| 1. |
- Andersson, Magnus, et al.
(författare)
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Fiskbestånd och miljö i hav och sötvatten : Resurs- och miljööversikt 2012
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Detta är den nionde utgåvan av den samlade översikten över fisk- och kräftdjursbeståndens status i våra vatten. Kunskap om fiskbestånden och miljön är en förutsättning för att utnyttjandet av fiskresurserna skall bli bärkraftigt. För svenska vattenområden beskrivs miljöutvecklingen i ett ekosystemsperspektiv, dels för att tydliggöra fiskens ekologiska roll och beskriva yttre miljöfaktorer som påverkar fiskbestånden, dels för att belysa fiskets effekter på miljön.Fiskbestånd och miljö i hav och sötvatten är utarbetad av Sveriges lantbruksuniversitet (SLU), Institutionen för akvatiska resurser (SLU Aqua), på uppdrag av Havs- och vattenmyndigheten. Rapporten sammanfattar utveckling och beståndsstatus för de kommersiellt viktigaste fisk- och kräftdjursarterna i våra vatten. Bedömningar och förvaltningsråd är baserade på Internationella Havsforskningsrådets (ICES) rådgivning, SLU Aquas nationella och regionala provfiskedata, samt yrkesfiskets rapportering.
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| 2. |
- Stenseke, Marie, et al.
(författare)
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Kris i naturen – vår existens har blivit sårbar
- 2019
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Ingår i: Svenska Dagbladet, Stockholm. - 1101-2412.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Fler arter än någonsin i mänsklighetens historia hotas av utrotning och den biologiska mångfalden lokalt har förändrats kraftigt i en stor del av världens ekosystem. Grundläggande förändringar behövs både i samhället och för individer, för att bromsa den negativa trenden, skriver en rad debattörer.
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| 3. |
- Andersson, Irene, 1978, et al.
(författare)
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Endothelial dysfunction in growth hormone transgenic mice
- 2006
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 110:2, s. 217-25
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Tidskriftsartikel (refereegranskat)abstract
- Acromegaly [overproduction of GH (growth hormone)] is associated with cardiovascular disease. Transgenic mice overexpressing bGH (bovine GH) develop hypertension and hypercholesterolaemia and could be a model for cardiovascular disease in acromegaly. The aims of the present study were to investigate the effects of excess GH on vascular function and to test whether oxidative stress affects endothelial function in bGH transgenic mice. We studied the ACh (acetylcholine)-induced relaxation response in aortic and carotid rings of young (9-11 weeks) and aged (22-24 weeks) female bGH transgenic mice and littermate control mice, without and with the addition of a free radical scavenger {MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride]}. We also measured mRNA levels of eNOS (endothelial nitric oxide synthase) and EC-SOD (extracellular superoxide dismutase). Intracellular superoxide anion production in the vascular wall was estimated using a dihydroethidium probe. Carotid arteries from bGH transgenic mice had an impaired ACh-induced relaxation response (young, 46 +/- 7% compared with 69 +/- 8%; aged, 52 +/- 5% compared with 80 +/- 3%; P < 0.05), whereas endothelial function in aorta was intact in young but impaired in aged bGH transgenic mice. Endothelial dysfunction was corrected by addition of MnTBAP in carotid arteries from young mice and in aortas from aged mice; however, MnTBAP did not correct endothelial dysfunction in carotid arteries from aged bGH transgenic mice. There was no difference in intracellular superoxide anion production between bGH transgenic mice and control mice, whereas mRNA expression of EC-SOD and eNOS was increased in aortas from young bGH transgenic mice compared with control mice (P < 0.05). We interpret these data to suggest that bGH overexpression is associated with a time- and vessel-specific deterioration in endothelial function, initially caused by increased oxidative stress and later by other alterations in vascular function.
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| 4. |
- Antonescu, Irina E., et al.
(författare)
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Acamprosate Is a Substrate of the Human Organic Anion Transporter (OAT) 1 without OAT3 Inhibitory Properties : Implications for Renal Acamprosate Secretion and Drug-Drug Interactions
- 2020
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Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Acamprosate is an anionic drug substance widely used in treating symptoms of alcohol withdrawal. It was recently shown that oral acamprosate absorption is likely due to paracellular transport. In contrast, little is known about the eliminating mechanism clearing acamprosate from the blood in the kidneys, despite the fact that studies have shown renal secretion of acamprosate. The hypothesis of the present study was therefore that renal organic anion transporters (OATs) facilitate the renal excretion of acamprosate in humans. The aim of the present study was to establish and apply OAT1 (gene product of SLC22A6) and OAT3 (gene product of SLC22A8) expressing cell lines to investigate whether acamprosate is a substrate or inhibitor of OAT1 and/or OAT3. The studies were performed in HEK293-Flp-In cells stably transfected with SLC22A6 or SLC22A8. Protein and functional data showed that the established cell lines are useful for studying OAT1- and OAT3-mediated transport in bi-laboratory studies. Acamprosate inhibited OAT1-mediated p-aminohippuric acid (PAH) uptake but did not inhibit substrate uptake via OAT3 expressing cells, neither when applied concomitantly nor after a 3 h preincubation with acamprosate. The uptake of PAH via OAT1 was inhibited in a competitive manner by acamprosate and cellular uptake studies showed that acamprosate is a substrate for OAT1 with a K-m-value of approximately 700 mu M. Probenecid inhibited OAT1-mediated acamprosate uptake with a K-i-value of approximately 13 mu M, which may translate into an estimated clinically significant DDI index. In conclusion, acamprosate was identified as a substrate of OAT1 but not OAT3.
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| 5. |
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| 6. |
- Bergström, Petra, et al.
(författare)
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Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons
- 2021
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Ingår i: Viruses-Basel. - : MDPI AG. - 1999-4915. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus 1 (HSV-1) and 2 (HSV-2) can infect the central nervous system (CNS) with dire consequences; in children and adults, HSV-1 may cause focal encephalitis, while HSV-2 causes meningitis. In neonates, both viruses can cause severe, disseminated CNS infections with high mortality rates. Here, we differentiated human induced pluripotent stem cells (iPSCs) towards cortical neurons for infection with clinical CNS strains of HSV-1 or HSV-2. Progenies from both viruses were produced at equal quantities in iPSCs, neuroprogenitors and cortical neurons. HSV-1 and HSV-2 decreased viability of neuroprogenitors by 36.0% and 57.6% (p < 0.0001), respectively, 48 h post-infection, while cortical neurons were resilient to infection by both viruses. However, in these functional neurons, both HSV-1 and HSV-2 decreased gene expression of two markers of synaptic activity, CAMK2B and ARC, and affected synaptic activity negatively in multielectrode array experiments. However, unaltered secretion levels of the neurodegeneration markers tau and NfL suggested intact axonal integrity. Viral replication of both viruses was found after six days, coinciding with 6-fold and 22-fold increase in gene expression of cellular RNA polymerase II by HSV-1 and HSV-2, respectively. Our results suggest a resilience of human cortical neurons relative to the replication of HSV-1 and HSV-2.
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| 7. |
- Bergström, Ulf, et al.
