| 1. |
- Carlsson, Per-Anders, 1972, et al.
(författare)
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A transient in situ FTIR and XANES study of CO oxidation over Pt/Al2O3 catalysts
- 2004
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Ingår i: Journal of Catalysis. - : Elsevier BV. - 0021-9517 .- 1090-2694. ; 226:2, s. 422-434
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Tidskriftsartikel (refereegranskat)abstract
- We report experimental results for the oxidation of CO over supported Pt/Al2O3 catalysts operating in oxygen excess at atmospheric pressure. To study the reaction kinetics under transient conditions we have employed step changes of the O2 concentration by intermittently switching off the O2 supply at various temperatures ranging from 523 to 623 K. Detailed in situ FTIR and XANES data for CO coverage and the chemical state of Pt, respectively, are presented together with the CO conversion, which in both cases was monitored by mass spectrometry. A red-shift of the vibrational frequency of linearly bonded CO which correlates with a blue-shift of the Pt LIII binding energy indicates that the Pt catalyst initially is partially oxidised and gradually reduced when the O2 supply is switched off. Control experiments with a NO2 oxidised Pt/Al2O3 catalyst support these findings. A hysteresis in the catalytic activity due to the different rates whereby Pt is oxidised and reduced as a function of gas-phase composition is observed. The activation energy for the Pt oxide reduction (decomposition) process is estimated to be about 50 kJ/mol. The results further emphasise that the conventional three-step Langmuir-Hinshelwood (LH) scheme used to interpret CO oxidation on Pt surfaces must be complemented by a Pt oxidation and reduction mechanism during transient conditions. Moreover, FTIR data suggest that during the extinction, the partially oxidised platinum surface is reduced by chemisorbed CO which should be explicitly accounted for in the modeling of the reaction mechanism.
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| 2. |
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| 3. |
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| 4. |
- Ahrén, Bo, et al.
(författare)
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Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes.
- 2002
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 25:5, s. 869-75
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Glucagon-like peptide-1 (GLP-1) has been proposed as a new treatment modality for type 2 diabetes. To circumvent the drawback of the short half-life of GLP-1, inhibitors of the GLP-1-degrading enzyme dipeptidyl peptidase IV (DPP IV) have been examined. Such inhibitors improve glucose tolerance in insulin-resistant rats and mice. In this study, we examined the 4-week effect of 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP DPP728), a selective, orally active inhibitor of DPP IV, in subjects with diet-controlled type 2 diabetes in a placebo-controlled double-blind multicenter study.RESEARCH DESIGN AND METHODS: A total of 93 patients (61 men and 32 women), aged 64 +/- 9 years (means +/- SD) and with BMI 27.3 +/- 2.7 kg/m(2), entered the study. Fasting blood glucose was 8.5 +/- 1.5 mmol/l, and HbA(1c) was 7.4 +/- 0.7%. Before and after treatment with NVP DPP728 at 100 mg x 3 (n = 31) or 150 mg x 5 (n = 32) or placebo (n = 30), subjects underwent a 24-h study with standardized meals (total 2,000 kcal).RESULTS: Compared with placebo, NVP DPP728 at 100 mg t.i.d. reduced fasting glucose by 1.0 mmol/l (mean), prandial glucose excursions by 1.2 mmol/l, and mean 24-h glucose levels by 1.0 mmol/l (all P < 0.001). Similar reductions were seen in the 150-mg b.i.d. treatment group. Mean 24-h insulin was reduced by 26 pmol/l in both groups (P = 0.017 and P = 0.023). Although not an efficacy parameter foreseen in the study protocol, HbA(1c) was reduced to 6.9 +/- 0.7% in the combined active treatment groups (P < 0.001). Laboratory safety and tolerability was good in all groups.CONCLUSIONS: We conclude that inhibition of DPP IV is a feasible approach to the treatment of type 2 diabetes in the early stage of the disease.
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| 5. |
- Axelsson, T., et al.
