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1.	Bergman, Fanny, et al. (author) Exposure to well-defined PM2.5 alters a contractile response in rat coronary arteries 2022 Conference paper (other academic/artistic)
2.	Bergman, Fanny, et al. (author) Physicochemical metamorphosis of re-aerosolized urban PM2.5 2024 In: Journal of Aerosol Science. - : Elsevier Ltd. - 0021-8502 .- 1879-1964. ; 181 Journal article (peer-reviewed)abstract The toxicity of particulate matter (PM) is dependent on particle physical and chemical properties and is commonly studied using in vivo and in vitro approaches. PM to be used for in vivo and in vitro studies is often collected on filters and then extracted from the filter surface using a solvent. During extraction and further PM sample handling, particle properties change, but this is often neglected in toxicology studies, with possible implications for health effect assessment. To address the current lack of knowledge and investigate changes in particle properties further, ambient PM with diameter less than 2.5 μm (PM2.5) was collected on filters at an urban site and extracted using a standard methanol protocol. After extraction, the PM was dried, dispersed in water and subsequently nebulized. The resulting aerosol properties were then compared to those of the ambient PM2.5. The number size distribution for the nebulized aerosol resembled the ambient in terms of the main mode diameter, and >90 % of particle mass in the nebulized size distribution was still in the PM2.5 range. Black carbon made up a similar fraction of PM mass in nebulized as in ambient aerosol. The sulfate content in the nebulized aerosol seemed depleted and the chemical composition of the organic fraction was altered, but it remains unclear to what extent other non-refractory components were affected by the extraction process. Trace elements were not distributed equally across size fractions, neither in ambient nor nebulized PM. Change in chemical form was studied for zinc, copper and iron. The form did not appear to be different between the ambient and nebulized PM for iron and copper, but seemed altered for zinc. Although many of the studied properties were reasonably well preserved, it is clear that the PM2.5 collection and re-aerosolization process affects particles, and thus potentially also their health effects. Because of this, the effect of the particle collection and extraction process must be considered when evaluating cellular and physiological outcomes upon PM2.5 exposure. © 2024 The Authors
3.	Bergman, Fanny, et al. (author) Physicochemical metamorphosis of re-aerosolized urban PM2.5 2024 In: Journal of Aerosol Science. - : Elsevier Ltd. - 0021-8502 .- 1879-1964. ; 181 Journal article (peer-reviewed)abstract The toxicity of particulate matter (PM) is dependent on particle physical and chemical properties and is commonly studied using in vivo and in vitro approaches. PM to be used for in vivo and in vitro studies is often collected on filters and then extracted from the filter surface using a solvent. During extraction and further PM sample handling, particle properties change, but this is often neglected in toxicology studies, with possible implications for health effect assessment. To address the current lack of knowledge and investigate changes in particle properties further, ambient PM with diameter less than 2.5 μm (PM2.5) was collected on filters at an urban site and extracted using a standard methanol protocol. After extraction, the PM was dried, dispersed in water and subsequently nebulized. The resulting aerosol properties were then compared to those of the ambient PM2.5. The number size distribution for the nebulized aerosol resembled the ambient in terms of the main mode diameter, and >90 % of particle mass in the nebulized size distribution was still in the PM2.5 range. Black carbon made up a similar fraction of PM mass in nebulized as in ambient aerosol. The sulfate content in the nebulized aerosol seemed depleted and the chemical composition of the organic fraction was altered, but it remains unclear to what extent other non-refractory components were affected by the extraction process. Trace elements were not distributed equally across size fractions, neither in ambient nor nebulized PM. Change in chemical form was studied for zinc, copper and iron. The form did not appear to be different between the ambient and nebulized PM for iron and copper, but seemed altered for zinc. Although many of the studied properties were reasonably well preserved, it is clear that the PM2.5 collection and re-aerosolization process affects particles, and thus potentially also their health effects. Because of this, the effect of the particle collection and extraction process must be considered when evaluating cellular and physiological outcomes upon PM2.5 exposure.
4.	Bergström, Lena, et al. (author) Effekter av havsbaserad vindkraft på marint liv : En syntesrapport om kunskapsläget 2021 2022 Reports (other academic/artistic)abstract Att öka tillgången på förnybar energi är nödvändigt för att motverka klimatförändringarna. Här förväntas havsbaserad vindkraft ha en viktig roll. Samtidigt medför planer på att bygga ut havsbaserad vindkraft viktiga frågeställningar kring hur marint liv och biologisk mångfald kan påverkas. I den här rapporten sammanställs det nuvarande kunskapsläget om hur havsbaserad vindkraft skulle kunna påverka marint liv, med fokus på svenska havsområden. Temamässigt omfattar rapporten bottennära miljöer, fisk, marina däggdjur och sjöfågel. Den strävar även efter att belysa kunskapsläget kring kumulativa effekter, samt frågor om under vilka förutsättningar havsbaserad vindkraft skulle kunna gynna marint liv.Bedömningarna beaktar även hur det tekniska utförandet har utvecklats, till exempel när det gäller vindparkernas utformning och dimensionering. Planeringen idag omfattar större vindparker och kraftverk, och bottenfasta vindkraftverk kan lokaliseras på allt större djup. De har hittills främst etablerats inom djupintervallet 5–40 meter, men kan numera anläggas på omkring 40–60 meters djup. Därtill förväntas flytande fundament, som klarar ännu större djup, bli vanligare. En annan viktig aspekt är hur tillämpningen av skadelindrande åtgärder har utvecklats.Havsbaserad vindkraft förväntas påverka marint liv på olika sätt under anläggnings- och driftsfasen, varför det är relevant att tydligt särskilja dessa i riskbedömningar. Rapporten berör även effekter under avvecklingsfasen.Under anläggningsfasen, som pågår någon dag per kraftverk, kan högintensivt ljud uppstå till exempel i samband med pålning av vindkraftverkens fundament. Åtgärder för att minska skadeverkningar av högintensivt ljud är viktiga, och kan förutsättas vara standard idag. Ofta finns det även behov att förbereda havsbotten, vilket leder till spridning av sedimentpartiklar. Omfattningen av både ljud- och sedimentspridning beror på lokala förhållanden. Därför behöver de lokala förhållandena beaktas för att ta fram en mer detaljerad kännedom om risker för marint liv. I synnerhet tumlare kan påverkas negativt av höga ljudnivåer vid anläggningsfasen, med risk för hörselpåverkan och kraftiga beteendestörningar om inte skadelindrande åtgärder används. Särskilda hänsyn i lokalisering och utförande kan även behövas för sälar, samt för fisk när det gäller områden och årstider som är viktiga för deras reproduktion. Under driftsfasen, som pågår upp emot cirka 40 år, bildar vindkraftverkens fundament och eventuella erosionsskydd fasta strukturer. Detta kan ge upphov till reveffekter då ytorna skapar plats för fastsittande arter. Med tiden kan även fiskar och marina däggdjur lockas dit, om förhållandena medger det. En viktig skillnad jämfört med andra typer av rev är att fundamenten går hela vägen upp till ytan, vilket ökar tillgången på hårda substrat i hela vattenpelaren. En möjlig risk är att de nya substraten skulle kunna gynna oönskade främmande arter, även om det saknas belägg för vindparkernas roll som en sådan spridningsväg.När elen produceras genereras undervattensljud, och överföringen av el i sjökablar kan leda till ett visst mått av elektromagnetiska fält i kablarnas närhet. Effekter av dessa påverkansfaktorer har varit svåra, om inte omöjliga, att notera i fältundersökningar. En generell slutsats skulle kunna vara att, om det förekommer negativa effekter av undervattensljud och elektromagnetiska fält, så är de oftast i styrka underordnade den attraktion som kommer av reveffekten. Aktuella studier tyder sammanfattningsvis på att havsbaserad vindkraft under driftsfasen inte är ett hot mot fiskar, säl eller tumlare. Särskild hänsyn när det gäller lokalisering kan dock behövas för skyddsvärda bottenmiljöer samt sjöfågel. Vissa sjöfågelarter kommer sannolikt att undvika området där vindparken etableras. Även åtgärder för att minska dödlighet kopplad till att fåglar kolliderar med kraftverken kan vara viktiga i vissa områden. Eftersom slutsatserna baseras på studier i andra miljöer än de som kan bli aktuella i Sverige framöver är en uppföljning av miljöeffekter viktig i de parker som etableras, för att ha möjlighet att säkerställa eller vid behov revidera kunskapsläget.Utveckling av kunskapsläget När det gäller vindkraftens effekter på bottennära livsmiljöer har kunskapsläget förbättrats angående mer långsiktig påverkan, liksom hur alg- och djursamhället i vindparken förändras över tid. Med åren blir det mer och mer likt det naturliga samhället på hårda bottnar i den aktuella regionen, även om arter med långlivade larvstadier främjas relativt sett mer. I viss mån saknas kunskap om vilken påverkan som kan förväntas om man bygger på större djup och om vindkraftverken står glesare, som planeras idag. Inga studier tyder dock på att etablering av vindkraftverk är ett hot mot vegetation eller bottenlevande djur i den här typen av miljöer, så länge särskilt skyddsvärda livsmiljöer undviks.Angående fisk och fisksamhällen har förståelsen för reveffekter ökat. Forskningen har övergått till att belysa reveffekter mer ingående, från att tidigare främst bekräfta om det blir en reveffekt eller inte. Sådana studier saknas dock idag för flera svenska havsområden eftersom det inte finns vindparker där.För marina däggdjur har kunskapsläget förbättrats framför allt när det gäller förståelsen av hur sälar och tumlare uppfattar och använder sig av ljud, samt hur ljud av olika frekvens och intensitet påverkar djuren.Kunskapen som hur havsbaserad vindkraft kan påverka sjöfågel har förbättrats framför allt för kustnära områden, men bedömningar begränsas fortfarande av otillräcklig kunskap om olika sjöfågelarters utbredning och dynamik i förekomst mellan år. Det här gäller speciellt områden längre ut till havs och med större djup än 30 meter. Den internationella forskningen har varit fokuserad på att bedöma kollisionsrisk, och ny teknik har gett ökad kunskap om fåglars flyghöjder och beteenden i förhållande till vindkraftverk.Kumulativa effekterFör att göra en sammanvägd bedömning av vindkraftens miljöeffekter är det relevant att sätta de enskilda bedömningarna i ett vidare sammanhang, där även till exempel aktuell miljöstatus och effekter av annan verksamhet ingår, så som omfattningen av fiske och sjöfart. I ett sådant perspektiv skulle införandet av en vindpark kunna leda till att den totala omfattningen av påverkan antingen ökar eller minskar i ett visst område. Etableringen kan också påverka samspelet mellan arter, med efterföljande indirekta effekter i ekosystemet. Att förstå sådana sammanvägda effekter är ett fortsatt viktigt forskningsområde. Det finns även ett behov av att utveckla metoder för att skatta kumulativa effekter i samband med havsbaserad vindkraft på olika rumsliga och tidsmässiga skalor. Utgående från det befintliga kunskapsläget kan risken för att havsbaserade vindparker bidrar med negativa kumulativa effekter på havsmiljön förväntas vara låg, under förutsättning att skadelindrande åtgärder tillämpas och bästa möjliga hänsyn tas. Under anläggningsfasen innebär sådana förutsättningar att skadliga nivåer av påverkansfaktorn minimeras, och att anläggningen sker under sådana rumsliga och tidsmässiga förhållanden att risken för ansamling av känsliga populationer av fisk och marina däggdjur minimeras. Bedömningen beror på att påverkan under anläggningsfasen är tidsmässigt övergående och inte förväntas upprepas vid mer än ett tillfälle per plats. Det baseras därför också på förutsättningen att annan motsvarande verksamhet inte sker samtidigt i området. För driftsfasen innebär förutsättningarna att driften sker med sådan teknik att nivån av elektromagnetiska fält är låg och att undervattensljud inte leder till negativa effekter på fisk eller marina däggdjur, och med undantag av att det fortsatt finns oklarheter kring hur sjöfågel kan påverkas.Vid en omfattande utbyggnad kommer gradvis högre hänsyn och anpassningar för att undvika kumulativa effekter att vara motiverade. Det ställer även ökade krav på nationell och internationell samordning för att undvika risker för kumulativ påverkan i samband med anläggningsfasen, till exempel om flera vindparker anläggs parallellt. Eftersom vindkraftens långsiktiga bidrag till kumulativ påverkan är svårbedömda i dagsläget, och förväntas variera både lokalt och mellan olika havsområden, vore det mycket viktigt att följa utvecklingen över tid i sådana parker som etableras, för att öka kunskapen och skapa möjlighet att vid behov införa åtgärder för att minska risker för specifika arter.Kan vindkraften ha positiva effekter på marint liv?Forskningen innehåller även exempel på när införandet av havsbaserad vindkraft kan ha gynnat arter, eller aspekter av biologisk mångfald och ekosystemtjänster. Det finns dock en svårighet med att generalisera kring om havsbaserad vindkraft kan gynna marint liv, eftersom utfallet i hög grad beror på vindparkens lokalisering, ekologiska förutsättningar, samt vilka andra aktiviteter som förekommer i närområdet. En viktig aspekt är även att mänskliga preferenser påverkar definitionen av om viss förändring i artsammansättning är ”positiv” eller ”negativ”, eftersom det här beror på hur olika arter och ekosystemstjänster värdesätts, det vill säga vilken typ av biologisk mångfald som är önskvärd i ett visst område. Rapporten redogör för olika typer av anpassningar som har förslagits för att gynna särskilda arter i samband med havsbaserad vindkraft, även om utvecklingen av sådana naturanpassade lösningar fortfarande är i sin linda.
