| 1. |
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| 2. |
- Frigstad, Svein Oskar, et al.
(author)
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The NIMO Scandinavian Study : A Prospective Observational Study of Iron Isomaltoside Treatment in Patients with Iron Deficiency
- 2017
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In: Gastroenterology Research and Practice. - : Hindawi Limited. - 1687-6121 .- 1687-630X. ; 2017
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Journal article (peer-reviewed)abstract
- Background. Intravenous iron allows for efficient and well-tolerated treatment in iron deficiency and is routinely used in diseases of the gastrointestinal tract. Objective. The aims of this study were to determine the probability of relapse of iron deficiency over time and to investigate treatment routine, effectiveness, and safety of iron isomaltoside. Methods. A total of 282 patients treated with iron isomaltoside were observed for two treatments or a minimum of one year. Results. Out of 282 patients, 82 had Crohn's disease and 67 had ulcerative colitis. Another 133 patients had chronic blood loss, malabsorption, or malignancy. Patients who received an iron isomaltoside dose above 1000 mg had a 65% lower probability of needing retreatment compared with those given 1000 mg. A clinically significant treatment response was shown, but in 71/191 (37%) of patients, anaemia was not corrected. The mean dose given was 1100 mg, lower than the calculated total iron need of 1481 mg. Adverse drug reactions were reported in 4% of patients. Conclusion. Iron isomaltoside is effective with a good safety profile, and high doses reduce the need for retreatment over time. Several patients were anaemic after treatment, indicating that doses were inadequate for full iron correction.
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| 3. |
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| 4. |
- Ahlberg, Erik, et al.
(author)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
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In: Dagens nyheter (DN debatt). - 1101-2447.
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Journal article (pop. science, debate, etc.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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| 5. |
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| 6. |
- Alenius, Malin, et al.
(author)
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Gene polymorphism influencing treatment response in psychotic patients in a naturalistic setting
- 2008
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In: Journal of Psychiatric Research. - : Elsevier BV. - 0022-3956 .- 1879-1379. ; 42:11, s. 884-893
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Journal article (peer-reviewed)abstract
- RATIONALE: Many patients with psychotic symptoms respond poorly to treatment. Factors possibly affecting treatment response include the presence of polymorphisms in genes coding for various receptor populations, drug-metabolizing enzymes or transport proteins. OBJECTIVES: To investigate whether genetic polymorphisms could be indicators of treatment response to antipsychotic drugs. The genes of interest were the dopamine D2 receptor gene (DRD2), the serotonin 2A and 2C receptor genes (HTR2A and HTR2C), the P-glycoprotein gene (ABCB1 or MDR1) and the drug-metabolizing cytochrome P450 2D6 gene (CYP2D6). MATERIAL AND METHODS: Data for this naturalistic, cross-sectional study of patients requiring antipsychotic drugs and attending the Psychosis Outpatient Care clinic in Jönköping, Sweden were obtained from patient interviews, blood samples and information from patient files. Blood samples were genotyped for DRD2 Taq1 A, Ins/Del and Ser311Cys, HTR2A T102C, HTR2C Cys23Ser, ABCB1 1236C>T, 2677G>T/A, 3435C>T and genetic variants of CYP2D6. The patients (n=116) were grouped according to the CANSEPT method regarding significant social and clinical needs and significant side effects. RESULTS: Patients on olanzapine homozygous for ABCB1 3435T, had more significant social and clinical needs than others. Patients with one or two DRD2 Taq1 A1 alleles had a greater risk of significant side effects, particularly if they were male, Caucasian, had a schizophrenic or delusional disorder or were taking strong dopamine D2-receptor antagonistic drugs. CONCLUSION: If these results are confirmed, patients carrying the DRD2 Taq1 A1 allele would benefit from using drugs without strong dopamine D2 receptor antagonistic properties.
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| 7. |
- Alenius, Malin, et al.
(author)
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Knowledge and insight in relation to functional remission in patients with long-term psychotic disorders
- 2010
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In: Social Psychiatry and Psychiatric Epidemiology. - : Springer Science and Business Media LLC. - 0933-7954 .- 1433-9285. ; 45:5, s. 523-529
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Journal article (peer-reviewed)abstract
- BACKGROUND: Patients with psychotic symptoms often respond poorly to treatment. Outcomes can be affected by biological, physiological and psychological factors according to the vulnerability-stress model. The patient's coping strategies and beliefs have been correlated with outcomes. OBJECTIVES: To investigate the knowledge and insight in relation to treatment response. METHODS: A naturalistic study was performed using patient interviews and information gathered from patient drug charts. Apart from the rating scales used for classification of treatment response (CANSEPT method), the SPKS knowledge of illness and drugs rating scale was utilized. RESULTS: In the group of patients in functional remission (FR; n = 38), 37% had insight into their illness as compared to 10% among those not in functional remission (non-FR; n = 78; P < 0.01). As much as 23% of the non-FR group had no strategy for responding to warning signs versus 8% in the FR group (P < 0.05). CONCLUSIONS: Better treatment outcomes appear to be associated with better insight into illness, higher knowledge of warning signs and better coping strategies.
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| 8. |
- Alenius, Malin, 1974-
(author)
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Treatment Response in Psychotic Patients in a Naturalistic Setting : Classification, Genes, Drugs, Insight and Social Networks
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Many patients with psychotic symptoms respond poorly to treatment. Various approaches have been made to classify these patients according to treatment response. However, existing classifications have been criticized for various reasons and a new classification system is needed. Further, no satisfactory explanation of the poor treatment response has been apparent. The general aim of this thesis was therefore to develop and validate a new classification method of functional remission in a naturalistic population of patients with psychosis and to utilize this classification to investigate the population from genetic, drug treatment, insight and social network points of view. Data for this cross-sectional study of patients (n=123) attending the Psychosis Outpatient Care clinic in the county of Jönköping, Sweden, were obtained from patient interviews, blood samples and information from patient files. The new classification method CANSEPT, which combines the CAN rating scale (CAN), the UKU side effect rating scale (SE) and the patient’s previous treatment history (PT), showed validity in discriminating the patients and was accepted well by the patients. CANSEPT was used to group the patients in the other studies in this thesis. The results indicated that the gene polymorphism ABCB1 3435T, was related to worse significant social and clinical needs for patients on olanzapine, while the polymorphism DRD2 Taq1 A1 was related to a greater risk of significant side effects; especially if male, or taking strong dopamine D2-receptor antagonistic drugs. Drug treatment factors were also related to treatment response; longer duration of untreated prodromal and early psychosis was seen for patients with current significant social and clinical needs and non-adherence to treatment was associated with worse significant side effects. Worse treatment outcomes also appeared to be associated with smaller social network groups, worse insight into illness, poorer knowledge of warning signs and worse coping strategies. In summary, CANSEPT was shown to be a useful valid, multidimensional tool for classification of treatment response. Gene polymorphisms, duration of untreated illness, non-adherence to treatment, social networks and knowledge should be taken into consideration when investigating inadequate treatment response.
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| 9. |
- Alenius, Malin, et al.