(författare)
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Long-term effects of no-take zones in Swedish waters
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Marine protected areas (MPAs) are increasingly established worldwide to protect and restore degraded ecosystems. However, the level of protection varies among MPAs and has been found to affect the outcome of the closure. In no-take zones (NTZs), no fishing or extraction of marine organisms is allowed. The EU Commission recently committed to protect 30% of European waters by 2030 through the updated Biodiversity Strategy. Importantly, one third of these 30% should be of strict protection. Exactly what is meant by strict protection is not entirely clear, but fishing would likely have to be fully or largely prohibited in these areas. This new target for strictly protected areas highlights the need to evaluate the ecological effects of NTZs, particularly in regions like northern Europe where such evaluations are scarce. The Swedish NTZs made up approximately two thirds of the total areal extent of NTZs in Europe a decade ago. Given that these areas have been closed for at least 10 years and can provide insights into long-term effects of NTZs on fish and ecosystems, they are of broad interest in light of the new 10% strict protection by 2030 commitment by EU member states.In total, eight NTZs in Swedish coastal and offshore waters were evaluated in the current report, with respect to primarily the responses of focal species for the conservation measure, but in some of the areas also ecosystem responses. Five of the NTZs were established in 2009-2011, as part of a government commission, while the other three had been established earlier. The results of the evaluations are presented in a synthesis and also in separate, more detailed chapters for each of the eight NTZs. Overall, the results suggest that NTZs can increase abundances and biomasses of fish and decapod crustaceans, given that the closed areas are strategically placed and of an appropriate size in relation to the life cycle of the focal species. A meta-regression of the effects on focal species of the NTZs showed that CPUE was on average 2.6 times higher after three years of protection, and 3.8 times higher than in the fished reference areas after six years of protection. The proportion of old and large individuals increased in most NTZs, and thereby also the reproductive potential of populations. The increase in abundance of large predatory fish also likely contributed to restoring ecosystem functions, such as top-down control. These effects appeared after a 5-year period and in many cases remained and continued to increase in the longer term (>10 years). In the two areas where cod was the focal species of the NTZs, positive responses were weak, likely as an effect of long-term past, and in the Kattegat still present, recruitment overfishing. In the Baltic Sea, predation by grey seal and cormorant was in some cases so high that it likely counteracted the positive effects of removing fisheries and led to stock declines in the NTZs. In most cases, the introduction of the NTZs has likely decreased the total fishing effort rather than displacing it to adjacent areas. In the Kattegat NTZ, however, the purpose was explicitly to displace an unselective coastal mixed bottom-trawl fishery targeting Norway lobster and flatfish to areas where the bycatches of mature cod were smaller. In two areas that were reopened to fishing after 5 years, the positive effects of the NTZs on fish stocks eroded quickly to pre-closure levels despite that the areas remained closed during the spawning period, highlighting that permanent closures may be necessary to maintain positive effects.We conclude from the Swedish case studies that NTZs may well function as a complement to other fisheries management measures, such as catch, effort and gear regulations. The experiences from the current evaluation show that NTZs can be an important tool for fisheries management especially for local coastal fish populations and areas with mixed fisheries, as well as in cases where there is a need to counteract adverse ecosystem effects of fishing. NTZs are also needed as reference for marine environmental management, and for understanding the effects of fishing on fish populations and other ecosystem components in relation to other pressures. MPAs where the protection of both fish and their habitats is combined may be an important instrument for ecosystembased management, where the recovery of large predatory fish may lead to a restoration of important ecosystem functions and contribute to improving decayed habitats.With the new Biodiversity Strategy, EUs level of ambition for marine conservation increases significantly, with the goal of 30% of coastal and marine waters protected by 2030, and, importantly, one third of these areas being strictly protected. From a conservation perspective, rare, sensitive and/or charismatic species or habitats are often in focus when designating MPAs, and displacement of fisheries is then considered an unwanted side effect. However, if the establishment of strictly protected areas also aims to rebuild fish stocks, these MPAs should be placed in heavily fished areas and designed to protect depleted populations by accounting for their home ranges to generate positive outcomes. Thus, extensive displacement of fisheries is required to reach benefits for depleted populations, and need to be accounted for e.g. by specific regulations outside the strictly protected areas. These new extensive EU goals for MPA establishment pose a challenge for management, but at the same time offer an opportunity to bridge the current gap between conservation and fisheries management.
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| 8. |
- Blomberg, Anders, et al.
(författare)
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Chronic Airflow Limitation, Emphysema and Impaired Diffusing Capacity in Relation to Smoking Habits in a Swedish Middle-Aged Population.
- 2024
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Ingår i: Annals of the American Thoracic Society. - 2329-6933 .- 2325-6621.
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure.OBJECTIVES: To study the prevalence of CAL, emphysema and impaired DLCO in relation to smoking and respiratory symptoms in a middle-aged population.METHODS: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DLCO, high-resolution computed tomography (HRCT) and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced expiratory volume (FEV1/FVC)<0.7.RESULTS: The overall prevalence was for CAL 8.8%, for impaired DLCO (DLCOCONCLUSIONS: In this large population-based study of middle-aged people, CAL and impaired DLCO were associated with common respiratory symptoms. Self-reported asthma was not associated with CAL in never-smokers. Our findings suggest that CAL in never-smokers signifies a separate clinical phenotype that may be monitored and, possibly, treated differently from smoking-related COPD. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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| 9. |
- Broesby-Olsen, Sigurd, et al.
(författare)
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Multidisciplinary Management of Mastocytosis : Nordic Expert Group Consensus
- 2016
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 96:5
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Tidskriftsartikel (refereegranskat)abstract
- Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.
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| 10. |
- Duong-Thi, Minh-Dao, et al.
(författare)
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Comparison of weak affinity chromatography and surface plasmon resonance in determining affinity of small molecules
- 2014
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 461, s. 57-59
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we compared affinity data from surface plasmon resonance (SPR) and weak affinity chromatography (WAC), two established techniques for determination of weak affinity (mM-mu M) small molecule-protein interactions. In the current comparison, thrombin was used as target protein. In WAC the affinity constant (K-D) was determined from retention times, and in SPR it was determined by Langmuir isotherm fitting of steady-state responses. Results indicate a strong correlation between the two methods (R-2 = 0.995, P < 0.0001). (C) 2014 Elsevier Inc. All rights reserved.
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| 11. |
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| 12. |
- Engström, Gunnar, et al.
(författare)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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| 13. |
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| 14. |
- Malinovschi, Andrei, 1978-, et al.
(författare)
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Assessment of Global Lung Function Initiative (GLI) reference equations for diffusing capacity in relation to respiratory burden in the Swedish CArdioPulmonary bioImage Study (SCAPIS)
- 2020
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Ingår i: European Respiratory Journal. - Lausanne, Switzerland : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 56:2
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Tidskriftsartikel (refereegranskat)abstract
- The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (DLCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired DLCO. We examined if the GLI LLN for DLCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden.Spirometry, DLCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15 040 participants, aged 50–64 years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women).Both the median and LLN for DLCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of DLCO DLCO >GLI LLN but DLCO >GLI LLN but versus 4.5%, p<0.001), chronic airflow limitation (8.5% versus 3.9%, p<0.001) and chronic bronchitis (8.3% versus 4.4%, p<0.01) than subjects (n=13 600) with normal DLCO (>GLI LLN and >SCAPIS LLN). No differences were found with regard to physician-diagnosed asthma.The GLI LLN for DLCO is lower than the estimated LLN in healthy, never-smoking, middle-aged Swedish adults. Individuals with DLCO above the GLI LLN but below the SCAPIS LLN had, to a larger extent, an increased respiratory burden. This suggests clinical implications for choosing an adequate LLN for studied populations.
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| 15. |
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| 16. |
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| 17. |
- Pattanaik, Bagmi, 1977, et al.
