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  • 1.
    Abassi, Marwa
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Effektivitet av kognitiv beteendeterapi vid Irritable bowel syndrome2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 2.
    Abdulbasid Samad, Delan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Farmaceut-patientkommunikation på öppenvårdsapotek i Kurdistan: En observationsstudie som undersöker i vilken omfattning apotekspersonalen informerar om läkemedelsanvändningen och dess verkan.2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Introduktion: Apotekens riktlinjer har utvecklats från att ha begränsat farmaceuter ideras utdelning av medicin till att ge råd eller erbjuda rådgivning om patientens medicinering. Det är viktigt att farmaceuter ger rådgivning kring patienters medicinering då det ger effektivt behandlingsresultat, ökad följsamhet och minskar konfusion och osäkerhet hos patienten. Studier har visat att den farmaceutiska rådgivningen varierar mycket på apotek. En svensk studie har visat att samtalet mellan farmaceut och patient fokuserar mer på ekonomi och regelverk än att ge farmaceutiskrådgivning. Det har tidigare inte gjorts studier på hur kommunikation samt den farmaceutiska rådgivningen fungerar i mellanöstern.

    Syfte: Syftet med den här studien är att undersöka kommunikationen mellan farmaceut och patient på öppenvårdsapotek i Kurdistan, Irak. Kommunikationen kommer att undersökas utifrån hur lång tid patientmötena tar och innehåll. Det som studeras är i vilken utsträckning apotekspersonalen konsulterar patienter samt den information som tillhandahålls till patienterna ur ett farmaceutiskt perspektiv.

    Metod: En kvantitativ och icke- deltagande observationsstudie där patientmöten observerades utifrån innehåll och tidsmätning av mötet. Observatören bockade avämnen som tas upp under mötet utefter en empirisk fastställd observationsmall.

    Resultat: 4 apotek deltog i studien och det gjordes sammanlagt 90 observationer varav 85 stycken inkluderades i studien. Apotekmiljön har en negativ påverkan på patientmötena, exempelvis att det saknas ett avskilt ställe för ett privatsamtal medpatienter, bullret i omgivningen och dålig organiserad läkemedel. Den stora delen av den medicinska konsulteringen är information om administrering, lite om läkemedelsverkan och nästan inget om biverkningar. Det icke-medicinska innehållet var frågor om pris och tillgänglighet av läkemedel.

    Diskussion: Det finns säkert många anledningar för varför kommunikationen inte är fokuserad på konsultering till patienter. En orsak kan vara otillräcklig kunskap bland informatörerna som konsultering kring biverkningar och läkemedels verkan exkluderas i kommunikationen. En annan förklaring kan vara att rådgivningen tar mer tid och at tapoteksägare upplever rådgivning som en dyr tjänst och av den anledningen inteprioriterar sin uppmärksamhet på läkemedelsrådgivning. Försäljningen som uppenbarligen inte ligger i att ge läkemedelsrådgivning till patienterna.

    Slutsats: Den här observationsstudien visade att mycket lite tid (medeltid 125,5 smin7 s/max 427 s) tillägnas till rådgivning kring patientens medicinering. Läkemedel är en stor behandlingsmetod inom hälso- och sjukvården av den orsaken borde farmaceutisk rådgivning vara tillgänglig för personer som besöker apotek. Resultatet avden här studien visar att dagens patientmöten på öppenvårdapotek i Kurdistan inte fokuserar på konsultering kring läkemedel. Eventuellt kommer patienten inte få ett nyttigt behandlingsresultat.

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  • 3.
    Abed, Ala
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Polyfarmaci och fall hos äldre2018Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 4.
    Abed, Kawsar
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Intressenter på apoteksmarknaden: En analys av vilka aktörer som intresserar sig i apoteksbranschen och vilka åsikter de har2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 5.
    Abed, Shahla
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Is adiponectin secreted via caveolae?: The importance of caveolae for stimulated adiponectin secretion in obesity2018Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
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  • 6.
    Abramsson, Linnea
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Följsamhet till behandling med bisfosfonater: En intervjustudie på ortopedavdelningen vid Norrlands Universitetssjukhus, Umeå2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
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    Följsamhet till behandling med bisfosfonater: En intervjustudie på ortopedavdelningen vid Norrlands Universitetssjukhus, Umeå
  • 7.
    Abramsson, Linnea
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    PREVALENCE OF DRUG RELATED PROBLEMS STOPP/START in elderly people with dementia2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
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  • 8.
    Abramsson, Linnea
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Gustafsson, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Adherence to Bisphosphonates among People Admitted to an Orthopaedic and Geriatric Ward at a University Hospital in Sweden2018In: Pharmacy, E-ISSN 2226-4787, Vol. 6, no 1, article id 20Article in journal (Refereed)
    Abstract [en]

    Oral bisphosphonates are the first choice of therapy to reduce the risk of osteoporotic fractures. These medications have generally poor oral bioavailability, which may further be reduced by concomitant intake of certain foods and drugs; therefore, it is vital to follow specific instructions. The aim with this study was to assess general adherence to oral bisphosphonates and adherence to specific administration instructions among people admitted to two wards at Umeå University hospital in Sweden. This interview study focuses on elderly patients living at home and prescribed oral bisphosphonates. Invited were 27 patients admitted to an orthopaedic ward and a geriatric ward during the period 28 March 2017 and 5 December 2017. In total, 21 patients were interviewed regarding their adherence to oral bisphosphonates. Out of 21 patients, 13 (62%) were considered non-adherent. The most common reason was calcium intake less than 2 h after oral administration of bisphosphonate (54%). The number of regularly prescribed drugs was significantly higher among patients rated non-adherent to bisphosphonates compared to those rated adherent (p = 0.004). Adherence to bisphosphonates administration instruction among elderly people living at home was limited. More research is needed to confirm these results and to investigate the reasons for non-adherence and how adherence to bisphosphonates can be improved.

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  • 9.
    Abramsson, Linnea
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Gustafsson, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Prevalence of drug-related problems using STOPP/START and medication reviews in elderly patients with dementia2020In: Research in Social and Administrative Pharmacy, ISSN 1551-7411, E-ISSN 1934-8150, Vol. 16, no 3, p. 308-314Article in journal (Refereed)
    Abstract [en]

    Background: Drug-related problems (DRPs) are common among elderly patients with dementia. STOPP/START is an explicit tool that has been used to detect DRPs among elderly patients.

    Objectives: The objective of this study was to compare prevalence and type of DRPs identified by STOPP/START with DRPs identified by clinical pharmacists among the same population. Secondary objectives were to investigate factors associated with the use of DRPs using the two methods.

    Method: Extracts from medical records were used to identify DRPs in 212 patients by using STOPP/START. The patients were ≥65 years of age with dementia or cognitive impairment. An earlier study was performed in the same study population in 2012–2014, where DRPs were identified by clinical pharmacists in order to decrease the number of rehospitalizations.