(author)
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Treatmentresponse in psychotic patients classified according to social and clinical needs, drug side effects, and previous treatment; a method to identify functional remission
- 2009
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In: Comprehensive Psychiatry. - : Elsevier BV. - 0010-440X .- 1532-8384. ; 50:5, s. 453-462
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Journal article (peer-reviewed)abstract
- BACKGROUND: Various approaches have been made over the years to classify psychotic patients according to inadequate treatment response, using terms such as treatment resistant or treatment refractory. Existing classifications have been criticized for overestimating positive symptoms; underestimating residual symptoms, negative symptoms, and side effects; or being to open for individual interpretation. The aim of this study was to present and evaluate a new method of classification according to treatment response and, thus, to identify patients in functional remission. METHOD: A naturalistic, cross-sectional study was performed using patient interviews and information from patient files. The new classification method CANSEPT, which combines the Camberwell Assessment of Need rating scale, the Udvalg for Kliniske Undersøgelser side effect rating scale (SE), and the patient's previous treatment history (PT), was used to group the patients according to treatment response. CANSEPT was evaluated by comparison of expected and observed results. RESULTS: In the patient population (n = 123), the patients in functional remission, as defined by CANSEPT, had higher quality of life, fewer hospitalizations, fewer psychotic symptoms, and higher rate of workers than those with the worst treatment outcome. CONCLUSION: In the evaluation, CANSEPT showed validity in discriminating the patients of interest and was well tolerated by the patients. CANSEPT could secure inclusion of correct patients in the clinic or in research.
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| 10. |
- Angelison, Leif, et al.
(author)
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Short and long-term efficacy of adalimumab in ulcerative colitis : a real-life study
- 2020
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:2, s. 154-162
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Journal article (peer-reviewed)abstract
- Objective: Randomized controlled trials have shown the effectiveness of Adalimumab in ulcerative colitis. However, real-life data is scarce. We aimed to assess the effectiveness and predictive factors of effectiveness in a large Swedish cohort. Methods: Retrospective capture of data from local registries at five Swedish IBD centers. Clinical response and remission rates were assessed at three months after starting adalimumab treatment and patients were followed until colectomy or need for another biological. Bio-naive patients were compared to bio experienced patients. Factors associated with short term responses were assessed using logistic regression model. Failure on drug was assessed using a Cox proportional hazards regression model. Results: 118 patients (59 males, 59 females) with median age 34.4 years (IQR 27.0–51.4) were included. Median disease duration was 4.3 years (IQR 2.0–9.0) and follow-up 1.27 years (IQR 0.33–4.1). A clinical corticosteroid-free remission was achieved by 38/118 (32.2%) and response by 91/118 (77%) after three months. CRP >3 mg/l at baseline was predictive of short-term failure to reach corticosteroid-free remission. Factors associated with survival on the drug were male gender, CRP <3 mg/l and absence of primary sclerosing cholangitis. Patients >42 years of age at diagnosis were more likely to respond to adalimumab and remain on treatment compared to patients <20 years. Conclusions: An elevated CRP-level, primary sclerosing cholangitis and female gender were predictors of treatment failure. In contrast older age at diagnosis was a predictor of short-term clinical response and drug survival. Prior infliximab failure, regardless of cause, did not influence the outcome of adalimumab treatment.
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| 11. |
- Befrits, Ragnar, et al.
(author)
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Anemia and iron deficiency in inflammatory bowel disease: an open, prospective, observational study on diagnosis, treatment with ferric carboxymaltose and quality of life
- 2013
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In: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 48:9, s. 1027-1032
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Journal article (peer-reviewed)abstract
- Objective. Iron deficiency and anemia are being increasingly recognized as a complication of inflammatory bowel disease (IBD). The aim of this study was to observe, in a non-interventional way, how Swedish gastroenterologists adhere to guidelines in IBD outpatients treated with intravenous ferric carboxymaltose (FCM), and the result of treatment. Material and methods. Altogether 394 IBD patients (Crohns disease (CD) 60%, ulcerative colitis (UC) 40%) from 14 centers were included. Group A (n = 216) was observed from November 2008 and group B (n = 178) from March 2010. Time of observation ranged from 12 to 29 months. Results. S-Ferritin (mmol/l) and transferrin saturation (T-Sat; %) were recorded at baseline in 62% and 50% in group A. Median values for Hb, ferritin and T-Sat at baseline were 111 g/l, 10 mu mol/l and 10%, respectively, and 134 g/l, 121 mmol/l and 20% after iron treatment (p andlt; 0.001 for all three parameters). Similar results were found in group B. Approximately three-quarters of all patients had only one iron infusion during the study period. Median time to reinfusion was 6 (1-25) months. Only previously described infusion reactions occurred in 27 (7%) patients. Conclusions. Adherence to European guidelines was rather poor and needs to be improved. The effect on iron parameters of intravenous FCM was significant, and resulted in a ferritin level that indicates an effect on the iron stores. The effect was mostly sustained for a year since only one-quarter of the patients were given repeated iron infusions. No unforeseen safety concerns emerged during the observation period.
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| 12. |
- Bengtsson, Jörgen, et al.
(author)
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The influence of age on the distribution of morphine and morphine-3-glucuronide across the blood-brain barrier in sheep
- 2009
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In: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 157:6, s. 1085-1096
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Journal article (peer-reviewed)abstract
- Background and purpose The effect of age on the distribution of morphine and morphine-3-glucuronide (M3G) across the blood-brain barrier (BBB) was studied in a sheep model utilizing intracerebral microdialysis. The effect of neonatal asphyxia on brain drug distribution was also studied. Experimental approach Microdialysis probes were inserted into the cortex, striatum and blood of 11 lambs (127 gestation days) and six ewes. Morphine, 1 mg.kg(-1), was intravenously administered as a 10 min constant infusion. Microdialysis and blood samples were collected for up to 360 min and analysed using liquid chromatography-tandem mass spectrometry. The half-life, clearance, volume of distribution, unbound drug brain : blood distribution ratio (K(p,uu)) and unbound drug volume of distribution in brain (V(u,brain)) were estimated. Key results Morphine K(p,uu) was 1.19 and 1.89 for the sheep and premature lambs, respectively, indicating that active influx into the brain decreases with age. Induced asphyxia did not affect transport of morphine or M3G across the BBB. Morphine V(u,brain) measurements were higher in sheep than in premature lambs. The M3G K(p,uu) values were 0.27 and 0.17 in sheep and premature lambs, indicating a net efflux from the brain in both groups. Conclusions and implications The morphine K(p,uu) was above unity, indicating active transport into the brain; influx was significantly higher in premature lambs than in adult sheep. These results in sheep differ from those in humans, rats, mice and pigs where a net efflux of morphine from the brain is observed.
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| 13. |
- Berglund, Ulla, et al.
(author)
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Landskapsanalys för transportinfrastruktur : en kunskaps- och metodredovisning för utveckling av väg- och järnvägsprojekt i enlighet med den Europeiska Landskapskonventionen
- 2013
-
Reports (other academic/artistic)abstract
- Rapporten ”Landskapsanalys för transportinfrastruktur” har tagits fram inom forskningsprojektet ”Bättre landskapsanalys för transportsektorn” (2010-2013) i samverkan mellan SLU och VTI och handlar om hur man kan arbeta med landskapsanalys (LA) i planläggningsprocessen för väg- ochjärnvägsprojekt. Vi kallar den ett kunskapsunderlag, och dess främsta syfte är att förmedla relevantkunskap från forskarsamhället till Trafikverkets landskapsexperter och därmed stödja Trafikverketsmöjligheter att leverera den landskapsanpassade infrastruktur som regeringen kräver.Fokus för arbetet har varit planläggningsfasen, dvs. när man enligt den sammanhållna vägprocessenkommit så långt att vägen/järnvägen ska prövas i en fysisk miljö.
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| 14. |
- Berglund, Ulla, et al.
