| 1. |
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| 2. |
- Andersson, Annica, et al.
(författare)
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Paths to a sustainable food sector guided by LCA – exemplified by pork production
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- To describe a more sustainable food sector, a supply chain approach is needed. Changing supply chains inevitably means that a range of attributes of the product and its system will change. This project will take on this challenge and deliver detailed descriptions of supply chains of six commodities from a Swedish region in 2012; Milk, cheese, beef, pork, chicken and bread. The set-up of the project was that experts on production along the supply chain design environmentally improved systems. The next step was to challenge the improvements considering their possible consequences on products and systems from different perspectives: food safety, sensory qualities, animal welfare, and consumer appreciation and (only for primary production) costs. The final supply chains were quantified by life cycle assessment (LCA), and they were again assessed from the perspectives mentioned above. Results will be generated during August 2014 and comprise both single-product LCA and region-wide impacts of the future scenarios.
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| 3. |
- Bertilsson, Fredrik
(författare)
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Frihetstida policyskapande : Uppfostringskommissionen och de akademiska konstitutionerna 1738–1766
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Regulating education is a vital part of government. This thesis is inspired by recent changes on the political landscape of higher education. It is guided by an interest in how political objectives and concepts of ideal social relationships are transformed and expressed through government university policies and their consequences. An early stage of what is now commonly referred to as the modern state and the modern research university, rather than present or relatively recent developments, will be explored. Instead of studying trends on the European continent, the thesis inquiries into an attempt made by the Swedish government to revise the constitutions of Swedish schools and universities through the so-called Educational Commission appointed in 1745.The purpose of the thesis is to apply a modern policy perspective to the Educational Commission’s attempt at reforming the constitution of the Swedish universities. The aim is to illuminate the construction of university regulations and to place this within a larger framework of policy making during the Age of Liberty (Frihetstiden) in Sweden.The Commission was an attempt by the Swedish government to implement educational changes based on a holistic view of the realm. It was one of several contemporary initiatives with nationwide ambitions. The Commission did not, however, succeed in reaching its formal objectives, but by placing too much emphasis on what the Commission did not achieve one risks overlooking other results and consequences. It initiated new communication structures, operating procedures and accountability schemes. It changed the regulations for assessing higher education making the university transparent and accountable to the government in new ways. New administrative routines for producing university reform were introduced.The Commission also provided university actors with a legitimate channel for voicing their opinions in relation to the government. They were given a legitimate position to formulate problems, questions and solutions regarding the university. The demands of the professors for increased autonomy in seeking knowledge and providing education stood against the claims made by the government for added control and insight into academic affairs. Through the Commission, the views of the professors were put into circulation in an official political context.
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| 4. |
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| 5. |
- Ghotbi, Roza, et al.
(författare)
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Allele-specific expression and gene methylation in the control of CYP1A2 mRNA level in human livers
- 2009
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Ingår i: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 9:3, s. 208-217
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Tidskriftsartikel (refereegranskat)abstract
- The basis for interindividual variation in the CYP1A2 gene expression is not fully understood and the known genetic polymorphisms in the gene provide no explanation. We investigated whether the CYP1A2 gene expression is regulated by DNA methylation and displays allele-specific expression (ASE) using 65 human livers. Forty-eight percent of the livers displayed ASE not associated to the CYP1A2 mRNA levels. The extent of DNA methylation of a CpG island including 17 CpG sites, close to the translation start site, inversely correlated with hepatic CYP1A2 mRNA levels (P=0.018). The methylation of two separate core CpG sites was strongly associated with the CYP1A2 mRNA levels (P=0.005) and ASE phenotype (P=0.01), respectively. The CYP1A2 expression in hepatoma B16A2 cells was strongly induced by treatment with 5-aza-2'-deoxycytidine. In conclusion, the CYP1A2 gene expression is influenced by the extent of DNA methylation and displays ASE, mechanisms contributing to the large interindividual differences in CYP1A2 gene expression.
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| 7. |
- Hatta, Fazleen H M, et al.