(författare)
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Polymorphisms in alpha 7 nicotinic acetylcholine receptor gene, CHRNA7, and its partially duplicated gene, CHRFAM7A, associate with increased inflammatory response in human peripheral mononuclear cells
- 2022
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Ingår i: Faseb Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 36:5
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Tidskriftsartikel (refereegranskat)abstract
- The vagus nerve can, via the alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR), regulate inflammation. The gene coding for the alpha 7nAChR, CHRNA7, can be partially duplicated, that is, CHRFAM7A, which is reported to impair the anti-inflammatory effect mediated via the alpha 7nAChR. Several single nucleotide polymorphisms (SNPs) have been described in both CHRNA7 and CHRFAM7A, however, the functional role of these SNPs for immune responses remains to be investigated. In the current study, we set out to investigate whether genetic variants of CHRNA7 and CHRFAM7A can influence immune responses. By investigating data available from the Swedish SciLifeLab SCAPIS Wellness Profiling (S3WP) study, in combination with droplet digital PCR and freshly isolated PBMCs from the S3WP participants, challenged with lipopolysaccharide (LPS), we show that CHRNA7 and CHRFAM7A are expressed in human PBMCs, with approximately four times higher expression of CHRFAM7A compared with CHRNA7. One SNP in CHRFAM7A, rs34007223, is positively associated with hsCRP in healthy individuals. Furthermore, gene ontology (GO)-terms analysis of plasma proteins associated with gene expression of CHRNA7 and CHRFAM7A demonstrated an involvement for these genes in immune responses. This was further supported by in vitro data showing that several SNPs in both CHRNA7 and CHRFAM7A are significantly associated with cytokine response. In conclusion, genetic variants of CHRNA7 and CHRFAM7A alters cytokine responses. Furthermore, given that CHRFAM7A SNP rs34007223 is associated with inflammatory marker hsCRY in healthy individuals suggests that CHRFAM7A may have a more pronounced role in regulating inflammatory processes in humans than previously been recognized.
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| 18. |
- Torén, Kjell, 1952, et al.
(författare)
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Occupational risks associated with severe COVID-19 disease and SARS-CoV-2 infection-a Swedish national case-control study conducted from October 2020 to December 2021
- 2023
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Ingår i: Scandinavian Journal of Work Environment & Health. - 0355-3140. ; 49:6, s. 386-394
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study aimed to investigate whether workplace factors and occupations are associated with SARSCoV-2 infection or severe COVID-19 in the later waves of the pandemic.Methods We studied 552 562 cases with a positive test for SARS-CoV-2 in the Swedish registry of communicable diseases, and 5985 cases with severe COVID-19 based on hospital admissions from October 2020 to December 2021. Four population controls were assigned the index dates of their corresponding cases. We linked job histories to job-exposure matrices to assess the odds for different transmission dimensions and different occupations. We used adjusted conditional logistic analyses to estimate odds ratios (OR) for severe COVID-19 and SARS-CoV-2 with 95% confidence intervals (CI).Results The highest OR for severe COVID-19 were for: regular contact with infected patients, (OR 1.37, 95% CI 1.23-1.54), close physical proximity (OR 1.47, 95% CI 1.34-1.61), and high exposure to diseases or infections (OR 1.72, 95% CI 1.52-1.96). Mostly working outside had lower OR (OR 0.77, 95% CI 0.57-1.06). The odds for SARS-CoV-2 when mostly working outside were similar (OR 0.83, 95% CI 0.80-0.86). The occupation with the highest OR for severe COVID-19 (compared with low-exposure occupations) was certified specialist physician (OR 2.05, 95% CI 1.31-3.21) among women and bus and tram drivers (OR 2.04, 95% CI 1.49-2.79) among men.Conclusions Contact with infected patients, close proximity and crowded workplaces increase the risks for severe COVID-19 and SARS-CoV-2 infection. Outdoor work is associated with decreased odds for SARS-CoV-2 infection and severe COVID-19.
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| 19. |
- Östman, Örjan, et al.
(författare)
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Estimating Competition between Wildlife and Humans-A Case of Cormorants and Coastal Fisheries in the Baltic Sea
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12, s. e83763-
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Tidskriftsartikel (refereegranskat)abstract
- Cormorants and other wildlife populations have come in real or perceived conflicts with humans over exploited fish stocks. From gut contents of cormorants, and using an extension of the Catch equation, we estimated the degree of short term competition between great cormorants and coastal fisheries in two areas along the Swedish Baltic Sea. Cormorants consumed 10 and 44%, in respective area, of the fish biomass of six fish species harvested by humans; eel, flounder, herring, perch, pike, and whitefish. On average, cormorants consumed smaller individuals than harvested in fisheries. But for perch, cod and flounder, cormorants consumed harvestable sized fish corresponding >20% of human catches. Our competition model estimated the direct decrease in fisheries catches due to cormorant predation to be <10% for all species except flounder (>30%) and perch (2-20%). When also including the indirect effects of cormorant predation on smaller fish that never reached harvestable size, the estimated decrease in fisheries catches at least doubled for perch (13-34%) and pike (8-19%). Despite large uncertainties, our model indicates that cormorants may locally have a direct impact on human catches of at least flounder, and when incorporating indirect effects also on perch and pike. The study indicates that the degree of competition between cormorants and humans varies substantially between areas. We also included economical values in the model and concluded that for the commercially most important species, eel and cod, the estimated economic impact of cormorants on fisheries was low.
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| 20. |
- Adamiak, Beata, et al.
(författare)
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Herpes simplex virus type 2 glycoprotein g is targeted by the sulfated oligo- and polysaccharide inhibitors of virus attachment to cells
- 2007
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Ingår i: Journal of Virology. - 0022-538X. ; 81:24, s. 13424-13434
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Tidskriftsartikel (refereegranskat)abstract
- Variants of herpes simplex virus type 2 (HSV-2) generated by virus passage in GMK-AH1 cells in the presence of the sulfated oligosaccharide PI-88 were analyzed. Many of these variants were substantially resistant to PI-88 in their initial infection of cells and/or their cell-to-cell spread. The major alteration detected in all variants resistant to PI-88 in the initial infection of cells was a frameshift mutation(s) in the glycoprotein G (gG) gene that resulted in the lack of protein expression. Molecular transfer of the altered gG gene into the wild-type background confirmed that the gG-deficient recombinants were resistant to PI-88. In addition to PI-88, all gG-deficient variants of HSV-2 were resistant to the sulfated polysaccharide heparin. The gG-deficient virions were capable of attaching to cells, and this activity was relatively resistant to PI-88. In addition to having a drug-resistant phenotype, the gG-deficient variants were inefficiently released from infected cells. Purified gG bound to heparin and showed the cell-binding activity which was inhibited by PI-88. Many PI-88 variants produced syncytia in cultured cells and contained alterations in gB, including the syncytium-inducing L792P amino acid substitution. Although this phenotype can enhance the lateral spread of HSV in cells, it conferred no virus resistance to PI-88. Some PI-88 variants also contained occasional alterations in gC, gD, gE, gK, and UL24. In conclusion, we found that glycoprotein gG, a mucin-like component of the HSV-2 envelope, was targeted by sulfated oligo- and polysaccharides. This is a novel finding that suggests the involvement of HSV-2 gG in interactions with sulfated polysaccharides, including cell surface glycosaminoglycans.
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| 21. |
- Adamo, Hanibal Hani, et al.