(författare)
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Nicotine infusion acutely impairs insulin sensitivity in type 2 diabetic patients but not in healthy subjects
- 2001
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Ingår i: J Intern Med. - 0954-6820. ; 249:6, s. 539-44
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to examine if an acute nicotine infusion alters insulin sensitivity to a similar degree in type 2 diabetic patients as in healthy control subjects. DESIGN: . Double-blind, cross-over, placebo-controlled, randomized experimental study. Nicotine 0.3 microg kg-1 min(-1) or NaCl was infused (2 h) during a euglycaemic hyperinsulinaemic clamp (4 h) to assess insulin sensitivity. SETTING: University research laboratory. SUBJECTS: Six male and female type 2 diabetic patients [DM2; age 54 +/- 10 (mean +/- SD) years; body mass index (BMI) 25.6 +/- 2.9 kg m(-2)] treated with diet or one oral hypoglycaemic agent and six age- and BMI-matched control subjects (Ctr). MAIN OUTCOME MEASURE: Insulin sensitivity (rate of glucose infusion per kg fat free body mass and minute), nicotine and free fatty acid (FFA) levels, pulse rate and blood pressure. RESULTS: The infusions produced similar nicotine levels in both groups. In the absence of nicotine, DM2 were more insulin resistant than Ctr (6.7 +/- 0.4 vs. 10.9 +/- 0.3 mg kg-1 LBM min(-1), respectively; P < 0.0001). This insulin resistance was further aggravated by the nicotine infusion in DM2 but not in Ctr (4.6 +/- 0.3 vs. 10.9 +/- 0.3 mg kg(-1) LBM min(-1); P < 0.0001). Only minor differences were seen in FFA levels, pulse rates and blood pressure. CONCLUSIONS: At this low infusion rate, nicotine aggravated the insulin resistance in DM2 but not in Ctr. This finding may be because of the (dysmetabolic) diabetic state per se or to an increased sensitivity to environmental factors associated with a genetic predisposition for type 2 diabetes. These results show that diabetic subjects are particularly susceptible to the detrimental effects of nicotine.
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| 6. |
- Brekke, Hilde Kristin, 1972, et al.
(författare)
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Lifestyle changes can be achieved through counseling and follow-up in first-degree relatives of patients with type 2 diabetes.
- 2003
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Ingår i: Journal of the American Dietetic Association. - 0002-8223. ; 103:7, s. 835-43
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe two lifestyle prevention strategies tested in first-degree relatives of patients with type 2 diabetes and to present the short-term effects of these strategies on nutrient intake, physical activity pattern, and body weight. DESIGN: In this 16-week controlled intervention trial, subjects were assigned to one of three treatment conditions: diet group (D) (n=25), diet and exercise group (DE) (n=30), or control group (C) (n=22). Subjects/setting Non-diabetic relatives of individuals with diabetes were recruited (n=77; men and women; age 25 to 55 years). INTERVENTION: Intervention groups received group counseling on two occasions and follow-up through unannounced telephone interviews every 10 days. Counseling regarding diet and physical activity was based on the Nordic Nutrition Recommendations. In addition, increased intake of fatty fish and low glycemic index foods were recommended. Main outcome measures Changes in diet (assessed by food frequency questionnaires), leisure time physical activity (assessed through interviews), fatty acid composition of erythrocyte membrane, and body weight. Statistical analysis One-way analysis of variance and Mann-Whitney U test were used to compare changes among groups. RESULTS: Compared with the control group, both intervention groups decreased intake of saturated fatty acids (percent of energy), increased intake of dietary fiber, and reduced average glycemic index of the diet. The ratio of n-6:n-3 fatty acids of the erythrocyte membranes decreased, confirming increased intake of fatty fish. Body weight decreased 1.7 kg (2.1%, P=.030) in group DE, and physical activity increased in the least-active subjects (+70 min/week, P<.01 within group). Applications/Conclusions Healthy individuals with heredity for type 2 diabetes can achieve desired changes in lifestyle factors associated with increased risk for the disease.
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| 7. |
- Grahn, Ammi, 1961, et al.
(författare)
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Determination of Lewis FUT3 gene mutations by PCR using sequence-specific primers enables efficient genotyping of clinical samples.