    Results: STOPP/START identified DRPs in 72.2% of the patients compared with 66.0% identified by the clinical pharmacists. The numbers of DRPs identified by the different methods were 326 and 310, respectively. Different types of DRPs were identified with the different tools. STOPP/START mainly identified DRPs in the categories “ineffective/inappropriate drug” and “needs additional drug therapy”, whereas the clinical pharmacists identified DRPs in several categories.

    Conclusion: Even though STOPP/START was able to identify a similar number of DRPs compared with DRPs identified by clinical pharmacists, STOPP/START failed to identify DRPs in several important categories. To cover all DRPs, STOPP/START might be used as a complement to implicit criteria.

  • 10.
    Abutaleb, Hind
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Biverkningar avsolskyddsprodukter: Retrospektiv analys av allvarliga biverkningarinrapporterade till Läkemedelsverket underperioden 2013–20172019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
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  • 11.
    Aden, Hassan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Apotekssystem i Kanada och Storbritannienrelaterat till Sveriges utveckling i enomreglerad apoteksmarknad2018Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 12.
    Ahmed Nazad, Zina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    MicroRNAs as biomarkers in some cardiovascular diseases: A bioinformatics and review study2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
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    MicroRNAs as biomarkers in some cardiovascular diseases: A bioinformatics and review study
  • 13.
    Akhatova, Elena
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Information och rådgivningvid e-handelpå apotek i Sverige.2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
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  • 14.
    Akpan, Joyce
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    The Prevalence of Potentially Inappropriate Drug Prescription among Elderly Patients Registered in Balder Clinic in Åmål, Sweden2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
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    The Prevalence of Potentially Inappropriate Drug Prescription among Elderly Patients Registered in Balder Clinic in Åmål, Sweden
  • 15.
    Al-ameri, Khalid
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Effektskillnad mellanmåldos och lågdos vidhjärtsviktsbehandling2018Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 16.
    Alfredji, Kaothar
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Effekt av tillskott av vitamin D på vårt immunförsvar2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
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    Effekt av tillskott av vitamin D på vårt immunförsvar
  • 17. Alhayali, Amani
    et al.
    Tavelin, Staffan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Velaga, Sitaram
    Dissolution and precipitation behavior of ternary solid dispersions of ezetimibe in biorelevant media2017In: Drug Development and Industrial Pharmacy, ISSN 0363-9045, E-ISSN 1520-5762, Vol. 43, no 1, p. 79-88Article in journal (Refereed)
    Abstract [en]

    The effects of different formulations and processes on inducing and maintaining the supersaturation of ternary solid dispersions of ezetimibe (EZ) in two biorelevant media fasted-state simulated intestinal fluid (FaSSIF) and fasted-state simulated gastric fluid (FaSSGF) at different temperatures (25 °C and 37 °C) were investigated in this work.

    Ternary solid dispersions of EZ were prepared by adding polymer PVP-K30 and surfactant poloxamer 188 using melt-quenching and spray-drying methods. The resulting solid dispersions were characterized using scanning electron microscopy, differential scanning calorimetry (DSC), modulated DSC, powder X-ray diffraction and Fourier transformation infrared spectroscopy. The dissolution of all the ternary solid dispersions was tested in vitro under non-sink conditions.

    All the prepared solid dispersions were amorphous in nature. In FaSSIF at 25 °C, the melt-quenched (MQ) solid dispersions of EZ were more soluble than the spray-dried (SD) solid dispersions and supersaturation was maintained. However, at 37 °C, rapid and variable precipitation behavior was observed for all the MQ and SD formulations. In FaSSGF, the melting method resulted in better solubility than the spray-drying method at both temperatures.

    Ternary solid dispersions show potential for improving solubility and supersaturation. However, powder dissolution experiments of these solid dispersions of EZ at 25 °C may not predict the supersaturation behavior at physiologically relevant temperatures.

  • 18.
    Alhouayek, Mireille
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology. Catholic Univ Louvain, Brussels, Belgium.
    Gouveia-Figueira, Sandra
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Swedish Univ Agr Sci, Umea, Sweden.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Fowler, Christopher J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Involvement of CYP1B1 in interferon gamma-induced alterations of epithelial barrier integrity2018In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 175, no 6, p. 877-890Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE CYP1B1 and CYP1A1 are important extra-hepatic cytochromes, expressed in the colon and involved in the metabolism of dietary constituents and exogenous compounds. CYP1B1 expression is increased by pro-inflammatory cytokines, and it has been recently implicated in regulation of blood brain barrier function. We investigated its involvement in the increased permeability of the intestinal epithelial barrier observed in inflammatory conditions. EXPERIMENTAL APPROACH Epithelial monolayers formed by human T84 colon carcinoma cells cultured on transwells, were disrupted by incubation with IFN gamma (10 ng.mL(-1)). Monolayer integrity was measured using transepithelial electrical resistance. CYP1A1 and CYP1B1 inhibitors or inducers were applied apically. Potential mechanisms of action were investigated using RT-qPCR. KEY RESULTS IFN gamma disrupts the barrier integrity of the T84 monolayers and increases CYP1B1 and HIF1 alpha mRNA expression. CYP1B1 induction is inhibited by the NF-kappa B inhibitor ammonium pyrrolidinedithiocarbamate (100 mu M) but not by the HIF1 alpha inhibitor 3-(5-hydroxymethyl-2-furyl)-1-benzyl indazole (50 mu M). Inhibition of CYP1B1 with the selective inhibitor 2,4,3,5-tetramethoxystilbene (100 nM) partly reverses the effects of IFN gamma on epithelial permeability. CONCLUSIONS AND IMPLICATIONS These data suggest that increased expression of CYP1B1 is involved in the effects of IFN gamma on epithelial permeability. Inhibition of CYP1B1 counteracts the alterations of epithelial barrier integrity induced by IFN gamma and could thus have a therapeutic potential in disorders of intestinal permeability associated with inflammation.

  • 19.
    Alhouayek, Mireille
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Rankin, Linda
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Gouveia-Figueira, Sandra C.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fowler, Christopher J
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Interferon γ treatment increases endocannabinoid and related N-acylethanolamine levels in T84 human colon carcinoma cells2019In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 176, no 10, p. 1470-1480Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Endocannabinoids and related N-acylethanolamines (NAEs) are involved in regulation of gut function, but relatively little is known as to whether inflammatory cytokines such as IFN affect their levels. We have investigated this in vitro using cultures of T84 colon cancer cells.

    Experimental approach: T84 cells, when cultured in monolayers, differentiate to form adult colonic crypt-like cells with excellent permeability barrier properties. The integrity of the permeability barrier in these monolayers was measured using transepithelial electrical resistance (TEER). NAE levels were determined by ultra-performance liquid chromatography-tandem mass spectrometric analysis. Expression of the enzymes involved in NAE and 2-arachidonoylglycerol (2-AG) turnover were assessed with qPCR.