(författare)
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Adaptive (TINT) Changes in the Tumor Bearing Organ Are Related to Prostate Tumor Size and Aggressiveness
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- In order to grow, tumors need to induce supportive alterations in the tumor-bearing organ, by us named tumor instructed normal tissue (TINT) changes. We now examined if the nature and magnitude of these responses were related to tumor size and aggressiveness. Three different Dunning rat prostate tumor cells were implanted into the prostate of immune-competent rats; 1) fast growing and metastatic MatLyLu tumor cells 2) fast growing and poorly metastatic AT-1 tumor cells, and 3) slow growing and non-metastatic G tumor cells. All tumor types induced increases in macrophage, mast cell and vascular densities and in vascular cell-proliferation in the tumor-bearing prostate lobe compared to controls. These increases occurred in parallel with tumor growth. The most pronounced and rapid responses were seen in the prostate tissue surrounding MatLyLu tumors. They were, also when small, particularly effective in attracting macrophages and stimulating growth of not only micro-vessels but also small arteries and veins compared to the less aggressive AT-1 and G tumors. The nature and magnitude of tumor-induced changes in the tumor-bearing organ are related to tumor size but also to tumor aggressiveness. These findings, supported by previous observation in patient samples, suggest that one additional way to evaluate prostate tumor aggressiveness could be to monitor its effect on adjacent tissues.
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| 22. |
- Ahlgren, Karin, et al.
(författare)
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De stora restaureringarna : Från Uppsala domkyrka till Skokloster
- 2004
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Rapport (populärvet., debatt m.m.)abstract
- De stora restaureringarna har varit årets tema. Genom att dokumentera och analysera teori och praktik i några av 1800- och 1900-talets största restaureringar - från genomgripande stilrestaureringar till ett mer återhållsamt och tekniskt skonsamt synsätt. Därmed får vi också ett bättre underlag även för dagens ställningstagande.Föremål för våra studier är Uppsala domkyrka, Gripsholms slott, Vreta klosterkyrka, Gustav 11I:s paviljong i Haga, Kungapalatset i Vadstena och Skoklosters slott. Vi hoppas att denna utställning skall bidra till en kritisk hållning och en ökad kunskap om restaureringskonsten, som kvalificerad yrkesuppgift, tidsspegel för historiesyn och som gestaltningsideal.
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| 23. |
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| 24. |
- Alvebratt, Caroline, et al.
(författare)
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A Modified In Situ Method to Determine Release from a Complex Drug Carrier in Particle-Rich Suspensions
- 2018
-
Ingår i: AAPS PharmSciTech. - : Springer Science and Business Media LLC. - 1530-9932. ; 19:7, s. 2859-2865
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Tidskriftsartikel (refereegranskat)abstract
- Effective and compound-sparing methods to evaluate promising drug delivery systems are a prerequisite for successful selection of formulations in early development stages. The aim of the study was to develop a small-scale in situ method to determine drug release and supersaturation in highly concentrated suspensions of enabling formulations. Mesoporous magnesium carbonate (MMC), which delivers the drug in an amorphous form, was selected as a drug carrier. Five model compounds were loaded into the MMC at a 1:10 ratio using a solvent evaporation technique. The μDiss Profiler was used to study the drug release from MMC in fasted-state simulated intestinal fluid. To avoid extensive light scattering previously seen in particle-rich suspensions in the μDiss Profiler, an in-house-designed protective nylon filter was placed on the in situ UV probes. Three types of release experiments were conducted for each compound: micronized crystalline drug with MMC present, drug-loaded MMC, and drug-loaded MMC with 0.01% w/w hydroxypropyl methyl cellulose. The nylon filters effectively diminished interference with the UV absorption; however, the release profiles obtained were heavily compound dependent. For one of the compounds, changes in the UV spectra were detected during the release from the MMC, and these were consistent with degradation of the compound. To conclude, the addition of protective nylon filters to the probes of the μDiss Profiler is a useful contribution to the method, making evaluations of particle-rich suspensions feasible. The method is a valuable addition to the current ones, allowing for fast and effective evaluation of advanced drug delivery systems.
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| 25. |
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| 26. |
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| 27. |
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| 28. |
- Alvebratt, Caroline
(författare)
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Advanced Methods for Evaluation of the Performance of Complex Drug Delivery System
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Low oral bioavailability of drugs originating from poor aqueous solubility is a common issue in drug development. Various enabling formulations have been presented to circumvent this limitation, many making use of supersaturation. In these, the drug is delivered to the gastro-intestinal lumen in a high energy state e.g. in amorphous form or a liquid lipid vehicle. Concentrations surpassing the equilibrium solubility of the crystalline drug are achieved, which facilitate increased absorption for dissolution-rate limited compounds. Meanwhile the use of the enabling formulation can be beneficial to increase the bioavailability of poorly water-soluble drugs, in vitro evaluation of these systems remain challenging. Limited methods have also evaluated several different types of enabling formulation in the same experimental setup. The overall aim of this thesis was therefore to develop assays to study the performance of various complex drug delivery systems. In the first part, a small scale dissolution apparatus, the µDiss Profiler, was used to study drug release from drug-loaded mesoporous magnesium carbonate (MMC). A protective filter was developed to minimize particle interference on the UV-measurements, enabling studies of supersaturation from the amorphous carrier. In the second paper, lipids were adsorbed onto the MMC. A modified in vitro lipolysis setup was established and the samples were analyzed with nuclear magnetic resonance spectroscopy. A stability study of the lipid-loaded MMC was also performed. The methods developed in the first two projects provided an insight to events occurring in the intestinal lumen. The intestinal absorption has however been shown to be a complex interplay between dissolution-digestion and permeation. In the final two projects, two devices comprising of a donor (luminal) chamber and a receiver (serosal) chamber were studied (the µFLUX and the enabling absorption, ENA, device). The two chambers were separated by a semipermeable membrane (cell-based and/or phospholipid-based). A wide range of enabling formulations were evaluated in the two assays. As the exposure in the donor correlated poorly with the exposure in the receiver compartment, this emphasizes the importance of in vitro methods taking both the dissolution-digestion and permeation into account. The ENA results also predicted the in vivo performance in rats well. To conclude, several models have been established in the thesis to study the in vitro performance of enabling formulations, which will be valuable for screening of appropriate drug delivery systems.
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| 29. |
- Alvebratt, Caroline, et al.
(författare)
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An in vitro dissolution–digestion–permeation assay for the study of advanced drug delivery systems
- 2020
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 149, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- Advanced drug delivery systems (ADDS) are widely explored to overcome poor aqueous solubility of orally administered drugs. However, the prediction of their in vivo performance is challenging, as in vitro models typically do not capture the interplay between processes occurring in the gut. In additions, different models are used to evaluate the different systems. We therefore present a method that allows monitoring of luminal processing (dissolution, digestion) and its interplay with permeation to better inform on the absorption of felodipine formulated as ADDS. Experiments were performed in a µFLUX-apparatus, consisting of two chambers, representing the intestinal and serosal compartment, separated by Caco-2 monolayers. During dissolution–digestion–permeation experiments, ADDS were added to the donor compartment containing simulated intestinal fluid and immobilized lipase. Dissolution and permeation in both compartments were monitored using in situ UV-probes or, when turbidity interfered the measurements, with HPLC analysis.The method showed that all ADDS increased donor and receiver concentrations compared to the condition using crystalline felodipine. A poor correlation between the compartments indicated the need for an serosal compartment to evaluate drug absorption from ADDS. The method enables medium-throughput assessment of: (i) dynamic processes occurring in the small intestine, and (ii) drug concentrations in real-time.
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| 30. |
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| 31. |
- Alvebratt, Caroline, et al.