(author)
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Landskapsanalys för transportinfrastruktur : en kunskaps- och metodredovisning för utveckling av väg- och järnvägsprojekt i enlighet med den Europeiska Landskapskonventionen
- 2013
-
Reports (other academic/artistic)abstract
- Rapporten ”Landskapsanalys för transportinfrastruktur …” har tagits fram inom forskningsprojektet ”Bättre landskapsanalys för transportsektorn” (2010-2013) i samverkan mellan SLU och VTI och handlar om hur man kan arbeta med landskapsanalys (LA) i planläggningsprocessen för väg- och järnvägsprojekt. Vi kallar den ett kunskapsunderlag, och dess främsta syfte är att förmedla relevant kunskap från forskarsamhället till Trafikverkets landskapsexperter och därmed stödja Trafikverkets möjligheter att leverera den landskapsanpassade infrastruktur som regeringen kräver. Fokus för arbetet har varit planläggningsfasen, dvs. när man enligt den sammanhållna vägprocessen kommit så långt att vägen/järnvägen ska prövas i en fysisk miljö. Den här rapporten tar vid efter det strategiska skede som hanteras i rapporten ”Landskap i långsiktig planering” (Trafikverket 2012). ”Projektet har utförts med utgångspunkt i att LA ska vara en grund på vilken MKBprocessen vilar men också ge viktig bakgrundskunskap för gestaltningsprogrammet (GP). En anledning till projektets tillkomst är de ökade krav på helhetssyn som den Europeiska landskapskonventionen (ECL), som trädde ikraft i Sverige 2011, ställer på projekt som påverkar landskap. Det gäller inte bara landskap som har bedömts som vetenskapligt värdefulla eller har erkänt stora skönhetsvärden, utan också de så kallade vardagslandskap som omger våra städer och samhällen. Det är landskap där många människor bor, arbetar och tillbringar sin fritid och där utbyggnad av transportinfrastruktur får stor påverkan på de värden som är viktiga för brukarna. ELC betonar landskapets betydelse som en del i människors utformande av sin egen identitet såväl som sin gruppidentitet och dessutom allas rätt att vara delaktiga i värderingen av de landskap som berör dem. Europarådet (2008) skriver i sina rekommendationer för implementeringen av ELC att allmänhetens medverkan bör finnas med genom hela planerings- och beslutsprocessen i frågor som rör landskap. För det anför man dels demokratiska skäl, som grundar sig i uppfattningen att alla människor har intressen i landskapet och i den meningen också är sakägare. Dels anförs kunskapsskäl, närmare bestämt att genom allmänhetens medverkan öka medvetenheten om landskapet och dess värden såväl hos allmänheten som hos berörda experter. Arbetet inom projektet har bland annat gått ut på att finna och beskriva metoder som passar att användas i infrastrukturprojekt och som på ett rimligt sätt motsvarar det ELC föreskriver och rekommenderar. Särskilt fokus har satts på frågan om hur den berörda allmänhetens syn på sina landskap ska kunna komplettera och samverka med den expertkunskap som hittills helt dominerat LA inom transportsektorn. Den utgångspunkt som vi valt är den väl beskrivna och prövade metodansatsen ”Landscape Character assessment” (LCA) från Storbritannien, som har ett brett angreppssätt men kan sägas vara mindre välutvecklad när det gäller frågor kring landskapets historia och utveckling. Därför visar vi hur man kan kombinera den med metoden ”Historic Landscape Characterisation” (HLC) och hur man kan arbeta i de båda faserna beskrivnings- respektive bedömningsfas. På svenska benämner vi dessa metoder: landskapskaraktärisering respektive historisk landskapskaraktärisering. Eftersom utvecklingen av allmänhetens medverkan i LA inte är så stark överhuvudtaget har vi också fångat upp och delvis själva utvecklat metoder för dialog med berörda människor, där deras värderingar står i fokus. Det gäller en kartbaserad enkät, kartnålsmetoden, och en variant på gåtursmetoden som vi här kort och gott kallar busstur. Frågan om ljud – inte bara buller – är också ett ämne där LA hittills varit relativt svag. Där har vi bedrivit utvecklingsarbete, som resulterat i en mobilapplikation för karaktärisering av ljudlandskap. I uppdraget för det här projektet har det inte ingått att studera ekologisk landskapsanalys i sig. Däremot har vi redovisat hur vi tänker att den ekologiska analysen, landskapskaraktäriseringen 8 landskapsanalys för transportinfrastruktur och den historiska landskapskaraktäriseringen ska kunna samverka för det eftersträvade helhetsperspektivet. För att nå detta menar vi vidare att metoderna kulturmiljöanalys (DIVE) och strukturanalys också kan ge viktiga bidrag. Vi presenterar kort dessa metoder och deras tänkta roller i LA för väg- och järnvägsprojekt. Landskapskaraktärisering är alltså inte en enhetlig metod utan det vi kallar ansats eller ramverk, som kan anpassas efter projektets art och skala och efter landskapets egenskaper, dess sårbarhet och vilka värden som kan förutses ha betydelse för allmänheten såväl som för vetenskap och andra intressen. I rapporten finns därför information om hur olika specifika metoder kan kombineras och dessutom viss information om hur man kan prioritera i olika fall, vilka underlagsmaterial som kan var lämpliga etc. Kravet på att ge berörd allmänhet såväl som andra sakägare möjlighet att medverka i landskapskaraktäriseringen innebär knappast att specialisterna, landskapsexperterna, får mindre ansvar i processen. Frågan om kommunikation med sakägarna och sammanvägning av olika intressen kräver stor omsorg och skicklighet. I rapporten noterar vi det och ger förslag om hur denna kommunikation ska kunna planeras och utföras på ett effektivt och kvalitativt gott sätt. I många väg- och järnvägsprojekt krävs att en MKB genomförs för att i förväg beskriva vilka konsekevenser för människors hälsa och för miljön som projektet ifråga kan komma att ge upphov till. Vi beskriver i rapporten hur kunskap från den genomförda LA kan användas som underlag för MKB i flera avseenden och vid olika tillfällen i vägplanläggningen. På motsvarande vis vill vi också peka på hur kunskap som tas fram inom LA kan vara till nytta i arbetet med det Gestaltningsprogram (GP) som arbetas fram inom planläggningsprocessen. MKB och GP kan i många fall ses som slutprodukter för en stor del av arbetet med LA. För att LA skall kunna bidra till väg- och järnvägsplanläggning och till MKB och GP behöver krav ställas på dem som har att genomföra LA. Vi har inom ramen för projektet undersökt vad som bör ingå av kvalitets- och kompetenskrav vid upphandling av LA. Detta redovisas i rapporten som ett förslag på vad en upphandling bör innehålla. Avslutningsvis finns i rapporten en översikt och beskrivning i tabellform av exempel på projekt och metoder som vi hänvisat till i texten. Den innehåller uppgifter om sammanhang, genomförande, mm. och länkar eller andra hänvisningar till källor för vidare läsning.
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| 15. |
- Berglund, Ulla, et al.