- 2001
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Ingår i: Human mutation. - : Hindawi Limited. - 1098-1004 .- 1059-7794. ; 18:4, s. 358-9
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a polymerase chain reaction method using sequence-specific primers (PCR-SSP) for rapid and correct genotyping of the common Lewis (FUT3) gene mutations 59T>G, 202T>C, 314C>T, 508G>A, and 1067T>A. The PCR-SSP method was validated on 20 healthy blood donors and 16 non-insulin-dependent diabetic patients. All individuals were in parallel genotyped by our established polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The FUT3 genotypes, determined with the PCR-SSP method, were in complete accordance with the results of the PCR-RFLP reference method. The PCR-SSP method could also be adapted to assign the presence of a specific mutation to the respective FUT3 alleles. We found the method to be reliable, rapid and cheap with no requirements for restriction enzyme processing.
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| 8. |
- Hellebö Johanson, Else, 1969, et al.
(författare)
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Early alterations in the postprandial VLDL1 apoB-100 and apoB-48 metabolism in men with strong heredity for type 2 diabetes
- 2004
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Ingår i: J Intern Med. - 0954-6820. ; 255:2, s. 273-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the postprandial triglyceride-rich lipoprotein (TRL) metabolism, specifically the concentrations of very low-density lipoproteins (VLDL); from intestine (apoB-48) and liver (apoB-100), in men with normal fasting triglycerides but at increased risk of developing type 2 diabetes. DESIGN: Cross-sectional study. SUBJECTS AND SETTINGS: Sixteen healthy men with at least two first-degree relatives with type 2 diabetes were individually matched with 16 control subjects without known diabetes heredity for: age, body mass index, and fasting triglyceride level. They underwent an 8-h meal tolerance test (919 kcal, 51 g fat) during which lipoproteins were separated by density gradient ultracentrifugation. They were characterized by euglycaemic hyperinsulinaemic clamp, peak VO2, 7-day diet registration and computed tomography. RESULTS: The relatives were, as expected, more insulin resistant than the controls and had increased concentration of postprandial VLDL1 particles (49% higher for VLDL1 apoB-48, P = 0.04 and 21% higher for VLDL1 apoB-100, P = 0.048). The elevation was related to insulin sensitivity, but not to lifestyle and body composition. Moreover, the concentration of postprandial triglycerides in VLDL1 fraction was inversely related to low-density lipoprotein (LDL) size in both relatives (rs = -0.60, P = 0.03) and controls (rs = -0.72, P = 0.004). There were no differences in the concentration of triglycerides or apoB-48 and apoB-100 particles in the other fractions (plasma, chylomicron or VLDL2). CONCLUSION: Increased postprandial concentration of TRLs in the VLDL1 fraction seems to be present at an early stage in the development of diabetes and probably contributes to the excess risk of future coronary events in insulin-resistant men.
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| 9. |
- Jansson, Per-Anders, 1961, et al.
(författare)
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Endocrine abnormalities in healthy first-degree relatives of type 2 diabetes patients--potential role of steroid hormones and leptin in the development of insulin resistance.
- 2002
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Ingår i: European journal of clinical investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 32:3, s. 172-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: First-degree relatives of type 2 diabetes patients are at risk of developing diabetes and they display several metabolic and hormonal perturbations. The interplay between insulin resistance, steroid hormones and circulating leptin is, however, still not fully explored in this group. DESIGN: Thirty-three healthy first-degree relatives of type 2 diabetic patients (relatives; M/F 19/14) were compared to 33 healthy subjects without a family history of diabetes (controls) and the groups were matched for gender, age and body mass index (BMI). We performed euglycaemic hyperinsulinaemic clamps and blood was sampled for hormone analyses. RESULTS: Relatives exhibited decreased insulin sensitivity (index of metabolic clearance rate of glucose; MCRI) but when genders were analysed separately, this difference was significant only in males (11.3 +/- 1.3 vs. 15.0 +/- 1.5 units, means +/- SEM, P = 0.030). In male relatives morning cortisol and testosterone levels were lower, whereas leptin was higher than in male controls (P = 0.018, 0.008 and 0.063, respectively). In male relatives plasma testosterone levels were significantly associated with insulin sensitivity (r = 0.48, P = 0.040). Circulating leptin levels were inversely correlated with insulin sensitivity in all subject groups (r-values -0.49 to -0.66; P < 0.05, except in female control subjects P = 0.063). These associations were present also when age and BMI or waist:hip ratio were included in stepwise multiple regression analyses. CONCLUSION: Male subjects genetically predisposed for type 2 diabetes display several endocrine abnormalities including leptin, cortisol and testosterone levels. Dysregulation of these hormones may be important in the development of insulin resistance and type 2 diabetes.