(författare)
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In Vitro Performance and Chemical Stability of Lipid-Based Formulations Encapsulated in a Mesoporous Magnesium Carbonate Carrier
- 2020
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Lipid-based formulations can circumvent the low aqueous solubility of problematic drug compounds and increase their oral absorption. As these formulations are often physically unstable and costly to manufacture, solidification has been suggested as a way to minimize these issues. This study evaluated the physicochemical stability and in vitro performance of lipid-loaded mesoporous magnesium carbonate (MMC) particles with an average pore size of 20 nm. A medium chain lipid was loaded onto the MMC carrier via physical adsorption. A modified in vitro lipolysis setup was then used to study lipid release and digestion with 1H nuclear magnetic resonance spectroscopy. The lipid loading efficiency with different solidification techniques was also evaluated. The MMC, unlike more commonly used porous silicate carriers, dissolved during the lipolysis assay, providing a rapid release of encapsulated lipids into solution. The digestion of the dispersed lipid-loaded MMC therefore resembled that of a coarse dispersion of the lipid. The stability data demonstrated minor degradation of the lipid within the pores of the MMC particles, but storage for three months did not reveal extensive degradation. To conclude, lipids can be adsorbed onto MMC, creating a solid powder from which the lipid is readily released into the solution during in vitro digestion. The chemical stability of the formulation does however merit further attention.
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| 32. |
- Anderhag, Per, et al.
(författare)
-
Kod som teknisk lösning : en studie om grundskoleeleversuppfattningar av ändamålsenlighet i derasspontana programspråk
- 2021
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Ingår i: NorDiNa. - : University of Oslo Library. - 1504-4556 .- 1894-1257. ; 17:1, s. 113-129
-
Tidskriftsartikel (refereegranskat)abstract
- This study examines primary school students’ perception of functionality in their spontaneous programminglanguage for controlling a simple robot. Classroom activities were designed in order to create opportunitiesfor the students (year 1 and year 4) to discuss and develop together with their teachers a sharedprogramming language for controlling a simple robot. The students spontaneously used (a) natural language,(b) images or (c) symbols when they created their programming language. The findings show thatthe students primarily perceived a code’s functionality as a question of readability, rather than how wellit fit the purpose of controlling the robot. Possible consequences of the findings for teaching in technologyeducation are discussed.
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| 33. |
- Andersson, Irene, 1978, et al.
(författare)
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Reduced sympathetic responsiveness as well as plasma and tissue noradrenaline concentration in growth hormone transgenic mice
- 2004
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Ingår i: Acta Physiol Scand. - 0001-6772. ; 182:4, s. 369-78
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Acromegaly [overproduction of growth hormone (GH)] and GH deficiency have both been associated with alterations in autonomic nervous system function. The aim of this study was to investigate autonomic nervous system influence on heart rate (HR) in transgenic mice overexpressing bovine GH (bGH). METHODS: HR and HR variability (HRV) were measured in conscious young (8-13 weeks) and old (5-6 months) female bGH and control mice using telemetry. HR control was studied using antagonists and an agonist of adrenergic and muscarinic receptors. Noradrenaline was measured in plasma, heart and kidney using high performance liquid chromatography. RESULTS: Average 24 h resting HR did not differ between bGH and control mice. After saline injection and after muscarinic blockade with methylscopolamine HR increase was blunted (in old) or absent (in young) bGH mice compared with control mice (P < 0.05). Phenylephrine caused a baroreflex mediated decrease in HR from around 550 to 300-350 beats min(-1), not different between bGH and control mice. Time- and frequency-domain measures of HRV were reduced in old bGH compared with control mice (P < 0.05). Noradrenaline concentrations were reduced by 25-49% in plasma and tissue of bGH compared with control mice (P < 0.05). CONCLUSION: The current study suggests reduced autonomic modulation of HR in bGH transgenic mice. Thus, GH appears to have marked effects on autonomic tone, reducing sympathetic nervous system function possibly via reduced noradrenaline stores.
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| 34. |
- Andersson, Maria, et al.
(författare)
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Coinfection with Enteric Pathogens in East African Children with Acute Gastroenteritis-Associations and Interpretations
- 2018
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Ingår i: American Journal of Tropical Medicine and Hygiene. - : American Society of Tropical Medicine and Hygiene. - 0002-9637 .- 1476-1645. ; 98:6, s. 1566-1570
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Tidskriftsartikel (refereegranskat)abstract
- Enteric coinfections among children in low-income countries are very common, but it is not well known if specific pathogen combinations are associated or have clinical importance. In this analysis, feces samples from children in Rwanda and Zanzibar less than 5 years of age, with (N = 994) or without (N = 324) acute diarrhea, were analyzed by realtime polymerase chain reaction targeting a wide range of pathogens. Associations were investigated by comparing codetection and mono-detection frequencies for all pairwise pathogen combinations. More than one pathogen was detected in 840 samples (65%). A negative association (coinfections being less common than expected from probability) was observed for rotavirus in combination with Shigella, Campylobacter, or norovirus genogroup II, but only in patients, which is statistically expected for agents that independently cause diarrhea. A positive correlation was observed, in both patients and controls, between Ct (threshold cycle) values for certain virulence factor genes in enteropathogenic Escherichia coli (EPEC) (eae and bfpA) and toxin genes in enterotoxigenic E. coli (eltB and estA), allowing estimation of how often these genes were present in the same bacteria. A significant positive association in patients only was observed for Shigella andEPEC-eae, suggesting that this coinfection might interact in a manner that enhances symptoms. Although interaction between pathogens that affect symptoms is rare, this work emphasizes the importance and difference in interpretation of coinfections depending on whether they are positively or negatively associated.
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| 35. |
- Andersson, Torbjörn, et al.
(författare)
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Sweden
- 2013
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Ingår i: Standing up for your right(s) in Europe. - Cambridge : Intersentia. - 1780681569 - 9781780681566 ; , s. 517-569
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 36. |
- Andresen Bergström, Moa, 1978, et al.
(författare)
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Detection of drugs and hepatitis C virus in used syringes from a needle exchange in Gothenburg, Sweden
- 2023
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Ingår i: Drug Testing and Analysis. - 1942-7603 .- 1942-7611.
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Tidskriftsartikel (refereegranskat)abstract
- People who inject drugs (PWID) are exposed to serious health risks such as lethal overdoses, addiction and infections. The patterns of drug use and the prevalence of hepatitis C virus (HCV) infection vary greatly between and even within countries. Data on drugs used for injection are important to inform PWID of risks and adapt healthcare. This study aimed to determine which substances are injected in Gothenburg, Sweden, and estimate the risk of HCV transmission. A total of 150 syringes handed in at the needle and syringe exchange program (NEP) in Gothenburg over a week in November 2021 were analysed for drug content using liquid chromatography coupled with high-resolution mass spectrometry. Using a dose-adjusted comparison, the main drug(s) injected was distinguished from the impurities in the syringes containing several drugs. HCV RNA was quantified by real-time PCR in an additional set of 150 syringes. Drugs were detected in >99% of analysed syringes, and the most common drugs were amphetamine (81%), followed by buprenorphine (8.0%), heroin (6.7%) and alprazolam (4.6%). Less common findings were testosterone (2.7%), methylphenidate (2.0%), MDMA (0.7%), trenbolone (0.7%) and zopiclone (0.7%). Eleven syringes (7.3%) contained more than one drug. HCV RNA was detected in 13% of the syringes, and one in 10 contained enough to potentially transmit an infection. This study underlines the importance of access to NEPs for PWID to reduce the risks associated with drug injection.