(author)
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Om landskap och landskapsanalys för väg och järnväg : ett kunskapsunderlag med fokus på begrepp och exempel
- 2011
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Reports (other academic/artistic)abstract
- Landskapets och landskapsanalysens roll i planeringen påverkas av implementeringen av den europeiska landskapskonventionen (ELC) som nyligen inletts i Sverige. Kravet ökar på hantering av landskapsfrågor och på medverkan från allmänheten i till exempel infrastrukturprojekt. Därför behöver olika aktörer få aktuell kunskap om landskap och analys av landskap och så långt möjligt skaffa sig gemensamma referensramar i ämnet. Vägar och järnvägar har en avgörande betydelse för människors möjligheter att uppleva landskap. Samtidigt utgör de ingrepp som kräver kunskap och respekt för de landskap med sina sociala sammanhang som påverkas. Genom ELC har fokus ökat på ”vardagslandskapet”, dvs. de landskap som används och värderas av människor oavsett sådana värden som utomstående experter kan bedöma. Den här rapporten är den första redovisningen i ett forskningsuppdrag från Trafikverket: Bättre landskapsanalys för transportsektorn. Vi kallar den kunskapsunderlag, och den ska vara en källa till bildning och utbildning i frågor som rör landskap och landskapsanalys med fokus på vägoch järnvägsplanering. Arbetet utgår från en bred genomgång av forskning om landskap som fenomen och begrepp, om upplevelse av landskap och om människors möjligheter att påverka landskap och landskapsplanering. Vi har inte begränsat oss till, men särkilt lyft fram sådan kunskap, som har direkt relevans för tranportinfrastruktur och för nordiska förhållanden. Rapporten redogör för ELC: s förhållande till landskapet som sådant och till olika aspekter av landskap. Ett särskilt fokus har lagts på att utreda begreppen landskap och identitet och relatera dem till andra, centrala begrepp som ”plats” och ”karaktär”. Ett avsnitt hanterar allmänhetens medverkan i landskapsanalyser och planering. Vidare diskuteras olika typer av landskapsanalyser och ett antal goda exempel presenteras och gås igenom. Landskapet finns överallt och landskapsbegreppet kan användasi olika skalor, inte bara om stora områden. Det har också relevans likaväl i städer som på landsbygden. Infrastrukturen berör alla slags landskap. Med den här rapporten hoppas vi bidra till ett ökat intresse för landskapet i sin helhet, särskilt hos dem som genom stora projekt sätter avgörande och långvariga avtryck i vår gemensamma livsmiljö
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| 16. |
- Bergqvist, Viktoria, et al.
(author)
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Switching from originator infliximab to the biosimilar CT-P13 in 313 patients with inflammatory bowel disease
- 2018
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In: Therapeutic Advances in Gastroenterology. - : SAGE Publications. - 1756-283X .- 1756-2848. ; 11
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Journal article (peer-reviewed)abstract
- BACKGROUND: As the patents of originator biologics are expiring, biosimilar versions are becoming available for the treatment of inflammatory bowel disease (IBD). However, published switch studies of the first infliximab biosimilar, CT-P13, have delivered ambiguous results that could be interpreted as showing a trend towards inferior effectiveness in Crohn's disease (CD) compared with ulcerative colitis (UC). The aim of this study was to investigate the effectiveness and safety of switching IBD patients from treatment with Remicade to CT-P13.METHODS: In this prospective observational cohort study, all adult IBD patients on Remicade treatment, at four hospitals, were switched to CT-P13. The primary endpoint was change in clinical disease activity at 2, 6, and 12 months after the switch. Secondary endpoints were subgroup analyses of patients with and without concomitant immunomodulators; changes in biomarkers, quality of life, drug trough levels and anti-drug antibodies (ADAbs); and adverse events.RESULTS: A total of 313 IBD patients were switched (195 CD; 118 UC). There were no significant changes in clinical disease activity, quality of life, biomarkers (except a small but significant increase in albumin in CD) including F-calprotectin, drug trough levels, or proportion of patients in remission. Disease worsening rates were 14.0% for CD and 13.8% for UC; and 2.7% developed ADAbs and 2.2% developed serious adverse events.CONCLUSIONS: This is the largest study of switched IBD patients published to date, and it demonstrates that switching from Remicade to CT-P13 may be done with preserved therapeutic effectiveness and safety in both CD and UC.
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| 17. |
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| 18. |
- Björnerås, Caroline, et al.
(author)
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Sediment Records Shed Light on Drivers of Decadal Iron Concentration Increase in a Boreal Lake
- 2022
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In: Journal of Geophysical Research - Biogeosciences. - : American Geophysical Union (AGU). - 2169-8953 .- 2169-8961. ; 127:3
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Journal article (peer-reviewed)abstract
- Increasing iron (Fe) concentrations are found in lakes on a wide geographical scale but exact causes are still debated. The observed trends might result from increased Fe loading from the terrestrial catchment, but also from changes in how Fe distributes between the water column and the sediments. To get a better understanding of the causes we investigated whether there has been any change in the sediment formation of Fe sulfides (FeS) as an Fe sink in response to declining atmospheric sulfur (S) deposition during recent decades. For our study, we chose Lake Bolmen in southern Sweden, a lake for which we confirmed that Fe concentrations in the water column have strongly increased along with water color during 1966-2018. Our investigations showed that Fe accumulation and speciation varied independently of S accumulation patterns in the Lake Bolmen sediment record. Thus, we were not able to relate the positive trend in Fe concentrations to reduced FeS binding in the sediments. Furthermore, we found that Fe accumulation rates increased along with lake water Fe concentrations, indicating that increased catchment loading rather than a change in the distribution between the sediments and the water column has driven the increase in Fe concentrations. The increased loading may be due to land-use change in the form of an extensive expansion of coniferous forest during the past century. Altered forest management practices and increased precipitation may have led to enhanced weathering and erosion of organic soil layers under aging coniferous forest.
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| 19. |
- Björnerås, Caroline, et al.
(author)
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The lake as an iron sink - new insights on the role of iron speciation
- 2021
-
In: Chemical Geology. - : Elsevier BV. - 0009-2541 .- 1872-6836. ; 584
-
Journal article (peer-reviewed)abstract
- The solubility and behavior of iron (Fe) in natural waters is tightly linked to Fe speciation, and Fe speciation likely influences how Fe distributes between the water column and sediments. In this study, the function of a lake as an Fe sink, with focus on the role of Fe speciation, was assessed for Lake Bolmen in southern Sweden. We found that a large fraction of the Fe flowing in to the lake was efficiently lost by sedimentation in the lake basin. Fe in inflowing water was a mix of organically complexed mononuclear Fe, Fe-(oxy)hydroxides and Fe-bearing clays, while surface sediments were composed of Fe-(oxy)hydroxides, Fe-bearing clays, Fe-bearing silicates and Fe sulfides. The absence of organically complexed Fe in the surface sediments indicates that the lake is mainly a sink for minerogenic fractions. Furthermore, while lakes are considered to be sinks of Fe, it has been suggested that this function may be impaired by increasing precipitation and consequently shorter water residence time. In this study there were large within- and between-year variations in precipitation and Fe concentrations. However, rather than smaller Fe losses to the sediments during wet years, within-lake losses tended to be larger due to higher loading of Fe from the catchment. Thus, forecasted increases in precipitation may result in enhanced catchment export and Fe loading to lakes, and subsequently enhanced Fe sequestration in sediments.
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| 20. |
- Bouw, R., et al.
(author)
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Increased blood-brain barrier permeability of morphine in a patient with severe brain lesions as determined by microdialysis
- 2001
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 45, s. 390-
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Journal article (peer-reviewed)abstract
- Intracerebral microdialysis was utilised to obtain information regarding how morphine is transported across the blood-brain barrier (BBB). In a patient with a severe brain injury, we measured simultaneously unbound extracellular fluid (ECF) concentrations of morphine in human brain and in subcutaneous fat tissue, which were compared to morphine levels in arterial blood. This report shows an increase in morphine levels near the trauma site in the brain compared to uninjured brain tissue. The half-life of morphine in uninjured and injured brain tissue of 178 min and 169 min, respectively, were comparable but were longer than in blood (64 min) and adipose tissue (63 min). This indicates that morphine is retained in brain tissue for a longer time than what could be expected from the blood concentration-time profile. These results show the potential of the microdialysis technique in providing new information regarding the pharmacokinetics of drug in the human brain close to the trauma site and in macroscopically intact tissue.
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| 21. |
- Ederoth, Per, et al.
