| 1. |
- Andreasson, Anna Nixon, et al.
(författare)
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Leptin and adiponectin : Distribution and associations with cardiovascular risk factors in men and women of the general population
- 2012
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Ingår i: American Journal of Human Biology. - : Wiley. - 1042-0533 .- 1520-6300. ; 24:5, s. 595-601
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In view of the increasing prevalence of obesity worldwide, understanding the role of the recently discovered adipokines leptin and adiponectin is of high clinical relevance. The aim of the present study was to assess the association between levels of leptin and adiponectin with age, known cardiovascular risk factors and to establish whether there are differences between men and women of the general population.METHODS: A total of 98 men and 107 women of the general population, aged between 20 and 74 years, underwent a medical examination at a clinical research center and fasting morning blood samples were also taken.RESULTS: Leptin (mean 7.5 μg l(-1) in men and 16.0 μg l(-1) in women) and adiponectin (mean 7.3 mg l(-1) in men and 11.9 mg l(-1) in women) levels were higher in women than men (Ps < 0.001). Both leptin and adiponectin levels increased with advancing age in both men and women (Ps < 0.05). Leptin was highly associated with factors for metabolic syndrome in men while in women, leptin was highly associated with inflammatory factors. Adiponectin was associated with blood lipids in both men and women, and glucose homeostasis more in women than in men.CONCLUSIONS: Leptin and adiponectin levels were ∼2 times and 1.5 times higher in women than in men, respectively. In addition, although leptin and adiponectin were associated to CVD risk factors in both men and women, we observed differences in specific CVD risk factor groups between men and women. These differences may be due to different regulatory mechanisms and effects of these adipokines in men and women.
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| 2. |
- Dahlgren, Markus, et al.
(författare)
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Design, Synthesis, and Multivariate Quantitative Structure-Activity Relationship of Salicylanilides-Potent Inhibitors of Type III Secretion in Yersinia
- 2007
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 50:24, s. 6177-6188
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Tidskriftsartikel (refereegranskat)abstract
- Analogues to the salicylanilide N-(4-Chlorophenyl)-2-acetoxy-3,5-diiodobenzamide, 1a, an inhibitor of type III secretion (T3S) in Yersinia, were selected, synthesized, and biologically evaluated in three cycles. First, a set of analogues with variations in the salicylic acid ring moiety was synthesized to probe possible structural variation. A basic structure-activity relationship was established and then used to cherry-pick compounds from a principal component analysis score plot of salicylanilides to generate a second set. A third set with increased likelihood of biological activity was designed using D-optimal onion design. A quantitative structure-activity relationship model using hierarchical partial least-square regression to latent structures (Hi-PLS) was computed using PLS score vectors of building blocks correlated to the % inhibition of T3S as a response. A PLS discriminant analysis (PLS-DA) model was derived using the same descriptor set as that for the Hi-PLS model. Both models were validated with an external test set.
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| 3. |
- Kauppi, Anna M., 1971-, et al.
(författare)
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Inhibitors of type III secretion in Yersinia : design, synthesis and multivariate QSAR of 2-sulfonamino-benzanilides
- 2007
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier Ltd. - 0968-0896 .- 1464-3391. ; 15:22, s. 6994-7011
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Compound 1, 2-(benzo[1,2,5]thiadiazole-4-sulfonylamino)-5-chloro-N-(3,4-dichloro-phenyl)-benzamide, was identified as a putative type III secretion inhibitor in Yersinia, and the compound thus has a potential to be used to prevent or treat bacterial infections. A set of seven analogues was synthesized and evaluated in a type III secretion dependent reporter-gene assay with viable bacterial to give basic SAR. A second set of 19 compounds was obtained by statistical molecular design in the building block and product space and subsequent synthesis. Evaluation in the reporter-gene assay showed that the compounds ranged from non-active to compounds more potent than 1. Based on the data multivariate QSAR models were established and the final Hi-PLS model showed good correlation between experimentally determined % inhibition and the calculated % inhibition of the reporter-gene signal.
