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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of applied ichthyology 5 (1989), S. 0 
    ISSN: 1439-0426
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: The distributions of length frequencies subdivided by age of orange roughy (Hoplostethus atlanticus: Trachichthyidae) had the modal characteristics of K-selected populations. Oceanographic data showed that the depth strata occupied by orange roughy have boundary characteristics which could lead to the development of non-equilibrium dissipative thermodynamic structures and which would account for the K-selection configuration of orange roughy stocks.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 11 (1997), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cyclo-oxygenase-1 (COX-1) is believed to produce prostaglandins vital to mucosal defence, whereas cyclo-oxygenase-2 (COX-2) is induced at sites of inflammation. Little is known about the regulation of COX-2 in the stomach, particularly during the period following mucosal injury. In this study, we examined COX-1 and COX-2 expression shortly after administration of NSAIDs or ethanol.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:Fasted rats were given aspirin, salicylate, indomethacin or ethanol (20% or 40%) orally. Three hours later the stomach was excised, the severity of damage scored and samples taken for RT-PCR of COX-1 and COX-2 mRNA and immunohistochemistry. Nitric oxide synthase mRNA (iNOS and eNOS) and activity were also measured.〈section xml:id="abs1-3"〉〈title type="main"〉Results:Aspirin, indomethacin and the higher concentration of ethanol produced widespread mucosal damage, whereas salicylate and 20% ethanol caused only superficial epithelial damage. Aspirin caused a significant increase in COX-2 mRNA expression and a marked increase in COX-2 immunoreactivity, particularly in the superficial mucosa. Expression of COX-1 (mRNA and protein) was unaffected by aspirin, as were NOS mRNA expression and enzyme activity. Pre-treatment with prostaglandin E2 prevented the induction of COX-2 by aspirin. Salicylate and indomethacin caused modest increases in COX-2 immunoreactivity but no change in COX-2 mRNA. Neither concentration of ethanol affected COX-2 mRNA or protein expression, suggesting that this was a specific response to the aspirin, rather than to injury.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:These results demonstrate a rapid up-regulation of COX-2 expression in response to aspirin, possibly representing a compensatory response to inhibition of gastric prostaglandin synthesis.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford BSL : Blackwell Science
    Alimentary pharmacology & therapeutics 11 (1997), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: A novel class of nitric oxide-releasing nonsteroidal anti-inflammatory drug (NO-NSAID) derivatives has recently been described which exert anti-inflammatory activities but produce significantly less gastrointestinal injury than the parent NSAID from which they are derived. The present studies were performed to determine if a nitroxybutylester derivative of naproxen was less ulcerogenic to the gastrointestinal tract than its parent NSAID, and if it exerted comparable analgesic and anti-inflammatory properties to the parent NSAID. Methods: The two drugs were compared in an acute gastric injury model, an antral ulcer model and after twice-daily administration for 18 days (small intestinal damage model). Anti-inflammatory activity was examined in the carrageenan-induced paw oedema model, while analgesia was examined in the acetic acid-induced writhing model. The pharmacokinetic profiles of naproxen vs. NO-naproxen were compared by HPLC analysis. Results: NO-naproxen was found to produce significantly less gastric damage despite inducing similar increases in plasma TNFα to naproxen. With chronic administration, small intestinal damage was markedly less with NO-naproxen than with the parent NSAID. However, NO-naproxen exerted superior analgesic and comparable anti-inflammatory effects to naproxen. NO-naproxen was not completely converted to naproxen, but the reduced plasma levels of the latter was not the underlying reason for reduced gastrointestinal toxicity of NO-naproxen. Conclusion: NO-naproxen represents a novel, gastrointestinal-sparing NSAID derivative with superior analgesic and comparable anti-inflammatory properties to naproxen.
    Type of Medium: Electronic Resource
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  • 4
    Publication Date: 2013-11-28
    Description: We agree with Davies that further studies are needed before psychiatric safety concerns about varenicline can be laid to rest.1 2We believe that our study provides reassuring evidence because we used...
