text Available Jens Dollerup,1 Jørgen Vestbo,2 Tarita Murray-Thomas,3 Alan Kaplan,4 Richard J Martin,5 Emilio Pizzichini,6 Marcia M M Pizzichini,6 Anne Burden,7 Jessica Martin,7 David B Price7,8 1Dollerup Medical Consultancy, Kongens Lyngby, Denmark; 2Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, Manchester, UK; 3Clinical Practice Research Datalink, Medicines and Healthcare products Regulatory Agency, London, UK; 4Family Physician Airways Group of Canada, Richmond Hill, ON, Canada; 5National Jewish Health, Denver, CO, USA; 6Federal University of Santa Catarina, Santa Catarina, Brazil; 7Observational and Pragmatic Research Institute Pte Ltd, Singapore; 8Centre for Academic Primary Care, University of Aberdeen, Aberdeen, UK Background: Previous research suggests exposure to nicotine replacement therapy (NRT may be associated with an increased risk of cardiovascular disease (CVD.Methods: Using data from the United Kingdom’s Clinical Practice Research Datalink, this study aimed to evaluate CVD events and survival among individuals who attempted smoking cessation with the support of NRT compared with those aided by smoking cessation advice only. We studied CVD outcomes over 4 and 52 weeks in 50,214 smokers attempting to quit – 33,476 supported by smoking cessation advice and 16,738 with the support of NRT prescribed by their primary care physician. Patients were matched (2 smoking cessation advice patients:1 NRT patient on demographic and clinical characteristics during a baseline year preceding their quit attempt. Cox proportional hazard regression, conditional negative binomial regression model, and conditional logistic regression were used to analyze data.Results: Mean (standard deviation population age was 47 (11.2 years; 51% were females. Time to first diagnosis of ischemic heart disease (IHD among NRT and smoking cessation advice patients was similar within the first 4 weeks, but

Predictors of treatment success in smoking cessation with varenicline combined with nicotine replacement therapy v varenicline alone

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F Noor

2018-12-01

Full Text Available Background. Identification of the predictors of treatment success in smoking cessation may help healthcare workers to improve the effectiveness of attempts at quitting.Objective. To identify the predictors of success in a randomised controlled trial comparing varenicline alone or in combination with nicotine replacement therapy (NRT.Methods. A post-hoc analysis of the data of 435 subjects who participated in a 24-week, multicentre trial in South Africa was performed. Logistic regression was used to analyse the effect of age, sex, age at smoking initiation, daily cigarette consumption, nicotine dependence, and reinforcement assessment on abstinence rates at 12 and 24 weeks. Point prevalence and continuous abstinence rates were self-reported and confirmed biochemically with exhaled carbon monoxide readings.Results. The significant predictors of continuous abstinence at 12 and 24 weeks on multivariate analysis were lower daily cigarette consumption (odds ratio (OR 1.86, 95% confidence interval (CI 1.21 - 2.87, p=0.005 and OR 1.83, 95% CI 1.12 - 2.98, p=0.02, respectively and older age (OR 1.52, 95% CI 1.00 - 2.31, p=0.049 and OR 1.79, 95% CI 1.13 - 2.84, p=0.01, respectively. There was no difference in the predictors of success in the univariate analysis, except that older age predicted point prevalence abstinence at 12 weeks (OR 1.47, 95% CI 1.00 - 2.15, p=0.049. The findings were inconclusive for an association between abstinence and lower nicotine dependence, older age at smoking initiation and positive reinforcement.Conclusion. Older age and lower daily cigarette consumption are associated with a higher likelihood of abstinence in patients using varenicline, regardless of the addition of NRT.

Comparative In Vitro Toxicity Profile of Electronic and Tobacco Cigarettes, Smokeless Tobacco and Nicotine Replacement Therapy Products: E-Liquids, Extracts and Collected Aerosols

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Manoj Misra

2014-10-01

Full Text Available The use of electronic cigarettes (e-cigs continues to increase worldwide in parallel with accumulating information on their potential toxicity and safety. In this study, an in vitro battery of established assays was used to examine the cytotoxicity, mutagenicity, genotoxicity and inflammatory responses of certain commercial e-cigs and compared to tobacco burning cigarettes, smokeless tobacco (SLT products and a nicotine replacement therapy (NRT product. The toxicity evaluation was performed on e-liquids and pad-collected aerosols of e-cigs, pad-collected smoke condensates of tobacco cigarettes and extracts of SLT and NRT products. In all assays, exposures with e-cig liquids and collected aerosols, at the doses tested, showed no significant activity when compared to tobacco burning cigarettes. Results for the e-cigs, with and without nicotine in two evaluated flavor variants, were very similar in all assays, indicating that the presence of nicotine and flavors, at the levels tested, did not induce any cytotoxic, genotoxic or inflammatory effects. The present findings indicate that neither the e-cig liquids and collected aerosols, nor the extracts of the SLT and NRT products produce any meaningful toxic effects in four widely-applied in vitro test systems, in which the conventional cigarette smoke preparations, at comparable exposures, are markedly cytotoxic and genotoxic.

Nicotine Vapor Method to Induce Nicotine Dependence in Rodents.

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Kallupi, Marsida; George, Olivier

2017-07-05

Nicotine, the main addictive component of tobacco, induces potentiation of brain stimulation reward, increases locomotor activity, and induces conditioned place preference. Nicotine cessation produces a withdrawal syndrome that can be relieved by nicotine replacement therapy. In the last decade, the market for electronic cigarettes has flourished, especially among adolescents. The nicotine vaporizer or electronic nicotine delivery system is a battery-operated device that allows the user to simulate the experience of tobacco smoking without inhaling smoke. The device is designed to be an alternative to conventional cigarettes that emits vaporized nicotine inhaled by the user. This report describes a procedure to vaporize nicotine in the air to produce blood nicotine levels in rodents that are clinically relevant to those that are observed in humans and produce dependence. We also describe how to construct the apparatus to deliver nicotine vapor in a stable, reliable, and consistent manner, as well as how to analyze air for nicotine content. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Nicotine and tobacco

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... ease your withdrawal symptoms. Health experts warn that e-cigarettes are not a replacement therapy for cigarette smoking. ... not known exactly how much nicotine is in e-cigarette cartridges, because information on labels is often wrong.

Nicorette reborn? E-cigarettes in light of the history of nicotine replacement technology.

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Elam, Mark J

2015-06-01

E-cigarettes are currently hotly debated as threatening to re-normalize cigarette smoking and make nicotine addiction publicly acceptable once more. In this paper I contextualize the e-cigarette controversy in light of longstanding disagreements about the meaning and significance of nicotine replacement technologies. A concerted effort to develop such technologies first emerged in Sweden at the end of the 1960s, embodying a vital tension. Two competing 'scripts' vied to influence and shape innovative designs. On the one hand, Nicorette chewing gum was conceived as a therapeutic device aiding smoking cessation. On the other hand, it was cast as a cigarette substitute designed to deliver nicotine 'in the right way', thereby advancing the creative destruction of the combustible cigarette as a drug delivery platform. Drawing on historical and archival research I outline how these two alternative innovation scripts started out entangled with each other before becoming disentangled, leading to the eventual stabilization of Nicorette gum as a therapeutic product to be deployed in the treatment of smoking as a dependence disorder. While a post-therapeutic future for nicotine replacement was charted by Michael Russell at the beginning of the 1990s, it is only with the rise of e-cigarettes after 2003 that such a future has started to verge on reality. E-cigarettes can be seen as resurrecting the historically marginalized script of nicotine replacement as dedicated to righting nicotine consumption and freeing it from the wrongful drug delivery of the modern cigarette. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of nicotine replacement therapy on cardiovascular outcomes after acute coronary syndromes.

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Woolf, Kevin J; Zabad, Mohammed Nour; Post, Jennifer M; McNitt, Scott; Williams, Geoffrey C; Bisognano, John D

2012-10-01

The optimal approach to encourage smoking cessation after acute coronary syndrome (ACS) remains unclear. The safety of nicotine replacement therapy (NRT) after ACS is not well established. The aim of the present study was to determine the relationship between NRT use and adverse cardiovascular outcomes after ACS. Using a pre-existing database, 663 smokers with ACS were identified. The patients were separated into the NRT (n = 184) or control (n = 479) groups according to whether NRT was prescribed on hospital discharge. Multivariate logistic regression analysis was used to account for the baseline differences between the 2 groups. Of the 663 patients, 202 had adverse events in the first year after ACS. No significant differences were seen with NRT use for the 1-year combined end point of death, myocardial infarction), repeat revascularization, or rehospitalization for angina, congestive heart failure or arrhythmia (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.61 to 1.30, p = 0.54). There were no differences in the individual 1-year end points of death (odds ratio 0.80, 95% confidence interval 0.33 to 1.91, p = 0.61), myocardial infarction (odds ratio 0.90, 95% confidence interval 0.40 to 2.06, p = 0.80), repeat revascularization (odds ratio 0.77, 95% confidence interval 0.44 to 1.36, p = 0.37), or rehospitalization for angina, congestive heart failure, or arrhythmia (odds ratio 1.01, 95% confidence interval 0.66 to 1.53, p = 0.97). In conclusion, NRT use was not associated with an increased risk of adverse cardiovascular events in the first year after ACS. Copyright © 2012 Elsevier Inc. All rights reserved.

Design, formulation and evaluation of nicotine chewing gum

OpenAIRE

Abolfazl Aslani; Sahar Rafiei

2012-01-01

Background: Nicotine replacement therapy (NRT) can help smokers to quit smoking. Nicotine chewing gum has attracted the attention from pharmaceutical industries to offer it to consumers as an easily accessible NRT product. However, the bitter taste of such gums may compromise their acceptability by patients. This study was, therefore, designed to develop 2 and 4 mg nicotine chewing gums of pleasant taste, which satisfy the consumers the most. Materials and Methods: Nicotine, sugar, liquid...

E-cigarettes for the management of nicotine addiction

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Knight-West O

2016-08-01

Full Text Available Oliver Knight-West, Christopher Bullen The National Institute for Health Innovation, School of Population Health, The University of Auckland, Auckland, New Zealand Abstract: In this review, we discuss current evidence on electronic cigarettes (ECs, a rapidly evolving class of nicotine delivery system, and their role in managing nicotine addiction, specifically in helping smokers to quit smoking and/or reduce the amount of tobacco they smoke. The current evidence base is limited to three randomized trials (only one compares ECs with nicotine replacement therapy and a growing number of EC user surveys (n=6, case reports (n=4, and cohort studies (n=8. Collectively, these studies suggest modest cessation efficacy and a few adverse effects, at least with the short-term use. On this basis, we provide advice for health care providers on providing balanced information for patients who enquire about ECs. More research, specifically well-conducted large efficacy trials comparing ECs with standard smoking cessation management (eg, nicotine replacement therapy plus behavioral support and long-term prospective studies for adverse events, are urgently needed to fill critical knowledge gaps on these products. Keywords: tobacco, smoking, nicotine, electronic cigarettes, cessation, addiction

General Practitioners' views on the provision of nicotine replacement therapy and bupropion

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West Robert

2001-10-01

Full Text Available Abstract Background Nicotine replacement therapies (NRT and a new drug, bupropion, are licensed in several countries as aids to smoking cessation. General practitioners (GPs play a crucial role in recommending or prescribing these medications. In the UK there has been discussion about whether the medications should be reimbursable by the National Health Service (NHS. This study assessed English GPs' attitudes towards reimbursement of NRT and bupropion. Methods Postal survey of a randomly selected national sample of GPs; 376 GPs completed the questionnaire after one reminder; effective response rate: 53%. There was no difference between the responses of GPs who responded to the initial request and those who responded only after a reminder suggesting minimal bias due to non-response. Results Attitudes of GPs were remarkably divided on most issues relating to the medications. Forty-three percent thought that bupropion should not be on NHS prescription while 42% thought that it should be (15% did not know; Fifty percent thought that NRT should not be on NHS prescription while 42% thought it should be (8% did not know. Requiring that smokers attend behavioural support programmes to be eligible to receive the medications on NHS prescription made no appreciable difference to the GPs' views. GPs were similarly divided on whether having the medications reimbursable would add unacceptably to their workload or offer a welcome opportunity to discuss smoking with their patients. A principal components analysis of responses to the individual questions on NRT and bupropion revealed that GPs' attitudes could be understood in terms of a single 'pro-con' dimension accounting for 53% of the total variance which made no distinction between the two medications. Conclusions GPs in England appear to be divided in their attitudes to medications to aid smoking cessation and appear not to discriminate in their views between different types of medication or different

Pharmacokinetic Evaluation of Two Nicotine Patches in Smokers.

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Rasmussen, Scott; Horkan, Kathleen Halabuk; Kotler, Mitchell

2018-02-02

Smoking continues to be a major preventable cause of early mortality worldwide, and nicotine replacement therapy has been demonstrated to increase rates of abstinence among smokers attempting to quit. Nicotine transdermal systems (also known as nicotine patches) attach to the skin via an adhesive layer composed of a mixture of different-molecular-weight polyisobutylenes (PIBs) in a specific ratio. This randomized, single-dose, 2-treatment, crossover pharmacokinetic (PK) trial assessed the bioequivalence of nicotine patches including a replacement PIB adhesive (test) compared with the PIB adhesive historically used on marketed patches (reference). The test and reference patches were bioequivalent, as determined by the PK parameters of C max and AUC 0-t . In addition, the parameters T max and t 1/2 did not significantly differ between the 2 patches, supporting the bioequivalence finding from the primary analysis. The tolerability profiles of the patches containing the replacement and previously used PIB adhesives were similar; application-site adverse events did not significantly differ between test and reference patches. Overall, these data establish the bioequivalence of the nicotine patch with the replacement PIB adhesive formulation and the previously utilized PIB adhesive formulation. © 2018 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Is nicotine replacement therapy overvalued in smoking cessation? Analysis of smokers' and quitters' communication in social media.

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Kurko, Terhi; Linden, Kari; Kolstela, Maija; Pietilä, Kirsi; Airaksinen, Marja

2015-12-01

Internet discussion forums provide new, albeit less used data sources for exploring personal experiences of illness and treatment strategies. To gain an understanding of how discussion forum participants value nicotine replacement therapy (NRT) in smoking cessation (SC). Finnish national Internet-based discussion forum, STUMPPI, supporting SC and consisting of ten free discussion areas, each with a different focus. The analysis was based on STUMPPI forum participants' postings (n = 24 481) in five discussion areas during January 2007-January 2012. Inductive content analysis of the postings concerning NRT use or comparing NRT to other SC methods. Three major themes related to NRT in SC emerged from the discussions. These were as follows: (I) distrust and negative attitude towards NRT; (II) neutral acceptance of NRT as a useful SC method; and (III) trust on the crucial role of NRT and other SC medicines. The negative attitude was related to following perceptions: NRT use maintains tobacco dependence, fear of NRT dependence or experience of not gaining help from NRT use. NRT was perceived to be useful particularly in the initiation of SC attempts and in dealing with physiological dependence. The most highlighted factors of successful quitting were quitters' own psychological empowerment and peer support from the discussion community. The majority of STUMPPI forum participants had low or balanced expectations towards the role of NRT in SC. More research from the smokers' and quitters' perspective is needed to assess the real value of NRT compared to other methods in SC. © 2014 John Wiley & Sons Ltd.

The impact of TV mass media campaigns on calls to a National Quitline and the use of prescribed nicotine replacement therapy: a structural vector autoregression analysis.

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Haghpanahan, Houra; Mackay, Daniel F; Pell, Jill P; Bell, David; Langley, Tessa; Haw, Sally

2017-07-01

To estimate (1) the immediate impact; (2) the cumulative impact; and (3) the duration of impact of Scottish tobacco control TV mass media campaigns (MMCs) on smoking cessation activity, as measured by calls to Smokeline and the volume of prescribed nicotine replacement therapy (NRT). Multivariate time-series analysis using secondary data on population level measures of exposure to TV MMCs broadcast and smoking cessation activity between 2003 and 2012. Population of Scotland. Adult television viewer ratings (TVRs) as a measure of exposure to Scottish mass media campaigns in the adult population; monthly calls to NHS Smokeline; and the monthly volume of prescribed NRT as measured by gross ingredient costs (GIC). Tobacco control TVRs were associated with an increase in calls to Smokeline but not an increase in the volume of prescribed NRT. A 1 standard deviation (SD) increase of 194 tobacco control TVRs led to an immediate and significant increase of 385.9 [95% confidence interval (CI) = 171.0, 600.7] calls to Smokeline (unadjusted model) within 1 month. When adjusted for seasonality the impact was reduced, but the increase in calls remained significant (226.3 calls, 95% CI = 37.3, 415.3). The cumulative impact on Smokeline calls remained significant for 6 months after broadcast in the unadjusted model and 18 months in the adjusted model. However, an increase in tobacco control TVRs of 194 failed to have a significant impact on the GIC of prescribed NRT in either the unadjusted (£1361.4, 95% CI = -£9138.0, £11860.9) or adjusted (£6297.1, 95% CI = -£2587.8, £15182.1) models. Tobacco control television mass media campaigns broadcast in Scotland between 2003 and 2012 were effective in triggering calls to Smokeline, but did not increase significantly the use of prescribed nicotine replacement therapy by adult smokers. The impact on calls to Smokeline occurred immediately within 1 month of broadcast and was sustained for at least 6 months. © 2017 The

Looking for boomerang effects: a pre-post experimental study of the effects of exposure of youth to television advertising for nicotine replacement therapy and Zyban.

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Durkin, Sarah; Wakefield, Melanie; Spittal, Matt

2006-12-01

In the context of concerns about unintended "boomerang" influences of advertising, this study aimed to examine effects of nicotine replacement therapy (NRT) and Zyban advertising on youth perceptions of the ease of quitting, health risks of smoking and future intentions to smoke. 718 youth aged 14-16years were randomly allocated to view four television ads promoting either: NRT; Zyban; non-pharmaceutical cessation services (telephone Quitline); or non-cessation messages on sun protection. Questionnaire measures were administered before and after viewing ads. There were no effects of advertising exposure on perceived health effects of smoking or intentions to smoke. Compared with the sun protection ads, but not the Quitline ads, those exposed to NRT ads reported stronger perceptions about the ease of quitting, but non-susceptible non-smokers primarily drove this difference. This study suggests that exposure to NRT and Zyban advertising in an experimental context does not reliably influence youth smoking-related beliefs, especially those vulnerable to becoming regular smokers.

Prolonged Intermittent Renal Replacement Therapy.

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Edrees, Fahad; Li, Tingting; Vijayan, Anitha

2016-05-01

Prolonged intermittent renal replacement therapy (PIRRT) is becoming an increasingly popular alternative to continuous renal replacement therapy in critically ill patients with acute kidney injury. There are significant practice variations in the provision of PIRRT across institutions, with respect to prescription, technology, and delivery of therapy. Clinical trials have generally demonstrated that PIRRT is non-inferior to continuous renal replacement therapy regarding patient outcomes. PIRRT offers cost-effective renal replacement therapy along with other advantages such as early patient mobilization and decreased nursing time. However, due to lack of standardization of the procedure, PIRRT still poses significant challenges, especially pertaining to appropriate drug dosing. Future guidelines and clinical trials should work toward developing consensus definitions for PIRRT and ensure optimal delivery of therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Predicting intention to use nicotine replacement therapy in people attending residential treatment for substance dependency.

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Kelly, Peter J; Townsend, Camilla J; Osborne, Briony A; Baker, Amanda L; Deane, Frank P; Keane, Carol; Ingram, Isabella; Lunn, Joanne

2018-02-28

Nicotine Replacement Therapy (NRT) is recommended as a frontline smoking cessation tool for people attending mental health and substance dependence treatment services. Previous research suggests that NRT is underutilized in these settings. To improve the use of NRT amongst people attending residential treatment for substance use disorders (SUDs) it is important that the factors influencing smokers' decisions to use NRT are understood. The study aimed to examine: (1) smoking cessation strategies used by participants in previous quit attempts, (2) participants' attitudes towards NRT (i.e. safety concerns and perceived efficacy), and (3) the predictors of participants' intention to use NRT to support future quit attempts. Participants completed a cross-sectional survey that examined their smoking behaviours, previous experiences using smoking cessation strategies, attitudes and beliefs regarding NRT, and intention to use NRT as part of future quit attempts (N = 218). All participants were attending residential treatment for substance use disorders provided by We Help Ourselves (WHOS), a large provider of specialist alcohol and other drug treatment in Australia. The majority of respondents (98%) reported that they had smoked regularly in their lifetime, and 89% were current smokers. Forty-five percent of the current smokers reported that they had previously used NRT to support a quit attempt, with 54% reporting that they intended to use NRT to support a future quit attempt. Intentions to use NRT were not related to the participants' mental health status or the participants' perceptions regarding the safety or potential drawbacks associated with using NRT. However, participants were more likely to report that they would use NRT to support future quit attempts if they were female, had previously used NRT and perceived NRT to be effective. Improving the use of evidence based smoking cessation strategies within substance use treatment continues to be a priority. To enhance

Effect of growth hormone replacement therapy on pituitary hormone secretion and hormone replacement therapies in GHD adults

DEFF Research Database (Denmark)

Hubina, Erika; Mersebach, Henriette; Rasmussen, Ase Krogh

2004-01-01

We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes.......We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes....

For Nicotine, Dose Matters | Center for Cancer Research

Science.gov (United States)

Nicotine replacement therapy (NRT) is frequently part of a person’s regimen for smoking cessation. The U.S. Food and Drug Administration has approved use of this approach for 12 weeks in supervised quitting programs. Unfortunately for some patients, though, this length of time is not long enough to break their addiction to tobacco. 

Hypnotherapy is more effective than nicotine replacement therapy for smoking cessation: results of a randomized controlled trial.

Science.gov (United States)

Hasan, Faysal M; Zagarins, Sofija E; Pischke, Karen M; Saiyed, Shamila; Bettencourt, Ann Marie; Beal, Laura; Macys, Diane; Aurora, Sanjay; McCleary, Nancy

2014-02-01

The efficacy of pharmacotherapy for smoking cessation is well documented. However, due to relapse rates and side effects, hypnotherapy is gaining attention as an alternative treatment option. The aim of this one-center randomized study was to compare the efficacy of hypnotherapy alone, as well as hypnotherapy with nicotine replacement therapy (NRT), to conventional NRT in patients hospitalized with a cardiac or pulmonary illness. We evaluated self-reported and biochemically verified 7-day prevalence smoking abstinence rates at 12 and 26 weeks post-hospitalization. Patients (n=164) were randomized into one of three counseling-based treatment groups: NRT for 30 days (NRT; n=41), a 90-min hypnotherapy session (H; n=39), and NRT with hypnotherapy (HNRT; n=37). Treatment groups were compared to a "self-quit" group of 35 patients who refused intervention. Hypnotherapy patients were more likely than NRT patients to be nonsmokers at 12 weeks (43.9% vs. 28.2%; p=0.14) and 26 weeks after hospitalization (36.6% vs. 18.0%; p=0.06). Smoking abstinence rates in the HNRT group were similar to the H group. There was no difference in smoking abstinence rates at 26 weeks between "self quit" and participants in any of the treatment groups. In multivariable regression analysis adjusting for diagnosis and demographic characteristics, H and HNRT were over three times more likely than NRT participants to abstain at 26-weeks post-discharge (RR=3.6; p=0.03 and RR=3.2; p=0.04, respectively). Hypnotherapy is more effective than NRT in improving smoking abstinence in patients hospitalized for a smoking-related illness, and could be an asset to post-discharge smoking cessation programs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Direct observation of Medicaid beneficiary attempts to fill prescriptions for nicotine replacement medications.

Science.gov (United States)

Richter, Kimber P; Shergina, Elena; Grodie, Amanda; Massey, Justin K; Ellerbeck, Edward F; Applegate, Amanda; Faseru, Babalola

2018-04-21

Although many states have expanded Medicaid coverage of cessation medications, utilization remains low. Anecdotal reports suggest that beneficiaries are at times denied coverage of cessation medications at the pharmacy counter. We conducted an observational community-wide case study of Medicaid beneficiary attempts to fill over-the-counter nicotine replacement therapy at pharmacies. We recruited tobacco-using beneficiaries from a Federally Qualified Health Center, whose providers wrote paper prescriptions for nicotine patches. Study staff escorted beneficiaries to all eligible pharmacies (n = 18) in a Midwestern community to observe fill attempts. Study staff recorded encounters via smartphone into a secure database on a university server. Seven of 18 pharmacies (39%) did not fill the prescription on the day of the attempt. Of these, 6 offered to order the patch for pick-up at a later date. All (4/4) chain pharmacies filled the prescription; 2/3 mass merchant pharmacies failed to fill. Combining successful same-day fills with offers to order for pick-up, 17/18 (94%) would ultimately have been able to obtain patches. This pilot study found that many beneficiaries left pharmacies without a prescription in hand. Successful same-day fills varied markedly by store type. For people with low incomes, transportation presents a major barrier for delayed pick-up. In addition, delays can fuel ambivalence toward quitting. Future research based on this pilot study might address whether patients who fail to secure a same-day prescription ever fill the prescription and, if not, the degree to which this barrier contributes to success or failure in quitting. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Hormone Replacement Therapy and Your Heart

Science.gov (United States)

Hormone replacement therapy and your heart Are you taking — or considering — hormone therapy to treat bothersome menopausal symptoms? Understand ... you. By Mayo Clinic Staff Long-term hormone replacement therapy used to be routinely prescribed for postmenopausal ...

Trial Protocol: Using genotype to tailor prescribing of nicotine replacement therapy: a randomised controlled trial assessing impact of communication upon adherence

Directory of Open Access Journals (Sweden)

Prevost A Toby

2010-11-01

Full Text Available Abstract Background The behavioural impact of pharmacogenomics is untested; informing smokers of genetic test results for responsiveness to smoking cessation medication may increase adherence to this medication. The objective of this trial is to estimate the impact upon adherence to nicotine replacement therapy (NRT of informing smokers that their oral dose of NRT has been tailored to a DNA analysis. Hypotheses to be tested are as follows: IAdherence to NRT is greater among smokers informed that their oral dose of NRT is tailored to an analysis of DNA (genotype, compared to one tailored to nicotine dependence questionnaire score (phenotype. II Amongst smokers who fail to quit at six months, motivation to make another quit attempt is lower when informed that their oral dose of NRT was tailored to genotype rather than phenotype. Methods/Design An open label, parallel groups randomised trial in which 630 adult smokers (smoking 10 or more cigarettes daily using National Health Service (NHS stop smoking services in primary care are randomly allocated to one of two groups: i. NRT oral dose tailored by DNA analysis (OPRM1 gene (genotype, or ii. NRT oral dose tailored by nicotine dependence questionnaire score (phenotype The primary outcome is proportion of prescribed NRT consumed in the first 28 days following an initial quit attempt, with the secondary outcome being motivation to make another quit attempt, amongst smokers not abstinent at six months. Other outcomes include adherence to NRT in the first seven days and biochemically validated smoking abstinence at six months. The primary outcome will be collected on 630 smokers allowing sufficient power to detect a 7.5% difference in mean proportion of NRT consumed using a two-tailed test at the 5% level of significance between groups. The proportion of all NRT consumed in the first four weeks of quitting will be compared between arms using an independent samples t-test and by estimating the 95

Understanding and use of nicotine replacement therapy and nonpharmacologic smoking cessation strategies among Chinese and Vietnamese smokers and their families.

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Tsang, Icarus K; Tsoh, Janice Y; Wong, Ching; Le, Khanh; Cheng, Joyce W; Nguyen, Anthony N; Nguyen, Tung T; McPhee, Stephen J; Burke, Nancy J

2014-02-20

Population-based studies have reported high rates of smoking prevalence among Chinese and Vietnamese American men. Although nicotine replacement therapy (NRT) is effective, recommended, and accessible without prescription, these populations underuse NRT for smoking cessation. The aim of this study was to assess understanding and use of NRT and nonpharmacologic treatments among Chinese and Vietnamese American male smokers and their families. In-depth qualitative interviews were conducted with 13 smoker-family pairs, followed by individual interviews with each participant. A total of 39 interviews were conducted in Vietnamese or Chinese, recorded, translated, and transcribed into English for analysis. Four themes were identified: use and understanding of NRT, nonpharmacologic strategies, familial and religious approaches, and willpower. Both smokers and their family members believed strongly in willpower and a sense of personal responsibility as the primary drivers for stopping smoking. Lack of these 2 qualities keeps many Chinese and Vietnamese men from using NRT to quit smoking. Those who do use NRT often use it incorrectly, following their own preferences rather than product instructions. Our findings indicate the importance of culturally appropriate patient education about NRT. It may be necessary to teach smokers and their families at an individual level about NRT as a complementary approach that can strengthen their resolve to quit smoking. At a community level, public health education on the indication and appropriate use of evidence-based smoking cessation resources, such as NRT, would be an important component of effective tobacco control.

First trimester nicotine exposure and the risk of infantile colic

DEFF Research Database (Denmark)

Milidou, Ioanna; Henriksen, Tine Brink; Jensen, Morten Søndergaard

Background: Although prenatal exposure to maternal smoking has been associated with infantile colic (IC), to date no published studies have reported on the relationship between the prenatal use of nicotine replacement therapy (NRT) and IC. Aim: We aimed to assess the relationship between fetal...... exposure to nicotine, coming from both cigarette smoking and use of NRT early in pregnancy, and IC. Methods: The study population consisted of 63,883 pregnancies that resulted in live born singletons enrolled in the Danish National Birth Cohort between 1997 and 2002. Mother’s smoking habits and use of NRT......: The results indicate that prenatal exposure to nicotine from any source during the first trimester of the pregnancy increases the risk of infantile colic....

Effects of nicotine versus placebo e-cigarette use on symptom relief during initial tobacco abstinence.

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Perkins, Kenneth A; Karelitz, Joshua L; Michael, Valerie C

2017-08-01

Because electronic cigarettes (e-cigs) containing nicotine may relieve smoking abstinence symptoms similar to nicotine replacement therapy medication, we used within-subjects designs to test these effects with a first-generation e-cig in nonquitting and quitting smokers. In Study 1, 28 nontreatment-seeking smokers abstained overnight prior to each of 3 sessions. Minnesota Nicotine Withdrawal Scale (MNWS) withdrawal (and craving item) relief was assessed following 4 exposures (each 10 puffs) over 2 hr to e-cigs that either did (36 mg/ml) or did not (i.e., placebo, 0 mg/ml) contain nicotine or after no e-cig. Relief was greater after nicotine versus placebo e-cig (p < .05) but not after placebo versus no e-cig, showing relief was due to nicotine per se and not simple e-cig use behavior. Using a crossover design in Study 2, smokers preparing to quit soon engaged in 2 experimental 4-day quit periods on separate weeks. In weeks 1 and 3, all received a nicotine or placebo e-cig on Monday to use ad libitum while trying to abstain from smoking on Tuesday through Friday. (Week 2 involved resumption of ad libitum smoking.) MNWS and Questionnaire of Smoking Urges (QSU) craving were assessed at daily visits following 24-hr abstinence. Of 17 enrolled, 12 quit for ≥24 hr at least once, allowing test of relief because of e-cig use on quit days. Withdrawal and craving were reduced because of nicotine versus placebo e-cig use (both p < .05). In sum, compared with placebo e-cigs, nicotine e-cigs can relieve smoking abstinence symptoms, perhaps in a manner similar to Food and Drug Administration-approved nicotine replacement therapy products, although much more research with larger samples is needed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Nicotine dependence and psychiatric disorders.

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Salín-Pascual, Rafael J; Alcocer-Castillejos, Natasha V; Alejo-Galarza, Gabriel

2003-01-01

, concentration, and memory. Finally there are several strategies to deal with nicotine dependence, Nicotine Replacement Therapy (NRT), which are nicotine chewing-gum, transdermal nicotine patches, and nicotine inhalators device. Also some antidepressants like bupropion has shown to be effective in smoking cessation treatment. To know more about nicotine phenomenon would be important, because that will allow a more mature perspective about the damage and beneficial effects of that substance.

Adverse effects of perinatal nicotine exposure on reproductive outcomes.

Science.gov (United States)

Wong, Michael K; Barra, Nicole G; Alfaidy, Nadia; Hardy, Daniel B; Holloway, Alison C

2015-12-01

Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women. © 2015 Society for Reproduction and Fertility.

Disparities in Access to Over-the-Counter Nicotine Replacement Products in New York City Pharmacies

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Cabral, Lisa; Maantay, Juliana; Peprah, Dorothy; Lounsbury, David; Maroko, Andrew; Murphy, Mary; Shelley, Donna

2009-01-01

Objectives. We surveyed the availability of tobacco products and nonprescription nicotine replacement therapy (NRT) in pharmacies in New York City, stratified by the race, ethnicity, and socioeconomic status (SES) of the surrounding neighborhoods to determine whether disparities in availability existed. Methods. Surveyors visited a random sample of retail pharmacies to record the availability of tobacco products and nonprescription NRT. We used census data and geographic information systems analysis to determine the SES of each neighborhood. We used logistic modeling to explore relations between SES and the availability of NRT and tobacco products. Results. Of 646 pharmacies sampled, 90.8% sold NRT and 46.9% sold cigarettes. NRT and cigarettes were slightly more available in pharmacies in neighborhoods with a higher SES. NRT was more expensive in poorer neighborhoods. Conclusions. Small disparities existed in access to nonprescription NRT and cigarettes. The model did not adequately account for cigarette access, because of availability from other retail outlets. These results may explain some of the excess prevalence of cigarette use in low-SES areas. PMID:19638596

Postmenopausal hormone replacement therapy--clinical implications

DEFF Research Database (Denmark)

Ravn, S H; Rosenberg, J; Bostofte, E

1994-01-01

The menopause is defined as cessation of menstruation, ending the fertile period. The hormonal changes are a decrease in progesterone level, followed by a marked decrease in estrogen production. Symptoms associated with these hormonal changes may advocate for hormonal replacement therapy....... This review is based on the English-language literature on the effect of estrogen therapy and estrogen plus progestin therapy on postmenopausal women. The advantages of hormone replacement therapy are regulation of dysfunctional uterine bleeding, relief of hot flushes, and prevention of atrophic changes...... in the urogenital tract. Women at risk of osteoporosis will benefit from hormone replacement therapy. The treatment should start as soon after menopause as possible and it is possible that it should be maintained for life. The treatment may be supplemented with extra calcium intake, vitamin D, and maybe calcitonin...

CHRNA3 genotype, nicotine dependence, lung function and disease in the general population

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Kaur-Knudsen, Diljit; Nordestgaard, Børge G; Bojesen, Stig E

2012-01-01

The CHRNA3 rs1051730 polymorphism has been associated to chronic obstructive pulmonary disease (COPD), lung cancer and nicotine dependence in case-control studies with high smoking exposure; however, its influence on lung function and COPD severity in the general population is largely unknown. We...... genotyped 57,657 adult individuals from the Copenhagen General Population Study, of whom 34,592 were ever-smokers. Information on spirometry, hospital admissions, smoking behaviour and use of nicotinic replacement therapy was recorded. In homozygous (11%), heterozygous (44%) and noncarrier (45%) ever...

Slower nicotine metabolism among postmenopausal Polish smokers.

Science.gov (United States)

Kosmider, Leon; Delijewski, Marcin; Koszowski, Bartosz; Sobczak, Andrzej; Benowitz, Neal L; Goniewicz, Maciej L

2018-06-01

A non-invasive phenotypic indicator of the rate of nicotine metabolism is nicotine metabolite ratio (NMR) defined as a ratio of two major metabolites of nicotine - trans-3'-hydroxycotinine/cotinine. The rate of nicotine metabolism has important clinical implications for the likelihood of successful quitting with nicotine replacement therapy (NRT). We conducted a study to measure NMR among Polish smokers. In a cross-sectional study of 180 daily cigarette smokers (42% men; average age 34.6±13.0), we collected spot urine samples and measured trans-3'-hydroxycotinine (3-HC) and cotinine levels with LC-MS/MS method. We calculated NMR (molar ratio) and analyzed variations in NMR among groups of smokers. In the whole study group, an average NMR was 4.8 (IQR 3.4-7.3). The group of women below 51 years had significantly greater NMR compared to the rest of the population (6.4; IQR 4.1-8.8 vs. 4.3; IQR 2.8-6.4). No differences were found among group ages of male smokers. This is a first study to describe variations in nicotine metabolism among Polish smokers. Our findings indicate that young women metabolize nicotine faster than the rest of population. This finding is consistent with the known effects of estrogen to induce CYP2A6 activity. Young women may require higher doses of NRT or non-nicotine medications for most effective smoking cessation treatment. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Nicotine pharmacokinetic profiles of the Tobacco Heating System 2.2, cigarettes and nicotine gum in Japanese smokers.

Science.gov (United States)

Brossard, Patrick; Weitkunat, Rolf; Poux, Valerie; Lama, Nicola; Haziza, Christelle; Picavet, Patrick; Baker, Gizelle; Lüdicke, Frank

2017-10-01

Two open-label randomized cross-over studies in Japanese smokers investigated the single-use nicotine pharmacokinetic profile of the Tobacco Heating System (THS) 2.2, cigarettes (CC) and nicotine replacement therapy (Gum). In each study, one on the regular and one on the menthol variants of the THS and CC, both using Gum as reference, 62 subjects were randomized to four sequences: Sequence 1: THS - CC (n = 22); Sequence 2: CC - THS (n = 22); Sequence 3: THS - Gum (n = 9); Sequence 4: Gum - THS (n = 9). Plasma nicotine concentrations were measured in 16 blood samples collected over 24 h after single use. Maximal nicotine concentration (C max ) and area under the curve from start of product use to time of last quantifiable concentration (AUC 0-last ) were similar between THS and CC in both studies, with ratios varying from 88 to 104% for C max and from 96 to 98% for AUC 0-last . Urge-to-smoke total scores were comparable between THS and CC. The THS nicotine pharmacokinetic profile was close to CC, with similar levels of urge-to-smoke. This suggests that THS can satisfy smokers and be a viable alternative to cigarettes for adult smokers who want to continue using tobacco. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Withdrawal-oriented therapy for smokers.

Science.gov (United States)

Hajek, P

1989-06-01

The treatment approach of the Maudsley Hospital Smokers Clinic is described. It stems from the notion that smokers seeking help are dependent on nicotine, and that withdrawal discomfort is a major block to their success in quitting. Accordingly, therapy focuses on helping clients overcome nicotine deprivation. It uses nicotine replacement and a special format of group treatment. Details are given of preparation of clients, use of nicotine chewing gum, use of group-oriented groupwork, use of information about withdrawal, and training in withdrawal-oriented therapy. Data are presented concerning characteristics of the clientele, treatment adherence, and treatment results. A number of controversial issues are addressed, such as the optimal duration of treatment, timing of the quit date, the value of educational input, and the value of individualization of treatment goals.

Validation of a LC-MS/MS method for quantifying urinary nicotine, six nicotine metabolites and the minor tobacco alkaloids--anatabine and anabasine--in smokers' urine.

Directory of Open Access Journals (Sweden)

James E McGuffey

Full Text Available Tobacco use is a major contributor to premature morbidity and mortality. The measurement of nicotine and its metabolites in urine is a valuable tool for evaluating nicotine exposure and for nicotine metabolic profiling--i.e., metabolite ratios. In addition, the minor tobacco alkaloids--anabasine and anatabine--can be useful for monitoring compliance in smoking cessation programs that use nicotine replacement therapy. Because of an increasing demand for the measurement of urinary nicotine metabolites, we developed a rapid, low-cost method that uses isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS for simultaneously quantifying nicotine, six nicotine metabolites, and two minor tobacco alkaloids in smokers' urine. This method enzymatically hydrolyzes conjugated nicotine (primarily glucuronides and its metabolites. We then use acetone pretreatment to precipitate matrix components (endogenous proteins, salts, phospholipids, and exogenous enzyme that may interfere with LC-MS/MS analysis. Subsequently, analytes (nicotine, cotinine, hydroxycotinine, norcotinine, nornicotine, cotinine N-oxide, nicotine 1'-N-oxide, anatabine, and anabasine are chromatographically resolved within a cycle time of 13.5 minutes. The optimized assay produces linear responses across the analyte concentrations typically found in urine collected from daily smokers. Because matrix ion suppression may influence accuracy, we include a discussion of conventions employed in this procedure to minimize matrix interferences. Simplicity, low cost, low maintenance combined with high mean metabolite recovery (76-99%, specificity, accuracy (0-10% bias and reproducibility (2-9% C.V. make this method ideal for large high through-put studies.

Gutkha Addiction: Nicotine Dependence or a Conditioned Reflex?

OpenAIRE

Joshi, Prathamesh Satish; Prashant, M C; Nagpal, Neelu; Patil, Atulkumar A; Ahuja, Rinky; Mathur, Vidhi

2015-01-01

Background: A pre-packaged mixture of areca nut, tobacco, slaked lime, catechu, and flavoring agents is popularly known as Gutkha. Aim of study is to analyze the addiction biology of Gutkha chewing and to assess efficacy of a cessation program based on nicotine replacement therapy (NRT). Materials and Methods: Patterns of addiction of 400 Gutkha chewers were analyzed with a questionnaire-based survey. Urine cotinine levels of 60 subjects undergoing NRT were periodically estimated using gas ch...

Key issues surrounding the health impacts of electronic nicotine delivery systems (ENDS) and other sources of nicotine.

Science.gov (United States)

Drope, Jeffrey; Cahn, Zachary; Kennedy, Rosemary; Liber, Alex C; Stoklosa, Michal; Henson, Rosemarie; Douglas, Clifford E; Drope, Jacqui

2017-11-01

Answer questions and earn CME/CNE Over the last decade, the use of electronic nicotine delivery systems (ENDS), including the electronic cigarette or e-cigarette, has grown rapidly. More youth now use ENDS than any tobacco product. This extensive research review shows that there are scientifically sound, sometimes competing arguments about ENDS that are not immediately and/or completely resolvable. However, the preponderance of the scientific evidence to date suggests that current-generation ENDS products are demonstrably less harmful than combustible tobacco products such as conventional cigarettes in several key ways, including by generating far lower levels of carcinogens and other toxic compounds than combustible products or those that contain tobacco. To place ENDS in context, the authors begin by reviewing the trends in use of major nicotine-containing products. Because nicotine is the common core-and highly addictive-constituent across all tobacco products, its toxicology is examined. With its long history as the only nicotine product widely accepted as being relatively safe, nicotine-replacement therapy (NRT) is also examined. A section is also included that examines snus, the most debated potential harm-reduction product before ENDS. Between discussions of NRT and snus, ENDS are extensively examined: what they are, knowledge about their level of "harm," their relationship to smoking cessation, the so-called gateway effect, and dual use/poly-use. CA Cancer J Clin 2017;67:449-471. © 2017 American Cancer Society. © 2017 American Cancer Society.

Pharmacokinetic characterization of three novel 4-mg nicotine lozenges
.

Science.gov (United States)

Sukhija, Manpreet; Srivastava, Reena; Kaushik, Aditya

2018-03-01

Nicotine replacement therapy (NRT) increases the probability of smoking cessation. This study was conducted to determine if three prototype 4-mg nicotine lozenges produced locally in India were bioequivalent to a globally marketed reference product, Nicorette® 4-mg nicotine lozenge. Healthy adult smokers (N = 39) were treated with three prototype 4-mg nicotine lozenges in comparison with a reference 4-mg lozenge in this single-center, randomized, open-label, single-dose, 4-way crossover study. Pharmacokinetic sampling was obtained to test for bioequivalence using maximal plasma concentration (Cmax) and extent of absorption (AUC0-t). Secondarily, AUC;0-∞, time to maximal plasma concentration (tmax), half-life (T1/2), elimination rate constant (Kel), and safety of the prototype lozenges versus the reference lozenge were compared. Each prototype 4-mg nicotine lozenge was found to be bioequivalent to the reference 4-mg nicotine lozenge based on the ratio of geometric means and 90% confidence intervals for Cmax, AUC0-t, and AUC;0-∞. Although tmax; was significantly longer for prototype III, all four lozenges achieved maximum plasma nicotine concentrations at a median of 1.5 hours. The safety profiles of the three prototype 4-mg lozenges did not differ from that of the 4-mg reference product. Each prototype 4-mg nicotine lozenge was bioequivalent to the reference 4-mg nicotine lozenge and was well tolerated. Furthermore, as these bioequivalent prototypes differed in in-vitro dissolution profiles, these data suggest that performance from the in -vitro method deployed is not a firm predictor of pharmacokinetic behavior.
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Population pharmacokinetic model of transdermal nicotine delivered from a matrix-type patch.

Science.gov (United States)

Linakis, Matthew W; Rower, Joseph E; Roberts, Jessica K; Miller, Eleanor I; Wilkins, Diana G; Sherwin, Catherine M T

2017-12-01

Nicotine addiction is an issue faced by millions of individuals worldwide. As a result, nicotine replacement therapies, such as transdermal nicotine patches, have become widely distributed and used. While the pharmacokinetics of transdermal nicotine have been extensively described using noncompartmental methods, there are few data available describing the between-subject variability in transdermal nicotine pharmacokinetics. The aim of this investigation was to use population pharmacokinetic techniques to describe this variability, particularly as it pertains to the absorption of nicotine from the transdermal patch. A population pharmacokinetic parent-metabolite model was developed using plasma concentrations from 25 participants treated with transdermal nicotine. Covariates tested in this model included: body weight, body mass index, body surface area (calculated using the Mosteller equation) and sex. Nicotine pharmacokinetics were best described with a one-compartment model with absorption based on a Weibull distribution and first-order elimination and a single compartment for the major metabolite, cotinine. Body weight was a significant covariate on apparent volume of distribution of nicotine (exponential scaling factor 1.42). After the inclusion of body weight in the model, no other covariates were significant. This is the first population pharmacokinetic model to describe the absorption and disposition of transdermal nicotine and its metabolism to cotinine and the pharmacokinetic variability between individuals who were administered the patch. © 2017 The British Pharmacological Society.

Enzyme Replacement Therapy for Fabry Disease

Directory of Open Access Journals (Sweden)

Maria Dolores Sanchez-Niño PhD

2016-11-01

Full Text Available Fabry disease is a rare X-linked disease caused by the deficiency of α-galactosidase that leads to the accumulation of abnormal glycolipid. Untreated patients develop potentially lethal complications by age 30 to 50 years. Enzyme replacement therapy is the current standard of therapy for Fabry disease. Two formulations of recombinant human α-galactosidase A (agalsidase are available in most markets: agalsidase-α and agalsidase-β, allowing a choice of therapy. However, the US Food and Drug Administration rejected the application for commercialization of agalsidase-α. The main difference between the 2 enzymes is the dose. The label dose for agalsidase-α is 0.2 mg/kg/2 weeks, while the dose for agalsidase-β is 1.0 mg/kg/2 weeks. Recent evidence suggests a dose-dependent effect of enzyme replacement therapy and agalsidase-β is 1.0 mg/kg/2 weeks, which has been shown to reduce the occurrence of hard end points (severe renal and cardiac events, stroke, and death. In addition, patients with Fabry disease who have developed tissue injury should receive coadjuvant tissue protective therapy, together with enzyme replacement therapy, to limit nonspecific progression of the tissue injury. It is likely that in the near future, additional oral drugs become available to treat Fabry disease, such as chaperones or substrate reduction therapy.

Study protocol of a pragmatic, randomised controlled pilot trial: clinical effectiveness on smoking cessation of traditional and complementary medicine interventions, including acupuncture and aromatherapy, in combination with nicotine replacement therapy

Science.gov (United States)

Jang, Soobin; Park, Sunju; Jang, Bo-Hyoung; Park, Yu Lee; Lee, Ju Ah; Cho, Chung-Sik; Go, Ho-Yeon; Shin, Yong Cheol; Ko, Seong-Gyu

2017-01-01

Introduction Nicotine dependence is a disease, and tobacco use is related to 6 million deaths annually worldwide. Recently, in many countries, there has been growing interest in the use of traditional and complementary medicine (T&CM) methods, especially acupuncture, as therapeutic interventions for smoking cessation. The aim of this pilot study is to investigate the effectiveness of T&CM interventions on smoking cessation. Methods and analysis The STOP (Stop Tobacco Programme using traditional Korean medicine) study is designed to be a pragmatic, open-label, randomised pilot trial. This trial will evaluate whether adding T&CM methods (ie, ear and body acupuncture, aromatherapy) to conventional cessation methods (ie, nicotine replacement therapy (NRT), counselling) increases smoking cessation rates. Forty participants over 19 years old who are capable of communicating in Korean will be recruited. They will be current smokers who meet one of the following criteria: (1) smoke more than 10 cigarettes a day, (2) smoke less than 10 cigarettes a day and previously failed to cease smoking, or (3) smoke fewer than 10 cigarettes a day and have a nicotine dependence score (Fagerstrom Test for Nicotine Dependence) of 4 points or more. The trial will consist of 4 weeks of treatment and a 20 week follow-up period. A statistician will perform the statistical analyses for both the intention-to-treat (all randomly assigned participants) and per-protocol (participants who completed the trial without any protocol deviations) data using SAS 9.1.3. Ethics and dissemination This study has been approved by the Institutional Review Board (IRB) of the Dunsan Korean Medicine Hospital of Daejeon University (IRB reference no: DJDSKH-15-BM-11–1, Protocol No. version 4.1.).The protocol will be reapproved by IRB if it requires amendment. The trial will be conducted according to the Declaration of Helsinki, 7th version (2013). This study is designed to minimise the risk to participants

Design, formulation and evaluation of nicotine chewing gum.

Science.gov (United States)

Aslani, Abolfazl; Rafiei, Sahar

2012-01-01

Nicotine replacement therapy (NRT) can help smokers to quit smoking. Nicotine chewing gum has attracted the attention from pharmaceutical industries to offer it to consumers as an easily accessible NRT product. However, the bitter taste of such gums may compromise their acceptability by patients. This study was, therefore, designed to develop 2 and 4 mg nicotine chewing gums of pleasant taste, which satisfy the consumers the most. Nicotine, sugar, liquid glucose, glycerin, different sweetening and taste-masking agents, and a flavoring agent were added to the gum bases at appropriate temperature. The medicated gums were cut into pieces of suitable size and coated by acacia aqueous solution (2% w/v), sugar dusting, followed by acacia-sugar-calcium carbonate until a smooth surface was produced. The gums' weight variation and content uniformity were determined. The release of nicotine was studied in pH 6.8 phosphate buffer using a mastication device which simulated the mastication of chewing gum in human. The Latin Square design was used for the evaluation of organoleptic characteristics of the formulations at different stages of development. Most formulations released 79-83% of their nicotine content within 20 min. Nicotine-containing sugar-coated gums in which aspartame as sweetener and cherry and eucalyptus as flavoring agents were incorporated (i.e. formulations F(19-SC) and F(20-SC), respectively) had optimal chewing hardness, adhering to teeth, and plumpness characteristics, as well as the most pleasant taste and highest acceptability to smokers. Taste enhancement of nicotine gums was achieved where formulations comprised aspartame as the sweetener and cherry and eucalyptus as the flavoring agents. Nicotine gums of pleasant taste may, therefore, be used as NRT to assist smokers quit smoking.

Avascular necrosis of bone complicating corticosteroid replacement therapy.

OpenAIRE

Williams, P L; Corbett, M

1983-01-01

Two patients who developed widespread severe avascular necrosis of bone while on steroid replacement therapy are described. One, a diabetic, underwent yttrium-90 pituitary ablation for retinopathy and developed avascular necrosis within 18 months of starting prednisolone. The other, who had Addison's disease, developed avascular necrosis within 14 months of starting cortisol replacement therapy. Both cases came to bilateral total hip replacement.

78 FR 19718 - Modifications To Labeling of Nicotine Replacement Therapy Products for Over-the-Counter Human Use

Science.gov (United States)

2013-04-02

... nicotine lozenge and mini-lozenge were approved directly for OTC use in 2002 and 2009, respectively. \\1\\ A... the Agency's Adverse Event Reporting System and to the Substance Abuse and Mental Health Services...

Hormone Replacement Therapy: MedlinePlus Health Topic

Science.gov (United States)

... of hormone therapy (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Hormone Replacement Therapy ... Estrogen overdose Types of hormone therapy Related Health Topics Menopause National Institutes of Health The primary NIH ...

Antibiotic Dosing in Continuous Renal Replacement Therapy.

Science.gov (United States)

Shaw, Alexander R; Mueller, Bruce A

2017-07-01

Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis. The addition of continuous renal replacement therapy makes achieving appropriate antibiotic dosing more difficult. The lack of continuous renal replacement therapy standardization results in treatment variability between patients and may influence whether appropriate antibiotic exposure is achieved. The aim of this study was to determine if continuous renal replacement therapy effluent flow rate impacts attaining appropriate antibiotic concentrations when conventional continuous renal replacement therapy antibiotic doses were used. This study used Monte Carlo simulations to evaluate the effect of effluent flow rate variance on pharmacodynamic target attainment for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam. Published demographic and pharmacokinetic parameters for each antibiotic were used to develop a pharmacokinetic model. Monte Carlo simulations of 5000 patients were evaluated for each antibiotic dosing regimen at the extremes of Kidney Disease: Improving Global Outcomes guidelines recommended effluent flow rates (20 and 35 mL/kg/h). The probability of target attainment was calculated using antibiotic-specific pharmacodynamic targets assessed over the first 72 hours of therapy. Most conventional published antibiotic dosing recommendations, except for levofloxacin, reach acceptable probability of target attainment rates when effluent rates of 20 or 35 mL/kg/h are used. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Study protocol of a pragmatic, randomised controlled pilot trial: clinical effectiveness on smoking cessation of traditional and complementary medicine interventions, including acupuncture and aromatherapy, in combination with nicotine replacement therapy.