    Key results: IFN treatment for 8 or 24h increased levels of both endocannabinoids (anandamide and 2-AG) and the related NAEs. The treatment did not affect the rate of hydrolysis of either anandamide or palmitoylethanolamide by intact cells, and in both cases, fatty acid amide hydrolase (FAAH) rather than NAE-hydrolysing acid amidase (NAAA) was mainly responsible for the hydrolysis of these NAEs. IFN treatment reduced the TEER of the cells in a manner that was not prevented by inhibition of either FAAH or NAAA but was partially reversed by apical administration of the NAE palmitoylethanolamide.

    Conclusion and implications: IFN treatment mobilized endocannabinoid and related NAE levels in T84 cells. However, blockade of anandamide or NAE hydrolysis was insufficient to negate the deleterious effects of this cytokine upon the permeability barrier of the cell monolayers.

  • 20.
    Alhouayek, Mireille
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Sorti, René
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Gilthorpe, Jonathan D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Fowler, Christopher J
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Role of pannexin-1 in the cellular uptake, release and hydrolysis of anandamide by T84 colon cancer cells2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 7622Article in journal (Refereed)
    Abstract [en]

    The large pore ion channel pannexin-1 (Panx1) has been reported to play a role in the cellular uptake and release of anandamide (AEA) in the hippocampus. It is not known whether this is a general mechanism or limited to the hippocampus. We have investigated this pharmacologically using T84 colon cancer cells. The cells expressed Panx1 at the mRNA level, and released ATP in a manner that could be reduced by treatment with the Panx1 inhibitors carbenoxolone and mefloquine and the Panxl substrate SR101. However, no significant effects of these compounds upon the uptake or hydrolysis of exogenously applied AEA was seen. Uptake by T84 cells of the other main endocannabinoid 2-arachidonoylglycerol and the AEA homologue palmitoylethanolamide was similarly not affected by carbenoxolone or mefloquine. Total release of tritium from [H-3]AEA-prelabelled T84 cells over 10 min was increased, rather than inhibited by carbenoxolone and mefloquine. Finally, AEA uptake by PC3 prostate cancer and SH-SY5Y neuroblastoma cells, which express functional Panx1 channels, was not inhibited by carbenoxolone. Thus, in contrast to the hippocampus, Panx1 does not appear to play a role in AEA uptake and release from the cells studied under the conditions used.

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  • 21.
    Ali Ebrahimi, Mozhdeh
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Psykisk stress och psoriasis2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 22.
    Al-Khafaji, Shadan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    EPILEPSI OCH PSYKISK OHÄLS2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 23.
    Al-Obaidi, Mays
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Effekt av vitamin A-tillskott på mortalitet och morbiditet hos barn mellan 6 månader och 6 års ålder: En litteraturstudie med fokus på effekter av vitaminA-tillskott på dödlighet och sjuklighet i diarré och luftvägsinfektioner hos barn i utvecklingsländer2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
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    Effekt av vitamin A-tillskott på mortalitet och morbiditet hos barn mellan 6 månader och 6 års ålder
  • 24.
    Al-Obaidi, Mays
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Läkemedelsundervisning i skolan: En enkätundersökning på gymnasieskole elever- och lärare i Skåne län2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
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  • 25.
    Altufaili, Muna
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    NSAID-användning under graviditet2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 26. Anand, Praveen
    et al.
    Whiteside, Garth
    Fowler, Christopher J
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Hohmann, Andrea G
    Targeting CB2 receptors and the endocannabinoid system for the treatment of pain2009In: Brain Research Reviews, ISSN 0165-0173, E-ISSN 1872-6321, Vol. 60, no 1, p. 255-266Article in journal (Refereed)
    Abstract [en]

    The endocannabinoid system consists of the cannabinoid (CB) receptors, CB(1) and CB(2), the endogenous ligands anandamide (AEA, arachidonoylethanolamide) and 2-arachidonoylglycerol (2-AG), and their synthetic and metabolic machinery. The use of cannabis has been described in classical and recent literature for the treatment of pain, but the potential for psychotropic effects as a result of the activation of central CB(1) receptors places a limitation upon its use. There are, however, a number of modern approaches being undertaken to circumvent this problem, and this review represents a concise summary of these approaches, with a particular emphasis upon CB(2) receptor agonists. Selective CB(2) agonists and peripherally restricted CB(1) or CB(1)/CB(2) dual agonists are being developed for the treatment of inflammatory and neuropathic pain, as they demonstrate efficacy in a range of pain models. CB(2) receptors were originally described as being restricted to cells of immune origin, but there is evidence for their expression in human primary sensory neurons, and increased levels of CB(2) receptors reported in human peripheral nerves have been seen after injury, particularly in painful neuromas. CB(2) receptor agonists produce antinociceptive effects in models of inflammatory and nociceptive pain, and in some cases these effects involve activation of the opioid system. In addition, CB receptor agonists enhance the effect of mu-opioid receptor agonists in a variety of models of analgesia, and combinations of cannabinoids and opioids may produce synergistic effects. Antinociceptive effects of compounds blocking the metabolism of anandamide have been reported, particularly in models of inflammatory pain. There is also evidence that such compounds increase the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs), raising the possibility that a combination of suitable agents could, by reducing the NSAID dose needed, provide an efficacious treatment strategy, while minimizing the potential for NSAID-induced gastrointestinal and cardiovascular disturbances. Other potential "partners" for endocannabinoid modulatory agents include alpha(2)-adrenoceptor modulators, peroxisome proliferator-activated receptor alpha agonists and TRPV1 antagonists. An extension of the polypharmacological approach is to combine the desired pharmacological properties of the treatment within a single molecule. Hopefully, these approaches will yield novel analgesics that do not produce the psychotropic effects that limit the medicinal use of cannabis.

  • 27.
    Anderholm, Louise
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Behandling av beteendemässiga ochpsykiska symtom med fokus påagitation hos äldre med Alzheimerssjukdom.: En jämförelse mellan neuroleptika ochacetylkolinesterashämmare2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Inledning: År 2030 uppskattas det vara ungefär 230 000 stycken människor i Sverige somhar drabbats av någon typ av demenssjukdom. Sjukdomens stadier delas in i begynnande,mild, måttlig och svår demens. Där första symtomen i den begynnande fasen brukar vara attden drabbade inte kommer ihåg vart den lagt sina saker. I den svåra fasen av sjukdomen ärpatienten förmodligen beroende av dygnet runt vård, patienten brukar även ha svårt attprata, enstaka ord eller meningar brukar upprepas. Beteendemässiga och psykiska symtom(BPSD) hos demenssjuka är symtom som kan orsaka lidande hos patienten och dessanhöriga. Symtomen delas in i fyra undergrupper affektiva, psykossymtom, hyperaktivitetoch apati. Riskfaktorn med högst evidens är Apolipoprotein E (ApoE), ApoEε4-allelen.Riskfaktorer med lägre evidensgrad är t.ex. låg utbildning och släktskap.