    Keywords: Clinical trials (epidemiology), Sleep disorders (neurology), Sleep disorders, Suicide (psychiatry), Sleep disorders (respiratory medicine), Drugs: musculoskeletal and joint diseases, Competing interests (ethics), Suicide (public health)
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 5
    Publication Date: 2013-10-12
    Description: Objective To compare the risk of suicide, self harm, and depression in patients prescribed varenicline or bupropion with those prescribed nicotine replacement therapy.Design Prospective cohort study...
    Keywords: Smoking and tobacco, Epidemiologic studies, General practice / family medicine, UK, Suicide (psychiatry), Health education, Health promotion, Smoking, Suicide (public health)
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 6
    Publication Date: 2016-12-15
    Description: Introduction Current treatments for Alzheimer's and other neurodegenerative diseases have only limited effectiveness meaning that there is an urgent need for new medications that could influence disease incidence and progression. We will investigate the potential of a selection of commonly prescribed drugs, as a more efficient and cost-effective method of identifying new drugs for the prevention or treatment of Alzheimer's disease, non-Alzheimer's disease dementias, Parkinson's disease and amyotrophic lateral sclerosis. Our research will focus on drugs used for the treatment of hypertension, hypercholesterolaemia and type 2 diabetes, all of which have previously been identified as potentially cerebroprotective and have variable levels of preclinical evidence that suggest they may have beneficial effects for various aspects of dementia pathology. Methods and analysis We will conduct a hypothesis testing observational cohort study using data from the Clinical Practice Research Datalink (CPRD). Our analysis will consider four statistical methods, which have different approaches for modelling confounding. These are multivariable adjusted Cox regression; propensity matched regression; instrumental variable analysis and marginal structural models. We will also use an intention-to-treat analysis, whereby we will define all exposures based on the first prescription observed in the database so that the target parameter is comparable to that estimated by a randomised controlled trial. Ethics and dissemination This protocol has been approved by the CPRD's Independent Scientific Advisory Committee (ISAC). We will publish the results of the study as open-access peer-reviewed publications and disseminate findings through national and international conferences as are appropriate.
    Keywords: Open access, Epidemiology, Neurology, Pharmacology and therapeutics
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 7
    Publication Date: 2016-11-09
    Print ISSN: 0300-5771
    Electronic ISSN: 1464-3685
    Topics: Medicine
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  • 8
    Publication Date: 2016-06-17
    Description: Introduction Evidence from observational studies and randomised controlled trials suggests that breastfeeding is positively associated with IQ, possibly because breast milk is a source of long-chain polyunsaturated fatty acids. Different studies have detected gene-breastfeeding interactions involving FADS2 variants and intelligence. However, findings are inconsistent regarding the direction of such effect modification. Methods/design To clarify how FADS2 and breastfeeding interact in their association with IQ, we are conducting a consortium-based meta-analysis of independent studies. Results produced by each individual study using standardised analysis scripts and harmonised data will be used. Inclusion criteria : breastfeeding, IQ and either rs174575 or rs1535 polymorphisms available; and being of European ancestry. Exclusion criteria : twin studies; only poorly imputed genetic data available; or unavailability of proper ethics approval. Studies will be invited based on being known to have at least some of the required data, or suggested by participating studies as potentially eligible. This inclusive approach will favour achieving a larger sample size and be less prone to publication bias. Discussion Improving current understanding of FADS2 -breastfeeding interaction may provide important biological insights regarding the importance of long-chain polyunsaturated fatty acids for the breastfeeding-IQ association. This meta-analysis will help to improve such knowledge by replicating earlier studies, conducting additional analysis and evaluating different sources of heterogeneity. Publishing this protocol will minimise the possibility of bias due to post hoc changes to the analysis protocol.
    Keywords: Open access, Epidemiology, Genetics and genomics
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 9
    Publication Date: 2015-11-08
    Description: Introduction 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. Methods 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 and dissemination 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.
    Keywords: Open access, Addiction, Epidemiology, General practice / Family practice, Research methods, Smoking and tobacco
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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