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| 37. |
- Angenete, Eva, 1972, et al.
(författare)
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Stenting for colorectal cancer obstruction compared to surgery-a study of consecutive patients in a single institution.
- 2012
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Ingår i: International journal of colorectal disease. - : Springer Science and Business Media LLC. - 1432-1262 .- 0179-1958. ; 27:5, s. 665-670
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Colonic obstruction is a common complication to colorectal cancer and surgical treatment is associated with high morbidity and mortality. Stenting has emerged as an alternative to surgery. The aim of this study was to compare short-term morbidity, mortality and hospital stay between treatment with self-expandable metallic stent and emergency surgery performed at our department during a 5-year period in a non-randomized setting. METHODS: Patients with colonic obstruction due to rectal or colon cancer referred to the Endoscopic Unit or Surgical Department for insertion of a colonic stent between 1 August 2003 and 1 August 2008 were prospectively registered and followed (n=112). A control group was identified using the hospital records of operations with the International Classification Code-10 (ICD-10) for bowel obstruction and colorectal cancer (n=60). Age, gender, indication, preoperative investigations, surgical procedure, complications and procedure-related mortality were registered. Patients were followed in accordance with local guidelines. RESULTS: The complication rate was similar in the two groups, although there was a trend toward a higher number of severe complications in the surgical group. The hospital stay was significantly lower in the stent group, median of 4 vs. 9days (p<0.0001). The procedure-related mortality was lower in the stent group; 7% vs. 20% (p<0.05). CONCLUSIONS: Stenting can be safely performed with lower or similar complication rate and lower mortality rate compared to surgery and results in significantly shorter hospital stay. The results support stenting as the treatment of choice in patients with acute colonic obstruction, especially in disseminated disease.
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| 38. |
- Antonescu, Irina E, et al.
(författare)
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The Permeation of Acamprosate Is Predominantly Caused by Paracellular Diffusion across Caco-2 Cell Monolayers : A Paracellular Modeling Approach
- 2019
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 16:11, s. 4636-4650
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Tidskriftsartikel (refereegranskat)abstract
- In drug development, estimating fraction absorbed (Fa) in man for permeability-limited compounds is important but challenging. To model Fa of such compounds from apparent permeabilities (Papp) across filter-grown Caco-2 cell monolayers, it is central to elucidate the intestinal permeation mechanism(s) of the compound. The present study aims to refine a computational permeability model to investigate the relative contribution of paracellular and transcellular routes to the Papp across Caco-2 monolayers of the permeability-limited compound acamprosate having a bioavailability of ∼11%. The Papp values of acamprosate and of several paracellular marker molecules were measured. These Papp values were used to refine system-specific parameters of the Caco-2 monolayers, that is, paracellular pore radius, pore capacity, and potential drop. The refined parameters were subsequently used as an input in modeling the permeability (Pmodeled) of the tested compounds using mathematical models collected from two published permeability models. The experimental data show that acamprosate Papp across Caco-2 monolayers is low and similar in both transport directions. The obtained acamprosate Papp, 1.56 ± 0.28 × 10-7 cm·s-1, is similar to the Papp of molecular markers for paracellular permeability, namely, mannitol (2.72 ± 0.24 × 10-7 cm·s-1), lucifer yellow (1.80 ± 0.35 × 10-7 cm·s-1), and fluorescein (2.10 ± 0.28 × 10-7 cm·s-1), and lower than that of atenolol (7.32 ± 0.60 × 10-7 cm·s-1; mean ± SEM, n = 3-6), while the end-point amount of acamprosate internalized by the cell monolayer, Qmonolayer, was lower than that of mannitol. Acamprosate did not influence the barrier function of the monolayers since it altered neither the Papp of the three paracellular markers nor the transepithelial electrical resistance (TEER) of the cell monolayer. The Pmodeled for all the paracellular markers and acamprosate was dominated by the Ppara component and matched the experimentally obtained Papp. Furthermore, acamprosate did not inhibit the uptake of probe substrates for solute carriers PEPT1, TAUT, PAT1, EAAT1, B0,+AT/rBAT, OATP2B1, and ASBT expressed in Caco-2 cells. Thus, the Pmodeled estimated well Ppara, and the paracellular route appears to be the predominant mechanism for acamprosate Papp across Caco-2 monolayers, while the alternative transcellular routes, mediated by passive diffusion or carriers, are suggested to only play insignificant roles.
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| 39. |
- Arroyo Vázquez, Jorge Alberto, 1979, et al.
(författare)
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Bacterial colonization of the stomach and duodenum in a Swedish population with and without proton pump inhibitor treatment
- 2020
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Ingår i: JGH Open. - : Wiley. - 2397-9070. ; 4:3, s. 405-409
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aim Microbial contamination of the abdominal cavity is a serious concern during transgastric endoscopic interventions and perforations, particularly in patients who have inhibited gastric acid secretion due to treatment with proton pump inhibitors (PPIs). The aim of this study was to investigate the gastric and duodenal bacterial flora in patients with and without PPI treatment. Methods Patients referred for gastroscopy, without recent antibiotic treatment, were eligible for inclusion. Use of PPIs was recorded. Samples for bacterial culturing were obtained from the antrum of the stomach and from the duodenal bulb through a gastroscope. Positive cultures were examined for bacterial types and subtypes. Biopsies were taken in the antrum for urease test to detect Helicobacter pylori. Results Bacterial cultures from the stomach were obtained from 103 patients, and duodenal samples were also cultured from 49 of them, for a total of 53 patients with PPI use and 50 patients without. Positive gastric cultures were found in 42 of 53 patients with PPI use and in 13 of 50 without (P < 0.0001). Duodenal cultures were positive in 20 of 24 with PPI and 8 of 25 without (P < 0.0001). The most commonly identified bacterial species were oral strains of Streptococcus, followed by Neisseria and Haemophilus influenzae. Of 103 patients, 10 had a positive urease test, indicating H. pylori infection, 1 with PPI and 9 without. Conclusions Bacterial growth in the stomach and duodenum is more common in patients with PPI treatment. The dominating bacterial species found in the stomach and duodenum originates from the oropharynx. Clinical trials registry: Trial registration number 98041 in Researchweb (FoU in Sweden).
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| 40. |
- Arroyo Vázquez, Jorge Alberto, 1979, et al.
(författare)
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Exploring pyloric dynamics in stenting using a distensibility technique
- 2018
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 30:12
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 John Wiley & Sons Ltd Background: Perforated duodenal ulcers can be treated with a covered stent. Stent migration is a severe complication, sometimes requiring surgery. Pyloric physiology during stent treatment has not been studied and mechanisms for migration are unknown. The aim of this study was to investigate the pyloric response to distention, mimicking stent treatment, using the EndoFLIP. Methods: A nonsurvival study in five pigs was carried out, followed by a pilot study in one volunteer. Animals were gastroscoped during anaesthesia and the EndoFLIP was placed straddling the pylorus. Baseline distensibility readings were performed at stepwise balloon distentions to 20, 30, 40, and 50mL, measuring pyloric cross-sectional area and pressure. Measurements were repeated after administration of a prokinetic drug and after a liquid meal. In the human study, readings were performed in conscious sedation at baseline and after stimulation with metoclopramide. Key Results: During baseline readings, the pylorus was shown to open more with increasing distention together with higher amplitude motility waves. Reaching maximum distention-volume (50mL), pyloric pressure increased significantly (P=0.016), and motility waves disappeared. After prokinetic stimulation, the pressure decreased and the motility waves increased in frequency and amplitude. After food stimulation, the pressure stayed low and the motility showed increase in amplitude. During both tests, the pylorus showed higher pressure and lack of motility waves at maximum probe distention. Conclusions and Inferences: The pylorus seems to act as a sphincter at low distention but when further dilated starts acting as a pump. Fully distended the pyloric motility disappears and the pressure remains high, suggesting that a stent with high-radial force might show less migration.