5.	Bergström, Lena, et al. (author) The effects of wind power on marine life : A Synthesis 2012 Reports (other academic/artistic)abstract As in many other countries, an expansion of wind power is expected in Sweden during the coming decades. The expansion is driven by rising prices on electricity and the need for an increased production of renewable energy. Since wind conditions at sea are good and relatively constant, several offshore wind farms are planned in Swedish waters. Offshore wind power with a total effect of about 2500 MW has been granted permission and an additional 5500 MW are being planned for. Examples of granted projects are Storgrundet with an effect of 265 MW, Stora Middelgrund with an effect of 860 MW and Kårehamn with an effect of 48 MW. The largest offshore wind farm in Sweden today is Lillgrund in Öresund, with its 48 turbines with an installed effect of 110 MW.Prior to this expected expansion, it is important to investigate the environmental impact of offshore wind power, and how possible negative effects can be minimized. This synopsis about the impact of wind power on the marine life in Swedish waters is based on more than 600 studies, most of which are scientific articles, but also reports by companies and authorities.Habitats and species in Swedish marine areasSwedish marine areas are characterized by a unique salinity gradient that varies from marine conditions in Skagerrak to almost limnic environments in the Gulf of Bothnia. There are also vast differences between areas in terms of environmental factors such as insolation, temperature and wave exposure. This entails variation in species composition, dominance by different populations and structural differences in plant and animal communities. Therefore, this synopsis provides environment descriptions of three widely separated marine areas: the Swedish West Coast (Kattegat and Skagerrak), the Baltic Proper and the Gulf of Bothnia (Bothnian Sea and Bothnian Bay). The main focus is on occurrence of species and communities within the depth interval that is of interest for establishing offshore wind power in Sweden.Offshore wind powerThere are mainly two types of foundation structures used in Sweden today: gravity-based foundations and monopile foundations. These are also the most commercially viable. Offshore wind farm projects affect the environment in different ways during installation, operation and decommissioning. The installation phase is assessed as having the largest impact on the environment, since high noise levels and sediment dispersal can affect marine organisms. A wind farm during operation can cause barrier effects as well as changes in the natural environment. The decommissioning phase can again enhance noise levels and lead to sediment dispersal in the wind park and its adjacent area. Effects on marine organisms and communities Since marine environmental conditions vary between different locations as well as over time, it is difficult to make universal assessments of the effects of offshore wind power. This increases the importance of well-designed pilot studies and monitoring programs of the local environment. Also, location-specific surveys minimize the risk that costly measures to reduce negative impact are used when they are not needed. In general, installation and decommissioning of offshore wind farms should be planned so that sensitive reproductive periods for marine species are avoided. Particular consideration might also be needed for constructions in important growth and spawning areas for fish and marine mammals, or specific environments, such as offshore banks with high natural values. Below is a list of the effects that, according to existing knowledge and accessible literature, might affect marine organisms and communities. Each effect has been assessed after how long, and to what scale, it affects the marine life in the wind farm area.Acoustic disturbances during the installationAs monopile foundations are being driven into the sea floor, a lot of noise is generated that spreads in the water. Cod and herring can potentially perceive noise from pile driving at a distance of 80 kilometres, experiencing physical damage and death at just a few meters from the place of installation. For all types of work involving noise, flight reactions in fish are expected within a distance of about one kilometre from the source. The greatest risk of significant harm to fish populations exists if the installation overlaps with important recruitment areas for threatened or weak populations. Among the marine mammals, porpoises have proved to get both impaired hearing and behavioural disturbances from noise associated with pile driving. There are no studies indicating any long-term negative effects on any of the seal species occurring in Swedish waters. It is not possible to draw any general conclusions of the effects on invertebrates from pile driving noise, since the group is too large and diverse. The few studies that exist, however, show that oysters are relatively sensitive, whilst mussels are not affected at all. The effects of high noise levels can be reduced by, for example, successively increasing the power and thus the noise during piling, so that larger animals such as fish, seal and porpoises are intimidated at an early stage and leave the construction area well before high noise levels are reached.Sediment dispersalDredging work during the construction of gravitational foundations, and laying of cables between the wind turbines and land, can cause sediment from the bottom to whirl up and disperse in the water mass. The amount of sediment dispersed depends on the type of sediment, water currents and which dredging method is being used. Increased concentrations of sediment in the water affect mainly fish fry and larval stages negatively. Invertebrates are often adapted to re-suspension of sediment, since it occurs naturally in their environment. The sediment dispersal at the construction of a wind farm is often confined to a short period. The effects are also relatively small due to the fact that the bottom sediment is usually coarse-grained. The overall assessment is therefore that sediment dispersal is a limited problem for most animal and plant communities, but specific consideration should be taken and fish recruitment periods should be avoided.Introduction of a new habitatThe foundations of wind turbines can function as artificial reefs and attract many fish species, particularly around gravitational foundations which have a structurally complex erosion protection. At first there is often a redistribution of fish from nearby areas to the wind park foundations, but over time an actual increased fish production within the park is possible, as long as the park is large enough and the fishing pressure is low. The structure of the erosion protection can bring local positive effects for crustaceans such as lobster and crab, by functioning as shelter as well as increasing their foraging area. One example of a species that seems to increase locally around foundation structures on the Swedish West Coast and the Baltic Proper is the blue mussel. Which species that will dominate depends on the salinity in the area. There are no studies showing that foundation structures will facilitate the distribution of new species to Swedish marine areas. One reason for this might be that the total amount of hard bottom surface formed by the foundations and their structures is relatively small compared to natural hard bottoms.Turbine noise and boat trafficMaintenance work on the wind turbines causes a certain increase in boat traffic in the area of an operating wind farm. Also, different parts of the turbines generate noise during operation that spreads through the water. The reactions of fish on noise from turbines and boat engines vary, but study results indicate that the effect on most fish species from noise produced in a wind farm is low. There are, however, no studies on long-term effects of stress due to an increased noise level or effects of noise disturbance on fish spawning behaviour. Porpoises especially, but to some extent also seals, are sensitive to noise disturbance. Today there are no studies showing negative effects from the operational sounds from a wind farm on populations of marine mammals. The noise of both strong winds and engines from ships often exceeds the underwater noise generated by operating wind farms.Electromagnetic fieldsThe electric cables leading from a wind turbine generates a magnetic field that decreases with distance from the cable. The expected effect on most fish species is low, but since the effect is ongoing throughout the entire operational stage, the risk should be considered in areas that are important to migrating fish species. No studies have been found that show how electromagnetic fields affect marine mammals. The few studies that have been found on invertebrates indicate that the electromagnetic fields around common transmission cables have no effect on either reproduction or survival.Exclusion of birdsMost birds do not avoid wind farm areas. An exception is several common diving ducks that avoid flying or swimming within wind farms and keep a safe distance of at least 500 meters to a turbine tower. The most common food for these species in the Baltic Sea is blue mussels. Areas within the Swedish economic zone where a large-scale expansion of wind power would have the greatest effect on the ducks, and thereby indirectly affect the benthic community, are the offshore banks in the central Baltic Proper, mainly Hoburg Bank and Northern Midsjö Bank, where two thirds of the oldsquaw populations in Europe overwinters. The level of impact will depend on the total area of the park, and the distance between the turbine towers. Large-scale studies are needed in order to assess if the effect might lead to substantial changes for the benthic community.Gaps of knowledgeThe basis of this synopsis is research results from studies concerning single wind turbines or small wind farms, which in many
6.	Bergström, Lena, et al. (author) Vindkraftens effekter på marint liv : En syntesrapport 2012 Reports (other academic/artistic)abstract Precis som i manga andra lander forvantas en utbyggnad av vindkraft i Sverige under de narmaste decennierna. Expansionen drivs bland annat av stigande elpriser och behovet av okad produktion av fornybar el. I Sverige har havsbaserad vindkraft med en total effekt pa ungefar 2500 MW fatt tillstand och ytterligare 5500 MW ar under utveckling. Exempel pa vindkraftsprojekt med fardiga tillstand ar Storgrundet med en effekt pa 265 MW, Stora Middelgrund med en effekt pa 860 MW och Karehamn med en effekt pa 48 MW. I dag utgor Lillgrund i Oresund med sina 48 vindkraftverk och 110 MW i installerad effekt, Sveriges storstahavsbaserade vindkraftpark. Infor denna forvantade expansion ar det viktigt att undersoka vindkraftens miljoeffekter, och hur eventuella negativa effekter kan minimeras. Over 600 studier, huvudsakligen vetenskapliga artiklar, men aven rapporter fran foretag och myndigheter, ligger till grund for slutsatserna och rekommendationerna i denna syntesrapport om paverkan av vindkraft pa det marina livet i svenska havsomraden. [...]