Science.gov (United States)

Jang, Soobin; Park, Sunju; Jang, Bo-Hyoung; Park, Yu Lee; Lee, Ju Ah; Cho, Chung-Sik; Go, Ho-Yeon; Shin, Yong Cheol; Ko, Seong-Gyu

2017-06-02

Nicotine dependence is a disease, and tobacco use is related to 6 million deaths annually worldwide. Recently, in many countries, there has been growing interest in the use of traditional and complementary medicine (T&CM) methods, especially acupuncture, as therapeutic interventions for smoking cessation. The aim of this pilot study is to investigate the effectiveness of T&CM interventions on smoking cessation. The STOP (Stop Tobacco Programme using traditional Korean medicine) study is designed to be a pragmatic, open-label, randomised pilot trial. This trial will evaluate whether adding T&CM methods (ie, ear and body acupuncture, aromatherapy) to conventional cessation methods (ie, nicotine replacement therapy (NRT), counselling) increases smoking cessation rates. Forty participants over 19 years old who are capable of communicating in Korean will be recruited. They will be current smokers who meet one of the following criteria: (1) smoke more than 10 cigarettes a day, (2) smoke less than 10 cigarettes a day and previously failed to cease smoking, or (3) smoke fewer than 10 cigarettes a day and have a nicotine dependence score (Fagerstrom Test for Nicotine Dependence) of 4 points or more. The trial will consist of 4 weeks of treatment and a 20 week follow-up period. A statistician will perform the statistical analyses for both the intention-to-treat (all randomly assigned participants) and per-protocol (participants who completed the trial without any protocol deviations) data using SAS 9.1.3. This study has been approved by the Institutional Review Board (IRB) of the Dunsan Korean Medicine Hospital of Daejeon University (IRB reference no: DJDSKH-15-BM-11-1, Protocol No. version 4.1.).The protocol will be reapproved by IRB if it requires amendment. The trial will be conducted according to the Declaration of Helsinki, 7th version (2013). This study is designed to minimise the risk to participants, and the investigators will explain the study to the

Renal replacement therapy in healthy adult horses.

Science.gov (United States)

Wong, D M; Witty, D; Alcott, C J; Sponseller, B A; Wang, C; Hepworth, K

2013-01-01

Renal replacement therapy (RRT) has been implemented extensively in people to facilitate recovery from acute renal failure (ARF). RRT has not been explored in horses, but might provide a further treatment option in horses with ARF. To investigate efficacy and safety of RRT in horses. Five healthy adult horses. A prospective study was performed on horses restrained in stocks and intravenously connected to a commercial RRT machine to allow continuous venovenous hemodiafiltration to be performed for 6 hours. The RRT machine was set at the following flow rates: blood flow rate 250 mL/min; dialysate rate 3,000 mL/h; prefilter replacement pump 3,000 mL/h; and postfilter replacement pump rate 2,000 mL/h. Balanced electrolyte solution was used as dialysate and replacement fluid. Heart rate, respiratory rate, body temperature, direct arterial blood pressure, urine output, and various clinicopathologic parameters were measured over the study period. Renal replacement therapy was successfully performed in horses, resulting in a mean creatinine clearance of 0.127 mL/kg/min (68.9 mL/min) and urea reduction ratio of 24%. No adverse effects were detected although a significant decrease in rectal temperature was observed (P ≤ .007). A significant increase in serum phosphorus (P ≤ .001) and decrease in BUN (P replacement therapy can safely and effectively be used in adult horses. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Nursing procedures during continuous renal replacement therapies: a national survey.

Science.gov (United States)

Ricci, Zaccaria; Benelli, Sonia; Barbarigo, Fabio; Cocozza, Giulia; Pettinelli, Noemi; Di Luca, Emanuela; Mettifogo, Mariangela; Toniolo, Andrea; Ronco, Claudio

2015-01-01

The current role of nurses in the management of critically ill patients needing continuous renal replacement therapies is clearly fundamental. The care of these complex patients is typically shared by critical care and dialysis nurses: their precise duties may vary from country to country. To clarify this issue we conducted a national-level survey at a recent Italian course on nursing practices during continuous renal replacement therapies. A total of 119 questionnaires were analysed. The participants, who were equally divided between critical care and dialysis nurses, came from 44 different hospitals and 35 Italian cities. Overall, 23% of participants answered that "the dialysis staff" were responsible for continuous renal replacement therapies in the Intensive Care Unit, while 39% answered "the critical care nurse", and 38% "a shared organization". Interestingly, less than the half of participants claimed specific continuous renal replacement therapies training was provided to employees before handling an acute dialysis machine. Finally, about 60% of participants had experience of extra-corporeal membrane oxygenation machines used in conjunction with continuous renal replacement therapies. Workload coordination and management of critically ill patients undergoing continuous renal replacement therapies in Italy is not standardized. At present, the duties of critical care and dialysis nurses vary significantly across the country. They frequently overlap or leave gaps in the assistance received by patients. The role of nurses involved in the care of continuous renal replacement therapies patients in Italy currently requires better organization, possibly starting with intensive standardized training and educational programs.

Hormone replacement therapy increases the risk of cranial meningioma

DEFF Research Database (Denmark)

Andersen, Lene; Friis, Søren; Hallas, Jesper

2013-01-01

We investigated the influence of hormone replacement therapy (HRT) use on the risk of meningioma in a population-based setting.......We investigated the influence of hormone replacement therapy (HRT) use on the risk of meningioma in a population-based setting....

QUALITY OF LIFE, COUNSELLING AND HORMONE REPLACEMENT THERAPY

Directory of Open Access Journals (Sweden)

Nena Kopčavar Guček

2008-12-01

Quality of life in menopause is a result of many factors and therefore it is very individual.Hormone replacement therapy is one of the possibilities of improvement. Therefore, it isessential that a woman is adequately informed about all the advantages and risks of thehormonal replacement therapy. Only an informed patient can be a partner in shareddecision making about the improvement of quality of life

Spontaneous Coronary Artery Dissection following Topical Hormone Replacement Therapy

Directory of Open Access Journals (Sweden)

Alexander L. Pan

2012-01-01

Full Text Available Spontaneous coronary artery dissection is a rare condition, usually presenting as an acute coronary syndrome, and is often seen in states associated with high systemic estrogen levels such as pregnancy or oral contraceptive use. While topical hormonal replacement therapy may result in increased estrogen levels similar to those documented with oral contraceptive use, there are no reported cases of spontaneous coronary dissection with topical hormonal replacement therapy. We describe a 53-year-old female who developed two spontaneous coronary dissections while on topical hormonal replacement therapy. The patient had no other risk factors for coronary dissection. After withdrawal from topical hormonal therapy, our patient has done well and has not had recurrent coronary artery dissections over a one-year follow-up period. The potential contributory role of topical hormonal therapy as a cause of spontaneous coronary dissection should be recognized.

[Effects of growth hormone replacement therapy on bone metabolism].

Science.gov (United States)

Yamamoto, Masahiro; Sugimoto, Toshitsugu

2014-06-01

Growth hormone (GH) as well as insulin like growth factor-1 (IGF-1) are essential hormones to maintain homeostasis of bone turnover by activating osteoblastogenesis and osteoclastogenesis. Results from GH replacement therapy for primary osteoporosis and adult-onset GH deficiency (AGHD) suggest that one year or more treatment period by this agent is required to gain bone mineral density (BMD) over the basal level after compensating BMD loss caused by dominant increase in bone resorption which was observed at early phase of GH treatment. A recent meta-analysis demonstrates the efficacy of GH replacement therapy on increases in BMD in male patients with AGHD. Additional analyses are needed to draw firm conclusions in female patients with AGHD, because insufficient amounts of GH might be administrated to them without considerations of influence of estrogen replacement therapy on IGF-1 production. Further observational studies are needed to clarify whether GH replacement therapy prevent fracture risk in these patients.

Risks and benefits of citrate anticoagulation for continuous renal replacement therapy.

Science.gov (United States)

Shum, H P; Yan, W W; Chan, T M

2015-04-01

Heparin, despite its significant side-effects, is the most commonly used anticoagulant for continuous renal replacement therapy in critical care setting. In recent years, citrate has gained much popularity by improving continuous renal replacement therapy circuit survival and decreasing blood transfusion requirements. However, its complex metabolic consequences warrant modification in the design of the citrate-based continuous renal replacement therapy protocol. With thorough understanding of the therapeutic mechanism of citrate, a simple and practicable protocol can be devised. Citrate-based continuous renal replacement therapy can be safely and widely used in the clinical setting with appropriate clinical staff training.

Iron replacement therapy

DEFF Research Database (Denmark)

Nielsen, Ole Haagen; Coskun, Mehmet; Weiss, Günter

2016-01-01

PURPOSE OF REVIEW: Approximately, one-third of the world's population suffers from anemia, and at least half of these cases are because of iron deficiency. With the introduction of new intravenous iron preparations over the last decade, uncertainty has arisen when these compounds should...... be administered and under which circumstances oral therapy is still an appropriate and effective treatment. RECENT FINDINGS: Numerous guidelines are available, but none go into detail about therapeutic start and end points or how iron-deficiency anemia should be best treated depending on the underlying cause...... of iron deficiency or in regard to concomitant underlying or additional diseases. SUMMARY: The study points to major issues to be considered in revisions of future guidelines for the true optimal iron replacement therapy, including how to assess the need for treatment, when to start and when to stop...

Randomized controlled trial of a web-based computer-tailored smoking cessation program as a supplement to nicotine patch therapy.

Science.gov (United States)

Strecher, Victor J; Shiffman, Saul; West, Robert

2005-05-01

To assess the efficacy of World Wide Web-based tailored behavioral smoking cessation materials among nicotine patch users. Two-group randomized controlled trial. World Wide Web in England and Republic of Ireland. A total of 3971 subjects who purchased a particular brand of nicotine patch and logged-on to use a free web-based behavioral support program. Web-based tailored behavioral smoking cessation materials or web-based non-tailored materials. Twenty-eight-day continuous abstinence rates were assessed by internet-based survey at 6-week follow-up and 10-week continuous rates at 12-week follow-up. Using three approaches to the analyses of 6- and 12-week outcomes, participants in the tailored condition reported clinically and statistically significantly higher continuous abstinence rates than participants in the non-tailored condition. In our primary analyses using as a denominator all subjects who logged-on to the treatment site at least once, continuous abstinence rates at 6 weeks were 29.0% in the tailored condition versus 23.9% in the non-tailored condition (OR = 1.30; P = 0.0006); at 12 weeks continuous abstinence rates were 22.8% versus 18.1%, respectively (OR = 1.34; P = 0.0006). Moreover, satisfaction with the program was significantly higher in the tailored than in the non-tailored condition. The results of this study demonstrate a benefit of the web-based tailored behavioral support materials used in conjunction with nicotine replacement therapy. A web-based program that collects relevant information from users and tailors the intervention to their specific needs had significant advantages over a web-based non-tailored cessation program.

[Survival in acute renal failure with conventional therapy or continuous replacement therapy].

Science.gov (United States)

Santibáñez-Velázquez, Martín; Sánchez-Montoya, Felipe; Alvirde-Gutiérrez, Luis

2014-01-01

To know the survival rate in patients with RIFLE I and II stages on acute renal failure, treated with supportive care or continuous renal replacement therapy with PRISMA machine, at an intensive care unit. There were included patients of both sexes, aged 16 to 69 years, with acute renal failure in RIFLE I and II stages and score of scale APACHE II lower than 36 points. The sample studied was divided in two groups: a group was treated with supportive care, and the other group received continuous renal replacement therapy via PRISMA machine. We compared mortality between both groups and the association with the RIFLE stages with Pearson's chi-squared test. The average score of the scale APACHE I was 14 points, and the probability of death was 15 %. The patients with acute renal failure RIFLE I were 54.5 % and RIFLE II 45.5 %, with mortality of 30.4 % and 38.8 %, respectively. Patients in RIFLE I stage who received supportive care and continuous replacement therapy had non-statistical differences in mortality (p = 0.356). The mortality in patients with acute renal failure in RIFLE II stage treated with continuous replacement therapy was higher (p = 0.000). Because of its accessibility and lower mortality, supportive care should be the initial procedure in patients with acute renal failure in RIFLE I and II stages.

Nicotine Acutely Enhances Reinforcement from Non-Drug Rewards in Humans

Directory of Open Access Journals (Sweden)

Kenneth A. Perkins

2017-05-01

smoking, potential individual differences in these effects, and the possibility that nicotine via nicotine replacement therapy and non-nicotine quit medications may attenuate loss of these effects upon quitting. Further study with humans of nicotine’s reinforcement-enhancing effects may provide a more complete understanding of smoking persistence and added mechanisms of cessation medication efficacy.

Nicotine increases brain functional network efficiency.

Science.gov (United States)

Wylie, Korey P; Rojas, Donald C; Tanabe, Jody; Martin, Laura F; Tregellas, Jason R

2012-10-15

Despite the use of cholinergic therapies in Alzheimer's disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network's tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer's disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function. Published by Elsevier Inc.

Renal transport and metabolism of nicotinic acid

International Nuclear Information System (INIS)

Schuette, S.; Rose, R.C.

1986-01-01

Renal metabolism and brush-border transport of nicotinic acid were studied in renal cortical slices and brush-border membrane vesicles exposed to a physiological concentration of vitamin (2.2-3.5 microM). Vesicle transport of [ 3 H]nicotinic acid was found to be Na+ dependent and concentrative. The presence of a Na+ gradient resulted in a fivefold increase in the rate of nicotinic acid uptake over that observed with mannitol and caused a transient nicotinic acid accumulation two- to fourfold above the equilibrium value. The effects of membrane potential, pH, and elimination of Na+-H+ exchange were also studied. Cortical slices and isolated tubules exposed to 2.2 microM [ 14 C]nicotinic acid took up vitamin and rapidly metabolized most of it to intermediates in the Preiss-Handler pathway for NAD biosynthesis; little free nicotinic acid was detectable intracellularly. The replacement of Na+ with Li+ in the bathing medium reduced total accumulation of 14 C label primarily as a result of reduced nicotinic acid uptake. Cortical tissue concentrated free nicotinic acid only when the involved metabolic pathways were saturated by levels of nicotinic acid far in excess of what occurs in vivo

Continuous renal replacement therapy for critically ill infants and children

DEFF Research Database (Denmark)

Pedersen, Ole; Jepsen, Søren Bruun; Toft, Palle

2012-01-01

Continuous renal replacement therapy (CRRT) is an important treatment in critically ill children with acute kidney injury (AKI). Over the past decade, CRRT has been the preferred method of renal replacement therapy. We compared children with CRRT-treated adults with AKI in terms of return of kidney...

Enzyme replacement and substrate reduction therapy for Gaucher disease.

Science.gov (United States)

Shemesh, Elad; Deroma, Laura; Bembi, Bruno; Deegan, Patrick; Hollak, Carla; Weinreb, Neal J; Cox, Timothy M

2015-03-27

Gaucher disease, a rare disorder, is caused by inherited deficiency of the enzyme glucocerebrosidase. It is unique among the ultra-orphan disorders in that four treatments are currently approved by various regulatory authorities for use in routine clinical practice. Hitherto, because of the relatively few people affected worldwide, many of whom started therapy during a prolonged period when there were essentially no alternatives to imiglucerase, these treatments have not been systematically evaluated in studies such as randomized controlled trials now considered necessary to generate the highest level of clinical evidence. To summarize all available randomized controlled study data on the efficacy and safety of enzyme replacement therapies and substrate reduction therapy for treating Gaucher disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register. Additional searches were conducted on ClinicalTrials.gov for any ongoing studies with potential interim results, and through PubMed. We also searched the reference lists of relevant articles and reviews.Date of last search: 07 August 2014. All randomized and quasi-randomized controlled studies (including open-label studies and cross-over studies) assessing enzyme replacement therapy or substrate reduction therapy, or both, in all types of Gaucher disease were included. Two authors independently assessed the risk of bias in the included studies, and extracted relevant data. Of the 488 studies retrieved by the electronic searches, eight met the inclusion criteria and were analysed (300 participants). Response parameters were restricted to haemoglobin concentration, platelet count, spleen and liver volume and serum biomarkers (chitotriosidase and CCL18). Only one publication reported a 'low risk of bias' score in all parameters assessed, and all studies included were randomized.Four studies reported the responses to enzyme replacement therapy of previously

Therapy of Hypoparathyroidism by Replacement with Parathyroid Hormone

Directory of Open Access Journals (Sweden)

Lars Rejnmark

2014-01-01

Full Text Available Hypoparathyroidism (HypoPT is a state of hypocalcemia due to inappropriate low levels of parathyroid hormone (PTH. HypoPT is normally treated by calcium supplements and activated vitamin D analogues. Although plasma calcium is normalized in response to conventional therapy, quality of life (QoL seems impaired and patients are at increased risk of renal complications. A number of studies have suggested subcutaneous injections with PTH as an alternative therapy. By replacement with the missing hormone, urinary calcium may be lowered and QoL may improve. PTH replacement therapy (PTH-RT possesses, nevertheless, a number of challenges. If PTH is injected only once a day, fluctuations in calcium levels may occur resulting in hypercalcemia in the hours following an injection. Twice-a-day injections seem to cause less fluctuation in plasma calcium but do stimulate bone turnover to above normal. Most recently, continuous delivery of PTH by pump has appeared as a feasible alternative to injections. Plasma calcium levels do not fluctuate, urinary calcium is lowered, and bone turnover is only stimulated modestly (into the normal range. Further studies are needed to assess the long-term effects. If beneficial, it seems likely that standard treatment of HypoPT in the future will change into replacement therapy with the missing hormone.

Improving compliance with hormonal replacement therapy in primary osteoporosis prevention

DEFF Research Database (Denmark)

Vestergaard, P; Hermann, A P; Gram, J

1997-01-01

To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule.......To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule....

Nicotine and caffeine modulate haloperidol-induced changes in postsynaptic density transcripts expression: Translational insights in psychosis therapy and treatment resistance.

Science.gov (United States)

de Bartolomeis, Andrea; Iasevoli, Felice; Marmo, Federica; Buonaguro, Elisabetta Filomena; Avvisati, Livia; Latte, Gianmarco; Tomasetti, Carmine

2018-04-01

Caffeine and nicotine are widely used by schizophrenia patients and may worsen psychosis and affect antipsychotic therapies. However, they have also been accounted as augmentation strategies in treatment-resistant schizophrenia. Despite both substances are known to modulate dopamine and glutamate transmission, little is known about the molecular changes induced by these compounds in association to antipsychotics, mostly at the level of the postsynaptic density (PSD), a site of dopamine-glutamate interplay. Here we investigated whether caffeine and nicotine, alone or combined with haloperidol, elicited significant changes in the levels of both transcripts and proteins of the PSD members Homer1 and Arc, which have been implicated in synaptic plasticity, schizophrenia pathophysiology, and antipsychotics molecular action. Homer1a mRNA expression was significantly reduced by caffeine and nicotine, alone or combined with haloperidol, compared to haloperidol. Haloperidol induced significantly higher Arc mRNA levels than both caffeine and caffeine plus haloperidol in the striatum. Arc mRNA expression was significantly higher by nicotine plus haloperidol vs. haloperidol in the cortex, while in striatum gene expression by nicotine was significantly lower than that by both haloperidol and nicotine plus haloperidol. Both Homer1a and Arc protein levels were significantly increased by caffeine, nicotine, and nicotine plus haloperidol. Homer1b mRNA expression was significantly increased by nicotine and nicotine plus haloperidol, while protein levels were unaffected. Locomotor activity was not significantly affected by caffeine, while it was reduced by nicotine. These data indicate that both caffeine and nicotine trigger relevant molecular changes in PSD sites when given in association with haloperidol. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

Transdermal testosterone replacement therapy in men

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Ullah MI

2014-01-01

Full Text Available M Iftekhar Ullah,1 Daniel M Riche,1,2 Christian A Koch1,31Department of Medicine, University of Mississippi Medical Center, 2Department of Pharmacy Practice, The University of Mississippi, 3GV (Sonny Montgomery VA Medical Center, Jackson, MS, USAAbstract: Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule.Keywords: hypogonadism, transdermal, testosterone, sexual function, testosterone replacement therapy, estradiol

Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone

Directory of Open Access Journals (Sweden)

Lars Rejnmark

2015-12-01

Full Text Available Hypoparathyroidism (HypoPT is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH. Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life (QoL and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human PTH (rhPTH(1-84 as well as therapy with the N-terminal PTH fragment (rhPTH(1-34 have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once a day injections cause large fluctuations in serum calcium. Twice a day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve QoL and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy.

Fetal and neonatal nicotine exposure in Wistar rats causes progressive pancreatic mitochondrial damage and beta cell dysfunction.

Directory of Open Access Journals (Sweden)

Jennifer E Bruin

Full Text Available Nicotine replacement therapy (NRT is currently recommended as a safe smoking cessation aid for pregnant women. However, fetal and neonatal nicotine exposure in rats causes mitochondrial-mediated beta cell apoptosis at weaning, and adult-onset dysglycemia, which we hypothesize is related to progressive mitochondrial dysfunction in the pancreas. Therefore in this study we examined the effect of fetal and neonatal exposure to nicotine on pancreatic mitochondrial structure and function during postnatal development. Female Wistar rats were given saline (vehicle control or nicotine bitartrate (1 mg/kg/d via subcutaneous injection for 2 weeks prior to mating until weaning. At 3-4, 15 and 26 weeks of age, oral glucose tolerance tests were performed, and pancreas tissue was collected for electron microscopy, enzyme activity assays and islet isolation. Following nicotine exposure mitochondrial structural abnormalities were observed beginning at 3 weeks and worsened with advancing age. Importantly the appearance of these structural defects in nicotine-exposed animals preceded the onset of glucose intolerance. Nicotine exposure also resulted in significantly reduced pancreatic respiratory chain enzyme activity, degranulation of beta cells, elevated islet oxidative stress and impaired glucose-stimulated insulin secretion compared to saline controls at 26 weeks of age. Taken together, these data suggest that maternal nicotine use during pregnancy results in postnatal mitochondrial dysfunction that may explain, in part, the dysglycemia observed in the offspring from this animal model. These results clearly indicate that further investigation into the safety of NRT use during pregnancy is warranted.

Pancreatic enzyme replacement therapy for people with cystic fibrosis.

Science.gov (United States)

Somaraju, Usha Rani; Solis-Moya, Arturo

2016-11-23

Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review. To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 15 July 2016.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 22 July 2016. Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. One

High Phenobarbital Clearance During Continuous Renal Replacement Therapy

Science.gov (United States)

Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

2014-01-01

Abstract Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring. A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure. Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus. The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed. Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring. PMID:25101986

Renal Replacement Therapy Modality in the ICU and Renal Recovery at Hospital Discharge.

Science.gov (United States)

Bonnassieux, Martin; Duclos, Antoine; Schneider, Antoine G; Schmidt, Aurélie; Bénard, Stève; Cancalon, Charlotte; Joannes-Boyau, Olivier; Ichai, Carole; Constantin, Jean-Michel; Lefrant, Jean-Yves; Kellum, John A; Rimmelé, Thomas

2018-02-01

Acute kidney injury requiring renal replacement therapy is a major concern in ICUs. Initial renal replacement therapy modality, continuous renal replacement therapy or intermittent hemodialysis, may impact renal recovery. The aim of this study was to assess the influence of initial renal replacement therapy modality on renal recovery at hospital discharge. Retrospective cohort study of all ICU stays from January 1, 2010, to December 31, 2013, with a "renal replacement therapy for acute kidney injury" code using the French hospital discharge database. Two hundred ninety-one ICUs in France. A total of 1,031,120 stays: 58,635 with renal replacement therapy for acute kidney injury and 25,750 included in the main analysis. None. PPatients alive at hospital discharge were grouped according to initial modality (continuous renal replacement therapy or intermittent hemodialysis) and included in the main analysis to identify predictors of renal recovery. Renal recovery was defined as greater than 3 days without renal replacement therapy before hospital discharge. The main analysis was a hierarchical logistic regression analysis including patient demographics, comorbidities, and severity variables, as well as center characteristics. Three sensitivity analyses were performed. Overall mortality was 56.1%, and overall renal recovery was 86.2%. Intermittent hemodialysis was associated with a lower likelihood of recovery at hospital discharge; odds ratio, 0.910 (95% CI, 0.834-0.992) p value equals to 0.0327. Results were consistent across all sensitivity analyses with odds/hazards ratios ranging from 0.883 to 0.958. In this large retrospective study, intermittent hemodialysis as an initial modality was associated with lower renal recovery at hospital discharge among patients with acute kidney injury, although the difference seems somewhat clinically limited.

Randomized controlled trial to evaluate tooth stain reduction with nicotine replacement gum during a smoking cessation program

LENUS (Irish Health Repository)

Whelton, Helen

2012-06-13

.011) and 12 weeks (p = 0.003) with greater lightening in the gum-group at each examination period.ConclusionThese results support the efficacy of the tested nicotine replacement gum in stain reduction and shade lightening. These findings may help dentists to motivate those wishing to quit smoking using a nicotine replacement gum.Trial registrationNCT01440985

Combined miglustat and enzyme replacement therapy in two patients with type 1 Gaucher disease: two case reports.

Science.gov (United States)

Amato, Dominick; Patterson, Mary Anne

2018-01-27

Intravenous enzyme replacement therapy is a first-line therapy for Gaucher disease type 1, and substrate reduction therapy represents an oral treatment alternative. Both enzyme replacement therapy and substrate reduction therapy are generally used as monotherapies in Gaucher disease. However, one randomized study and several case reports have described combination therapy over short time periods. We report two female Gaucher disease type 1 patients of mainly Anglo-Saxon descent, where combined enzyme replacement therapy and miglustat substrate reduction therapy were administered to overcome refractory clinical symptoms. The first patient was diagnosed at age 17 and developed Gaucher disease-related bone manifestations that worsened despite starting imiglucerase enzyme replacement therapy. After switching to miglustat substrate reduction therapy, her bone symptoms improved, but she developed tremors and eventually switched back to enzyme replacement therapy. Miglustat was later recommenced in combination with ongoing enzyme replacement therapy due to continued bone pain, and her bone symptoms improved along with maintained visceral manifestations. Enzyme replacement therapy was subsequently tapered off and the patient has since been successfully maintained on miglustat. The second patient was diagnosed aged 3, and commenced imiglucerase enzyme replacement therapy aged 15. After 9 years on enzyme replacement therapy she switched to miglustat substrate reduction therapy and her core symptoms were maintained/stable for 3 years. Imiglucerase enzyme replacement therapy was later added as a boost to therapy and her symptoms were subsequently maintained over a 2.3-year period. However, miglustat was discontinued due to her relocation, necessitating an increase in enzyme replacement therapy dose. Overall, both patients benefited from combination therapy. While the majority of Gaucher disease type 1 patients will not need treatment with both substrate reduction therapy

Calculating evidence-based renal replacement therapy - Introducing an excel-based calculator to improve prescribing and delivery in renal replacement therapy - A before and after study.

Science.gov (United States)

Cottle, Daniel; Mousdale, Stephen; Waqar-Uddin, Haroon; Tully, Redmond; Taylor, Benjamin

2016-02-01

Transferring the theoretical aspect of continuous renal replacement therapy to the bedside and delivering a given "dose" can be difficult. In research, the "dose" of renal replacement therapy is given as effluent flow rate in ml kg -1  h -1 . Unfortunately, most machines require other information when they are initiating therapy, including blood flow rate, pre-blood pump flow rate, dialysate flow rate, etc. This can lead to confusion, resulting in patients receiving inappropriate doses of renal replacement therapy. Our aim was to design an excel calculator which would personalise patient's treatment, deliver an effective, evidence-based dose of renal replacement therapy without large variations in practice and prolong filter life. Our calculator prescribes a haemodialfiltration dose of 25 ml kg -1  h -1 whilst limiting the filtration fraction to 15%. We compared the episodes of renal replacement therapy received by a historical group of patients, by retrieving their data stored on the haemofiltration machines, to a group where the calculator was used. In the second group, the data were gathered prospectively. The median delivered dose reduced from 41.0 ml kg -1  h -1 to 26.8 ml kg -1  h -1 with reduced variability that was significantly closer to the aim of 25 ml kg -1 .h -1 ( p  < 0.0001). The median treatment time increased from 8.5 h to 22.2 h ( p  = 0.00001). Our calculator significantly reduces variation in prescriptions of continuous veno-venous haemodiafiltration and provides an evidence-based dose. It is easy to use and provides personal care for patients whilst optimizing continuous veno-venous haemodiafiltration delivery and treatment times.

Wound healing and infection in surgery

DEFF Research Database (Denmark)

Sørensen, Lars Tue

2012-01-01

: The aim was to clarify how smoking and nicotine affects wound healing processes and to establish if smoking cessation and nicotine replacement therapy reverse the mechanisms involved.......: The aim was to clarify how smoking and nicotine affects wound healing processes and to establish if smoking cessation and nicotine replacement therapy reverse the mechanisms involved....

Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer.

Science.gov (United States)

Zhang, Jingmei; Kamdar, Opal; Le, Wei; Rosen, Glenn D; Upadhyay, Daya

2009-02-01

Continued smoking causes tumor progression and resistance to therapy in lung cancer. Carcinogens possess the ability to block apoptosis, and thus may induce development of cancers and resistance to therapy. Tobacco carcinogens have been studied widely; however, little is known about the agents that inhibit apoptosis, such as nicotine. We determine whether mitochondrial signaling mediates antiapoptotic effects of nicotine in lung cancer. A549 cells were exposed to nicotine (1 muM) followed by cisplatin (35 muM) plus etoposide (20 muM) for 24 hours. We found that nicotine prevented chemotherapy-induced apoptosis, improved cell survival, and caused modest increases in DNA synthesis. Inhibition of mitogen-activated protein kinase (MAPK) and Akt prevented the antiapoptotic effects of nicotine and decreased chemotherapy-induced apoptosis. Small interfering RNA MAPK kinase-1 blocked antiapoptotic effects of nicotine, whereas small interfering RNA MAPK kinase-2 blocked chemotherapy-induced apoptosis. Nicotine prevented chemotherapy-induced reduction in mitochondrial membrane potential and caspase-9 activation. Antiapoptotic effects of nicotine were blocked by mitochondrial anion channel inhibitor, 4,4'diisothiocyanatostilbene-2,2'disulfonic acid. Chemotherapy enhanced translocation of proapoptotic Bax to the mitochondria, whereas nicotine blocked these effects. Nicotine up-regulated Akt-mediated antiapoptotic X-linked inhibitor of apoptosis protein and phosphorylated proapoptotic Bcl2-antagonist of cell death. The A549-rho0 cells, which lack mitochondrial DNA, demonstrated partial resistance to chemotherapy-induced apoptosis, but blocked the antiapoptotic effects of nicotine. Accordingly, we provide evidence that nicotine modulates mitochondrial signaling and inhibits chemotherapy-induced apoptosis in lung cancer. The mitochondrial regulation of nicotine imposes an important mechanism that can critically impair the treatment of lung cancer, because many cancer

Enzyme replacement therapy for infantile-onset Pompe disease.

Science.gov (United States)

Chen, Min; Zhang, Lingli; Quan, Shuyan

2017-11-20

Infantile-onset Pompe disease is a rare and progressive autosomal-recessive disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Current treatment involves enzyme replacement therapy (with recombinant human alglucosidase alfa) and symptomatic therapies (e.g. to control secretions). Children who are cross-reactive immunological material (CRIM)-negative require immunomodulation prior to commencing enzyme replacement therapy.Enzyme replacement therapy was developed as the most promising therapeutic approach for Pompe disease; however, the evidence is lacking, especially regarding the optimal dose and dose frequency. To assess the effectiveness, safety and appropriate dose regimen of enzyme replacement therapy for treating infantile-onset Pompe disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register, which is compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the Cochrane Central Register of Controlled Trials (CENTRAL), Embase (Ovid), PubMed and LILACS, and CBM, CNKI, VIP, and WANFANG for literature published in Chinese. In addition, we searched three online registers: WHO International Clinical Trials Registry Platform ClinicalTrials.gov, and www.genzymeclinicalresearch.com. We also searched the reference lists of relevant articles and reviews.Date of last search of the Group's Inborn Errors of Metabolism Trials Register: 24 November 2016. Randomized and quasi-randomized controlled trials of enzyme replacement therapy in children with infantile-onset Pompe disease. Two authors independently selected relevant trials, assessed the risk of bias and extracted data. We contacted investigators to obtain important missing information. We found no trials comparing the effectiveness and safety of enzyme replacement therapy to another intervention, no intervention or placebo.We found one trial (18 participants

Calculating evidence-based renal replacement therapy – Introducing an excel-based calculator to improve prescribing and delivery in renal replacement therapy – A before and after study

OpenAIRE

Cottle, Daniel; Mousdale, Stephen; Waqar-Uddin, Haroon; Tully, Redmond; Taylor, Benjamin

2015-01-01

Background Transferring the theoretical aspect of continuous renal replacement therapy to the bedside and delivering a given “dose” can be difficult. In research, the “dose” of renal replacement therapy is given as effluent flow rate in ml kg−1 h−1. Unfortunately, most machines require other information when they are initiating therapy, including blood flow rate, pre-blood pump flow rate, dialysate flow rate, etc. This can lead to confusion, resulting in patients receiving inappropriate doses...

of surfactant replacement therapy at Johannesburg Hospital ...

African Journals Online (AJOL)

To assess the impact of surfactant replacement therapy (SRl) on the outcome of ... oxygen requirements) was compared with that of a historical control group of ... The use of SRT added to the total cost of treating a patient ventilated for HMD.

Nicotinic receptor blockade decreases fos immunoreactivity within orexin/hypocretin-expressing neurons of nicotine-exposed rats.

Science.gov (United States)

Simmons, Steven J; Gentile, Taylor A; Mo, Lili; Tran, Fionya H; Ma, Sisi; Muschamp, John W

2016-11-01

Tobacco smoking is the leading cause of preventable death in the United States. Nicotine is the principal psychoactive ingredient in tobacco that causes addiction. The structures governing nicotine addiction, including those underlying withdrawal, are still being explored. Nicotine withdrawal is characterized by negative affective and cognitive symptoms that enhance relapse susceptibility, and suppressed dopaminergic transmission from ventral tegmental area (VTA) to target structures underlies behavioral symptoms of nicotine withdrawal. Agonist and partial agonist therapies help 1 in 4 treatment-seeking smokers at one-year post-cessation, and new targets are needed to more effectively aid smokers attempting to quit. Hypothalamic orexin/hypocretin neurons send excitatory projections to dopamine (DA)-producing neurons of VTA and modulate mesoaccumbal DA release. The effects of nicotinic receptor blockade, which is commonly used to precipitate withdrawal, on orexin neurons remain poorly investigated and present an attractive target for intervention. The present study sought to investigate the effects of nicotinic receptor blockade on hypothalamic orexin neurons using mecamylamine to precipitate withdrawal in rats. Separate groups of rats were treated with either chronic nicotine or saline for 7-days at which point effects of mecamylamine or saline on somatic signs and anxiety-like behavior were assessed. Finally, tissue from rats was harvested for immunofluorescent analysis of Fos within orexin neurons. Results demonstrate that nicotinic receptor blockade leads to reduced orexin cell activity, as indicated by lowered Fos-immunoreactivity, and suggest that this underlying cellular activity may be associated with symptoms of nicotine withdrawal as effects were most prominently observed in rats given chronic nicotine. We conclude from this study that orexin transmission becomes suppressed in rats upon nicotinic receptor blockade, and that behavioral symptoms associated

Study protocol for a non-inferiority trial of cytisine versus nicotine replacement therapy in people motivated to stop smoking

Directory of Open Access Journals (Sweden)

Walker Natalie

2011-11-01

Full Text Available Abstract Background Smokers need effective support to maximise the chances of successful quit attempts. Current smoking cessation medications, such as nicotine replacement therapy (NRT, bupropion, nortriptyline or varenicline, have been shown to be effective in clinical trials but are underused by smokers attempting to quit due to adverse effects, contraindications, low acceptability and/or high cost. Cytisine is a low-cost, plant-based alkaloid that has been sold as a smoking cessation aid in Eastern Europe for 50 years. A systematic review of trial evidence suggests that cytisine has a positive impact on both short- and long-term abstinence rates compared to placebo. However, the quality of the evidence is poor and insufficient for licensing purposes in many Western countries. A large, well-conducted placebo-controlled trial (n = 740 of cytisine for smoking cessation has recently been published and confirms the findings of earlier studies, with 12-month continuous abstinence rates of 8.4% in the cytisine group compared to 2.4% in the placebo group (Relative risk = 3.4, 95% confidence intervals 1.7-7.1. No research has yet been undertaken to determine the effectiveness of cytisine relative to that of NRT. Methods/design A single-blind, randomised controlled, non-inferiority trial has been designed to determine whether cytisine is at least as effective as NRT in assisting smokers to remain abstinent for at least one month. Participants (n = 1,310 will be recruited through the national telephone-based Quitline service in New Zealand and randomised to receive a standard 25-day course of cytisine tablets (Tabex® or usual care (eight weeks of NRT patch and/or gum or lozenge. Participants in both study arms will also receive a behavioural support programme comprising an average of three follow-up telephone calls delivered over an eight-week period by Quitline. The primary outcome is continuous abstinence from smoking at one month, defined as not

Enzyme replacement therapy in Fabry disease, towards individualized treatment

NARCIS (Netherlands)

Arends, M.

2017-01-01

Fabry disease is a very heterogeneous disorder for which expensive enzyme replacement therapy is available since more than 15 years. Because of the variety of symptoms and disease course, individual choices need to be made to improve the appropriate use of therapy. Supported by ZONWM, we have been

Prevalence of Use of Electronic Nicotine Delivery Systems (ENDS) to Vape Recreational Drugs by Club Patrons in South London.

Science.gov (United States)

Thurtle, Natalie; Abouchedid, Rachelle; Archer, John R H; Ho, James; Yamamoto, Takahiro; Dargan, Paul I; Wood, David M

2017-03-01

Electronic nicotine delivery systems (ENDS, often called e-cigarettes) are nicotine delivery devices that heat nicotine into vapour that is inhaled, a process called 'vaping'. Use eclipsed nicotine-replacement therapy (NRT) in 2014 but ENDS role in smoking cessation remains controversial. Safety has not been proven and there have been reports to US poison centres regarding potential ENDS-related nicotine toxicity. A further concern is use of ENDS to vape recreational drugs, but there is limited data to substantiate this. The aim of this study was to report on ENDS use to vape recreational drugs in patrons of a South London nightclub where high prevalence of recreational drug use has previously been shown. A convenience sample of 101 participants was surveyed in March 2015 as part of a larger survey on drug use. Individuals were asked if they used ENDS to vape nicotine and/or other substances (and if so which substances). Ninety (89.1 %) of respondents were male with median age of 28 years (IQR 23-34). Eighty (79.2 %) currently smoked cigarettes; 20 (19.8 %) currently used ENDS for nicotine. Six (5.9 %) reported using ENDS to take other substances: 2 for 'liquid cannabis' and 4 did not elaborate on the substance(s) used. Of these 6, 3 were using ENDS to vape nicotine and 3 had never used them for nicotine. 5.9 % of individuals in this sample reported using ENDS to vape substances other than nicotine. Further work is required in larger populations to determine how common this is, evaluate which agents are being vaped and to inform appropriate public education.

Hormone replacement therapy and risk of glioma

DEFF Research Database (Denmark)

Andersen, Lene; Friis, Søren; Hallas, Jesper

2013-01-01

Aim: Several studies indicate that use of hormone replacement therapy (HRT) is associated with an increased risk of intracranial meningioma, while associations between HRT use and risk of other brain tumors have been less explored. We investigated the influence of HRT use on the risk of glioma...

Brain indices of nicotine's effects on attentional bias to smoking and emotional pictures and to task-relevant targets.

Science.gov (United States)

Gilbert, David G; Sugai, Chihiro; Zuo, Yantao; Rabinovich, Norka E; McClernon, F Joseph; Froeliger, Brett

2007-03-01

Aversive and smoking-related stimuli are related to smoking urges and relapse and can be potent distractors of selective attention. It has been suggested that the beneficial effect of nicotine replacement therapy may be mediated partly by the ability of nicotine to reduce distraction by such stimuli and thereby to facilitate attention to task-relevant stimuli. The present study tested the hypothesis that nicotine reduces distraction by aversive and smoking-related stimuli as indexed by the parietal P3b brain response to a task-relevant target digit. We assessed the effect of nicotine on distraction by emotionally negative, positive, neutral, and smoking-related pictures immediately preceding target digits during a rapid visual information processing task in 16 smokers in a double-blind, counterbalanced, within-subjects design. The study included two experimental sessions. After overnight smoking deprivation (12+ hr), active nicotine patches were applied to participants during one of the sessions and placebo patches were applied during the other session. Nicotine enhanced P3b responses associated with target digits immediately subsequent to negative emotional pictures bilaterally and subsequent to smoking-related pictures only in the right hemisphere. No effects of nicotine were observed for P3bs subsequent to positive and neutral distractor pictures. Another measure of attention, contingent negative variation amplitude in anticipation of the target digits also was increased by nicotine, especially in the left hemisphere and at posterior sites. Together, these findings suggest that nicotine reduces the distraction by emotionally negative and smoking-related stimuli and promotes attention to task-related stimuli by modulating somewhat lateralized and task-specific neural networks.

Transdermal testosterone replacement therapy in men

Science.gov (United States)

Ullah, M Iftekhar; Riche, Daniel M; Koch, Christian A

2014-01-01

Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule. PMID:24470750

Effects of varenicline and nicotine replacement therapy on arterial elasticity, endothelial glycocalyx and oxidative stress during a 3-month smoking cessation program.

Science.gov (United States)

Ikonomidis, Ignatios; Marinou, Margarita; Vlastos, Dimitrios; Kourea, Kallirhoe; Andreadou, Ioanna; Liarakos, Nikolaos; Triantafyllidi, Helen; Pavlidis, George; Tsougos, Elias; Parissis, John; Lekakis, John

2017-07-01

The effects of medically-aided smoking cessation on vascular function and oxidative stress are not fully clarified. One hundred eighty-eight current smokers were randomized to varenicline or nicotine replacement treatment (NRT) for a 3-month period. We assessed: (a) augmentation index (Aix) and pulse wave velocity (PWV); (b) perfusion boundary region (PBR) of sublingual microvasculature (range:5-25 μm), an index of the endothelial glycocalyx thickness, using Sideview, Darkfield imaging; (c) the exhaled CO; and (d) the malondialdehyde (MDA) and protein carbonyls (PC) plasma levels, as markers of oxidative stress, at baseline and after 3 and 12 months. After 3 months of treatment, CO, MDA, PC and Aix were decreased in all subjects (median CO: 25 vs. 6 ppm, MDA: 0.81 vs. 0.63 nmol/L, PC: 0.102, vs. 0.093 nmol/mg protein, Aix: 13% vs. 9%, p smoking (n = 84 out of 188), while the above markers and PWV deteriorated in relapsed smokers (p smoking cessation program using varenicline or NRT for 3 months resulted in a decrease of CO, oxidative stress, arterial stiffness and restored endothelial glycocalyx. These effects were more evident after varenicline treatment, likely because of a greater CO reduction, and were maintained after 1 year only in subjects who abstained from smoking. Copyright © 2017 Elsevier B.V. All rights reserved.

Nicotine addiction management following surgery: a quality improvement approach in the post anesthesia care unit.

Science.gov (United States)

Finegan, Barry A; Roblin, Daniel; Hammal, Fadi

2018-03-14

For smokers, hospital admission is accompanied by forced involuntary nicotine abstinence due to smoke-free site/grounds policies. An audit of patients admitted to our surgical wards revealed that identification of smoking status was inadequate and that nicotine addiction management (NAM) was infrequently offered. The project aimed to enhance both these metrics by initiating NAM in the post anesthesia care unit (PACU). Out of 744 patients admitted to our PACU in August 2015, 54% had their smoking status documented. The 200 patients (27%) out of the 744 were smokers and only 50% were offered NAM before discharge. PACU unit staff to determine the smoking status of every patient before discharge from the PACU (later changed to OR nursing staff) and, if a patient was identified as a smoker, to offer NRT (patch and mouth spray only) and initiate therapy prior to transfer of the patient to the ward. Data about number of patients admitted, presence of documented smoking status, number of identified smokers, and number offered/accepted nicotine replacement therapy (NRT) were collected at baseline and thereafter quarterly. Engaging video education sessions addressed the education gaps highlighted in a needs assessment. Identification of smoking status was made part of preoperative checklist and NRT was made available in post-operative recovery room. These interventions resulted in an increase in screening for tobacco use from 54% at baseline to 95% and the offer of NRT to smokers from 50 to 89%.

Waterpipe tobacco products: nicotine labelling versus nicotine delivery.

Science.gov (United States)

Vansickel, Andrea R; Shihadeh, Alan; Eissenberg, Thomas

2012-05-01

Waterpipe tobacco package labelling typically indicates "0.0% tar" and "0.05% or 0.5% nicotine". To determine the extent to which nicotine labeling is related to nicotine delivery. 110 waterpipe smokers engaged in a 45-minute waterpipe smoking session. Puff topography and plasma nicotine were measured. Three waterpipe tobacco brands were used: Nakhla (0.5% nicotine), Starbuzz (0.05% nicotine), and Al Fakher (0.05% nicotine). Data were analyzed by one-way ANOVA. Topography did not differ across brands. Peak plasma nicotine varied significantly across brands. Al Fakher had the highest nicotine delivery (11.4 ng/ml) followed by Nakhla (9.8 ng/ml) and Starbuzz (5.8 ng/ml). Nicotine labelling on waterpipe tobacco products does not reflect delivery; smoking a brand with a "0.05% nicotine" label led to greater plasma nicotine levels than smoking a brand with a "0.5% nicotine" label. Waterpipe tobacco products should be labelled in a manner that does not mislead consumers.

Associations between the number of natural teeth in postmenopausal women and hormone replacement therapy.

Science.gov (United States)

Han, Kyungdo; Ko, Youngkyung; Park, Yong-Gyu; Park, Jun-Beom

2016-12-01

Increasing research suggests that periodontal status is associated with hormone replacement therapy in postmenopausal women. This study was performed to assess the relationship between the number of natural teeth and ever use of hormone replacement therapy in postmenopausal women using nationally representative Korean data. Data from the Korea National Health and Nutrition Examination Survey between 2010 and 2012 were used, and the analysis in this study was confined to a total of 4869 respondents over 19 years old who had gone through menopause and who had no missing data for the reproductive factors and outcome variables in that study. The total number of natural teeth was then calculated after excluding third molars. The time of day when tooth brushing was done was recorded as representative oral health behavior. Multiple logistic regression analyses were used to assess association between the number of natural teeth and the use of hormone replacement therapy. Among participants who had ever used hormone replacement therapy, the proportions (percentage and standard error) with no teeth, 1-9 teeth, 10-19 teeth, 20-27 teeth, and 28 teeth were 5.0±2.4%, 6.7±1.4%, 12.5±1.7%, 18.9±1.0%, and 20.7±1.6%, respectively (Preplacement therapy, after adjustments. The analysis revealed that the use of hormone replacement therapy by postmenopausal women showed positive effects for retention of natural teeth. Lack of hormone replacement therapy may be considered to be an independent risk indicator for tooth loss in Korean postmenopausal women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Quantitative liver functions in Turner syndrome with and without hormone replacement therapy

DEFF Research Database (Denmark)

Gravholt, Claus Højbjerg; Poulsen, H.E.; Ott, Peter

2007-01-01

Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes.......Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes....

The optimal management of anti-thrombotic therapy after valve replacement: certainties and uncertainties.

Science.gov (United States)

Iung, Bernard; Rodés-Cabau, Josep

2014-11-07

Anti-thrombotic therapy after valve replacement encompasses a number of different situations. Long-term anticoagulation of mechanical prostheses uses vitamin K antagonists with a target international normalized ratio adapted to the characteristics of the prosthesis and the patient. The association of low-dose aspirin is systematic in the American guidelines and more restrictive in the European guidelines. Early heparin therapy is frequently used early after mechanical valve replacement, although there are no precise recommendations regarding timing, type, and dose of drug. Direct oral anticoagulants are presently contraindicated in patients with mechanical prosthesis. The main advantage of bioprostheses is the absence of long-term anticoagulant therapy. Early anticoagulation is indicated after valve replacement for mitral bioprostheses, whereas aspirin is now favoured early after bioprosthetic valve replacement in the aortic position. Early dual antiplatelet therapy is indicated after transcatheter aortic valve implantation, followed by single antiplatelet therapy. However, this relies on low levels of evidence and optimization of anti-thrombotic therapy is warranted in these high-risk patients. Although guidelines are consistent in most instances, discrepancies and the low-level of evidence of certain recommendations highlight the need for further controlled trials, in particular with regard to the combination of antiplatelet therapy with oral anticoagulant and the early post-operative anti-thrombotic therapy following the procedure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

What are the effects of varenicline compared with nicotine replacement therapy on long-term smoking cessation and clinically important outcomes? Protocol for a prospective cohort study.

Science.gov (United States)

Davies, Neil M; Taylor, Gemma; Taylor, Amy E; Thomas, Kyla H; Windmeijer, Frank; Martin, Richard M; Munafò, Marcus R

2015-11-05

Smoking is a major avoidable cause of ill-health and premature death. Treatments that help patients successfully quit smoking have an important effect on health and life expectancy. Varenicline is a medication that can help smokers successfully quit smoking. However, there are concerns that it may cause adverse effects, such as increase in the occurrence of depression, self-harm and suicide and cardiovascular disease. In this study we aim to examine the effects of varenicline versus other smoking cessation pharmacotherapies on smoking cessation, health service use, all-cause and cause-specific mortality and physical and mental health conditions. In this project we will investigate the effects of varenicline compared to nicotine replacement therapies on: (1) long-term smoking cessation and whether these effects differ by area level deprivation; and (2) the following clinically-important outcomes: rate of general practice and hospital attendance; all-cause mortality and death due to diseases of the respiratory system and cardiovascular disease; and a primary care diagnosis of respiratory illness, myocardial infarction or depression and anxiety. The study is based on a cohort of patients prescribed these smoking cessation medications from the Clinical Practice Research Datalink (CPRD). We will use three methods to overcome confounding: multivariable adjusted Cox regression, propensity score matched Cox regression, and instrumental variable regression. The total expected sample size for analysis will be at least 180,000. Follow-up will end with the earliest of either an 'event' or censoring due to the end of registration or death. Ethics approval was not required for this study. This project has been approved by the CPRD's Independent Scientific Advisory Committee (ISAC). We will disseminate our findings via publications in international peer-reviewed journals and presentations at international conferences. Published by the BMJ Publishing Group Limited. For permission

Extended nicotine self-administration increases sensitivity to nicotine, motivation to seek nicotine and the reinforcing properties of nicotine-paired cues.

Science.gov (United States)

Clemens, Kelly J; Lay, Belinda P P; Holmes, Nathan M

2017-03-01

An array of pharmacological and environmental factors influence the development and maintenance of tobacco addiction. The nature of these influences likely changes across the course of an extended smoking history, during which time drug seeking can become involuntary and uncontrolled. The present study used an animal model to examine the factors that drive nicotine-seeking behavior after either brief (10 days) or extended (40 days) self-administration training. In Experiment 1, extended training increased rats' sensitivity to nicotine, indicated by a leftward shift in the dose-response curve, and their motivation to work for nicotine, indicated by an increase in the break point achieved under a progressive ratio schedule. In Experiment 2, extended training imbued the nicotine-paired cue with the capacity to maintain responding to the same high level as nicotine itself. However, Experiment 3 showed that the mechanisms involved in responding for nicotine or a nicotine-paired cue are dissociable, as treatment with the partial nicotine receptor agonist, varenicline, suppressed responding for nicotine but potentiated responding for the nicotine-paired cue. Hence, across extended nicotine self-administration, pharmacological and environmental influences over nicotine seeking increase such that nicotine seeking is controlled by multiple sources, and therefore highly resistant to change. © 2015 Society for the Study of Addiction.

Hypogonadism and Sex Steroid Replacement Therapy in Girls with Turner Syndrome.

Science.gov (United States)

Gawlik, Aneta; Hankus, Magdalena; Such, Kamila; Drosdzol-Cop, Agnieszka; Madej, Paweł; Borkowska, Marzena; Zachurzok, Agnieszka; Malecka-Tendera, Ewa

2016-12-01

Turner syndrome is the most common example of hypergonadotropic hypogonadism resulting from gonadal dysgenesis. Most patients present delayed, or even absent, puberty. Premature ovarian failure can be expected even if spontaneous menarche occurs. Laboratory markers of gonadal dysgenesis are well known. The choice of optimal hormone replacement therapy in children and adolescents remains controversial, particularly regarding the age at which therapy should be initiated, and the dose and route of estrogen administration. On the basis of a review of the literature, we present the most acceptable schedule of sex steroid replacement therapy in younger patients with Turner syndrome. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Neonatal varicella pneumonia, surfactant replacement therapy

Directory of Open Access Journals (Sweden)

Mousa Ahmadpour-kacho

2015-12-01

Full Text Available Background: Chickenpox is a very contagious viral disease that caused by varicella-zoster virus, which appears in the first week of life secondary to transplacental transmission of infection from the affected mother. When mother catches the disease five days before and up to two days after the delivery, the chance of varicella in neonate in first week of life is 17%. A generalized papulovesicular lesion is the most common clinical feature. Respiratory involvement may lead to giant cell pneumonia and respiratory failure. The mortality rate is up to 30% in the case of no treatment, often due to pneumonia. Treatment includes hospitalization, isolation and administration of intravenous acyclovir. The aim of this case report is to introduce the exogenous surfactant replacement therapy after intubation and mechanical ventilation for respiratory failure in neonatal chickenpox pneumonia and respiratory distress. Case Presentation: A seven-day-old neonate boy was admitted to the Neonatal Intensive Care Unit at Amirkola Children’s Hospital, Babol, north of Iran, with generalized papulovesicular lesions and respiratory distress. His mother has had a history of Varicella 4 days before delivery. He was isolated and given supportive care, intravenous acyclovir and antibiotics. On the second day, he was intubated and connected to mechanical ventilator due to severe pneumonia and respiratory failure. Because of sever pulmonary involvement evidenced by Chest X-Ray and high ventilators set-up requirement, intratracheal surfactant was administered in two doses separated by 12 hours. He was discharged after 14 days without any complication with good general condition. Conclusion: Exogenous surfactant replacement therapy can be useful as an adjunctive therapy for the treatment of respiratory failure due to neonatal chickenpox.