(author)
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Blood-brain barrier transport of morphine in patients with severe brain trauma
- 2004
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In: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 57:4, s. 427-435
-
Journal article (peer-reviewed)abstract
- AIMS: In experimental studies, morphine pharmacokinetics is different in the brain compared with other tissues due to the properties of the blood-brain barrier, including action of efflux pumps. It was hypothesized in this clinical study that active efflux of morphine occurs also in human brain, and that brain injury would alter cerebral morphine pharmacokinetics. METHODS: Patients with traumatic brain injury, equipped with one to three microdialysis catheters in the brain and one in abdominal subcutaneous fat for metabolic monitoring, were studied. The cerebral catheter locations were classified as 'better' and 'worse' brain tissue, referring to the degree of injury. Morphine (10 mg) was infused intravenously over a 10-min period in seven patients in the intensive care setting. Tissue and plasma morphine concentrations were obtained during the subsequent 3-h period with microdialysis and regular blood sampling. RESULTS: The area under the concentration-time curve (AUC) ratio of unbound morphine in brain tissue to plasma was 0.64 (95% confidence interval 0.40, 0.87) in 'better' brain tissue (P < 0.05 vs. the subcutaneous fat/plasma ratio), 0.78 (0.49, 1.07) in 'worse' brain tissue and 1.00 (0.86, 1.13) in subcutaneous fat. The terminal half-life and T(max) were longer in the brain vs. plasma and fat, respectively. The relative recovery for morphine was higher in 'better' than in 'worse' brain tissue. The T(max) value tended to be shorter in 'worse' brain tissue. CONCLUSIONS: The unbound AUC ratio below unity in the 'better' human brain tissue demonstrates an active efflux of morphine across the blood-brain barrier. The 'worse' brain tissue shows a decrease in relative recovery for morphine and in some cases also an increase in permeability for morphine over the blood-brain barrier.
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| 22. |
- Fredh, Daniel, et al.
(author)
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The effect of local land-use changes on floristic diversity during the past 1000 years in southern Sweden
- 2017
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In: Holocene. - : SAGE Publications. - 0959-6836. ; 27:5, s. 694-711
-
Journal article (peer-reviewed)abstract
- The relationship between land-use and floristic diversity in the landscape, for the last millennia, is analysed from two small lakes in southern Sweden. Pollen analysis and the Local Vegetation Estimates (LOVE) model are used to quantify land-cover at local scales with 100-year time windows. Floristic richness is estimated using palynological richness, and we introduce LOVE-based evenness as a proxy for floristic evenness on a local scale based on the LOVE output. The results reveal a dynamic land-use pattern, with agricultural expansion during the 13th century, a partly abandoned landscape around AD 1400, re-establishment during the 15th–17th centuries and a transition from traditional to modern land-use during the 20th century. We suggest that the more heterogeneous landscape and the more dynamic land-use during the 13th–19th centuries were of substantial importance for achieving the high floristic diversity that characterises the traditional landscape. Pollen-based studies of this type are helpful in identifying landscape characteristics and land-use practices that are important for floristic diversity and may therefore guide the development of ecosystem management strategies aiming at mitigating the on-going loss of species seen in the landscape of southern Sweden and many other regions worldwide.
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| 23. |
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| 24. |
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| 25. |
- Hammarlund, Per, et al.
(author)
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Large neural network simulations on multiple hardware platforms
- 1998
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In: Journal of Computational Neuroscience. - 0929-5313 .- 1573-6873. ; 5:4, s. 443-459
-
Journal article (peer-reviewed)abstract
- To efficiently simulate very large networks of interconnected neurons, particular consideration has to be given to the computer architecture being used. This article presents techniques for implementing simulators for large neural networks on a number of different computer architectures. The neuronal simulation task and the computer architectures of interest are first characterized, and the potential bottlenecks are highlighted. Then we describe the experience gained from adapting an existing simulator, sWIM, to two very different architectures-vector computers and multiprocessor workstations. This work lead to the implementation of a new simulation library, SPLIT, designed to allow efficient simulation of large networks on several architectures. Different computer architectures put different demands on the organization of both data structures and computations. Strict separation of such architecture considerations from the neuronal models and other simulation aspects makes it possible to construct both portable and extendible code.
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| 26. |
- Hansson, Anton, et al.
(author)
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Shoreline Displacement, Coastal Environments and Human Subsistence in the Hanö Bay Region during The Mesolithic
- 2019
-
In: Quaternary. - : MDPI AG. - 2571-550X. ; 2:1
-
Journal article (peer-reviewed)abstract
- Southern Scandinavia experienced significant environmental changes during the early Holocene. Shoreline displacement reconstructions and results from several zooarchaeological studies were used to describe the environmental changes and the associated human subsistence and settlement development in the Hanö Bay region of southern Sweden during the Mesolithic. GIS-based palaeogeographic reconstructions building on shoreline displacement records from eastern Skåne and western Blekinge together with a sediment sequence from an infilled coastal lake were used to describe the environmental changes during five key periods. The results show a rapid transformation of the coastal landscape during the Mesolithic. During this time, the investigated coastal settlements indicate a shift towards a more sedentary lifestyle and a subsistence focused on large-scale freshwater fishing. The development of permanent settlements coincided with an extended period of coastline stability and the development of rich coastal environments in a more closed forest vegetation. This study provides a regional synthesis of the shoreline displacement, coastal landscape dynamics and settlement development during the Mesolithic. It also demonstrates a new way of combining zooarchaeological and palaeoecological approaches, which can produce multi-faceted and highly resolved palaeoenvironmental reconstructions in a wide range of settings.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Larsson, Andreas, et al.
(author)
-
Thermal Management System for Particle Sensors Design, Performance and Verification
- 2012
-
In: IEEE Sensors Journal. - : Institute of Electrical and Electronics Engineers (IEEE). - 1530-437X .- 1558-1748. ; 12:6, s. 2299-2305
-
Journal article (peer-reviewed)abstract
- This paper presents the thermal performance of a proposed thermal management device (patented in 2009) intended for a thermophoresis-based soot sensor. The performance was studied for temperatures ranging from 50 to 400 degrees C and for exhaust speeds up to 10 m/s. It also presents the design and basic concepts. The performance study and design development were performed with finite element analysis (FEA). The FEA results were then verified with experiments in a heated wind tunnel. The relative performance of the device was found to increase for higher temperatures and lower wind speeds. The main conclusion drawn from this paper was that it is feasible to cool a sensor surface enough for a thermophoresis-based soot sensor in a diesel exhaust system.
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| 35. |
- Lundquist, Pinelopi, et al.
(author)
-
5-hydroxy-L-[beta-C-11]tryptophan versus alpha-[C-11]methyl-L-tryptophan for positron emission tomography imaging of serotonin synthesis capacity in the rhesus monkey brain
- 2007
-
In: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 27:4, s. 821-830
-
Journal article (peer-reviewed)abstract
- The purpose of this study was to compare two positron emission tomography (PET) tracers that were developed to follow serotonin (5HT) synthesis by performing sequential PET scanning of the same rhesus monkey (n=4) on the same day. α-[11C]Methyl-L-tryptophan ([11C]AMT) and 5-Hydroxy-L-[β-11C]tryptophan ([11C]HTP) are substrates in the first and second enzymatic steps, respectively, in the biosynthesis of 5HT. Regional net accumulation rate constants were derived from kinetic (two-tissue compartment model with irreversible tracer trapping) and graphic (Patlak) analyses, using the arterial plasma concentrations as input. The kinetic data analysis showed that the rate constant for the transfer of [11C]HTP into the brain (K1) was higher than that for [11C]AMT in the striatum and thalamus but was similar in other brain regions. The rate constant for tracer trapping (k3) was also higher for [11C]HTP than for [11C]AMT in the striatum (0.046±0.024 versus 0.019±0.006 min-1) and thalamus (0.039±0.013 versus 0.016±0.007 min-1). In agreement with previously reported regional HTP accumulation rates, the net accumulation rate constant (Kacc) for [11C]HTP was also higher in these regions than in other brain regions; this is in contrast to the uniform distribution of [11C]AMT Kacc values. This suggests that the regional net accumulation rates obtained with these two PET tracers will be of different magnitude, which might be related to the activity of each targeted enzyme.