7.	Duan, Rui-Dong, et al. (author) Human meconium contains significant amounts of alkaline sphingomyelinase, neutral ceramidase, and sphingolipid metabolites. 2007 In: Pediatric Research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 61:1, s. 61-66 Journal article (peer-reviewed)abstract Intestinal alkaline sphingomyelinase (Alk-SMase) and neutral ceramidase may catalyze the hydrolysis of endogenous sphin-gomyelin (SM) and milk SM in human-milk fed infants. The enzymes generate sphingolipid metabolites that may influence gut maturation. Alk-SMase also inactivates platelet-activating factor (PAF) that is involved in the pathogenesis of necrotizing enterocolitis (NEC). We examined whether the two enzymes are expressed in both preterm and term infants and analyzed Alk-SMase, neutral ceramidase, SM, and sphingolipid metabolites in meconium. Meconium was collected from 46 preterm (gestational ages 23-36 wk) and 38 term infants (gestational ages 37-42 wk) and analyzed for Alk-SMase using C-14-choline-labeled SM and for neutral ceramidase using C-14-octanoyl-sphingosine as substrates. Molecular species of SM, ceramide, and sphingosine were analyzed by high-performance liquid chromatography mass spectroscopy. Meconium contained significant levels of Alk-SMase and ceramidase at all gestational ages. It also contained 16-24 carbon molecular species of SM, palmitoyl-and stearoyl-sphingosine, and sphingosine. There were positive correlations between levels of SM and ceramide and between ceramide and sphingosine levels. In conclusion, Alk-SMase and ceramidase are expressed in the gut of both preterm and term newborn infants and may generate bioactive sphingolipid messengers.
8.	Erlandsson, Lena, et al. (author) Preliminary evidence that blocking the uptake of placenta-derived preeclamptic extracellular vesicles protects the vascular endothelium and prevents vasoconstriction 2023 In: Scientific Reports. - 2045-2322. ; 13:1 Journal article (peer-reviewed)abstract Preeclampsia (PE) is a pregnancy syndrome characterized by hypertension and organ damage manifesting after 20 gestational weeks. The etiology is of multifactorial origin, where placental stress causes increased levels of placenta-derived extracellular vesicles (STBEVs) in the maternal circulation, shown to cause inflammation, endothelial activation, vasoconstriction, and anti-angiogenic activity. General endothelial dysfunction is believed to be initiated by endothelial insult during pregnancy that alters vascular function resulting in increased arterial stiffness, cardiac dysfunction, and increased risk of cardiovascular disease later in life. We compared the effect of normal and PE derived STBEVs in vitro on vascular contractility of human subcutaneous arteries using wire myography. Cellular structures of exposed vessels were investigated by transmission electron microscopy. We explored strategies to pharmacologically block the effects of the STBEVs on human vessels. The PE STBEVs caused significantly stronger angiotensin II-mediated contractions and extended structural damage to human subcutaneous arteries compared to normal STBEVs. These negative effects could be reduced by blocking vesicle uptake by endothelial cells, using chlorpromazine or specific antibodies towards the LOX-1 receptor. The therapeutic potential of blocking vesicle uptake should be further explored, to reduce the permanent damage caused on the vasculature during PE pregnancy to prevent future cardiovascular risk.
9.	Ohlsson, Lena, et al. (author) Expression of intestinal and lung alkaline sphingomyelinase and neutral ceramidase in cystic fibrosis f508del transgenic mice. 2008 In: Journal of Pediatric Gastroenterology and Nutrition - Jpgn. - 1536-4801. ; 47:5, s. 547-554 Journal article (peer-reviewed)abstract OBJECTIVES: The intestinal brush border enzymes alkaline sphingomyelinase (alk-SMase) and neutral ceramidase (CDase) digest milk sphingomyelin in suckling neonates. In addition, alk-SMase, CDase, and acid sphingomyelinase (acid-SMase) have been implicated in sphingolipid signaling, which exhibits abnormalities in cystic fibrosis (CF). In this study, we tested the hypothesis that the expression of these enzymes is different in CF. MATERIALS AND METHODS: We used mice with F508del (Cftr) mutation, a CF mouse model with well-characterized intestinal pathology. Enzyme activities were measured using radiolabeled sphingolipid substrates incubated with tissue homogenates from different organs and intestinal contents of wild-type mice, homozygous, and heterozygous F508del mice. RESULTS: No difference was found in levels of CDase and alk-SMase in the small intestinal mucosa or in their longitudinal distribution. Acid-SMase activity was significantly lower in the mucosa of the distal half of the small intestine of F508del compared with wild-type mice. Despite a lower body weight of F508del mice, length and weight of the small intestine and weight per centimeter of colon were larger than in wild-type. Neutral CDase and alk-SMase activities in lungs were lower than in the gut, whereas acid-SMase activity was comparable in both organs. CDase activity in the spleen was significantly higher in F508del than in wild-type mice. CONCLUSIONS: Alk-SMase and neutral CDase are normally expressed in F508del CF mice, whereas activity of acid-SMase in the distal small intestine is decreased. We found no differences in activity of these enzymes in lungs in this mouse model.
10.	Ohlsson, Lena, et al. (author) Short-term exposure to urban PM2.5 particles induces histopathological and inflammatory changes in the rat small intestine 2022 In: Physiological Reports. - : Wiley. - 2051-817X. ; 10:7 Journal article (peer-reviewed)abstract Air pollution and exposure to fine airborne particles with aerodynamic diameter <2.5 μm (PM2.5) negatively impacts human health. Airways constitute a primary route of exposure but PM2.5-contaminated food, drinks as well as mucociliary and hepatobiliary clearance all constitute potential entry points into the intestine. This study evaluated intestinal histopathological and inflammatory changes as well as enteric neuronal numbers after short- or long-term exposure to urban PM2.5. Using a nebulizer, male rats were exposed to a mist with a concentration of 5.3mg PM2.5/m3 for 8 h (short term) or 1.8 mg PM2.5/m3 for 3 h/day, 5 days/week for 8 weeks (long-term) with controls run in parallel. Samples were taken from three regions of the small intestine as well as the colon. Results showed that short-term exposure to PM2.5 induces mucosal lesions and reduces IL1β levels in the small intestine but not colon. No significant changes were observed after long-term exposure, suggesting the presence of intestinal adaptation to environmental stressors in the PM2.5. To our knowledge, this is the first study to systematically characterize regional effects along the intestine.
11.	Ohlsson, Lena, et al. (author) Sphingolipids in human ileostomy content after meals containing milk sphingomyelin. 2010 In: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 91, s. 672-678 Journal article (peer-reviewed)abstract BACKGROUND: Sphingomyelin occurs in modest amounts in the diet, in sloughed mucosal cells, and in bile. It is digested by the mucosal enzymes alkaline sphingomyelinase and ceramidase. In humans, alkaline sphingomyelinase is also secreted in bile. The digestion of sphingomyelin is slow and incomplete, which has been linked to the inhibition of cholesterol absorption and colonic carcinogenesis. OBJECTIVE: We evaluated whether the supply of moderate amounts of milk sphingomyelin increases the exposure of the colon to sphingomyelin and its metabolites. DESIGN: Two experimental series were performed. In experiment A, we measured the content of sphingomyelin and ceramide in human ileostomy content by HPLC during 8 h after consumption of a test meal containing 250 mg milk sphingomyelin. In experiment B, we measured the molecular species of sphingomyelin and ceramide by HPLC-tandem mass spectrometry after doses of 50, 100, or 200 mg sphingomyelin. RESULTS: In experiment A, the average increase in ileostomy content of ceramide plus sphingomyelin amounted to 19% of the fed dose of sphingomyelin. In experiment B, the output of C-22:0-sphingomyelin, C-23:0-sphingomyelin, C-24:0-sphingomyelin, and sphingosine increased significantly and palmitoyl-sphingomyelin increased proportionally less. Outputs and concentrations of palmitoyl-ceramide and sphingosine showed great individual variation, and stearoyl-sphingomyelin and stearoyl-ceramide did not increase after the meals. Although the output of long-chain sphingomyelin species increased significantly, the data indicated that >81% of all measured sphingomyelin species had been digested. CONCLUSIONS: Humans digest and absorb most of the sphingomyelin in normal diets. The level of sphingolipid metabolites to which the colon is exposed can, however, be influenced by realistic amounts of dietary sphingomyelin.
12.	Ohlsson, Sophie, et al. (author) Neutrophils from ANCA-associated vasculitis patients show an increased capacity to activate the complement system via the alternative pathway after ANCA stimulation 2019 In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:6, s. 0218272-0218272 Journal article (peer-reviewed)abstract Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), are autoimmune conditions associated with small vessel inflammation. Earlier studies indicate that complement activation via the alternative pathway plays a major role in the pathogenesis. In this study we have investigated if ANCA-activation of neutrophils from AAV patients leads to activation of the alternative complement pathway. C5a-primed neutrophils (PMN) from 10 AAV patients and 10 healthy controls (HC) were stimulated with PMA or IgG purified from PR3-ANCA positive patients (ANCA IgG). The supernatants were analyzed for release of complement proteins and markers of different granules by ELISA, and release of microparticles (MP) by flow cytometry. The ability of the supernatants to activate the alternative complement pathway was determined by incubation with normal serum and C3bBbP and C5a were measured by ELISA. MP were analyzed by flow cytometry and removed by centrifugation. The supernatants from the AAV patients' neutrophils produced significantly more C3bBbP compared with HCs (p = 0.0001). C3bBbP levels correlated with the number of MP. After removal of MP from the supernatants, alternative pathway activation was significantly lower. This study shows that primed and ANCA-stimulated neutrophils from AAV patients have a greater ability to activate the alternative complement pathway compared to primed neutrophils from healthy controls. This finding emphasizes the role of complement in the pathogenesis of AAV - underlining the therapeutic potential of C5a and other complement blockade.
13.	Ohlsson, Susanne, et al. (author) Neutrophils from vasculitis patients exhibit an increased propensity for activation by anti-neutrophil cytoplasmic antibodies 2014 In: Clinical and Experimental Immunology. - : Wiley-Blackwell. - 0009-9104 .- 1365-2249. ; 176:3, s. 363-372 Journal article (peer-reviewed)abstract Anti-neutrophil cytoplasmic antibodies (ANCA) are thought to be pathogenic in ANCA-associated vasculitis (AAV) by stimulating polymorphonuclear leucocytes (PMNs) to degranulate and produce reactive oxygen species (ROS). The aim of this study was to investigate if PMNs from AAV patients are stimulated more readily by ANCA compared with PMNs from healthy controls (HCs). Differences in ANCA characteristics that can account for different stimulation potential were also studied. PMNs from five AAV patients and five HCs were stimulated with 10 different immunoglobulins (Ig)Gs, purified from PR3-ANCA-positive patients, and ROS production, degranulation and neutrophil extracellular trap (NET) formation was measured. ANCA levels, affinity and clinical data of the AAV donors were recorded. The results show that PMNs from AAV patients produce more intracellular ROS (P=0 center dot 019), but degranulate to a similar extent as PMNs from HCs. ROS production correlated with NET formation. Factors that may influence the ability of ANCA to activate PMNs include affinity and specificity for N-terminal epitopes. In conclusion, our results indicate that PMNs from AAV patients in remission behave quite similarly to HC PMNs, with the exception of a greater intracellular ROS production. This could contribute to more extensive NET formation and thus an increased exposure of the ANCA autoantigens to the immune system.