Lifetime risk of renal replacement therapy in Europe

DEFF Research Database (Denmark)

van den Brand, Jan A J G; Pippias, Maria; Stel, Vianda S

2017-01-01

Background: Upcoming KDIGO guidelines for the evaluation of living kidney donors are expected to move towards a personal risk-based evaluation of potential donors. We present the age and sex-specific lifetime risk of renal replacement therapy (RRT) for end-stage renal disease in 10 European...

The Role of Nicotine Dependence in E-Cigarettes' Potential for Smoking Reduction.

Science.gov (United States)

Selya, Arielle S; Dierker, Lisa; Rose, Jennifer S; Hedeker, Donald; Mermelstein, Robin J

2017-07-07

remains unclear. The use of e-cigarettes as a quit aid was not associated with reductions in conventional smoking, consistent with most other quit aids in this sample except for nicotine replacement therapy, which was only effective for the most dependent smokers. Notably, these findings highlight the necessity of accounting for smokers' nicotine dependence levels when examining tobacco use patterns. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Original Research: Metabolic alterations from early life thyroxine replacement therapy in male Ames dwarf mice are transient.

Science.gov (United States)

Darcy, Justin; Fang, Yimin; Hill, Cristal M; McFadden, Sam; Sun, Liou Y; Bartke, Andrzej

2016-10-01

Ames dwarf mice are exceptionally long-lived due to a Prop1 loss of function mutation resulting in deficiency of growth hormone, thyroid-stimulating hormone and prolactin. Deficiency in thyroid-stimulating hormone and growth hormone leads to greatly reduced levels of circulating thyroid hormones and insulin-like growth factor 1, as well as a reduction in insulin secretion. Early life growth hormone replacement therapy in Ames dwarf mice significantly shortens their longevity, while early life thyroxine (T4) replacement therapy does not. Possible mechanisms by which early life growth hormone replacement therapy shortens longevity include deleterious effects on glucose homeostasis and energy metabolism, which are long lasting. A mechanism explaining why early life T4 replacement therapy does not shorten longevity remains elusive. Here, we look for a possible explanation as to why early life T4 replacement therapy does not impact longevity of Ames dwarf mice. We found that early life T4 replacement therapy increased body weight and advanced the age of sexual maturation. We also find that early life T4 replacement therapy does not impact glucose tolerance or insulin sensitivity, and any deleterious effects on oxygen consumption, respiratory quotient and heat production are transient. Lastly, we find that early life T4 replacement therapy has long-lasting effects on bone mineral density and bone mineral content. We suggest that the transient effects on energy metabolism and lack of effects on glucose homeostasis are the reasons why there is no shortening of longevity after early life T4 replacement therapy in Ames dwarf mice. © 2016 by the Society for Experimental Biology and Medicine.

E-Cigarette Liquid Nicotine Ingestion in a Child: Case Report and Discussion.

Science.gov (United States)

Gill, Natasha; Sangha, Gurinder; Poonai, Naveen; Lim, Rodrick

2015-11-01

Nicotine poisoning is well described in the pediatric population, and even small oral doses may result in toxic effects. The source of nicotine is usually tobacco products and nicotine replacement products such as gum and patches. With the more frequent use of novel products such as e-cigarettes, concern has arisen regarding liquid nicotine. As there are no regulations regarding childproof bottling and packaging, there may be increased potential for unintentional ingestion of these colorfully and appealingly packaged products by children. We present and discuss a case of this nature, as we feel emergency physicians should be aware of this new mode of poisoning, and public health efforts should be made to minimize such exposures.

Opioid Analgesics and Nicotine: More Than Blowing Smoke.

Science.gov (United States)

Yoon, Jin H; Lane, Scott D; Weaver, Michael F

2015-09-01

Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs.

Nicotine inhibits potassium currents in Aplysia bag cell neurons

Science.gov (United States)

White, Sean H.; Sturgeon, Raymond M.

2016-01-01

Acetylcholine and the archetypal cholinergic agonist, nicotine, are typically associated with the opening of ionotropic receptors. In the bag cell neurons, which govern the reproductive behavior of the marine snail, Aplysia californica, there are two cholinergic responses: a relatively large acetylcholine-induced current and a relatively small nicotine-induced current. Both currents are readily apparent at resting membrane potential and result from the opening of distinct ionotropic receptors. We now report a separate current response elicited by applying nicotine to cultured bag cell neurons under whole cell voltage-clamp. This current was ostensibly inward, best resolved at depolarized voltages, presented a noncooperative dose-response with a half-maximal concentration near 1.5 mM, and associated with a decrease in membrane conductance. The unique nicotine-evoked response was not altered by intracellular perfusion with the G protein blocker GDPβS or exposure to classical nicotinic antagonists but was occluded by replacing intracellular K+ with Cs+. Consistent with an underlying mechanism of direct inhibition of one or more K+ channels, nicotine was found to rapidly reduce the fast-inactivating A-type K+ current as well as both components of the delayed-rectifier K+ current. Finally, nicotine increased bag cell neuron excitability, which manifested as reduction in spike threshold, greater action potential height and width, and markedly more spiking to continuous depolarizing current injection. In contrast to conventional transient activation of nicotinic ionotropic receptors, block of K+ channels could represent a nonstandard means for nicotine to profoundly alter the electrical properties of neurons over prolonged periods of time. PMID:26864763

Dispelling Myths about Nicotine Replacement Therapy

Science.gov (United States)

... are typically consumed many years. 6 Compare the price of the NRT products to the average price of $3.51 for a package of 20 ... your doctor to determine if NRT is the right choice for your quit plan. References 1. Silagy ...

Effects of Electronic Cigarette Liquid Nicotine Concentration on Plasma Nicotine and Puff Topography in Tobacco Cigarette Smokers: A Preliminary Report.

Science.gov (United States)

Lopez, Alexa A; Hiler, Marzena M; Soule, Eric K; Ramôa, Carolina P; Karaoghlanian, Nareg V; Lipato, Thokozeni; Breland, Alison B; Shihadeh, Alan L; Eissenberg, Thomas

2016-05-01

population. Finding a product that delivers nicotine as effectively as a tobacco cigarette, as we report here, may be essential for smokers who want to replace completely their combustible tobacco cigarettes with ECIGs. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence.

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Jackson, Asti; Bagdas, Deniz; Muldoon, Pretal P; Lichtman, Aron H; Carroll, F Ivy; Greenwald, Mark; Miles, Michael F; Damaj, M Imad

2017-05-15

Chronic tobacco use dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. The main addictive component of tobacco, nicotine, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). Activation of the homomeric α7 nAChR reduces nicotine's rewarding properties in conditioned place preference (CPP) test and i.v. self-administration models, but the mechanism underlying these effects is unknown. Recently, the nuclear receptor peroxisome proliferator-activated receptor type-α (PPARα) has been implicated as a downstream signaling target of the α7 nAChR in ventral tegmental area dopamine cells. The present study investigated PPARα as a possible mediator of the effect of α7 nAChR activation in nicotine dependence. Our results demonstrate the PPARα antagonist GW6471 blocks actions of the α7 nAChR agonist PNU282987 on nicotine reward in an unbiased CPP test in male ICR adult mice. These findings suggests that α7 nAChR activation attenuates nicotine CPP in a PPARα-dependent manner. To evaluate PPARα activation in nicotine dependence we used the selective and potent PPARα agonist, WY-14643 and the clinically used PPARα activator, fenofibrate, in nicotine CPP and we observed attenuation of nicotine preference, but fenofibrate was less potent. We also studied PPARα in nicotine dependence by evaluating its activation in nicotine withdrawal. WY-14643 reversed nicotine withdrawal signs whereas fenofibrate had modest efficacy. This suggests that PPARα plays a role in nicotine reward and withdrawal and that further studies are warranted to elucidate its function in mediating the effects of α7 nAChRs in nicotine dependence. Copyright © 2017 Elsevier Ltd. All rights reserved.

Risk of fracture in adults on renal replacement therapy

DEFF Research Database (Denmark)

Hansen, Ditte; Olesen, Jonas B; Gislason, Gunnar H

2016-01-01

BACKGROUND: Patients on dialysis treatment or living with a transplanted kidney have several risk factors for bone fracture, especially disturbances in mineral metabolism and immunosuppressive therapy. We describe the incidence of fracture in this retrospective national Danish cohort study and ex....... Differences in age, gender, drug use and comorbidity only partly explain this increased risk. Further studies are warranted to explore the reason for this increased fracture risk in patients on renal replacement therapy....

Renal Replacement Therapy Resources in Africa | Matri | Arab ...

African Journals Online (AJOL)

However, there is a general impression that it is at least three to four times more frequent than in more developed countries Methods: a survey on renal replacement therapy in Africa was conducted in the context of the African Association of Nephrology (AFRAN) Congress 2007. A questionnaire was sent to leading African ...

Interventions to facilitate smoking cessation | Okuyemi | South ...

African Journals Online (AJOL)

Family physicians, who see most of these patients in their offices every year, have an ... Assist, and Arrange) model when treating patients with nicotine addiction. ... (a non-nicotine therapy) and nicotine replacement therapies in the form of a ...

Hormone replacement therapy in Denmark, 1995-2004

DEFF Research Database (Denmark)

Løkkegaard, Ellen; Lidegaard, Ojvind; Møller, Lisbeth Nørgaard

2007-01-01

Recently, the Danish National Register of Medicinal Product Statistics (NRM) was opened for research purposes, and therefore, on an individual basis, can merge with other national registers. The aim of this study was to analyse the use of hormones based on the individual data of the entire Danish...... female population, with the focus on a detailed evaluation of specific hormone regimens and factors associated with systemic hormone replacement therapy (HRT)....

Belief about nicotine Modulates subjective craving and insula activity in Deprived smokers

DEFF Research Database (Denmark)

Gu, X. S.; Lohrenz, Terry; Salas, Ramiro

2016-01-01

Little is known about the specific neural mechanisms through which cognitive factors influence craving and associated brain responses, despite the initial success of cognitive therapies in treating drug addiction. In this study, we investigated how cognitive factors such as beliefs influence...... subjective craving and neural activities in nicotine-addicted individuals using model-based functional magnetic resonance imaging (fMRI) and neuropharmacology. Deprived smokers (N = 24) participated in a two-by-two balanced placebo design, which crossed beliefs about nicotine (told "nicotine" vs. told "no......, smokers demonstrated significantly reduced craving after smoking when told "nicotine in cigarette" but showed no change in craving when told "no nicotine." Second, neural activity in the insular cortex related to craving was only significant when smokers were told "nicotine" but not when told "no nicotine...

Safety and tolerability of prolonged-release nicotinic acid in statin-treated patients

NARCIS (Netherlands)

Birjmohun, R. S.; Kastelein, J. J. P.; Poldermans, D.; Stroes, E. S. G.; Hostalek, U.; Assmann, G.

2007-01-01

Objective: To evaluate the safety and tolerability of prolonged -release nicotinic acid (Niaspan*) added to statin therapy in patients at increased cardiovascular risk. Methods: This was a 6-month, prospective, observational, multicentre, open-label evaluation of prolonged-release nicotinic acid

Estrogen replacement therapy, Alzheimer's disease, and mild cognitive impairment.

Science.gov (United States)

Mulnard, Ruth A; Corrada, Marìa M; Kawas, Claudia H

2004-09-01

This article highlights the latest findings regarding estrogen replacement therapy in the treatment and prevention of Alzheimer's disease (AD) and mild cognitive impairment in women. Despite considerable evidence from observational studies, recent randomized clinical trials of conjugated equine estrogens, alone and in combination with progestin, have shown no benefit for either the treatment of established AD or for the short-term prevention of AD, mild cognitive impairment, or cognitive decline. Based on the evidence, there is no role at present for estrogen replacement therapy in the treatment or prevention of AD or cognitive decline, despite intriguing results from the laboratory and from observational studies. However, numerous questions remain about the biologic effects of estrogens on brain structure and function. Additional basic and clinical investigations are necessary to examine different forms and dosages of estrogens, other populations, and the relevance of timing and duration of exposure.

Reduced-Nicotine Cigarettes in Young Smokers: Impact of Nicotine Metabolism on Nicotine Dose Effects.

Science.gov (United States)

Faulkner, Paul; Ghahremani, Dara G; Tyndale, Rachel F; Cox, Chelsea M; Kazanjian, Ari S; Paterson, Neil; Lotfipour, Shahrdad; Hellemann, Gerhard S; Petersen, Nicole; Vigil, Celia; London, Edythe D

2017-07-01

The use of cigarettes delivering different nicotine doses allows evaluation of the contribution of nicotine to the smoking experience. We compared responses of 46 young adult smokers to research cigarettes, delivering 0.027, 0.110, 0.231, or 0.763 mg nicotine, and conventional cigarettes. On five separate days, craving, withdrawal, affect, and sustained attention were measured after overnight abstinence and again after smoking. Participants also rated each cigarette, and the nicotine metabolite ratio (NMR) was used to identify participants as normal or slow metabolizers. All cigarettes equally alleviated craving, withdrawal, and negative affect in the whole sample, but normal metabolizers reported greater reductions of craving and withdrawal than slow metabolizers, with dose-dependent effects. Only conventional cigarettes and, to a lesser degree, 0.763-mg nicotine research cigarettes increased sustained attention. Finally, there were no differences between ratings of lower-dose cigarettes, but the 0.763-mg cigarettes and (even more so) conventional cigarettes were rated more favorably than lower-dose cigarettes. The findings indicate that smoking-induced relief of craving and withdrawal reflects primarily non-nicotine effects in slow metabolizers, but depends on nicotine dose in normal metabolizers. By contrast, relief of withdrawal-related attentional deficits and cigarette ratings depend on nicotine dose regardless of metabolizer status. These findings have bearing on the use of reduced-nicotine cigarettes to facilitate smoking cessation and on policy regarding regulation of nicotine content in cigarettes. They suggest that normal and slow nicotine metabolizers would respond differently to nicotine reduction in cigarettes, but that irrespective of metabolizer status, reductions to <0.763 mg/cigarette may contribute to temporary attentional deficits.

Nicotine poisoning

Science.gov (United States)

Nicotine is found in: Chewing tobacco Cigarettes E-cigarettes Liquid nicotine Nicotine gum (Nicorette) Nicotine patches (Habitrol, Nicoderm) Pipe tobacco Some insecticides Tobacco leaves Note: This list may not be all-inclusive.

Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes

International Nuclear Information System (INIS)

Delijewski, Marcin; Beberok, Artur; Otręba, Michał; Wrześniok, Dorota; Rok, Jakub; Buszman, Ewa

2014-01-01

Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC 50 was determined to be 7.43 mM. Nicotine inhibited a melanization process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine. - Graphical abstract: Nicotine inhibits melanogenesis and induces oxidative stress in HEMn-LP melanocytes. - Highlights: • Nicotine induces concentration-dependent loss in melanocytes viability. • Nicotine in non-cytotoxic concentrations inhibits melanogenesis. • Nicotine in higher concentrations induces oxidative stress

Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes

Energy Technology Data Exchange (ETDEWEB)

Delijewski, Marcin; Beberok, Artur; Otręba, Michał; Wrześniok, Dorota; Rok, Jakub; Buszman, Ewa, E-mail: ebuszman@sum.edu.pl

2014-10-15

Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC{sub 50} was determined to be 7.43 mM. Nicotine inhibited a melanization process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine. - Graphical abstract: Nicotine inhibits melanogenesis and induces oxidative stress in HEMn-LP melanocytes. - Highlights: • Nicotine induces concentration-dependent loss in melanocytes viability. • Nicotine in non-cytotoxic concentrations inhibits melanogenesis. • Nicotine in higher concentrations induces oxidative stress.

Trends in Testosterone Replacement Therapy Use from 2003 to 2013 among Reproductive-Age Men in the United States.

Science.gov (United States)

Rao, Pravin Kumar; Boulet, Sheree L; Mehta, Akanksha; Hotaling, James; Eisenberg, Michael L; Honig, Stanton C; Warner, Lee; Kissin, Dmitry M; Nangia, Ajay K; Ross, Lawrence S

2017-04-01

Although testosterone replacement therapy use in the United States has increased dramatically in the last decade, to our knowledge trends in testosterone replacement therapy use among reproductive-age men have not been investigated. We assessed changes in testosterone replacement therapy use and practice patterns among 18 to 45-year-old American men from 2003 to 2013 and compared them to older men. This is a retrospective, cross-sectional analysis of men 18 to 45 and 56 to 64 years old who were enrolled in the Truven Health MarketScan® Commercial Claims Databases throughout each given calendar year from 2003 to 2013, including 5,094,868 men in 2013. Trends in the yearly rates of testosterone replacement therapy use were calculated using Poisson regression. Among testosterone replacement therapy users, the Cochran-Armitage test was used to assess temporal trends in age, formulation type, semen analysis and serum testosterone level testing during the 12 months preceding the documented use of testosterone replacement therapy. Between 2003 and 2013, there was a fourfold increase in the rate of testosterone use among 18 to 45-year-old men from 29.2/10,000 person-years to 118.1/10,000 person-years (p replacement therapy users, topical gel formulations were initially most used. Injection use then doubled between 2009 and 2012 (23.5% and 46.2%, respectively) and surpassed topical gel use in 2013. In men 56 to 64 years old there was a statistically significant threefold increase in testosterone replacement therapy use (p replacement therapy use increased fourfold in men 18 to 45 years old compared to threefold in older men. This younger age group should be a focus for future studies due to effects on fertility and unknown long-term sequelae. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Chronic nicotine differentially alters spontaneous recovery of contextual fear in male and female mice.

Science.gov (United States)

Tumolo, Jessica M; Kutlu, Munir Gunes; Gould, Thomas J

2018-04-02

Post-traumatic stress disorder (PTSD) is a devastating disorder with symptoms such as flashbacks, hyperarousal, and avoidance of reminders of the traumatic event. Exposure therapy, which attempts to extinguish fear responses, is a commonly used treatment for PTSD but relapse following successful exposure therapy is a frequent problem. In rodents, spontaneous recovery (SR), where extinguished fear responses resurface following extinction treatment, is used as a model of fear relapse. Previous studies from our lab showed that chronic nicotine impaired fear extinction and acute nicotine enhanced SR of contextual fear in adult male mice. In addition, we showed that acute nicotine's effects were specific to SR as acute nicotine did not affect recall of contextual fear conditioning in the absence of extinction. However, effects of chronic nicotine administration on SR are not known. Therefore, in the present study, we investigated if chronic nicotine administration altered SR or recall of contextual fear in adult male and female C57BL/6J mice. Our results showed that chronic nicotine significantly enhanced SR in female mice and significantly decreased SR in males. Chronic nicotine had no effect on recall of contextual fear in males or females. Female sham mice also had significantly less baseline SR than male sham mice. Overall, these results demonstrate sex differences in SR of fear memories and that chronic nicotine modulates these effects on SR but nicotine does not alter recall of contextual fear. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of a men's Preference for Testosterone Replacement Therapy (P-TRT instrument

Directory of Open Access Journals (Sweden)

Szeinbach SL

2012-08-01

Full Text Available Sheryl L Szeinbach,1 Enrique Seoane-Vazquez,2 Kent H Summers31Ohio State University, College of Pharmacy, Columbus, OH, USA; 2International Center for Pharmaceutical Economics and Policy, Massachusetts College of Pharmacy and Health Sciences, Boston, MA, 3Endo Health Solutions, Chadds Ford, PA, USABackground: This study used a standard research approach to create a final conceptual model and the Preference for the Testosterone Replacement Therapy (P-TRT instrument.Methods: A discussion guide was developed from a literature review and expert opinion to direct one-on-one interviews with participants who used testosterone replacement therapy and consented to participate in the study. Data from telephone interviews were transcribed for theme analysis using NVivo 9 qualitative analysis software, analyzed descriptively from a saturation grid, and used to evaluate men's P-TRT. Data from cognitive debriefing for five participants were used to evaluate the final conceptual model and validate the initial P-TRT instrument.Results: Item saturation and theme exhaustion was achieved by 58 male participants of mean age 55.0 ± 10.0 (22–69 years who had used testosterone replacement therapy for a mean of 175.0 ± 299.2 days. The conceptual model was developed from items and themes obtained from the participant interviews and saturation grid. Items comprising eight dimensions were used for instrument development, ie, ease of use, effect on libido, product characteristics, physiological impact, psychological impact, side effects, treatment experience, and preference. Results from the testosterone replacement therapy preference evaluation provide a detailed insight into why most men preferred a topical gel product over an injection or patch.Conclusion: Items and themes relating to use of testosterone replacement therapy were in concordance with the final conceptual model and 29-item P-TRT instrument. The standard research approach used in this study produced the

Discontinuation of continuous renal replacement therapy: A post hoc analysis of a prospective multicenter observational study

NARCIS (Netherlands)

Uchino, Shigehiko; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Ettiene; Gibney, Noel; Tolwani, Ashita; Oudemans-van Straaten, Heleen; Ronco, Claudio; Kellum, John A.

2009-01-01

Objectives: To describe current practice for the discontinuation of continuous renal replacement therapy in a multinational setting and to identify variables associated with successful discontinuation. The approach to discontinue continuous renal replacement therapy may affect patient outcomes.

Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM

NARCIS (Netherlands)

Brussaard, H.E.; Gevers Leuven, J.A.; Frölich, M.; Kluft, C.; Krans, H.M.J.

1997-01-01

Oestrogen replacement therapy is associated with a decreased risk of cardiovascular disease in postmenopausal women. Patients with non-insulin- dependent diabetes mellitus (NIDDM) have an increased cardiovascular risk. However, oestrogen replacement therapy is only reluctantly prescribed for

Kefir protective effects against nicotine cessation-induced anxiety and cognition impairments in rats

Directory of Open Access Journals (Sweden)

Negin Noori

2014-01-01

Conclusion: This study revealed that Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols.

Seeking optimal renal replacement therapy delivery in intensive care units.

Science.gov (United States)

Kocjan, Marinka; Brunet, Fabrice P

2010-01-01

Globally, critical care environments within health care organizations strive to provide optimal quality renal replacement therapy (RRT), an artificial replacement for lost kidney function. Examination of RRT delivery model literature and a case study review of the multidisciplinary-mixed RRT delivery model utilized within a closed medical surgical intensive care unit illustrates the organizational and clinical management of specialized resource and multidisciplinary roles. The successful utilization of a specific RRT delivery model is dependent upon resource availability.

Use of Nicotine in Electronic Nicotine and Non-Nicotine Delivery Systems by US Adults, 2015.

Science.gov (United States)

Weaver, Scott R; Kemp, Catherine B; Heath, J Wesley; Pechacek, Terry F; Eriksen, Michael P

Nicotine in electronic nicotine and non-nicotine delivery systems (ENDS/ENNDS) may present a risk of harm to those with cardiovascular disease and the fetuses of pregnant women. We assessed the extent to which adult users of ENDS/ENNDS used these products with nicotine. We obtained data for this study from a national probability survey of 6051 US adults that was conducted in August and September 2015. Of 399 adult ENDS/ENNDS users who were current smokers, 337 (80.7%) used ENDS/ENNDS containing nicotine, whereas only 29 of 71 (36.9%) ENDS/ENNDS users who were never smokers used ENDS/ENNDS containing nicotine. Assessments of the population health impact of ENDS/ENNDS use among never smokers should take into account the extent to which use involves nicotine.

A new machine for continuous renal replacement therapy: from development to clinical testing.

Science.gov (United States)

Ricci, Zaccaria; Salvatori, Gabriella; Bonello, Monica; Ratanarat, Ranistha; Andrikos, Emilios; Dan, Maurizio; Piccinni, Pasquale; Ronco, Claudio

2005-01-01

A new continuous renal replacement therapy machine has been designed to fulfill the expectations of nephrologists and intensivists operating in the common ground of critical care nephrology. The new equipment is called Prismaflex and it is the natural evolution of the PRISMA machine that has been utilized worldwide for continuous renal replacement therapy in the last 10 years. The authors performed a preliminary alpha-trial to establish the usability, flexibility and reliability of the new device. Accuracy was also tested by recording various operational parameters during different intermittent and continuous renal replacement modalities during 62 treatments. This article will describe our first experience with this new device and touch upon the historic and technologic background leading to its development.

The Activity and Enthalpy of Vaporization of Nicotine from Tobacco at Moderate Temperatures

Directory of Open Access Journals (Sweden)

St.Charles F. Kelley

2016-01-01

Full Text Available The vapor pressure of nicotine has been reported for unprotonated nicotine and for nicotine-water solutions. Yet no published values exist for nicotine in any commercially relevant matrix or for protonated forms (e.g., tobacco, smoke, electronic cigarette solutions, nicotine replacement products, nicotine salts. Therefore a methodology was developed to measure nicotine activity (defined as the vapor pressure from a matrix divided by the vapor pressure of pure nicotine. The headspace concentration of nicotine was measured for pure nicotine and tobacco stored at 23, 30, and 40 °C which allowed for conversion to vapor pressure and nicotine activity and for the estimation of enthalpy of vaporization. Burley, Flue-cured, Oriental, and cigarette blends were tested. Experiments were conducted with pure nicotine initially until the storage and sampling techniques were validated by comparison with previously published values. We found that the nicotine activity from tobacco was less than 1% with Burley > Flue-cured > Oriental. At 23 °C the nicotine vapor pressure averaged by tobacco type was 0.45 mPa for Oriental tobacco, 1.8 mPa for Flue-cured, 13 mPa for Burley while pure nicotine was 2.95 Pa. In general, the nicotine activity increased as the (calculated unprotonated nicotine concentration increased. The nicotine enthalpy of vaporization from tobacco ranged from 77 kJ/mol to 92 kJ/mol with no obvious trends with regard to tobacco origin, type, stalk position or even the wide range of nicotine activity. The mean value for all tobacco types was 86.7 kJ/mol with a relative standard deviation of 6.5% indicating that this was an intrinsic property of the nicotine form in tobacco rather than the specific tobacco properties. This value was about 30 kJ/mol greater than that of pure nicotine and is similar to the energy needed to remove a proton from monoprotonated nicotine.

Effects of Nicotine Metabolites on Nicotine Withdrawal Behaviors in Mice.

Science.gov (United States)

Elhassan, Sagi; Bagdas, Deniz; Damaj, M Imad

2017-06-01

Rodent studies suggest that nicotine metabolites and minor tobacco alkaloids such as nornicotine and cotinine may promote cigarette smoking by enhancing nicotine rewarding and reinforcing effects. However, there is little information on the effects of these minor tobacco alkaloids on nicotine withdrawal. The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine and cotinine exhibit nicotine-like behavioral effects in a mouse model of spontaneous nicotine withdrawal. Mice were infused with nicotine or saline for 14 days. Experiments were conducted on day 15, 18-24 hours after minipump removal. Ten minutes prior to testing, nicotine-dependent ICR male mice received an acute injection of nicotine (0.05 and 0.5 mg/kg), nornicotine (2.5 and 25 mg/kg), or cotinine (5 and 50 mg/kg) to determine effects on somatic signs, anxiety-like behaviors, and hyperalgesia spontaneous signs of withdrawal. Nicotine and the minor tobacco alkaloid nornicotine, but not cotinine, produced dose-dependent reversal of nicotine withdrawal signs in the mouse. The minor tobacco alkaloid and nicotine metabolite nornicotine at high doses have nicotinic like effects that may contribute to tobacco consumption and dependence. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

Science.gov (United States)

Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

2016-12-01

Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

Review of the Scientific Literature and Preparation of an Annotated Bibliography on Effects of Cigarette Smoking and Nicotine on Human Performance. Volume 2

Science.gov (United States)

1985-01-01

RUSSELL N A H, CARRUTHERS M E, FEYERABEND C 222 EFFECT OF NICOTINE REPLACEMENT ON THE CIGARETTE WITHDRAWAL SYNDROME BRITISH JOURNAL ADDICTION 79:215-219...RUSSELL M A, JARVIS M J, FEYERABEND C 147 DOES SWITCHING TO AN ULTRA LOW NICOTINE CIGARETTE INDUCE NICOTINE WITHDRAWAL EFFECTS? PSYCHOPHARMACOLOGY, 84:120

Known and Novel Sources of Variability in the Nicotine Metabolite Ratio in a Large Sample of Treatment-Seeking Smokers

Science.gov (United States)

Chenoweth, Meghan J.; Novalen, Maria; Hawk, Larry W.; Schnoll, Robert A.; George, Tony P.; Cinciripini, Paul M.; Lerman, Caryn; Tyndale, Rachel F.

2014-01-01

Background The ratio of 3′hydroxycotinine to cotinine, or nicotine metabolite ratio (NMR), is strongly associated with CYP2A6 genotype, CYP2A6-mediated nicotine and cotinine metabolism, and nicotine clearance. Higher NMR (faster nicotine clearance) is associated retrospectively with heavier smoking and lower cessation rates. Methods NMR as a predictive biomarker of cessation outcomes is being investigated (NCT01314001). In addition to strong CYP2A6-genetic influences on NMR, demographic and hormonal factors alter NMR. Here we analyzed, for the first time together, these sources of variation on NMR in smokers screened for this clinical trial (N=1672). Results Participants (mean age=45.9) were 65.1% Caucasian, 34.9% African American, and 54.8% male. Mean NMR (SD) was higher in Caucasians vs. African Americans (0.41(0.20) vs. 0.33(0.21); P<0.001), and in females vs. males (0.41(0.22) vs. 0.37(0.20); P<0.001). Among females, birth control pill use (N=17) and hormone replacement therapy (N=14) were associated with 19.5% (P=0.09) and 29.3% (P=0.06) higher mean NMR, respectively, albeit non-significantly. BMI was negatively associated with NMR (Rho=−0.14; P<0.001), while alcohol use (Rho=0.11; P<0.001) and cigarette consumption (Rho=0.12; P<0.001) were positively associated with NMR. NMR was 16% percent lower in mentholated cigarette users (P<0.001). When analyzed together in a linear regression model, these predictors (each ≤2%) accounted for <8% of total NMR variation. Conclusions While these factors significantly affected NMR, they contributed little (together <8%; each ≤2%) to total NMR variation. Impact Thus when using NMR, for example to prospectively guide smoking cessation therapy, these sources of variation are unlikely to cause NMR misclassification. PMID:25012994

Understanding cost of care for patients on renal replacement therapy: looking beyond fixed tariffs.

Science.gov (United States)

Li, Bernadette; Cairns, John A; Fotheringham, James; Tomson, Charles R; Forsythe, John L; Watson, Christopher; Metcalfe, Wendy; Fogarty, Damian G; Draper, Heather; Oniscu, Gabriel C; Dudley, Christopher; Johnson, Rachel J; Roderick, Paul; Leydon, Geraldine; Bradley, J Andrew; Ravanan, Rommel

2015-10-01

In a number of countries, reimbursement to hospitals providing renal dialysis services is set according to a fixed tariff. While the cost of maintenance dialysis and transplant surgery are amenable to a system of fixed tariffs, patients with established renal failure commonly present with comorbid conditions that can lead to variations in the need for hospitalization beyond the provision of renal replacement therapy. Patient-level cost data for incident renal replacement therapy patients in England were obtained as a result of linkage of the Hospital Episodes Statistics dataset to UK Renal Registry data. Regression models were developed to explore variations in hospital costs in relation to treatment modality, number of years on treatment and factors such as age and comorbidities. The final models were then used to predict annual costs for patients with different sets of characteristics. Excluding the cost of renal replacement therapy itself, inpatient costs generally decreased with number of years on treatment for haemodialysis and transplant patients, whereas costs for patients receiving peritoneal dialysis remained constant. Diabetes was associated with higher mean annual costs for all patients irrespective of treatment modality and hospital setting. Age did not have a consistent effect on costs. Combining predicted hospital costs with the fixed costs of renal replacement therapy showed that the total cost differential for a patient continuing on dialysis rather than receiving a transplant is considerable following the first year of renal replacement therapy, thus reinforcing the longer-term economic advantage of transplantation over dialysis for the health service. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Neural Signatures of Cognitive Flexibility and Reward Sensitivity Following Nicotinic Receptor Stimulation in Dependent Smokers: A Randomized Trial.

Science.gov (United States)

Lesage, Elise; Aronson, Sarah E; Sutherland, Matthew T; Ross, Thomas J; Salmeron, Betty Jo; Stein, Elliot A

2017-06-01

Withdrawal from nicotine is an important contributor to smoking relapse. Understanding how reward-based decision making is affected by abstinence and by pharmacotherapies such as nicotine replacement therapy and varenicline tartrate may aid cessation treatment. To independently assess the effects of nicotine dependence and stimulation of the nicotinic acetylcholine receptor on the ability to interpret valence information (reward sensitivity) and subsequently alter behavior as reward contingencies change (cognitive flexibility) in a probabilistic reversal learning task. Nicotine-dependent smokers and nonsmokers completed a probabilistic reversal learning task during acquisition of functional magnetic resonance imaging (fMRI) in a 2-drug, double-blind placebo-controlled crossover design conducted from January 21, 2009, to September 29, 2011. Smokers were abstinent from cigarette smoking for 12 hours for all sessions. In a fully Latin square fashion, participants in both groups underwent MRI twice while receiving varenicline and twice while receiving a placebo pill, wearing either a nicotine or a placebo patch. Imaging analysis was performed from June 15, 2015, to August 10, 2016. A well-established computational model captured effects of smoking status and administration of nicotine and varenicline on probabilistic reversal learning choice behavior. Neural effects of smoking status, nicotine, and varenicline were tested for on MRI contrasts that captured reward sensitivity and cognitive flexibility. The study included 24 nicotine-dependent smokers (12 women and 12 men; mean [SD] age, 35.8 [9.9] years) and 20 nonsmokers (10 women and 10 men; mean [SD] age, 30.4 [7.2] years). Computational modeling indicated that abstinent smokers were biased toward response shifting and that their decisions were less sensitive to the available evidence, suggesting increased impulsivity during withdrawal. These behavioral impairments were mitigated with nicotine and varenicline

A cost-effectiveness analysis of hormone replacement therapy in the menopause.

Science.gov (United States)

Cheung, A P; Wren, B G

1992-03-02

To evaluate the cost-effectiveness of hormone replacement therapy in the menopause with particular reference to osteoporotic fracture and myocardial infarction. The multiple-decrement form of the life table was the mathematical model used to follow women of age 50 through their lifetime under the "no hormone replacement" and "hormone replacement" assumptions. Standard demographic and health economic techniques were used to calculate the corresponding lifetime differences in direct health care costs (net costs in dollars) and health effects ("net effectiveness" in terms of life expectancy and quality, in "quality-adjusted life-years"). This was then expressed as a cost-effectiveness ratio or the cost ($) per quality-adjusted life-year (QALY) for each of the chosen hormone replacement regimens. All women of age 50 in New South Wales, Australia (n = 27,021). The analysis showed that the lifetime net increments in direct medical care costs were largely contributed by hormone drug and consultation costs. Hormone replacement was associated with increased quality-adjusted life expectancy, a large percentage of which was attributed to a relief of menopausal symptoms. Cost-effectiveness ratios ranged from under 10,000 to over a million dollars per QALY. Factors associated with improved cost-effectiveness were prolonged treatment duration, the presence of menopausal symptoms, minimum progestogen side effects (in the case of oestrogen with progestogen regimens), oestrogen use after hysterectomy and the inclusion of cardiac benefits in addition to fracture prevention. Hormone replacement therapy for symptomatic women is cost-effective when factors that enhance its efficiency are considered. Short-term treatment of asymptomatic women for prevention of osteoporotic fractures and myocardial infarction is an inefficient use of health resources. Cost-effectiveness of hormone replacement in asymptomatic women is dependent on the magnitude of cardiac benefits associated with hormone

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African Journals Online (AJOL)

Family physicians, who see most of these patients ... model when treating patients with nicotine addiction. Physicians ... Administration for treatment of tobacco dependence include bupropion (a non-nicotine therapy) and nicotine replacement.

US smokers' reactions to a brief trial of oral nicotine products

Directory of Open Access Journals (Sweden)

Mahoney Martin C

2011-01-01

Full Text Available Abstract Background It has been suggested that cigarette smokers will switch to alternative oral nicotine delivery products to reduce their health risks if informed of the relative risk difference. However, it is important to assess how smokers are likely to use cigarette alternatives before making predictions about their potential to promote individual or population harm reduction. Objectives This study examines smokers' interest in using a smokeless tobacco or a nicotine replacement product as a substitute for their cigarettes. Methods The study included 67 adult cigarette smokers, not currently interested in quitting, who were given an opportunity to sample four alternative oral nicotine products: 1 Camel Snus, 2 Marlboro Snus, 3 Stonewall dissolvable tobacco tablets, and 4 Commit nicotine lozenges. At visit 1, subjects were presented information about the relative benefits/risks of oral nicotine delivery compared to cigarettes. At visit 2, subjects were given a supply of each of the four products to sample at home for a week. At visit 3, subjects received a one-week supply of their preferred product to see if using such products reduced or eliminated cigarette use. Results After multiple product sampling, participants preferred the Commit lozenges over the three smokeless tobacco products (p = 0.011. Following the one week single-product trial experience, GEE models controlling for gender, age, level of education, baseline cigarettes use, and alternative product chosen, indicated a significant decline in cigarettes smoked per day across one week of single-product sampling (p Conclusions Findings from this study show that smokers, who are currently unwilling to make a quit attempt, may be willing to use alternative products in the short term as a temporary substitute for smoking. However, this use is more likely to be for partial substitution (i.e. they will continue to smoke, albeit at a lower rate rather than complete substitution. Of the

[Combined l-thyroxine and l-triiodothyronine replacement therapy in congenital hypothyroidism].

Science.gov (United States)

Péter, Ferenc; Muzsnai, Agota

2013-05-12

L-thyroxine replacement therapy is the treatment of choice for hypothyroidism. Recently, several studies suggested to complete it with l-triiodothyronine in acquired hypothyroidism. To study the role of combined l-thyroxine and l-triiodothyronine therapy in special cases with congenital hypothyroidism. Data of 16 patients (age: 11.9 ± 6.3 years; mean ± SD) are presented who had high serum free thyroxine values or even above the upper limit of reference range (21.16 ± 2.5 pmol/l) together with nonsuppressed TSH levels (15.7 ± 5.7 mIU/l), and therefore received l-triiodothyronine in completion (0.18 ± 0.09 μg/kg) once a day. The combined replacement therapy resulted in a rapid improvement of the hormone parameters (TSH: 4.2 ± 3.15 mIU/l; free thyroxine: 16.55 ± 2.4 and free triiodothyronine: 7.4 ± 1.8 pmol/l). The efficiency of this combined therapy proved to be more evident (TSH: 4.33 ± 3.2 mIU/l; free thyroxine: 16.85 ± 3.1 and free triiodothyronine: 6.4 ± 0.85 pmol/l) in 10 patients treated for a longer period of time (duration of treatment: 2.9 ± 2.0 years). The dose of thyroxine substitution decreased from 2.6 ± 0.9 to 2.18 ± 0.6 μg/kg/day), the ratio of these hormones was between 5:1 and 19:1 and the quotient of free fractions was normalized (3.8 ± 0.4→2.6 ± 0.3) during the replacement therapy. According to the observation of the authors a serious disturbance of feed-back mechanism may develop in some (>5%) children with congenital hypothyroidism (increased TSH release despite elevated free thyroxine level) after normal function of the feed-back system for years. Hormone parameters of these patients improve, then become normal on combined therapy supporting the rationale for this treatment method.

Cigarette nicotine yields and nicotine intake among Japanese male workers

OpenAIRE

Ueda, K; Kawachi, I; Nakamura, M; Nogami, H; Shirokawa, N; Masui, S; Okayama, A; Oshima, A

2002-01-01

Objectives: To analyse brand nicotine yield including "ultra low" brands (that is, cigarettes yielding ≤ 0.1 mg of nicotine by Federal Trade Commission (FTC) methods) in relation to nicotine intake (urinary nicotine, cotinine and trans-3'-hydroxycotinine) among 246 Japanese male smokers.

Nicotine Lozenges

Science.gov (United States)

Nicotine lozenges are used to help people stop smoking. Nicotine lozenges are in a class of medications called smoking cessation aids. They work by providing nicotine to your body to decrease the withdrawal symptoms ...

The effect of hormone replacement therapy on serum homocysteine levels in perimenopausal women : a randomized controlled trial

NARCIS (Netherlands)

Hak, AE; Bak, AAA; Lindemans, J; Planellas, J; Bennink, HJTC; Hofman, A; Grobbee, DE; Witteman, JCM

2001-01-01

Serum homocysteine levels may be lowered by hormone replacement therapy, but randomized controlled trial data are scarce. We performed a single center randomized placebo-controlled trial to assess the 6 months effect of hormone replacement therapy compared with placebo on fasting serum homocysteine

Métodos para abandono do tabagismo e tratamento da dependência da nicotina Methods for smoking cessation and treatment of nicotine dependence

Directory of Open Access Journals (Sweden)

Aracy Pereira Silveira Balbani

2005-12-01

symptoms in addicted individuals: anxiety, anger, sleep disorders, hunger, cognitive dysfunction and cigarette craving. Medical advice is the cornerstone of smoking cessation. Pharmacotherapy of nicotine addiction comprises first-line (bupropion and nicotine replacement therapy and second-line (clonidine and nortriptyline drugs. Bupropion is a non-tricyclic antidepressant that inhibits dopamine uptake, whose contraindications are: epilepsy, eating disorders, uncontrolled hypertension, recent alcohol abstinence and current therapy with MAO inhibitors. Nicotine replacement therapy can be done with patches or gums. Counseling groups and behavioral interventions are efficacious. The effects of acupuncture on smoking cessation are not fully elucidated. Prompt smoking cessation or gradual reduction strategies have similar success rates.

Revisiting the Cutaneous Impact of Oral Hormone Replacement Therapy

Directory of Open Access Journals (Sweden)

Gérald E. Piérard

2013-01-01

Full Text Available Menopause is a key point moment in the specific aging process of women. It represents a universal evolution in life. Its initiation is defined by a 12-month amenorrhea following the ultimate menstrual period. It encompasses a series of different biologic and physiologic characteristics. This period of life appears to spot a decline in a series of skin functional performances initiating tissue atrophy, withering, and slackness. Any part of the skin is possibly altered, including the epidermis, dermis, hypodermis, and hair follicles. Hormone replacement therapy (oral and nonoral and transdermal estrogen therapy represent possible specific managements for women engaged in the climacteric phase. All the current reports indicate that chronologic aging, climacteric estrogen deficiency, and adequate hormone therapy exert profound effects on various parts of the skin.

Nicotine self-administration and reinstatement of nicotine-seeking in male and female rats.

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Feltenstein, Matthew W; Ghee, Shannon M; See, Ronald E

2012-03-01

Tobacco addiction is a relapsing disorder that constitutes a substantial worldwide health problem, with evidence suggesting that nicotine and nicotine-associated stimuli play divergent roles in maintaining smoking behavior in men and women. While animal models of tobacco addiction that utilize nicotine self-administration have become more widely established, systematic examination of the multiple factors that instigate relapse to nicotine-seeking have been limited. Here, we examined nicotine self-administration and subsequent nicotine-seeking in male and female Sprague-Dawley rats using an animal model of self-administration and relapse. Rats lever pressed for nicotine (0.03 and 0.05 mg/kg/infusion, IV) during 15 daily 2-h sessions, followed by extinction of lever responding. Once responding was extinguished, we examined the ability of previously nicotine-paired cues (tone+light), the anxiogenic drug yohimbine (2.5mg/kg, IP), a priming injection of nicotine (0.3mg/kg, SC), or combinations of drug+cues to reinstate nicotine-seeking. Both males and females readily acquired nicotine self-administration and displayed comparable levels of responding and intake at both nicotine doses. Following extinction, exposure to the previously nicotine-paired cues or yohimbine, but not the nicotine-prime alone, reinstated nicotine-seeking in males and females. Moreover, when combined with nicotine-paired cues, both yohimbine and nicotine enhanced reinstatement. No significant sex differences or estrous cycle dependent changes were noted across reinstatement tests. These results demonstrate the ability to reinstate nicotine-seeking with multiple modalities and that exposure to nicotine-associated cues during periods of a stressful state or nicotine can increase nicotine-seeking. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Hormone replacement therapy: short-term versus long-term use.

Science.gov (United States)

Rousseau, Mary Ellen

2002-01-01

Midwives manage health care of women throughout the life cycle including prescribing hormone replacement therapy (HRT). This article presents a history of research on the use of HRT, as well as risks and benefits. Older research on the effects of HRT on heart disease, osteoporosis, and breast cancer is included. The results and recommendations of the Women's Health Initiative are examined.

Language Profile in Congenital Hypothyroid Children Receiving Replacement Therapy.

Science.gov (United States)

Soliman, Hend; Abdel Hady, Aisha Fawzy; Abdel Hamid, Asmaa; Mahmoud, Heba

2016-01-01

The aim of this work was to evaluate receptive and expressive language skills in children with congenital hypothyroidism receiving early hormonal replacement treatment before the age of 3 months and to identify any subtle areas of weaknesses in their language development to check the necessity for future language intervention. The study was conducted on 30 hypothyroid children receiving hormonal replacement. They were subdivided into group I (5-8 years 11 months; 12 cases) and group II (9-12 years 11 months; 18 cases). All patients were subjected to a protocol of assessment applied in the Diabetes, Endocrine and Metabolism Pediatric Unit (DEMPU) and evaluation of language skills by the REAL scale. The younger group reached average Arabic language scores, while the older group showed moderate language delay. Early replacement therapy supports language development in young children. However, longitudinal and follow-up studies are required to identify difficulties presenting at older ages that may affect children in the academic settings. © 2016 S. Karger AG, Basel.

Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

International Nuclear Information System (INIS)

Ma, Noelle; Nicholson, Catherine J.; Wong, Michael; Holloway, Alison C.; Hardy, Daniel B.

2014-01-01

While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced

Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

Energy Technology Data Exchange (ETDEWEB)

Ma, Noelle [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada); Nicholson, Catherine J. [Department of Obstetrics and Gynecology, McMaster University (Canada); Wong, Michael [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada); Holloway, Alison C. [Department of Obstetrics and Gynecology, McMaster University (Canada); Hardy, Daniel B., E-mail: Daniel.Hardy@schulich.uwo.ca [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Children' s Health Research Institute, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada)

2014-02-15

While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced

The benefits and risks of testosterone replacement therapy: a review

Directory of Open Access Journals (Sweden)

Nazem Bassil

2009-06-01

Full Text Available Nazem Bassil1, Saad Alkaade2, John E Morley1,31Division of Geriatric Medicine; 2Internal Medicine, Saint Louis University Health Sciences Center, St. Louis, Missouri, USA; 3GRECC, VA Medical Center, St. Louis, Missouri, USAAbstract: Increased longevity and population aging will increase the number of men with late onset hypogonadism. It is a common condition, but often underdiagnosed and undertreated. The indication of testosterone-replacement therapy (TRT treatment requires the presence of low testosterone level, and symptoms and signs of hypogonadism. Although controversy remains regarding indications for testosterone supplementation in aging men due to lack of large-scale, long-term studies assessing the benefits and risks of testosterone-replacement therapy in men, reports indicate that TRT may produce a wide range of benefits for men with hypogonadism that include improvement in libido and sexual function, bone density, muscle mass, body composition, mood, erythropoiesis, cognition, quality of life and cardiovascular disease. Perhaps the most controversial area is the issue of risk, especially possible stimulation of prostate cancer by testosterone, even though no evidence to support this risk exists. Other possible risks include worsening symptoms of benign prostatic hypertrophy, liver toxicity, hyperviscosity, erythrocytosis, worsening untreated sleep apnea or severe heart failure. Despite this controversy, testosterone supplementation in the United States has increased substantially over the past several years. The physician should discuss with the patient the potential benefits and risks of TRT. The purpose of this review is to discuss what is known and not known regarding the benefits and risks of TRT.Keywords: hypogonadism, testosterone replacement therapy, erectile dysfunction, osteoporosis, cardiovascular disease

Cue Reactivity in Nicotine and Alcohol Addiction: A Cross-Cultural View

Science.gov (United States)

Lv, Wanwan; Wu, Qichao; Liu, Xiaoming; Chen, Ying; Song, Hongwen; Yang, Lizhuang; Zhang, Xiaochu

2016-01-01

A wealth of research indicates that cue reactivity is critical to understanding the neurobiology of nicotine and alcohol addiction and developing treatments. Functional magnetic resonance imaging (fMRI) and electroencephalograph (EEG) studies have shown abnormal cue reactivity in various conditions between nicotine or alcohol addicts and the healthy. Although the causes of these abnormalities are still unclear, cultural effect can not be ignored. We conduct an review of fMRI and EEG studies about the cue reactivity in nicotine and alcohol addiction and highlight the cultural perspective. We suggest that cultural cue reactivity is a field worth of exploring which may has an effect on addictive behavior through emotion and attention. The cultural role of nicotine and alcohol addiction would provide new insight into understanding the mechanisms of nicotine and alcohol addiction and developing culture-specific therapies. We consider that culture as a context may be a factor that causes confusing outcomes in exploring nicotine and alcohol addiction which makes it possible to control the cultural influences and further contribute to the more consistent results. PMID:27635123

Evaluation of nicotine in tobacco-free-nicotine commercial products.

Science.gov (United States)

Hellinghausen, Garrett; Lee, Jauh T; Weatherly, Choyce A; Lopez, Diego A; Armstrong, Daniel W

2017-06-01

Recently, a variety of new tobacco-free-nicotine, TFN, products have been commercialized as e-liquids. Tobacco-derived nicotine contains predominantly (S)-(-)-nicotine, whereas TFN products may not. The TFN products are said to be cleaner, purer substances, devoid of toxic components that come from the tobacco extraction process. A variety of commercial tobacco and TFN products were analyzed to identify the presence and composition of each nicotine enantiomer. A rapid and effective enantiomeric separation of nicotine has been developed using a modified macrocyclic glycopeptide bonded to superficially porous particles. The enantiomeric assay can be completed in nicotine, which is present in much greater quantities in commercial TFN products compared to commercial tobacco-derived products. Such studies are required by the FDA for new enantiomeric pharmacological products. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of urinary pH and nicotine excretion rate on plasma nicotine during cigarette smoking and chewing nicotine gum

Science.gov (United States)

Feyerabend, C.; Russell, M. A. H.

1978-01-01

1 Plasma nicotine levels produced by chewing nicotine gum were compared with those obtained by cigarette smoking under conditions of controlled urinary pH. 2 Although absorption was slower, plasma levels comparable to cigarette smoking were built up on 4 mg (but not 2 mg) nicotine gum. 3 Urinary excretion of nicotine was influenced markedly by pH and the rate of urine flow. 4 Plasma nicotine was higher under alkaline compared to acidic conditions (P < 0.001) but the rate of urinary nicotine excretion appeared to have little effect on the plasma level.

Renal replacement therapy in Europe

DEFF Research Database (Denmark)

Pippias, Maria; Stel, Vianda S; Abad Diez, José Maria

2015-01-01

BACKGROUND: This article summarizes the 2012 European Renal Association-European Dialysis and Transplant Association Registry Annual Report (available at www.era-edta-reg.org) with a specific focus on older patients (defined as ≥65 years). METHODS: Data provided by 45 national or regional renal...... disease (ESRD) receiving renal replacement therapy (RRT) and renal transplantation rates for 2012 are presented. RESULTS: In 2012, the overall unadjusted incidence rate of patients with ESRD receiving RRT was 109.6 per million population (pmp) (n = 69 035), ranging from 219.9 pmp in Portugal to 24.2 pmp...... to 32% between countries. The overall renal transplantation rate in 2012 was 28.3 pmp (n = 15 673), with the highest rate seen in the Spanish region of Catalonia. The proportion of patients ≥65 years receiving a transplant ranged from 0 to 35%. Five-year adjusted survival for all RRT patients was 59...

Nicotine response and nicotinic receptors in long-sleep and short-sleep mice.

Science.gov (United States)

De Fiebre, C M; Medhurst, L J; Collins, A C

1987-01-01

Nicotine response and nicotinic receptor binding were characterized in long-sleep (LS) and short-sleep (SS) mice which have been selectively bred for differential "sleep-time" following ethanol administration. LS mice are more sensitive than SS mice to nicotine as measured by a battery of behavioral and physiological tests and as measured by sensitivity to nicotine-induced seizures. The greater sensitivity of the LS mice is not due to differences in binding of [3H]nicotine. Unlike inbred mouse strains which differ in sensitivity to nicotine-induced seizures, these selected mouse lines do not differ in levels of binding of [125I]alpha-bungarotoxin (BTX) in the hippocampus. Significant differences in BTX binding were found in the cerebellum and striatum. Although these two mouse lines do not differ in blood levels of nicotine following nicotine administration, they differ slightly in brain levels of nicotine indicating differential distribution of the drug. Since this distribution difference is much smaller than the observed behavioral differences, these mice probably differ in CNS sensitivity to nicotine; however, follow-up studies are necessary to test whether the differential response of these mice is due to subtle differences in distribution of nicotine to the brain.