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| 36. |
- Lundquist, Pinelopi, et al.
(author)
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Effect on [11C]DASB binding after tranylcypromine-induced increase in serotonin concentration : positron emission tomography studies in monkeys and rats
- 2007
-
In: Synapse. - : Wiley. - 0887-4476 .- 1098-2396. ; 61:6, s. 440-449
-
Journal article (peer-reviewed)abstract
- Several research groups have demonstrated that under specific conditions, in vivo neuroreceptor binding techniques can be used to measure acute changes in the concentrations of endogenous transmitters in the vicinity of neuroreceptors. The aim of this study was to investigate whether [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile ([11C]DASB) binding to the plasma membrane serotonin transporter (SERT) in the rhesus monkey and rat brain decreased after a pharmacologically-induced increase in the interstitial serotonin (5HT) concentration. Three rhesus monkeys were given repeated single boluses of [11C]DASB in sequential positron emission tomography (PET) experiments. Rats were given the tracer as a bolus dose plus a constant infusion. In vivo binding in both models was studied before and after presumably having increased interstitial 5HT concentrations using tranylcypromine (TCP), which inhibits the enzyme (monoamine oxidase, MAO), that degrades 5HT. The rat brain tissue was analyzed using high-performance liquid chromatography (HPLC) to determine the proportion of the PET signal comprising unchanged [11C]DASB. The binding of [11C]DASB in the thalamus decreased in both rhesus monkeys and rats after TCP administration. The possibility of using [11C]DASB as a tool for monitoring changes in endogenous serotonin concentrations merits further investigation.
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| 37. |
- Lundquist, Pinelopi, 1975-
(author)
-
Imaging and Quantification of Brain Serotonergic Activity using PET
- 2006
-
Doctoral thesis (other academic/artistic)abstract
- This thesis investigates the potential of using positron emission tomography (PET) to study the biosynthesis and release of serotonin (5HT) at the brain serotonergic neuron. As PET requires probe compounds with specific attributes to enable imaging and quantification of biological processes, emphasis was placed on the evaluation of these attributes. The experiments established that the 5HT transporter radioligand [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile, [11C]DASB, is suitable for imaging and quantification of transporters in rats and rhesus monkeys. In addition, the binding of [11C]DASB in brain tissue is decreased when 5HT concentrations are increased by tranylcypromine administration. The sensitivity of [11C]DASB binding, under these experimental conditions, to increased endogenous 5HT concentrations demonstrates the potential of in vivo monitoring of 5HT release in rat and monkey models. The irreversible binding of 5-hydroxy-L-[β-11C]tryptophan, [11C]HTP, in the monkey brain was lower in the presence of NSD1015, which was used to inhibit the decarboxylase step in 5HT synthesis. [11C]HTP seems thus to have potential for tracking changes in the activity of this biosynthesis enzyme. In contrast, the accumulation of [11C]HTP was unaffected by clorgyline, which was used to inhibit metabolism of the probe in the brain. This appears to indicate that elimination of the main metabolite from the brain could be negligible and thus will not alter [11C]HTP quantification. The extent and distribution of the irreversible binding of a substrate for the first enzyme in 5HT formation, α-[11C]methyl-L-tryptophan, [11C]AMT, was different from those for [11C]HTP. This suggests that the two studied probe compounds provide estimates related to the enzyme activity of different steps in the 5HT biosynthesis pathway. A reference tissue version of the Patlak method for the analysis of data obtained by PET was also developed. This approach takes into account irreversible binding in the reference region and appears, therefore, to yield more reliable parameter estimates than the conventional reference Patlak analysis. The method is recommended for parameter estimation of [11C]HTP data when no metabolite-corrected plasma curve is available. Knowledge of altered 5HT synthesis and release in disease states and the consequences for effective pharmacotherapy can improve our knowledge of the aetiology of certain psychiatric and neurological diseases and enhance our ability to design more effective drugs.
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| 38. |
- Lundquist, Pinelopi, et al.
(author)
-
Validation studies on the 5-hydroxy-L-[beta-11C]-tryptophan/PET method for probing the decarboxylase step in serotonin synthesis
- 2006
-
In: Synapse. - : Wiley. - 0887-4476 .- 1098-2396. ; 59:8, s. 521-531
-
Journal article (peer-reviewed)abstract
- The two-tissue compartment model, including irreversible trapping in the second compartment (2TCM) is used to describe the kinetics of 5-Hydroxy-L-[beta-(11)C]-tryptophan ([(11)C]HTP), a radioligand used in positron emission tomography (PET) for probing the second enzymatic step in the biosynthesis of serotonin. In this study, we examined the capacity of the model to track pharmacological changes in this biological process. We also investigated the potential loss of [(11)C]HTP-derived radioactivity during a PET study, since loss should be negligible not to alter quantification. Six rhesus monkeys were investigated using bolus [(11)C]HTP/PET methodology before and after pharmacological intervention. The second enzymatic step in serotonin synthesis was inhibited using the aromatic L-amino acid decarboxylase inhibitor NSD1015 (10 mg/kg). The extent of [(11)C]-derived radioactivity loss from the brain was studied by inhibition of the enzyme responsible for formation of the tissue metabolite, monoamine oxidase A, using clorgyline (2 mg/kg). After NSD1015, the uptake of [(11)C]HTP-derived radioactivity was increased in all the investigated brain regions, while the parameter used to reflect decarboxylase activity, the net accumulation rate constant (K(acc)), was decreased by 37% in the striatum, compared with baseline. Pretreatment with clorgyline did not change the brain uptake of [(11)C]HTP-derived radioactivity or K(acc). This study demonstrates that the 2TCM for [(11)C]HTP/PET is able to detect changes occurring during alteration of the biological process (i.e., the conversion of HTP to serotonin). Elimination of the radiotracer metabolite [(11)C]HIAA from the brain may be considered negligible if the PET study is limited to 60 min.
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| 39. |
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| 40. |
- Luptáková, Dominika, et al.
(author)
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Neuropharmacokinetic visualization of regional and subregional unbound antipsychotic drug transport across the blood-brain barrier.
- 2021
-
In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26, s. 7732-7745
-
Journal article (peer-reviewed)abstract
- Comprehensive determination of the extent of drug transport across the region-specific blood-brain barrier (BBB) is a major challenge in preclinical studies. Multiple approaches are needed to determine the regional free (unbound) drug concentration at which a drug engages with its therapeutic target. We present an approach that merges in vivo and in vitro neuropharmacokinetic investigations with mass spectrometry imaging to quantify and visualize both the extent of unbound drug BBB transport and the post-BBB cerebral distribution of drugs at regional and subregional levels. Direct imaging of the antipsychotic drugs risperidone, clozapine, and olanzapine using this approach enabled differentiation of regional and subregional BBB transport characteristics at 20-µm resolution in small brain regions, which could not be achieved by other means. Our approach allows investigation of heterogeneity in BBB transport and presents new possibilities for molecular psychiatrists by facilitating interpretation of regional target-site exposure results and decision-making.
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| 41. |
- Löndahl, Magnus, et al.
(author)
-
Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes.