14.	Persson, Lena, 1951-, et al. (author) Acute leukaemia and malignant lymphoma patients' experiences of disease, treatment and nursing care during the active treatment phase : an explorative study 1995 In: European Journal of Cancer Care. - : John Wiley & Sons Inc.. - 0961-5423 .- 1365-2354. ; 4:3, s. 133-142 Journal article (peer-reviewed)abstract Five acute leukaemia or high malignant lymphoma patients at a hospital in southern Sweden were interviewed about their daily living problems, their coping strategies and their opinions about the nursing care they received during the active phase of their treatment. In addition the EORTC QLQ-C30, the Global Life Quality and the Sense of Coherence scales were administered. The data were analysed from a hermeneutic phenomenological perspective and interpreted to indicate that the patients sensed a threat to their lives, loss of control and having to live in uncertainty stemming from the disease and the treatment. They had problems with such things as fatigue, diarrhoea, nausea and vomiting, loss of appetite, sore mouth, and high temperature. However they seemed to minimise the importance of these problems and instead focused on gaining control of the situation, developing their knowledge of the disease and relying on the support of their family. Contradictions appeared in their statements about the quality of care; the information given was said to be good but difficult to understand, though the quality of the nursing care was judged to be high it had to be asked for i.e. help was received on request. In conclusion the entire situation of the patients perspective of both from the family and the nurses, needs to be studied in further research in order to fully understand the patients´ coping strategies and how nursing care can support them.
15.	Voss, Ulrikke, et al. (author) Airway exposure to urban aerosolized PM2.5 particles induces neuroinflammation and endothelin-mediated contraction of coronary arteries in adult rats 2022 In: Environmental Advances. - : Elsevier BV. - 2666-7657. ; 8 Journal article (peer-reviewed)abstract Ambient airborne particles with an aerodynamic diameter of <2.5 µm (PM2.5), which contain particles from combustion processes, are linked to increased risks for cardiovascular and respiratory diseases. In this experimental study, the short-term and long-term physiologic consequences of PM2.5 inhalation were investigated with the focus on inflammatory parameters and vascular tonus. PM2.5 collected from urban environments in southern Sweden were aerosolized with a nebulizer and delivered to male Sprague Dawley rats. The rats were divided into two treatment groups (n=8 in each): short-term exposed (8 h with an estimated lung exposure rate of 90 μg PM2.5/h); and long-term exposed (3 h/day, 5 days/week, for 8 weeks, with an estimated lung exposure rate of 30 μg PM2.5/h). A group of non-particle-exposed control animals (n=8) was run in parallel with each test group. The results showed that short-term exposure increased the numbers of lymphocytes in the bronchoalveolar lavage fluids. Long-term exposure led to impaired substance P-induced relaxation and increased endothelin-1-induced contraction of the coronary arteries. The contractile response was found to be mediated by endothelin receptor A. Long-term exposure led to increased interleukin-6 levels in brain tissues, as compared to the controls. In summary, this explorative study reveals that exposure to aerosolized, ambient PM2.5 leads to impaired coronary artery function and neuroinflammation. Further investigations into the impacts on health effects of short-term and long-term exposures to urban air pollution are warranted.
16.	Aleksandrova, Krasimira, et al. (author) The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury : data from the European Prospective Investigation into Cancer and Nutrition 2015 In: American Journal of Clinical Nutrition. - : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 102:6, s. 1498-1508 Journal article (peer-reviewed)abstract Background: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. Objective: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer-hepatocellular carcinoma (HCC). Design: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. Results: The multivariable-adjusted RR of having >= 4 cups (600mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and total bilirubin, which-in combination-attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. Conclusion: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.
17.	Ansved, Tor, et al. (author) Enzyme-histochemical and morphological characteristics of fast- and slow-twitch skeletal muscle after brain infarction in the rat 1996 In: Journal of the Neurological Sciences. - 1878-5883. ; 144:1-2, s. 14-20 Journal article (peer-reviewed)abstract The right middle cerebral artery was permanently occluded in 12-week-old male spontaneously hypertensive rats. After the surgery the rats were subjected to repeated behavioural tests during the observation period. Fourteen weeks after surgery the fast-twitch extensor digitorum longus (EDL) and the slow-twitch soleus muscle of both sides were removed and examined with regard to muscle fibre characteristics obtained by histochemical and morphometrical methods. Comparisons were made with age-matched controls. Limb placement and the ability to traverse a beam or a rotating pole were repeatedly tested 2-13 weeks after the operation. In spite of permanent sensorimotor deficits in limb placement and when traversing a rotating pole or beam, no increase in pathological changes was noted in either EDL or soleus. The number and proportion of fibre types remained unchanged in both muscles. There was no difference in muscle fibre size in either EDL or soleus. It is concluded that brain infarction in the rat, although causing marked impairment of contralateral motor function, does not have a major influence on the muscle-fibre morphology or fibre-type composition, irrespective of muscle type.
18.	Bajahzer, Mohammed F., 1983- (author) Influence of dietary carbohydrates on plasma fatty acid composition : Results from interventional and observational studies 2024 Doctoral thesis (other academic/artistic)abstract Given reporting bias in dietary questionnaires, biomarkers offer objective assessments. Measuring circulating fatty acid (FA) composition is an established method for evaluating dietary fat quality. However, the influence of carbohydrates and sugars on plasma FA composition is less clear. This thesis investigates how carbohydrates impact circulating FAs synthesized through de novo lipogenesis (DNL). We assessed palmitate and other FAs in circulating lipids. The hypothesis was that increased dietary carbohydrate intake elevates plasma palmitate levels. In Paper I, a randomized crossover study (with all meals provided) investigated the impact of three diets varying in carbohydrate amount and type on plasma palmitate levels in healthy adults. Results showed no influence of either carbohydrate quantity or quality on plasma palmitate. However, palmitoleate increased in higher-carbohydrate diets, and carbohydrate quality affected myristate levels. In Paper II, a parallel-groups study explored the impact of high intake of sugar-sweetened soda (SS) and semi-skimmed milk (milk) on plasma palmitate among Danish adults. Both SS and milk increased palmitate in phospholipids (PL) compared with water. Excessive SS, but not milk, increased palmitoleate in all lipid fractions. In Paper III, a prospective study in Swedish children found no association between plasma palmitate in PL and incident overweight. Palmitate did not correlate with carbohydrate or sugar intake. Only stearate was associated with overweight incidence. Again, stearate was not associated with carbohydrate or sugar intake. In Paper IV, a cross-sectional study in older men found no association between serum palmitate and carbohydrate or sucrose intake, even after considering BMI or insulin sensitivity. Instead, stearate was positively associated with carbohydrate and sucrose intake, while oleate was inversely associated with sucrose and fiber intake. In conclusion, this thesis suggests that moderate changes in carbohydrate quantity or quality do not alter plasma palmitate, although overfeeding with liquid sugar causes higher palmitate in plasma PL. Stearate, but not palmitate, was linked to incident overweight in children, but none of these FAs reflected higher carbohydrate or sugar intake. Overall, palmitoleate seems to be more responsive to increased carbohydrate intake than palmitate, whereas the latter does not appear as a useful biomarker of high carbohydrate intake in Nordic populations.
19.	Beausang, Angela, et al. (author) "Möjligheten att rädda några av dessa kvinnors liv har inte vägts in" 2014 In: Dagens Medicin. - : Dagens Medicin. Journal article (pop. science, debate, etc.)abstract Namnet på Socialstyrelsens vägledning lyder: Hur upptäcka våldsutsatthet? Ja, det kan man verkligen fråga sig efter att ha läst detta föga vägledande dokument, skriver ett stort antal kritiska debattörer.
20.	Benrick, Anna, 1979, et al. (author) A non-conservative polymorphism in the IL-6 signal transducer (IL6ST)/gp130 is associated with myocardial infarction in a hypertensive population. 2008 In: Regulatory peptides. - : Elsevier BV. - 0167-0115. ; 146:1-3, s. 189-96 Journal article (peer-reviewed)abstract Inflammation is a key component in the development of atherosclerosis, and myocardial infarction (MI); therefore we investigated the association between an interleukin-6 signal transducer (IL6ST)/gp130 polymorphism, gp130 function and risk of MI. Structural modeling suggested that a non-conservative single nucleotide polymorphism in the gp130, Gly148Arg, can change the stability and functional properties of the molecule. In vitro studies were done with BAF/3 cells lacking endogenous gp130. Cells stably transfected with the gp130 148Arg variant proliferated less and showed slightly lower STAT-3 phosphorylation in response to gp130 stimulation as compared to cells transfected with gp130 148Gly. In a prospectively followed hypertensive cohort we identified 167 patients who suffered a MI during the study and compared them to matched controls (mean age 57 years, 73% males, n=482). Carriers of the 148Arg variant (f(Arg)=0.12) of the gp130 receptor had decreased odds ratio for MI in univariate analysis (0.56, 95% CI 0.34-0.91, p=0.02). In conclusion, a genetically determined structural variant of the IL-6 receptor subunit gp130 is, independently of other known risk factors, associated with decreased risk of MI. The variant is also associated with decreased IL-6 responsiveness and could lead to a configuration change in the gp130 receptor.
21.	Benyamine, Isak, 1963- (author) Konstnärliga undervisningspraktiker : Genealogier, diskurser och makt 2019 Doctoral thesis (other academic/artistic)abstract This dissertation is about art teaching practices at upper secondary schools with a focus on theatre and at university arts programmes with a focus on film. More specifically, it addresses the factors that have contributed to current teaching practices in art education today and how students and teachers in interaction with each other shape, become part of and identify with the norms and values that emerge through these practices.The overarching question concerns how norms and values emerge as power/knowledge processes in the teaching process. The genealogical study presented examines how art education is constructed at a policy level. The study discusses how, in past eras, investigators, researchers and educators described what students needed to do during their education to develop into professional artists, how teaching practices were designed and justified, and how art was distinct from other activities and forms of knowledge in education. The interaction study presented examines the act of teaching. It discusses how, the participants shape each other and establish norms and values in relation to notions of what art “is” and can be.The conditions of possibilities in art teaching practices has been identified in three discourses. The discourse of conversation governs the format and organisation of the teaching practice. It is assumed that through conversation the students can develop their artistic ability. The discourse of freedom identifies how students submit to the vague, flexible and ever-changing notions of what art signifies. The discourse of production describes how the artistic work in the teaching practice takes precedence over an acquisition of established knowledge.The importance of the participants’ own experiences and feelings, therapeutic conversations, the liberation from conventional education discourses, confession practices and the establishment of a production discourse all emerge as important techniques in art teaching practices. Core values and norms are expressed through these techniques.The study shows that participants in art teaching practices develop the skills of self-evaluation, self-analysis and self-governance. The notion of an individualised, exploratory educational experience clashes with a process that directs the students to align themselves with the shared norms and values of the art world, of its content and expression. Students perceive their artistic output as unique while the art produced can be understood as expression of a normalisation process that strives to maintain the values and norms in art teaching practices. In summery the dissertation shows that the participants’ learning process is of an exploratory nature. Rather than acquiring and assimilating established knowledge, the participants learn by finding their own paths in a knowledge-formation process in which they discover the artistic potential of their own experiences and insights.