Neuronal replacement therapy: previous achievements and challenges ahead

Science.gov (United States)

Grade, Sofia; Götz, Magdalena

2017-10-01

Lifelong neurogenesis and incorporation of newborn neurons into mature neuronal circuits operates in specialized niches of the mammalian brain and serves as role model for neuronal replacement strategies. However, to which extent can the remaining brain parenchyma, which never incorporates new neurons during the adulthood, be as plastic and readily accommodate neurons in networks that suffered neuronal loss due to injury or neurological disease? Which microenvironment is permissive for neuronal replacement and synaptic integration and which cells perform best? Can lost function be restored and how adequate is the participation in the pre-existing circuitry? Could aberrant connections cause malfunction especially in networks dominated by excitatory neurons, such as the cerebral cortex? These questions show how important connectivity and circuitry aspects are for regenerative medicine, which is the focus of this review. We will discuss the impressive advances in neuronal replacement strategies and success from exogenous as well as endogenous cell sources. Both have seen key novel technologies, like the groundbreaking discovery of induced pluripotent stem cells and direct neuronal reprogramming, offering alternatives to the transplantation of fetal neurons, and both herald great expectations. For these to become reality, neuronal circuitry analysis is key now. As our understanding of neuronal circuits increases, neuronal replacement therapy should fulfill those prerequisites in network structure and function, in brain-wide input and output. Now is the time to incorporate neural circuitry research into regenerative medicine if we ever want to truly repair brain injury.

Cost-effectiveness of raising HDL cholesterol by adding prolonged-release nicotinic acid to statin therapy in the secondary prevention setting: a French perspective.

Science.gov (United States)

Roze, S; Ferrières, J; Bruckert, E; Van Ganse, E; Chapman, M J; Liens, D; Renaudin, C

2007-11-01

To evaluate the cost-effectiveness of raising high-density lipoprotein cholesterol (HDL-C) with add-on nicotinic acid in statin-treated patients with coronary heart disease (CHD) and low HDL-C, from the French healthcare system perspective. Computer simulation economic modelling incorporating two decision analytic submodels was used. The first submodel generated a cohort of 2000 patients and simulated lipid changes using baseline characteristics and treatment effects from the ARterial Biology for the Investigation of the Treatment Effects of Reducing cholesterol (ARBITER 2) study. Prolonged-release (PR) nicotinic acid (1 g/day) was added in patients with HDL-C costs were accounted from a third party payer perspective [2004 Euros (euro)] and discounted by 3%. Addition of PR nicotinic acid to statin therapy resulted in substantial health gain and increased life expectancy, at a cost well within the threshold (cost-effective in France at a level considered to represent good value for money by reimbursement authorities in Europe. This strategy was highly cost-effective in CHD patients with type 2 diabetes.

E-Cigarette Users' Attitudes on the Banning of Sales of Nicotine E-Liquid, Its Implication on E-Cigarette Use Behaviours and Alternative Sources of Nicotine E-Liquid.

Science.gov (United States)

Wong, Li Ping; Alias, Haridah; Agha Mohammadi, Nasrin; Ghadimi, Azadeh; Hoe, Victor Chee Wai

2017-12-01

The banning of sales of nicotine e-liquid in e-cigarette shops has been implemented in several states in Malaysia. The distribution of nicotine e-liquid can only be allowed by licensed pharmacies or registered medical practitioners. This study aimed to evaluate e-cigarette users' responses to the control policy in a cross-sectional survey of 851 e-cigarette users by utilizing a self-report questionnaire that assessed (1) attitudes on regulation policy of e-cigarette banning; (2) e-cigarette use behaviors; and (3) sources of e-liquid after the regulation policy has been implemented. Participants from the state of Selangor where the banning policy was implemented were surveyed. The majority (95.8%) opposed the banning and believed e-cigarettes should be sold to anyone aged 18 years or above as with tobacco cigarettes, only a minority believed that nicotine e-liquid should only be available for sale over the counter in pharmacy stores (14.6%) and in clinics with a doctor's prescription (11.8%). The majority (44.2%) reported that they would continue their e-cigarette use as before the banning policy, while 20% plan to completely stop e-cigarette usage without replacing it with any alternatives. The vast majority (87.9%) was still able to obtained nicotine e-liquid from e-cigarette shops in spite of the ban and the second most common source was from online purchase (63.1%). The sales of nicotine e-liquid from black-market were evidenced as many reported obtaining zero nicotine e-liquid from the black market (54.4%). Self- or home-made (30.8%) nicotine e-liquid was also reported. Majority of respondents that self-made e-liquid were from the average monthly income group (below MYR3000). Obtaining nicotine from the pharmacy was least preferred (21.4%). Provision of professional advice to nicotine e-liquid users along with the ban may lessen the likelihood of users switching to tobacco cigarettes or other nicotine alternatives. Banning of sales of nicotine e-liquid in e

Acute effects of nicotine amplify accumbal neural responses during nicotine-taking behavior and nicotine-paired environmental cues.

Directory of Open Access Journals (Sweden)

Karine Guillem

Full Text Available Nicotine self-administration (SA is maintained by several variables, including the reinforcing properties of nicotine-paired cues and the nicotine-induced amplification of those cue properties. The nucleus accumbens (NAc is implicated in mediating the influence of these variables, though the underlying neurophysiological mechanisms are not yet understood. In the present study, Long-Evans rats were trained to self-administer nicotine. During SA sessions each press of a lever was followed by an intravenous infusion of nicotine (30 µg/kg paired with a combined light-tone cue. Extracellular recordings of single-neuron activity showed that 20% of neurons exhibited a phasic change in firing during the nicotine-directed operant, the light-tone cue, or both. The phasic change in firing for 98% of neurons was an increase. Sixty-two percent of NAc neurons additionally or alternatively showed a sustained decrease in average firing during the SA session relative to a presession baseline period. These session decreases in firing were significantly less prevalent in a group of neurons that were activated during either the operant or the cue than in a group of neurons that were nonresponsive during those events (referred to as task-activated and task-nonactivated neurons, respectively. Moreover, the session decrease in firing was dose-dependent for only the task-nonactivated neurons. The data of the present investigation provide supportive correlational evidence for two hypotheses: (1 excitatory neurophysiological mechanisms mediate the NAc role in cue-maintenance of nicotine SA, and (2 a differential nicotine-induced inhibition of task-activated and task-nonactivated neurons mediates the NAc role in nicotine-induced amplification of cue effects on nicotine SA.

The secondary hypothyroidism after radioiodine therapy and the replacement treatment

International Nuclear Information System (INIS)

Xu Ying; Xu Xiaohui

2004-01-01

The secondary hypothyroidism is the most important intercurrent disease after radioiodine therapy. The early hypothyroidism and the late hypothyroidism are incompletely different in pathogenesis. It needs researching further. there has not yet been an affirmable answer to choose the distillates from animal hypothyroid extract or complex preparation of levo-thyroxine in replacement treatment. (authors)

Effects of nicotine and nicotine expectancy on attentional bias for emotional stimuli.

Science.gov (United States)

Adams, Sally; Attwood, Angela S; Munafò, Marcus R

2015-06-01

Nicotine's effects on mood are thought to enhance its addictive potential. However, the mechanisms underlying the effects of nicotine on affect regulation have not been reliably demonstrated in human laboratory studies. We investigated the effects of nicotine abstinence (Experiment 1), and nicotine challenge and expectancy (Experiment 2) on attentional bias towards facial emotional stimuli differing in emotional valence. In Experiment 1, 46 nicotine-deprived smokers were randomized to either continue to abstain from smoking or to smoke immediately before testing. In Experiment 2, 96 nicotine-deprived smokers were randomized to smoke a nicotinized or denicotinized cigarette and to be told that the cigarette did or did not contain nicotine. In both experiments participants completed a visual probe task, where positively valenced (happy) and negatively valenced (sad) facial expressions were presented, together with neutral facial expressions. In Experiment 1, there was evidence of an interaction between probe location and abstinence on reaction time, indicating that abstinent smokers showed an attentional bias for neutral stimuli. In Experiment 2, there was evidence of an interaction between probe location, nicotine challenge and expectation on reaction time, indicating that smokers receiving nicotine, but told that they did not receive nicotine, showed an attentional bias for emotional stimuli. Our data suggest that nicotine abstinence appears to disrupt attentional bias towards emotional facial stimuli. These data provide support for nicotine's modulation of attentional bias as a central mechanism for maintaining affect regulation in cigarette smoking. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

High phenobarbital clearance during continuous renal replacement therapy: a case report and pharmacokinetic analysis.

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Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

2014-08-01

Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring.A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure.Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus.The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed.Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring.

Does early use of enzyme replacement therapy alter the natural history of mucopolysaccharidosis I? Experience in three siblings.

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Laraway, Sarah; Breen, Catherine; Mercer, Jean; Jones, Simon; Wraith, James E

2013-07-01

Enzyme replacement therapy is widely used as treatment for mucopolysaccharidosis I (MPS I), and there is evidence that this produces improvement in certain clinical domains. There does appear to be variation in the response of clinical features to treatment once these are established. In a reported sibling pair, when enzyme replacement therapy was commenced pre-symptomatically in the younger child, the natural history of the condition appeared to be affected. We present data from three siblings treated with enzyme replacement therapy at different ages which supports this finding. Copyright © 2013 Elsevier Inc. All rights reserved.

The efficacy of surfactant replacement therapy in the growth restricted preterm infant: what is the evidence?

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Atul eMalhotra

2014-10-01

Full Text Available Background: Surfactant replacement therapy (SRT is an integral part of management of preterm surfactant deficiency (respiratory distress syndrome, RDS. Its role in the management of RDS has been extensively studied. However its efficacy in the management of lung disease in preterm infants born with intrauterine growth restriction (IUGR has not been systematically studied.Objective: To evaluate the efficacy of exogenous surfactant replacement therapy in the management of preterm IUGR lung disease. Methods: A systematic search of all available randomised clinical trials (RCT of surfactant replacement therapy in preterm IUGR infants was done according to the standard Cochrane collaboration search strategy. Neonatal respiratory outcomes were compared between the preterm IUGR and appropriately-grown for gestational age (AGA preterm infant populations in eligible studies. Results: No study was identified which evaluated the efficacy or responsiveness of exogenous surfactant replacement therapy in preterm IUGR infants as compared to preterm AGA infants. The only study identified through the search strategy used small for gestational age (SGA; defined as less than 10th centile for birth weight as a proxy for IUGR. The RCT evaluated the efficacy or responsiveness of SRT in preterm SGA group as compared to AGA infants. The rate of intubation, severity of RDS, rate of surfactant administration, pulmonary air leaks and days on the ventilator did not differ between both groups. However, the requirement for prolonged nasal CPAP (p< 0.001, supplemental oxygen therapy (p <0.01 and the incidence of bronchopulmonary dysplasia at 28 days and 36 weeks (both p<0.01 was greater in SGA infants. Discussion: There is currently insufficient data available to evaluate the efficacy of SRT in preterm IUGR lung disease. A variety of research strategies will be needed to enhance our understanding of the role and rationale for use of surfactant replacement therapy in preterm

Nicotinic plant poisoning.

Science.gov (United States)

Schep, Leo J; Slaughter, Robin J; Beasley, D Michael G

2009-09-01

A wide range of plants contain nicotinic and nicotinic-like alkaloids. Of this diverse group, those that have been reported to cause human poisoning appear to have similar mechanisms of toxicity and presenting patients therefore have comparable toxidromes. This review describes the taxonomy and principal alkaloids of plants that contain nicotinic and nicotinic-like alkaloids, with particular focus on those that are toxic to humans. The toxicokinetics and mechanisms of toxicity of these alkaloids are reviewed and the clinical features and management of poisoning due to these plants are described. This review was compiled by systematically searching OVID MEDLINE and ISI Web of Science. This identified 9,456 papers, excluding duplicates, all of which were screened. Reviewed plants and their principal alkaloids. Plants containing nicotine and nicotine-like alkaloids that have been reported to be poisonous to humans include Conium maculatum, Nicotiana glauca and Nicotiana tabacum, Laburnum anagyroides, and Caulophyllum thalictroides. They contain the toxic alkaloids nicotine, anabasine, cytisine, n-methylcytisine, coniine, n-methylconiine, and gamma-coniceine. These alkaloids act agonistically at nicotinic-type acetylcholine (cholinergic) receptors (nAChRs). The nicotinic-type acetylcholine receptor can vary both in its subunit composition and in its distribution within the body (the central and autonomic nervous systems, the neuromuscular junctions, and the adrenal medulla). Agonistic interaction at these variable sites may explain why the alkaloids have diverse effects depending on the administered dose and duration of exposure. Nicotine and nicotine-like alkaloids are absorbed readily across all routes of exposure and are rapidly and widely distributed, readily traversing the blood-brain barrier and the placenta, and are freely distributed in breast milk. Metabolism occurs predominantly in the liver followed by rapid renal elimination. Following acute exposure

Effectiveness of a clinical practice change intervention in increasing the provision of nicotine dependence treatment in inpatient psychiatric facilities: an implementation trial.

Science.gov (United States)

Wye, Paula M; Stockings, Emily A; Bowman, Jenny A; Oldmeadow, Chris; Wiggers, John H

2017-02-07

Despite clinical practice guidelines recommending the routine provision of nicotine dependence treatment to smokers in inpatient psychiatric facilities, the prevalence of such treatment provision is low. The aim of this study was to examine the effectiveness of a clinical practice change intervention in increasing clinician recorded provision of nicotine dependence treatment to patients in inpatient psychiatric facilities. We undertook an interrupted time series analysis of nicotine dependence treatment provision before, during and after a clinical practice change intervention to increase clinician recorded provision of nicotine dependence treatment for all hospital discharges (aged >18 years, N = 4175) over a 19 month period in two inpatient adult psychiatric facilities in New South Wales, Australia. The clinical practice change intervention comprised six key strategies: leadership and consensus, enabling systems and procedures, training and education, information and resources, audit and feedback and an on-site practice change support officer. Systematic medical record audit and segmented logistic regression was used to determine differences in proportions for each nicotine dependence treatment outcome measure between the 'pre', 'during' and 'post-intervention' periods. The prevalence of all five outcome measures increased significantly between the pre and post-intervention periods, including clinician recorded: assessment of patient smoking status (36.43 to 51.95%; adjusted odds ratio [AOR] = 2.39, 99% Confidence Interval [CI]: 1.23 to 4.66); assessment of patient nicotine dependence status (4.74 to 11.04%; AOR = 109.67, 99% CI: 35.35 to 340.22); provision of brief advice to quit (0.85 to 8.81%; AOR = 97.43, 99% CI: 31.03 to 306.30); provision of nicotine replacement therapy (8.06 to 26.25%; AOR = 19.59, 99% CI: 8.17 to 46.94); and provision of nicotine dependence treatment on discharge (8.82 to 13.45%, AOR = 12.36; 99% CI: 6.08 to 25

A review of the effects of very low nicotine content cigarettes on behavioral and cognitive performance.

Science.gov (United States)

Keith, Diana R; Kurti, Allison N; Davis, Danielle R; Zvorsky, Ivori A; Higgins, Stephen T

2017-11-01

The present systematic review examines whether very low nicotine content (VLNC) cigarettes ameliorate withdrawal-induced impairments in behavioral/cognitive performance. PubMed, PsycInfo, and Web of Science were searched for performance effects of VLNC cigarettes. For inclusion, reports had to be in English, published in a peer-reviewed journal through June 2017, examine VLNC cigarettes (articles reviewed met inclusion criteria. Poorer performance after smoking VLNC versus normal nicotine content (NNC) cigarettes was observed across 7 of 10 domains, including reaction time (8/11), short-term memory (3/10), sustained attention (4/6), inhibitory control (1/4), long-term memory (3/3 studies), and response variability (2/2). In two studies, combining VLNC smoking with nicotine replacement therapy (NRT) resulted in performance that was comparable to performance after NNC smoking. VLNC versus NNC differences were not discerned in motor control/functioning (0/2), visuospatial processing (0/2), learning (0/1), or verbal fluency (0/1). Eleven of nineteen (58%) studies were rated of Good or Excellent quality. Overall, VLNC cigarettes may not fully ameliorate withdrawal-induced disruptions in performance, although this varies by domain, with the strongest evidence for reaction time. Importantly, combining VLNC cigarettes with NRT appears to ameliorate withdrawal that is not reduced by VLNC cigarettes alone. As only 19 studies were identified, many domains are under-investigated. A more thorough evaluation of the extent to which VLNC cigarettes affect withdrawal-impaired performance may be warranted. Copyright © 2017. Published by Elsevier Inc.

Controversies in hormone replacement therapy

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A. Baziad

2001-09-01

Full Text Available Deficiency of estrogen hormone will result in either long-term or short-term health problems which may reduce the quality of life. There are numerous methods by which the quality of female life can be achieved. Since the problems occuring are due to the deficiency of estrogen hormone, the appropriate method to tackle the problem is by administration of estrogen hormone. The administration of hormone replacement therapy (HRT with estrogen may eliminate climacteric complaints, prevent osteoporosis, coronary heart disease, dementia, and colon cancer. Although HRT has a great deal of advantage, its use is still low and may result in controversies. These controversies are due to fact that both doctor and patient still hold on to the old, outmoded views which are not supported by numerous studies. Currently, the use of HRT is not only based on experience, or temporary observation, but more on evidence based medicine. (Med J Indones 2001; 10: 182-6Keywords: controversies, HRT

JCL Roundtable: enzyme replacement therapy for lipid storage disorders.

Science.gov (United States)

Brown, W Virgil; Desnick, Robert J; Grabowski, Gregory A

2014-01-01

There are several inherited disorders that involve abnormal storage of lipids in tissues leading to severe compromise of organs. Sadly, these are often accompanied by lifelong morbidity and early mortality. Disorders such as Gaucher, Fabry, and lysosomal acid lipase deficiencies (Wolman and cholesteryl ester storage diseases) have been known for many years, and provide a difficult and frustrating set of problems for patients, their families, and their physicians. With recombinant methods of protein synthesis, it is now possible to literally replace the defective enzymes that underlie the basic pathophysiology of many such disorders. The delivery of these enzymes into the affected cells is possible because of their location in the lysosomes where the natural degradation of their lipid substrates occurs. I have asked 2 well-known investigators to join us for this Roundtable. These are professors who have been involved with the research that has made this type of therapy possible and who have participated in the clinical trials that demonstrated the value of enzyme replacement therapy. They are Dr. Robert Desnick, dean of Genetic and Genomic Medicine and professor and chairman emeritus of the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai in New York City, and Dr. Gregory Grabowski, professor of Microbiology, Biochemistry, and Pediatrics, at the University of Cincinnati College of Medicine. Dr. Grabowski recently retired from that school to become the chief science officer of Synageva, a company involved in producing enzymes for this type of therapy. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism?

Science.gov (United States)

Biondi, Bernadette; Wartofsky, Leonard

2012-07-01

Levothyroxine therapy is the traditional lifelong replacement therapy for hypothyroid patients. Over the last several years, new evidence has led clinicians to evaluate the option of combined T(3) and T(4) treatment to improve the quality of life, cognition, and peripheral parameters of thyroid hormone action in hypothyroidism. The aim of this review is to assess the physiological basis and the results of current studies on this topic. We searched Medline for reports published with the following search terms: hypothyroidism, levothyroxine, triiodothyronine, thyroid, guidelines, treatment, deiodinases, clinical symptoms, quality of life, cognition, mood, depression, body weight, heart rate, cholesterol, bone markers, SHBG, and patient preference for combined therapy. The search was restricted to reports published in English since 1970, but some reports published before 1970 were also incorporated. We supplemented the search with records from personal files and references of relevant articles and textbooks. Parameters analyzed included the rationale for combination treatment, the type of patients to be selected, the optimal T(4)/T(3) ratio, and the potential benefits of this therapy on symptoms of hypothyroidism, quality of life, mood, cognition, and peripheral parameters of thyroid hormone action. The outcome of our analysis suggests that it may be time to consider a personalized regimen of thyroid hormone replacement therapy in hypothyroid patients. Further prospective randomized controlled studies are needed to clarify this important issue. Innovative formulations of the thyroid hormones will be required to mimic a more perfect thyroid hormone replacement therapy than is currently available.

Use of Renal Replacement Therapy May Influence Graft Outcomes following Liver Transplantation for Acute Liver Failure: A Propensity-Score Matched Population-Based Retrospective Cohort Study.

Science.gov (United States)

Knight, Stephen R; Oniscu, Gabriel C; Devey, Luke; Simpson, Kenneth J; Wigmore, Stephen J; Harrison, Ewen M

2016-01-01

Acute kidney injury is associated with a poor prognosis in acute liver failure but little is known of outcomes in patients undergoing transplantation for acute liver failure who require renal replacement therapy. A retrospective analysis of the United Kingdom Transplant Registry was performed (1 January 2001-31 December 2011) with patient and graft survival determined using Kaplan-Meier methods. Cox proportional hazards models were used together with propensity-score based full matching on renal replacement therapy use. Three-year patient and graft survival for patients receiving renal replacement therapy were 77.7% and 72.6% compared with 85.1% and 79.4% for those not requiring renal replacement therapy (Prenal replacement therapy was a predictor of both patient death (hazard ratio (HR) 1.59, 95% CI 1.01-2.50, P = 0.044) but not graft loss (HR 1.39, 95% CI 0.92-2.10, P = 0.114). In groups fully matched on baseline covariates, those not receiving renal replacement therapy with a serum creatinine greater than 175 μmol/L had a significantly worse risk of graft failure than those receiving renal replacement therapy. In patients being transplanted for acute liver failure, use of renal replacement therapy is a strong predictor of patient death and graft loss. Those not receiving renal replacement therapy with an elevated serum creatinine may be at greater risk of early graft failure than those receiving renal replacement therapy. A low threshold for instituting renal replacement therapy may therefore be beneficial.

Hormone replacement therapy and risk of non-fatal stroke

DEFF Research Database (Denmark)

Pedersen, A T; Lidegaard, O; Kreiner, S

1997-01-01

haemorrhage, 846 thromboembolic infarction, 321 transient ischaemic attack) and 3171 controls. FINDINGS: After adjustment for confounding variables and correction for the trend in sales of HRT preparations, no significant associations were detected between current use of unopposed oestrogen replacement...... influence on the risk of subarachnoid haemorrhage (1.22 [0.79-1.89]), intracerebral haemorrhage (1.17 [0.64-2.13]), or thromboembolic infarction (1.17 [0.92-1.47]). A significantly increased incidence of transient ischaemic attacks among former users of HRT and among current users of unopposed oestrogen may...... to some extent be explained by selection--HRT users being more aware of symptoms than non-users. INTERPRETATION: Unopposed oestrogen and combined oestrogen-progestagen replacement therapy have no influence on the risk of non-fatal thromboembolic or haemorrhagic stroke in women aged 45-64 years....

Cost-effectiveness of varenicline for smoking cessation

DEFF Research Database (Denmark)

Keiding, Hans

2009-01-01

Smoking cessation therapies are among the most cost-effective preventive healthcare measures. Varenicline is a relatively new drug developed especially for this purpose, and it has been shown to achieve better quit rates than nicotine replacement therapies and the non-nicotine-based drug, bupropion...

Successful switch from enzyme replacement therapy to miglustat in an adult patient with type 1 Gaucher disease: a case report.

Science.gov (United States)

Giuffrida, Gaetano; Lombardo, Rita; Di Francesco, Ernesto; Parrinello, Laura; Di Raimondo, Francesco; Fiumara, Agata

2016-11-08

Gaucher disease is one of the most common lipid-storage disorders, affecting approximately 1 in 75,000 births. Enzyme replacement therapy with recombinant glucocerebrosidase is currently considered the first-line treatment choice for patients with symptomatic Gaucher disease type 1. Oral substrate reduction therapy is generally considered a second-line treatment option for adult patients with mild to moderate Gaucher disease type 1 who are unable or unwilling to receive lifelong intravenous enzyme infusions. The efficacy and safety of the oral substrate reduction therapy miglustat (Zavesca®) in patients with Gaucher disease type 1 have been established in both short-term clinical trials and long-term, open-label extension studies. Published data indicate that miglustat can be used as maintenance therapy in patients with stable Gaucher disease type 1 switched from previous enzyme replacement therapy. We report a case of a 44-year-old Caucasian man with Gaucher disease type 1 who was initially treated with enzyme replacement therapy but, owing to repeated cutaneous allergic reactions, had to be switched to miglustat after several attempts with enzyme replacement therapy. Despite many attempts, desensitization treatment did not result in improved toleration of imiglucerase infusions, and the patient became unwilling to continue with any intravenous enzyme replacement therapy. He subsequently agreed to switch to oral substrate reduction therapy with miglustat 100 mg twice daily titrated up to 100 mg three times daily over a short period. Long-term miglustat treatment maintained both hemoglobin and platelet levels within acceptable ranges over 8 years. The patient's spleen volume decreased, his plasma chitotriosidase levels stayed at reduced levels, and his bone mineral density findings have remained stable throughout follow-up. The patient's quality of life has remained satisfactory. Miglustat showed good gastrointestinal tolerability in this patient, and no

R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

Science.gov (United States)

Wang, Xiao-Fei; Bi, Guo-Hua; He, Yi; Yang, Hong-Ju; Gao, Jun-Tao; Okunola-Bakare, Oluyomi M; Slack, Rachel D; Gardner, Eliot L; Xi, Zheng-Xiong; Newman, Amy Hauck

2015-01-01

(±)-Modafinil (MOD) is used clinically for the treatment of sleep disorders and has been investigated as a potential medication for the treatment of psychostimulant addiction. However, the therapeutic efficacy of (±)-MOD for addiction is inconclusive. Herein we used animal models of self-administration and in vivo microdialysis to study the pharmacological actions of R-modafinil (R-MOD) and S-modafinil (S-MOD) on nicotine-taking and nicotine-seeking behavior, and mechanisms underlying such actions. We found that R-MOD is more potent and effective than S-MOD in attenuating nicotine self-administration in Long–Evans rats. As Long–Evans rats did not show a robust reinstatement response to nicotine, we used alcohol-preferring rats (P-rats) that display much higher reinstatement responses to nicotine than Long–Evans rats. We found that R-MOD significantly inhibited intravenous nicotine self-administration, nicotine-induced reinstatement, and nicotine-associated cue-induced drug-seeking behavior in P-rats. R-MOD alone neither sustained self-administration in P-rats previously self-administering nicotine nor reinstated extinguished nicotine-seeking behavior. The in vivo brain microdialysis assays demonstrated that R-MOD alone produced a slow-onset moderate increase in extracellular DA. Pretreatment with R-MOD dose-dependently blocked nicotine-induced dopamine (DA) release in the nucleus accumbens (NAc) in both naive and nicotine self-administrating rats, suggesting a DA-dependent mechanism underlying mitigation of nicotine's effects. In conclusion, the present findings support further investigation of R-MOD for treatment of nicotine dependence in humans. PMID:25613829

Does hormone replacement therapy and use of oral contraceptives increase the risk of non-melanoma skin cancer?

DEFF Research Database (Denmark)

Birch-Johansen, Fatima; Jensen, Allan; Olesen, Anne Braae

2012-01-01

We aimed to examine whether use of hormone replacement therapy (HRT) and oral contraceptives (OC) affect the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in women.......We aimed to examine whether use of hormone replacement therapy (HRT) and oral contraceptives (OC) affect the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in women....

Nicotine dose-concentration relationship and pregnancy outcomes in rat: Biologic plausibility and implications for future research

International Nuclear Information System (INIS)

Hussein, Jabeen; Farkas, Svetlana; MacKinnon, Yolanda; Ariano, Robert E.; Sitar, Daniel S.; Hasan, Shabih U.

2007-01-01

Cigarette smoke (CS) exposure during pregnancy can lead to profound adverse effects on fetal development. Although CS contains several thousand chemicals, nicotine has been widely used as its surrogate as well as in its own right as a neuroteratogen. The justification for the route and dose of nicotine administration is largely based on inferential data suggesting that nicotine 6 mg/kg/day infused continuously via osmotic mini pumps (OMP) would mimic maternal CS exposure. We provide evidence that 6 mg/kg/day nicotine dose as commonly administered to pregnant rats leads to plasma nicotine concentrations that are 3-10-fold higher than those observed in moderate to heavy smokers and pregnant mothers, respectively. Furthermore, the cumulative daily nicotine dose exceeds by several hundred fold the amount consumed by human heavy smokers. Our study does not support the widely accepted notion that regardless of the nicotine dose, a linear nicotine dose-concentration relationship exists in a steady-state OMP model. We also show that total nicotine clearance increases with advancing pregnancy but no significant change is observed between the 2nd and 3rd trimester. Furthermore, nicotine infusion even at this extremely high dose has little effect on a number of maternal and fetal biologic variables and pregnancy outcome suggesting that CS constituents other than nicotine mediate the fetal growth restriction in infants born to smoking mothers. Our current study has major implications for translational research in developmental toxicology and pharmacotherapy using nicotine replacement treatment as an aid to cessation of cigarette smoking in pregnant mothers

Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice.

Science.gov (United States)

Kotagale, Nandkishor R; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

2015-05-05

Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c., four times daily, for 10 days) significantly increased somatic signs viz. rearing, grooming, jumping, genital licking, leg licking, head shakes with associated depression (increased immobility in forced swim test) as well as anxiety (decreased the number of entries and time spent in open arm in elevated plus maze) in nicotine dependent animals. The peak effect was observed at 24h time point of nicotine withdrawal. Repeated administration of agmatine (40-80µg/mouse, i.c.v.) before the first daily dose of nicotine from day 5 to 10 attenuated the elevated scores of somatic signs and abolished the depression and anxiety like behavior induced by nicotine withdrawal in dependent animals. However, in separate groups, its acute administration 30min before behavior analysis of nicotine withdrawal was ineffective. This result clearly shows the role of agmatine in development of nicotine dependence and its withdrawal. In extension to behavioral experiments, brain agmatine analyses, carried out at 24h time point of nicotine withdrawal demonstrated marked decrease in basal brain agmatine concentration as compared to control animals. Taken together, these data support the role of agmatine as common biological substrate for somatic signs and affective symptoms of nicotine withdrawal. This data may project therapies based on agmatine in anxiety, depression and mood changes associated with tobacco withdrawal. Copyright © 2015 Elsevier B.V. All rights reserved.

Renal replacement therapy in sepsis-induced acute renal failure

Directory of Open Access Journals (Sweden)

Rajapakse Senaka

2009-01-01

Full Text Available Acute renal failure (ARF is a common complication of sepsis and carries a high mortality. Renal replacement therapy (RRT during the acute stage is the mainstay of therapy. Va-rious modalities of RRT are available. Continuous RRT using convective methods are preferred in sepsis-induced ARF, especially in hemodynamically unstable patients, although clear evidence of benefit over intermittent hemodialysis is still not available. Peritoneal dialysis is clearly inferior, and is not recommended. Early initiation of RRT is probably advantageous, although the optimal timing of dialysis is yet unknown. Higher doses of RRT are more likely to be beneficial. Use of bio-compatible membranes and bicarbonate buffer in the dialysate are preferred. Anticoagulation during dialysis must be carefully adjusted and monitored.

Salivary cortisol day curves in assessing glucocorticoid replacement therapy in Addison's disease

NARCIS (Netherlands)

Smans, L.; Lentjes, E.G.W.M.; Hermus, A.R.; Zelissen, P.M.J.

2013-01-01

OBJECTIVE: Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects.

Mortality risk disparities in children receiving chronic renal replacement therapy for the treatment of end-stage renal disease across Europe

DEFF Research Database (Denmark)

Chesnaye, Nicholas C; Schaefer, Franz; Bonthuis, Marjolein

2017-01-01

HR) and the explained variation were modelled for patient-level and country-level factors with multilevel Cox regression. The primary outcome studied was all-cause mortality while on renal replacement therapy. FINDINGS: Between Jan 1, 2000, and Dec 31, 2013, the overall 5 year renal replacement therapy mortality rate......BACKGROUND: We explored the variation in country mortality rates in the paediatric population receiving renal replacement therapy across Europe, and estimated how much of this variation could be explained by patient-level and country-level factors. METHODS: In this registry analysis, we extracted...... patient data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry for 32 European countries. We included incident patients younger than 19 years receiving renal replacement therapy. Adjusted hazard ratios (a...

Modelling a budgetary impact analysis for funding drug-based smoking cessation therapies for patients with major depressive disorder in Spain.

Science.gov (United States)

Rejas-Gutiérrez, J; Bruguera, E; Cedillo, S

2017-09-01

Smoking is associated with high healthcare resource utilisation and cost to society. Patients with major depressive disorder (MDD) exhibit high susceptibility to nicotine dependence. Varenicline, bupropion and nicotine replacement therapy are all indicated for smoking cessation; however funding by the Spanish national health system (SNHS) is limited. We modelled a budgetary impact analysis (BIA) to estimate the impact of the SNHS funding drug-based therapies for smoking cessation in smokers with MDD. The BIA compared the current unfunded scenario versus a funded scenario (varenicline, bupropion, nicotine replacement therapy combined with medical follow-up and counselling) using the Spanish SNHS and societal perspectives. The BIA design was a hybrid model using a decision tree algorithm (population size: smokers with MDD) and Markov chains (smoking cessation attempts) over a 5-year horizon. Smoking cessation drug efficacy was derived from clinical trials, and smoking cessation costs avoided were taken from an analysis of the Spanish National Health Survey. Results were shown as incremental cost savings. Scenarios and threshold univariate sensitivity analyses tested model robustness. The funded scenario resulted in an increase of 43,478 cessation attempts and 8930 fewer smokers after 5 years compared to the unfunded scenario. The cost of funding was €25.3 million and costs avoided were €26.5 million. There was a cumulative 5-year incremental cost saving of €1.2 million to Spanish society. Results were robust using alternative scenarios. Funding smoking cessation drugs in patients with MDD is of economic benefit to Spain and could produce net savings from the third year of implementation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Acute renal insufficiency and renal replacement therapy after pediatric cardiopulmonary bypass surgery

NARCIS (Netherlands)

Kist-van Holthe tot Echten, J. E.; Goedvolk, C. A.; Doornaar, M. B.; van der Vorst, M. M.; Bosman-Vermeeren, J. M.; Brand, R.; van der Heijden, A. J.; Schoof, P. H.; Hazekamp, M. G.

2001-01-01

The aim of the study was to investigate renal function and renal replacement therapy after cardiopulmonary bypass surgery in children. Patient characteristics (sex, age, diagnosis), operation type, and death were listed. The study was performed retrospectively using serum creatinine level before,

The Influence of Puff Characteristics, Nicotine Dependence, and Rate of Nicotine Metabolism on Daily Nicotine Exposure in African American Smokers.

Science.gov (United States)

Ross, Kathryn C; Dempsey, Delia A; St Helen, Gideon; Delucchi, Kevin; Benowitz, Neal L

2016-06-01

African American (AA) smokers experience greater tobacco-related disease burden than Whites, despite smoking fewer cigarettes per day (CPD). Understanding factors that influence daily nicotine intake in AA smokers is an important step toward decreasing tobacco-related health disparities. One factor of interest is smoking topography, or the study of puffing behavior. (i) to create a model using puff characteristics, nicotine dependence, and nicotine metabolism to predict daily nicotine exposure, and (ii) to compare puff characteristics and nicotine intake from two cigarettes smoked at different times to ensure the reliability of the puff characteristics included in our model. Sixty AA smokers smoked their preferred brand of cigarette at two time points through a topography device. Plasma nicotine, expired CO, and changes in subjective measures were measured before and after each cigarette. Total nicotine equivalents (TNE) was measured from 24-hour urine collected during ad libitum smoking. In a model predicting daily nicotine exposure, total puff volume, CPD, sex, and menthol status were significant predictors (R(2) = 0.44, P smokers. Cancer Epidemiol Biomarkers Prev; 25(6); 936-43. ©2016 AACR. ©2016 American Association for Cancer Research.

Modern iron replacement therapy: clinical and pathophysiological insights.

Science.gov (United States)

Girelli, Domenico; Ugolini, Sara; Busti, Fabiana; Marchi, Giacomo; Castagna, Annalisa

2018-01-01

Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era. In the meantime, advances in the pharmaceutical technologies are producing newer iron formulations aimed at minimizing the problems inherent with traditional approaches. The pharmacokinetic of oral and parenteral iron is substantially different, and diversities have become even clearer in light of the hepcidin master role in regulating systemic iron homeostasis. Here we review how iron therapy is changing because of such important advances in both pathophysiology and pharmacology.

Nicotine delivery to users from cigarettes and from different types of e-cigarettes.

Science.gov (United States)

Hajek, Peter; Przulj, Dunja; Phillips, Anna; Anderson, Rebecca; McRobbie, Hayden

2017-03-01

Delivering nicotine in the way smokers seek is likely to be the key factor in e-cigarette (EC) success in replacing cigarettes. We examined to what degree different types of EC mimic nicotine intake from cigarettes. Twelve participants ('dual users' of EC and cigarettes) used their own brand cigarette and nine different EC brands. Blood samples were taken at baseline and at 2-min intervals for 10 min and again at 30 min. Eleven smokers provided usable data. None of the EC matched cigarettes in nicotine delivery (C max  = 17.9 ng/ml, T max  = 4 min and AUC 0->30  = 315 ng/ml/min). The EC with 48 mg/ml nicotine generated the closest PK profile (C max  = 13.6 ng/ml, T max  = 4 min, AUC 0->30  = 245 ng/ml/min), followed by a third generation EC using 20 mg/ml nicotine (C max  = 11.9 ng/ml, T max  = 6 min, AUC 0->30  = 232 ng/ml/min), followed by the tank system using 20 mg/ml nicotine (C max  = 9.9 ng/ml, T max  = 6 min, AUC 0->30  = 201 ng/ml/min). Cig-a-like PK values were similar, ranging from C max 7.5 to 9.7 ng/ml, T max 4-6 min, and AUC 0->30 144 to 173 ng/ml/min. Moderate differences in e-liquid nicotine concentrations had little effect on nicotine delivery, e.g. the EC with 24 mg/ml cartridge had the same PK profile as ECs with 16 mg/ml cartridges. Using similar strength e-liquid, the tank EC provided significantly more nicotine than cig-a-like ECs. EC brands we tested do not deliver nicotine as efficiently as cigarettes, but newer EC products deliver nicotine more efficiently than cig-a-like brands. Moderate variations in nicotine content of e-liquid have little effect on nicotine delivery. Smokers who are finding cig-a-like EC unsatisfactory should be advised to try more advanced systems.

Percutaneous 17ß-estradiol replacement therapy in hypertensive postmenopausal women

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M.C. Osório-Wender

1997-09-01

Full Text Available The present study evaluated the short-term effects of percutaneous 17ß-estradiol on blood pressure, metabolic profile and hormonal levels in postmenopausal women with systemic arterial hypertension. After a wash-out period of 15 days, 10 hypertensive patients were treated with guanabenz acetate to control blood pressure, followed by 17ß-estradiol in the form of hydroalcoholic gel administered for 21 of 28 days of each cycle, for 3 cycles. Patients were evaluated before, during and 2 months after estrogen administration. Systolic and diastolic blood pressure or heart rate did not present any significant change in any patient when compared to those periods with the antihypertensive drug only (pretreatment period and 60 days after estrogen therapy was discontinued. Plasma biological markers of hepatic estrogenic action (plasma renin activity, antithrombin III, triglycerides, total cholesterol and lipoproteins also remained unchanged during the study. Hormone treatment was effective, as indicated by the relief of menopausal symptoms, a decrease in FSH levels (73.48 ± 27.21 to 35.09 ± 20.44 IU/l, P<0.05, and an increase in estradiol levels (15.06 ± 8.76 to 78.7 ± 44.6 pg/ml, P<0.05. There was no effect on LH (18.0 ± 9.5 to 14.05 ± 8.28 IU/l. Hormone levels returned to previous values after estrogen treatment was discontinued. The data indicate that short-term percutaneous 17ß-estradiol replacement therapy, at the dose used, seems to be a safe hormone therapy for hypertensive menopausal women. Nevertheless, a controlled, prospective, randomized clinical assay with a larger number of subjects is needed to definitely establish both the beneficial and harmful effects of hormone replacement therapy in hypertensive women

Moderation of Nicotine Effects on Covert Orienting of Attention Tasks by Poor Placebo Performance and Cue Validity

Science.gov (United States)

Gilbert, David G.; Rzetelny, Adam; Rabinovich, Norka E.

2016-01-01

Introduction and Rationale Given baseline-dependent effects of nicotine on other forms of attention, there is reason to believe that inconsistent findings for the effects of nicotine on attentional orienting may be partly due to individual differences in baseline (abstinence state) functioning. Individuals with low baseline attention may benefit more from nicotine replacement. Method The effects of nicotine as a function of baseline performance (bottom, middle, and top third of mean reaction times during placebo) were assessed in 52 habitual abstinent smokers (26 females/26 males) utilizing an arrow-cued covert orienting of attention task. Results Compared to a placebo patch, a 14 mg nicotine patch produced faster overall reaction times (RTs). In addition, individuals with slower RTs during the placebo condition benefitted more from nicotine on cued trials than did those who had shorter (faster) RTs during placebo. Nicotine also enhanced the validity effect (shorter RTs to validly vs. invalidly cued targets), but this nicotine benefit did not differ as a function of overall placebo-baseline performance. Conclusions These findings support the view that nicotine enhances cued spatial attentional orienting in individuals who have slower RTs during placebo (nicotine-free) conditions; however, baseline-dependent effects may not generalize to all aspects of spatial attention. These findings are consistent with findings indicating that nicotine’s effects vary as a function of task parameters rather than simple RT speeding or cognitive enhancement. PMID:27461547

T-type calcium channel antagonism decreases motivation for nicotine and blocks nicotine- and cue-induced reinstatement for a response previously reinforced with nicotine.

Science.gov (United States)

Uslaner, Jason M; Vardigan, Joshua D; Drott, Jason M; Uebele, Victor N; Renger, John J; Lee, Ariel; Li, Zhaoxia; Lê, A D; Hutson, Pete H

2010-10-15

Recent evidence suggests an involvement of T-type calcium channels in the effects of drugs of abuse. We examined the influence of the novel, potent, and selective T-type calcium channel antagonist [2-(4-cyclopropylphenyl)-N-((1R)-1-{5-[2,2,2-trifluoroethyl]oxo}pyridine-2-yl)ethyl]acetamide] (TTA-A2) (.3, 1, or 3 mg/kg) on motivation for nicotine, as measured by nicotine self-administration on a progressive ratio (PR) schedule, and nicotine- and cue-induced reinstatement for a response previously reinforced with nicotine delivery (n = 11 or 12 Long Evans rats/group). Furthermore, we examined the specificity of the TTA-A2 effects by characterizing its influence on PR responding for food (in the absence or presence of nicotine-potentiated responding), food- versus nicotine-induced cue-potentiated reinstatement for a response previously reinforced by food administration (n = 11 or 12 Wistar Hannover rats/group), and its ability to induce a conditioned place aversion. TTA-A2 dose-dependently decreased self-administration of nicotine on a PR schedule and the ability of both nicotine and a cue paired with nicotine to reinstate responding. The effects were specific for nicotine's incentive motivational properties, as TTA-A2 did not influence responding for food on a PR schedule but did attenuate the ability of nicotine to potentiate responding for food. Likewise, TTA-A2 did not alter food-induced cue-potentiated reinstatement for a response previously reinforced by food but did decrease nicotine-induced cue-potentiated reinstatement. Finally, TTA-A2 did not produce an aversive state, as indicated by a lack of ability to induce conditioned place aversion. These data suggest that T-type calcium channel antagonists have potential for alleviating nicotine addiction by selectively decreasing the incentive motivational properties of nicotine. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Nicotine delivery efficiency of first- and second-generation e-cigarettes and its impact on relief of craving during the acute phase of use.

Science.gov (United States)

Rüther, Tobias; Hagedorn, Dieter; Schiela, Konstantin; Schettgen, Thomas; Osiander-Fuchs, Helga; Schober, Wolfgang

2018-03-01

Knowledge about the change in blood nicotine concentrations during the first five minutes (acute phase) of e-cigarette vaping is important to determine whether the used product has a dependence potential or may be an efficient nicotine replacement product. To address this issue, we monitored blood nicotine levels during the acute phase in volunteers using disposable cigalikes (CLs) and a tank model (TM) and compared them with blood nicotine levels in subjects using a tobacco cigarette (TC). In parallel, heart rate changes were continually measured and withdrawal symptoms and craving were assessed with the Questionnaire on Smoking Urges before and immediately after the vaping/smoking sessions. Additionally, at the end of each session negative health effects were rated on a visual analog scale. After five minutes of e-cigarette or TC use, the mean nicotine plasma concentrations were as follows: CLs, 5.5ng/ml; TM, 9.3ng/ml; TC, 17.1ng/ml. Nicotine levels increased significantly faster in the first 4min of consuming a TC than with the CLs and the TM. The highest rate of increase in nicotine concentration was found with the TC (6.8ng/ml) and TM (2.3ng/ml) between the 1st and 2nd minute, whereas the CLs showed comparatively small changes in the amount delivered over the five minutes. Withdrawal and craving for smoking decreased with the TM by the same amount as with the TC, even though less nicotine was delivered to the blood and considerably fewer side effects occurred. The heart rate of TM users was also markedly lower than that of the TC users. Unlike CLs, TM e-cigarettes represent an effective source of nicotine and might be used as an alternative nicotine replacement product to aid smoking cessation. However, nicotine plasma levels observed in TM users after short-time vaping have also the potential to produce and sustain nicotine addiction. Copyright © 2017 Elsevier GmbH. All rights reserved.

Nicotine Withdrawal Disrupts Contextual Learning but Not Recall of Prior Contextual Associations: Implications for Nicotine Addiction

OpenAIRE

Portugal, George S.; Gould, Thomas J.

2008-01-01

Interactions between nicotine and learning could contribute to nicotine addiction. Although previous research indicates that nicotine withdrawal disrupts contextual learning, the effects of nicotine withdrawal on contextual memories acquired before withdrawal are unknown. The present study investigated whether nicotine withdrawal disrupted recall of prior contextual memories by examining the effects of nicotine withdrawal on recall of nicotine conditioned place preference (CPP) and contextual...

Thermochemical Properties of Nicotine Salts

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Riggs DM

2014-12-01

Full Text Available The thermal gravimetric analysis (TGA and differential scanning calorimetry (DSC results presented in this report clearly show that the thermal stability and the endothermic peak nicotine release temperatures are different for different nicotine salts and these temperatures appear to be linked to the general microstructural details of the salt itself. In addition, the peak nicotine release temperatures are highly dependent upon the sample size used. The heat of vaporization for neat (non-protonated nicotine is also sample-size dependent. The TGA data showed that the least stable of the salts tested at elevated temperatures was the liquid salt nicotine triacetate followed by the crystalline materials (e.g., nicotine gallate and finally, the amorphous salts (e.g., nicotine alginate. The DSC results revealed that the liquid and crystalline salts exhibit nicotine release endotherms that are strongly related to the sample weight being tested. The amorphous salts show nicotine endotherm peak temperatures that are nearly independent of the sample weight. The range of peak nicotine release temperatures varied depending upon the specific salts and the sample size from 83 oC to well over 200 oC. Based on these results, the evolution of nicotine from the nicotine salt should be expected to vary based on the composition of the salt, the details of its microstructure, and the amount of nicotine salt tested.

Hair cortisol content in patients with adrenal insufficiency on hydrocortisone replacement therapy.

Science.gov (United States)

Gow, Rachel; Koren, Gideon; Rieder, Michael; Van Uum, Stan

2011-06-01

Patients with adrenal insufficiency (AI) require life-long replacement therapy with exogenous glucocorticoids. Several studies have shown impaired subjective health status in these patients as well as increased morbidity and mortality risk, which may be caused by glucocorticoid over-replacement. As a measure of long-term cortisol exposure, the usefulness of hair cortisol analysis in patients receiving glucocorticoid replacement therapy was investigated. Hair samples, demographics, medical history and perceived stress scale questionnaires were collected from 93 patients across North America diagnosed with primary or secondary AI. Sixty-two household partners served as a control group. Cortisol was measured in the proximal 2 cm of hair, representing the most recent 2 months of exposure. A modified enzyme immunoassay was used for the measurement of cortisol. The male patients had significantly higher hair cortisol levels than the male controls (P cortisol content correlated significantly with glucocorticoid dose (r = 0·3, P cortisol content correlates with hydrocortisone (HC) dose in patients with AI. Our results suggest that some AI patients may be over-treated and hence may be at risk for the adverse effects of cortisol. Measurement of HC in hair may become a useful monitoring tool for long-term cortisol exposure in patients treated with glucocorticoids. © 2011 Blackwell Publishing Ltd.

Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation.

Science.gov (United States)

Lam, Sum; Patel, Priti N

2007-01-01

Tobacco smoking remains a significant health problem in the United States. It has been associated with staggering morbidity and mortality, specifically due to malignancies and cardiovascular disease. Smoking cessation can be difficult and frequently requires pharmacologic interventions in addition to nonpharmacologic measures. Previously available agents are nicotine replacement products and bupropion, which increased quit rates by about 2-fold compared with placebo. Varenicline is the first drug in a new class known as the selective alpha4beta2 nicotinic receptor partial agonists. In several randomized, double-blind, 52-week clinical trials involving healthy chronic smokers, varenicline demonstrated superiority to placebo and bupropion in terms of efficacy measures. Additionally, it improved tobacco withdrawal symptoms and reinforcing effects of smoking in relapsed patients. Patients should start therapy in combination with tobacco cessation counseling 1 week before quit date and continue the regimen for 12 weeks. The dose of varenicline should be titrated to minimize nausea. The recommended dosage is 0.5 mg once daily (QD) on days 1-3; titrate to 0.5 mg twice daily (BID) on days 4-7; and 1 mg BID starting on day 8. An additional 12-week maintenance therapy may be considered for those who achieve abstinence. The most common side effects are nausea (30%), insomnia (18%), headache (15%), abnormal dreams (13%), constipation (8%), and abdominal pain (7%). Overall, varenicline is a breakthrough in the management of tobacco addiction and has demonstrated good efficacy in motivated quitters. It also provides an option for smokers who cannot tolerate other pharmacologic interventions.

Postoperative radiation therapy after hip replacement in high-risk patients for development of heterotopic bone formation

International Nuclear Information System (INIS)

Hashem, R.; Rene, N.; Souhami, L.; Tanzer, M.; Evans, M.

2011-01-01

Purpose. - To report the results of postoperative radiation therapy in preventing the development of heterotopic bone formation after hip replacement surgery in high-risk patients. Patients and methods. - Between 1991 and 2007, 44 patients were preventively treated with postoperative RT after total hip replacement. In total, 47 hips were treated. All patients were considered at high risk for developing heterotopic bone formation. Most patients (63.5%) were treated because of a history of severe osteoarthritis or ankylosing spondylitis. All patients were treated with shaped parallel-opposed fields with a single fraction of 7 Gy using 6 or 18 MV photons. Most patients (94%) received radiation therapy within 72 hours postoperative and in only three patients radiation therapy was delivered after 72 hours post-surgery (5-8 days). Results. - Minimum follow-up was 1 year. There were 18 females and 26 males. Median age was 63 years (range: 18-80). Treatments were well tolerated and no acute toxicity was seen post-radiation therapy. Only one of the 47 hips (2%) developed heterotopic bone formation. This patient received postoperative radiation therapy to both hips but only developed heterotopic bone formation in one of them. None of the three patients treated beyond 72 hours failed. To date no late toxicity has been observed. Conclusion. - The use of postoperative radiation therapy was an effective and safe treatment in the prevention of heterotopic bone formation in a high-risk group of patients undergoing total hip replacement. (authors)

Nicotine enhances proliferation, migration, and radioresistance of human malignant glioma cells through EGFR activation

International Nuclear Information System (INIS)

Khalil, A.A.; Jameson, M.J.; Broaddus, W.C.; Lin, P.S.; Chung, T.D.

2013-01-01

It has been suggested that continued tobacco use during radiation therapy contributes to maintenance of neoplastic growth despite treatment with radiation. Nicotine is a cigarette component that is an established risk factor for many diseases, neoplastic and otherwise. The hypothesis of this work is that nicotine promotes the proliferation, migration, and radioresistance of human malignant glioma cells. The effect of nicotine on cellular proliferation, migration, signaling, and radiation sensitivity were evaluated for malignant glioma U87 and GBM12 cells by use of the AlamarBlue, scratch healing, and clonogenic survival assays. Signal transduction was assessed by immunoblotting for activated EGFR, extracellular regulated kinase (ERK), and AKT. At concentrations comparable with those found in chronic smokers, nicotine induced malignant glioma cell migration, growth, colony formation, and radioresistance. Nicotine increased phosphorylation of EGFR tyr992 , AKT ser473 , and ERK. These molecular effects were reduced by pharmacological inhibitors of EGFR, PI3K, and MEK. It was therefore concluded that nicotine stimulates the malignant behavior of glioma cells in vitro by activation of the EGFR and downstream AKT and ERK pathways. (author)

Systematic review of hormone replacement therapy in the infertile man

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Amr El Meliegy

2018-03-01

Full Text Available Objectives: To highlight alternative treatment options other than exogenous testosterone administration for hypogonadal men with concomitant infertility or who wish to preserve their fertility potential, as testosterone replacement therapy (TRT inhibits spermatogenesis, representing a problem for hypogonadal men of reproductive age. Materials and methods: We performed a comprehensive literature review for the years 1978–2017 via PubMed. Also abstracts from major urological/surgical conferences were reviewed. Review was consistent with the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA criteria. We used Medical Subject Heading terms for the search including ‘testosterone replacement therapy’ or ‘TRT’ and ‘male infertility’. Results: In all, 91 manuscripts were screened and the final number used for the review was 56. All studies included were performed in adults, were written in English and had an abstract available. Conclusions: Exogenous testosterone inhibits spermatogenesis. Hypogonadal men wanting to preserve their fertility and at the same time benefiting from TRT effects can be prescribed selective oestrogen receptor modulators or testosterone plus low-dose human chorionic gonadotrophin (hCG. Patients treated for infertility with hypogonadotrophic hypogonadism can be prescribed hCG alone at first followed by or in combination from the start with follicle-stimulating hormone preparations. Keywords: Gonadotrophins, Hypogonadism, Infertility, Systematic review, Testosterone therapy

Functional and molecular neuroimaging of menopause and hormone replacement therapy

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Erika eComasco

2014-12-01

Full Text Available The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. This review summarizes the findings of thirty-four studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri- and postmenopausal women treated with estrogen, or estrogen-progestagen replacement therapy. Seven studies using gonadotropin-releasing hormone agonist intervention as a model of hormonal withdrawal are also included. Cognitive paradigms are employed by the majority of studies evaluating the effect of unopposed estrogen or estrogen-progestagen treatment on peri- and postmenopausal women’s brain. In randomized-controlled trials, estrogen treatment enhances activation of fronto-cingulate regions during cognitive functioning, though in many cases no difference in cognitive performance was present. Progestagens seems to counteract the effects of estrogens. Findings on cognitive functioning during acute ovarian hormone withdrawal suggest a decrease in activation of the inferior frontal gyrus, thus essentially corroborating the findings in postmenopausal women. Studies of the cholinergic and serotonergic systems indicate these systems as biological mediators of hormonal influences on the brain. More, hormonal replacement appears to increase cerebral blood flow in cortical regions. On the other hand, studies on emotion processing in postmenopausal women are lacking. These results call for well-powered randomized-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal

Nicotine Dependence and Urinary Nicotine, Cotinine and Hydroxycotinine Levels in Daily Smokers

OpenAIRE

Van Overmeire, Ilse P. I.; De Smedt, Tom; Dendale, Paul; Nackaerts, Kristiaan; Vanacker, Hilde; Vanoeteren, Jan F. A.; Van Laethem, Danny M. G.; Van Loco, Joris; De Cremer, Koen A. J.