- 2010
-
In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 33:5, s. 998-1003
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Chronic diabetic foot ulcers are a source of major concern for both patients and health care systems. The aim of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) in the management of chronic diabetic foot ulcers. RESEARCH DESIGN AND METHODS: The Hyperbaric Oxygen Therapy in Diabetics with Chronic Foot Ulcers (HODFU) study was a randomized, single-center, double-blinded, placebo-controlled clinical trial. The outcomes for the group receiving HBOT were compared with those of the group receiving treatment with hyperbaric air. Treatments were given in a multi-place hyperbaric chamber for 85-min daily (session duration 95 min), five days a week for eight weeks (40 treatment sessions). The study was performed in an ambulatory setting. RESULTS: Ninety-four patients with Wagner grade 2, 3, or 4 ulcers, which had been present for >3 months, were studied. In the intention-to-treat analysis, complete healing of the index ulcer was achieved in 37 patients at 1-year of follow-up: 25/48 (52%) in the HBOT group and 12/42 (29%) in the placebo group (P = 0.03). In a sub-analysis of those patients completing >35 HBOT sessions, healing of the index ulcer occurred in 23/38 (61%) in the HBOT group and 10/37 (27%) in the placebo group (P = 0.009). The frequency of adverse events was low. CONCLUSIONS: The HODFU study showed that adjunctive treatment with HBOT facilitates healing of chronic foot ulcers in selected patients with diabetes.
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| 42. |
- Löndahl, Magnus, et al.
(author)
-
Relationship between ulcer healing after hyperbaric oxygen therapy and transcutaneous oximetry, toe blood pressure and ankle-brachial index in patients with diabetes and chronic foot ulcers.
- 2011
-
In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 54, s. 65-68
-
Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: The randomised, double-blind, placebo-controlled Hyperbaric Oxygen Therapy (HBOT) in Diabetic Patients with Chronic Foot Ulcers (HODFU) study showed beneficial effect of HBOT. As this treatment is expensive and time-consuming, being able to select patients for therapy would be very useful. The aim of this study was to evaluate whether circulatory variables could help in predicting outcome of HBOT. METHODS: All HODFU study participants who completed therapy, predefined as receiving at least 36 out of 40 scheduled HBOT/placebo sessions, were included in this study (n = 75). Baseline transcutaneous oximetry (TcPO(2)), toe blood pressure (TBP) and ankle-brachial index (ABI) were measured. Ulcer healing rate was registered at the 9-month follow-up visit. An ulcer was considered healed when it was completely epithelialised and remained so at the 12-month follow-up. RESULTS: In the HBOT group TcPO(2) were significantly lower for patients whose ulcer did not heal as compared with those whose ulcers healed. A significantly increased healing frequency was seen with increasing TcPO(2) levels in the HBOT group (TcPO(2)/healing rate: <25 mmHg/0%; 26-50 mmHg/50%; 51-75 mmHg/73%; and >75 mmHg/100%). No statistically significant relation between the level of TBP or ABI and healing frequency was seen. CONCLUSIONS/INTERPRETATION: Our results indicate that TcPO(2) in contrast to ABI and TBP correlates to ulcer healing following HBOT. We suggest HBOT as a feasible adjunctive treatment modality in diabetic patients with chronic non-healing foot ulcers when basal TcPO(2) at the dorsum of the foot is above 25 mmHg. TRIAL REGISTRATION: NCT00953186 FUNDING: Mrs Thelma Zoegas Foundation and Faculty of Medicine, Lund University.
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| 43. |
- Marklund, Matti, et al.
(author)
-
Chain length of dietary alkylresorcinols affects their in vivo elimination kinetics in rats
- 2013
-
In: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 143:10, s. 1573-1578
-
Journal article (peer-reviewed)abstract
- Two phenolic acids, 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)- propanoic acid (DHPPA), are the major metabolites of cereal alkylresorcinols (ARs). Like their precursors, AR metabolites have been suggested as biomarkers for intake of whole-grain wheat and rye and as such could aid the understanding of diet-disease associations. This study estimated and compared pharmacokinetic parameters of ARs and their metabolites in rats and investigated differences in metabolite formation after ingestion of different AR homologs. Rats were i.v. infused for 30 min with 2, 12, or 23 μmol/kg DHBA or DHPPA or orally given the same amounts of the AR homologs, C17:0 and C25:0. Repeated plasma samples, obtained from rats for 6 h (i.v.) or 36 h (oral), were simultaneously analyzed for ARs and their metabolites by GC-mass spectrometry. Pharmacokinetic parameters were estimated by population-based compartmental modeling and noncompartmental calculation. A 1-compartment model best described C25:0 pharmacokinetics, whereas C17:0 and AR metabolites best fitted 2-compartment models. Combined models for simultaneous prediction of AR and metabolite concentration were more complex, with less reliable estimates of pharmacokinetic parameters. Although the AUC of C17:0 was lower than that of C25:0 (P < 0.05), the total amount and composition of AR metabolites did not differ between rats given C17:0 or C25:0. The elimination half-life of ARs and their metabolites increased with length of the side chain (P-trend < 0.001) and ranged from 1.2 h (DHBA) to 8.8 h (C25:0). The formation of AR metabolites was slower than their elimination, indicating that the rate of AR metabolism and not excretion of DHBA and DHPPA determines their plasma concentrations in rats.
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| 44. |
- Möller, Per, et al.
(author)
-
Deglaciation history and subsequent lake dynamics in the Siljan region, south-central Sweden, based on new LiDAR evidence and sediment records
- 2022
-
In: Earth Surface Processes and Landforms. - : Wiley. - 0197-9337 .- 1096-9837. ; 47, s. 3515-3545
-
Journal article (peer-reviewed)abstract
- The Siljan region hosts Europe´s largest impact structure. The high-relief landscape, with a central granite dome bordered by lake basins, contains an array of glacial and shore-level landforms. We investigated its deglaciation history by mapping and analysing landforms on high resolution LiDAR-based Digital Surface Models coupled with well-dated sediment successions from peat and lake sediment cores. The granite dome and bordering areas are characterized by streamlined terrain and ribbed moraine with a streamlined overprint. These suggest an ice-flow direction from NNW with wet-based thermal conditions prior to deglaciation. During its retreat, the ice sheet was split into thinner plateau ice and thicker basin ice. Sets of low-gradient glaciofluvial erosion channels suggest intense ice-lateral meltwater drainage across gradually ice-freed slopes, while 'down-the-slope' erosion channels and eskers show meltwater drainage from stagnated plateau ice. Thick basin ice receded with a subaqueous margin across the deep Siljan–Orsasjön Basin c. 10,700–10,500 cal. BP. During ice recession the ingression of the Baltic Ancylus Lake led to diachronous formation of highest shoreline marks, from c. 207 m in the south to c. 220 m a.s.l. in the north. Differential uplift resulted in shallowing of the water body, which led to the isolation of the Siljan–Orsasjön Basin from the Baltic Basin at c. 9800 cal. BP. The post-isolation water body – the ‘Ancient Lake Siljan' – was drained through the ancient Åkerö Channel with a water level at 168–169 m a.s.l. during c. 1000 years. A later rerouting of the outlet to the present course was initiated at c. 8800 cal. BP, which led to a lake-level lowering of 6–7 m to today’s level of Lake Siljan (c. 162 m a.s.l.). This study shows the strength of an integrated methodological approach for deciphering the evolution of a complex landscape, combining highly resolved geomorphological analysis with well-dated sediment successions.
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| 45. |
- Möller, Per, et al.