22.	Björk, Peter, et al. (author) Release of dog polymorphonuclear leukocyte cathepsin g, normally and in endotoxin and pancreatitic shock : Isolation and partial characterization of dog polymorphonuclear leukocyte cathepsin g 1991 In: Biological Chemistry Hoppe-Seyler. - : Walter de Gruyter GmbH. - 0177-3593. ; 372:1, s. 419-426 Journal article (peer-reviewed)abstract Dog polymorphonuclear leukocyte cathepsin G was isolated from a granule extract using a two-step procedure including affinity chromatography on aTrasylol-Sepharose gel and ion-exchange chromatography on a CM 52 column. 22 of the first 24 N-terminal amino acids were determined and showed 83% and 71% identity to those of human and rat cathepsin G, respectively. Total amino-acid composition demonstrated the basic nature of the protein. In an SDS/polyacrylamide-gel electrophoresis the protein showed an Mr of 29400 compared to the Mr of 26800 calculated from the total amino-acid composition. The enzyme was shown to form complexes with α1α2-macroglobulin and arproteinase inhibitor. A specific enzyme-linked immunosorbent assay was developed for the determination of cathepsin G/α proteinase inhibitor complex in dog plasma and tissue fluids. The mean concentration of cathepsin G in normal dog plasma was determined to be 38 μ/l, measured as cathepsin G/α1-proteinase inhibitor complex. When active dog cathepsin G was added to normal dog plasma in vitro, approximately 56% could be measured by the assay. Slow intravenous infusion of a lethal dose of endotoxin in dogs was followed by a marked drop in white blood cell count and thrombocytes and a simultaneous rapid increase in plasma cathepsin G concentration, reaching a maximum level of 150 β/l. Bile-induced experimental pancreatitis in dogs was accompanied by successive increase in cathepsin G levels in plasma as well as in peritoneal exudates, reaching a maximum level of about 300 μ/l in plasma and 18 mg/ l in the exudates during the late stages of disease. & by Walter de Gruyter & Co
23.	Blixt, Frank W., et al. (author) MEK/ERK/1/2 sensitive vascular changes coincide with retinal functional deficit, following transient ophthalmic artery occlusion 2019 In: Experimental Eye Research. - : Elsevier BV. - 0014-4835. ; 179, s. 142-149 Journal article (peer-reviewed)abstract Retinal ischemia remains a major cause of blindness in the world with few acute treatments available. Recent emphasis on retinal vasculature and the ophthalmic artery's vascular properties after ischemia has shown an increase in vasoconstrictive functionality, as previously observed in cerebral arteries following stroke. Specifically, endothelin-1 (ET-1) receptor-mediated vasoconstriction regulated by the MEK/ERK1/2 pathway. In this study, the ophthalmic artery of rats was occluded for 2 h with the middle cerebral artery occlusion model. MEK/ERK1/2 inhibitor U0126 was administered at 0, 6, and 24 h following reperfusion and the functional properties of the ophthalmic artery were evaluated at 48 h post reperfusion. Additionally, retinal function was evaluated at day 1, 4, and 7 after reperfusion. Occlusion of the ophthalmic artery led to a significant increase of endothelin-1 mediated vasoconstriction which can be attenuated by U0126 treatment, most evident at higher ET-1 concentrations of 10−7 M (Emax151.0 ± 22.0% of 60 mM K+), vs non-treated ischemic arteries Emax 212.1 ± 14.7% of 60 mM K+). Retinal function also deteriorated following ischemia and was improved with treatment with a-wave amplitudes of 725 ± 36 μV in control, 560 ± 21 μV in non-treated, and 668 ± 73 μV in U0126 treated at 2 log cd*s/m2 luminance in the acute stages (1 days post-ischemia). Full spontaneous retinal recovery was observed at day 7 regardless of treatment. In conclusion, this is the first study to show a beneficial in vivo effect of U0126 on vascular contractility following ischemia in the ophthalmic artery. Coupled with the knowledge obtained from cerebral vasculature, these results point towards a novel therapeutic approach following ischemia-related injuries to the eye.
24.	Cheng, Yajun, et al. (author) Curcumin decreases acid sphingomyelinase activity in colon cancer caco-2 cells 2007 In: Planta Medica. - : Georg Thieme Verlag KG. - 0032-0943 .- 1439-0221. ; 73:8, s. 725-730 Journal article (peer-reviewed)abstract Curcumin has been shown to inhibit cell growth and induce apoptosis in colon cancer cells. The metabolism of sphingomyelin has implications in the development of colon cancer. We examined whether curcumin affects the enzymes that hydrolyse sphingomyelin in Caco-2 cells. The cells were cultured in both monolayer and polarized conditions and stimulated with curcumin. The activities of sphingomyelinases were determined. Sphingomyelin and its hydrolytic products were analysed by thin layer chromatography. The changes of acid sphingomyelinase protein were examined by Western blotting. We found that curcumin reduced the hydrolytic capacity of the cells against choline-labelled sphingomyelin, associated with a mild increase of cellular sphingomyelin in the cells. Analysis of the hydrolytic products revealed that the activity was derived from acid sphingomyelinase not from phospholipase D. The curcumin-induced reduction of acid SMase required more than 8 h stimulation. Western blotting showed reduced acid sphingomyelinase protein after curcumin stimulation. The inhibitory effect was more potent in monolayer cells than in polarised cells. No changes of other sphingomyelinases were identified. In the concentrations inhibiting acid sphingomyelinase, curcumin inhibited DNA synthesis and induced cell death. In conclusion, curcumin inhibits acid sphingomyelinase and the effect might be involved in its anti proliferative property against colon cancer cells.
25.	Cheng, Yajun, et al. (author) Psyllium and fat in diets differentially affect the activities and expressions of colonic sphingomyelinases and caspase in mice. 2004 In: British Journal of Nutrition. - 1475-2662. ; 91:5, s. 715-723 Journal article (peer-reviewed)abstract Dietary fibre and fat affect colonic tumourigenesis and inflammation. Sphingomyelin metabolism may have implications for the pathogenesis of colonic tumours and ulcerative colitis. The present study examined the effects of psyllium and fat on the enzymes responsible for sphingomyelin metabolism and apoptosis in the colon. Mice were fed control, psyllium-containing (100 g/kg), high-fat (313 g/kg, 53 % energy as fat) or high-fat plus psyllium diets for 4 weeks. The activities of acid, neutral and alkaline sphingomyelinase (SMase), neutral ceramidase, and caspase 3, 8 and 9 in colonic mucosa were determined. The expressions of alkaline SMase and caspase 3 were examined. The psyllium-containing diet was found to increase significantly the activities of alkaline SMase and caspase 3 and decreased those of acid SMase and neutral ceramidase. The high-fat diet had opposite effects on these enzymes and attenuated the effects of psyllium. Western blotting showed that psyllium increased and high-fat decreased the levels of alkaline SMase and caspase 3 in colonic mucosa. The change in caspase 3 activity was positively correlated with that of alkaline SMase and negatively with acid SMase. No similar changes of acid and alkaline phosphatase activities in the colon or acid and neutral SMase activity in the liver were identified. In conclusion, colonic sphingomyelin metabolism and apoptosis were affected by psyllium and fat in an opposite manner. The results may have implications for colorectal tumourigenesis and inflammation.
26.	Dias, Joana A., et al. (author) Inflammatory potential of the diet and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study 2018 In: American Journal of Clinical Nutrition. - : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 107:4, s. 607-616 Journal article (peer-reviewed)abstract Chronic inflammation plays a critical role in the pathogenesis of the 2 major types of gastric cancer. Several foods, nutrients, and nonnutrient food components seem to be involved in the regulation of chronic inflammation. We assessed the association between the inflammatory potential of the diet and the risk of gastric carcinoma, overall and for the 2 major subsites: cardia cancers and noncardia cancers. A total of 476,160 subjects (30% men, 70% women) from the European Investigation into Cancer and Nutrition (EPIC) study were followed for 14 y, during which 913 incident cases of gastric carcinoma were identified, including 236 located in the cardia, 341 in the distal part of the stomach (noncardia), and 336 with overlapping or unknown tumor site. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated with the use of 28 dietary components and their corresponding inflammatory scores. The association between the ISD and gastric cancer risk was estimated by HRs and 95% CIs calculated by multivariate Cox regression models adjusted for confounders. The inflammatory potential of the diet was associated with an increased risk of gastric cancer. The HR (95% CI) for each increase in 1 SD of the ISD were 1.25 (1.12, 1.39) for all gastric cancers, 1.30 (1.06, 1.59) for cardia cancers, and 1.07 (0.89, 1.28) for noncardia cancers. The corresponding values for the highest compared with the lowest quartiles of the ISD were 1.66 (1.26, 2.20), 1.94 (1.14, 3.30), and 1.07 (0.70, 1.70), respectively. Our results suggest that low-grade chronic inflammation induced by the diet may be associated with gastric cancer risk. This pattern seems to be more consistent for gastric carcinomas located in the cardia than for those located in the distal stomach. This study is listed on the ISRCTN registry as ISRCTN12136108.
27.	Djerf, Olle, et al. (author) Industriavtalet - köpkraft och konkurrenskraft 2003 Reports (pop. science, debate, etc.)
28.	Djerf, Olle, et al. (author) Köpkraft och konkurrenskraft – tredje avtalsrörelsen med Industriavtalet 2003 In: Ekonomisk Debatt. - 0345-2646. ; 31:8, s. 16-26 Journal article (other academic/artistic)abstract Parterna inom industrin slöt ett samarbets- och förhandlingsavtal 1997. Under Industriavtalets första period 1998–2000 ökade reallönerna med 3 procent per år medan det relativa kostnadsläget förbättrades med 4 procent årligen. Industrisysselsättningen ökade. Industriavtalets andra period 2001–2003 har präglats av en betydligt sämre konjunktur. Reallönerna har dock ökat med ca 1 1⁄2 procent per år. Det relativa kostnadsläget har varit oförändrat medan sysselsättningen minskat med 3 procent årligen. Viktigt för den nya avtalsperioden är att Sverige har en trovärdig inflationsnorm och att de viktigaste konkurrenternas arbetskraftskostnader kommer att öka långsamt. Fortsatt återhållsamma ökningar av nominallönerna är av stor betydelse för produktions- och sysselsättningsutvecklingen i Sverige.
29.	Djerf, Olle, et al. (author) Svensk industri i globaliseringens tid 2005 Reports (pop. science, debate, etc.)
30.	Duan, Rui-Dong, et al. (author) Evidence for specific ceramidase present in the intestinal contents of rats and humans. 2001 In: Lipids. - : Wiley. - 0024-4201 .- 1558-9307. ; 36:8, s. 807-812 Journal article (peer-reviewed)abstract A neutral ceramidase activity stimulated by bile salt was previously identified in the intestinal content. Recently, bile salt stimulated lipase (BSSL) was found to have ceramidase activity. It is unknown whether the ceramidase activity previously found is attributable to BSSL. To address this question, we compared the behaviors of high quaternary aminoethyl (HQ) anion exchange chromatography, the distributions, the stability, and the responses to lipase inhibitor between ceramidase and pancreatic BSSL. The proteins from whole small intestinal contents of humans and rats were precipitated by acetone and dissolved in 20 mM Tris buffer pH 8.2. These proteins had neutral ceramidase activity but not BSSL activity against p‐nitrophenyl acetate. When the proteins were subject to HQ chromatography, two peaks of ceramidase activity were identified, which had acid and neutral pH optima, respectively. Neither of them had BSSL activity against p‐nitrophenyl acetate. Western blot using BSSL antiserum failed to identify BSSL protein in the fractions, with high neutral ceramidase activity. In rat intestinal tract, pancreatic BSSL activity was high in the duodenum and declined rapidly in the small intestine, whereas neutral ceramidase activity was low in the duodenum and maintained a high level until the distal part of the small intestine. In addition, orlistat, the inhibitor of lipase, abolished human BSSL activity against p‐nitrophenyl acetate and slightly reduced its activity against ceramide but had no inhibitory effect on ceramidase activity isolated by HQ chromatography. In conclusion, we provide the evidence for a specific ceramidase other than pancreatic BSSL present in the intestinal content. The enzyme may play important roles in digestion of dietary sphingolipids.