    Sjukdomen orsakas av att nervcellerna i hjärnan dör, framförallt i delen av hjärnan därminnet sitter. En röntgen av hjärnan visar onormala proteininlagringar, amyloida plack.Amyloidhypotesen påstår att det blir en överproduktion av amyloid-beta proteinet vilken trosvara den patologiska händelsen vid Alzheimers sjukdom. Tauproteinet hyperfosfyleras till enisoform som är tre gånger större än i en frisk hjärna, om överproduktion av tau på specifikaställen eller hela hjärnan orsakar sjukdomen har forskarna inte kommit fram till ännu. Mildtill måttlig Alzheimers sjukdom behandlas med acetylkolinesterashämmarna donepezil,rivastagmin och galantamin. Svår Alzheimers sjukdom behandlas med en NMDAreceptoragonist,memantin.

    Syfte: Att undersöka om acetylkolinesterashämmare eller neuroleptika fungerar bäst vidsymtom som uppkommer vid BPSD, samt undersöka vilka biverkningar som är vanligast.

    Metod: PubMed har använts för att hitta studier som stämmer in på inklusionskriterierna.Studier som exkluderas är de som undersökt fel substans, fel indikation eller fel preparat t.ex.omega-3.

    Resultat: De vanligaste biverkningarna som rapporterats hos acetylkolinesterashämmarnaär bland annat illamående och kräkningar. Av neuroleptika preparaten verkar det varasömnighet som är den mest rapporterade biverkningen. Studierna som undersökteneuroleptika kom fram till ungefär samma sak, att preparaten kan förbättra symtomen. Av destudier som undersökte acetylkolinesterashämmarna var det tre studier som drog slutsatsenatt de kan ha effekt. En studie säger att det inte sågs någon skillnad mellan donepezil ochplacebo vid dessa typer av symtom.

    Diskussion: Då de olika studierna som använts i arbetet har undersökt olika effektmått hardet varit svårt att göra en rättvis bedömning om läkemedlen fungerar eller ej. Då i de flestafall bara gått och jämföra ett effektmått från studierna. Hade jag bestämt vilka effektmåttsom fick finnas i varje studie redan från början och sedan gjort en exkludering utifrån det,hade det varit enklare att jämföra studierna och därefter kommit fram till en bra slutsats. Viden jämförelse mellan de olika substanserna ur neuroleptikagruppen, är sömnighet denvanligaste biverkningen i tre av fyra grupper. Viktökning är också en av de vanligastebiverkningarna i två av grupperna där ungefär 32% drabbades av just denna biverkning.Varför patienterna ökat i vikt framgår inte i studierna.

    Slutsats: Acetylkolinesterashämmare och neuroleptika kan ha effekt vid symtom somuppkommer vid BPSD. Acetylkolinesterashämmarna bör provas i första hand om intebehandlingen redan är insatt.

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  • 28. Andersen, Toril
    et al.
    Bleher, Stefan
    Flaten, Goril Eide
    Tho, Ingunn
    Mattsson, Sofia
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Skalko-Basnet, Natasa
    Chitosan in Mucoadhesive Drug Delivery: Focus on Local Vaginal Therapy2015In: Marine Drugs, ISSN 1660-3397, E-ISSN 1660-3397, Vol. 13, no 1, p. 222-236Article in journal (Refereed)
    Abstract [en]

    Mucoadhesive drug therapy destined for localized drug treatment is gaining increasing importance in today's drug development. Chitosan, due to its known biodegradability, bioadhesiveness and excellent safety profile offers means to improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to develop liposomes able to ensure prolonged residence time at vaginal site. Two types of mucoadhesive liposomes, namely the chitosan-coated liposomes and chitosan-containing liposomes, where chitosan is both embedded and surface-available, were made of soy phosphatidylcholine with entrapped fluorescence markers of two molecular weights, FITC-dextran 4000 and 20,000, respectively. Both liposomal types were characterized for their size distribution, zeta potential, entrapment efficiency and the in vitro release profile, and compared to plain liposomes. The proof of chitosan being both surface-available as well as embedded into the liposomes in the chitosan-containing liposomes was found. The capability of the surface-available chitosan to interact with the model porcine mucin was confirmed for both chitosan-containing and chitosan-coated liposomes implying potential mucoadhesive behavior. Chitosan-containing liposomes were shown to be superior in respect to the simplicity of preparation, FITC-dextran load, mucoadhesiveness and in vitro release and are expected to ensure prolonged residence time on the vaginal mucosa providing localized sustained release of entrapped model substances.

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  • 29. Andersen, Toril
    et al.
    Mishchenko, Ekaterina
    Flaten, Gøril Eide
    Ericson Sollid, Johanna U.
    Mattsson, Sofia
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Tho, Ingunn
    Škalko-Basnet, Nataša
    Chitosan-Based Nanomedicine to Fight Genital Candida Infections: Chitosomes2017In: Marine Drugs, ISSN 1660-3397, E-ISSN 1660-3397, Vol. 15, no 3, article id 64Article in journal (Refereed)
    Abstract [en]

    Vaginal infections are associated with high recurrence, which is often due to a lack of efficient treatment of complex vaginal infections comprised of several types of pathogens, especially fungi and bacteria. Chitosan, a mucoadhesive polymer with known antifungal effect, could offer a great improvement in vaginal therapy; the chitosan-based nanosystem could both provide antifungal effects and simultaneously deliver antibacterial drugs. We prepared chitosan-containing liposomes, chitosomes, where chitosan is both embedded in liposomes and surface-available as a coating layer. For antimicrobial activity, we entrapped metronidazole as a model drug. To prove that mucoadhesivness alone is not sufficient for successful delivery, we used Carbopol-containing liposomes as a control. All vesicles were characterized for their size, zeta potential, entrapment efficiency, and in vitro drug release. Chitosan-containing liposomes were able to assure the prolonged release of metronidazole. Their antifungal activity was evaluated in a C. albicans model; chitosan-containing liposomes exhibited a potent ability to inhibit the growth of C. albicans. The presence of chitosan was crucial for the system's antifungal activity. The antifungal efficacy of chitosomes combined with antibacterial potential of the entrapped metronidazole could offer improved efficacy in the treatment of mixed/complex vaginal infections.