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| 10. |
- Jansson, Per, et al.
(författare)
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Liquid-tin-jet laser-plasma extreme ultraviolet generation
- 2004
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 84:13, s. 2556-2258
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the applicability of liquid-metal jets in vacuum as regenerative targets for laser-plasma generation of extreme ultraviolet (EUV) and soft x-ray radiation. This extends the operation of liquid jet laser-plasma,sources to high-temperature, high-Z, high-density, low-vapor-pressure materials with new spectral signatures. The system is demonstrated using tin (Sn) as the target due to its strong emission around lambdaapproximate to13 nm, which makes the material suitable for EUV lithography. We show a conversion efficiency of 2.5% into (2% BW x 2pi x sr) and report quantitative measurements of the ionic/atomic as well as particulate debris emission.
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| 11. |
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| 12. |
- Johanson, Else H, et al.
(författare)
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Fat distribution, lipid accumulation in the liver, and exercise capacity do not explain the insulin resistance in healthy males with a family history for type 2 diabetes.
- 2003
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 88:9, s. 4232-8
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Tidskriftsartikel (refereegranskat)abstract
- To explore the mechanisms for the insulin resistance associated with a family history of type 2 diabetes, we studied 16 healthy men with at least two first-degree relatives with type 2 diabetes and 16 control subjects without known heredity. They were pair-wise matched for age, body mass index, and fasting triglycerides and underwent an oral glucose tolerance test, iv glucose infusion to measure the early insulin secretion, euglycemic hyperinsulinemic clamp, computed tomography scan, 7-d food record, and a cardiopulmonary exercise test to measure peak oxygen uptake. Insulin sensitivity index was 30% lower (P = 0.02) in relatives, compared with controls, but fasting and 2-h blood glucose and first-phase insulin secretion were similar. There were no differences in mean fasting free fatty acid levels, amount of sc or visceral adipose tissue, or fat accumulation in the liver. Dietary intake and peak oxygen uptake were also similar. However, multiple regression analysis of both groups showed that fat in the liver and physical capacity were, like known heredity for type 2 diabetes, independent predictors of insulin sensitivity. Thus, lipid accumulation in the liver and physical capacity are related to insulin sensitivity, but neither of these factors nor the amount and distribution of the body fat can explain the insulin resistance associated with a family history for type 2 diabetes.
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| 13. |
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| 14. |
- Johansson, Per-Ola, et al.
(författare)
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Design and synthesis of potent inhibitors of the malaria aspartyl proteases plasmepsin I and II : Use of solid-phase synthesis to explore novel statine motifs
- 2004
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 47:13, s. 3353-3366
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Tidskriftsartikel (refereegranskat)abstract
- Picomolar to low nanomolar inhibitors of the two aspartic proteases plasmepsin (Plm) I and II, from the malaria parasite Plasmodium falciparum, have been identified from sets of libraries containing novel statine-like templates modified at the amino and carboxy terminus. The syntheses of the novel statine templates were carried out in solution phase using efficient synthetic routes and resulting in excellent stereochemical control. The most promising statine template was attached to solid support and diversified by use of parallel synthesis. The products were evaluated for their Plm I and II inhibitory activity as well as their selectivity over cathepsin D. Selected inhibitors were, in addition, evaluated for their inhibition of parasite growth in cultured infected human red blood cells. The most potent inhibitor in this report, compound 16, displays Ki values of 0.5 and 2.2 nM for Plm I and II, respectively. Inhibitor 16 is also effective in attenuating parasite growth in red blood cells showing 51% inhibition at a concentration of 5 μM. Several inhibitors have been identified that exhibit Ki values between 0.5 and 74 nM for both Plm I and II. Some of these inhibitors also show excellent selectivity vs cathepsin D.
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| 16. |
- Rehbein, Stefan, et al.