31.	Emek, Sinan Cem, et al. (author) Pigments protect the light harvesting proteins of chloroplast thylakoid membranes against digestion by gastrointestinal proteases 2011 In: Food Hydrocolloids. - : Elsevier BV. - 0268-005X. ; 25:6, s. 1618-1626 Journal article (peer-reviewed)abstract Chloroplast thylakoid membranes inhibit pancreatic lipase/colipase activity in vitro and, when included in food, induce satiety signals. As thylakoid membranes themselves are nutrients, containing lipids and proteins, it is of interest to study the digestion of thylakoids by enzymes of the gastrointestinal tract. Thylakoid membranes were treated with pepsin, trypsin, gastric and pancreatic juice at 37 degrees C and the resulting enzymatic breakdown was analyzed by gel electrophoresis, electron microscopy and mass spectroscopy. In all cases, several of the proteins were degraded within half an hour, while the main parts of the pigment-protein complexes were resistant for hours. Oil emulsified thylakoids were more resistant towards the enzymatic breakdown. Electron microscopy demonstrated that, after treatments, the thylakoids still remained in a membrane vesicular form. The capacity of thylakoid membranes to inhibit the lipase/colipase activity was partly reduced in all cases. About 50% of the inhibition capacity remained after treatment with pancreatic juice when the thylakoids were present in an oil emulsion. Delipidated thylakoids and plasma membranes, which lack the photosynthetic pigments, were degraded rapidly by pancreatic juice. Conclusion: The pigments, closely bound to the trans-membrane helices of thylakoid membrane proteins protect these from digestion by pepsin, trypsin, gastric and pancreatic juice. This supports the notion that a substantial inhibition of lipase/colipase takes place during the first 2 h in the intestine resulting in a retardation and prolongation of lipolysis in vivo. (C) 2010 Elsevier Ltd. All rights reserved.
32.	Eriksson, Anna-Lena, 1971, et al. (author) Association between the low activity genotype of catechol-O-methyltransferase and myocardial infarction in a hypertensive population 2004 In: Eur Heart J. ; 25:5, s. 386-91 Journal article (peer-reviewed)abstract AIM: Estrogens regulate several biological processes involved in the pathogenesis of myocardial infarction. Catechol-O-methyltransferase (COMT) is a key enzyme in the degradation of estrogens. There is a functional polymorphism in the COMT gene (Val158Met), affecting the activity of the enzyme. We investigated if the low activity genotype of COMT is associated with an altered risk of myocardial infarction. METHODS AND RESULTS: In a prospectively followed hypertensive cohort we identified 174 patients who suffered a myocardial infarction during the study and compared them to 348 controls from the same cohort. The COMT polymorphism and serum levels of sex hormones were analysed. Patients homozygous for the low activity COMT genotype had a decreased risk of myocardial infarction compared to those with the high activity genotype, odds ratio 0.65 (95% CI 0.44-0.97, p=0.033 ). The protective effect of the low activity genotype was most evident among older patients (> 58 years of age), odds ratio 0.43 (95% CI 0.23-0.79, p=0.006 ). Serum levels of estradiol were increased ( p=0.006 ) in males with the low activity genotype. CONCLUSIONS: Our findings suggest that the low activity COMT genotype is protective against myocardial infarction. One may speculate that the altered estrogen status could be involved in this effect.
33.	Eriksson, Anna-Lena, 1971, et al. (author) Genetic Determinants of Circulating Estrogen Levels and Evidence of a Causal Effect of Estradiol on Bone Density in Men. 2018 In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 103:3, s. 991-1004 Journal article (peer-reviewed)abstract Serum estradiol (E2) and estrone (E1) levels exhibit substantial heritability.To investigate the genetic regulation of serum E2 and E1 in men.Genome-wide association study in 11,097 men of European origin from nine epidemiological cohorts.Genetic determinants of serum E2 and E1 levels.Variants in/near CYP19A1 demonstrated the strongest evidence for association with E2, resolving to three independent signals. Two additional independent signals were found on the X chromosome; FAMily with sequence similarity 9, member B (FAM9B), rs5934505 (P = 3.4 × 10-8) and Xq27.3, rs5951794 (P = 3.1 × 10-10). E1 signals were found in CYP19A1 (rs2899472, P = 5.5 × 10-23), in Tripartite motif containing 4 (TRIM4; rs17277546, P = 5.8 × 10-14), and CYP11B1/B2 (rs10093796, P = 1.2 × 10-8). E2 signals in CYP19A1 and FAM9B were associated with bone mineral density (BMD). Mendelian randomization analysis suggested a causal effect of serum E2 on BMD in men. A 1 pg/mL genetically increased E2 was associated with a 0.048 standard deviation increase in lumbar spine BMD (P = 2.8 × 10-12). In men and women combined, CYP19A1 alleles associated with higher E2 levels were associated with lower degrees of insulin resistance.Our findings confirm that CYP19A1 is an important genetic regulator of E2 and E1 levels and strengthen the causal importance of E2 for bone health in men. We also report two independent loci on the X-chromosome for E2, and one locus each in TRIM4 and CYP11B1/B2, for E1.
34.	Eriksson, Anna-Lena, 1971, et al. (author) Genetic variations in sex steroid-related genes as predictors of serum estrogen levels in men. 2009 In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94:3, s. 1033-41 Journal article (peer-reviewed)abstract CONTEXT: The risk of many conditions, including prostate cancer, breast cancer, and osteoporosis, is associated with serum levels of sex steroids. OBJECTIVE: The aim of the study was to identify genetic variations in sex steroid-related genes that are associated with serum levels of estradiol (E2) and/or testosterone in men. DESIGN: Genotyping of 604 single nucleotide polymorphisms in 50 sex steroid-related candidate genes was performed in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study (n = 1041 men; age, 18.9 +/- 0.6 yr). Replications of significant associations were performed in the Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2568 men; age, 75.5 +/- 3.2 yr) and in the MrOS US study (n = 1922 men; age, 73.5 +/- 5.8 yr). Serum E2, testosterone, and estrone (E1) levels were analyzed using gas chromatography/mass spectrometry. RESULTS: The screening in the GOOD cohort identified the single nucleotide polymorphism rs2470152 in intron 1 of the CYP19 gene, which codes for aromatase, responsible for the final step of the biosynthesis of E2 and E1, to be most significantly associated with serum E2 levels (P = 2 x 10(-6)). This association was confirmed both in the MrOS Sweden study (P = 9 x 10(-7)) and in the MrOS US study (P = 1 x 10(-4)). When analyzed in all subjects (n = 5531), rs2470152 was clearly associated with both E2 (P = 2 x 10(-14)) and E1 (P = 8 x 10(-19)) levels. In addition, this polymorphism was modestly associated with lumbar spine BMD (P < 0.01) and prevalent self-reported fractures (P < 0.05). CONCLUSIONS: rs2470152 of the CYP19 gene is clearly associated with serum E2 and E1 levels in men.
35.	Eriksson, Anna-Lena, 1971, et al. (author) High-Sensitivity CRP Is an Independent Risk Factor for All Fractures and Vertebral Fractures in Elderly Men : The MrOS Sweden Study 2014 In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 29:2, s. 418-423 Journal article (peer-reviewed)abstract Epidemiological studies have shown low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) to be associated with fracture risk in women. However, it is still unclear whether hs-CRP is also associated with fracture risk in men. We therefore measured serum levels of hs-CRP in 2910 men, mean age 75 years, included in the prospective population-based MrOS Sweden cohort. Study participants were divided into tertile groups based on hs-CRP level. Fractures occurring after the baseline visit were validated (average follow-up 5.4 years). The incidence for having at least one fracture after baseline was 23.9 per 1000 person-years. In Cox proportional hazard regression analyses adjusted for age, hs-CRP was related to fracture risk. The hazard ratio (HR) of fracture for the highest tertile of hs-CRP, compared with the lowest and the medium tertiles combined, was 1.48 (95% CI, 1.20-1.82). Multivariate adjustment for other risk factors for fractures had no major effect on the associations between hs-CRP and fracture. Results were essentially unchanged after exclusion of subjects with hs-CRP levels greater than 7.5mg/L, as well as after exclusion of subjects with a first fracture within 3 years of follow-up, supporting that the associations between hs-CRP and fracture risk were not merely a reflection of a poor health status at the time of serum sampling. Femoral neck bone mineral density (BMD) was not associated with hs-CRP, and the predictive role of hs-CRP for fracture risk was essentially unchanged when femoral neck BMD was added to the model (HR, 1.37; 95% CI, 1.09-1.72). Exploratory subanalyses of fracture type demonstrated that hs-CRP was clearly associated with clinical vertebral fractures (HR, 1.61; 95% CI, 1.12-2.29). We demonstrate, using a large prospective population-based study, that elderly men with high hs-CRP have increased risk of fractures, and that these fractures are mainly vertebral. The association between hs-CRP and fractures was independent of BMD. (c) 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
36.	Eriksson, Anna-Lena, 1971, et al. (author) SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density. 2006 In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:12, s. 5029-37 Journal article (peer-reviewed)abstract CONTEXT: SHBG regulates free sex steroid levels, which in turn regulate skeletal homeostasis. Twin studies have demonstrated that genetic factors largely account for interindividual variation in SHBG levels. Glucuronidated androgen metabolites have been proposed as markers of androgenic activity. OBJECTIVE: Our objective was to investigate whether polymorphisms in the SHBG gene promoter [(TAAAA)(n) microsatellite and rs1799941 single-nucleotide polymorphism] are associated with serum levels of SHBG, sex steroids, or bone mineral density (BMD) in men. DESIGN AND STUDY SUBJECTS: We conducted a population-based study of two cohorts of Swedish men: elderly men (MrOS Sweden; n congruent with 3000; average age, 75.4 yr) and young adult men (GOOD study; n = 1068; average age, 18.9 yr). MAIN OUTCOME MEASURES: We measured serum levels of SHBG, testosterone, estradiol, dihydrotestosterone, 5alpha-androstane-3alpha,17beta-diol glucuronides, androsterone glucuronide, and BMD determined by dual-energy x-ray absorptiometry. RESULTS: In both cohorts, (TAAAA)(n) and rs1799941 genotypes were associated with serum levels of SHBG (P < 0.001), dihydrotestosterone (P < 0.05), and 5alpha-androstane-3alpha,17beta-diol glucuronides (P < 0.05). In the elderly men, they were also associated with testosterone and BMD at all hip bone sites. The genotype associated with high levels of SHBG was also associated with high BMD. Interestingly, male mice overexpressing human SHBG had increased cortical bone mineral content in the femur, suggesting that elevated SHBG levels may cause increased bone mass. CONCLUSIONS: Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men.