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| 41. |
- Arroyo Vázquez, Jorge Alberto, 1979, et al.
(författare)
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Stent treatment or surgical closure for perforated duodenal ulcers: a prospective randomized study.
- 2021
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Ingår i: Surgical endoscopy. - : Springer Science and Business Media LLC. - 1432-2218 .- 0930-2794. ; 35, s. 7183-7190
-
Tidskriftsartikel (refereegranskat)abstract
- Perforated peptic ulcer is a life-threatening condition. Traditional treatment is surgery. Esophageal perforations and anastomotic leakages can be treated with endoscopically placed covered stents and drainage. We have treated selected patients with a perforated duodenal ulcer with a partially covered stent. The aim of this study was to compare surgery with stent treatment for perforated duodenal ulcers in a multicenter randomized controlled trial.All patients presenting at the ER with abdominal pain, clinical signs of an upper G-I perforation, and free air on CT were approached for inclusion and randomized between surgical closure and stent treatment. Age, ASA score, operation time, complications, and hospital stay were recorded. Laparoscopy was performed in all patients to establish diagnosis. Surgical closure was performed using open or laparoscopic techniques. For stent treatment, a per-operative gastroscopy was performed and a partially covered stent was placed through the scope. Abdominal lavage was performed in all patients, and a drain was placed. All patients received antibiotics and intravenous PPI. Stents were endoscopically removed after 2-3weeks. Complications were recorded and classified according to Clavien-Dindo (C-D).43 patients were included, 28 had a verified perforated duodenal ulcer, 15 were randomized to surgery, and 13 to stent. Median age was 77.5years (23-91) with no difference between groups. ASA score was unevenly distributed between the groups (p=0.069). Operation time was significantly shorter in the stent group, 68min (48-107) versus 92min (68-154) (p=0.001). Stents were removed after a median of 21days (11-37 days) without complications. Six patients in the surgical group had a complication and seven patients in the stent group (C-D 2-5) (n.s.).Stent treatment together with laparoscopic lavage and drainage offers a safe alternative to traditional surgical closure in perforated duodenal ulcer. A larger sample size would be necessary to show non-inferiority regarding stent treatment.
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| 42. |
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| 43. |
- Bastidas Venegas, Vladimir, 1974-, et al.
(författare)
-
Sweden
- 2018
-
Ingår i: White Collar Crime –. - : Hart Publishing Ltd. - 9781509917891
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In recent years, criminal justice systems have faced important global challenges in the field of economic and financial crime. The 2008 crisis revealed how strongly financial markets and economies are interconnected and illustrated that misconduct in the economic and financial sectors is often of a systemic nature. The prevention, control and punishment of such crimes is thus confronted with a strong globalisation. Legislators and law enforcers have been searching for adequate responses to combat economic and financial crime by adapting existing policies, norms and practices and by creating new enforcement mechanisms. The aim of this volume is to examine how various national criminal justice systems across Europe deal with the aforementioned challenges. In the first part, it will take a closer look at the following national systems: France, Germany, Poland and Sweden. Furthermore, it will compare the European approach with the American one, as a source of inspiration for unresolved difficulties and future developments. It then goes further to explore those challenging issues regarding the field of economic and financial crime including: the Senior Managers Regime, corporate criminal liability, and whistle-blowers protection. Timely and pertinent, this an important new work on a fast moving field
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| 44. |
- Baudin, Maria, 1982-
(författare)
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Rift Valley fever : consequences of virus-host interactions
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rift Valley fever virus (RVFV) is a mosquito-borne virus which has the ability to infect a large variety of animals including humans in Africa and Arabian Peninsula. The abortion rate among these animals are close to 100%, and young animals develop severe disease which often are lethal.In humans, Rift Valley fever (RVF) presents in most cases as a mild illness with influenza-like symptoms. However, in about 8% of the cases it progresses into a more severe disease with a high case fatality rate. Since there is such a high abortion rate among infected animals, a link between human miscarriage and RVFV has been suggested, but never proven.We could in paper I for the first time show an association between acute RVFV infection and miscarriage in humans. We observed an increase in pregnant women arriving at the Port Sudan Hospital with fever of unknown origin, and several of the patients experienced miscarriage. When we analysed their blood samples for several viral diseases we found that many had an acute RVFV infection and of these, 54% experienced a miscarriage. The odds of having a miscarriage was 7 times higher for RVFV patients compared to the RVFV negative women of which only 12% miscarried. These results indicated that RVFV infection could be a contributing factor to miscarriage.RVFV is an enveloped virus containing the viral glycoproteins n and c (Gn and Gc respectively), where Gn most likely is responsible for the initial cellular contact. The protein DC-SIGN on dendritic cells and the glycosaminoglycan heparan sulfate has been suggested as cellular receptors for RVFV, however other mechanisms are probably also involved in binding and entry. Charge is a driving force for molecular interaction and has been shown to be important for cellular attachment of several viruses, and in paper II we could show that when the charge around the cells was altered, the infection was affected. We also showed that Gn most likely has a positive charge at a physiological pH.When we added negatively charged molecules to the viral particles before infection, we observed a decreased infection efficiency, which we also observed after removal of carbohydrate structures from the cell surface.Our results suggested that the cellular interaction partner for initial attachment is a negatively charged carbohydrate. Further investigations into the mechanisms of RVFV cellular interactions has to be undertaken in order to understand, and ultimately prevent, infection and disease.There is currently no vaccine approved for human use and no specific treatments for RVF, so there is a great need for developing safe effective drugs targeting this virus. We designed a whole-cell based high-throughput screen (HTS) assay which we used to screen libraries of small molecular compounds for anti-RVFV properties. After dose-response and toxicity analysis of the initial hits, we identified six safe and effective inhibitors of RVFV infection that with further testing could become drug candidates for treatment of RVF. This study demonstrated the application of HTS using a whole-cell virus replication reporter gene assay as an effective method to identify novel compounds with potential antiviral activity against RVFV.
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| 45. |
- Berg, Staffan, et al.
(författare)
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Evaluation in pig of an intestinal administration device for oral peptide delivery
- 2023
-
Ingår i: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 353, s. 792-801
-
Tidskriftsartikel (refereegranskat)abstract
- The bioavailability of peptides co-delivered with permeation enhancers following oral administration remains low and highly variable. Two factors that may contribute to this are the dilution of the permeation enhancer in the intestinal fluid, as well as spreading of the released permeation enhancer and peptide in the lumen by intestinal motility. In this work we evaluated an Intestinal Administration Device (IAD) designed to reduce the luminal dilution of drug and permeation enhancer, and to minimize movement of the dosage form in the intestinal lumen. To achieve this, the IAD utilizes an expanding design that holds immediate release mini tablets and places these in contact with the intestinal epithelium, where unidirectional drug release can occur. The expanding conformation limits movement of the IAD in the intestinal tract, thereby enabling drug release at a single focal point in the intestine. A pig model was selected to study the ability of the IAD to promote intestinal absorption of the peptide MEDI7219 formulated together with the permeation enhancer sodium caprate. We compared the IAD to intestinally administered enteric coated capsules and an intestinally administered solution. The IAD restricted movement of the immediate release tablets in the small intestine and histological evaluation of the mucosa indicated that high concentrations of sodium caprate were achieved. Despite significant effect of the permeation enhancer on the integrity of the intestinal epithelium, the bioavailability of MEDI7219 was of the same order of magnitude as that achieved with the solution and enteric coated capsule formulations (2.5–3.8%). The variability in plasma concentrations of MEDI7219 were however lower when delivered using the IAD as compared to the solution and enteric coated capsule formulations. This suggests that dosage forms that can limit intestinal dilution and control the position of drug release can be a way to reduce the absorptive variability of peptides delivered with permeation enhancers but do not offer significant benefits in terms of increasing bioavailability.