2016-01-01

Nicotine dependence and smoking frequency are critical factors for smoking cessation. The aims of this study are (1) to determine if nicotine dependence Fagerstrom Test for Nicotine Dependence (FTND) scores are associated with urinary levels of nicotine metabolites, (2) to assess the relationship of hydroxycotinine/cotinine ratio with FTND score and cigarettes smoked per day (CPD), and (3) to identify significant predictors of cigarettes per day among biomarker concentrations and individual F...

The effect of nicotine on reproduction and attachment of human gingival fibroblasts in vitro.

Science.gov (United States)

Peacock, M E; Sutherland, D E; Schuster, G S; Brennan, W A; O'Neal, R B; Strong, S L; Van Dyke, T E

1993-07-01

The ability of fibroblasts to reproduce and attach to teeth is of paramount importance in re-establishing the lost connective tissue attachment after periodontal therapy. This study examined the effect of nicotine, a major component of the particulate phase of tobacco smoke, on human gingival fibroblast (HGF) reproduction and attachment to tissue culture surfaces. Pooled HGF cultures made from explants of gingival biopsies were utilized between passages 5 and 10 and plated in 96-well plates at 1.0 x 10(4) cells per well. Cell numbers were determined using 3-(4,5-dimethylthiazol-2-y)-2,5-diphenyl tetrazolium bromide (MTT), which is a reflection of mitochondrial dehydrogenase activity. The concentrations of nicotine used were 0.025, 0.05, 0.1, 0.2, and 0.4 microM, the average serum concentration for a smoker being approximately 0.1 microM. The effect of continuous nicotine exposure on HGF reproduction was determined by incubating cell cultures and media containing nicotine for up to 48 hours. Residual toxicity was determined by preincubating cells with nicotine for 1 or 6 hours. HGF suspensions and increasing concentrations of nicotine were added together to determine the effect on attachment. Results showed an enhanced effect of nicotine on HGF attachment, with increasing numbers of cells attaching with increasing nicotine concentrations, compared to the control. Low concentrations of nicotine had a stimulatory effect on cell replication, while higher concentrations of nicotine appear to have no significant effect on HGF reproduction. The responses of cells to some concentrations of nicotine may persist after its removal.

CRISPR/Cas9 and mitochondrial gene replacement therapy: promising techniques and ethical considerations.

Science.gov (United States)

Fogleman, Sarah; Santana, Casey; Bishop, Casey; Miller, Alyssa; Capco, David G

2016-01-01

Thousands of mothers are at risk of transmitting mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for preventing and treating mitochondrial disease: mitochondrial replacement therapy, and CRISPR/Cas9. Mitochondrial replacement therapy has emerged as a promising tool that has the potential to prevent transmission in patients with higher mutant mitochondrial loads. This method is the subject of many ethical concerns due its use of a donor embryo to transplant the patient's nuclear DNA; however, it has ultimately been approved for use in the United Kingdom and was recently declared ethically permissible by the FDA. The leading-edge CRISPR/Cas9 technology exploits the principles of bacterial immune function to target and remove specific sequences of mutated DNA. This may have potential in treating individuals with disease caused by mutant mitochondrial DNA. As the technology progresses, it is important that the ethical considerations herein emerge and become more established. The purpose of this review is to discuss current research surrounding the procedure and efficacy of the techniques, compare the ethical concerns of each approach, and look into the future of mitochondrial gene replacement therapy.

Racial differences in the relationship between rate of nicotine metabolism and nicotine intake from cigarette smoking.

Science.gov (United States)

Ross, Kathryn C; Gubner, Noah R; Tyndale, Rachel F; Hawk, Larry W; Lerman, Caryn; George, Tony P; Cinciripini, Paul; Schnoll, Robert A; Benowitz, Neal L

2016-09-01

Rate of nicotine metabolism has been identified as an important factor influencing nicotine intake and can be estimated using the nicotine metabolite ratio (NMR), a validated biomarker of CYP2A6 enzyme activity. Individuals who metabolize nicotine faster (higher NMR) may alter their smoking behavior to titrate their nicotine intake in order to maintain similar levels of nicotine in the body compared to slower nicotine metabolizers. There are known racial differences in the rate of nicotine metabolism with African Americans on average having a slower rate of nicotine metabolism compared to Whites. The goal of this study was to determine if there are racial differences in the relationship between rate of nicotine metabolism and measures of nicotine intake assessed using multiple biomarkers of nicotine and tobacco smoke exposure. Using secondary analyses of the screening data collected in a recently completed clinical trial, treatment-seeking African American and White daily smokers (10 or more cigarettes per day) were grouped into NMR quartiles so that the races could be compared at the same NMR, even though the distribution of NMR within race differed. The results indicated that rate of nicotine metabolism was a more important factor influencing nicotine intake in White smokers. Specifically, Whites were more likely to titrate their nicotine intake based on the rate at which they metabolize nicotine. However, this relationship was not found in African Americans. Overall there was a greater step-down, linear type relationship between NMR groups and cotinine or cotinine/cigarette in African Americans, which is consistent with the idea that differences in blood cotinine levels between the African American NMR groups were primarily due to differences in CYP2A6 enzyme activity without titration of nicotine intake among faster nicotine metabolizers. Copyright © 2016 Elsevier Inc. All rights reserved.

Renal replacement therapy registries--time for a structured data quality evaluation programme

NARCIS (Netherlands)

Couchoud, Cécile; Lassalle, Mathilde; Cornet, Ronald; Jager, Kitty J.

2013-01-01

Registries in the area of renal replacement therapy (RRT) are intended to be a tool for epidemiological research, health care planning and improvement of quality of care. In this perspective, the value of a population-based RRT registry and its ability to achieve its goals rely heavily on the

Prepubertal Gynecomastia Due to Indirect Exposure to Nonformulary Bioidentical Hormonal Replacement Therapy: A Case Report.

Science.gov (United States)

De Pinho, Joao Correia; Aghajanova, Lusine; Herndon, Christopher N

2016-01-01

Gynecomastia is a disorder of the endocrine system characterized by an abnormal presence of a palpable unilateral or bilateral enlargement and proliferation of glandular ductal benign breast tissue in male individuals. This case discusses the medical implications of an unregulated, indirect exposure to nonformulary, bioidentical hormone replacement therapy in male children. An 8-year-old boy presented with prepubertal gynecomastia secondary to estrogen exposure from maternal use of bioidentical hormonal replacement therapy (the Wiley protocol). We review the literature on prepubertal gynecomastia secondary to exogenous estrogen exposure, evaluation, clinical surveillance of the pubertal development, and relevant short- and long-term implications. Indirect exposure to nonformulary hormonal replacement in our case report was an etiologic factor in the development of prepubertal gynecomastia. This novel estrogen exposure source has important implications in the differential diagnosis of prepubertal gynecomastia and potential adverse effects secondary to precocious hormonal exposure.

Chronic Nicotine Treatment During Adolescence Attenuates the Effects of Acute Nicotine in Adult Contextual Fear Learning.

Science.gov (United States)

Holliday, Erica D; Gould, Thomas J

2017-01-01

Adolescent onset of nicotine abuse is correlated with worse chances at successful abstinence in adulthood. One reason for this may be due to enduring learning deficits resulting from nicotine use during adolescence. Previous work has indicated that chronic nicotine administration beginning in late adolescence (PND38) caused learning deficits in contextual fear when tested in adulthood. The purpose of this study was to determine if chronic nicotine treatment during adolescence would alter sensitivity to nicotine's cognitive enhancing properties in adulthood. C57BL/6J mice received saline or chronic nicotine (12.6mg/kg/day) during adolescence (postnatal day 38) or adulthood (postnatal day 54) for a period of 12 days. Following a 30-day protracted abstinence, mice received either an acute injection of saline or nicotine (0.045, 0.18, and 0.36mg/kg) prior to training and testing a mouse model of contextual fear. It was found that chronic nicotine administration in adult mice did not alter sensitivity to acute nicotine following a protracted abstinence. In adolescent mice, chronic nicotine administration disrupted adult learning and decreased sensitivity to acute nicotine in adulthood as only the highest dose tested (0.36mg/kg) was able to enhance contextual fear learning. These results suggest that adolescent nicotine exposure impairs learning in adulthood, which could increase the risk for continued nicotine use in adulthood by requiring administration of higher doses of nicotine to reverse learning impairments caused by adolescent nicotine exposure. Results from this study add to the growing body of literature suggesting chronic nicotine exposure during adolescence leads to impaired learning in adulthood and demonstrates that nicotine exposure during adolescence attenuates the cognitive enhancing effects of acute nicotine in adulthood, which suggests altered cholinergic function. © The Author 2016. Published by Oxford University Press on behalf of the Society for

Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

OpenAIRE

Xue, Peng; Wang, Yan; Yang, Jie; Li, Yukun

2013-01-01

Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochr...

Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.

Science.gov (United States)

Briggs, Scott A; Hall, Brandon J; Wells, Corinne; Slade, Susan; Jaskowski, Paul; Morrison, Margaret; Rezvani, Amir H; Rose, Jed E; Levin, Edward D

2016-03-01

Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3β4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2C agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with the lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, an acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (pdextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self-administration replicating previous findings. Augmenting interactions were observed with

Stabilized incidence of diabetic patients referred for renal replacement therapy in Denmark

DEFF Research Database (Denmark)

Sørensen, V R; Hansen, P M; Heaf, J

2006-01-01

Despite an improvement in diabetes care during the last 20 years, the number of diabetic patients starting renal replacement therapy (RRT) has continued to increase in the Western world. The aim was to study the incidence of patients starting RRT in Denmark from 1990 to 2004. Data were obtained f...

Electronic Nicotine Delivery Systems.

Science.gov (United States)

Walley, Susan C; Jenssen, Brian P

2015-11-01

Electronic nicotine delivery systems (ENDS) are rapidly growing in popularity among youth. ENDS are handheld devices that produce an aerosolized mixture from a solution typically containing concentrated nicotine, flavoring chemicals, and propylene glycol to be inhaled by the user. ENDS are marketed under a variety of names, most commonly electronic cigarettes and e-cigarettes. In 2014, more youth reported using ENDS than any other tobacco product. ENDS pose health risks to both users and nonusers. Nicotine, the major psychoactive ingredient in ENDS solutions, is both highly addictive and toxic. In addition to nicotine, other toxicants, carcinogens, and metal particles have been detected in solutions and aerosols of ENDS. Nonusers are involuntarily exposed to the emissions of these devices with secondhand and thirdhand aerosol. The concentrated and often flavored nicotine in ENDS solutions poses a poisoning risk for young children. Reports of acute nicotine toxicity from US poison control centers have been increasing, with at least 1 child death reported from unintentional exposure to a nicotine-containing ENDS solution. With flavors, design, and marketing that appeal to youth, ENDS threaten to renormalize and glamorize nicotine and tobacco product use. There is a critical need for ENDS regulation, legislative action, and counter promotion to protect youth. ENDS have the potential to addict a new generation of youth to nicotine and reverse more than 50 years of progress in tobacco control. Copyright © 2015 by the American Academy of Pediatrics.

Cerebral magnetic resonance findings during enzyme replacement therapy in mucopolysaccharidosis

International Nuclear Information System (INIS)

Matsubara, Yoshiko; Miyazaki, Osamu; Nosaka, Shunsuke; Kosuga, Motomichi; Okuyama, Torayuki

2017-01-01

Although enzyme replacement therapy (ERT) is an effective treatment for mucopolysaccharidosis (MPS) types I, II, IVA and VI, its effectiveness in children with central nervous system (CNS) disorders is said to be poor because the blood-brain barrier cannot be penetrated by ERT drugs. To assess CNS involvement in mucopolysaccharidosis at the start of enzyme replacement therapy and to investigate the time course of ERT in the central nervous system. We performed brain MRI in 17 children and young adults who underwent ERT. The clinical severity was classified as attenuated or severe by a specialist pediatrician, based on the clinical symptoms and genotypes. At the start of ERT, we scored nine parameters using two- or three-point scales based on the severity of the disease revealed on MRI scans. After the start of ERT, we compared the initial and follow-up MRI scans, and classified the findings as no change, improved or worse. We then compared the results with the changes in clinical findings. At the start of ERT, comparison of the clinical symptoms and image scores revealed differences between severe and attenuated mucopolysaccharidosis. The scores in patients with severe MPS ranged from 9 to 16 (mean 12.2); for patients with attenuated MPS, they ranged from 2 to 11 (mean 6.4). Images of the four patients with severe MPS showed ventricular dilation and brain atrophy. Such findings were made in only 2 of 13 patients with attenuated MPS. The results after the start of ERT showed that 11/17 (65%) patients manifested improvement or no change. All five patients with MPS I experienced improvement in some regions. There were no new lesions. One patient with MPS II experienced worsening of his CNS symptoms, and his MRI findings revealed more severe ventricular dilation, brain atrophy and white matter lesions. Ventricular dilation and brain atrophy on imaging studies might represent useful markers in predicting the severity of mucopolysaccharidosis and worsening of CNS

Cerebral magnetic resonance findings during enzyme replacement therapy in mucopolysaccharidosis

Energy Technology Data Exchange (ETDEWEB)

Matsubara, Yoshiko [Division of Radiology, National Center for Child Health and Development, Tokyo (Japan); Hiroshima University, Department of Diagnostic Radiology, Hiroshima (Japan); Miyazaki, Osamu; Nosaka, Shunsuke [Division of Radiology, National Center for Child Health and Development, Tokyo (Japan); Kosuga, Motomichi [Division of Medical Genetics, National Center for Child Health and Development, Tokyo (Japan); Okuyama, Torayuki [Department of Clinical Laboratory Medicine, National Center for Child Health and Development, Tokyo (Japan)

2017-11-15

Although enzyme replacement therapy (ERT) is an effective treatment for mucopolysaccharidosis (MPS) types I, II, IVA and VI, its effectiveness in children with central nervous system (CNS) disorders is said to be poor because the blood-brain barrier cannot be penetrated by ERT drugs. To assess CNS involvement in mucopolysaccharidosis at the start of enzyme replacement therapy and to investigate the time course of ERT in the central nervous system. We performed brain MRI in 17 children and young adults who underwent ERT. The clinical severity was classified as attenuated or severe by a specialist pediatrician, based on the clinical symptoms and genotypes. At the start of ERT, we scored nine parameters using two- or three-point scales based on the severity of the disease revealed on MRI scans. After the start of ERT, we compared the initial and follow-up MRI scans, and classified the findings as no change, improved or worse. We then compared the results with the changes in clinical findings. At the start of ERT, comparison of the clinical symptoms and image scores revealed differences between severe and attenuated mucopolysaccharidosis. The scores in patients with severe MPS ranged from 9 to 16 (mean 12.2); for patients with attenuated MPS, they ranged from 2 to 11 (mean 6.4). Images of the four patients with severe MPS showed ventricular dilation and brain atrophy. Such findings were made in only 2 of 13 patients with attenuated MPS. The results after the start of ERT showed that 11/17 (65%) patients manifested improvement or no change. All five patients with MPS I experienced improvement in some regions. There were no new lesions. One patient with MPS II experienced worsening of his CNS symptoms, and his MRI findings revealed more severe ventricular dilation, brain atrophy and white matter lesions. Ventricular dilation and brain atrophy on imaging studies might represent useful markers in predicting the severity of mucopolysaccharidosis and worsening of CNS

Changes in arterial stiffness, carotid intima-media thickness, and epicardial fat after L-thyroxine replacement therapy in hypothyroidism.

Science.gov (United States)

del Busto-Mesa, Abdel; Cabrera-Rego, Julio Oscar; Carrero-Fernández, Lisván; Hernández-Roca, Cristina Victoria; González-Valdés, Jorge Luis; de la Rosa-Pazos, José Eduardo

2015-01-01

To assess the relationship between primary hypothyroidism and subclinical atherosclerosis and its potential changes with L-thyroxine replacement therapy. A prospective cohort study including 101 patients with primary hypothyroidism and 101 euthyroid patients as controls was conducted from July 2011 to December 2013. Clinical, anthropometrical, biochemical, and ultrasonographic parameters were assessed at baseline and after one year of L-thyroxine replacement therapy. At baseline, hypothyroid patients had significantly greater values of blood pressure, total cholesterol, VLDL cholesterol, left ventricular mass, epicardial fat, and carotid intima-media thickness as compared to controls. Total cholesterol, VLDL cholesterol, ventricular diastolic function, epicardial fat, carotid intima-media thickness, carotid local pulse wave velocity, pressure strain elastic modulus, and β arterial stiffness index showed a significant and positive correlation with TSH levels. After one year of replacement therapy, patients with hypothyroidism showed changes in total cholesterol, VLDL cholesterol, TSH, carotid intima-media thickness, and arterial stiffness parameters. Primary hypothyroidism is characterized by an increased cardiovascular risk. In these patients, L-thyroxine replacement therapy for one year is related to decreased dyslipidemia and improvement in markers of subclinical carotid atherosclerosis. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Brain nicotinic acetylcholine receptors are involved in stress-induced potentiation of nicotine reward in rats.

Science.gov (United States)

Javadi, Parastoo; Rezayof, Ameneh; Sardari, Maryam; Ghasemzadeh, Zahra

2017-07-01

The aim of the present study was to examine the possible role of nicotinic acetylcholine receptors of the dorsal hippocampus (CA1 regions), the medial prefrontal cortex or the basolateral amygdala in the effect of acute or sub-chronic stress on nicotine-induced conditioned place preference. Our results indicated that subcutaneous administration of nicotine (0.2 mg/kg) induced significant conditioned place preference. Exposure to acute or sub-chronic elevated platform stress potentiated the response of an ineffective dose of nicotine. Pre-conditioning intra-CA1 (0.5-4 µg/rat) or intra-medial prefrontal cortex (0.2-0.3 µg/rat) microinjection of mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist) reversed acute stress-induced potentiation of nicotine reward as measured in the conditioned place preference paradigm. By contrast, pre-conditioning intra-basolateral amygdala microinjection of mecamylamine (4 µg/rat) potentiated the effects of acute stress on nicotine reward. Our findings also showed that intra-CA1 or intra-medial prefrontal cortex, but not intra-basolateral amygdala, microinjection of mecamylamine (4 µg/rat) prevented the effect of sub-chronic stress on nicotine reward. These findings suggest that exposure to elevated platform stress potentiates the rewarding effect of nicotine which may be associated with the involvement of nicotinic acetylcholine receptors. It seems that there is a different contribution of the basolateral amygdala, the medial prefrontal cortex or the CA1 nicotinic acetylcholine receptors in stress-induced potentiation of nicotine-induced conditioned place preference.

Partial resolution of bone lesions. A child with severe combined immunodeficiency disease and adenosine deaminase deficiency after enzyme-replacement therapy

International Nuclear Information System (INIS)

Yulish, B.S.; Stern, R.C.; Polmar, S.H.

1980-01-01

A child with severe combined immunodeficiency disease and adenosine deaminase deficiency, with characteristic bone dysplasia, was treated with transfusions of frozen irradiated RBCs as a means of enzyme replacement. This therapy resulted in restoration of immunologic competence and partial resolution of the bone lesions. Although the natural history of these lesions without therapy is not known, enzyme-replacement therapy may have played a role in the resolution of this patient's bone lesions

Nicotine Dependence and Urinary Nicotine, Cotinine and Hydroxycotinine Levels in Daily Smokers.

Science.gov (United States)

Van Overmeire, Ilse P I; De Smedt, Tom; Dendale, Paul; Nackaerts, Kristiaan; Vanacker, Hilde; Vanoeteren, Jan F A; Van Laethem, Danny M G; Van Loco, Joris; De Cremer, Koen A J

2016-09-01

Nicotine dependence and smoking frequency are critical factors for smoking cessation. The aims of this study are (1) to determine if nicotine dependence Fagerström Test for Nicotine Dependence (FTND) scores are associated with urinary levels of nicotine metabolites, (2) to assess the relationship of hydroxycotinine/cotinine ratio with FTND score and cigarettes smoked per day (CPD), and (3) to identify significant predictors of cigarettes per day among biomarker concentrations and individual FTND items. Urine samples and questionnaire data of 239 daily smokers were obtained. Nicotine, cotinine and hydroxycotinine urinary levels were determined by UPLC MS/MS.Multiple linear regression models were developed to explore the relationship between nicotine, cotinine, hydroxycotinine levels and separate FTND scores (for all six items). We found significant correlations between the different urinary biomarker concentrations, and the FTND score. The time before the first cigarette after waking (TTFC) was significantly associated with the nicotine, cotinine and hydroxycotinine concentrations. No association was found between the ratio of hydroxycotinine to cotinine and either the FTND or the CPD. A model including four FTND questions, sex, age, and the cotinine concentration, accounted for 45% of the variance of CPD. There are significant relationships between urinary levels of nicotine, cotinine, and hydroxycotinine and the FTND score. Especially the FTND question about TTFC is relevant for explaining the biomarker concentrations. CPD (below 15) was significantly explained by four FTND dependence items and urinary cotinine levels in a regression model. We investigated associations between urinary levels of nicotine, cotinine, and hydroxycotinine in daily smokers and the FTND scores for nicotine dependence. We did not find association between the hydroxycotinine/cotinine ratio and CPD. We developed a model that explains the cigarettes smoked daily (CPD) in a group of light

Comparison of survival analysis and palliative care involvement in patients aged over 70 years choosing conservative management or renal replacement therapy in advanced chronic kidney disease.

Science.gov (United States)

Hussain, Jamilla A; Mooney, Andrew; Russon, Lynne

2013-10-01

There are limited data on the outcomes of elderly patients with chronic kidney disease undergoing renal replacement therapy or conservative management. We aimed to compare survival, hospital admissions and palliative care access of patients aged over 70 years with chronic kidney disease stage 5 according to whether they chose renal replacement therapy or conservative management. Retrospective observational study. Patients aged over 70 years attending pre-dialysis clinic. In total, 172 patients chose conservative management and 269 chose renal replacement therapy. The renal replacement therapy group survived for longer when survival was taken from the time estimated glomerular filtration rate management, in patients older than 80 years or with a World Health Organization performance score of 3 or more. There was also a significant reduction in the effect of renal replacement therapy on survival in patients with high Charlson's Comorbidity Index scores. The relative risk of an acute hospital admission (renal replacement therapy vs conservative management) was 1.6 (p management patients died in hospital, compared to 69% undergoing renal replacement therapy (Renal Registry data). Seventy-six percent of the conservative management group accessed community palliative care services compared to 0% of renal replacement therapy patients. For patients aged over 80 years, with a poor performance status or high co-morbidity scores, the survival advantage of renal replacement therapy over conservative management was lost at all levels of disease severity. Those accessing a conservative management pathway had greater access to palliative care services and were less likely to be admitted to or die in hospital.

GH replacement therapy and second neoplasms in adult survivors of childhood cancer: a retrospective study from a single institution.

Science.gov (United States)

Brignardello, E; Felicetti, F; Castiglione, A; Fortunati, N; Matarazzo, P; Biasin, E; Sacerdote, C; Ricardi, U; Fagioli, F; Corrias, A; Arvat, E

2015-02-01

Growth hormone deficiency (GHD) is the most common endocrine late effect observed in childhood cancer survivors (CCS) previously submitted to cranial irradiation. Radiation therapy can also increase the risk of second neoplasms (SNs). Since in previous studies GH replacement therapy was associated with increased incidence of neoplasia, we explored the association between SNs and GH replacement therapy in a cohort of CCS with GHD. Within the clinical cohort of CCS referred to the Transition Unit for Childhood Cancer Survivors of Turin between November 2001 and December 2012, we considered all patients who developed GHD as a consequence of cancer therapies. GHD was always diagnosed in childhood. To evaluate the quality of data, our cohort was linked to the Childhood Cancer Registry of Piedmont. GHD was diagnosed in 49 out of 310 CCS included in our clinical cohort. At least one SN was diagnosed in 14 patients, meningioma and basal cell carcinoma being the most common SNs. The cumulative incidence of SNs was similar in GH-treated and -untreated patients (8 SNs out of 26 GH-treated and 6 out of 23 GH-untreated patients; p = 0.331). Age, sex and paediatric cancer type had no impact on SNs development. In our CCS, GH replacement therapy does not seem to increase the risk of SNs. Anyway, independently from replacement therapy, in these patients we observed an elevated risk of SNs, possibly related to previous radiation therapy, which suggests the need of a close long-term follow-up.

History of renal replacement therapy in Baltic countries.

Science.gov (United States)

Kuzminskis, Vytautas; Rosenberg, Mai; Cernevskis, Harijs; Bumblyte, Inga Arūne

2011-01-01

The history of renal replacement therapy (RRT) in the 3 Baltic countries can be divided into 2 periods: the Soviet period (1944-1991) with strict central regulation and isolation from Western countries, and the period of independence (1991 to the present). Between 1963 and 1967, hemodialysis was used in cases of acute kidney injury and later in chronic renal failure, but only for patients suitable for kidney transplantation. The first renal transplant was performed in 1968, in Tartu, Estonia, and shortly thereafter, in Lithuania and Latvia. During the period of independence, development of RRT has been extremely rapid, and now this field of the health system has no major differences from that in other developed countries.

Cost-effectiveness of enzyme replacement therapy with alglucosidase alfa in classic-infantile patients with Pompe disease

NARCIS (Netherlands)

T.A. Kanters (Tim A.); I Hoogenboom-Plug (Iris); M.P.M.H. Rutten-van Mölken (Maureen); W.K. Redekop (Ken); A.T. van der Ploeg (Ans); L. van Hakkaart-van Roijen (Leona)

2014-01-01

textabstractBackground: Infantile Pompe disease is a rare metabolic disease. Patients generally do not survive the first year of life. Enzyme replacement therapy (ERT) has proven to have substantial effects on survival in infantile Pompe disease. However, the costs of therapy are very high. In this

Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy

DEFF Research Database (Denmark)

Sørensen, M B; Rosenfalck, A M; Højgaard, L

2001-01-01

OBJECTIVE: Menopause is linked to an increase in fat mass and a decrease in lean mass exceeding age-related changes, possibly related to reduced output of ovarian steroids. In this study we examined the effect of combined postmenopausal hormone replacement therapy (HRT) on the total and regional ......, which in turn, prevents disease in the elderly....

Effect of long-term Hormone Replacement Therapy on Plasma Homocysteine in Postmenopausal Women

DEFF Research Database (Denmark)

Madsen, Jonna S; Kristensen, Søren R; Klitgaard, Niels A

2002-01-01

hormone replacement therapy had significantly lower total homocysteine concentrations than women in the control group; median total homocysteine values were 8.6 micromol/L and 9.7 micromol/L, respectively, in a per-protocol analysis (P =.02). The effect was comparable in all methylenetetrahydrofolate...

Trends in Renal Replacement Therapy in Bosnia and Herzegovina 2002-2008

Directory of Open Access Journals (Sweden)

Halima Resić

2010-04-01

Full Text Available Renal Registry (RR of Bosnia and Herzegovina was established in 2002, with aim to follow up the trends of Renal Replacement Therapy in Bosnia and Herzegovina. The prevalence of Renal Replacement Therapy (RRT in Bosnia and Herzegovina is rising steadily. One reason for this is an increasing number of patients starting RRT. The aim is to present the epidemiology and treatment of all aspects of RRT in Bosnia and Herzegovina in period 2002-2008. Centre-related and patient-related questionnaires were sent to all 25 dialysis centres in Bosnia and Herzegovina. The demographic data, prevalence and incidence, type of renal replacement therapy, cause of ESRD, erythropoietin administration, cause of death, and type of vascular access were obtained from the questionnaires. Collected data were analysed using SPSS statistics. The number of patients treated by Renal Replacement Therapy (RRT increased steadily from 1,531 patients in 2002 to the 2,206 at the 2008 (43%. The prevalence has increased from 399 pmp in 2002 to 696 pmp. in 2008. Incidence (new patients in 2002 was 110 pmp and incidence rate in 2008 was 163, and there were 249 new patients (day 1. The mean age for new patients increased from 60 years in 2002 to 63.5 years in 2008 and the population over 75 years rate from 8.79% to 11.3%. Most ESRD patients in Bosnia and Herzegovina are undergoing intermittent hemodialysis (92%, while some patients (8% are treated by peritoneal dialysis and transplantation. The most significant cause of ESRD in 2008 was chronic glomerulonephritis (421 patients, 19.2%, followed by pyelonephritis (414 patients, 18.9%, BEN (14.7% and Diabetes mellitus (12.2%. Hepatitis B and C virus infections had 397 (16.3% patients, out of them 22 had both type of infections and 98 patients had B type infection. Only 10.5% of patients were tested on MRSA and 3 patients were positive on MRSA. There were no HIV-positive patients on RRT. The most common type of vascular access was AV fistula

Faster Blood Flow Rate Does Not Improve Circuit Life in Continuous Renal Replacement Therapy: A Randomized Controlled Trial.

Science.gov (United States)

Fealy, Nigel; Aitken, Leanne; du Toit, Eugene; Lo, Serigne; Baldwin, Ian

2017-10-01

To determine whether blood flow rate influences circuit life in continuous renal replacement therapy. Prospective randomized controlled trial. Single center tertiary level ICU. Critically ill adults requiring continuous renal replacement therapy. Patients were randomized to receive one of two blood flow rates: 150 or 250 mL/min. The primary outcome was circuit life measured in hours. Circuit and patient data were collected until each circuit clotted or was ceased electively for nonclotting reasons. Data for clotted circuits are presented as median (interquartile range) and compared using the Mann-Whitney U test. Survival probability for clotted circuits was compared using log-rank test. Circuit clotting data were analyzed for repeated events using hazards ratio. One hundred patients were randomized with 96 completing the study (150 mL/min, n = 49; 250 mL/min, n = 47) using 462 circuits (245 run at 150 mL/min and 217 run at 250 mL/min). Median circuit life for first circuit (clotted) was similar for both groups (150 mL/min: 9.1 hr [5.5-26 hr] vs 10 hr [4.2-17 hr]; p = 0.37). Continuous renal replacement therapy using blood flow rate set at 250 mL/min was not more likely to cause clotting compared with 150 mL/min (hazards ratio, 1.00 [0.60-1.69]; p = 0.68). Gender, body mass index, weight, vascular access type, length, site, and mode of continuous renal replacement therapy or international normalized ratio had no effect on clotting risk. Continuous renal replacement therapy without anticoagulation was more likely to cause clotting compared with use of heparin strategies (hazards ratio, 1.62; p = 0.003). Longer activated partial thromboplastin time (hazards ratio, 0.98; p = 0.002) and decreased platelet count (hazards ratio, 1.19; p = 0.03) were associated with a reduced likelihood of circuit clotting. There was no difference in circuit life whether using blood flow rates of 250 or 150 mL/min during continuous renal replacement therapy.

From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

Science.gov (United States)

Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

2005-05-01

Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

Does the number of free nicotine patches given to smokers calling a quitline influence quit rates: results from a quasi-experimental study

Directory of Open Access Journals (Sweden)

Mahoney Martin

2010-04-01

Full Text Available Abstract Background The offer of free nicotine replacement therapy (NRT can be a cost-effective marketing strategy to induce smokers to call a telephone quitline for quitting assistance. However, the most cost-effective supply of free NRT to provide to smokers who call a quitline remains unknown. This study tests the hypothesis that smokers who call a telephone quitline and are given more free nicotine patches would report higher quit rates upon follow-up 12 months later. Methods A quasi-experimental design was used to assess nicotine patch usage patterns and quit rates among five groups of smokers who called the New York State Smokers' Quitline (NYSSQL between April 2003 and May 2006 and were mailed 2-, 4-, 6- or 8-week supplies of free nicotine patches. The study population included 2,442 adult (aged 18 years or older current daily smokers of 10 or more cigarettes per day, who were willing to make a quit attempt, and reported no contraindications for using the nicotine patch. Outcome variables assessed included the percentage of smokers who reported that they had not smoked for at least 7-days at the time of a 12 months telephone follow-up survey, sustained quitting, delayed quitting and nicotine patch use. Results Quit rates measured at 12 months were higher for smokers in the groups who received either 2, 6, or 8 weeks of free patches. The lowest quit rate was observed among the group of Medicaid/uninsured smokers who were eligible to receive up to six weeks of free patches. The quit rate for the 4-week supply group did not differ significantly from the 6-week or 8-week groups. These patterns remained similar in an intent-to-treat analysis of 12-month quit rates and in an analysis of sustained quitting. Conclusion No clear cut dose response relationship was observed between the number of free nicotine patches sent to smokers and smoking outcomes. Baseline diferences in the characteristics of the groups compared could account for the null

Characteristics and survival of young adults who started renal replacement therapy during childhood

NARCIS (Netherlands)

Kramer, Anneke; Stel, Vianda S.; Tizard, Jane; Verrina, Enrico; Rönnholm, Kai; Pálsson, Runólfur; Maxwell, Heather; Jager, Kitty J.

2009-01-01

BACKGROUND: Little is known about the group of children on renal replacement therapy (RRT) who reach the age of 18 years and are transferred from paediatric to adult nephrology services. The aim of this study was to describe patient demographics, primary renal diseases, treatment history and

Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with turner syndrome: a systematic review and meta-analysis.

Science.gov (United States)

Cintron, Dahima; Rodriguez-Gutierrez, Rene; Serrano, Valentina; Latortue-Albino, Paula; Erwin, Patricia J; Murad, Mohammad Hassan

2017-02-01

Patients with Turner syndrome have adverse bone and cardiovascular outcomes from chronic estrogen deficiency. Hence, long-term estrogen replacement therapy is the cornerstone treatment. The estimates of its effect and optimal use, however, remain uncertain. We aimed to summarize the benefits and harms of estrogen replacement therapy on bone, cardiovascular, vasomotor and quality of life outcomes in patients with Turner syndrome. A comprehensive search of four databases was performed from inception through January 2016. Randomized clinical trials and observational cohort studies studying the effect of estrogen replacement therapy in patients with Turner syndrome under the age of 40 were included. Independently and in duplicate reviewers selected studies, extracted data and assessed risk of bias. Subgroup analyses were based on route of administration and type of estrogen formulation. Twenty-five studies at moderate to high risk of bias (12 randomized trials, 13 cohort studies) with 771 patients were included. Using random-effects models, estrogen replacement therapy showed an increase in bone mineral density [weighted mean change from baseline 0.09 g/cm2 (0.04-0.14)] that differed by type of estrogen but not route of administration. Oral estrogen replacement therapy showed a higher increase in high density lipoprotein cholesterol levels when compared to transdermal [weighted mean difference 9.33 mg/dl (4.82-13.85)] with no significant effect on other lipid fractions. The current evidence suggests possible benefit of estrogen replacement therapy on bone mineral density and high density lipoprotein cholesterol. Whether this improvement translates into changes in patient important outcomes (cardiovascular events or fractures) remains uncertain. Larger randomized clinical trials with direct comparisons on patient important outcomes are necessary.

Electronic cigarettes and nicotine clinical pharmacology.

Science.gov (United States)

Schroeder, Megan J; Hoffman, Allison C

2014-05-01

To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products' ability to support and maintain nicotine dependence. Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products' impact on public health.

Electronic cigarettes and nicotine clinical pharmacology

Science.gov (United States)

Schroeder, Megan J; Hoffman, Allison C

2014-01-01

Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Results Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products’ ability to support and maintain nicotine dependence. Conclusions Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products’ impact on public health. PMID:24732160

Delay in onset of metabolic alkalosis during regional citrate anti-coagulation in continous renal replacement therapy with calcium-free replacement solution

Directory of Open Access Journals (Sweden)

See Kay

2009-01-01

Full Text Available Regional citrate anti-coagulation for continuous renal replacement therapy chelates calcium to produce the anti- coagulation effect. We hypothesise that a calcium-free replacement solution will require less citrate and produce fewer metabolic side effects. Fifty patients, in a Medical Intensive Care Unit of a tertiary teaching hospital (25 in each group, received continuous venovenous hemofiltration using either calcium-containing or calcium-free replacement solutions. Both groups had no significant differences in filter life, metabolic alkalosis, hypernatremia, hypocalcemia, and hypercalcemia. However, patients using calcium-containing solution developed metabolic alkalosis earlier, compared to patients using calcium-free solution (mean 24.6 hours,CI 0.8-48.4 vs. 37.2 hours, CI 9.4-65, P = 0.020. When calcium-containing replacement solution was used, more citrate was required (mean 280ml/h, CI 227.2-332.8 vs. 265ml/h, CI 203.4-326.6, P = 0.069, but less calcium was infused (mean 21.2 ml/h, CI 1.2-21.2 vs 51.6ml/h, CI 26.8-76.4, P ≤ 0.0001.

Decreased sensitivity to nicotine-induced seizures as a consequence of nicotine pretreatment in long-sleep and short-sleep mice.

Science.gov (United States)

de Fiebre, C M; Collins, A C

1988-01-01

Male and female long-sleep (LS) and short-sleep (SS) mice were pretreated with a subseizure-producing dose of nicotine (2.0 mg/kg) 7.5, 15 and 30 minutes prior to challenge with seizure-producing doses of this drug. Nicotine pretreated animals were less susceptible to nicotine-induced seizures than were saline pretreated animals. The latency to seizure following nicotine challenge was greater in nicotine pretreated animals than in saline controls. Nicotine pretreated LS mice show a greater decrease in nicotine-induced seizure susceptibility than do nicotine pretreated SS mice. This decrease in seizure susceptibility is consistent with induction of nicotinic receptor desensitization via nicotine pretreatment. It is hypothesized that LS and SS mice might differ in sensitivity to nicotine in part because they differ in baseline levels of desensitized versus functional nicotinic receptors.

Liquid L-thyroxine versus tablet L-thyroxine in patients on L- thyroxine replacement or suppressive therapy: a meta-analysis.

Science.gov (United States)

Laurent, Irakoze; Tang, Siying; Astère, Manirakiza; Wang, Kan Ran; Deng, Shuhua; Xiao, Ling; Li, Qi Fu

2018-03-23

To compare the effectiveness of liquid L-T4 (L-thyroxine) and tablet L-T4 in patients on L-T4 replacement or suppressive therapy. The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to identify relevant articles. All prospective or randomized controlled studies (RCTs) comparing liquid L-T4 and tablet L-T4 in patients on L-T4 replacement or suppressive therapy were included in the analysis. Overall, the initial search of the four databases identified 1278 published studies; of these, eight studies were ultimately included in the meta-analysis. TSH (thyroid stimulating hormone) levels were significantly suppressed in patients on liquid L-T4 compared with those on tablet L-T4, in patients on L-T4 suppressive therapy with L-T4 malabsorption (Mean Difference (MD) = -2.26, 95% Confidence Interval (CI): -3.59, -0.93; P = 0.0009)). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 suppressive therapy without malabsorption (MD = 0.08, 95% CI: -0.31, 0.47; P = 0.69). TSH levels were significantly normalized in patients on liquid L-T4 compared with those on tablet L-T4, in Patients on L-T4 replacement therapy with L-T4 malabsorption (MD = -3.20, 95% CI: -5.08, -1.32; P = 0.0009). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 replacement therapy without malabsorption (MD = 0.91, 95% CI: -0.03, 1.86; P = 0.06). Liquid L-T4 is more efficient than tablet L-T4 in patients on L-T4 replacement or suppressive therapy with malabsorption. No significant differences were observed in patients without malabsorption. Further studies should be conducted to verify these findings.

Hearing loss in adult patients with Fabry disease treated with enzyme replacement therapy

NARCIS (Netherlands)

Suntjens, Eefje B.; Smid, Bouwien E.; Biegstraaten, Marieke; Dreschler, Wouter A.; Hollak, Carla E. M.; Linthorst, Gabor E.

2015-01-01

Data on prevalence, natural history, and effect of enzyme replacement therapy (ERT) on hearing loss (HL) in Fabry disease (FD) are scarce. This is a retrospective study with cross-sectional and longitudinal analyses. Low and high-frequency HL in the Dutch FD cohort was studied in four groups:

Pancreatic Enzyme Therapy and Coefficient of Fat Absorption in Children and AdolReplacement escents With Cystic Fibrosis

NARCIS (Netherlands)

Woestenenk, Janna W; van der Ent, Cornelis K.; Houwen, Roderick H J; van der Ent, CK

Objectives: Pancreatic enzyme replacement therapy (PERT) is the proven therapy to substantially reduce fat malabsorption in patients with cystic fibrosis (CF). Few details of the daily practice regarding PERT and the resulting coefficient of fat absorption (CFA) are known. We therefore recorded the

Early identification of risk factors for refractory secondary hyperparathyroidism in patients with long-term renal replacement therapy

NARCIS (Netherlands)

Jorna, Francisca Hillegonda; Tobe, TJM; Huisman, RM; de Jong, PE; Plukker, JTM; Stegeman, CA

Background. Secondary hyperparathyroidism can complicate renal replacement therapy (RRT) in patients with end-stage renal disease. Current medical therapies often result in hypercalcaemia and fail to correct hyperparathyroidism, but might be more effective at an early stage of disease. The aim of

Sympathomimetic Effects of Acute E-Cigarette Use: Role of Nicotine and Non-Nicotine Constituents.

Science.gov (United States)

Moheimani, Roya S; Bhetraratana, May; Peters, Kacey M; Yang, Benjamin K; Yin, Fen; Gornbein, Jeffrey; Araujo, Jesus A; Middlekauff, Holly R

2017-09-20

Chronic electronic (e) cigarette users have increased resting cardiac sympathetic nerve activity and increased susceptibility to oxidative stress. The purpose of the present study is to determine the role of nicotine versus non-nicotine constituents in e-cigarette emissions in causing these pathologies in otherwise healthy humans. Thirty-three healthy volunteers who were not current e-cigarette or tobacco cigarette smokers were studied. On different days, each participant used an e-cigarette with nicotine, an e-cigarette without nicotine, or a sham control. Cardiac sympathetic nerve activity was determined by heart rate variability, and susceptibility to oxidative stress was determined by plasma paraoxonase activity. Following exposure to the e-cigarette with nicotine, but not to the e-cigarette without nicotine or the sham control, there was a significant and marked shift in cardiac sympathovagal balance towards sympathetic predominance. The decrease in high-frequency component and the increases in the low-frequency component and the low-frequency to high-frequency ratio were significantly greater following exposure to the e-cigarette with nicotine compared with exposure to the e-cigarette without nicotine or to sham control. Oxidative stress, as estimated by plasma paraoxonase, did not increase following any of the 3 exposures. The acute sympathomimetic effect of e-cigarettes is attributable to the inhaled nicotine, not to non-nicotine constituents in e-cigarette aerosol, recapitulating the same heart rate variability pattern associated with increased cardiac risk in multiple populations with and without known cardiac disease. Evidence of oxidative stress, as estimated by plasma paraoxonase activity, was not uncovered following acute e-cigarette exposure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Kefir protective effects against nicotine cessation-induced anxiety and cognition impairments in rats.

Science.gov (United States)

Noori, Negin; Bangash, Mohammad Yasan; Motaghinejad, Majid; Hosseini, Pantea; Noudoost, Behshad

2014-01-01

Nicotine as one of the potent psychostimulant drugs is characterized by its parasympathomimetic activity. Upon the abrupt discontinuation of nicotine intake, a number of symptoms such as anxiety, depression and cognition impairment develop. Kefir as a food supplement is rich in tryptophan. In this study, we have evaluated the effects of Kefir on nicotine cessation-induced anxiety, depression and cognition impairment. Forty adult male rats were divided into four groups. All the groups received 6 mg/kg/day of nicotine for 17 days and then the negative control groups got 5 mg/kg/day of normal saline. The positive control groups were given 40 mg/kg/day of Sertraline HCl for 7 days. The group treated with Cow Milk Kefir (CMK) and Soy Milk Kefir (SMK) received 5 mg/kg/day for 7 days. On the 25(th) day, Elevated Plus Maze (EPM), Open Field Test (OFT) and Forced Swim Test (FST) were used to investigate anxiety and depression. In addition, Moris Water Maze was applied to evaluate learning and memory in the animals between the 20(th) and 25(th) days. The results showed that administration of CMK, SMK and Sertraline had higher anti-depression and anxiolytic effects on nicotine withdrawal-induced depression and anxiety in rats (P Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols.

Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease

DEFF Research Database (Denmark)

Biegstraaten, Marieke; Arngrímsson, Reynir; Barbey, Frederic

2015-01-01

INTRODUCTION: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed ...

'Real-world' compensatory behaviour with low nicotine concentration e-liquid: subjective effects and nicotine, acrolein and formaldehyde exposure.

Science.gov (United States)

Dawkins, Lynne; Cox, Sharon; Goniewicz, Maciej; McRobbie, Hayden; Kimber, Catherine; Doig, Mira; Kośmider, Leon

2018-06-07

To compare the effects of i) high versus low nicotine concentration e-liquid, ii) fixed versus adjustable power and iii) the interaction between the two on: a) vaping behaviour, b) subjective effects, c) nicotine intake, and d) exposure to acrolein and formaldehyde in e-cigarette users vaping in their everyday setting. Counterbalanced, repeated measures with four conditions: i) low nicotine (6 mg/mL)/fixed power; ii) low nicotine/adjustable power; iii) high nicotine (18 mg/mL)/fixed power; iv) high nicotine/adjustable power. London and the South East, England. Twenty experienced e-cigarette users (recruited between September 2016 and February 2017) vaped ad libitum using an eVic Supreme™ with a 'Nautilus Aspire' tank over four weeks (one week per condition). Puffing patterns (daily puff number [PN], puff duration [PD], inter-puff interval [IPI]), mL of e-liquid consumed, changes to power (where permitted), and subjective effects (urge to vape, nicotine withdrawal symptoms) were measured in each condition. Nicotine intake was measured via salivary cotinine. 3-hydroxypropylmercapturic acid (3-HPMA), a metabolite of the toxicant acrolein, and formate, a metabolite of the carcinogen formaldehyde, were measured in urine. There was a significant nicotine concentration x power interaction for PD (p<0.01). PD was longer with low nicotine/fixed power compared with i) high nicotine/fixed power (p< 0.001 and ii) low nicotine/adjustable power (p< 0.01). PN and liquid consumed were higher in the low versus high nicotine condition (main effect of nicotine, p<0.05). Urge to vape and withdrawal symptoms were lower, and nicotine intake was higher, in the high nicotine condition (main effects of nicotine: p<0.01). Whilst acrolein levels did not differ, there was a significant nicotine x power interaction for formaldehyde (p<0.05). Use of a lower nicotine concentration e-liquid may be associated with compensatory behaviour (e.g., higher number and duration of puffs) and increases

Parental experience of enzyme replacement therapy for Hunter syndrome.

Science.gov (United States)

Buraczewska, M; O'Leary, D; Walsh, O; Monavari, A; Crushell, E

2013-04-01

We aimed to establish the profile of Irish patients with Hunter Syndrome (Mucopolysaccharidosis type II, MPS II) receiving weekly intravenous Enzyme Replacement Therapy (ERT) with recombinant iduronate-2-sulfatase and to assess the social impact and parental opinion of ERT through the use of a parental questionnaire. Nine patients aged 3.5- 14 years have received a mean of 2 (range 0.5-3.5) years of ERT. Treatment was associated with clinical improvements from baseline in hepatosplenomegaly in 6/7 (85%) respiratory manifestations in 4/6 (67%) and a mean reduction in urinary glycosaminoglycan excretion of 62%. Changes noted by parents included increased energy 3/9 (33%) and softening of skin, hair and facial features 8/9 (89%). Parents report that seven hours weekly were spent on hospitalizations for ERT. Parental employment was adversely affected in 8 (89%) families. One day of school/preschool (20%) was lost every week for 8 (89%) children. All parents believed the benefits of ERT out-weigh the difficulties involved. All families would welcome the introduction of home based therapy. In conclusion the social and educational burden of hospital-based ERT on these children and their families is significant. The introduction of home-based therapy is likely to improve overall quality of life for MPSII patients and their families.

Potential efficacy of enzyme replacement and substrate reduction therapy in three siblings with Gaucher disease type III

NARCIS (Netherlands)

Cox-Brinkman, J.; van Breemen, M. J.; van Maldegem, B. T.; Bour, L.; Donker, W. E.; Hollak, C. E. M.; Wijburg, F. A.; Aerts, J. M. F. G.

2008-01-01

We report three siblings with Gaucher disease type III, born between 1992 and 2004. During this period, new developments resulted in different potential therapies, changing clinical practice. The two eldest siblings received enzyme replacement therapy (ERT) from the age of 24 and 5 months

Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy.

Science.gov (United States)

Grebenstein, Patricia E; Burroughs, Danielle; Roiko, Samuel A; Pentel, Paul R; LeSage, Mark G

2015-06-01

The FDA is considering reducing the nicotine content in tobacco products as a population-based strategy to reduce tobacco addiction. Research is needed to determine the threshold level of nicotine needed to maintain smoking and the extent of compensatory smoking that could occur during nicotine reduction. Sources of variability in these measures across sub-populations also need to be identified so that policies can take into account the risks and benefits of nicotine reduction in vulnerable populations. The present study examined these issues in a rodent nicotine self-administration model of nicotine reduction policy to characterize individual differences in nicotine reinforcement thresholds, degree of compensation, and elasticity of demand during progressive reduction of the unit nicotine dose. The ability of individual differences in baseline nicotine intake and nicotine pharmacokinetics to predict responses to dose reduction was also examined. Considerable variability in the reinforcement threshold, compensation, and elasticity of demand was evident. High baseline nicotine intake was not correlated with the reinforcement threshold, but predicted less compensation and less elastic demand. Higher nicotine clearance predicted low reinforcement thresholds, greater compensation, and less elastic demand. Less elastic demand also predicted lower reinforcement thresholds. These findings suggest that baseline nicotine intake, nicotine clearance, and the essential value of nicotine (i.e. elasticity of demand) moderate the effects of progressive nicotine reduction in rats and warrant further study in humans. They also suggest that smokers with fast nicotine metabolism may be more vulnerable to the risks of nicotine reduction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy*

Science.gov (United States)

Grebenstein, Patricia E.; Burroughs, Danielle; Roiko, Samuel A.; Pentel, Paul R.; LeSage, Mark G.

2015-01-01

Background The FDA is considering reducing the nicotine content in tobacco products as a population-based strategy to reduce tobacco addiction. Research is needed to determine the threshold level of nicotine needed to maintain smoking and the extent of compensatory smoking that could occur during nicotine reduction. Sources of variability in these measures across sub-populations also need to be identified so that policies can take into account the risks and benefits of nicotine reduction in vulnerable populations. Methods The present study examined these issues in a rodent nicotine self- administration model of nicotine reduction policy to characterize individual differences in nicotine reinforcement thresholds, degree of compensation, and elasticity of demand during progressive reduction of the unit nicotine dose. The ability of individual differences in baseline nicotine intake and nicotine pharmacokinetics to predict responses to dose reduction was also examined. Results Considerable variability in the reinforcement threshold, compensation, and elasticity of demand was evident. High baseline nicotine intake was not correlated with the reinforcement threshold, but predicted less compensation and less elastic demand. Higher nicotine clearance predicted low reinforcement thresholds, greater compensation, and less elastic demand. Less elastic demand also predicted lower reinforcement thresholds. Conclusions These findings suggest that baseline nicotine intake, nicotine clearance, and the essential value of nicotine (i.e. elasticity of demand) moderate the effects of progressive nicotine reduction in rats and warrant further study in humans. They also suggest that smokers with fast nicotine metabolism may be more vulnerable to the risks of nicotine reduction. PMID:25891231

Continuous Renal Replacement Therapy Applications on Extracorporeal Membrane Oxygenation Circuit.

Science.gov (United States)

Yetimakman, Ayse Filiz; Tanyildiz, Murat; Kesici, Selman; Kockuzu, Esra; Bayrakci, Benan

2017-06-01

Continuous venovenous hemofiltration or hemodiafiltration is used frequently in pediatric patients, but experience of continuous renal replacement therapy (CRRT) application on extracorporeal membrane oxygenation (ECMO) circuit is still limited. Among several methods used for applying CRRT on ECMO patients, we aim to share our experience on inclusion of a CRRT device in the ECMO circuit which we believe is easier and safer to apply. The data were collected on demographics, outcomes, and details of the treatment of ECMO patients who had CRRT. During the study period of 3 years, venous cannula of ECMO circuit before pump was used for CRRT access for both the filter inlet and outlet of CRRT machine to minimize the thromboembolic complications. The common indication for CRRT was fluid overload. CRRT was used in 3.68% of a total number of patients admitted and 43% of patients on ECMO. The patients have undergone renal replacement therapy for periods of time ranging between 24 h and 25 days (260 h mean). The survival rate of this group of patients with multiorgan failure was 33%. Renal recovery occurred in all of the survivors. Complications such as electrolyte imbalance, hypothermia, and bradykinin syndrome were easily managed. Adding a CRRT device on ECMO circuit is a safe and effective technique. The major advantages of this technique are easy to access, applying CRRT without extra anticoagulation process, preventing potential hemodynamic disturbances, and increased clearance of solutes and fluid overload using larger hemofilter.

Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition : A Randomized Controlled Trial

NARCIS (Netherlands)

Bartels, Rosalie H.; Bourdon, Celine; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A.; Mponda, John S.; Kobold, Anneke C. Muller; Bandsma, Robert H.; van Hensbroek, Michael Boele; Voskuijl, Wieger P.

Objective: To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. Study design: We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth

Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial

NARCIS (Netherlands)

Bartels, Rosalie H.; Bourdon, Céline; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A.; Mponda, John S.; Muller Kobold, Anneke C.; Bandsma, Robert H.; Boele van Hensbroek, Michael; Voskuijl, Wieger P.

2017-01-01

Objective To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. Study design We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth Central

Long term enzyme replacement therapy for Fabry disease: effectiveness on kidney, heart and brain

NARCIS (Netherlands)

Rombach, Saskia M.; Smid, Bouwien E.; Bouwman, Machtelt G.; Linthorst, Gabor E.; Dijkgraaf, Marcel G. W.; Hollak, Carla E. M.

2013-01-01

Fabry disease is an X-linked lysosomal storage disorder caused by α-galactosidase A deficiency leading to renal, cardiac, cerebrovascular disease and premature death. Treatment with α-galactosidase A (enzyme replacement therapy, ERT) stabilises disease in some patients, but long term effectiveness

Mitochondrial Replacement Therapy: Halachic Considerations for Enrolling in an Experimental Clinical Trial

Science.gov (United States)

Tendler, Rabbi Moshe D.; Loike, John D.

2015-01-01

The transition of new biotechnologies into clinical trials is a critical step in approving a new drug or therapy in health care. Ethically recruiting appropriate volunteers for these clinical trials can be a challenging task for both the pharmaceutical companies and the US Food and Drug Administration. In this paper we analyze the Jewish halachic perspectives of volunteering for clinical trials by focusing on an innovative technology in reproductive medicine, mitochondrial replacement therapy. The halachic perspective encourages individuals to volunteer for such clinical trials under the ethical principles of beneficence and social responsibility, when animal studies have shown that health risks are minimal. PMID:26241230

Mitochondrial Replacement Therapy: Halachic Considerations for Enrolling in an Experimental Clinical Trial

Directory of Open Access Journals (Sweden)

Rabbi Moshe D. Tendler

2015-07-01

Full Text Available The transition of new biotechnologies into clinical trials is a critical step in approving a new drug or therapy in health care. Ethically recruiting appropriate volunteers for these clinical trials can be a challenging task for both the pharmaceutical companies and the US Food and Drug Administration. In this paper we analyze the Jewish halachic perspectives of volunteering for clinical trials by focusing on an innovative technology in reproductive medicine, mitochondrial replacement therapy. The halachic perspective encourages individuals to volunteer for such clinical trials under the ethical principles of beneficence and social responsibility, when animal studies have shown that health risks are minimal.

Randomised Controlled Trial (RCT) of cannabinoid replacement therapy (Nabiximols) for the management of treatment-resistant cannabis dependent patients: a study protocol.

Science.gov (United States)

Bhardwaj, Anjali K; Allsop, David J; Copeland, Jan; McGregor, Iain S; Dunlop, Adrian; Shanahan, Marian; Bruno, Raimondo; Phung, Nghi; Montebello, Mark; Sadler, Craig; Gugusheff, Jessica; Jackson, Melissa; Luksza, Jennifer; Lintzeris, Nicholas

2018-05-18

The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches. A phase III multi-site outpatient, randomised, double-blinded, placebo controlled parallel design, comparing a 12-week course of nabiximols to placebo, with follow up at 24 weeks after enrolment. Four specialist drug and alcohol outpatient clinics in New South Wales, Australia. One hundred forty-two treatment seeking cannabis dependent adults, with no significant medical, psychiatric or other substance use disorders. Nabiximols is an oromucosal spray prescribed on a flexible dose regimen to a maximum daily dose of 32 sprays; 8 sprays (total 21.6 mg tetrahydrocannabinol (THC) and 20 mg cannabidiol (CBD)) four times a day, or matching placebo, dispensed weekly. All participants will receive six-sessions of individual cognitive behavioural therapy (CBT) and weekly clinical reviews. Primary endpoints are use of non-prescribed cannabis (self-reported cannabis use days, urine toxicology), safety measures (adverse events and abuse liability), and cost effectiveness (incremental cost effectiveness in achieving additional Quality Adjusted Life Years). Secondary outcomes include, improvement in physical and mental health parameters, substance use other than cannabis, cognitive functioning and patient satisfaction measures. This is the first outpatient community-based randomised controlled study of nabiximols as an agonist replacement medication for treating cannabis dependence, targeting individuals who have not previously responded to conventional treatment approaches. The study and treatment design is modelled upon an earlier study with

Toward a comprehensive long term nicotine policy.

Science.gov (United States)

Gray, N; Henningfield, J E; Benowitz, N L; Connolly, G N; Dresler, C; Fagerstrom, K; Jarvis, M J; Boyle, P

2005-06-01

Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source.

Insight into nicotine addiction

Directory of Open Access Journals (Sweden)

Sahil Handa

2017-01-01

Full Text Available The emergence of the epidemic of nicotine addiction in India and other nations is a global public health tragedy of untoward proportions. Smoking or chewing tobacco can seriously affect general, as well as oral health. Smoking-caused disease is a consequence of exposure to toxins in tobacco smoke and addiction to nicotine is the proximate cause of these diseases. This article focuses on nicotine as a determinant of addiction to tobacco and the pharmacologic effects of nicotine that sustain cigarette smoking. The pharmacologic reasons for nicotine use are an enhancement of mood, either directly or through relief of withdrawal symptoms and augmentation of mental or physical functions. Tobacco cessation is necessary to reduce morbidity and mortality related to tobacco use. Strategies for tobacco cessation involves 5A's and 5R's approach and pharmacotherapy. Dental professionals play an important role in helping patients to quit tobacco at the community and national levels, to promote tobacco prevention and control nicotine addiction. Dentists are in a unique position to educate and motivate patients concerning the hazards of tobacco to their oral and systemic health, and to provide intervention programs as a part of routine patient care.

Surveillance of smokeless tobacco nicotine, pH, moisture, and unprotonated nicotine content.

Science.gov (United States)

Richter, Patricia; Spierto, Francis W

2003-12-01

Smokeless tobacco is a complex chemical mixture, including not only the components of the tobacco leaf but also chemicals added during the manufacturing process. Smokeless tobacco contains the addictive chemical nicotine and more than 20 cancer-causing chemicals, including the potent tobacco-specific nitrosamines. The National Toxicology Program of the National Institutes of Health has concluded that oral use of smokeless tobacco is a human carcinogen. Therefore, smokeless tobacco is not a safe alternative to cigarettes. In fact, smokeless tobacco use begins primarily during early adolescence and can lead to nicotine dependence and increased risk of becoming a cigarette smoker. Under the Comprehensive Smokeless Tobacco Health Education Act of 1986 (15 U.S.C. 4401 et seq., Pub. L. 99-252), tobacco manufacturers report annually to the Centers for Disease Control and Prevention (CDC) on the total nicotine, unprotonated nicotine, pH, and moisture content of their smokeless tobacco products. This information is considered "trade secret," or confidential, in accordance with 5 U.S.C. 552(b)(4) and 18 U.S.C. 1905 and cannot be released to the public. In an effort to provide consumers and researchers with information on the nicotine content of smokeless tobacco, CDC arranged for the analysis of popular brands of smokeless tobacco. The results of this CDC study show that pH is a primary factor in the amount of nicotine that is in the most readily absorbable, unprotonated form. Furthermore, this study found that the brands of moist snuff smokeless tobacco with the largest amount of unprotonated nicotine also are the most frequently sold brands.

Potential contribution of aromatase inhibition to the effects of nicotine and related compounds on the brain

Directory of Open Access Journals (Sweden)

Anat eBiegon

2012-11-01

Full Text Available Cigarette smoking continues to be a major public health problem, and while smoking rates in men have shown some decrease over the last few decades, smoking rates among girls and young women are increasing. Practically all of the important aspects of cigarette smoking are sexually dimorphic. Women become addicted more easily than men, while finding it harder to quit. Nicotine replacement appears to be less effective in women. This may be linked to the observation that women are more sensitive than men to non-nicotine cues or ingredients in cigarettes. The reasons for these sex differences are mostly unknown. Several lines of evidence suggest that many of the reported sex differences related to cigarette smoking may stem from the inhibitory effects of nicotine and other tobacco alkaloids on estrogen synthesis via the enzyme aromatase (cyp19a gene product. Aromatase is the last enzyme in estrogen biosynthesis, catalyzing the conversion of androgens to estrogens. This review provides a summary of experimental evidence supporting brain aromatase as a potential mediator and/or modulator of nicotine actions in the brain, contributing to sex differences in smoking behavior. Additional research on the interaction between tobacco smoke, nicotine and aromatase may help devise new, sex specific methods for prevention and treatment of smoking addiction.

Better prevention than cure: optimal patient preparation for renal replacement therapy.

Science.gov (United States)

Huang, Xiaoyan; Carrero, Juan Jesús

2014-03-01

A generous proportion of end-stage renal disease patients may not be adequately prepared for initiation of renal replacement therapy (RRT). Here we review potential benefits of early patient referral to nephrologists and optimal preparation for RRT. We place this evidence in the context of the epidemiological study by Kurella Tamura et al., which shows that voluntary community kidney disease screening and education is associated with better patient preparation and, importantly, improved survival upon initiation of RRT.

Surfactant replacement therapy--economic impact.

Science.gov (United States)

Pejaver, R K; al Hifzi, I; Aldussari, S

2001-06-01

Surfactant replacement is an effective treatment for neonatal respiratory distress syndrome. (RDS). As widespread use of surfactant is becoming a reality, it is important to assess the economic implications of this new form of therapy. A comparison study was carried out at the Neonatal Intensive Care Unit (NICU) of Northwest Armed Forces Hospital, Saudi Arabia. Among 75 infants who received surfactant for RDS and similar number who were managed during time period just before the surfactant was available, but by set criteria would have made them eligible for surfactant. All other management modalities except surfactant were the same for all these babies. Based on the intensity of monitoring and nursing care required by the baby, the level of care was divided as: Level IIIA, IIIB, Level II, Level I. The cost per day per bed for each level was calculated, taking into account the use of hospital immovable equipment, personal salaries of nursing, medical, ancillary staff, overheads and maintenance, depreciation and replacement costs. Medications used, procedures done, TPN, oxygen, were all added to individual patient's total expenditure. 75 infants in the Surfactant group had 62 survivors. They spent a total of 4300 days in hospital. (av 69.35) Out of which 970 d (av 15.65 per patient) were ventilated days. There were 56 survivors in the non-surfactant group of 75. They had spent a total of 5023 days in the hospital (av 89.69/patient) out of which 1490 were ventilated days (av 26.60 d). Including the cost of surfactant (two doses), cost of hospital stay for each infant taking the average figures of stay would be SR 118, 009.75 per surfactant treated baby and SR 164, 070.70 per non-surfactant treated baby. The difference of 46,061 SR is 39.03% more in non-surfactant group. One Saudi rial = 8 Rs (approx at the time study was carried out.) Medical care cost varies from place to place. However, it is definitely cost-effective where surfactant is concerned. Quality adjusted

The effects of nicotine and non-nicotine smoking factors on working memory and associated brain function.

Science.gov (United States)

McClernon, Francis Joseph; Froeliger, Brett; Rose, Jed E; Kozink, Rachel V; Addicott, Merideth A; Sweitzer, Maggie M; Westman, Eric C; Van Wert, Dana M

2016-07-01

Smoking abstinence impairs executive function, which may promote continued smoking behavior and relapse. The differential influence of nicotine and non-nicotine (i.e. sensory, motor) smoking factors and related neural substrates is not known. In a fully factorial, within-subjects design, 33 smokers underwent fMRI scanning following 24 hours of wearing a nicotine or placebo patch while smoking very low nicotine content cigarettes or remaining abstinent from smoking. During scanning, blood oxygenation level-dependent (BOLD) signal was acquired while participants performed a verbal N-back task. Following 24-hour placebo (versus nicotine) administration, accuracy on the N-back task was significantly worse and task-related BOLD signal lower in dorsomedial frontal cortex. These effects were observed irrespective of smoking. Our data provide novel evidence that abstinence-induced deficits in working memory and changes in underlying brain function are due in large part to abstinence from nicotine compared with non-nicotine factors. This work has implications both for designing interventions that target abstinence-induced cognitive deficits and for nicotine-reduction policy. © 2015 Society for the Study of Addiction.

Children with Pompe disease: clinical characteristics, peculiar features and effects of enzyme replacement therapy

NARCIS (Netherlands)

C.I. van Capelle (Carine)

2014-01-01

markdownabstract__Abstract__ Pompe disease is a metabolic myopathy. Since the first description of the disease in 1932 by J.C. Pompe,1 tremendous progress has been made from discovering the biochemical and genetic basis of the disease to developing enzyme replacement therapy (ERT). With this

Activation of Peripheral κ-Opioid Receptors Normalizes Caffeine Effects Modified in Nicotine-Dependent Rats during Nicotine Withdrawal.

Science.gov (United States)

Sudakov, S K; Bogdanova, N G

2016-10-01

The study examined the effect of peripheral (intragastric) ICI-204,448, an agonist of gastric κ-opioid receptors, on the psychostimulating and anxiolytic effects of caffeine in nicotinedependent rats at the stage of nicotine withdrawal. In these rats, the effects of caffeine (10 mg/kg) were perverted. In nicotine-dependent rats, caffeine produced an anxiolytic effect accompanied by pronounced stimulation of motor activity, in contrast to anxiogenic effect induced by caffeine in intact rats without nicotine dependence. During nicotine withdrawal, nicotine-dependent rats demonstrated enhanced sensitivity to nicotine. Intragastric administration of κ-opioid receptor agonist ICI-204,448 normalized the effect of caffeine in nicotinedependent rats. We have previously demonstrated that activation of peripheral κ-opioid receptors inhibited central κ-opioid activity and eliminated manifestations of nicotine withdrawal syndrome in nicotine-dependent rats, e.g. metabolism activation, stimulation of motor activity, and enhancement of food consumption. In its turn, inhibition of central κ-opioid structures activates the brain adenosine system, which can attenuate the caffeine-induced effects in nicotine-dependent rats.

Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells

Energy Technology Data Exchange (ETDEWEB)

Soeda, Junpei; Morgan, Maelle; McKee, Chad; Mouralidarane, Angelina; Lin, ChingI [University College London, Centre for Hepatology, Royal Free Hospital, London NW3 2PF (United Kingdom); Roskams, Tania [Department of Morphology and Molecular Pathology, University of Leuven (Belgium); Oben, Jude A., E-mail: j.oben@ucl.ac.uk [University College London, Centre for Hepatology, Royal Free Hospital, London NW3 2PF (United Kingdom); Department of Gastroenterology and Hepatology, Guy' s and St Thomas' Hospital, London SE1 7EH (United Kingdom)

2012-01-06

Highlights: Black-Right-Pointing-Pointer Cigarette smoke may induce liver fibrosis via nicotine receptors. Black-Right-Pointing-Pointer Nicotine induces proliferation of hepatic stellate cells (HSCs). Black-Right-Pointing-Pointer Nicotine activates hepatic fibrogenic pathways. Black-Right-Pointing-Pointer Nicotine receptor antagonists attenuate HSC proliferation. Black-Right-Pointing-Pointer Nicotinic receptor antagonists may have utility as novel anti-fibrotic agents. -- Abstract: Background and aims: Cigarette smoke (CS) may cause liver fibrosis but possible involved mechanisms are unclear. Among the many chemicals in CS is nicotine - which affects cells through nicotinic acetylcholine receptors (nAChR). We studied the effects of nicotine, and involved pathways, on human primary hepatic stellate cells (hHSCs), the principal fibrogenic cells in the liver. We then determined possible disease relevance by assaying nAChR in liver samples from human non-alcoholic steatohepatitis (NASH). Methods: hHSC were isolated from healthy human livers and nAChR expression analyzed - RT-PCR and Western blotting. Nicotine induction of hHSC proliferation, upregulation of collagen1-{alpha}2 and the pro-fibrogenic cytokine transforming growth factor beta 1 (TGF-{beta}1) was determined along with involved intracellular signaling pathways. nAChR mRNA expression was finally analyzed in whole liver biopsies obtained from patients diagnosed with non-alcoholic steatohepatitis (NASH). Results: hHSCs express muscle type ({alpha}1, {beta}1, delta and epsilon) and neuronal type ({alpha}3, {alpha}6, {alpha}7, {beta}2 and {beta}4) nAChR subunits at the mRNA level. Among these subunits, {alpha}3, {alpha}7, {beta}1 and {epsilon} were predominantly expressed as confirmed by Western blotting. Nicotine induced hHSC proliferation was attenuated by mecamylamine (p < 0.05). Additionally, collagen1-{alpha}2 and TGF-{beta}1 mRNA expression were significantly upregulated by nicotine and inhibited by

Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells

International Nuclear Information System (INIS)

Soeda, Junpei; Morgan, Maelle; McKee, Chad; Mouralidarane, Angelina; Lin, ChingI; Roskams, Tania; Oben, Jude A.

2012-01-01

Highlights: ► Cigarette smoke may induce liver fibrosis via nicotine receptors. ► Nicotine induces proliferation of hepatic stellate cells (HSCs). ► Nicotine activates hepatic fibrogenic pathways. ► Nicotine receptor antagonists attenuate HSC proliferation. ► Nicotinic receptor antagonists may have utility as novel anti-fibrotic agents. -- Abstract: Background and aims: Cigarette smoke (CS) may cause liver fibrosis but possible involved mechanisms are unclear. Among the many chemicals in CS is nicotine – which affects cells through nicotinic acetylcholine receptors (nAChR). We studied the effects of nicotine, and involved pathways, on human primary hepatic stellate cells (hHSCs), the principal fibrogenic cells in the liver. We then determined possible disease relevance by assaying nAChR in liver samples from human non-alcoholic steatohepatitis (NASH). Methods: hHSC were isolated from healthy human livers and nAChR expression analyzed – RT-PCR and Western blotting. Nicotine induction of hHSC proliferation, upregulation of collagen1-α2 and the pro-fibrogenic cytokine transforming growth factor beta 1 (TGF-β1) was determined along with involved intracellular signaling pathways. nAChR mRNA expression was finally analyzed in whole liver biopsies obtained from patients diagnosed with non-alcoholic steatohepatitis (NASH). Results: hHSCs express muscle type (α1, β1, delta and epsilon) and neuronal type (α3, α6, α7, β2 and β4) nAChR subunits at the mRNA level. Among these subunits, α3, α7, β1 and ε were predominantly expressed as confirmed by Western blotting. Nicotine induced hHSC proliferation was attenuated by mecamylamine (p < 0.05). Additionally, collagen1-α2 and TGF-β1 mRNA expression were significantly upregulated by nicotine and inhibited by mecamylamine. α1 and α3-nAChR mRNA expression was significantly upregulated in NASH fibrosis compared to normal livers. Conclusion: Nicotine at levels in smokers’ blood is pro-fibrogenic, through

Cost-Effectiveness of Nicotine Patches for Smoking Cessation in Pregnancy: A Placebo Randomized Controlled Trial (SNAP).

Science.gov (United States)

Essex, Holly N; Parrott, Steve; Wu, Qi; Li, Jinshuo; Cooper, Sue; Coleman, Tim

2015-06-01

Smoking during pregnancy is the most important, preventable cause of adverse pregnancy outcomes including miscarriage, premature birth, and low birth weight with huge financial costs to the National Health Service. However, there are very few published economic evaluations of smoking cessation interventions in pregnancy and previous studies are predominantly U.S.-based and do not present incremental cost-effectiveness ratios (ICER). A number of studies have demonstrated cost-effectiveness of nicotine replacement therapy (NRT) in the general population, but this has yet to be tested among pregnant smokers. A cost-effectiveness analysis was undertaken alongside the smoking, nicotine, and pregnancy trial to compare NRT patches plus behavioral support to behavioral support alone, for pregnant women who smoked. At delivery, biochemically verified quit rates were slightly higher at 9.4% in the NRT group compared to 7.6% in the control group (odds ratio = 1.26, 95% CI = 0.82-1.96), at an increased cost of around £90 per participant. Higher costs in the NRT group were mainly attributable to the cost of NRT patches (mean = £46.07). The incremental cost-effectiveness ratio associated with NRT was £4,926 per quitter and a sensitivity analysis including only singleton births yielded an ICER of £4,156 per quitter. However, wide confidence intervals indicated a high level of uncertainty. Without a specific willingness to pay threshold, and due to high levels of statistical uncertainty, it is hard to determine the cost-effectiveness of NRT in this population. Furthermore, future research should address compliance issues, as these may dilute any potential effects of NRT, thus reducing the cost-effectiveness. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Clinical review: Optimal dose of continuous renal replacement therapy in acute kidney injury.

Science.gov (United States)

Prowle, John R; Schneider, Antoine; Bellomo, Rinaldo

2011-01-01

Continuous renal replacement therapy (CRRT) is the preferred treatment for acute kidney injury in intensive care units (ICUs) throughout much of the world. Despite the widespread use of CRRT, controversy and center-specific practice variation in the clinical application of CRRT continue. In particular, whereas two single-center studies have suggested survival benefit from delivery of higher-intensity CRRT to patients with acute kidney injury in the ICU, other studies have been inconsistent in their results. Now, however, two large multi-center randomized controlled trials - the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study and the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement Therapy Study - have provided level 1 evidence that effluent flow rates above 25 mL/kg per hour do not improve outcomes in patients in the ICU. In this review, we discuss the concept of dose of CRRT, its relationship with clinical outcomes, and what target optimal dose of CRRT should be pursued in light of the high-quality evidence now available.

A Multi-Route Model of Nicotine-Cotinine Pharmacokinetics, Pharmacodynamics and Brain Nicotinic Acetylcholine Receptor Binding in Humans

Energy Technology Data Exchange (ETDEWEB)

Teeguarden, Justin G.; Housand, Conrad; Smith, Jordan N.; Hinderliter, Paul M.; Gunawan, Rudy; Timchalk, Charles

2013-02-01

The pharmacokinetics of nicotine, the pharmacologically active alkaloid in tobacco responsible for addiction, are well characterized in humans. We developed a physiologically based pharmacokinetic/pharmacodynamic model of nicotine pharmacokinetics, brain dosimetry and brain nicotinic acetylcholine receptor (nAChRs) occupancy. A Bayesian framework was applied to optimize model parameters against multiple human data sets. The resulting model was consistent with both calibration and test data sets, but in general underestimated variability. A pharmacodynamic model relating nicotine levels to increases in heart rate as a proxy for the pharmacological effects of nicotine accurately described the nicotine related changes in heart rate and the development and decay of tolerance to nicotine. The PBPK model was utilized to quantitatively capture the combined impact of variation in physiological and metabolic parameters, nicotine availability and smoking compensation on the change in number of cigarettes smoked and toxicant exposure in a population of 10,000 people presented with a reduced toxicant (50%), reduced nicotine (50%) cigarette Across the population, toxicant exposure is reduced in some but not all smokers. Reductions are not in proportion to reductions in toxicant yields, largely due to partial compensation in response to reduced nicotine yields. This framework can be used as a key element of a dosimetry-driven risk assessment strategy for cigarette smoke constituents.

Low Nicotine Content Descriptors Reduce Perceived Health Risks and Positive Cigarette Ratings in Participants Using Very Low Nicotine Content Cigarettes.

Science.gov (United States)

Denlinger-Apte, Rachel L; Joel, Danielle L; Strasser, Andrew A; Donny, Eric C

2017-10-01

Understanding how smokers perceive reduced nicotine content cigarettes will be important if the FDA and global regulatory agencies implement reduced nicotine product standards for cigarettes. Prior research has shown that some smokers incorrectly believe "light" cigarettes are less harmful than regular cigarettes. Similar misunderstandings of health risk could also apply to reduced nicotine cigarettes. To date, most studies of reduced nicotine cigarettes have blinded subjects to the nicotine content. Therefore, little is known about how smokers experience reduced nicotine content cigarettes when they are aware of the reduced content, and how use may be impacted. The present study was a within-subjects experiment with 68 adult daily smokers who smoked two identical very low nicotine content Quest 3 (0.05 mg nicotine yield) cigarettes. Subjects were told that one cigarette contained "average" nicotine content, and the other contained "very low" nicotine content. After smoking each cigarette, subjects completed subjective measures about their smoking experience. Subjects rated the "very low" nicotine cigarette as less harmful to their health overall compared to the "average" nicotine cigarette; this effect held true for specific smoking-related diseases. Additionally, they rated the "very low" nicotine cigarette as having less desirable subjective effects than the "average" nicotine cigarette and predicted having greater interest in quitting smoking in the future if only the "very low" nicotine cigarette was available. Explicit knowledge of very low nicotine content changes smokers' perceptions of very low nicotine content cigarettes, resulting in reduced predicted harm, subjective ratings and predicted future use. Before a reduced nicotine product standard for cigarettes can be implemented, it is important to understand how product information impacts how smokers think about and experience very low nicotine content cigarettes. Prior research has shown that smokers

[Application of continuous renal replacement therapy in the treatment of myonephropathic metabolic syndrome caused by acute lower extremity ischemia].

Science.gov (United States)

Sun, Jianping; Wang, Tengke; Zhang, Jinglan

2014-09-16

To summarize the experiences of using continuous renal replacement therapy in the treatment of myonephropathic metabolic syndrome caused by acute lower limb ischemia. Retrospective study of patients diagnosed acute lower limb ischemia with surgical treatment between January 2008 and December 2013, among which 22 patients with myonephropathic metabolic syndrome received continuous renal replacement therapy. Summarize the change tendency of myoglobin, urine volume and serum creatinine levels during treatment and analysis the condition changes and prognosis of the patients. Among them, 2 patients were amputated and two died after surgery. The major causes of death were acute renal failure, metabolic acidosis, circulation failure and liver failure, etc. Myoglobin was significantly higher at Day 1 after surgery than that was before surgery (P metabolic syndrome, early targeted continuous renal replacement therapy may decrease the serum concentrations of myoglobin and CK, improve urine volume, maintain homeostasis, prevent renal function deterioration and improve the prognosis of patients. And it is highly recommended.

Liquid crystalline systems containing Vitamin E TPGS for the controlled transdermal nicotine delivery

Directory of Open Access Journals (Sweden)

Lívia Neves Borgheti-Cardoso

Full Text Available ABSTRACT Transdermal nicotine patches have been used in smoking cessation therapy, suggested for the treatment of skin disorders with eosinophilic infiltration and have been found to improve attention performance in patients with Alzheimer's disease and age-associated memory impairment. However, skin irritation with extended patch use is still a problem. The aim of this work was to develop a simple to prepare liquid crystalline system containing vitamin E TPGS that would be able to control nicotine delivery and reduce irritation and sensitization problems. The liquid crystalline phases were macroscopically characterized by visual analysis and examined microscopically under a polarized light microscope. Topical and transdermal delivery of nicotine were investigated in vitro using porcine ear skin mounted on a Franz diffusion cell. Nicotine skin permeation from the developed cubic phase followed zero-order kinetics (r = 0.993 and was significantly enhanced after 12 h when compared to the control formulation (nicotine solution (p < 0.05 (138.86 ± 20.44 and 64.91 ± 4.06 μg/cm2, respectively. Cubic phase was also able to target viable skin layers in comparison to control solution (8.18 ± 1.89 and 2.63 ± 2.51 μg/cm2, respectively. Further studies to evaluate skin sensitization and irritation are now necessary.

Replacing SUs with incretin-based therapies for type 2 diabetes mellitus

DEFF Research Database (Denmark)

Knop, Filip K; Holst, Jens Juul; Vilsbøll, Tina

2008-01-01

Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by insulin resistance, a steady decline in glucose-induced insulin secretion (most likely caused by a progressive decrease in functional beta-cell mass), and inappropriately regulated glucagon secretion; in combination...... are glucose-dependent, reducing the risk of hypoglycemia. GLP-1 inhibits glucagon secretion and decreases gastrointestinal motility, in turn reducing food intake and body weight. This feature review focuses on the challenges and feasibilities of replacing SU with incretin-based therapy in patients with T2DM....... - glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). More importantly, incretin-based therapies potentiate glucose-stimulated insulin secretion and may restore reduced glucose-induced insulin secretion in T2DM. Furthermore, the insulinotropic effects of GLP-1 and GIP...

Interruption of enzyme replacement therapy in Gaucher disease.

Science.gov (United States)

Goldblatt, J; Fletcher, J M; McGill, J; Szer, J; Wilson, M

2016-05-25

In Australia, 58 patients with Gaucher disease were managed by a Gaucher Disease Advisory Committee (GDAC) through a centrally adminis-tered national programme, the Life Savings Drug Program (LSDP). In June 2009, Genzyme Corporation, which manufactures imiglucerase (Cerezyme), the only enzyme replacement therapy (ERT) registered for the treatment of Gaucher disease in Australia at that time, announced that due to a viral contamination problem there would be no further shipments of Cerezyme to Australia prior to the end of 2009. The GDAC allocated available drug supplies in order to maintain treatment to those most in need on a hierarchal clinical severity basis. A cohort of 24 patients with Type 1 Gaucher disease was withdrawn from therapy, 22 of whom had no discernible clinically significant adverse effects when reviewed off therapy for up to 6 months. In this paper, we review the course of 20 of the patients who have been on imiglucerase for periods of at least 24 months after the end of their 'drug holiday'. No patient experienced a bone crisis nor clinical nor magnetic resonance imaging evidence of new avascular necrosis events during this period. Two years after recommencing ERT after a 6-month drug holiday, no patient had developed an overt irreversible complication of their Gaucher disease, with the majority returning to their previous clinical status.

Nicotine concentration of e-cigarettes used by adolescents.

Science.gov (United States)

Morean, Meghan E; Kong, Grace; Cavallo, Dana A; Camenga, Deepa R; Krishnan-Sarin, Suchitra

2016-10-01

E-cigarettes are popular among youth, but little is known about the nicotine concentrations of e-liquids used by adolescents. In Spring, 2014, we conducted cross-sectional surveys in four Connecticut high schools and two middle schools. Among past-30-day e-cigarette users (n=513, 45% female, mean age 15.9 [SD=1.4]), we examined what nicotine concentration adolescents typically used in their e-cigarettes (range 0-30mg/mL and "I don't know"). We first examined whether age, sex, smoking status, e-cigarette use frequency, and/or e-cigarette acquisition source were associated with using nicotine-free e-liquid, nicotine e-liquid, or not knowing the e-liquid nicotine concentration. Among nicotine users (n=185), we then examined whether the aforementioned variables were associated with using higher nicotine concentrations. Adolescents reported using nicotine-free e-liquid (28.5%), nicotine e-liquid (37.4%), or not knowing their e-liquid nicotine concentration (34.1%). Nicotine users comprised more smokers and heavier e-cigarette users compared to nicotine-free e-liquid users and those who did not know their nicotine concentration. Nicotine users also comprised more males and were more likely to purchase e-cigarettes online or from tobacco shops compared to those who did not know their nicotine concentration. Among nicotine users, cigarette smoking, male sex, and purchasing e-cigarettes from tobacco shops predicted using higher nicotine concentrations. Adolescents reported using e-liquids with variable nicotine concentrations. Smokers, males, and those who purchased their own e-cigarettes reported using the highest nicotine levels. Of concern, many adolescents were unaware of the nicotine concentration in their e-liquid, raising concerns about inadvertent nicotine exposure among youth. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Decreased plasma cholesterol esterification and cholesteryl ester transfer in hypopituitary patients on glucocorticoid replacement therapy

NARCIS (Netherlands)

Beentjes, JAM; Van Tol, A; Sluiter, WJ; Dullaart, RPF

Cardiovascular risk is increased in hypopituitary patients. No data are available with respect to the effect of glucocorticoid replacement therapy on high density lipoproteins (HDL) metabolism in such patients. Plasma lecithin:choresterol acyl transferase (LCAT), cholesteryl ester transfer protein

Effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with idiopathic hypogonadotropic hypogonadism.

Science.gov (United States)

Doğan, Berçem Ayçiçek; Karakılıç, Ersen; Tuna, Mazhar Müslüm; Arduç, Ayşe; Berker, Dilek; Güler, Serdar

2015-03-01

Idiopathic hypogonadotropic hypogonadism is a rare disorder. This study evaluated the effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with this disorder. Forty-three male patients aged 30 (range: 24-39 years) who were newly diagnosed with idiopathic hypogonadotropic hypogonadism and 20 age-, sex- and weight-matched controls (range: 26-39 years) were included in the study. Androgen replacement therapy was given according to the Algorithm of Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes (2010; Journal of Clinical Endocrinology and Metabolism, 95, 2536). The patients were assessed at a pretreatment visit and 3 and 6 months after the treatment. Inflammatory markers and lipid parameters were evaluated. Endothelial function was assessed with brachial flow-mediated dilation of a brachial artery and high-resolution ultrasonography of the carotid intima-media thickness. The carotid intima-media thickness (P hypogonadism compared to the control subjects at the pretreatment visit. There was a negative correlation between the total testosterone level and carotid intima-media thickness (r = -0·556, P = hypogonadism and that androgen replacement therapy significantly reduces atherosclerotic risk markers in these patients after 6 months. © 2014 John Wiley & Sons Ltd.

An intervention to reduce the number of convenience stores selling tobacco: feasibility study.

Science.gov (United States)

Paynter, Janine; Glover, Marewa; Bullen, Chris; Sonia, Deepika

2016-05-01

Reduction of the availability of tobacco has been proposed as a means of reducing and denormalising tobacco use. Some retailers have stopped selling tobacco. Therefore, we investigated how willing New Zealand convenience store owners were to stop selling tobacco or sell nicotine replacement therapy. Promotion of their stores was offered as an incentive to stop selling tobacco. We asked convenience store owners in the Auckland metropolitan region of New Zealand to choose one of three actions. The first was to stop selling tobacco for a short period of time; the second was to restrict the hours that they sold tobacco; the third was to display and sell nicotine replacement therapy. All participating retailers completed a short interview about selling tobacco. We also surveyed customers about nicotine replacement and cessation. One-third of eligible retailers agreed to participate. Most who participated (93%) were unwilling to stop or restrict tobacco sales and 2 (7%) had already stopped selling tobacco. Tobacco was perceived as a key product for their businesses. Very few customers who purchased cigarettes noticed nicotine replacement therapy or obtained it from convenience stores. Substantially reducing the availability of tobacco in communities is likely to require legislative approaches, underpinned by sustained community pressure and support for convenience store owners who are willing to change their business model. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Nicotine reward and affective nicotine withdrawal signs are attenuated in calcium/calmodulin-dependent protein kinase IV knockout mice.

Directory of Open Access Journals (Sweden)

Kia J Jackson

Full Text Available The influx of Ca(2+ through calcium-permeable nicotinic acetylcholine receptors (nAChRs leads to activation of various downstream processes that may be relevant to nicotine-mediated behaviors. The calcium activated protein, calcium/calmodulin-dependent protein kinase IV (CaMKIV phosphorylates the downstream transcription factor cyclic AMP response element binding protein (CREB, which mediates nicotine responses; however the role of CaMKIV in nicotine dependence is unknown. Given the proposed role of CaMKIV in CREB activation, we hypothesized that CaMKIV might be a crucial molecular component in the development of nicotine dependence. Using male CaMKIV genetically modified mice, we found that nicotine reward is attenuated in CaMKIV knockout (-/- mice, but cocaine reward is enhanced in these mice. CaMKIV protein levels were also increased in the nucleus accumbens of C57Bl/6 mice after nicotine reward. In a nicotine withdrawal assessment, anxiety-related behavior, but not somatic signs or the hyperalgesia response are attenuated in CaMKIV -/- mice. To complement our animal studies, we also conducted a human genetic association analysis and found that variants in the CaMKIV gene are associated with a protective effect against nicotine dependence. Taken together, our results support an important role for CaMKIV in nicotine reward, and suggest that CaMKIV has opposing roles in nicotine and cocaine reward. Further, CaMKIV mediates affective, but not physical nicotine withdrawal signs, and has a protective effect against nicotine dependence in human genetic association studies. These findings further indicate the importance of calcium-dependent mechanisms in mediating behaviors associated with drugs of abuse.

Neonatal Nicotine Exposure Increases Excitatory Synaptic Transmission and Attenuates Nicotine-stimulated GABA release in the Adult Rat Hippocampus

Science.gov (United States)

Damborsky, Joanne C.; Griffith, William H.; Winzer-Serhan, Ursula H.

2014-01-01

Developmental exposure to nicotine has been linked to long-lasting changes in synaptic transmission which may contribute to behavioral abnormalities seen in offspring of women who smoke during pregnancy. Here, we examined the long-lasting effects of developmental nicotine exposure on glutamatergic and GABAergic neurotransmission, and on acute nicotine-induced glutamate and GABA release in the adult hippocampus, a structure important in cognitive and emotional behaviors. We utilized a chronic neonatal nicotine treatment model to administer nicotine (6 mg/kg/day) to rat pups from postnatal day (P) 1–7, a period that falls developmentally into the third human trimester. Using whole-cell voltage clamp recordings from CA1 pyramidal neurons in hippocampal slices, we measured excitatory and inhibitory postsynaptic currents in neonatally control- and nicotine-treated young adult males. Neonatal nicotine exposure significantly increased AMPA receptor-mediated spontaneous and evoked excitatory signaling, with no change in glutamate release probability in adults. Conversely, there was no increase in spontaneous GABAergic neurotransmission in nicotine-males. Chronic neonatal nicotine treatment had no effect on acute nicotine-stimulated glutamate release in adults, but acute nicotine-stimulated GABA release was significantly attenuated. Thus, neonatal nicotine exposure results in a persistent net increase in excitation and a concurrent loss of nicotinic acetylcholine receptor (nAChR)-mediated regulation of presynaptic GABA but not glutamate release, which would exacerbate excitation following endogenous or exogenous nAChR activation. Our data underscore an important role for nAChRs in hippocampal excitatory synapse development, and suggest selective long-term changes at specific presynaptic nAChRs which together could explain some of the behavioral abnormalities associated with maternal smoking. PMID:24950455

Nicotine affects hydrogen sulfide concentrations in mouse kidney and heart but not in brain and liver tissues.

Science.gov (United States)

Wiliński, Jerzy; Wiliński, Bogdan; Somogyi, Eugeniusz; Piotrowska, Joanna; Kameczura, Tomasz; Zygmunt, Małgorzata

2017-01-01

Nicotine, a potent parasympathomimetic alkaloid with stimulant effects, is contributing to addictive properties of tobacco smoking and is though used in the smoking cessation therapy. Hydrogen sulfide (H2S) is involved in physiology and pathophysiology of various systems in mammals. The interactions between nicotine and H2S are not fully recognized. The aim of the study is to assess the influence of nicotine on the H2S tissue concentrations in different mouse organs. Adult CBA male mice were administered intraperitoneally 1.5 mg/kg b.w. per day of nicotine (group D1, n = 10) or 3 mg/ kg b.w. per day of nicotine (group D2, n = 10). The control group (n = 10) received physiological saline. The measurements of the free and acid-labile H2S tissue concentrations were performed with the Siegel spectrophotometric modi ed method. ere was a significant increase in H2S concentrations in both nicotine doses groups in the kidney (D1 by 54.2%, D2 by 40.0%). In the heart the higher nicotine dose caused a marked decrease in H2S tissue level (by 65.4%), while the lower dose did not affect H2S content. Nicotine administration had no effect on H2S concentrations in the brain and liver. In conclusion, nicotine affects H2S tissue concentrations in kidney and heart but not in the liver and brain tissues.

Neuronal nicotinic acetylcholine receptors: Common molecular substrates of nicotine and alcohol dependence

Directory of Open Access Journals (Sweden)

Linzy M. Hendrickson

2013-04-01

Full Text Available Alcohol and nicotine are often co-abused. As many as 80-95% of alcoholics are also smokers, suggesting that ethanol and nicotine, the primary addictive component of tobacco smoke, may functionally interact in the central nervous system and/or share a common mechanism of action. While nicotine initiates dependence by binding to and activating neuronal nicotinic acetylcholine receptors (nAChRs, ligand-gated cation channels normally activated by endogenous acetylcholine (ACh, ethanol is much less specific with the ability to modulate multiple gene products including those encoding voltage-gated ion channels, and excitatory/inhibitory neurotransmitter receptors. However, emerging data indicate that ethanol interacts with nAChRs, both directly and indirectly, in the mesocorticolimbic dopaminergic (DAergic reward circuitry to affect brain reward systems. Like nicotine, ethanol activates DAergic neurons of the ventral tegmental area (VTA which project to the nucleus accumbens (NAc. Blockade of VTA nAChRs reduces ethanol-mediated activation of DAergic neurons, NAc DA release, consumption, and operant responding for ethanol in rodents. Thus, ethanol may increase ACh release into the VTA driving activation of DAergic neurons through nAChRs. In addition, ethanol potentiates distinct nAChR subtype responses to ACh and nicotine in vitro and in DAergic neurons. The smoking cessation therapeutic and nAChR partial agonist, varenicline, reduces alcohol consumption in heavy drinking smokers and rodent models of alcohol consumption. Finally, single nucleotide polymorphisms in nAChR subunit genes are associated with alcohol dependence phenotypes and smoking behaviors in human populations. Together, results from preclinical, clinical, and genetic studies indicate that nAChRs may have an inherent role in the abusive properties of ethanol, as well as in nicotine and alcohol co-dependence.

Genotoxicity study on nicotine and nicotine-derived nitrosamine by accelerator mass spectrometry

International Nuclear Information System (INIS)

Li, X.S.; Wang, H.F.; Shi, J.Y.; Wang, X.Y.; Liu, Y.F.; Li, K.; Lu, X.Y.; Wang, J.J.; Liu, K.X.; Guo, Z.Y.

1997-01-01

The authors have studied DNA adduction with 14 C-labelled nicotine and nicotine-derived nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), by accelerator mass spectrometry (AMS) in mouse liver at doses equivalent to low-level exposure of humans. The dose ranges of nicotine and NNK administered were from 0.4 μg to 4.0 x 10 2 μg·kg -1 , and from 0.1 μg to 2.0 x 10 4 μg·kg -1 , respectively. In the exposure of mice to either nicotine or NNK, the number of DNA adducts increased linearly with increasing dose. The detection limit of DNA adducts was 1 adduct per 10 11 nucleotide molecules. This limit is 1-4 orders of magnitude lower than that of other techniques used for quantification of DNA adducts. The results of the animal experiments enabled us to speculate that nicotine is a potential carcinogen. According to the procedure for 14 C-labelled-NNK synthesis, the authors discuss the ultimate chemical speciation of NNK bound to DNA. From the animal tests the authors derived a directly perceivable relation between tobacco consumption and DNA adduction as the carcinogenic risk assessment

Pathogenesis of Abdominal Aortic Aneurysms: Role of Nicotine and Nicotinic Acetylcholine Receptors

Directory of Open Access Journals (Sweden)

Zong-Zhuang Li

2012-01-01

Full Text Available Inflammation, proteolysis, smooth muscle cell apoptosis, and angiogenesis have been implicated in the pathogenesis of abdominal aortic aneurysms (AAAs, although the well-defined initiating mechanism is not fully understood. Matrix metalloproteinases (MMPs such as MMP-2 and -9 and other proteinases degrading elastin and extracellular matrix are the critical pathogenesis of AAAs. Among the risk factors of AAAs, cigarette smoking is an irrefutable one. Cigarette smoke is practically involved in various aspects of the AAA pathogenesis. Nicotine, a major alkaloid in tobacco leaves and a primary component in cigarette smoke, can stimulate the MMPs expression by vascular SMCs, endothelial cells, and inflammatory cells in vascular wall and induce angiogenesis in the aneurysmal tissues. However, for the inflammatory and apoptotic processes in the pathogenesis of AAAs, nicotine seems to be moving in just the opposite direction. Additionally, the effects of nicotine are probably dose dependent or associated with the exposure duration and may be partly exerted by its receptors—nicotinic acetylcholine receptors (nAChRs. In this paper, we will mainly discuss the pathogenesis of AAAs involving inflammation, proteolysis, smooth muscle cell apoptosis and angiogenesis, and the roles of nicotine and nAChRs.

Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic levels in postmenopausal women

NARCIS (Netherlands)

Giltay, E.J.; Duschek, E.J.J.; Katan, M.B.; Neele, S.J.; Netelenbos, J.C.; Zock, P.L.

2004-01-01

Estrogens may affect the essential n-6 and n-3 fatty acids arachidonic acid (AA; C20:4n-6) and docosahexaenoic acid (DHA; C22:6n-3). Therefore, we investigated the long-term effects of hormone replacement therapy and raloxifene, a selective estrogen-receptor modulator, in two randomized,

Effect of renal replacement therapy on retinol-binding protein 4 isoforms

DEFF Research Database (Denmark)

Frey, Simone K; Henze, Andrea; Nagl, Britta

2009-01-01

Retinol-binding protein 4 (RBP4) levels are elevated in the serum of patients with kidney dysfunction. We recently showed that RBP4 isoforms including apo-RBP4 (RBP4 not bound to retinol) and RBP4 truncated at the C-terminus (RBP4-L, RBP4-LL) are increased in the serum of patients with kidney dis...... diseases but not in serum of patients with various liver diseases. The aim of this study was to investigate the effect of renal replacement therapy on RBP4 isoforms....

The changing trends and outcomes in renal replacement therapy: data from the ERA-EDTA Registry

NARCIS (Netherlands)

Pippias, Maria; Jager, Kitty J.; Kramer, Anneke; Leivestad, Torbjørn; Sánchez, Manuel Benítez; Caskey, Fergus J.; Collart, Frederic; Couchoud, Cécile; Dekker, Friedo W.; Finne, Patrik; Fouque, Denis; Heaf, James G.; Hemmelder, Marc H.; Kramar, Reinhard; de Meester, Johan; Noordzij, Marlies; Palsson, Runolfur; Pascual, Julio; Zurriaga, Oscar; Wanner, Christoph; Stel, Vianda S.

2016-01-01

This study examines the time trends in incidence, prevalence, patient and kidney allograft survival and causes of death (COD) in patients receiving renal replacement therapy (RRT) in Europe. Eighteen national or regional renal registries providing data to the European Renal Association-European

Overweight, insulin resistance and type II diabetes in type I Gaucher disease patients in relation to enzyme replacement therapy

NARCIS (Netherlands)

Langeveld, M.; de Fost, M.; Aerts, J. M. F. G.; Sauerwein, H. P.; Hollak, C. E. M.

2008-01-01

Type I Gaucher disease, a lysosomal storage disorder is associated with metabolic abnormalities such as high resting energy expenditure, low circulating adiponectin and peripheral insulin resistance. Treatment with enzyme replacement therapy (enzyme therapy) leads to a decrease in resting energy

Habenular expression of rare missense variants of the β4 nicotinic receptor subunit alters nicotine consumption

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Marta A Ślimak

2014-01-01

Full Text Available The CHRNA5-CHRNA3-CHRNB4 gene cluster, encoding the α5, α3 and β4 nicotinic acetylcholine receptor (nAChR subunits, has been linked to nicotine dependence. The habenulo-interpeduncular (Hb-IPN tract is particularly enriched in α3β4 nAChRs. We recently showed that modulation of these receptors in the medial habenula (MHb in mice altered nicotine consumption. Given that β4 is rate-limiting for receptor activity and that single nucleotide polymorphisms (SNPs in CHRNB4 have been linked to altered risk of nicotine dependence in humans, we were interested in determining the contribution of allelic variants of β4 to nicotine receptor activity in the MHb. We screened for missense SNPs with allele frequencies > 0.0005 and introduced the corresponding substitutions in Chrnb4. Fourteen variants were analyzed by co-expression with α3. We found that β4A90I and β4T374I variants, previously shown to associate with reduced risk of smoking, and an additional variant β4D447Y, significantly increased nicotine-evoked current amplitudes, while β4R348C, the mutation most frequently encountered in sporadic amyotrophic lateral sclerosis (sALS, showed reduced nicotine currents. We employed lentiviruses to express β4 or β4 variants in the MHb. Immunoprecipitation studies confirmed that β4 lentiviral-mediated expression leads to specific upregulation of α3β4 but not β2 nAChRs in the Mhb. Mice injected with the β4-containing virus showed pronounced aversion to nicotine as previously observed in transgenic Tabac mice overexpressing Chrnb4 at endogenous sites including the MHb. Habenular expression of the β4 gain-of-function allele T374I also resulted in strong aversion, while transduction with the β4 loss-of function allele R348C failed to induce nicotine aversion. Altogether, these data confirm the critical role of habenular β4 in nicotine consumption, and identify specific SNPs in CHRNB4 that modify nicotine-elicited currents and alter nicotine

Change in the use of hormone replacement therapy and the incidence of fracture in Oslo.

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Meyer, H E; Lofthus, C M; Søgaard, A J; Falch, J A

2009-05-01

Fracture incidence in Oslo decreased from the 1970s to the 1990s in younger postmenopausal women, but not in older women or in men. Concurrently, hormone replacement therapy increased considerably. Using data from the Oslo Health Study, we estimated that roughly half the decline might be attributed hormone replacement therapy. Between the late 1970s and the late 1990s, the incidence of hip fracture and distal forearm fracture decreased in younger postmenopausal women in Oslo, but not in elderly women or in men. The purpose of this report is to evaluate whether the decreased incidence was coherent with trends in use of hormone replacement therapy (HRT). Data on estrogens were collected from official drug statistics, data on fractures from published studies and data on bone mineral density (BMD) from the Oslo Health Study. The sale of all estrogens increased 22 times from 1979 to 1999, and the sub-category estradiol combined with progestin increased 35 times. In the corresponding period the incidence of distal forearm fracture in women aged 50-64 years decreased by 33% and hip fracture by 39%. Based on differences in BMD between users and non-users of HRT, we estimated that up to half of this decline might be due to HRT. The reduction in fracture incidence in postmenopausal women in Oslo occurred in a period with a substantial increase in the use of HRT. Future surveillance will reveal whether the last years' decline in use of HRT will be translated into increasing fracture rates.

Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

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Peng Xue

2013-01-01

Full Text Available Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochrane Library were undertaken to identify studies in humans of the association between growth hormone treatment and bone mineral density in growth hormone deficient adults. Random effects model was used for this meta-analysis. Results. A total of 20 studies (including one outlier study with 936 subjects were included in our research. We detected significant overall association of growth hormone treatment with increased bone mineral density of spine, femoral neck, and total body, but some results of subgroup analyses were not consistent with the overall analyses. Conclusions. Our meta-analysis suggested that growth hormone replacement therapy could have beneficial influence on bone mineral density in growth hormone deficient adults, but, in some subject populations, the influence was not evident.

Factors predicting successful discontinuation of continuous renal replacement therapy.

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Katayama, S; Uchino, S; Uji, M; Ohnuma, T; Namba, Y; Kawarazaki, H; Toki, N; Takeda, K; Yasuda, H; Izawa, J; Tokuhira, N; Nagata, I

2016-07-01

This multicentre, retrospective observational study was conducted from January 2010 to December 2010 to determine the optimal time for discontinuing continuous renal replacement therapy (CRRT) by evaluating factors predictive of successful discontinuation in patients with acute kidney injury. Analysis was performed for patients after CRRT was discontinued because of renal function recovery. Patients were divided into two groups according to the success or failure of CRRT discontinuation. In multivariate logistic regression analysis, urine output at discontinuation, creatinine level and CRRT duration were found to be significant variables (area under the receiver operating characteristic curve for urine output, 0.814). In conclusion, we found that higher urine output, lower creatinine and shorter CRRT duration were significant factors to predict successful discontinuation of CRRT.

NICOTINE EFFECTS ON THE MOTOR ACTIVITY OF MICE EXPOSED PRENATALLY TO THE NICOTINIC AGONIST ANATOXIN-A.

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Several studies in the literature have shown that exposure of mice and rats to nicotine early in development alters its effects when the rodents are subsequently challenged with nicotine. Anatoxin-a is a nicotinic agonist produced by several genera of cyanobacteria, and has caus...

Central estrogenic pathways protect against the depressant action of acute nicotine on reflex tachycardia in female rats

International Nuclear Information System (INIS)

El-Mas, Mahmoud M.; Fouda, Mohamed A.; El-gowilly, Sahar M.; Saad, Evan I.

2012-01-01

We have previously shown that acute exposure of male rats to nicotine preferentially attenuates baroreceptor-mediated control of reflex tachycardia in contrast to no effect on reflex bradycardia. Here, we investigated whether female rats are as sensitive as their male counterparts to the baroreflex depressant effect of nicotine and whether this interaction is modulated by estrogen. Baroreflex curves relating reflex chronotropic responses evoked by i.v. doses (1–16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), were constructed in conscious freely moving proestrus, ovariectomized (OVX), and estrogen (50 μg/kg/day s.c., 5 days)-replaced OVX (OVXE 2 ) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRS PE and BRS SNP ). Nicotine (100 μg/kg i.v.) reduced BRS SNP in OVX rats but not in proestrus or OVXE 2 rats. The attenuation of reflex tachycardia by nicotine was also evident in diestrus rats, which exhibited plasma estrogen levels similar to those of OVX rats. BRS PE was not affected by nicotine in all rat preparations. Experiments were then extended to determine whether central estrogenic receptors modulate the nicotine–BRS SNP interaction. Intracisteral (i.c.) treatment of OVX rats with estrogen sulfate (0.2 μg/rat) abolished the BRS SNP attenuating effect of i.v. nicotine. This protective effect of estrogen disappeared when OVX rats were pretreated with i.c. ICI 182,780 (50 μg/rat, selective estrogen receptor antagonist). Together, these findings suggest that central neural pools of estrogen receptors underlie the protection offered by E 2 against nicotine-induced baroreceptor dysfunction in female rats. -- Highlights: ► Estrogen protects against the depressant effect of nicotine on reflex tachycardia. ► The baroreflex response and estrogen status affect the nicotine–BRS interaction. ► The protection offered by estrogen is mediated via central estrogen receptors.