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| 4. |
- Undén, Anna-Lena, et al.
(författare)
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Gender Differences in Self-Rated Health, Quality of Life, Quality of Care, and Matebolic Control in Patients with Diabetes
- 2008
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Ingår i: Gender Medicine. - : Elsevier BV. - 1550-8579 .- 1878-7398. ; 5:2, s. 162-180
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Tidskriftsartikel (refereegranskat)abstract
- Background: Because the projected increase in the number of diabetic patients is expected to strain the capabilities of health care providers worldwide, we are challenged to find ways of reducing the burden of diabetes. Maintaining and improving health-related quality of life (QoL) for diabetic patients may be viewed as public health goals.Objective: The aim of this cross-sectional study was to compare different aspects of health, QoL, and quality of care (QoC) between men and women with diabetes as a basis for planning and managing diabees care.Methods: All patients in 2 age groups (aged 20–30 years [younger age group] and aged 50–60 years [middle-aged group]) who were registered with the Department of Endocrinology, Metabolism, and Diabetes at Karolinska University Hospital, Stockholm, Sweden, in October 2004, were recruited for a survey. Questions were included about self-rated health (SRH), QoL, QoC, diabetes-related worries, occupational status, physical activity level, living arrangements, and educational background. Glycosylated hemoglobin (HbA1c) values were obtained from medical records.Results: Of the 223 eligible patients (109 men, 114 women) in the younger age group, 49 men and 74 women responded to the questionnaire; of the 300 eligible patients (170 men, 130 women) in the middle-aged group, 120 men and 93 women responded. Middle-aged women rated their mental well-being and QoL as worse compared with men (P < 0.001 and P < 0.05, respectively). In both age groups, women reported more diabetes-related worries and less ability to cope (P < 0.05 for the younger age group and P < 0.001 for the middle-aged group for both variables), thus the differences were more marked for middleaged women. Although there were no gender differences in metabolic control, middle-aged women reported less satisfaction with diabetes care (P < 0.001). Higher HbA1c was related to worse SRH in both men and women when analyzing the age groups together (P < 0.05). This association was most prominent in young women, in whom having more diabetes-related worries was also related to higher HbA1c (P < 0.01).Conclusion: In this study, women with diabetes appeared to have worse QoL and mental well-being compared with men with diabetes. Therefore, identifying strategies to improve SRH and QoL among diabetic patients, especially among women, is of great importance.
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| 5. |
- Undén, Anna-Lena, et al.
(författare)
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Inflammatory cytokines, behaviour and age as determinants of self-rated health in women
- 2007
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 112:5-6, s. 363-373
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Tidskriftsartikel (refereegranskat)abstract
- Self-rated health is a powerful and independent predictor of long-term health, but its biological basis is unknown. We have shown previously that self-rated health is associated with increased levels of circulating cytokines in women. The main aim of the present study was to increase the understanding of the association between markers of wellbeing, such as self-rated health, and cytokines and to investigate the impact of age on these associations. In 174 female consecutive primary health care patients divided into three age groups, we examined subjective ratings of health and aspects of wellbeing and circulating levels of IL (interleukin)-1beta, IL-1ra (IL-1 receptor antagonist), IL-6 and TNF-alpha (tumour necrosis factor-alpha). Poor self-rated health was significantly associated with higher levels of TNF-alpha in all of the age groups. For IL-1beta and IL-1ra, the correlations with self-rated health were significant only in the oldest age group. Lower ratings of other measurements of health and wellbeing were related to higher levels of cytokines, most pronounced for TNF-alpha and IL-1beta, and in the middle and olderst age groups. More symptoms resembling a sickness response induced by inflammation were implicated to be associated with lower self-rated health. The strength of the association between inflammatory cytokines and poor health perception increased with advanced age, indicating an increased vulnerability for inflammatory activity during aging. It is suggested that higher levels of TNF-alpha are connected to a sickness response that, in turn, is connected to self-rated health. The results provide a possible psychobiological basis to understand better diffuse subjective symptoms and poor subjective health in women.