(författare)
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Differences in CYP2C9 Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine : Role of Ethnicity, Genotype, Smoking, Age, and Sex
- 2015
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Ingår i: Omics. - : Mary Ann Liebert Inc. - 1536-2310 .- 1557-8100. ; 19:6, s. 346-353
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Tidskriftsartikel (refereegranskat)abstract
- Global personalized medicine demands the characterization of person-to-person and between-population differences in drug pharmacokinetics and pharmacodynamics. CYP2C9 pharmacokinetic pathway is subject to modulation by both genetic and environmental factors. CYP2C9 genotype-based dose recommendations (e.g., for warfarin) is advocated. However, the overall contribution of genotype for variation in enzyme activity may differ between populations. We evaluated the importance of ethnicity, genotype, smoking, body weight, age, and sex for CYP2C9 enzyme activity. CYP2C9 genotype and phenotype was determined in 148 Swedes and 146 Koreans using losartan as a probe. CYP2C9 enzyme activity was assessed using urinary losartan/metabolite E-3174 ratio. The frequency of CYP2C9 defective variant alleles (*2 and *3) was significantly higher in Swedes (10.8% and 12.5%) than in Koreans (0% and 5.8%). In matched genotypes, CYP2C9 enzyme activity was significantly lower in Swedes compared to Koreans (p<0.0001). In a univariate analysis, age, weight, ethnicity, genotype, and smoking were significant predictors of CYP2C9 phenotype. A stepwise multivariate analysis indicated ethnicity, genotype, and smoking remained as significant predictors of CYP2C9 enzyme activity, accounting for 50% of the total variance. In both study populations, CYP2C9 genotype was a significant predictor of CYP2C9 enzyme activity, but its contribution in explaining the total variance was lower in Koreans (26.6%) than Swedes (40%). In conclusion, we report significantly lower CYP2C9 enzyme activity in Swedes compared to Koreans, partly but not exclusively due to CYP2C9 pharmacogenetic variations. Ethnicity and environment factors need to be considered together with genotype for population-specific dose optimization and global personalized medicine.
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| 8. |
- Helldén, Anders, et al.
(författare)
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Fluconazole-induced intoxication with phenytoin in a patient with ultra-high activity of CYP2C9
- 2010
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 66:8, s. 791-5
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The cytochrome P450 enzyme CYP2C9 metabolizes several important drugs, such as warfarin and oral antidiabetic drugs. The enzyme is polymorphic, and all known alleles, for example, CYP2C9*2 and*3, give decreased activity. Ultra-high activity of the enzyme has not yet been reported.METHODS: We present a patient with Behçet's disease who required treatment with high doses of phenytoin. When fluconazole, a potent inhibitor of CYP2C9, was added to the treatment regimen, the patient developed ataxia, tremor, fatigue, slurred speech and somnolence, indicating phenytoin intoxication. On suspicion of ultra-high activity of CYP2C9, a phenotyping test for CYP2C9 with losartan was performed.RESULTS: The patient was shown to have a higher activity of CYP2C9 than any of the 190 healthy Swedish Caucasians used as controls.CONCLUSIONS: Our finding of an ultrarapid metabolism of losartan and phenytoin may apply to other CYP2C9 substrates, where inhibition of CYP2C9 may cause severe adverse drug reactions.