(författare)
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Fabrication and characterization of a condenser zone plate for compact x-ray microscopy
- 2004
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Ingår i: Journal of Vacuum Science & Technology B. - : American Vacuum Society. - 1071-1023 .- 1520-8567. ; 22:3, s. 1118-1122
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Tidskriftsartikel (refereegranskat)abstract
- We describe the in-house fabrication and characterization of a condenser zone plate for a compact laser-plasma-based soft x-ray microscope operating at 2.478 nm wavelength. The fabricated condenser has a diameter of 4.53 mm and an outermost zone width of 49 nm. The pattern is generated by a small-write-field e-beam lithography system and 656 single, 100 mum wide write fields are stitched together to obtain the whole pattern. An in-house method based on a laser-plasma source was developed to characterize the condenser zone plate with regards to diffraction efficiency and imaging properties. The measured groove efficiency of the fabricated condenser zone plate was determined to 11%+/-2% and the imaging properties were found to follow the expectations concerning the object field illumination purpose in the x-ray microscope. The in-house characterization method allows faster process improvement in the small-scale laboratory compared to presently used synchrotron-based methods.
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| 17. |
- Rotter Sopasakis, Victoria, 1972, et al.
(författare)
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High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator
- 2004
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Ingår i: Obes Res. - 1071-7323. ; 12:3, s. 454-60
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the possibility that interleukin-6 (IL-6) can act as a paracrine regulator in adipose tissue by examining effects on adipogenic genes and measuring interstitial IL-6 concentrations in situ. RESEARCH METHODS AND PROCEDURES: Circulating and interstitial IL-6 concentrations in abdominal and femoral adipose tissue were measured using the calibrated microdialysis technique in 20 healthy male subjects. The effects of adipose cell enlargement on gene expression and IL-6 secretion were examined, as well as the effect of IL-6 in vitro on gene expression of adiponectin and other markers of adipocyte differentiation. RESULTS: The IL-6 concentration in the interstitial fluid was approximately 100-fold higher than that in plasma, suggesting that IL-6 may be a paracrine regulator of adipose tissue. This was further supported by the finding that adding IL-6 in vitro at similar concentrations down-regulated the expression of adiponectin, aP2, and PPARgamma-2 in cultured human adipose tissue. In addition, gene expression and release of IL-6, both in vivo and in vitro, correlated with adipose cell size. DISCUSSION: These data suggest that IL-6 may be a paracrine regulator of adipose tissue. Furthermore, increased adipose tissue production of IL-6 after hypertrophic enlargement of the adipose cells may detrimentally affect systemic insulin action by inducing adipose tissue dysfunction with impaired differentiation of the pre-adipocytes and/or adipocytes and lower adiponectin.
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| 18. |
- Yang, Xiao Lin, 1955, et al.
(författare)
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Evidence of impaired adipogenesis in insulin resistance
- 2004
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Ingår i: Biochem Biophys Res Commun. - : Elsevier BV. - 0006-291X. ; 317:4, s. 1045-51
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the roles of adipose tissue and skeletal muscle in the early development of insulin resistance, we characterized gene expression profiles of isolated adipose cells and skeletal muscle of non-diabetic insulin-resistant first-degree relatives of type 2 diabetic patients using oligonucleotide microarrays. About 600 genes and expressed sequence tags, which displayed a gene expression pattern of cell proliferation, were differentially expressed in the adipose cells. The differentially expressed genes in the skeletal muscle were mostly related to the cellular signal transduction and transcriptional regulation. To verify the microarray findings, we studied expression of genes participating in adipogenesis. The expression of Wnt signaling genes, WNT1, FZD1, DVL1, GSK3beta, beta-catenin, and TCF1, and adipogenic transcription factors, C/EBPalpha and beta and delta, PPARgamma, and SREBP-1, was reduced in the adipose tissue. The expression of adipose-specific proteins related to terminal differentiation, such as adiponectin and aP2, was reduced both in the adipose tissue and in the adipose cells isolated from portions of the biopsies. The adipose cells were enlarged in the insulin-resistant relatives and the cell size inversely correlated with the expression of the Wnt signaling genes, adiponectin, and aP2. Our findings suggest that insulin resistance is associated with an impaired adipogenesis.
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