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| 6. |
- Andersson, C David, et al.
(författare)
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Discovery of Ligands for ADP-Ribosyltransferases via Docking-Based Virtual Screening
- 2012
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:17, s. 7706-7718
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Tidskriftsartikel (refereegranskat)abstract
- The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyses the transfer of ADP-ribose units onto substrate proteins, using nicotinamide adenine dinucleotide (NAD(+)) as a co-substrate. They have a documented role in chromatin remodelling and DNA repair; and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The detailed function of most other ARTDs is still unknown. Using virtual screening we identified small ligands of ARTD7 (PARP15/BAL3) and ARTD8 (PARP14/BAL2). Thermal-shift assays confirmed that 16 compounds, belonging to eight structural classes, bound to ARTD7/ARTD8. Affinity measurements with isothermal titration calorimetry for two isomers of the most promising hit compound confirmed binding in the low micromolar range to ARTD8. Crystal structures showed anchoring of the hits in the nicotinamide pocket. These results form a starting point in the development of chemical tools for the study of the role and function of ARTD7 and ARTD8.
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| 7. |
- Andersson, Sara-Linnea, et al.
(författare)
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Plug-in Hybrid Electric Vehicles as Regulating Power Providers - Case Studies of Sweden and Germany
- 2010
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Ingår i: Energy Policy. - : Elsevier BV. - 0301-4215. ; 38:6, s. 2751-2762
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates plug-in hybrid electric vehicles (PHEVs) as providers of regulating power in the form of primary, secondary and tertiary frequency control. Previous studies have shown that PHEVs could generate substantial profits while providing ancillary services. This study investigates under what conditions PHEVs can generate revenues using actual market data, i.e. prices and activations of regulating power, from Sweden and Germany from four months in 2008. PHEV market participation is modelled for individual vehicles in a fleet subject to a simulated movement pattern. Costs for infrastructure and vehicle-to-grid equipment are not included in the analysis. The simulation results indicate that maximum average profits generated on the German markets are in the range 30–80 h per vehicle and month whereas the Swedish regulating power markets give no profit.In addition, an analysis is performed to identify strengths, weaknesses, opportunities, and threats (SWOT) of PHEVs as regulating power providers. Based on the simulation results and the SWOT analysis, characteristics for an ideal regulating power market for PHEVs are presented.
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| 8. |
- Basmarke-Wehelie, Rahma, et al.
(författare)
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The complement regulator CD46 is bactericidal to Helicobacter pylori and blocks urease activity
- 2011
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Ingår i: Gastroenterology. - Baltimore : Elsevier BV. - 0016-5085 .- 1528-0012. ; 141:3, s. 918-928
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the interaction between CD46 and Helicobacter pylori (a bacterium that colonizes the human gastric mucosa and causes gastritis), peptic ulcers, and cancer.METHODS: Using gastric epithelial cells, we analyzed a set of H pylori strains and mutants for their ability to interact with CD46 and/or influence CD46 expression. Bacterial interaction with full-length CD46 and small CD46 peptides was evaluated by flow cytometry, fluorescence microscopy, enzyme-linked immunosorbent assay, and bacterial survival analyses.RESULTS: H pylori infection caused shedding of CD46 into the extracellular environment. A soluble form of CD46 bound to H pylori and inhibited growth, in a dose- and time-dependent manner, by interacting with urease and alkyl hydroperoxide reductase, which are essential bacterial pathogenicity-associated factors. Binding of CD46 or CD46-derived synthetic peptides blocked the urease activity and ability of bacteria to survive in acidic environments. Oral administration of one CD46 peptide eradicated H pylori from infected mice.CONCLUSIONS: CD46 is an antimicrobial agent that can eradicate H pylori. CD46 peptides might be developed to treat H pylori infection.
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