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  • 30.
    Anna-Karin, Nordgren
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Effekt och säkerhet av passionsblomma vid tillfälliga sömnsvårigheter eller lindrig oro2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 31.
    Arakji Jawad, Ola
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Effekter av begränsad förpackningsstorlek för paracetamol2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
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    Effekter av begränsad förpackningsstorlek för paracetamol
  • 32.
    Asi Rebatti, Lava
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Premedicinering av barn: - en jämförelse mellan alfa-2-adrenoceptoragonister ochmidazolam2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Premedicinering innebär att en patient behandlas med lugnande läkemedel inför enoperation eller ett ingrepp för att dämpa dennes oro och smärta. Inom den pediatriskapopulationen är detta vanligt då yngre patienter kan uppleva oro eftersom de inte alltidförstår syftet med ingreppet och kan känna rädsla då de ska separeras från sinaföräldrar. Bensodiazepinet midazolam har länge använts inom premedicinering tillbarn och har väl dokumenterad effekt. Det har dock påvisats att läkemedlet kan geupphov till så kallade paradoxala reaktioner, en biverkan som innebär att barnen fåroväntade reaktioner i form av t ex agitation. Det har därför föreslagits att substansenbör ersättas med alfa-2-adrenoceptoragonister som t ex klonidin eller dexmedetomidin,vilka har samma indikationer som midazolam, men utan att orsaka paradoxalareaktioner.

    Syftet med detta examensarbete är att undersöka om alfa-2-adrenoceptoragonister äröverlägsna midazolam vid premedicinering av barn. Arbetet är en litteraturstudie somfrämst jämfört resultaten från kliniska prövningar av olika läkemedelsbehandlingar isamband med premedicinering av barn avseende effekt och kvalitet, samt uppkomst avbiverkningar mellan de tre substanserna midazolam, klonidin och dexmedetomidin. Deprimära parametrar som jämförts är sedationsdjup, tillslagstid, substansernasanxiolytiska effekt och återhämtningsprofil. De sekundära parametrarna är hanteringav separation från föräldrar, föräldrarnas betyg samt läkemedels-/maskacceptans.

    Resultatet visar att de två alfa-2-adrenoceptoragonisterna klonidin ochdexmedetomidin är bättre än midazolam vad gäller sedationsdjup, separation frånföräldrar, läkemedelsacceptans och återhämtningsprofil, samt var denläkemedelsgrupp som gavs högst betyg av föräldrarna. Anxiolytisk effekt ochmaskacceptans var likvärdiga mellan de två grupperna, medan midazolam hadesnabbast tillslagstid. Paradoxala reaktioner förekom i relativt hög frekvens vidmidazolamsedering, medan alfa-2-adrenoceptoragonisterna gav biverkningar i form avhemodynamiska förändringar som sänkt blodtryck och puls.

    Avslutningsvis visar resultaten i denna studie att alfa-2-adrenoceptoragonister är attföredra framför midazolam. Speciellt avsaknaden av paradoxala reaktioner vid sederingmed alfa-2-adrenoceptoragonister gör att den gruppen av läkemedel har en stor fördelframför midazolam vid sedering av barn. Men i de fall där barnet har hemodynamiskabesvär i form av exempelvis bradykardi, bör man undvika alfa-2-adrenoceptoragonisteroch istället premedicinera med midazolam.

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  • 33.
    Attebäck, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Är metformin ett effektivt och säkert behandlingsalternativ till insulin vid graviditetsdiabetes?: - En litteraturstudie av det vetenskapliga kunskapsläget2018Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 34.
    Attebäck, Sofie
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Behandling medSGLT2-hämmare:Är det skillnad i förekomst avdiabetisk ketoacidos mellansubstanser hos typ 2-diabetiker och kan egenmätning av blodketonerförebygga detta tillstånd?2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 35. Baird, Denis A.
    et al.
    Evans, Daniel S.
    Kamanu, Frederick K.
    Gregory, Jennifer S.
    Saunders, Fiona R.
    Giuraniuc, Claudiu V.
    Barr, Rebecca J.
    Aspden, Richard M.
    Jenkins, Deborah
    Kiel, Douglas P.
    Orwoll, Eric S.
    Cummings, Steven R.
    Lane, Nancy E.
    Mullin, Benjamin H.
    Williams, Frances M.K.
    Richards, J. Brent
    Wilson, Scott G.
    Spector, Tim D.
    Faber, Benjamin G.
    Lawlor, Deborah A.
    Grundberg, Elin
    Ohlsson, Claes
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Capellini, Terence D
    Richard, Daniel
    Beck, Thomas J
    Evans, David M
    Paternoster, Lavinia
    Karasik, David
    Tobias, Jonathan H.
    Identification of Novel Loci Associated With Hip Shape: A Meta-Analysis of Genomewide Association Studies.2019In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 34, no 2, p. 241-251Article in journal (Refereed)
    Abstract [en]

    We aimed to report the first genomewide association study (GWAS) meta-analysis of dual-energy X-ray absorptiometry (DXA)-derived hip shape, which is thought to be related to the risk of both hip osteoarthritis and hip fracture. Ten hip shape modes (HSMs) were derived by statistical shape modeling using SHAPE software, from hip DXA scans in the Avon Longitudinal Study of Parents and Children (ALSPAC; adult females), TwinsUK (mixed sex), Framingham Osteoporosis Study (FOS; mixed), Osteoporotic Fractures in Men study (MrOS), and Study of Osteoporotic Fractures (SOF; females) (total N = 15,934). Associations were adjusted for age, sex, and ancestry. Five genomewide significant (p < 5 × 10-9 , adjusted for 10 independent outcomes) single-nucleotide polymorphisms (SNPs) were associated with HSM1, and three SNPs with HSM2. One SNP, in high linkage disequilibrium with rs2158915 associated with HSM1, was associated with HSM5 at genomewide significance. In a look-up of previous GWASs, three of the identified SNPs were associated with hip osteoarthritis, one with hip fracture, and five with height. Seven SNPs were within 200 kb of genes involved in endochondral bone formation, namely SOX9, PTHrP, RUNX1, NKX3-2, FGFR4, DICER1, and HHIP. The SNP adjacent to DICER1 also showed osteoblast cis-regulatory activity of GSC, in which mutations have previously been reported to cause hip dysplasia. For three of the lead SNPs, SNPs in high LD (r2  > 0.5) were identified, which intersected with open chromatin sites as detected by ATAC-seq performed on embryonic mouse proximal femora. In conclusion, we identified eight SNPs independently associated with hip shape, most of which were associated with height and/or mapped close to endochondral bone formation genes, consistent with a contribution of processes involved in limb growth to hip shape and pathological sequelae. These findings raise the possibility that genetic studies of hip shape might help in understanding potential pathways involved in hip osteoarthritis and hip fracture. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

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  • 36.
    Bate, Andrew
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    The use of Bayesian confidence propagation neural network in pharmacovigilance2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The WHO database contains more than 2.8 million case reports of suspected adverse drug reactions reported from 70 countries worldwide since 1968. The Uppsala Monitoring Centre maintains and analyses this database for new signals on behalf of the WHO Programme for International Drug Monitoring. A goal of the Programme is to detect signals, where a signal is defined as "Reported information on a possible causal relationship between an adverse event and a drug, the relationship being unknown or incompletely documented previously."