Orthosteric and Allosteric Ligands of Nicotinic Acetylcholine Receptors for Smoking Cessation

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Tasnim S. Mohamed

2015-11-01

Full Text Available Nicotine addiction, the result of tobacco use, leads to over six million premature deaths world-wide, a number that is expected to increase by a third within the next two decades. While more than half of smokers want and attempt to quit, only a small percentage of smokers are able to quit without pharmacological interventions. Therefore, over the past decades, researchers in academia and the pharmaceutical industry have focused their attention on the development of more effective smoking cessation therapies, which is now a growing 1.9 billion dollar market. Because the role of neuronal nicotinic acetylcholine receptors (nAChR in nicotine addiction is well established, nAChR based therapeutics remain the leading strategy for smoking cessation. However, the development of neuronal nAChR drugs that are selective for a nAChR subpopulation is challenging, and only few neuronal nAChR drugs are clinically available. Among the many neuronal nAChR subtypes that have been identified in the brain, the α4β2 subtype is the most abundant and plays a critical role in nicotine addiction. Here, we review the role of neuronal nAChRs, especially the α4β2 subtype, in the development and treatment of nicotine addiction. We also compare available smoking cessation medications and other nAChR orthosteric and allosteric ligands that have been developed with emphasis on the difficulties faced in the development of clinically useful compounds with high nAChR subtype selectivity.

Assessment of nicotine concentration in electronic nicotine delivery system (ENDS) liquids and precision of dosing to aerosol.

Science.gov (United States)

Kosmider, Leon; Sobczak, Andrzej; Szołtysek-Bołdys, Izabela; Prokopowicz, Adam; Skórka, Agnieszka; Abdulafeez, Oluyadi; Koszowski, Bartosz

2015-01-01

Global use of electronic nicotine delivery systems (ENDS; also called electronic cigarettes, e-cigarettes) has increased dramatically in recent years. However, due to the limited safety studies and growing concerns on the potential toxicity from long term use of ENDS, many national and international governments have employed regulatory measures to curtail its use. One of the most significant challenges regulators of ENDS encounter is the lack of quality standards to assess ENDS, e-liquid (solution used with ENDS which contain nicotine--a highly toxic and addictive substance), and amount of nicotine delivery to aerosol during ENDS use. Aims of the study were to (1) measure and compare nicotine concentration in e-liquids to values reported by manufacturers on packaging labels; (2) assess the precision of nicotine delivery from tank during aerosol formation. Methods: Nine popular Polish e-liquids (based on the market share data from October 2014) were purchased for the study. The labelled nicotine concentration for the selected e-liquids ranged between 11-25 mg/mL. All e-liquids were aerosolized in the laboratory using a smoking simulation machine (Palaczbot). Each e-liquid was aerosolized in a series of 6 consecutive bouts. A single bout consisted of 15 puffs with the following puff topography: 65 mL puff volume, 2.8 sec. puff duration, and 19 sec. interpuff interval. A total of 90 puffs were generated from each e-liquid. Nicotine content in the e-liquids and the aerosol generated were determined by gas chromatography with thermionic sensitive detection (GC-TSD). For seven of nine analyzed e-liquids, the difference between measured and manufacturer labeled nicotine concentration was less than 10%. Nicotine dose in aerosol per bout ranged between 0.77-1.49 mg (equivalent to one-half the nicotine a smoker inhales from a single combustible cigarette). Our analysis showed the high consistency between the labeled and measured nicotine concentration for popular on the

A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation

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Muelken, Peter; Schmidt, Clare E.; Shelley, David; Tally, Laura; Harris, Andrew C.

2015-01-01

Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models

Nicotine Impairs Macrophage Control of Mycobacterium tuberculosis.

Science.gov (United States)

Bai, Xiyuan; Stitzel, Jerry A; Bai, An; Zambrano, Cristian A; Phillips, Matthew; Marrack, Philippa; Chan, Edward D

2017-09-01

Pure nicotine impairs macrophage killing of Mycobacterium tuberculosis (MTB), but it is not known whether the nicotine component in cigarette smoke (CS) plays a role. Moreover, the mechanisms by which nicotine impairs macrophage immunity against MTB have not been explored. To neutralize the effects of nicotine in CS extract, we used a competitive inhibitor to the nicotinic acetylcholine receptor (nAChR)-mecamylamine-as well as macrophages derived from mice with genetic disruption of specific subunits of nAChR. We also determined whether nicotine impaired macrophage autophagy and whether nicotine-exposed T regulatory cells (Tregs) could subvert macrophage anti-MTB immunity. Mecamylamine reduced the CS extract increase in MTB burden by 43%. CS extract increase in MTB was also significantly attenuated in macrophages from mice with genetic disruption of either the α7, β2, or β4 subunit of nAChR. Nicotine inhibited autophagosome formation in MTB-infected THP-1 cells and primary murine alveolar macrophages, as well as increased the intracellular MTB burden. Nicotine increased migration of THP-1 cells, consistent with the increased number of macrophages found in the lungs of smokers. Nicotine induced Tregs to produce transforming growth factor-β. Naive mouse macrophages co-cultured with nicotine-exposed Tregs had significantly greater numbers of viable MTB recovered with increased IL-10 production and urea production, but no difference in secreted nitric oxide as compared with macrophages cocultured with unexposed Tregs. We conclude that nicotine in CS plays an important role in subverting macrophage control of MTB infection.

Estrogen replacement therapy and cardioprotection: mechanisms and controversies

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M.T.R. Subbiah

2002-03-01

Full Text Available Epidemiological and case-controlled studies suggest that estrogen replacement therapy might be beneficial in terms of primary prevention of coronary heart disease (CHD. This beneficial effect of estrogens was initially considered to be due to the reduction of low density lipoproteins (LDL and to increases in high density lipoproteins (HDL. Recent studies have shown that estrogens protect against oxidative stress and decrease LDL oxidation. Estrogens have direct effects on the arterial tissue and modulate vascular reactivity through nitric oxide and prostaglandin synthesis. While many of the effects of estrogen on vascular tissue are believed to be mediated by estrogen receptors alpha and ß, there is evidence for `immediate non-genomic' effects. The role of HDL in interacting with 17ß-estradiol including its esterification and transfer of esterified estrogens to LDL is beginning to be elucidated. Despite the suggested positive effects of estrogens, two recent placebo-controlled clinical trials in women with CHD did not detect any beneficial effects on overall coronary events with estrogen therapy. In fact, there was an increase in CHD events in some women. Mutations in thrombogenic genes (factor V Leiden, prothrombin mutation, etc. in a subset of women may play a role in this unexpected finding. Thus, the cardioprotective effect of estrogens appears to be more complicated than originally thought and requires more research.

Role of telehealth in renal replacement therapy education.

Science.gov (United States)

Malkina, Anna; Tuot, Delphine S

2018-03-01

The prevalence of end-stage renal disease is rising in the United States, which bears high financial and public health burden. The most common modality of renal replacement therapy (RRT) in the United States is in-center hemodialysis. Many patients report lack of comprehensive and timely education about their treatment options, which may preclude them from participating in home-based dialysis therapies and kidney transplantation evaluation. While RRT education has traditionally been provided in-person, the rise of telehealth has afforded new opportunities to improve upon the status quo. For example, technology-augmented RRT education has recently been implemented into telehealth nephrology clinics, informational websites and mobile applications maintained by professional organizations, patient-driven forums on social media, and multimodality programs. The benefits of technology in RRT education are increased access for geographically isolated and/or medically frail patients, versatility of content delivery, information repetition to enhance knowledge retention, and interpersonal connection for educational content and emotional support. Challenges center around privacy and accuracy of information sharing, in addition to differential access to technology due to age and socioeconomic status. A review of available scholarly and social media resources suggests that technology-aided delivery of education about treatment options for end-stage renal disease provides an important alternative and/or supplemental resource for patients and families. © 2018 Wiley Periodicals, Inc.

Measurement of nicotine in household dust

International Nuclear Information System (INIS)

Kim, Sungroul; Aung, Ther; Berkeley, Emily; Diette, Gregory B.; Breysse, Patrick N.

2008-01-01

An analytical method of measuring nicotine in house dust was optimized and associations among three secondhand smoking exposure markers were evaluated, i.e., nicotine concentrations of both house dust and indoor air, and the self-reported number of cigarettes smoked daily in a household. We obtained seven house dust samples from self-reported nonsmoking homes and 30 samples from smoking homes along with the information on indoor air nicotine concentrations and the number of cigarettes smoked daily from an asthma cohort study conducted by the Johns Hopkins Center for Childhood Asthma in the Urban Environment. House dust nicotine was analyzed by isotope dilution gas chromatography-mass spectrometry (GC/MS). Using our optimized method, the median concentration of nicotine in the dust of self-reported nonsmoking homes was 11.7 ng/mg while that of smoking homes was 43.4 ng/mg. We found a substantially positive association (r=0.67, P<0.0001) between house dust nicotine concentrations and the numbers of cigarettes smoked daily. Optimized analytical methods showed a feasibility to detect nicotine in house dust. Our results indicated that the measurement of nicotine in house dust can be used potentially as a marker of longer term SHS exposure

Rationalization of a nanoparticle-based nicotine nanovaccine as an effective next-generation nicotine vaccine: A focus on hapten localization.

Science.gov (United States)

Zhao, Zongmin; Hu, Yun; Harmon, Theresa; Pentel, Paul; Ehrich, Marion; Zhang, Chenming

2017-09-01

A lipid-polymeric hybrid nanoparticle-based next-generation nicotine nanovaccine was rationalized in this study to combat nicotine addiction. A series of nanovaccines, which had nicotine-haptens localized on carrier protein (LPKN), nanoparticle surface (LPNK), or both (LPNKN), were designed to study the impact of hapten localization on their immunological efficacy. All three nanovaccines were efficiently taken up and processed by dendritic cells. LPNKN induced a significantly higher immunogenicity against nicotine and a significantly lower anti-carrier protein antibody level compared to LPKN and LPNK. Meanwhile, it was found that the anti-nicotine antibodies elicited by LPKN and LPNKN bind nicotine stronger than those elicited by LPKN, and LPNK and LPNKN resulted in a more balanced Th1-Th2 immunity than LPKN. Moreover, LPNKN exhibited the best ability to block nicotine from entering the brain of mice. Collectively, the results demonstrated that the immunological efficacy of the hybrid nanoparticle-based nicotine vaccine could be enhanced by modulating hapten localization, providing a promising strategy to combatting nicotine addiction. Copyright © 2017 Elsevier Ltd. All rights reserved.

Demographics of paediatric renal replacement therapy in Europe

DEFF Research Database (Denmark)

Chesnaye, Nicholas; Bonthuis, Marjolein; Schaefer, Franz

2014-01-01

BACKGROUND: The ESPN/ERA-EDTA Registry collects data on European children with end-stage renal disease receiving renal replacement therapy (RRT) who are listed on national and regional renal registries in Europe. In this paper we report on the analysis of demographic data collected from 2009...... to 2011. METHODS: Data on primary renal disease, incidence, prevalence, 4-year survival, transplantation rate and causes of death in paediatric patients receiving RRT were extracted from the ESPN/ERA-EDTA Registry for 37 European countries. RESULTS: The incidence of RRT in paediatric patients in Europe...... during the study period was 5.5 cases per million age-related population (pmarp) in patients aged 0-14 years and varied markedly between countries (interquartile range 3.4-7.0 years). The prevalence of RRT was 27.9 pmarp and increased with age, with 67 % of prevalent patients living with a functioning...

Renouncement of renal replacement therapy: withdrawal and refusal

Directory of Open Access Journals (Sweden)

José Andrade Moura Neto

Full Text Available Abstract Renouncement of renal replacement therapy (RRT is a medical dilemma. This review covers the concept, the magnitude, the prognosis, and discusses strategies and management approaches about this subject in patients with CKD and AKI. Evidence suggests that refusal is more frequent and carries a more guarded prognosis than withdrawal of RRT. When RRT is not expected to be beneficial in terms of survival or quality of life, conservative treatment and palliative care are alternatives. We review the historical evolution of guidelines about renouncement of RRT and palliative care, and highlight the absence of specific recommendations in Brazil. However renouncement of RRT may be ethically and legally accepted in Brazil, as the right to a dignified death. Longer life expectancy, economic pressures, and greater awareness will require a more detailed discussion about indications and sustainable use of RRT, and possibly the elaboration of national guidelines.

Precision Fluid Management in Continuous Renal Replacement Therapy.

Science.gov (United States)

Murugan, Raghavan; Hoste, Eric; Mehta, Ravindra L; Samoni, Sara; Ding, Xiaoqiang; Rosner, Mitchell H; Kellum, John A; Ronco, Claudio

2016-01-01

Fluid management during continuous renal replacement therapy (CRRT) in critically ill patients is a dynamic process that encompasses 3 inter-related goals: maintenance of the patency of the CRRT circuit, maintenance of plasma electrolyte and acid-base homeostasis and regulation of patient fluid balance. In this article, we report the consensus recommendations of the 2016 Acute Disease Quality Initiative XVII conference on 'Precision Fluid Management in CRRT'. We discuss the principles of fluid management, describe various prescription methods to achieve circuit integrity and introduce the concept of integrated fluid balance for tailoring fluid balance to the needs of the individual patient. We suggest that these recommendations could serve to develop the best clinical practice and standards of care for fluid management in patients undergoing CRRT. Finally, we identify and highlight areas of uncertainty in fluid management and set an agenda for future research. © 2016 S. Karger AG, Basel.

Thyroid hormone replacement therapy

NARCIS (Netherlands)

Wiersinga, W. M.

2001-01-01

Thyroid hormone replacement has been used for more than 100 years in the treatment of hypothyroidism, and there is no doubt about its overall efficacy. Desiccated thyroid contains both thyroxine (T(4)) and triiodothyronine (T(3)); serum T(3) frequently rises to supranormal values in the absorption

Early stage cognitive impairment in Parkinson’s disease and the influence of dopamine replacement therapy

NARCIS (Netherlands)

Miah, I.P.; Olde Dubbelink, K.T.E.; Stoffers, D.; Deijen, J.B.; Berendse, H.W.

2012-01-01

Background and purpose: The aim of this study was to establish the cognitive profile of newly diagnosed untreated (de novo) patients with Parkinson's disease (PD) and more advanced, treated patients, and to determine the effects of dopamine (DA) replacement therapy. Methods: A cohort of 23 de novo

Should we start and continue growth hormone (GH) replacement therapy in adults with GH deficiency?

NARCIS (Netherlands)

ter Maaten, JC

2000-01-01

During the last decade, growth hormone deficiency (GHD) in adults has been described as a clinical syndrome. Central features of this entity include increased fat mass, reduced muscle and bone mass, as well as impaired exercise capacity and quality of life. GH replacement therapy has been initiated

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

Energy Technology Data Exchange (ETDEWEB)

Zago, A. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Leão, R.M.; Carneiro-de-Oliveira, P.E. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil); Marin, M.T.; Cruz, F.C. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Planeta, C.S. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil)

2011-11-18

Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

International Nuclear Information System (INIS)

Zago, A.; Leão, R.M.; Carneiro-de-Oliveira, P.E.; Marin, M.T.; Cruz, F.C.; Planeta, C.S.

2011-01-01

Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

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A. Zago

2012-01-01

Full Text Available Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although cross-sensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P 28-37 and adult (P60-67 rats received nicotine (0.4 mg/kg, sc or saline (0.9% NaCl, sc and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

Prefrontal gamma-aminobutyric acid type A receptor insertion controls cue-induced relapse to nicotine seeking.

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Lubbers, Bart R; van Mourik, Yvar; Schetters, Dustin; Smit, August B; De Vries, Taco J; Spijker, Sabine

2014-11-01

Current smoking cessation therapies offer limited success, as relapse rates remain high. Nicotine, which is the major component of tobacco smoke, is thought to be primarily responsible for the addictive properties of tobacco. However, little is known about the molecular mechanisms underlying nicotine relapse, hampering development of more effective therapies. The objective of this study was to elucidate the role of medial prefrontal cortex (mPFC) glutamatergic and gamma-aminobutyric acid (GABA)ergic receptors in controlling relapse to nicotine seeking. Using an intravenous self-administration model, we studied glutamate and gamma-aminobutyric acid receptor regulation in the synaptic membrane fraction of the rat mPFC following extinction and cue-induced relapse to nicotine seeking. Subsequently, we locally intervened at the level of GABAergic signaling by using a mimetic peptide of the GABA receptor associated protein-interacting domain of GABA type A (GABAA) receptor subunit γ2 (TAT-GABAγ2) and muscimol, a GABAA receptor agonist. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate receptors were not regulated after the 30-min relapse test. However, GABAA receptor subunits α1 and γ2 were upregulated, and interference with GABAA receptor insertion in the cell membrane using the TAT-GABAγ2 peptide in the dorsal mPFC, but not the ventral mPFC, significantly increased responding during relapse. Increasing GABAA transmission with muscimol in the dorsal and ventral mPFC attenuated relapse. These data indicate that cue-induced relapse entails a GABAergic plasticity mechanism that limits nicotine seeking by restoring inhibitory control in the dorsal mPFC. GABAA receptor-mediated neurotransmission in the dorsal mPFC constitutes a possible future therapeutic target for maintaining smoking abstinence. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

High-affinity α4β2 nicotinic receptors mediate the impairing effects of acute nicotine on contextual fear extinction.

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Kutlu, Munir Gunes; Holliday, Erica; Gould, Thomas J

2016-02-01

Previously, studies from our lab have shown that while acute nicotine administered prior to training and testing enhances contextual fear conditioning, acute nicotine injections prior to extinction sessions impair extinction of contextual fear. Although there is also strong evidence showing that the acute nicotine's enhancing effects on contextual fear conditioning require high-affinity α4β2 nicotinic acetylcholine receptors (nAChRs), it is unknown which nAChR subtypes are involved in the acute nicotine-induced impairment of contextual fear extinction. In this study, we investigated the effects of acute nicotine administration on contextual fear extinction in knock-out (KO) mice lacking α4, β2 or α7 subtypes of nAChRs and their wild-type (WT) littermates. Both KO and WT mice were first trained and tested for contextual fear conditioning and received a daily contextual extinction session for 4 days. Subjects received intraperitoneal injections of nicotine (0.18 mg/kg) or saline 2-4 min prior to each extinction session. Our results showed that the mice that lack α4 and β2 subtypes of nAChRs showed normal contextual fear extinction but not the acute nicotine-induced impairment while the mice that lack the α7 subtype showed both normal contextual extinction and nicotine-induced impairment of contextual extinction. In addition, control experiments showed that acute nicotine-induced impairment of contextual fear extinction persisted when nicotine administration was ceased and repeated acute nicotine administrations alone did not induce freezing behavior in the absence of context-shock learning. These results clearly demonstrate that high-affinity α4β2 nAChRs are necessary for the effects of acute nicotine on contextual fear extinction. Copyright © 2015 Elsevier Inc. All rights reserved.

Attenuated nicotine‐like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily

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Cunningham, Colin S; Moerke, Megan J; Javors, Martin A; Carroll, F Ivy

2016-01-01

Background and Purpose Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. Experimental Approach The impact of daily nicotine treatment on the effects of nicotinic ACh receptor (nAChR) agonists was examined in two groups of rhesus monkeys discriminating nicotine (1.78 mg·kg−1 base weight) from saline. One group received additional nicotine treatment post‐session (1.78 mg·kg−1 administered five times daily, each dose 2 h apart; i.e. Daily group), and the second group did not (Intermittent group). Key Results Daily repeated nicotine treatment produced a time‐related increase in saliva cotinine. There was no significant difference in the ED50 values of the nicotine discriminative stimulus between the Daily and Intermittent group. Mecamylamine antagonized the effects of nicotine, whereas dihydro‐β‐erythroidine did not. Midazolam produced 0% nicotine‐lever responding. The nAChR agonists epibatidine, RTI‐36, cytisine and varenicline produced >96% nicotine‐lever responding in the Intermittent group. The respective maximum effects in the Daily group were 100, 72, 59 and 28%, which shows that the ability of varenicline to produce nicotine‐like responding was selectively decreased in the Daily as compared with the Intermittent group. When combined with nicotine, both varenicline and cytisine increased the potency of nicotine to produce discriminative stimulus effects. Conclusion and Implications Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. Collectively, these results strongly suggest that varenicline differs from nicotine in its selectivity for multiple nAChR subtypes. PMID:27667659

A pilot study on nicotine residues in houses of electronic cigarette users, tobacco smokers, and non-users of nicotine-containing products.

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Bush, Derek; Goniewicz, Maciej L

2015-06-01

Nicotine deposited on the surfaces has been shown to react with airborne chemicals leading to formation of carcinogens and contributing to thirdhand exposure. While prior studies revealed nicotine residues in tobacco smokers' homes, none have examined the nicotine residue in electronic cigarette (e-cigarette) users' homes. We measured nicotine on the surfaces in households of 8 e-cigarette users, 6 cigarette smokers, and 8 non-users of nicotine-containing products in Western New York, USA. Three surface wipe samples were taken from the floor, wall and window. Nicotine was extracted from the wipes and analyzed using gas chromatography. Half of the e-cigarette users' homes had detectable levels of nicotine on surfaces whereas nicotine was found in all of the tobacco cigarette smokers' homes. Trace amounts of nicotine were also detected in half of the homes of non-users of nicotine-containing products. Nicotine levels in e-cigarette users homes was significantly lower than that found in cigarette smokers homes (average concentration 7.7±17.2 vs. 1303±2676 μg/m2; pe-cigarette users and non-users (p>0.05). Nicotine is a common contaminant found on indoor surfaces. Using e-cigarettes indoors leads to significantly less thirdhand exposure to nicotine compared to smoking tobacco cigarettes. Copyright © 2015 Elsevier B.V. All rights reserved.

Nicotine, adolescence, and stress: A review of how stress can modulate the negative consequences of adolescent nicotine abuse.

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Holliday, Erica; Gould, Thomas J

2016-06-01

In order to continue the decline of smoking prevalence, it is imperative to identify factors that contribute to the development of nicotine and tobacco addiction, such as adolescent initiation of nicotine use, adolescent stress, and their interaction. This review highlights the biological differences between adolescent and adults in nicotine use and resulting effects, and examines the enduring consequences of adolescent nicotine administration. A review of both clinical and preclinical literature indicates that adolescent, but not adult, nicotine administration leads to increased susceptibility for development of long-lasting impairments in learning and affect. Finally, the role stress plays in normal adolescent development, the deleterious effects stress has on learning and memory, and the negative consequences resulting from the interaction of stress and nicotine during adolescence is reviewed. The review concludes with ways in which future policies could benefit by addressing adolescent stress as a means of reducing adolescent nicotine abuse. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adolescents' understanding and use of nicotine in e-cigarettes.

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Pepper, Jessica K; Farrelly, Matthew C; Watson, Kimberly A

2018-07-01

Nicotine harms adolescent brain development and contributes to addiction. Some adolescents report using nicotine-free e-cigarettes, but the accuracy of their reporting is unclear. We explored adolescents' use of nicotine-free e-cigarettes and understanding of chemicals in e-cigarettes, including nicotine. Using social media, we recruited 1589 US adolescents (aged 15-17) who reported past 30-day use of e-cigarettes in 2016. We assessed perceptions of the nicotine source in e-liquid and whether e-cigarette aerosol is just "water vapor." We explored differences among adolescents who usually used e-cigarettes with nicotine (n = 473) and without nicotine (n = 452). We used weights to calibrate our sample to the Youth Risk Behavior Survey. Twenty-nine percent usually used e-cigarettes without nicotine, 28% with nicotine, 39% with "both," and 5% were "not sure." Few participants (17% of non-nicotine users vs. 34% of nicotine users, p e-cigarette aerosol was just water vapor were more likely to usually use without nicotine. Older adolescents and current tobacco users were less likely to usually use without nicotine. The adolescents who reported usually using e-cigarettes without nicotine had poorer knowledge of e-cigarettes. This lack of understanding could contribute to inaccurate reporting of nicotine use. Most youth thought the nicotine in e-cigarettes was artificial, potentially indicating a belief that this nicotine is "safer." The US Food & Drug Administration will require nicotine warnings on e-cigarettes in 2018; a complementary educational campaign could address youths' misperceptions about nicotine and other chemicals in e-cigarette aerosol. Copyright © 2018 Elsevier Ltd. All rights reserved.

Menopause and hormone replacement therapy

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Ali Baziad

2001-12-01

Full Text Available The global population in the 21st century has reached 6.2 billion people, by the year 2025 it is to be around 8.3-8.5 billion, and will increase further. Elderly people are expected to grow rapidly than other groups. The fastest increase in the elderly population will take place in Asia. Life expectancy is increasing steadily throughout developed and developing countries. For many  menopausal women, increased life expectancy will accompanied by many health problems. The consequences of estrogen deficiency are the menopausal symptoms. The treatment of menopause related complaints and diseases became an  important socioeconomic and medical issue. Long term symptoms, such as the increase in osteoporosis fractures, cardio and cerebrovascular disesses and dementia, created a large financial burden on individuals and society. All these health problems can be lreated or prevented by hormone replacement therapy (HRT. Natural HRT is usually prefened. Synthetic  estrogen in oral contraceptives (oc are not recommended for HRT. Many contra-indications for oc, but now it is widely usedfor HRT. The main reasons for discontinuing HRT are unwanted bleeding, fear of cancer, and negative side effects. Until now there are sill debates about the rebrtonship between HRT and the incidence of breast cancer. Many data showed that there were no clear relationship between the use of HRT and breast cancer. ThereÎore, nwny experts advocate the use of HRTfrom the first sign of climacteric complaints until death. (Med J Indones 2001;10: 242-51Keywords: estrogen deficiency, climacteric phases, tibolone.

Vitamin E Nicotinate

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Kimbell R. Duncan

2017-03-01

Full Text Available Vitamin E refers to a family of compounds that function as lipid-soluble antioxidants capable of preventing lipid peroxidation. Naturally occurring forms of vitamin E include tocopherols and tocotrienols. Vitamin E in dietary supplements and fortified foods is often an esterified form of α-tocopherol, the most common esters being acetate and succinate. The vitamin E esters are hydrolyzed and converted into free α-tocopherol prior to absorption in the intestinal tract. Because its functions are relevant to many chronic diseases, vitamin E has been extensively studied in respect to a variety of diseases as well as cosmetic applications. The forms of vitamin E most studied are natural α-tocopherol and the esters α-tocopheryl acetate and α-tocopheryl succinate. A small number of studies include or focus on another ester form, α-tocopheryl nicotinate, an ester of vitamin E and niacin. Some of these studies raise the possibility of differences in metabolism and in efficacy between vitamin E nicotinate and other forms of vitamin E. Recently, through metabolomics studies, we identified that α-tocopheryl nicotinate occurs endogenously in the heart and that its level is dramatically decreased in heart failure, indicating the possible biological importance of this vitamin E ester. Since knowledge about vitamin E nicotinate is not readily available in the literature, the purpose of this review is to summarize and evaluate published reports, specifically with respect to α-tocopheryl nicotinate with an emphasis on the differences from natural α-tocopherol or α-tocopheryl acetate.

Effects of the nicotinic agonist varenicline, nicotinic antagonist r-bPiDI, and DAT inhibitor (R)-modafinil on co-use of ethanol and nicotine in female P rats.

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Maggio, Sarah E; Saunders, Meredith A; Baxter, Thomas A; Nixon, Kimberly; Prendergast, Mark A; Zheng, Guangrong; Crooks, Peter; Dwoskin, Linda P; Slack, Rachel D; Newman, Amy H; Bell, Richard L; Bardo, Michael T

2018-05-01

Co-users of alcohol and nicotine are the largest group of polysubstance users worldwide. Commonalities in mechanisms of action for ethanol (EtOH) and nicotine proposes the possibility of developing a single pharmacotherapeutic to treat co-use. Toward developing a preclinical model of co-use, female alcohol-preferring (P) rats were trained for voluntary EtOH drinking and i.v. nicotine self-administration in three phases: (1) EtOH alone (0 vs. 15%, two-bottle choice), (2) nicotine alone (0.03 mg/kg/infusion, active vs. inactive lever), and (3) concurrent access to both EtOH and nicotine. Using this model, we examined the effects of (1) varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist with high affinity for the α4β2* subtype; (2) r-bPiDI, a subtype-selective antagonist at α6β2* nAChRs; and (3) (R)-modafinil, an atypical inhibitor of the dopamine transporter (DAT). In phases 1 and 2, pharmacologically relevant intake of EtOH and nicotine was achieved. In the concurrent access phase (phase 3), EtOH consumption decreased while nicotine intake increased relative to phases 1 and 2. For drug pretreatments, in the EtOH access phase (phase 1), (R)-modafinil (100 mg/kg) decreased EtOH consumption, with no effect on water consumption. In the concurrent access phase, varenicline (3 mg/kg), r-bPiDI (20 mg/kg), and (R)-modafinil (100 mg/kg) decreased nicotine self-administration but did not alter EtOH consumption, water consumption, or inactive lever pressing. These results indicate that therapeutics which may be useful for smoking cessation via selective inhibition of α4β2* or α6β2* nAChRs, or DAT inhibition, may not be sufficient to treat EtOH and nicotine co-use.

Continuous renal replacement therapy improves renal recovery from acute renal failure.

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Jacka, Michael J; Ivancinova, Xenia; Gibney, R T Noel

2005-03-01

Acute renal failure (ARF) occurs in up to 10% of critically ill patients, with significant associated morbidity and mortality. The optimal mode of renal replacement therapy (RRT) remains controversial. This retrospective study compared continuous renal replacement therapy (CRRT) and intermittent hemodialysis (IHD) for RRT in terms of intensive care unit (ICU) and hospital mortality, and renal recovery. We reviewed the records of all patients undergoing RRT for the treatment of ARF over a 12-month period. Patients were compared according to mode of RRT, demographics, physiologic characteristics, and outcomes of ICU and hospital mortality and renal recovery using the Chi square, Student's t test, and multiple logistic regression as appropriate. 116 patients with renal insufficiency underwent RRT during the study period. Of these, 93 had ARF. The severity of illness of CRRT patients was similar to that of IHD patients using APACHE II (25.1 vs 23.5, P = 0.37), but they required significantly more intensive nursing (therapeutic intervention scale 47.8 vs 37.6, P = 0.0001). Mortality was associated with lower pH at presentation (P = 0.003) and increasing age (P = 0.03). Renal recovery was significantly more frequent among patients initially treated with CRRT (21/24 vs 5/14, P = 0.0003). Further investigation to define optimal timing, dose, and duration of RRT may be beneficial. Although further study is needed, this study suggests that renal recovery may be better after CRRT than IHD for ARF. Mortality was not affected significantly by RRT mode.

Tying up Nicotine: New Selective Competitive Antagonist of the Neuronal Nicotinic Acetylcholine Receptors

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Petersen, Ida Nymann; Crestey, François; Jensen, Anders A

2015-01-01

Conformational restriction of the pyrrolidine nitrogen in nicotine by the introduction of an ethylene bridge provided a potent and selective antagonist of the α4β2-subtype of the nicotinic acetylcholine receptors. Resolution by chiral SFC, pharmacological characterization of the two enantiomers...

Nicotine Contamination in Particulate Matter Sampling

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Eric Garshick

2009-02-01

Full Text Available We have addressed potential contamination of PM2.5 filter samples by nicotine from cigarette smoke. We collected two nicotine samples – one nicotine sampling filter was placed in-line after the collection of PM2.5 and the other stood alone. The overall correlation between the two nicotine filter levels was 0.99. The nicotine collected on the “stand-alone” filter was slightly greater than that on the “in-line” filter (mean difference = 1.10 μg/m3, but the difference was statistically significant only when PM2.5 was low (≤ 50 μg/m3. It is therefore important to account for personal and secondhand smoke exposure while assessing occupational and environmental PM.

Views and Preferences for Nicotine Products as an Alternative to Smoking: A Focus Group Study of People Living with Mental Disorders

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Carla Meurk

2016-11-01

Full Text Available Aims and Background: People living with mental disorders experience a disproportionately higher burden of tobacco-related disease than the general population. Long-term substitution with less harmful nicotine products could reduce the tobacco-related harm among this population. This study investigated the views and preferences of people with mental health disorders about different nicotine products and their use as long-term substitutes for cigarettes. Methods: Semi-structured focus group discussion followed by a brief questionnaire. The discussion transcripts were analysed for content and themes and quantitative data summarised with descriptive statistics. Results: Twenty-nine participants took part in four focus groups. Vaping devices were the most acceptable nicotine products discussed; however preferences for nicotine products were individual and varied along aesthetic, pragmatic, sensory and symbolic dimensions. The concept of tobacco harm reduction was unfamiliar to participants, however they generally agreed with the logic of replacing cigarettes with less harmful nicotine products. Barriers to activating tobacco harm reduction included the symbolism of smoking and quitting; the importance placed on health; the consumer appeal of alternatives; and cost implications. Discussion and Conclusions: Engaging this population in tobacco harm reduction options will require communication that challenges black and white thinking (a conceptual framework in which smoking cigarettes or quitting all nicotine are the only legitimate options as in practice this serves to support the continuance of smoking. Consumers should be encouraged to trial a range of nicotine products to find the most acceptable alternative to smoking that reduces health harms. Providing incentives to switch to nicotine products could help overcome barriers to using less harmful nicotine products among mental health consumers.

Fetal Nicotine Exposure Increases Preference for Nicotine Odor in Early Postnatal and Adolescent, but Not Adult, Rats

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Mantella, Nicole M.; Kent, Paul F.; Youngentob, Steven L.

2013-01-01

Human studies demonstrate a four-fold increased possibility of smoking in the children of mothers who smoked during pregnancy. Nicotine is the active addictive component in tobacco-related products, crossing the placenta and contaminating the amniotic fluid. It is known that chemosensory experience in the womb can influence postnatal odor-guided preference behaviors for an exposure stimulus. By means of behavioral and neurophysiologic approaches, we examined whether fetal nicotine exposure, using mini-osmotic pumps, altered the response to nicotine odor in early postnatal (P17), adolescent (P35) and adult (P90) progeny. Compared with controls, fetal exposed rats displayed an altered innate response to nicotine odor that was evident at P17, declined in magnitude by P35 and was absent at P90 - these effects were specific to nicotine odor. The behavioral effect in P17 rats occurred in conjunction with a tuned olfactory mucosal response to nicotine odor along with an untoward consequence on the epithelial response to other stimuli – these P17 neural effects were absent in P35 and P90 animals. The absence of an altered neural effect at P35 suggests that central mechanisms, such as nicotine-induced modifications of the olfactory bulb, bring about the altered behavioral response to nicotine odor. Together, these findings provide insights into how fetal nicotine exposure influences the behavioral preference and responsiveness to the drug later in life. Moreover, they add to a growing literature demonstrating chemosensory mechanisms by which patterns of maternal drug use can be conveyed to offspring, thereby enhancing postnatal vulnerability for subsequent use and abuse. PMID:24358374

Understanding the continuous renal replacement therapy circuit for acute renal failure support: a quality issue in the intensive care unit.

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Boyle, Martin; Baldwin, Ian

2010-01-01

Delivery of renal replacement therapy is now a core competency of intensive care nursing. The safe and effective delivery of this form of therapy is a quality issue for intensive care, requiring an understanding of the principles underlying therapy and the functioning of machines used. Continuous hemofiltration, first described in 1977, used a system where blood flowed from arterial to venous cannulas through a small-volume, low-resistance, and high-flux filter. Monitoring of these early systems was limited, and without a machine interface, less nursing expertise was required. Current continuous renal replacement therapy machines offer user-friendly interfaces, cassette-style circuits, and comprehensive circuit diagnostics and monitoring. Although these machines conceal complexity behind a user-friendly interface, it remains important that nurses have sufficient knowledge for their use and the ability to compare and contrast circuit setups and functions for optimal and efficient treatment.

Effect of a nicotine vaccine on nicotine binding to the beta2-nAChRs in vivo in human tobacco smokers

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Esterlis, Irina; Hannestad, Jonas O.; Perkins, Evgenia; Bois, Frederic; D’Souza, D. Cyril; Tyndale, Rachel F.; Seibyl, John P.; Hatsukami, Dorothy M.; Cosgrove, Kelly P.; O’Malley, Stephanie S.

2013-01-01

Objective Nicotine acts in the brain to promote smoking in part by binding to the beta2-containing nicotinic acetylcholine receptors (β2*-nAChRs) and acting in the mesolimbic reward pathway. The effects of nicotine from smoking one tobacco cigarette are significant (80% of β2*-nAChRs occupied for >6h). This likely contributes to the maintenance of smoking dependence and low cessation outcomes. Development of nicotine vaccines provides potential for alternative treatments. We used [123I]5IA-85380 SPECT to evaluate the effect of 3′-AmNic-rEPA on the amount of nicotine that binds to the β2*-nAChRs in the cortical and subcortical regions in smokers. Method Eleven smokers (36years (SD=13); 19cig/day (SD=11) for 10years (SD=7) who were dependent on nicotine (Fagerström Test of Nicotine Dependence score =5.5 (SD=3); plasma nicotine 9.1 ng/mL (SD=5)) participated in 2 SPECT scan days: before and after immunization with 4–400μg doses of 3′-AmNic-rEPA. On SPECT scan days, 3 30-min baseline emission scans were obtained, followed by administration of IV nicotine (1.5mg/70kg) and up to 9 30-min emission scans. Results β2*-nAChR availability was quantified as VT/fP and nicotine binding was derived using the Lassen plot approach. Immunization led to a 12.5% reduction in nicotine binding (F=5.19, df=1,10, p=0.05). Significant positive correlations were observed between nicotine bound to β2*-nAChRs and nicotine injected before but not after vaccination (p=0.05 vs. p=0.98). There was a significant reduction in the daily number of cigarettes and desire for a cigarette (p=.01 and p=.04, respectively). Conclusions This proof-of-concept study demonstrates that immunization with nicotine vaccine can reduce the amount of nicotine binding to β2*-nAChRs and disrupt the relationship between nicotine administered vs. nicotine available to occupy β2*-nAChRs. PMID:23429725

Effects of a selective cannabinoid CB2 agonist and antagonist on intravenous nicotine self administration and reinstatement of nicotine seeking.

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Islam Gamaleddin

Full Text Available Over the last decade there have been significant advances in the discovery and understanding of the cannabinoid system along with the development of pharmacologic tools that modulate its function. Characterization of the crosstalk between nicotine addiction and the cannabinoid system may have significant implications on our understanding of the neurobiological mechanisms underlying nicotine dependence. Two types of cannabinoid receptors (CB1 and CB2 have been identified. CB1 receptors are expressed in the brain and modulate drug taking and drug seeking for various drugs of abuse, including nicotine. CB2 receptors have been recently identified in the brain and have been proposed to play a functional role in mental disorders and drug addiction. Our objective was to explore the role of CB2 receptors on intravenous nicotine self administration under two schedules of reinforcement (fixed and progressive ratio and on nicotine seeking induced by nicotine priming or by nicotine associated cues. For this, we evaluated the effects of various doses of the selective CB2 antagonist AM630 (1.25 to 5 mg/kg and CB2 agonist AM1241 (1 to 10 mg/kg on these behavioral responses in rats. Different groups of male Long Evans rats were trained to lever press for nicotine at a unit dose of 30 µg/kg/infusion. Subsequently, animals were randomized using a Latin-square design and injected with either AM1241 or AM630 using a counterbalanced within subject design. Administration of the CB2 ligands did not affect either nicotine-taking nicotine-seeking behavior. Our results do not support the involvement of CB2 receptors in nicotine-taking or nicotine-seeking behavior.

Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs

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Walther Donna

2007-04-01

Full Text Available Abstract Background Classical genetic studies indicate that nicotine dependence is a substantially heritable complex disorder. Genetic vulnerabilities to nicotine dependence largely overlap with genetic vulnerabilities to dependence on other addictive substances. Successful abstinence from nicotine displays substantial heritable components as well. Some of the heritability for the ability to quit smoking appears to overlap with the genetics of nicotine dependence and some does not. We now report genome wide association studies of nicotine dependent individuals who were successful in abstaining from cigarette smoking, nicotine dependent individuals who were not successful in abstaining and ethnically-matched control subjects free from substantial lifetime use of any addictive substance. Results These data, and their comparison with data that we have previously obtained from comparisons of four other substance dependent vs control samples support two main ideas: 1 Single nucleotide polymorphisms (SNPs whose allele frequencies distinguish nicotine-dependent from control individuals identify a set of genes that overlaps significantly with the set of genes that contain markers whose allelic frequencies distinguish the four other substance dependent vs control groups (p vs unsuccessful abstainers cluster in small genomic regions in ways that are highly unlikely to be due to chance (Monte Carlo p Conclusion These clustered SNPs nominate candidate genes for successful abstinence from smoking that are implicated in interesting functions: cell adhesion, enzymes, transcriptional regulators, neurotransmitters and receptors and regulation of DNA, RNA and proteins. As these observations are replicated, they will provide an increasingly-strong basis for understanding mechanisms of successful abstinence, for identifying individuals more or less likely to succeed in smoking cessation efforts and for tailoring therapies so that genotypes can help match smokers

Nicotine transport in lung and non-lung epithelial cells.

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Takano, Mikihisa; Kamei, Hidetaka; Nagahiro, Machi; Kawami, Masashi; Yumoto, Ryoko

2017-11-01

Nicotine is rapidly absorbed from the lung alveoli into systemic circulation during cigarette smoking. However, mechanism underlying nicotine transport in alveolar epithelial cells is not well understood to date. In the present study, we characterized nicotine uptake in lung epithelial cell lines A549 and NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Characteristics of [ 3 H]nicotine uptake was studied using these cell lines. Nicotine uptake in A549 cells occurred in a time- and temperature-dependent manner and showed saturation kinetics, with a Km value of 0.31mM. Treatment with some organic cations such as diphenhydramine and pyrilamine inhibited nicotine uptake, whereas treatment with organic cations such as carnitine and tetraethylammonium did not affect nicotine uptake. Extracellular pH markedly affected nicotine uptake, with high nicotine uptake being observed at high pH up to 11.0. Modulation of intracellular pH with ammonium chloride also affected nicotine uptake. Treatment with valinomycin, a potassium ionophore, did not significantly affect nicotine uptake, indicating that nicotine uptake is an electroneutral process. For comparison, we assessed the characteristics of nicotine uptake in another lung epithelial cell line NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Interestingly, these cell lines showed similar characteristics of nicotine uptake with respect to pH dependency and inhibition by various organic cations. The present findings suggest that a similar or the same pH-dependent transport system is involved in nicotine uptake in these cell lines. A novel molecular mechanism of nicotine transport is proposed. Copyright © 2017 Elsevier Inc. All rights reserved.

The effects of nicotine in the neonatal quinpirole rodent model of psychosis: Neural plasticity mechanisms and nicotinic receptor changes.

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Peterson, Daniel J; Gill, W Drew; Dose, John M; Hoover, Donald B; Pauly, James R; Cummins, Elizabeth D; Burgess, Katherine C; Brown, Russell W

2017-05-15

Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal's lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine. Male and female Sprague-Dawley rats were neonatally treated with quinpirole (1mg/kg) or saline from postnatal days (P)1-21. Animals were given ip injections of either saline or nicotine (0.5mg/kg free base) every second day from P33 to P49 and tested on behavioral sensitization. Before each injection, animals were ip administered the α7 nAChR antagonist methyllycaconitine (MLA; 2 or 4mg/kg) or the α4β2 nAChR antagonist dihydro beta erythroidine (DhβE; 1 or 3mg/kg). Results revealed NQ enhanced nicotine sensitization that was blocked by DhβE. MLA blocked the enhanced nicotine sensitization in NQ animals, but did not block nicotine sensitization. NQ enhanced the NAcc BDNF response to nicotine which was blocked by both antagonists. In Experiment 2, NQ enhanced nicotine sensitization and enhanced α4β2, but not α7, nAChR upregulation in the NAcc. These results suggest a relationship between accumbal BDNF and α4β2 nAChRs and their role in the behavioral response to nicotine in the NQ model which has relevance to schizophrenia, a behavioral disorder with high rates of tobacco smoking. Copyright © 2017. Published by Elsevier B.V.

Primary prevention of cardiovascular disease with hormone replacement therapy

DEFF Research Database (Denmark)

Schierbeck, L

2015-01-01

Many peri- and postmenopausal women suffer from a reduced quality of life due to menopausal symptoms and preventable diseases. The importance of cardiovascular disease in women must be emphasized, as it is the leading cause of mortality and morbidity in women. It is well known that female hormones...... contribute to the later onset of cardiovascular disease in women. The effect of estrogens has for decades been understood from observational studies of postmenopausal women treated with hormone replacement therapy (HRT). Later, treatment with HRT was disregarded due to the fear of side......-effects and an ambiguity of the cardiovascular advantages. Accumulating knowledge from the large number of trials and studies has elucidated the cause for the disparity in results. In this paper, the beneficial effects of HRT, with emphasis on cardiovascular disease are explained, and the relative and absolute risks...

A distinct urinary biomarker pattern characteristic of female Fabry patients that mirrors response to enzyme replacement therapy.

Directory of Open Access Journals (Sweden)

Andreas D Kistler

Full Text Available Female patients affected by Fabry disease, an X-linked lysosomal storage disorder, exhibit a wide spectrum of symptoms, which renders diagnosis, and treatment decisions challenging. No diagnostic test, other than sequencing of the alpha-galactosidase A gene, is available and no biomarker has been proven useful to screen for the disease, predict disease course and monitor response to enzyme replacement therapy. Here, we used urine proteomic analysis based on capillary electrophoresis coupled to mass spectrometry and identified a biomarker profile in adult female Fabry patients. Urine samples were taken from 35 treatment-naïve female Fabry patients and were compared to 89 age-matched healthy controls. We found a diagnostic biomarker pattern that exhibited 88.2% sensitivity and 97.8% specificity when tested in an independent validation cohort consisting of 17 treatment-naïve Fabry patients and 45 controls. The model remained highly specific when applied to additional control patients with a variety of other renal, metabolic and cardiovascular diseases. Several of the 64 identified diagnostic biomarkers showed correlations with measures of disease severity. Notably, most biomarkers responded to enzyme replacement therapy, and 8 of 11 treated patients scored negative for Fabry disease in the diagnostic model. In conclusion, we defined a urinary biomarker model that seems to be of diagnostic use for Fabry disease in female patients and may be used to monitor response to enzyme replacement therapy.

A hierarchical instrumental decision theory of nicotine dependence.

Science.gov (United States)

Hogarth, Lee; Troisi, Joseph R

2015-01-01

It is important to characterize the learning processes governing tobacco-seeking in order to understand how best to treat this behavior. Most drug learning theories have adopted a Pavlovian framework wherein the conditioned response is the main motivational process. We favor instead a hierarchical instrumental decision account, wherein expectations about the instrumental contingency between voluntary tobacco-seeking and the receipt of nicotine reward determines the probability of executing this behavior. To support this view, we review titration and nicotine discrimination research showing that internal signals for deprivation/satiation modulate expectations about the current incentive value of smoking, thereby modulating the propensity of this behavior. We also review research on cue-reactivity which has shown that external smoking cues modulate expectations about the probability of the tobacco-seeking response being effective, thereby modulating the propensity of this behavior. Economic decision theory is then considered to elucidate how expectations about the value and probability of response-nicotine contingency are integrated to form an overall utility estimate for that option for comparison with qualitatively different, nonsubstitute reinforcers, to determine response selection. As an applied test for this hierarchical instrumental decision framework, we consider how well it accounts for individual liability to smoking uptake and perseveration, pharmacotherapy, cue-extinction therapies, and plain packaging. We conclude that the hierarchical instrumental account is successful in reconciling this broad range of phenomenon precisely because it accepts that multiple diverse sources of internal and external information must be integrated to shape the decision to smoke.

Compound list: nicotinic acid [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available nicotinic acid NIC 00081 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Hum...an/in_vitro/nicotinic_acid.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/R...at/in_vitro/nicotinic_acid.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vivo/Liver/Single/nicotinic_acid.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosc

Discriminating nicotine and non-nicotine containing e-liquids using infrared spectroscopy.

Science.gov (United States)

Deconinck, E; Bothy, J L; Barhdadi, S; Courselle, P

2016-02-20

In a few countries, including Belgium, nicotine-containing e-cigarettes and e-liquids are considered medicines, and therefore cannot freely be sold, but should be distributed in a pharmacy. The fact that in the neighbouring countries these products are freely available, poses a problem for custom personnel, the more the nicotine content of the products is not always labelled, especially when they are bought through internet. Therefore there is a need for easy-to-use equipment and methods to perform a first on site screening of intercepted samples, both for border control as to check label compliance of the sample. The use of attenuated total reflectance-infrared spectroscopy (ATR-IR) and near infrared spectroscopy (NIR), combined with chemometrics was evaluated for the discrimination between nicotine containing and non-nicotine containing samples. It could be concluded that both ATR-IR and NIR could be used for the discrimination when combined with the appropriate chemometric techniques. The presented techniques do not need sample preparation and result in models with a minimum of false negative samples. If a large enough training set can be established the interpretation can be fully automated, making the presented approach suitable for on-site screening of e-liquid samples. Copyright © 2015 Elsevier B.V. All rights reserved.

In vivo imaging of nicotinic receptor upregulation following chronic (-)-nicotine treatment in baboon using SPECT

International Nuclear Information System (INIS)

Kassiou, Michael; Eberl, Stefan; Meikle, Steven R.; Birrell, Alex; Constable, Chris; Fulham, Michael J.; Wong, Dean F.; Musachio, John L.

2001-01-01

To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT studies were performed with 5-[ 123 I]-iodo-A-85380 in baboons pre and post chronic treatment with (-)-nicotine or saline control. Infusion of (-)-nicotine at a dose of 2.0 mg/kg/24h for 14 days resulted in plasma (-)-nicotine levels of 27.3 ng/mL. This is equivalent to that found in an average human smoker (20 cigarettes a day). In the baboon brain the regional distribution of 5-[ 123 I]-iodo-A-85380 was consistent with the known densities of nAChRs (thalamus > frontal cortex > cerebellum). Changes in nAChR binding were estimated from the volume of distribution (V d ) and binding potential (BP) derived from 3-compartment model fits. In the (-)-nicotine treated animal V d was significantly increased in the thalamus (52%) and cerebellum (50%) seven days post cessation of (-)-nicotine treatment, suggesting upregulation of nAChRs. The observed 33% increase in the frontal cortex failed to reach significance. A significant increase in BP was seen in the thalamus. In the saline control animal no changes were observed in V d or BP under any experimental conditions. In this preliminary study, we have demonstrated for the first time in vivo upregulation of neuronal nAChR binding following chronic (-)-nicotine treatment

Subgroup analysis of continuous renal replacement therapy in severely burned patients.

Directory of Open Access Journals (Sweden)

Jaechul Yoon

Full Text Available Continuous renal replacement therapy (CRRT is administered to critically ill patients with renal injuries as renal replacement or renal support. We aimed to identify predictors of mortality among burn patients receiving CRRT, and to investigate clinical differences according to acute kidney injury (AKI status. This retrospective observational study evaluated 216 Korean burn patients who received CRRT at a burn intensive care unit. Patients were categorized by AKI status. Data were collected regarding arterial pH, laboratory results, ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF ratio, and urine production. Among surviving patients, CRRT duration and the sequential organ failure assessment score were 6.5 days and 4.7 in the non-AKI group and 23.4 days and 7.4 in the AKI group, respectively (p = 0.003 and p = 0.008. On logistic regression analyses, mortality was significantly associated with a pH of 5.0 mEg/L (p = 0.045, creatinine levels of >2.0 mg/dL (p = 0.011, lactate levels of >2 mmol/L (p2 mmol/L, and a platelet count of 2 mg/dL. In the non-AKI group, poor outcomes were associated with lactate levels of >1.5 mmol/L, a PF ratio of 1.2 mg/dL. Duration of the CRRT application and the requirement for either renal replacement or renal support at the initiation of CRRT application are important considerations depending on its application.

Replacement therapy with levothyroxine modulates platelet activation in recent-onset post-thyroidectomy subclinical hypothyroidism.

Science.gov (United States)

Desideri, G; Bocale, R; D'Amore, A; Necozione, S; Boscherini, M; Carnassale, G; Barini, A; Barini, A; Bellantone, R; Lombardi, C P

2017-10-01

Subclinical hypothyroidism has been linked to increased risk of atherosclerotic disease. Soluble CD40 ligand (sCD40L), mainly derived from activated platelets, and the lipid peroxidation product 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) are known to play a relevant pathophysiological role in atherogenesis. In this study, we analyzed the relationship between thyroid hormones and circulating levels of sCD40L and 8-iso-PGF 2α in patient with recent-onset post-thyroidectomy subclinical hypothyroidism under replacement therapy. Circulating levels of thyroid hormones, sCD40L, and 8-iso-PGF 2α were assessed in 40 recently thyroidectomized patients (33 females, mean age 52.0 ± 11.7 years) at baseline (5-7 day after surgery) and after 2 months under replacement therapy with levothyroxine (LT-4). At baseline, circulating levels of thyroid hormones were indicative of a subclinical hypothyroidism (TSH 7.7 ± 3.9 μU/mL, FT3 1.8 ± 0.6 pg/mL, and FT3 8.9 ± 3.0 pg/mL). Circulating levels of sCD40L and 8-iso-PGF 2α were directly correlated with each other (r = 0.360, p = 0.023) and with TSH levels (r = 0.322, p = 0.043 and r = 0.329 p = 0.038, respectively). After 2 months under the replacement therapy with LT-4 circulating levels of TSH (from 7.7 ± 3.9 to 2.7 ± 2.8 μU/mL, p hypothyroidism to develop atherosclerotic disease. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Central estrogenic pathways protect against the depressant action of acute nicotine on reflex tachycardia in female rats

Energy Technology Data Exchange (ETDEWEB)

El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com; Fouda, Mohamed A.; El-gowilly, Sahar M.; Saad, Evan I.