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| 46. |
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| 47. |
- Bergefall, Kicki, 1975, et al.
(författare)
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Chondroitin sulfate characterized by the E-disaccharide unit is a potent inhibitor of herpes simplex virus infectivity and provides the virus binding sites on gro2C cells.
- 2005
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Ingår i: The Journal of biological chemistry. - 0021-9258. ; 280:37, s. 32193-9
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Tidskriftsartikel (refereegranskat)abstract
- Although cell surface chondroitin sulfate (CS) is regarded as an auxiliary receptor for binding of herpes simplex virus to cells, and purified CS chain types A, B, and C are known to interfere poorly or not at all with the virus infection of cells, we have found that CS type E (CS-E), derived from squid cartilage, exhibited potent antiviral activity. The IC(50) values ranged from 0.06 to 0.2 mug/ml and substantially exceeded the antiviral potency of heparin, the known inhibitor of virus binding to cells. Furthermore, in mutant gro2C cells that express CS but not heparan sulfate, CS-E showed unusually high anti-herpes virus activity with IC(50) values of <1 ng/ml. Enzymatic degradation of CS-E with chondroitinase ABC abolished its antiviral activity. CS-E inhibited the binding to cells of the purified virus attachment protein gC. A direct interaction of gC with immobilized CS-E and inhibition of this binding by CS-E oligosaccharide fragments greater than octasaccharide were demonstrated. Likewise, the gro2C-specific CS chains interfered with the binding of viral gC to these cells and were found to contain a considerable proportion (13%) of the E-disaccharide unit, suggesting that this unit is an essential component of the CS receptor for herpes simplex virus on gro2C cells and that the antiviral activity of CS-E was due to interference with the binding of viral gC to a CS-E-like receptor on the cell surface. Knowledge of the determinants of antiviral properties of CS-E will help in the development of inhibitors of herpes simplex virus infections in humans.
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| 48. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
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Platelet proteome and function in X-linked thrombocytopenia with thalassemia and in silico comparisons with gray platelet syndrome
- 2021
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:11
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Tidskriftsartikel (refereegranskat)abstract
- In X-linked thrombocytopenia with thalassemia (XLTT; OMIM 314050), caused by the mutation p.R216Q in exon 4 of the GATA1 gene, male hemizygous patients display macrothrombocytopenia, bleeding diathesis and a β-thalassemia trait. Herein, we describe findings in two unrelated Swedish XLTT families with a bleeding tendency exceeding what is expected from the thrombocytopenia. Blood tests revealed low P-PAI-1 and P-factor 5, and elevated S-thrombopoietin levels. Transmission electron microscopy showed diminished numbers of platelet α- and dense granules. The proteomes of isolated blood platelets from 5 male XLTT patients, compared to 5 gender- and age matched controls, were explored. Quantitative mass spectrometry showed alterations of 83 proteins (fold change ≥±1.2, q< .05). Of 46 downregulated proteins, 39 were previously reported to be associated with platelet granules. Reduced protein levels of PTGS1 and SLC35D3 were validated in megakaryocytes of XLTT bone marrow biopsies by immunohistochemistry. Platelet function testing by flow cytometry revealed low dense- and α-granule release and fibrinogen binding in response to ligation of receptors for ADP, the thrombin receptor PAR4 and the collagen receptor GPVI. Significant reductions of a number of α-granule proteins overlapped with a previous platelet proteomics investigation in the inherited macrothrombocytopenia gray platelet syndrome (GPS). In contrast, Ca2+ transporter proteins that facilitate dense granule release were downregulated in XLTT but upregulated in GPS. Ingenuity Pathway Analysis showed altered Coagulation System and Protein Ubiquitination pathways in the XLTT platelets. Collectively, the results revealed protein and functional alterations affecting platelet α- and dense granules in XLTT, probably contributing to bleeding.
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| 49. |
- Bergström, Annika, 1964, et al.
(författare)
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Får äldre vara med i mediesamhället? Rapport 19 Delegationen för senior arbetskraft S 2018:10
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den bild som medierna ger av äldre har betydelse för hur vi förstår och hanterar livets senare skeden. Medier kan bekräfta, förstärka eller utmana stereotypa föreställningar om människor, och detta gäller inte minst synen på ålder och äldres roll i samhället. En fjärdedel av befolkningen är över 60 år, men i det breda medieutbudet förekommer de sällan. Osynliggörandet är något som kan påverka självbilden hos äldre, men också andra generationers synsätt och attityder. Huvudslutsatsen i rapporten är att mediebilden av äldre är problematisk och riskerar att bidra till diskriminering. Medierna pratar ofta om äldre som en svag och homogen grupp, när det i själva verket finns stora variationer inom gruppen. En förklaring till den ensidiga mediebilden kan vara att journalisters och medieproducenters kunskapsnivå kring äldre är låg. Vidare är ålder en av de viktigaste faktorerna när det gäller att förstå hur digitala klyftor uppstår och vidmakthålls. Digitaliseringen ger tillgång till ett ständigt ökande utbud av tjänster via nätet, vilket kan underlätta människors vardag, men också skapa stress om den upplevs som dyr, otillgänglig och komplicerad. Utifrån den äldre medborgarens perspektiv kan digitaliseringen innebära fördelar om man själv är aktiv och har möjlighet att skaffa sig de varor och tjänster man är intresserad av. För vissa äldre kan digitaliseringen däremot innebära nackdelar om krav ställs på att samhällsservice ska ske på sådant sätt som kräver dator, internetuppkoppling och smartphone. Rapporten är fri att ladda ner, open access.
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| 50. |
- Bergström, Annika, 1964, et al.
(författare)
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Invisible or Powerful? Ageing in a Mediatised Society
- 2022
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Ingår i: A Multidisciplinary Approach to Capability in Age and Ageing. International Perspectives on Aging, vol 31. - Cham. : Springer. - 9783030780623 ; , s. 191-205
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Bokkapitel (refereegranskat)abstract
- In order to live your rights and achieve your goals, you need to be informed, have a voice and be listened to, and have the opportunity to engage in society, regardless of age. Freedom of expression and freedom of information are core human rights values that connect the concept of capability with the role of the media in society. The media can be a tool for enhancing a person’s capabilities, but it can also be seen as hindering a good life if technology and its applications are perceived as awkward and/or difficult to access. At a structural level, a wider discussion of media responsibility has the potential to contribute to enhancing people’s capabilities in later life. One critical issue is who should be held accountable and responsible for media content that lacks diverse stories about older people and their voices, possibly reinforcing ageism. Furthermore, where the responsibility lies for ensuring that older people have the technological means to act as digital citizens is somewhat unclear. In an increasingly mediatised environment, we might see a stronger relationship between media literacy, health and ageing, which in turn could emphasise the importance of the role of the media in enhancing capabilities. The chapter is written within the multidisciplinary Centre for ageing and health, AgeCap. at the University of Gothenburg.
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