    The analysis of such a large amount of data on a case by case basis is impossible with the resources available. Therefore a quantitative, data mining procedure has been developed to improve the focus of the clinical signal detection process. The method used, is referred to as the BCPNN (Bayesian Confidence Propagation Neural Network). This not only assists in the early detection of adverse drug reactions (ADRs) but also further analysis of such signals. The method uses Bayesian statistical principles to quantify apparent dependencies in the data set. This quantifies the degree to which a specific drug- ADR combination is different from a background (in this case the WHO database). The measure of disproportionality used, is referred to as the Information Component (IC) because of its' origins in Information Theory. A confidence interval is calculated for the IC of each combination. A neural network approach allows all drug-ADR combinations in the database to be analysed in an automated manner. Evaluations of the effectiveness of the BCPNN in signal detection are described.

    To compare how a drug association compares in unexpectedness to related drugs, which might be used for the same clinical indication, the method is extended to consideration of groups of drugs. The benefits and limitations of this approach are discussed with examples of known group effects (ACE inhibitors - coughing and antihistamines - heart rate and rhythm disorders.) An example of a clinically important, novel signal found using the BCPNN approach is also presented. The signal of antipsychotics linked with heart muscle disorder was detected using the BCPNN and reported.

    The BCPNN is now routinely used in signal detection to search single drug - single ADR combinations. The extension of the BCPNN to discover 'unexpected' complex dependencies between groups of drugs and adverse reactions is described. A recurrent neural network method has been developed for finding complex patterns in incomplete and noisy data sets. The method is demonstrated on an artificial test set. Implementation on real data is demonstrated by examining the pattern of adverse reactions highlighted for the drug haloperidol. Clinically important, complex relationships in this kind of data are previously unexplored.

    The BCPNN method has been shown and tested for use in routine signal detection, refining signals and in finding complex patterns. The usefulness of the output is influenced by the quality of the data in the database. Therefore, this method should be used to detect, rather than evaluate signals. The need for clinical analyses of case series remains crucial.

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  • 37.
    Bate, Andrew
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Lindquist, M.
    Edwards, I.R.
    Olsson, S.
    Orre, R.
    Lansner, A.
    De Freitas, R.M.
    A Bayesian neural network method for adverse drug reaction signal generation1998In: European Journal of Clinical Pharmacology, ISSN 0031-6970, Vol. 54, no 4, p. 315-321Article in journal (Refereed)
  • 38.
    Bedro, Edward
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Användningen av β-blockerare vid långt QT-syndrom: - Litteraturstudie med fokus på skillnader i effekt av olika β-blockerare2018Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 39. Benetou, V.
    et al.
    Orfanos, P
    Feskanich, D
    Michaëlsson, K
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Ahmed, L A
    Peasey, A
    Wolk, A
    Brenner, H
    Bobak, M
    Wilsgaard, T
    Schöttker, B
    Saum, K-U
    Bellavia, A
    Grodstein, F
    Klinaki, E
    Valanou, E
    Papatesta, E-M
    Boffetta, P
    Trichopoulou, A
    Education, marital status, and risk of hip fractures in older men and women: the CHANCES project2015In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 26, no 6, p. 1733-1746Article in journal (Refereed)
    Abstract [en]

    The role of socioeconomic status in hip fracture incidence is unclear. In a diverse population of elderly, higher education was found to be associated with lower, whereas living alone, compared to being married/cohabiting, with higher hip fracture risk. Educational level and marital status may contribute to hip fracture risk.

    INTRODUCTION: The evidence on the association between socioeconomic status and hip fracture incidence is limited and inconsistent. We investigated the potential association of education and marital status with hip fracture incidence in older individuals from Europe and USA.

    METHODS: A total of 155,940 participants (79 % women) aged 60 years and older from seven cohorts were followed up accumulating 6456 incident hip fractures. Information on education and marital status was harmonized across cohorts. Hip fractures were ascertained through telephone interviews/questionnaires or through record linkage with registries. Associations were assessed through Cox proportional hazard regression adjusting for several factors. Summary estimates were derived using random effects models.

    RESULTS: Individuals with higher education, compared to those with low education, had lower hip fracture risk [hazard ratio (HR) = 0.84, 95 % confidence interval (CI) 0.72-0.95]. Respective HRs were 0.97 (95 % CI 0.82-1.13) for men and 0.75 (95 % CI 0.65-0.85) for women. Overall, individuals living alone, especially those aged 60-69 years, compared to those being married/cohabiting, tended to have a higher hip fracture risk (HR = 1.12, 95 % CI 1.02-1.22). There was no suggestion for heterogeneity across cohorts (P heterogeneity > 0.05).

    CONCLUSIONS: The combined data from >150,000 individuals 60 years and older suggest that higher education may contribute to lower hip fracture risk. Furthermore, this risk may be higher among individuals living alone, especially among the age group 60-69 years, when compared to those being married/cohabiting.

  • 40. Benetou, V.
    et al.
    Orfanos, P.
    Feskanich, D.
    Michaëlsson, K.
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Byberg, L.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Grodstein, F.
    Wolk, A.
    Jankovic, N.
    de Groot, L. C. P. G. M.
    Boffetta, P.
    Trichopoulou, A.
    Mediterranean diet and hip fracture incidence among older adults: the CHANCES project2018In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, no 7, p. 1591-1599Article in journal (Refereed)
    Abstract [en]

    The association between adherence to Mediterranean diet (MD) and hip fracture incidence is not yet established. In a diverse population of elderly, increased adherence to MD was associated with lower hip fracture incidence. Except preventing major chronic diseases, adhering to MD might have additional benefits in lowering hip fracture risk.

    INTRODUCTION: Hip fractures constitute a major public health problem among older adults. Latest evidence links adherence to Mediterranean diet (MD) with reduced hip fracture risk, but still more research is needed to elucidate this relationship. The potential association of adherence to MD with hip fracture incidence was explored among older adults.

    METHODS: A total of 140,775 adults (116,176 women, 24,599 men) 60 years and older, from five cohorts from Europe and the USA, were followed-up for 1,896,219 person-years experiencing 5454 hip fractures. Diet was assessed at baseline by validated, cohort-specific, food-frequency questionnaires, and hip fractures were ascertained through patient registers or telephone interviews/questionnaires. Adherence to MD was evaluated by a scoring system on a 10-point scale modified to be applied also to non-Mediterranean populations. In order to evaluate the association between MD and hip fracture incidence, cohort-specific hazard ratios (HR), adjusted for potential confounders, were estimated using Cox proportional-hazards regression and pooled estimates were subsequently derived implementing random-effects meta-analysis.

    RESULTS: A two-point increase in the score was associated with a significant 4% decrease in hip fracture risk (pooled adjusted HR 0.96; 95% confidence interval (95% CI) 0.92-0.99, pheterogeneity = 0.446). In categorical analyses, hip fracture risk was lower among men and women with moderate (HR 0.93; 95% CI 0.87-0.99) and high (HR 0.94; 95% CI 0.87-1.01) adherence to the score compared with those with low adherence.