2012-02-01

We have previously shown that acute exposure of male rats to nicotine preferentially attenuates baroreceptor-mediated control of reflex tachycardia in contrast to no effect on reflex bradycardia. Here, we investigated whether female rats are as sensitive as their male counterparts to the baroreflex depressant effect of nicotine and whether this interaction is modulated by estrogen. Baroreflex curves relating reflex chronotropic responses evoked by i.v. doses (1–16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), were constructed in conscious freely moving proestrus, ovariectomized (OVX), and estrogen (50 μg/kg/day s.c., 5 days)-replaced OVX (OVXE{sub 2}) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRS{sub PE} and BRS{sub SNP}). Nicotine (100 μg/kg i.v.) reduced BRS{sub SNP} in OVX rats but not in proestrus or OVXE{sub 2} rats. The attenuation of reflex tachycardia by nicotine was also evident in diestrus rats, which exhibited plasma estrogen levels similar to those of OVX rats. BRS{sub PE} was not affected by nicotine in all rat preparations. Experiments were then extended to determine whether central estrogenic receptors modulate the nicotine–BRS{sub SNP} interaction. Intracisteral (i.c.) treatment of OVX rats with estrogen sulfate (0.2 μg/rat) abolished the BRS{sub SNP} attenuating effect of i.v. nicotine. This protective effect of estrogen disappeared when OVX rats were pretreated with i.c. ICI 182,780 (50 μg/rat, selective estrogen receptor antagonist). Together, these findings suggest that central neural pools of estrogen receptors underlie the protection offered by E{sub 2} against nicotine-induced baroreceptor dysfunction in female rats. -- Highlights: ► Estrogen protects against the depressant effect of nicotine on reflex tachycardia. ► The baroreflex response and estrogen status affect the nicotine–BRS interaction. ► The protection offered by estrogen is mediated via central estrogen receptors.

Chronic Underactivity of Medial Frontal Cortical β2-Containing Nicotinic Receptors Increases Clozapine-Induced Working Memory Impairment in Female Rats

Science.gov (United States)

Levin, Edward D.; Perkins, Abigail; Brotherton, Terrell; Qazi, Melissa; Berez, Chantal; Montalvo-Ortiz, Janitza; Davis, Kasey; Williams, Paul; Christopher, N. Channelle

2009-01-01

Nicotinic receptor decreases in the frontal cortex and hippocampus are important mediators of cognitive impairment in both schizophrenia and Alzheimer's disease. Drug treatments for these diseases should take into account the impacts of compromised brain function on drug response. This study investigated the impact of compromised nicotinic receptor activity in the frontal cortex in rats on memory function. Since both Alzheimer's disease and schizophrenia can involve psychosis, antipsychotic drugs are often given. The impacts of antipsychotic drugs on cognitive function have been found to be quite variable. It is the hypothesis of this and previous studies that the cognitive effects of antispychotic drugs on cognitive function depend on the integrity of brain systems involved in cognition. Previously in studies of the hippocampus, we found that chronic inhibition of β2-containing nicotinic receptors with dihydro-β-erythrodine (DHβE) impaired working memory and that this effect was attenuated by the antipsychotic drug clozapine. In contrast, chronic hippocampal α7 nicotinic receptor blockade with methyllycaconitine (MLA) potentiated the clozapine-induced memory impairment which is seen in rats without compromised nicotinic receptor activity. The current study determined medial frontal cortical α7 and β2-containing nicotinic receptor involvement in memory and the interactions with antipsychotic drug therapy with clozapine. Chronic DHβE and MLA infusion effects and interactions with systemic clozapine were assessed in female rats tested for memory on the radial-arm maze. Antipsychotic drug interactions with chronic systemic nicotine were investigated because nicotinic procognitive treatment has been proposed. The same local infusion DHβE dose that impaired memory with hippocampal infusion did not impair memory when infused in the medial frontal cortex. Frontal DHβE infusion potentiated clozapine-induced memory impairment, whereas previously the memory

Chronic underactivity of medial frontal cortical beta2-containing nicotinic receptors increases clozapine-induced working memory impairment in female rats.

Science.gov (United States)

Levin, Edward D; Perkins, Abigail; Brotherton, Terrell; Qazi, Melissa; Berez, Chantal; Montalvo-Ortiz, Janitza; Davis, Kasey; Williams, Paul; Christopher, N Channelle

2009-03-17

Nicotinic receptor decreases in the frontal cortex and hippocampus are important mediators of cognitive impairment in both schizophrenia and Alzheimer's disease. Drug treatments for these diseases should take into account the impacts of compromised brain function on drug response. This study investigated the impact of compromised nicotinic receptor activity in the frontal cortex in rats on memory function. Since both Alzheimer's disease and schizophrenia can involve psychosis, antipsychotic drugs are often given. The impacts of antipsychotic drugs on cognitive function have been found to be quite variable. It is the hypothesis of this and previous studies that the cognitive effects of antispychotic drugs on cognitive function depend on the integrity of brain systems involved in cognition. Previously in studies of the hippocampus, we found that chronic inhibition of beta2-containing nicotinic receptors with dihydro-beta-erythrodine (DHbetaE) impaired working memory and that this effect was attenuated by the antipsychotic drug clozapine. In contrast, chronic hippocampal alpha7 nicotinic receptor blockade with methyllycaconitine (MLA) potentiated the clozapine-induced memory impairment which is seen in rats without compromised nicotinic receptor activity. The current study determined medial frontal cortical alpha7 and beta2-containing nicotinic receptor involvement in memory and the interactions with antipsychotic drug therapy with clozapine. Chronic DHbetaE and MLA infusion effects and interactions with systemic clozapine were assessed in female rats tested for memory on the radial-arm maze. Antipsychotic drug interactions with chronic systemic nicotine were investigated because nicotinic procognitive treatment has been proposed. The same local infusion DHbetaE dose that impaired memory with hippocampal infusion did not impair memory when infused in the medial frontal cortex. Frontal DHbetaE infusion potentiated clozapine-induced memory impairment, whereas previously

In vivo human buccal permeability of nicotine

DEFF Research Database (Denmark)

Adrian, Charlotte L; Olin, Helle B D; Dalhoff, Kim

2006-01-01

The aim was to examine the in vivo buccal pH-dependent permeability of nicotine in humans and furthermore compare the in vivo permeability of nicotine to previous in vitro permeability data. The buccal permeability of nicotine was examined in a three-way cross-over study in eight healthy non......-smokers using a buccal perfusion cell. The disappearance of nicotine from perfusion solutions with pH 6.0, 7.4, and 8.1 was studied for 3h. The apparent permeability of nicotine (P(app)) was determined at each pH value. Parotid saliva was collected in an attempt to assess systemic levels of nicotine....... The disappearance rate of nicotine increased significantly as the pH increased, which resulted in P(app) values of 0.57+/-0.55 x 10(-4), 2.10+/-0.23 x 10(-4), and 3.96+/-0.54 x 10(-4)cms(-1) (mean+/-S.D.) at pH 6.0, 7.4, and 8.1, respectively. A linear relationship (R(2)=0.993) was obtained between the P...

Bioelectronic sniffer for nicotine using enzyme inhibition.

Science.gov (United States)

Mitsubayashi, Kohji; Nakayama, Kazumi; Taniguchi, Midori; Saito, Hirokazu; Otsuka, Kimio; Kudo, Hiroyuki

2006-07-28

A novel bioelectronic sniffer for nicotine in the gas phase was developed with enzyme inhibition principle to butyrylcholinesterase activity. The bioelectronic devices for nicotine in the gas and liquid phases were constructed using a Clark-type dissolved oxygen electrode and a membrane immobilized butyrylcholinesterase and choline oxidase. After the assessment of the sensor performances to choline and butyrylcholine as pre-examinations, the characteristics of the biosensor and bio-sniffer for nicotine were evaluated in the liquid and gas phases, respectively. The sensor signal of the bio-devices with 300 micromol l(-1) of butyrylcholine decreased quickly following application of nicotine and reached to the steady-state current, thus relating the concentration of nicotine in the liquid and gas phases. The biosensor was used to measure nicotine solution from 10 to 300 micromol l(-1). In the gas-phase experiment, the current signal of the bio-sniffer was also found to be linearly to the nicotine concentration over the range of 10.0-1000 ppb including 75.0 ppb as threshold limit value (TLV) by American Conference of Governmental Industrial Hygienists (ACGIH).

Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications

NARCIS (Netherlands)

van Dussen, Laura; Biegstraaten, Marieke; Dijkgraaf, Marcel Gw; Hollak, Carla Em

2014-01-01

Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on

Nicotine adsorption on single wall carbon nanotubes

Energy Technology Data Exchange (ETDEWEB)

Girao, Eduardo C. [Departamento de Fisica, Universidade Federal do Ceara, Caixa Postal 6030, Campus do Pici, 60455-900 Fortaleza, Ceara (Brazil); Fagan, Solange B.; Zanella, Ivana [Area de Ciencias Tecnologicas, Centro Universitario Franciscano - UNIFRA, 97010-032 Santa Maria, RS (Brazil); Filho, Antonio G. Souza, E-mail: agsf@fisica.ufc.br [Departamento de Fisica, Universidade Federal do Ceara, Caixa Postal 6030, Campus do Pici, 60455-900 Fortaleza, Ceara (Brazil)

2010-12-15

This work reports a theoretical study of nicotine molecules interacting with single wall carbon nanotubes (SWCNTs) through ab initio calculations within the framework of density functional theory (DFT). Different adsorption sites for nicotine on the surface of pristine and defective (8,0) SWCNTs were analyzed and the total energy curves, as a function of molecular position relative to the SWCNT surface, were evaluated. The nicotine adsorption process is found to be energetically favorable and the molecule-nanotube interaction is intermediated by the tri-coordinated nitrogen atom from the nicotine. It is also predicted the possibility of a chemical bonding between nicotine and SWCNT through the di-coordinated nitrogen.

Stable isotope studies of nicotine kinetics and bioavailability

International Nuclear Information System (INIS)

Benowitz, N.L.; Jacob, P. III; Denaro, C.; Jenkins, R.

1991-01-01

The stable isotope-labeled compound 3',3'-dideuteronicotine was used to investigate the disposition kinetics of nicotine in smokers, the systemic absorption of nicotine from cigarette smoke, and the bioavailability of nicotine ingested as oral capsules. Blood levels of labeled nicotine could be measured for 9 hours after a 30-minute intravenous infusion. Analysis of disposition kinetics in 10 healthy men revealed a multiexponential decline after the end of an infusion, with an elimination half-life averaging 203 minutes. This half-life was longer than that previously reported, indicating the presence of a shallow elimination phase. Plasma clearance averaged 14.6 ml/min/kg. The average intake of nicotine per cigarette was 2.29 mg. A cigarette smoke-monitoring system that directly measured particulate matter in smoke was evaluated in these subjects. Total particulate matter, number of puffs on the cigarette, total puff volume, and time of puffing correlated with the intake of nicotine from smoking. The oral bioavailability of nicotine averaged 44%. This bioavailability is higher than expected based on the systemic clearance of nicotine and suggests that there may be significant extrahepatic metabolism of nicotine

Characterization and Genome Analysis of a Nicotine and Nicotinic Acid-Degrading Strain Pseudomonas putida JQ581 Isolated from Marine.

Science.gov (United States)

Li, Aiwen; Qiu, Jiguo; Chen, Dongzhi; Ye, Jiexu; Wang, Yuhong; Tong, Lu; Jiang, Jiandong; Chen, Jianmeng

2017-05-31

The presence of nicotine and nicotinic acid (NA) in the marine environment has caused great harm to human health and the natural environment. Therefore, there is an urgent need to use efficient and economical methods to remove such pollutants from the environment. In this study, a nicotine and NA-degrading bacterium-strain JQ581-was isolated from sediment from the East China Sea and identified as a member of Pseudomonas putida based on morphology, physio-biochemical characteristics, and 16S rDNA gene analysis. The relationship between growth and nicotine/NA degradation suggested that strain JQ581 was a good candidate for applications in the bioaugmentation treatment of nicotine/NA contamination. The degradation intermediates of nicotine are pseudooxynicotine (PN) and 3-succinoyl-pyridine (SP) based on UV, high performance liquid chromatography, and liquid chromatography-mass spectrometry analyses. However, 6-hydroxy-3-succinoyl-pyridine (HSP) was not detected. NA degradation intermediates were identified as 6-hydroxynicotinic acid (6HNA). The whole genome of strain JQ581 was sequenced and analyzed. Genome sequence analysis revealed that strain JQ581 contained the gene clusters for nicotine and NA degradation. This is the first report where a marine-derived Pseudomonas strain had the ability to degrade nicotine and NA simultaneously.

Higher dosage nicotine patches increase one-year smoking cessation rates : results from the European CEASE trial

NARCIS (Netherlands)

Tonnesen, P; Paoletti, P; Gustavsson, G; Russell, MA; Saracci, R; Gulsvik, A; Rijcken, B

The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study, The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six

Transcatheter Aortic Valve Replacement in Europe

DEFF Research Database (Denmark)

Mylotte, Darren; Osnabrugge, Ruben L J; Windecker, Stephan

2013-01-01

The authors sought to examine the adoption of transcatheter aortic valve replacement (TAVR) in Western Europe and investigate factors that may influence the heterogeneous use of this therapy.......The authors sought to examine the adoption of transcatheter aortic valve replacement (TAVR) in Western Europe and investigate factors that may influence the heterogeneous use of this therapy....

Inside-out neuropharmacology of nicotinic drugs.

Science.gov (United States)

Henderson, Brandon J; Lester, Henry A

2015-09-01

Upregulation of neuronal nicotinic acetylcholine receptors (AChRs) is a venerable result of chronic exposure to nicotine; but it is one of several consequences of pharmacological chaperoning by nicotine and by some other nicotinic ligands, especially agonists. Nicotinic ligands permeate through cell membranes, bind to immature AChR oligomers, elicit incompletely understood conformational reorganizations, increase the interaction between adjacent AChR subunits, and enhance the maturation process toward stable AChR pentamers. These changes and stabilizations in turn lead to increases in both anterograde and retrograde traffic within the early secretory pathway. In addition to the eventual upregulation of AChRs at the plasma membrane, other effects of pharmacological chaperoning include modifications to endoplasmic reticulum stress and to the unfolded protein response. Because these processes depend on pharmacological chaperoning within intracellular organelles, we group them as "inside-out pharmacology". This term contrasts with the better-known, acute, "outside-in" effects of activating and desensitizing plasma membrane AChRs. We review current knowledge concerning the mechanisms and consequences of inside-out pharmacology. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Meta-Analysis of the Efficacy of Bupropion Sustained-Release for Smoking Cessation in Heavy Smokers

Directory of Open Access Journals (Sweden)

Adrian Paszek

2017-09-01

Full Text Available Cigarette smoking damages just about every organ in the body and reduces overall health. Even with the prevalence of accessible nicotine replacement therapies and behavioral counseling, there remains a need for alternative therapies to improve the odds of successfully abstaining from smoking in the long term. Bupropion sustained-release (SR is a pharmacological, prescription-only intervention that is approved as a first-line treatment for smoking cessation. This meta-analysis examines the effectiveness of bupropion sustained-release for smoking cessation amongst heavy smokers, defined as those who consistently smoke at least fifteen or more cigarettes per day. Across five qualifying studies, bupropion SR increased odds of cessation over placebo treatment at six and twelve months. Bupropion SR is a well-tolerated, non-nicotinic therapy for smoking cessation. Treatment with bupropion SR reduces initial cravings and withdrawal effects but does not appear to address the multi-faceted problem of cigarette addiction, resulting in decreased abstinence rates over time. An integrated approach incorporating bupropion SR with other interventions, such as nicotine replacement therapies and psychotherapy, may provide the necessary means to achieve lasting cessation and promote well-being.

Tolerance to and cross tolerance between ethanol and nicotine.

Science.gov (United States)

Collins, A C; Burch, J B; de Fiebre, C M; Marks, M J

1988-02-01

Female DBA mice were subjected to one of four treatments: ethanol-containing or control diets, nicotine (0.2, 1.0, 5.0 mg/kg/hr) infusion or saline infusion. After removal from the liquid diets or cessation of infusion, the animals were challenged with an acute dose of ethanol or nicotine. Chronic ethanol-fed mice were tolerant to the effects of ethanol on body temperature and open field activity and were cross tolerant to the effects of nicotine on body temperature and heart rate. Nicotine infused animals were tolerant to the effects of nicotine on body temperature and rotarod performance and were cross tolerant to the effects of ethanol on body temperature. Ethanol-induced sleep time was decreased in chronic ethanol- but not chronic nicotine-treated mice. Chronic drug treatment did not alter the elimination rate of either drug. Chronic ethanol treatment did not alter the number or affinity of brain nicotinic receptors whereas chronic nicotine treatment elicited an increase in the number of [3H]-nicotine binding sites. Tolerance and cross tolerance between ethanol and nicotine is discussed in terms of potential effects on desensitization of brain nicotinic receptors.

Transdermal nicotine absorption handling e-cigarette refill liquids.

Science.gov (United States)

Maina, Giovanni; Castagnoli, Carlotta; Passini, Valter; Crosera, Matteo; Adami, Gianpiero; Mauro, Marcella; Filon, Francesca Larese

2016-02-01

The concentrated nicotine in e-cigarette refill liquids can be toxic if inadvertently ingested or absorbed through the skin. Reports of poisonings due to accidental ingestion of nicotine on refill liquids are rapidly increasing, while the evaluation of nicotine dermally absorbed still lacks. For that reason we studied transdermal nicotine absorption after the skin contamination with e-liquid. Donor chambers of eight Franz diffusion cells were filled with 1 mL of 0.8 mg/mL nicotine e-liquid for 24 h. The concentration of nicotine in the receiving phase was determined by high-performance liquid chromatography (LOD:0.1 μg/mL). Nicotine was detectable in receiving solution 2 h after the start of exposure and increased progressively. The medium flux calculated was 4.82 ± 1.05 μg/cm(2)/h with a lag time of 3.9 ± 0.1 h. After 24 h, the nicotine concentration in the receiving compartment was 101.02 ± 22.35 μg/cm(2) corresponding to 3.04 mg of absorbed nicotine after contamination of a skin surface of 100 cm(2). Skin contamination with e-liquid can cause nicotine skin absorption: caution must be paid when handling refill e-liquids. Copyright © 2015 Elsevier Inc. All rights reserved.

Mortality risk disparities in children receiving chronic renal replacement therapy for the treatment of end-stage renal disease across Europe: an ESPN-ERA/EDTA registry analysis.

Science.gov (United States)

Chesnaye, Nicholas C; Schaefer, Franz; Bonthuis, Marjolein; Holman, Rebecca; Baiko, Sergey; Baskın, Esra; Bjerre, Anna; Cloarec, Sylvie; Cornelissen, Elisabeth A M; Espinosa, Laura; Heaf, James; Stone, Rosário; Shtiza, Diamant; Zagozdzon, Ilona; Harambat, Jérôme; Jager, Kitty J; Groothoff, Jaap W; van Stralen, Karlijn J

2017-05-27

We explored the variation in country mortality rates in the paediatric population receiving renal replacement therapy across Europe, and estimated how much of this variation could be explained by patient-level and country-level factors. In this registry analysis, we extracted patient data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry for 32 European countries. We included incident patients younger than 19 years receiving renal replacement therapy. Adjusted hazard ratios (aHR) and the explained variation were modelled for patient-level and country-level factors with multilevel Cox regression. The primary outcome studied was all-cause mortality while on renal replacement therapy. Between Jan 1, 2000, and Dec 31, 2013, the overall 5 year renal replacement therapy mortality rate was 15·8 deaths per 1000 patient-years (IQR 6·4-16·4). France had a mortality rate (9·2) of more than 3 SDs better, and Russia (35·2), Poland (39·9), Romania (47·4), and Bulgaria (68·6) had mortality rates more than 3 SDs worse than the European average. Public health expenditure was inversely associated with mortality risk (per SD increase, aHR 0·69, 95% CI 0·52-0·91) and explained 67% of the variation in renal replacement therapy mortality rates between countries. Child mortality rates showed a significant association with renal replacement therapy mortality, albeit mediated by macroeconomics (eg, neonatal mortality reduced from 1·31 [95% CI 1·13-1·53], p=0·0005, to 1·21 [0·97-1·51], p=0·10). After accounting for country distributions of patient age, the variation in renal replacement therapy mortality rates between countries increased by 21%. Substantial international variation exists in paediatric renal replacement therapy mortality rates across Europe, most of which was explained by disparities in public health expenditure, which seems to limit the availability and

Effects of early changes in organ dysfunctions on the outcomes of critically ill patients in need of renal replacement therapy

Directory of Open Access Journals (Sweden)

Elizabeth Maccariello

2008-01-01

Full Text Available INTRODUCTION: Acute kidney injury usually develops in critically ill patients in the context of multiple organ dysfunctions. OBJECTIVE: To evaluate the effect of changes in associated organ dysfunctions over the first three days of renal replacement therapy on the outcomes of patients with acute kidney injury. METHODS: Over a 19-month period, we evaluated 260 patients admitted to the intensive care units of three tertiary-care hospitals who required renal replacement therapy for > 48 h. Organ dysfunctions were evaluated by SOFA score (excluding renal points on the first (D1 and third (D3 days of renal replacement therapy. Absolute (A-SOFA and relative (D-SOFA changes in SOFA scores were also calculated. RESULTS: Hospital mortality rate was 75%. Organ dysfunctions worsened (A-SOFA>0 in 53%, remained unchanged (A-SOFA=0 in 17% and improved (A-SOFA<0 in 30% of patients; and mortality was lower in the last group (80% vs. 84% vs. 61%, p=0.003. SOFA on D1 (p<0.001, SOFA on D3 (p<0.001, A-SOFA (p=0.019 and D-SOFA (p=0.016 were higher in non-survivors. However, neither A-SOFA nor D-SOFA discriminated survivors from non-survivors on an individual basis. Adjusting for other covariates (including SOFA on D1, A-SOFA and D-SOFA were associated with increased mortality, and patients in whom SOFA scores worsened or remained unchanged had poorer outcomes. CONCLUSIONS: In addition to baseline values, early changes in SOFA score after the start of renal replacement therapy were associated with hospital mortality. However, no prognostic score should be used as the only parameter to predict individual outcomes.

Myxedema coma and cardiac ischemia in relation to thyroid hormone replacement therapy in a 38-year-old Japanese woman.

Science.gov (United States)

Taguchi, Takafumi; Iwasaki, Yasumasa; Asaba, Koichi; Takao, Toshihiro; Hashimoto, Kozo

2007-12-01

Although thyroid hormone deficiency, either clinical or subclinical, is an established risk factor for cardiovascular disease, coronary ischemia in a premenopausal woman in her 30s is relatively rare. A 38-year-old woman was referred to our hospital with severe breathlessness and depressed consciousness. Physical examination found facial, abdominal, and pretibial edema; coarse hair, hoarse voice, and dry skin; engorged jugular veins; a distant heart sound; and reduced bilateral entry of air into the chest. Laboratory examinations revealed severe hypothyroidism, hyperlipidemia, and elevated serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125). A computed tomography scan showed massive pleural and pericardial effusions. After 3 months of levothyroxine replacement therapy (initial dose: 12.5 microg/d; maintenance dose: 125 microg/d), all abnormal laboratory values associated with hypothyroidism returned to within normal ranges, with the exception of a transient and paradoxical rise in serum thyroid-stimulating hormone levels. However, 3 weeks after the initiation of therapy, the patient reported intermittent chest pains during the course of therapy, and a coronary artery angiogram revealed diffuse stenosis of all 3 branches. The patient underwent coronary artery bypass grafting, with subsequent improvement in coronary perfusion. Careful cardiovascular evaluation is recommended before the start of thyroid hormone replacement therapy. In addition, care should be taken in the interpretation of serum biomarkers of malignancy (eg, CEA, CA125) in patients with myxedema, as values may be elevated in a hypothyroid state. Long-standing hypothyroidism may be associated with severe coronary atherosclerosis, even in a relatively young, premenopausal woman. The potential adverse cardiovascular effects of thyroid hormone must be considered during replacement therapy, even in relatively young patients.

A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans

Energy Technology Data Exchange (ETDEWEB)

Saylor, Kyle, E-mail: saylor@vt.edu; Zhang, Chenming, E-mail: chzhang2@vt.edu

2016-09-15

Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down into different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies' ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. - Highlights: • Modelling of nicotine disposition in the presence of anti-nicotine antibodies • Key vaccine efficacy factors are evaluated in silico in rats and in humans. • Model predicts insufficient antibody binding in past human nicotine vaccines. • Improving immunogenicity and antibody specificity may lead to vaccine success.

A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans

International Nuclear Information System (INIS)

Saylor, Kyle; Zhang, Chenming

2016-01-01

Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down into different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies' ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. - Highlights: • Modelling of nicotine disposition in the presence of anti-nicotine antibodies • Key vaccine efficacy factors are evaluated in silico in rats and in humans. • Model predicts insufficient antibody binding in past human nicotine vaccines. • Improving immunogenicity and antibody specificity may lead to vaccine success.

REINFORCEMENT ENHANCING EFFECTS OF ACUTE NICOTINE VIA ELECTRONIC CIGARETTES

Science.gov (United States)

Perkins, Kenneth A.; Karelitz, Joshua L.; Michael, Valerie C.

2015-01-01

Background Recent human studies confirm animal research showing that nicotine enhances reinforcement from rewards unrelated to nicotine. These effects of acute nicotine via tobacco smoking may also occur when consumed from non-tobacco products. Methods We assessed acute effects of nicotine via electronic cigarettes (“e-cigarettes”) on responding reinforced by music, video, or monetary rewards, or for no reward (control). In a fully within-subjects design, adult dependent smokers (N=28) participated in three similar experimental sessions, each following overnight abstinence (verified by CO≤10 ppm). Varying only in e-cigarette condition, sessions involved controlled exposure to a nicotine (labeled “36 mg/ml”) or placebo (“0”) e-cigarette, or no e-cigarette use. A fourth session involved smoking one’s own tobacco cigarette brand after no abstinence, specifically to compare responses under typical nicotine satiation with these acute e-cigarette conditions after abstinence. Results Reinforced responding for video reward, but not the other rewards, was greater due to use of the nicotine versus placebo e-cigarette (i.e., nicotine per se), while no differences were found between the placebo e-cigarette and no e-cigarette conditions (i.e., e-cigarette use per se). For nicotine via tobacco smoking, responding compared to the nicotine e-cigarette was similar for video but greater for music, while both video and music reward were enhanced relative to the non-nicotine conditions (placebo and no e-cigarette). Conclusions Acute nicotine from a non-tobacco product has some reinforcement enhancing effects in humans, in a manner partly consistent with nicotine via tobacco smoking and perhaps contributing to the rising popularity of nicotine e-cigarette use. PMID:26070455

Reinforcement enhancing effects of acute nicotine via electronic cigarettes.

Science.gov (United States)

Perkins, Kenneth A; Karelitz, Joshua L; Michael, Valerie C

2015-08-01

Recent human studies confirm animal research showing that nicotine enhances reinforcement from rewards unrelated to nicotine. These effects of acute nicotine via tobacco smoking may also occur when consumed from non-tobacco products. We assessed acute effects of nicotine via electronic cigarettes ("e-cigarettes") on responding reinforced by music, video, or monetary rewards, or for no reward (control). In a fully within-subjects design, adult dependent smokers (N=28) participated in three similar experimental sessions, each following overnight abstinence (verified by CO≤10ppm). Varying only in e-cigarette condition, sessions involved controlled exposure to a nicotine (labeled "36mg/ml") or placebo ("0″) e-cigarette, or no e-cigarette use. A fourth session involved smoking one's own tobacco cigarette brand after no abstinence, specifically to compare responses under typical nicotine satiation with these acute e-cigarette conditions after abstinence. Reinforced responding for video reward, but not the other rewards, was greater due to use of the nicotine versus placebo e-cigarette (i.e., nicotine per se), while no differences were found between the placebo e-cigarette and no e-cigarette conditions (i.e., e-cigarette use per se). For nicotine via tobacco smoking, responding compared to the nicotine e-cigarette was similar for video but greater for music, while both video and music reward were enhanced relative to the non-nicotine conditions (placebo and no e-cigarette). Acute nicotine from a non-tobacco product has some reinforcement enhancing effects in humans, in a manner partly consistent with nicotine via tobacco smoking and perhaps contributing to the rising popularity of nicotine e-cigarette use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Detoxification and elimination of nicotine by nectar-feeding birds.

Science.gov (United States)

Lerch-Henning, S; Du Rand, E E; Nicolson, S W

2017-05-01

Many dilute nectars consumed by bird pollinators contain secondary metabolites, potentially toxic chemicals produced by plants as defences against herbivores. Consequently, nectar-feeding birds are challenged not only by frequent water excess, but also by the toxin content of their diet. High water turnover, however, could be advantageous to nectar consumers by enabling them to excrete secondary metabolites or their transformation products more easily. We investigated how the alkaloid nicotine, naturally present in nectar of Nicotiana species, influences osmoregulation in white-bellied sunbirds Cinnyris talatala and Cape white-eyes Zosterops virens. We also examined the metabolic fate of nicotine in these two species to shed more light on the post-ingestive mechanisms that allow nectar-feeding birds to tolerate nectar nicotine. A high concentration of nicotine (50 µM) decreased cloacal fluid output and increased its osmolality in both species, due to reduced food intake that led to dehydration. White-eyes excreted a higher proportion of the ingested nicotine-containing diet than sunbirds. However, sugar concentration did not affect nicotine detoxification and elimination. Both species metabolised nicotine, excreting very little unchanged nicotine. Cape white-eyes mainly metabolised nicotine through the cotinine metabolic pathway, with norcotinine being the most abundant metabolite in the excreta, while white-bellied sunbirds excreted mainly nornicotine. Both species also utilized phase II conjugation reactions to detoxify nicotine, with Cape white-eyes depending more on the mercapturic acid pathway to detoxify nicotine than white-bellied sunbirds. We found that sunbirds and white-eyes, despite having a similar nicotine tolerance, responded differently and used different nicotine-derived metabolites to excrete nicotine.

An update on renal replacement therapy in Europe: ERA-EDTA Registry data from 1997 to 2006

NARCIS (Netherlands)

Kramer, Anneke; Stel, Vianda; Zoccali, Carmine; Heaf, James; Ansell, David; Grönhagen-Riska, Carola; Leivestad, Torbjørn; Simpson, Keith; Pálsson, Runólfur; Postorino, Maurizio; Jager, Kitty

2009-01-01

Background. Recent studies have indicated a stabilization in the incidence rates of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in a number of European countries. The aim of this study was to provide an update on the incidence, prevalence and outcomes of RRT in Europe over the

The epidemic of aging in renal replacement therapy: an update on elderly patients and their outcomes

NARCIS (Netherlands)

Jager, K. J.; van Dijk, P. C. W.; Dekker, F. W.; Stengel, B.; Simpson, K.; Briggs, J. D.

2003-01-01

Background: In the past 2 decades, a rapid growth has occurred in the number of patients over 65 years of age accepted for renal replacement therapy (RRT) with an increasing need for dialysis resources as a consequence. The aim of this study is to describe the trends in incidence, treatment and

Use of nonsteroidal anti-inflammatory drugs prior to chronic renal replacement therapy initiation

DEFF Research Database (Denmark)

Kristensen, Søren Lund; Fosbøl, Emil L; Kamper, Anne-Lise

2012-01-01

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with severe renal complications, including acute renal failure, reduced glomerular filtration rate and interstitial nephritis. Caution against NSAIDs is therefore recommended in advanced chronic kidney disease. In this study......, we examined NSAID use, aetiology and comorbidity among a national cohort of patients before the initiation of chronic renal replacement therapy (RRT). METHODS: Patients initiated on chronic RRT in the period 1997-2006 were identified in the Danish National Registry on Regular Dialysis...

Promise and deceit: pharmakos, drug replacement therapy, and the perils of experience.

Science.gov (United States)

Meyers, Todd

2014-06-01

The problem of lying as a feature of medication compliance has been well documented in anthropological and clinical literatures. Yet the role of the lie-its destabilizing effects on the continuity of drug treatment and therapy, as a technology of drug misuse, or as a way to understand the neuro-chemical processes of treatment (pharmacotherapy "tricking" or lying to the brain)-has been less considered, particularly in the context of opioid replacement therapy. The following paper is set against the backdrop of a three-year study of adolescents receiving a relatively new drug (buprenorphine) for the treatment of opiate dependency inside and outside of highly monitored treatment environments in the United States. Lies give order not only to the experience of addiction but also to the experience of therapy as well. In order to better understand this ordering of experience, the paper puts the widely discussed conceptual duality of the pharmakon (healing and poison) in conversation with a perilously overlooked subject in the critical study of pharmacotherapy, namely the pharmakos or the personification of sacrifice. The paper demonstrates how the patient-subject comes to represent therapeutic promise by allowing for the possibility of (and often performing) deceit.

Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice.

Science.gov (United States)

Lee, Bridgin G; Anastasia, Agustin; Hempstead, Barbara L; Lee, Francis S; Blendy, Julie A

2015-12-01

Nicotine withdrawal is characterized by both affective and cognitive symptoms. Identifying genetic polymorphisms that could affect the symptoms associated with nicotine withdrawal are important in predicting withdrawal sensitivity and identifying personalized cessation therapies. In the current study we used a mouse model of a non-synonymous single nucleotide polymorphism in the translated region of the brain-derived neurotrophic factor (BDNF) gene that substitutes a valine (Val) for a methionine (Met) amino acid (Val66Met) to examine the relationship between the Val66Met single nucleotide polymorphism and nicotine dependence. This study measured proBDNF and the BDNF prodomain levels following nicotine and nicotine withdrawal and examined a mouse model of a common polymorphism in this protein (BDNF(Met/Met)) in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test. Using the BDNF knock-in mouse containing the BDNF Val66Met polymorphism we found: (1) blunted anxiety-like behavior in BDNF(Met/Met) mice following withdrawal in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test; (2) the anxiolytic effects of chronic nicotine are absent in BDNF(Met/Met) mice; and (3) an increase in BDNF prodomain in BDNF(Met/Met) mice following nicotine withdrawal. Our study is the first to examine the effect of the BDNF Val66Met polymorphism on the affective symptoms of withdrawal from nicotine in mice. In these mice, a single-nucleotide polymorphism in the translated region of the BDNF gene can result in a blunted withdrawal, as measured by decreased anxiety-like behavior. The significant increase in the BDNF prodomain in BDNF(Met/Met) mice following nicotine cessation suggests a possible role of this ligand in the circuitry remodeling after withdrawal. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For

Menthol Enhances Nicotine Reward-Related Behavior by Potentiating Nicotine-Induced Changes in nAChR Function, nAChR Upregulation, and DA Neuron Excitability.

Science.gov (United States)

Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; McKinney, Sheri; Lester, Henry A

2017-11-01

Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone. Menthol also enhances nicotine-induced changes in DA neuron excitability. In a conditioned place preference (CPP) assay, we observed that menthol plus nicotine produces greater reward-related behavior than nicotine alone. Our results connect changes in midbrain DA neurons to menthol-induced enhancements of nicotine reward-related behavior and may help explain how smokers of menthol cigarettes exhibit reduced cessation rates.

Electronic nicotine delivery system (ENDS) use during smoking cessation: a qualitative study of 40 Oklahoma quitline callers.

Science.gov (United States)

Vickerman, Katrina A; Beebe, Laura A; Schauer, Gillian L; Magnusson, Brooke; King, Brian A

2017-04-01

Approximately 10% (40 000) of US quitline enrollees who smoke cigarettes report current use of electronic nicotine delivery systems (ENDS); however, little is known about callers' ENDS use. Our aim was to describe why and how quitline callers use ENDS, their beliefs about ENDS and the impact of ENDS use on callers' quit processes and use of FDA-approved cessation medications. Qualitative interviews conducted 1-month postregistration. Interviews were recorded, transcribed, double-coded and analysed to identify themes. Oklahoma Tobacco Helpline. 40 callers aged ≥18 who were seeking help to quit smoking were using ENDS at registration and completed ≥1 programme calls. At 1-month postregistration interview, 80% of callers had smoked cigarettes in the last 7 days, almost two-thirds were using ENDS, and half were using cessation medications. Nearly all believed ENDS helped them quit or cut down on smoking; however, participants were split on whether they would recommend cessation medications, ENDS or both together for quitting. Confusion and misinformation about potential harms of ENDS and cessation medications were reported. Participants reported using ENDS in potentially adaptive ways (eg, using ENDS to cut down and nicotine replacement therapy to quit, and stepping down nicotine in ENDS to wean off ENDS after quitting) and maladaptive ways (eg, frequent automatic ENDS use, using ENDS in situations they did not previously smoke, cutting down on smoking using ENDS without a schedule or plan to quit), which could impact the likelihood of quitting smoking or continuing ENDS use. These qualitative findings suggest quitline callers who use ENDS experience confusion and misinformation about ENDS and FDA-approved cessation medications. Callers also use ENDS in ways that may not facilitate quitting smoking. Opportunities exist for quitlines to educate ENDS users and help them create a coordinated plan most likely to result in completely quitting combustible tobacco

Hormone replacement therapy in cancer survivors: Utopia?

Science.gov (United States)

Angioli, Roberto; Luvero, Daniela; Armento, Grazia; Capriglione, Stella; Plotti, Francesco; Scaletta, Giuseppe; Lopez, Salvatore; Montera, Roberto; Gatti, Alessandra; Serra, Giovan Battista; Benedetti Panici, Pierluigi; Terranova, Corrado

2018-04-01

As growing of old women population, menopausal women will also increase: an accurate estimation of postmenopausal population is an essential information for health care providers considering that with aging, the incidence of all cancers is expected to increase. Hormone replacement therapy (HRT) has proven to be highly effective in alleviating menopausal symptoms such as hot flashes, night sweats, dyspareunia, sexual disorders, and insomnia and in preventing osteoporosis. According to preclinical data, estrogen and progesterone are supposed to be involved in the induction and progression of breast and endometrial cancers. Similarly, in epithelial ovarian cancer (EOC), the pathogenesis seems to be at least partly hormonally influenced. Is HRT in gynecological cancer survivors possible? The literature data are controversial. Many clinicians remain reluctant to prescribe HRT for these patients due to the fear of relapse and the risk to develop coronary heart disease or breast cancer. Before the decision to use HRT an accurate counselling should be mandatory in order to individualizing on the basis of potential risks and benefits, including a close follow-up. Nevertheless, we do believe that with strong informed consent doctors may individually consider to prescribe some course of HRT in order to minimize menopausal symptoms and disease related to hormonal reduction. Copyright © 2018 Elsevier B.V. All rights reserved.

Airborne Nicotine, Secondhand Smoke, and Precursors to Adolescent Smoking.

Science.gov (United States)

McGrath, Jennifer J; Racicot, Simon; Okoli, Chizimuzo T C; Hammond, S Katharine; O'Loughlin, Jennifer

2018-01-01

Secondhand smoke (SHS) directly increases exposure to airborne nicotine, tobacco's main psychoactive substance. When exposed to SHS, nonsmokers inhale 60% to 80% of airborne nicotine, absorb concentrations similar to those absorbed by smokers, and display high levels of nicotine biomarkers. Social modeling, or observing other smokers, is a well-established predictor of smoking during adolescence. Observing smokers also leads to increased pharmacological exposure to airborne nicotine via SHS. The objective of this study is to investigate whether greater exposure to airborne nicotine via SHS increases the risk for smoking initiation precursors among never-smoking adolescents. Secondary students ( N = 406; never-smokers: n = 338, 53% girls, mean age = 12.9, SD = 0.4) participated in the AdoQuest II longitudinal cohort. They answered questionnaires about social exposure to smoking (parents, siblings, peers) and known smoking precursors (eg, expected benefits and/or costs, SHS aversion, smoking susceptibility, and nicotine dependence symptoms). Saliva and hair samples were collected to derive biomarkers of cotinine and nicotine. Adolescents wore a passive monitor for 1 week to measure airborne nicotine. Higher airborne nicotine was significantly associated with greater expected benefits ( R 2 = 0.024) and lower expected costs ( R 2 = 0.014). Higher social exposure was significantly associated with more temptation to try smoking ( R 2 = 0.025), lower aversion to SHS ( R 2 = 0.038), and greater smoking susceptibility ( R 2 = 0.071). Greater social exposure was significantly associated with more nicotine dependence symptoms; this relation worsened with higher nicotine exposure (cotinine R 2 = 0.096; airborne nicotine R 2 = 0.088). Airborne nicotine exposure via SHS is a plausible risk factor for smoking initiation during adolescence. Public health implications include limiting airborne nicotine through smoking bans in homes and cars, in addition to stringent restrictions

Nicotine pharmacokinetics and its application to intake from smoking.

Science.gov (United States)

Feyerabend, C; Ings, R M; Russel, M A

1985-01-01

Five subjects were given 25 micrograms/kg nicotine intravenously over 1 min, before and after a loading period involving the smoking of six cigarettes. Plasma nicotine concentrations declined in a biphasic manner, the half-lives of the initial and terminal phases averaging 9 min and 133 min respectively. Terminal half-lives before and after the loading period were essentially the same suggesting the absence of saturation kinetics at nicotine concentrations that build up during smoking. The plasma clearance of nicotine and the volume of distribution were very high averaging 915 ml/min and 1731, respectively. Two approaches were used to calculate the nicotine intake from smoking. The average dose of nicotine absorbed from one cigarette was 1.06 mg which was 82% of the standard machine-smoked yield of 1.3 mg. To illustrate their potential use in 'nicotine titration' studies, these approaches were used to compare nicotine intake from smoking a high (2.4 mg) and low (0.6 mg) nicotine cigarette. The dose of nicotine absorbed averaged 1.14 mg and 0.86 mg per cigarette respectively, being 48% and 143% of the machine-smoked yields. PMID:3986082

Timing of renal replacement therapy and clinical outcomes in critically ill patients with severe acute kidney injury

NARCIS (Netherlands)

Bagshaw, Sean M.; Uchino, Shigehiko; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Ettiene; Gibney, Noel; Tolwani, Ashita; Oudemans-van Straaten, Heleen M.; Ronco, Claudio; Kellum, John A.; French, Craig; Mulder, John; Pinder, Mary; Roberts, Brigit; Botha, John; Mudholkar, Pradeen; Holt, Andrew; Hunt, Tamara; Honoré, Patrick Maurice; Clerbaux, Gaetan; Schetz, Miet Maria; Wilmer, Alexander; Yu, Luis; Macedo, Ettiene V.; Laranja, Sandra Maria; Rodrigues, Cassio José; Suassuna, José Hermógenes Rocco; Ruzany, Frederico; Campos, Bruno; Leblanc, Martine; Senécal, Lynne; Gibney, R. T. Noel; Johnston, Curtis; Brindley, Peter; Tan, Ian K. S.; Chen, Hui De; Wan, Li; Rokyta, Richard; Krouzecky, Ales; Neumayer, Hans-Helmut; Detlef, Kindgen-Milles; Mueller, Eckhard; Tsiora, Vicky; Sombolos, Kostas; Mustafa, Iqbal; Suranadi, Iwayan; Bar-Lavie, Yaron; Nakhoul, Farid; Ceriani, Roberto; Bortone, Franco; Zamperetti, Nereo; Pappalardo, Federico; Marino, Giovanni; Calabrese, Prospero; Monaco, Francesco; Liverani, Chiara; Clementi, Stefano; Coltrinari, Rosanna; Marini, Benedetto; Fuke, Nobuo; Miyazawa, Masaaki; Katayama, Hiroshi; Kurasako, Toshiaki; Hirasaw, Hiroyuki; Oda, Shigeto; Tanigawa, Koichi; Tanaka, Keiichi; Oudemans-van Straaten, Helena Maria; de Pont, Anne-Cornelie J. M.; Bugge, Jan Frederik; Riddervold, Fridtjov; Nilsen, Paul Age; Julsrud, Joar; Teixeira e Costa, Fernando; Marcelino, Paulo; Serra, Isabel Maria; Yaroustovsky, Mike; Grigoriyanc, Rachik; Lee, Kang Hoe; Loo, Shi; Singh, Kulgit; Barrachina, Ferran; Llorens, Julio; Sanchez-Izquierdo-Riera, Jose Angel; Toral-Vazquez, Darío; Wizelius, Ivar; Hermansson, Dan; Gaspert, Tomislav; Maggiorini, Marco; Davenport, Andrew; Lombardi, Raúl; Llopart, Teresita; Venkataraman, Ramesh; Kellum, John; Murray, Patrick; Trevino, Sharon; Benjamin, Ernest; Hufanda, Jerry; Paganini, Emil; Warnock, David; Guirguis, Nabil

2009-01-01

The aim of this study is to evaluate the relationship between timing of renal replacement therapy (RRT) in severe acute kidney injury and clinical outcomes. This was a prospective multicenter observational study conducted at 54 intensive care units (ICUs) in 23 countries enrolling 1238 patients.

NICOTINE EFFECTS ON THE ACTIVITY OF MICE EXPOSED PRENATALLY TO THE NICOTINIC AGONIST ANATOXIN-A.

Science.gov (United States)

Considerable research has shown long-lasting effects of early exposure in experimental animals to nicotine. Anatoxin-a is produced by cyanobacteria and has been shown to be a potent nicotinic agonist. This experiment evaluated the motor activity of adult mice, and their respons...

Continuous renal replacement therapy in neonates and small infants: development and first-in-human use of a miniaturised machine (CARPEDIEM).

Science.gov (United States)

Ronco, Claudio; Garzotto, Francesco; Brendolan, Alessandra; Zanella, Monica; Bellettato, Massimo; Vedovato, Stefania; Chiarenza, Fabio; Ricci, Zaccaria; Goldstein, Stuart L

2014-05-24

Peritoneal dialysis is the renal replacement therapy of choice for acute kidney injury in neonates, but in some cases is not feasible or effective. Continuous renal replacement therapy (CRRT) machines are used off label in infants smaller than 15 kg and are not designed specifically for small infants. We aimed to design and create a CRRT machine specifically for neonates and small infants. We prospectively planned a 5-year project to conceive, design, and create a miniaturised Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM), specifically for neonates and small infants. We created the new device and assessed it with in-vitro laboratory tests, completed its development to meet regulatory requirements, and obtained a licence for human use. Once approved, we used the machine to treat a critically ill neonate The main characteristics of CARPEDIEM are the low priming volume of the circuit (less than 30 mL), miniaturised roller pumps, and accurate ultrafiltration control via calibrated scales with a precision of 1 g. In-vitro tests confirmed that both hardware and software met the specifications. We treated a 2·9 kg neonate with haemorrhagic shock, multiple organ dysfunction, and severe fluid overload for more than 400 h with the CARPEDIEM, using continuous venovenous haemofiltration, single-pass albumin dialysis, blood exchange, and plasma exchange. The patient's 65% fluid overload, raised creatinine and bilirubin concentrations, and severe acidosis were all managed safely and effectively. Despite the severity of the illness, organ function was restored and the neonate survived and was discharged from hospital with only mild renal insufficiency that did not require renal replacement therapy. The CARPEDIEM CRRT machine can be used to provide various treatment modalities and support for multiple organ dysfunction in neonates and small infants. The CARPEDIEM could reduce the range of indications for peritoneal dialysis, widen the range of indications for CRRT

Effect of nicotine on negative affect among more impulsive smokers.

Science.gov (United States)

Doran, Neal; McChargue, Dennis; Spring, Bonnie; VanderVeen, Joe; Cook, Jessica Werth; Richmond, Malia

2006-08-01

In the present study, the authors tested the hypothesis that nicotine would provide greater relief from negative affect for more impulsive smokers than for less impulsive smokers. Euthymic adult smokers (N=70) participated in 2 laboratory sessions, during which they underwent a negative mood induction (music + autobiographical memory), then smoked either a nicotinized or de-nicotinized cigarette. Mixed-effects regression yielded a significant Impulsivity x Condition (nicotinized vs. de-nicotinized) x Time interaction. Simple effects analyses showed that heightened impulsivity predicted greater negative affect relief after smoking a nicotinized cigarette but not after smoking a de-nicotinized cigarette. These data suggest that nicotine may be a disproportionately powerful negative reinforcer for highly impulsive smokers, promoting higher levels of nicotine dependence and inhibiting smoking cessation.

Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.

Science.gov (United States)

Tumkosit, Prem; Kuryatov, Alexander; Luo, Jie; Lindstrom, Jon

2006-10-01

Nicotinic acetylcholine receptors (AChRs) containing alpha6 subunits are typically found at aminergic nerve endings where they play important roles in nicotine addiction and Parkinson's disease. alpha6* AChRs usually contain beta3 subunits. beta3 subunits are presumed to assemble only in the accessory subunit position within AChRs where they do not participate in forming acetylcholine binding sites. Assembly of subunits in the accessory position may be a critical final step in assembly of mature AChRs. Human alpha6 AChRs subtypes were permanently transfected into human tsA201 human embryonic kidney (HEK) cell lines. alpha6beta2beta3 and alpha6beta4beta3 cell lines were found to express much larger amounts of AChRs and were more sensitive to nicotine-induced increase in the amount of AChRs than were alpha6beta2 or alpha6beta4 cell lines. The increased sensitivity to nicotine-induced up-regulation was due not to a beta3-induced increase in affinity for nicotine but probably to a direct effect on assembly of AChR subunits. HEK cells express only a small amount of mature alpha6beta2 AChRs, but many of these subunits are on the cell surface. This contrasts with Xenopus laevis oocytes, which express a large amount of incorrectly assembled alpha6beta2 subunits that bind cholinergic ligands but form large amorphous intracellular aggregates. Monoclonal antibodies (mAbs) were made to the alpha6 and beta3 subunits to aid in the characterization of these AChRs. The alpha6 mAbs bind to epitopes C-terminal of the extracellular domain. These data demonstrate that both cell type and the accessory subunit beta3 can play important roles in alpha6* AChR expression, stability, and up-regulation by nicotine.

Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-alpha-bungarotoxin

International Nuclear Information System (INIS)

Clarke, P.B.; Schwartz, R.D.; Paul, S.M.; Pert, C.B.; Pert, A.

1985-01-01

Three radioligands have been commonly used to label putative nicotinic cholinoceptors in the mammalian central nervous system: the agonists [ 3 H]nicotine and [ 3 H]acetylcholine ([ 3 H]ACh--in the presence of atropine to block muscarinic receptors), and the snake venom extract, [ 125 I]-alpha-bungarotoxin([ 125 I]BTX), which acts as a nicotinic antagonist at the neuromuscular junction. Binding studies employing brain homogenates indicate that the regional distributions of both [ 3 H]nicotine and [ 3 H]ACh differ from that of [ 125 I]BTX. The possible relationship between brain sites bound by [ 3 H]nicotine and [ 3 H]ACh has not been examined directly. The authors have used the technique of autoradiography to produce detailed maps of [ 3 H]nicotine, [ 3 H]ACh, and [ 125 I]BTX labeling; near-adjacent tissue sections were compared at many levels of the rat brain. The maps of high affinity agonist labeling are strikingly concordant, with highest densities in the interpeduncular nucleus, most thalamic nuclei, superior colliculus, medial habenula, presubiculum, cerebral cortex (layers I and III/IV), and the substantia nigra pars compacta/ventral tegmental area. The pattern of [ 125 I]BTX binding is strikingly different, the only notable overlap with agonist binding being the cerebral cortex (layer I) and superior colliculus. [ 125 I]BTX binding is also dense in the inferior colliculus, cerebral cortex (layer VI), hypothalamus, and hippocampus, but is virtually absent in thalamus. Various lines of evidence suggest that the high affinity agonist-binding sites in brain correspond to nicotinic cholinergic receptors similar to those found at autonomic ganglia; BTX-binding sites may also serve as receptors for nicotine and are possibly related to neuromuscular nicotinic cholinoceptors

Nicotine Reduction Revisited: Science and Future Directions

Science.gov (United States)

Hatsukami, Dorothy K.; Perkins, Kenneth A.; LeSage, Mark G.; Ashley, David L.; Henningfield, Jack E.; Benowitz, Neal L.; Backinger, Cathy; Zeller, Mitch

2015-01-01

Regulation of nicotine levels in cigarettes and other tobacco products is now possible with the passage of the Family Smoking Prevention and Tobacco Control Act (FSPTCA) in 2009 giving the U.S. Food and Drug Administration authority to regulate tobacco products, and with Articles 9-11 of the World Health Organization Framework Convention on Tobacco Control.[1-2] Both regulatory approaches allow establishing product standards for tobacco constituents, including nicotine. The FSPTCA does not allow nicotine levels to be decreased to zero, although FDA has the authority to reduce nicotine yields to very low, presumably non-addicting levels. The proposal to reduce levels of nicotine to a level that is non-addicting was originally suggested in 1994.[3] Reduction of nicotine in tobacco products could potentially have a profound impact on reducing tobacco-related morbidity and mortality. To examine this issue, two meetings were convened in the United States with non-tobacco-industry scientists of varied disciplines, tobacco control policy-makers and representatives of government agencies. This article provides an overview of the current science in the area of reduced nicotine content cigarettes and key conclusions and recommendations for research and policy that emerged from the deliberations of the meeting members. PMID:20876072