37.	Eriksson, Anna-Lena, 1971, et al. (author) The Bone Sparing Effects of 2-Methoxyestradiol Are Mediated via Estrogen Receptor-α in Male Mice. 2016 In: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 157:11, s. 4200-4205 Journal article (peer-reviewed)abstract 2-Methoxyestradiol (2ME2), a metabolite of 17β-estradiol (E2), exerts bone sparing effects in animal models. We hypothesized that the underlying mechanism is back conversion of 2ME2 to E2, which subsequently acts via estrogen receptor (ER)α. We measured serum E2 levels in orchidectomized wild-type (WT) mice treated with 2ME2 66.6 μg/d or placebo. In placebo-treated animals, E2 was below the detection limit. In 2ME2-treated mice, the serum E2 level was 4.97 ± 0.68 pg/mL. This corresponds to the level found in diesterus in cycling female mice. Next, we investigated bone parameters in orchidectomized WT and ERα knockout mice treated with 2ME2 or placebo for 35 days. 2ME2 (6.66 μg/d) preserved trabecular and cortical bone in WT mice. Trabecular volumetric-bone mineral density was 64 ± 20%, and trabecular bone volume/total volume was 60 ± 20% higher in the metaphyseal region of the femur in the 2ME2 group, compared with placebo (P < .01). Both trabecular number and trabecular thickness were increased (P < .01). Cortical bone mineral content in the diaphyseal region of the femur was 31 ± 3% higher in the 2ME2 group, compared with placebo (P < .001). This was due to larger cortical area (P < .001). Three-point bending showed an increased bone strength in WT 2ME2-treated animals compared with placebo (maximum load [Fmax] +19±5% in the 2ME2 group, P < .05). Importantly, no bone parameter was affected by 2ME2 treatment in ERα knockout mice. In conclusion, 2ME2 treatment of orchidectomized mice results in increased serum E2. ERα mediates the bone sparing effects of 2ME2. The likely mediator of this effect is E2 resulting from back conversion of 2ME2.
38.	Eriksson, Anna-Lena, 1971, et al. (author) The COMT val158met polymorphism is associated with early pubertal development, height and cortical bone mass in girls. 2005 In: Pediatric research. - 0031-3998. ; 58:1, s. 71-7 Journal article (peer-reviewed)abstract Estrogens are involved in accretion of bone mass during puberty. Catechol-O-Methyltransferase (COMT) is involved in the degradation of estrogens. In this cross-sectional study we investigated associations between the COMT val158met polymorphism, which results in a 60-75% difference in enzyme activity between the val (high activity = H) and the met (low activity = L) variant, and skeletal phenotypes in 246 healthy pre/early pubertal girls. Girls with COMT(LL) were 5.4 cm taller than COMT(HH) girls. Dual x-ray absorptiometry showed higher values of bone mineral content (BMC), and larger areas of total body, femur and spine in COMT(LL). Cortical BMC, measured by peripheral quantitative computerized tomography in the tibia, was 9.8% higher in COMT(LL) compared with COMT(HH). This was due to a larger cortical cross sectional area while the cortical volumetric bone mineral density was not associated with COMT genotype. COMT(LL) girls had higher serum levels of free estradiol and insulin like growth factor. Regression models indicated that COMT genotype exerted effects on skeletal growth mainly via a regulation of free estradiol, resulting in an affected pubertal development (Tanner staging). We propose that the COMT(LL) genotype results in higher free estradiol levels and earlier pubertal development, leading to an increased skeletal growth in pre/early pubertal girls. Possible consequences for the adult skeleton however can be determined only after cessation of growth.
39.	Eriksson, Anna-Lena, 1971, et al. (author) The COMT val158met polymorphism is associated with prevalent fractures in Swedish men. 2008 In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 42:1, s. 107-12 Journal article (peer-reviewed)abstract INTRODUCTION: Sex steroids are important for growth and maintenance of the skeleton. Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT val158met polymorphism results in a 60-75% difference in enzyme activity between the val (high activity=H) and met (low activity=L) variants. We have previously reported that this polymorphism is associated with bone mineral density (BMD) in young men. The aim of this study was to investigate associations between COMT val158met, BMD and fractures in elderly men. METHODS: Population-based study of Swedish men 75.4, SD 3.2, years of age. Fractures were reported using standardized questionnaires. Fracture and genotype data were available from 2,822 individuals. RESULTS: Total number of individuals with self-reported fracture was 989 (35.0%). Prevalence of >or=1 fracture was 37.2% in COMT(LL), 35.7% in COMT(HL) and 30.4% in COMT(HH) (p<0.05). Early fractures (50 years of age). The OR for fracture of the non-weight bearing skeleton in COMT(HH) compared with COMT(LL+HL) was 0.74 (95% CI 0.59-0.92). No associations between COMT val158met and BMD were found in this cohort of elderly men. CONCLUSIONS: The COMT val158met polymorphism is associated with life time fracture prevalence in elderly Swedish men. This association is mainly driven by early fractures (
40.	Feng, Dan, et al. (author) Curcumin inhibits cholesterol uptake in Caco-2 cells by down-regulation of NPC1L1 expression 2010 In: Lipids in Health and Disease. - 1476-511X. ; 9 Journal article (peer-reviewed)abstract Background: Curcumin is a polyphenol and the one of the principle curcuminoids of the spice turmeric. Its antioxidant, anti-cancer and anti-inflammatory effects have been intensively studied. Previous in vivo studies showed that administration of curcumin also decreased cholesterol levels in the blood, and the effects were considered to be related to upregulation of LDL receptor. However, since plasma cholesterol levels are also influenced by the uptake of cholesterol in the gut, which is mediated by a specific transporter Niemann-Pick Cl-like 1 (NPC1L1) protein, the present study is to investigate whether curcumin affects cholesterol uptake in the intestinal Caco-2 cells. Methods: Caco-2 cells were cultured to confluence. The micelles composed of bile salt, monoolein, and C-14-cholesterol were prepared. We first incubated the cells with the micelles in the presence and absence of ezetimibe, the specific inhibitor of NPC1L1, to see whether the uptake of the cholesterol in the cells was mediated by NPC1L1. We then pretreated the cells with curcumin at different concentrations for 24 h followed by examination of the changes of cholesterol uptake in these curcumin-treated cells. Finally we determined whether curcumin affects the expression of NPC1L1 by both Western blot analysis and qPCR quantification. Results: We found that the uptake of radioactive cholesterol in Caco-2 cells was inhibited by ezetimibe in a dose-dependent manner. The results indicate that the uptake of cholesterol in this study was mediated by NPC1L1. We then pretreated the cells with 25-100 mu M curcumin for 24 h and found that such a treatment dose-dependently inhibited cholesterol uptake with 40% inhibition obtained by 100 mu M curcumin. In addition, we found that the curcumin-induced inhibition of cholesterol uptake was associated with significant decrease in the levels of NPC1L1 protein and NPC1L1 mRNA, as analyzed by Western blot and qPCR, respectively. Conclusion: Curcumin inhibits cholesterol uptake through suppression of NPC1L1 expression in the intestinal cells.
41.	Feng, Dan, et al. (author) Generating Ceramide from Sphingomyelin by Alkaline Sphingomyelinase in the Gut Enhances Sphingomyelin-Induced Inhibition of Cholesterol Uptake in Caco-2 Cells. 2010 In: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; Mar 4, s. 3377-3383 Journal article (peer-reviewed)abstract BACKGROUND: Sphingomyelin (SM) is present in dietary products and cell plasma membranes. We previously showed that dietary SM inhibited cholesterol absorption in rats. In the intestinal tract, SM is mainly hydrolyzed by alkaline sphingomyelinase (alk-SMase) to ceramide. AIMS: We investigated the influence of SM and its hydrolytic products ceramide and sphingosine on cholesterol uptake in intestinal Caco-2 cells. METHODS: Micelles containing bile salt, monoolein, and (14)C-cholesterol were prepared with or without SM, ceramide, or sphingosine. The micelles were incubated with Caco-2 cells, and uptake of radioactive cholesterol was quantified. RESULTS: We found that confluent monolayer Caco-2 cells expressed NPC1L1, and the uptake of cholesterol in the cells was inhibited by ezetimibe, a specific inhibitor of NPC1L1. Incorporation of SM in the cholesterol micelles inhibited cholesterol uptake dose-dependently; 38% inhibition occurred at an equal mole ratio of SM and cholesterol. The inhibition was further enhanced to 45% by pretreating the cholesterol/SM micelles with recombinant alk-SMase, which hydrolyzed SM in the micelles by 85%, indicating ceramide has stronger inhibitory effects on cholesterol uptake. To confirm this, we further replaced SM in the micelles with ceramide and sphingosine, and found that at equal mole ratio to cholesterol, ceramide exhibited stronger inhibitory effect (50% vs 38%) on cholesterol uptake than SM, whereas sphingosine only had a weak effect at high concentrations. CONCLUSION: Both SM and ceramide inhibit cholesterol uptake, the effect of ceramide being stronger than that of SM. Alk-SMase enhances SM-induced inhibition of cholesterol uptake by generating ceramide in the intestinal lumen.
42.	Frederiksen, Simona Denise, et al. (author) Expression of Pituitary Adenylate Cyclase-activating Peptide, Calcitonin Gene-related Peptide and Headache Targets in the Trigeminal Ganglia of Rats and Humans 2018 In: Neuroscience. - : Elsevier BV. - 0306-4522. ; 393, s. 319-332 Journal article (peer-reviewed)abstract Neurotransmitter and headache target localization in the trigeminal ganglia (TG) might increase the understanding of sites of action, and mechanisms related to headache therapy. The overall aim of the study was to investigate the presence of migraine targets in the TG with particular emphasis on pituitary adenylate cyclase-activating peptide (PACAP) and calcitonin gene-related peptide (CGRP), known to be involved in cranial pain processing, and selected headache targets. Rat- and human TG were processed for immunohistochemistry. PACAP-38, CGRP and the headache targets were expressed in rat and human TG. PACAP receptors were confined to neurons and satellite glial cells (SGCs), however with variability between the receptor subtypes PACAP type I receptor (PAC1) and vasoactive intestinal peptide/PACAP receptors 1/2 (VPAC1/2). 5-Hydroxytryptamine (5-HT) receptors were expressed in neuronal somas in rat and human TG (human TG frequency: 5-HT1D > 5-HT1B/1F). Synaptosomal-associated protein 25 kDa (SNAP25) was primarily expressed in SGCs in humans, and neurons in rats, while synaptic vesicle glycoprotein 2A (SV2-A) was confined to SGCs and some neurons in rats and humans. Occasionally, PACAP-38-positive cells also expressed VPAC1, SNAP25 and SV2-A. VPAC1 was generally detected in SGCs enveloping PACAP-38-positive and -negative neuronal somas. Our study revealed potential sites of actions for anti-headache drugs such as PACAP receptor antagonists, Lasmiditan (5-HT1F agonist) and Botox (blocks exocytosis through SV2-A/SNAP25) in rat and human TG and considerable overlap between species in expression to specific cell types, except for VPAC1 and SNAP25.