(author)
-
Deglaciation history and subsequent lake dynamics in the Siljan region, south-central Sweden - LiDAR evidence and sediment records
- 2024
-
Conference paper (other academic/artistic)abstract
- The Siljan region hosts Europe´s largest impact structure. The high-relief landscape, with a central granite dome bordered by lake basins, contains an array of glacial and shore-level landforms. We investigated its deglaciation history by mapping and analysing landforms on high resolution LiDAR-based Digital Surface Models coupled with well-dated sediment successions from peat and lake sediment cores. The granite dome and bordering areas are characterized by streamlined terrain and ribbed moraine with a streamlined overprint. These suggest an ice-flow direction from NNW with wet-based thermal conditions prior to deglaciation. During its retreat, the ice sheet was split into thinner plateau ice and thicker basin ice. Sets of low-gradient glaciofluvial erosion channels suggest intense ice-lateral meltwater drainage across gradually ice-freed slopes, while 'down-the-slope' erosion channels and eskers show meltwater drainage from stagnated plateau ice. Thick basin ice receded with a subaqueous margin across the deep Siljan–Orsasjön Basin c. 10,700–10,500 cal. BP. During ice recession the ingression of the Baltic Ancylus Lake led to diachronous formation of highest shoreline marks, from 207 m in the south to 220 m a.s.l. in the north. Differential uplift resulted in shallowing of the water body, which led to the isolation of the Siljan¬–Orsasjön Basin from the Baltic Basin at c. 9800 cal. BP. The post-isolation water body – the ‘Ancient Lake Siljan' – was drained through the ancient Åkerö Channel with a water level at 168–169 m a.s.l. during c. 1000 years. A later rerouting of the outlet to the present course was initiated at c. 8800 cal. BP, which led to a lake-level lowering of 6–7 m to today’s level of Lake Siljan (162 m a.s.l.). This study shows the strength of an integrated methodological approach for deciphering the evolution of a complex landscape, combining highly resolved geomorphological analysis with well-dated sediment successions.
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| 46. |
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| 47. |
- Olsson Gisleskog, Per, et al.
(author)
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The pharmacokinetic modelling of GI198745 (dutasteride), a compound with parallel linear and nonlinear elimination
- 1999
-
In: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 47:1, s. 53-58
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Journal article (peer-reviewed)abstract
- AIMS To characterize the pharmacokinetics of the dual 5alpha-reductase inhibitor GI198745 (dutasteride) to allow for more accurate predictions of GI198745 concentrations after different dosing schedules. METHODS In this randomized, single-blind, parallel group study, 32 healthy male volunteers received single oral doses of GI198745 ranging from 0.01 to 40 mg. Data were analysed by nonlinear mixed effects modelling using NONMEM where both linear and nonlinear pharmacokinetic models were examined. RESULTS The time course of GI198745 serum concentrations indicated concentration dependent elimination, with the apparent half-life increasing with dose. Data were best described by a two-compartment model with first order absorption and parallel linear and nonlinear elimination pathways. Drug absorption was rapid, and was followed by a short distribution phase. A high volume of distribution (511 l) and a low linear clearance (0.58 l h(-1)) combined to give a half-life of up to 5 (1-7) weeks at high concentrations. As concentrations declined towards Km (0.96 ng ml(-1)), the proportion eliminated by the relatively rapid saturable elimination pathway, with a maximum clearance of 6.2 l h(-1), increased and the half-life reduced to about 3 days. The estimated inter individual variability for the linear clearance was high (CV = 70%). CONCLUSIONS G1198745 pharmacokinetics are well described by a pharmacokinetic model with parallel linear and nonlinear elimination. Simulations using this model show that at daily doses of 0.1 mg the steady state drug concentrations, and the rate at which these are achieved, are mainly influenced by the nonlinear pathway, while at daily doses above 1 mg they are almost entirely influenced by the linear pathway.
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| 48. |
- Philipsen, Mai H., et al.
(author)
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Distinct Cholesterol Localization in Glioblastoma Multiforme Revealed by Mass Spectrometry Imaging
- 2023
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In: ACS Chemical Neuroscience. - 1948-7193. ; 14:9, s. 1602-1609
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Journal article (peer-reviewed)abstract
- Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor in adults and is highly resistant to chemo- and radiotherapies. GBM has been associated with alterations in lipid contents, but lipid metabolism reprogramming in tumor cells is not fully elucidated. One of the key hurdles is to localize the lipid species that are correlated with tumor growth and invasion. A better understanding of the localization of abnormal lipid metabolism and its vulnerabilities may open up to novel therapeutic approaches. Here, we use time-of-flight secondary ion mass spectrometry (ToF-SIMS) to spatially probe the lipid composition in a GBM biopsy from two regions with different histopathologies: one region with most cells of uniform size and shape, the homogeneous part, and the other with cells showing a great variation in size and shape, the heterogeneous part. Our results reveal elevated levels of cholesterol, diacylglycerols, and some phosphatidylethanolamine in the homogeneous part, while the heterogeneous part was dominated by a variety of fatty acids, phosphatidylcholine, and phosphatidylinositol species. We also observed a high expression of cholesterol in the homogeneous tumor region to be associated with large cells but not with macrophages. Our findings suggest that ToF-SIMS can distinguish in lipid distribution between parts within a human GBM tumor, which can be linked to different molecular mechanisms.
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| 49. |
- Philipsen, Mai H., et al.
(author)
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Mapping the chemistry of hair strands by mass spectrometry imaging - A Review
- 2021
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In: Molecules. - : MDPI AG. - 1420-3049 .- 1420-3049. ; 26:24
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Journal article (peer-reviewed)abstract
- Hair can record chemical information reflecting our living conditions, and, therefore, strands of hair have become a potent analytical target within the biological and forensic sciences. While early efforts focused on analyzing complete hair strands in bulk, high spatial resolution mass spectrometry imaging (MSI) has recently come to the forefront of chemical hair-strand analysis. MSI techniques offer a localized analysis, requiring fewer de-contamination procedures per default and making it possible to map the distribution of analytes on and within individual hair strands. Applying the techniques to hair samples has proven particularly useful in investigations quantifying the exposure to, and uptake of, toxins or drugs. Overall, MSI, combined with optimized sample preparation protocols, has improved precision and accuracy for identifying several elemental and molecular species in single strands of hair. Here, we review different sample preparation protocols and use cases with a view to make the methodology more accessible to researchers outside of the field of forensic science. We conclude that-although some challenges remain, including contamination issues and matrix effects-MSI offers unique opportunities for obtaining highly resolved spatial information of several compounds simultaneously across hair surfaces.
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| 50. |
- Rodrigues Silva, Vagner Ramon, 1985, et al.
(author)
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Somatic ablation of IKKβ in liver and leukocytes is not tolerated in obese mice but hepatic IKKβ deletion improves fatty liver and insulin sensitivity.
- 2022
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In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - 1530-6860. ; 36:9
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Journal article (peer-reviewed)abstract
- The kinase IKKβ controls pro-inflammatory gene expression, and its activity in the liver and leukocytes was shown to drive metabolic inflammation and insulin resistance in obesity. However, it was also proposed that liver IKKβ signaling protects obese mice from insulin resistance and endoplasmic reticulum (ER) stress by increasing XBP1s protein stability. Furthermore, mice lacking IKKβ in leukocytes display increased lethality to lipopolysaccharides. This study aims at improving our understanding of the role of IKKβ signaling in obesity. We induced IKKβ deletion in hematopoietic cells and liver of obese mice by Cre-LoxP recombination, using an INF-inducible system, or a liver-specific IKKβ deletion in obese mice by adenovirus delivery of the Cre recombinase. The histopathological, immune, and metabolic phenotype of the mice was characterized. IKKβ deletion in the liver and hematopoietic cells was not tolerated in mice with established obesity exposed to the TLR3 agonist poly(I:C) and exacerbated liver damage and ER-stress despite elevated XBP1s. By contrast, liver-specific ablation of IKKβ in obese mice reduced steatosis and improved insulin sensitivity in association with increased XBP1s protein abundance and reduced expression of de-novo lipogenesis genes. We conclude that IKKβ blockage in liver and leukocytes is not tolerated in obese mice exposed to TLR3 agonists. However, selective hepatic IKKβ ablation improves fatty liver and insulin sensitivity in association with increased XBP1s protein abundance and reduced expression of lipogenic genes.
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