    CONCLUSIONS: In this large sample of older adults from Europe and the USA, increased adherence to MD was associated with lower hip fracture incidence.

  • 41. Benetou, V
    et al.
    Orfanos, P
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Bergström, Ulrica
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Berrino, F
    Tumino, R
    Borch, K B
    Lund, E
    Peeters, P H M
    Grote, V
    Li, K
    Altzibar, J M
    Key, T
    Boeing, H
    von Ruesten, A
    Norat, T
    Wark, P A
    Riboli, E
    Trichopoulou, A
    Mediterranean diet and incidence of hip fractures in a European cohort2013In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 24, no 5, p. 1587-1598Article in journal (Refereed)
    Abstract [en]

    Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. INTRODUCTION: Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. METHODS: A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. RESULTS: Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89-0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79-0.94) and high fruit (HR = 0.89; 95 % CI = 0.82-0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06-1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32-2.31) was also a risk factor. CONCLUSIONS: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.

  • 42. Benetou, Vassiliki
    et al.
    Orfanos, Philippos
    Feskanich, Diane
    Michaëlsson, Karl
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Grodstein, Francine
    Wolk, Alicja
    Bellavia, Andrea
    Ahmed, Luai A
    Boffeta, Paolo
    Trichopoulou, Antonia
    Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women: The CHANCES Project2016In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 31, no 9, p. 1743-1752Article in journal (Refereed)
    Abstract [en]

    The role of fruit and vegetable intake in relation to fracture prevention during adulthood and beyond is not adequately understood. We investigated the potential association between fruit and vegetable intake and hip fracture incidence in a large sample of elderly from Europe and United States. A total of 142,018 individuals (among which 116,509 women), aged ≥60 years old, from five cohorts, were followed-up prospectively for 1,911,482 person-years accumulating 5,552 hip fractures. Fruit and vegetable intake was assessed by validated, cohort-specific, food-frequency questionnaires. Ηip fractures were ascertained through national patient registers or telephone interviews/questionnaires. Adjusted hazard ratios (HR) derived by Cox proportional-hazards regression were estimated for each cohort and subsequently pooled using random-effects meta-analysis. Intake of ≤ 1 servings/day of fruit and vegetables combined was associated with 39% higher hip fracture risk [pooled adjusted HR:1.39, 95% Confidence Intervals (CIs): 1.20, 1.58] in comparison to moderate intake (>3 and ≤5 servings/day) (pfor heterogeneity  = 0.505), whereas higher intakes (>5 servings/day) were not associated with lower risk in comparison to the same reference. Associations were more evident among women. We concluded that a daily intake of one or less servings of fruits and vegetables was associated with increased hip fracture risk in relation to moderate daily intakes. Older adults with such low fruit and vegetable consumption may benefit from raising their intakes to moderate amounts in order to reduce their hip fracture risk. 

  • 43.
    Berg, Emma
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Utvärdering av farmaceutiska tjänster – en litteraturstudie2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    En farmaceuts roll på ett öppenvårdsapotek är att erbjuda trygga och effektivaprodukter samt kunna ge råd om dessa. Genom sin kompetens inom läkemedel är öppenvårdsapotek är en viktig del i sjukvårdssektorn. Apoteken i Sverige är till stordel privatägda och de olika kedjorna konkurrera med varandra. Det är därför av intresse för apoteken att inte bara kunna erbjuda bra produkter utan även att generera vinst.

    Syftet med studien är att undersöka vilka metoder och resultat som används för att utvärdera farmaceutiska tjänster på öppenvårdsapotek.

    Studien är en litteraturstudie och litteraturen som användes bestod till största delen av artiklar som hämtades från sökmotorn PubMed. Olika nyckelord användes i olika kombinationer vid sökning och artiklarna valdes ut efter relevans i rubrik och”abstract”. Från de relevanta artiklarna kunde också relaterade artiklar hittas. Utöver artiklarna och några av deras källor användes en rapport från Läkemedelsverket ochen C-uppsats.

    Resultaten från artiklarna delades in i fem kategorier: kliniskt utfall, livskvalitetsförändringar, följsamhet till läkemedelsanvändning, apotekskundens upplevelse och farmaceutens upplevelse. Under kategorin kliniskt utfall hittades studier som genom sjukhuskontroll kunde visa på att ökad farmaceutisk vård gav bättre kliniskt utfall. Den ökade farmaceutiska vården gjorde att användning av läkemedel förbättrades vilket gjorde att deltagarnas sjukdomsbild förändrades till det bättre. Vid livskvalitetsförändringar visade en studie att deltagarna hade fått bättre hälsa och mindre risker för ytterligare sjukdomar genom att de fått ökad farmaceutisk vård och bättre användning av läkemedel. Studien använde sig av självrapportering och sjukhuskontroll. För att visa på förbättrad följsamhet till läkemedelsanvändning användes självrapportering och räkning av läkemedel där mängden läkemedel som användes jämfördes med mängden som borde ha används. Här kunde två av studierna visa på en positiv förändring av följsamheten medan en tredje studie inte visade på någon skillnad av följsamheten med ökad farmaceutiskvård. För att mäta apotekskundens och farmaceutens upplevelse användes kundmöten och intervjuer. Här mättes deltagarnas upplevelse utifrån om de varnöjda och i studierna som användes var resultatet positivt, både för kunder och förfarmaceuter, då ökad farmaceutisk vård användes.

    De resultat som visar kliniskt utfall, livskvalitetsförändringar och följsamhet till läkemedelsanvändning ger ett konkret värde som visar på positiva förändringar efteråtgärder. De visar dock inte deltagarnas upplevelse. De resultat som visar apotekskundens och farmaceutens upplevelse visar inte om användningen av läkemedel förbättrats och om den ökade farmaceutiska vården gav resultat. De flesta av resultaten i studierna visade positiva förändringar vid ökad farmaceutisk vård. För att införa ökad farmaceutisk vård på öppenvårdsapotek i Sverige krävs vissa resurser.

    Genom att kombinera flera metoder kan bättre resultat för att utvärdera farmaceutiska tjänster ges. Resultaten av de olika metoderna ger olika typer av utfall. Denna studie kan utgöra underlag för att kunna lägga mer resurser på att öka den farmaceutiska vården och ge farmaceuter en större roll inom hälso- och sjukvård. Detskulle leda till bättre läkemedelsanvändning och förbättrad hälsa för kunder och patienter.