43.	Frej Ohlsson, Lena (author) Statistical Implications of the Stability and Growth Pact: Creative accounting and the role of Eurostat 2007 Reports (other academic/artistic)abstract This study covers the relation between the political and accounting implications of the Stability and Growth Pact, which entered into force in 1996. It describes the underlying legal framework and accounting rules and the role of the European Commission and Eurostat in this respect. Additionally, a complete description of the work in the context of the excessive deficit procedure is provided, including the provision of data by Member States, the validation process by Eurostat, the procedures in case of disagreements and the main methodological decisions taken by Eurostat in recent years. Furthermore, the implementation of the statistical framework and rules by the Member States is analysed in detail. Apart from a general chapter on the concept and use of creative accounting, a range of case studies are presented, based on the national accounts framework ESA95. The countries included in the study are Portugal, Italy, France, Germany and Sweden. A separate chapter is devoted to Greece, due to the importance and consequence of the case. The results of the analysis in the case studies show not only the complexity of the statistical framework as such and its implementation, but also the political influence. Finally, as an outcome of the developments in some countries, and in particular in Germany and France in 2003, as well as the Greek tragedy, the SGP was revised. The content and outcome of this revision are also covered.
44.	Gjertsson, Peter, et al. (author) Clinical data do not improve artificial neural network interpretation of myocardial perfusion scintigraphy. 2011 In: Clinical Physiology and Functional Imaging. - 1475-0961. ; 31:3, s. 240-245 Journal article (peer-reviewed)abstract Artificial neural networks interpretation of myocardial perfusion scintigraphy (MPS) has so far been based on image data alone. Physicians reporting MPS often combine image and clinical data. The aim was to evaluate whether neural network interpretation would be improved by adding clinical data to image data. Four hundred and eighteen patients were used for training and 532 patients for testing the neural networks. First, the network was trained with image data alone and thereafter with image data in combination with clinical parameters (age, gender, previous infarction, percutaneous coronary intervention, coronary artery bypass grafting, typical chest pain, present smoker, hypertension, hyperlipidaemia, diabetes, peripheral vascular disease and positive family history). Expert interpretation was used as gold standard. Receiver operating characteristic (ROC) curves were calculated, and the ROC areas for the networks trained with and without clinical data were compared for the diagnosis of myocardial infarction and ischaemia. There was no statistically significant difference in ROC area for the diagnosis of myocardial infarction between the neural network trained with the combination of clinical and image data (95·8%) and with image data alone (95·2%). For the diagnosis of ischaemia, there was no statistically significant difference in ROC area between the neural network trained with the combination of clinical and image data (87·9%) and with image data alone (88·0%). Neural network interpretation of MPS is not improved when clinical data are added to perfusion and functional data. One reason for this could be that experts base their interpretations of MPS mainly on the images and to a lesser degree on clinical data.
45.	Hadad, Ronza, 1984-, et al. (author) First National Genomic Epidemiological Study of Neisseria gonorrhoeae Strains Spreading Across Sweden in 2016 2022 In: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 12 Journal article (peer-reviewed)abstract The increasing transmission and antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global health concern with worrying trends of decreasing susceptibility to also the last-line extended-spectrum cephalosporin (ESC) ceftriaxone. A dramatic increase of reported gonorrhea cases has been observed in Sweden from 2016 and onward. The aim of the present study was to comprehensively investigate the genomic epidemiology of all cultured N. gonorrhoeae isolates in Sweden during 2016, in conjunction with phenotypic AMR and clinical and epidemiological data of patients. In total, 1279 isolates were examined. Etest and whole-genome sequencing (WGS) were performed, and epidemiological data obtained from the Public Health Agency of Sweden. Overall, 51.1%, 1.7%, and 1.3% resistance to ciprofloxacin, cefixime, and azithromycin, respectively, was found. No isolates were resistant to ceftriaxone, however, 9.3% of isolates showed a decreased susceptibility to ceftriaxone and 10.5% to cefixime. In total, 44 penA alleles were found of which six were mosaic (n = 92). Using the typing schemes of MLST, NG-MAST, and NG-STAR; 133, 422, and 280 sequence types, respectively, and 93 NG-STAR clonal complexes were found. The phylogenomic analysis revealed two main lineages (A and B) with lineage A divided into two main sublineages (A1 and A2). Resistance and decreased susceptibility to ESCs and azithromycin and associated AMR determinants, such as mosaic penA and mosaic mtrD, were predominantly found in sublineage A2. Resistance to cefixime and azithromycin was more prevalent among heterosexuals and MSM, respectively, and both were predominantly spread through domestic transmission. Continuous surveillance of the spread and evolution of N. gonorrhoeae, including phenotypic AMR testing and WGS, is essential for enhanced knowledge regarding the dynamic evolution of N. gonorrhoeae and gonorrhea epidemiology.
46.	Hellström-Westas, Lena, et al. (author) Livshotande trombos av navelkärlskateter. "Vanligt" ingrepp kan ge sällsynt komplikation 1994 In: Läkartidningen. - 0023-7205. ; 91:38, s. 3397-3401 Journal article (peer-reviewed)
47.	Hulthén, Lena, 1947, et al. (author) Salt intake in young Swedish men. 2010 In: Public health nutrition. - 1475-2727. ; 13:5, s. 601-5 Journal article (peer-reviewed)abstract OBJECTIVE: To measure dietary salt intake in a Swedish population. DESIGN: A cross-sectional study with measured 24 h urinary excretion of Na and K. Completeness of urine collection was assessed using p-aminobenzoic acid. The subjects were interviewed on their habitual food intake. SETTING: Sahlgrenska University Hospital, Gothenburg, Sweden. SUBJECTS: Eighty-six young men (age 18-20 years), randomly selected from the population of Gothenburg. Seven men were excluded due to incomplete urine collection. RESULTS: The mean excretion of Na and K over 24 h was 198 and 84 mmol, respectively (corresponding to 11.5 g NaCl and 3.3 g K). The mean 24 h excretion in the highest quartile of Na excretion was 297 mmol Na and 105 mmol K, and in the lowest quartile, 100 mmol Na and 68 mmol K. The mean Na:K ratio was 2.3, and respectively 3.2 and 1.8 in the highest and lowest Na excretion quartiles. Calculated energy intake did not differ between the highest and lowest quartiles of Na excretion, but body weight, BMI and the intake of certain foods known to be Na-rich did. CONCLUSIONS: Salt intake in young men was alarming high and even subjects in the lowest quartile of Na excretion did not meet present recommendations to limit salt intake to 5-6 g/d. At this point we can only speculate what the consequences of the high salt intake may be for CVD and stroke later in life. Regulation of the salt content in processed and fast food and in snacks is advocated, to curtail the salt burden on society imposed by the food industry.
48.	Hägg, Daniel, 1974, et al. (author) Oxidized LDL induces a coordinated up-regulation of the glutathione and thioredoxin systems in human macrophages. 2006 In: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 185:2, s. 282-9 Journal article (peer-reviewed)abstract Using DNA microarray analysis, we found that human macrophages respond to oxidized low-density lipoprotein (oxLDL) by activating the antioxidative glutathione and thioredoxin systems. Several genes of the glutathione and thioredoxin systems were expressed at high levels in macrophages when compared to 80 other human tissues and cell types, indicating that these systems may be of particular importance in macrophages. The up-regulation of three genes in these systems, thioredoxin (P < 0.005), thioredoxin reductase 1 (P < 0.001) and glutathione reductase (P < 0.001) was verified with real-time RT-PCR, using human macrophages from 10 healthy donors. To investigate the possible role of these antioxidative systems in the development of atherosclerosis, expression levels in macrophages from 15 subjects with atherosclerosis (12 men, 3 women) and 15 matched controls (12 men, 3 women) were analyzed using DNA microarrays. Two genes in the glutathione system Mn superoxide dismutase (P < 0.05) and catalase (P < 0.05) differed in expression between the groups. We conclude that macrophage uptake of oxidized LDL induces a coordinated up-regulation of genes of the glutathione and thioredoxin systems, suggesting that these systems may participate in the cellular defense against oxidized LDL and possibly modulate the development of atherosclerosis.
49.	Jakobsson, Jenny, et al. (author) Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism. 2006 In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:2, s. 687-93 Journal article (peer-reviewed)abstract CONTEXT: The reproductive endocrinology in Asians and Caucasians is of great interest in view of large differences in prostate cancer rate and sensitivity to pharmacological male contraception. In addition, interpretation of certain antidoping tests is confounded by interethnic variation in androgen disposition. Uridine diphosphoglucuronosyl transferases have a key role in the homeostasis and metabolism of androgens. Recently a deletion polymorphism was detected in the UGT2B17 gene. OBJECTIVE: The objective of the study was to evaluate the contribution of the UGT2B17 deletion polymorphism to the interindividual and interethnic variation of androgen metabolism and excretion. METHODS AND RESULTS: Urine from 122 Swedish and 74 Korean healthy men was analyzed for several androgen glucuronides including testosterone. The distribution of the natural logarithms of urinary testosterone concentrations showed a distinct bimodal pattern in both groups, suggesting a monogenic inheritance. When the UGT2B17 genotypes were compared with urinary testosterone levels, all of the individuals of the UGT2B17 homozygous deletion/deletion genotype had no or negligible amounts of urinary testosterone. The deletion/deletion genotype was seven times more common in the Korean (66.7%) than the Swedish population (9.3%). In addition, the Swedes had significantly higher levels of serum testosterone, compared with the Koreans. CONCLUSIONS: Our results show that the UGT2B17 polymorphism is strongly associated with the bimodal distribution of the testosterone excretion and also with the large differences in testosterone excretion between Koreans and Swedes.
50.	Jiang, Jieying, et al. (author) Association of genetic variations in aromatase gene with serum estrogen and estrogen/testosterone ratio in Chinese elderly men. 2010 In: Clinica chimica acta. - : Elsevier BV. - 1873-3492 .- 0009-8981. ; 411:1-2, s. 53-8 Journal article (peer-reviewed)abstract BACKGROUND: Single nucleotide polymorphism (SNP) rs2470152 of the gene CYP19A1 is associated with serum estradiol (E2) levels in Caucasian men. However, it remains to be verified if rs2470152 is the sole determinant accounting for the association. We determined whether 2 CYP19A1 SNPs tagging different haploblocks (rs2470152 and rs2899470) are associated with sex steroid levels in Chinese men. METHOD: Serum sex steroid level including E2, estrone (E1) and testosterone (T), of 1402 Chinese men aged > or = 65 years were analyzed. Genotyping of the two CYP19A1 SNPs was performed using Tm-shift allele-specific PCR. RESULTS: SNP rs2899470 was significantly associated with serum E2, E1 levels and E2/T ratio (p<0.001). However, SNP rs2470152 was only modestly associated with E2/T ratio (p=0.023). Analysis of haplotype showed a significant association between C-G, T-T haplotype with serum E2/T ratio (p=0.019 and p=1 x 10(-5), respectively). Similarly, E2 levels was also associated the T-T and T-G haplotypes (p=1 x 10(-5)). CONCLUSION: The genetic variation of CYP19A1 was associated with circulating estrogen levels in Chinese elderly men. In addition, it revealed that haplotype of rs2899470 and rs2470152, rather than rs2899470 alone, was a better indicator for the serum E2/T ratio and E2 levels.

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