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| 9. |
- Hosseinpour, Fardin, 1965-
(författare)
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Cytochrome P450 Enzymes in the Metabolism of Vitamin D3
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A cytochrome P450 enzyme in pig kidney that catalyzes the hydroxylations of vitamin D3 and C27-sterols was cloned. DNA sequence analysis of the cDNA revealed that the enzyme belongs to the CYP27 family. The recombinant kidney CYP27A enzyme catalyzed the 25-hydroxylation of vitamin D3 and the 27-oxygenation of C27-sterols. It was shown that human embryonic kidney cells express CYP27A mRNA and are able to catalyze the same reactions. Microsomal vitamin D3 25-hydroxylase (CYP2D25), purified from pig liver, converted vitamin D3 into 25- hydroxyvitamin D3 in substrate concentrations which are within the physiological range. The enzyme also converted tolterodine, a substrate for CYP2D6, into its 5-hydroxymethyl metabolite. RT-PCR experiments revealed that CYP2D25 mRNA is expressed not only in liver and kidney but also in other organs. Experiments with human liver microsomes and recombinant human CYP2D6 indicate that the microsomal 25-hydroxylation of vitamin D3 in human liver is catalyzed by an enzyme different from CYP2D6. Five residues in SRS-3 of CYP2D25 were simultaneously mutated to the equivalent residues in CYP2D6, an enzyme not active in 25-hydroxylation. Both wild-type and mutated CYP2D25 were expressed in the Saccharomyces cerevisiae W(R) strain. The 25-hydroxylase activity of recombinant mutant CYP2D25 was completely lost whereas the activity toward tolterodine remained unaffected. These results indicate that residues in SRS-3 of CYP2D25 are important determinants for its function in vitamin D3 metabolism. A cDNA homologous with the hepatic CYP2D25 was cloned from pig kidney. The enzyme purified from pig kidney and the recombinant enzyme expressed in COS cells catalyzed 25-hydroxylation of vitamin D3 and, in addition, lα-hydroxylation of 25-hydroxyvitamin D3. Immunohistochemistry experiments indicate that CYP2D25 is expressed almost exclusively in the cells of cortical proximal tubules. The expression of CYP2D25 in kidney, but not in liver, was much higher in the adult pig than in the newborn. The results imply that CYP2D25 has a biological role in kidney. Results from experiments with inhibitors in primary cultures of porcine hepatocytes suggest that both CYP2D25 and CYP27A1 contribute to the total 25-hydroxylation in hepatocytes and are equally important in the bioactivation of vitamin D3. Phenobarbital treatment increased the CYP2D25 mRNA levels but did not affect the CYP27A1 mRNA levels. The rate of 25-hydroxylation by phenobarbital-treated hepatocytes was markedly reduced. These results show that primary cultures of porcine hepatocytes are suitable as a model to study the metabolism of vitamin D3 and the regulation of the CYP enzymes involved in the 25-hydroxylation o vitamin D3.
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| 10. |
- Kishida, Ikuko, et al.
(författare)
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Monoamine metabolites level in CSF is related to the 5-HTT gene polymorphism in treatment-resistant depression.
- 2007
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Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X. ; 32:10, s. 2143-51
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Tidskriftsartikel (refereegranskat)abstract
- The serotonin (5-hydroxytryptamine) transporter (5-HTT) is considered to affect the pathogenesis of mood disorders. Large number of genetic association studies between 5-HTT functional polymorphisms and vulnerability of mood disorders and therapeutic response to antidepressants has been carried out. We investigated the influence of 5-HTT-linked polymorphic region (5-HTTLPR) and 5-HTT 17 bp variable number of tandem repeat polymorphism (5-HTTVNTR) polymorphisms on concentrations of monoamine metabolites in cerebrospinal fluid (CSF) among treatment-resistant patients with mood disorders. Subjects were 119 Swedish patients with persistent mood disorders and 141 healthy subjects. In 112 of these patients, we measured 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol in CSF. Genotyping for 5-HTT polymorphisms from genomic DNA was carried out by PCR. There was no significant difference in allele/genotype frequency between patients and healthy subjects. In patients with mood disorders, we found significant difference in mean 5-HIAA concentration between 5-HTTLPR genotypes (p=0.03). Although the 5-HIAA concentration showed a tendency to be higher in short (S) carriers than in non-S carriers of the 5-HTTLPR in patients (p=0.06), when considering patients with major depressive disorder (MDD), the 5-HIAA concentration was significantly higher among S carriers than among non-S carriers (p=0.02). Moreover, the 5-HIAA concentration was higher in S/S subjects compared to long (L)/L (p=0.0001) and L/S (p=0.002) subjects in patients with MDD. Similarly, there was higher HVA concentration in S/S subjects compared to L/L (p=0.002) and L/S subjects (p=0.002). There was no effect of 5-HTTVNTR. Our findings show that the 5-HTTLPR polymorphism affects 5-HIAA and HVA concentrations among treatment-resistant patients with mood disorders.
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