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  • 44.
    Berglund, Nadja
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Inkjet Printing and Personalised Medicine:Possibilities and Practicalities2018Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 45.
    Bergqvist, Tanja
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Minitabletter till barn: Acceptans och formulering vid oral administrering2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
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    Minitabletter till barn
  • 46.
    Berthelsen, Isabell
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Astma och Kol -Inhalationsteknik: Vad är de vanligaste felen och skulle fördjupad rådgivning på svenska apotek uppskattas av kunderna?2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
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  • 47.
    Birzniece, Vita
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Johansson, Inga-Maj
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lindblad, Charlotte
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lundgren, Per
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Löfgren, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ragagnin, Gianna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Taube, Magdalena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Turkmen, Sahruh
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Wahlström, Göran
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Wang, Ming-De
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Wihlbäck, Anna-Carin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Zhu, Di
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Neuroactive steroid effects on cognitive functions with a focus on the serotonin and GABA systems.2006In: Brain Research Reviews, ISSN 0165-0173, E-ISSN 1872-6321, Vol. 51, no 2, p. 212-239Article in journal (Refereed)
  • 48.
    Birzniece, Vita
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Türkmen, Sahruh
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lindblad, Charlotte
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Zhu, Di
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Johansson, Inga-Maj
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Wahlström, Göran
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    GABA(A) receptor changes in acute allopregnanolone tolerance2006In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 535, no 1-3, p. 125-134Article in journal (Refereed)
    Abstract [en]

    To study acute tolerance, rats were anesthetized with interrupted i.v. allopregnanolone infusions where the "silent second" in the electroencephalogram (EEG) was the target. Animals were killed either directly at the first silent second or at the silent second level after 30 or 90 min of anaesthesia. Acute tolerance was demonstrated at 90 min of anaesthesia as earlier shown. In situ hybridization showed a decreased expression of the gamma-aminobutyric acid(A) (GABA(A)) receptor subunit alpha4mRNA amount in the thalamus ventral-posteriomedial nucleus of the tolerant rats. A parallel change in the abundance of the alpha4 subunit was detected with immunohistochemistry. The increase in maintenance dose rate (MDR) was significantly negatively correlated with the alpha4mRNA in the thalamus ventral-posteriomedial nucleus, and positively correlated with alpha2mRNA in different hippocampal subregions. There was also a positive relationship between the alpha1mRNA amounts in the different hippocampal subregions, with significant differences between groups. These changes in GABA(A) receptor subunits mRNA expression and protein (alpha4) might be of importance for the development of acute tolerance to allopregnanolone.

  • 49.
    Björklund, Emmelie
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    The endocannabinoid system: a translational study from Achilles tendinosis to cyclooxygenase2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The endogenous cannabinoids anandamide (arachidonoyl ethanolamide, AEA) and 2-arachidonoyl glycerol (2-AG) exert their effect by activating cannabinoid receptors (CB). These receptors mediate a broad range of physiological functions such as beneficial effects in pain and inflammation, although little is known about the expression of CB receptors in human pain conditions. AEA and 2-AG are short- lived molecules due to their rapid cellular accumulation and metabolism. The enzymes primarily responsible for their degradation are fatty acid amide hydrolase (FAAH) for AEA and monoacylglycerol lipase (MGL) for 2-AG. Inhibition of endocannabinoid metabolism is a potential approach for drug development, and there is a need for the identification of novel compounds with inhibitory effects upon FAAH and MGL.

    In Paper I of this thesis, the expression of CB1 receptors in human Achilles tendon was examined. We found expression of CB1 receptors in tenocytes, blood vessel wall as well as in the perineurium of the nerve. A semi-quantitative analysis showed an increase of CB1 receptors in painful human Achilles tendinosis.

    In papers II and III, termination of AEA signalling was investigated via inhibition of FAAH. In Paper II, Flu-AM1, an analogue of flurbiprofen, was investigated. The compound inhibited both FAAH and the oxygenation of 2-AG by cyclooxygenase-2. In Paper III the antifungal compound ketoconazole was shown to inhibit the cellular uptake of AEA in HepG2, CaCo-2 and C6 cell lines in a manner consistent with inhibition of FAAH.

    The role of FAAH in gating the cellular accumulation of AEA was investigated in Paper IV. FAAH has been shown to control the concentration gradient of AEA across the plasmamembrane in RBL2H3 cells, whereas no such effect is seen in other FAAH-expressing cell lines. To determine whether this effect is assay dependent or due to intrinsic differences between the cell lines, we assayed four cell lines with different levels of FAAH expression using the same methodology. We found that the sensitivity of FAAH uptake inhibition was not dependent on the expression level of FAAH, suggesting that factors other than FAAH are important for uptake.

    Paper V is focused on the inhibition of MGL. Prior to this study no selective inhibitors of the enzyme had been described. Thus, we screened a number of compounds for their inhibitory effect on MGL. Troglitazone was found to be an inhibitor of MGL, although its potency was dependent upon the enzyme assay used. 

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    The endocannabinoid system: A translational study from Achilles tendinosis to cyclooxygenase
  • 50.
    Björklund, Emmelie
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Blomqvist, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Joel, Hedlin
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Persson, Emma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Fowler, Christopher
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Involvement of Fatty Acid Amide Hydrolase and Fatty Acid Binding Protein 5 in the Uptake of Anandamide by Cell Lines with Different Levels of Fatty Acid Amide Hydrolase Expression: A Pharmacological Study2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 7, p. e103479-Article in journal (Refereed)
    Abstract [en]

    Background:

    The endocannabinoid ligand anandamide (AEA) is removed from the extracellular space by a process ofcellular uptake followed by metabolism. In many cells, such as the RBL-2H3 cell line, inhibition of FAAH activity reduces theobserved uptake, indicating that the enzyme regulates uptake by controlling the intra- : extracellular AEA concentrationgradient. However, in other FAAH-expressing cells, no such effect is seen. It is not clear, however, whether these differencesare methodological in nature or due to properties of the cells themselves. In consequence, we have reinvestigated the roleof FAAH in gating the uptake of AEA.Methodology/Principal Findings: The effects of FAAH inhibition upon AEA uptake were investigated in four cell lines: AT1rat prostate cancer, RBL-2H3 rat basophilic leukaemia, rat C6 glioma and mouse P19 embryonic carcinoma cells. SemiquantitativePCR for the cells and for a rat brain lysate confirmed the expression of FAAH. No obvious expression of atranscript with the expected molecular weight of FLAT was seen. FAAH expression differed between cells, but all four couldaccumulate AEA in a manner inhibitable by the selective FAAH inhibitor URB597. However, there was a difference in thesensitivities seen in the reduction of uptake for a given degree of FAAH inhibition produced by a reversible FAAH inhibitor,with C6 cells being more sensitive than RBL-2H3 cells, despite rather similar expression levels and activities of FAAH. Thefour cell lines all expressed FABP5, and AEA uptake was reduced in the presence of the FABP5 inhibitor SB-FI-26, suggestingthat the different sensitivities to FAAH inhibition for C6 and RBL2H3 cells is not due to differences at the level of FABP-5.Conclusions/Significance: When assayed using the same methodology, different FAAH-expressing cells display differentsensitivities of uptake to FAAH inhibition.

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    Involvement of Fatty Acid Amide Hydrolase and Fatty Acid Binding Protein 5 in the Uptake of Anandamide by Cell Lines with Different Levels of Fatty Acid Amide Hydrolase Expression: A Pharmacological Study
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