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- Isaksson, B, et al.
(författare)
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Obstructive jaundice results in increased liver expression of uncoupling protein 2 and intact skeletal muscle glucose metabolism in the rat
- 2002
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 37:1, s. 104-111
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Tidskriftsartikel (refereegranskat)abstract
- Background: A majority of patients with pancreatic cancer have obstructive jaundice and diabetes with skeletal muscle insulin resistance. Surgery for these patients is associated with significant morbidity. Uncoupling protein 2 (UCP2) has been proposed to regulate energy expenditure and promote liver vulnerability. The effects of obstructive jaundice on muscle glucose metabolism and expression of UCP2 in liver and muscle are unknown. Methods: Rats were operated with bile duct ligation (BDL). After 7 days, UCP2 mRNA levels were determined in liver and muscle. Simultaneously, insulin-stimulated glucose transport and glycogen synthesis in skeletal muscle were analyzed in vitro. Results: The jaundiced rats lost more weight than pair-fed controls. UCP2 mRNA levels were increased 5-fold in liver but not in muscle in jaundiced rats compared to pair-fed controls. The jaundiced rats were hypoglycemic and hypoinsulinemic but demonstrated intact or enhanced insulin action on skeletal muscle glucose transport and glycogen synthesis in vitro. Muscle glycogen content was increased in the jaundiced rats. Conclusions: Experimental obstructive jaundice in the rat is associated with increased liver expression of UCP2. rapid weight loss, and intact insulin action on skeletal Muscle glucose metabolism. Obstructive jaundice. by upregulated liver UCP2. may contribute to the cachexia and high surgical morbidity observed in these patients, but not to skeletal muscle insulin resistance in pancreatic cancer patients.
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- Pohjola, V, et al.
(författare)
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Effect of periodic melting on geochemical and isotopic signals in an ice core from Lomonosovfonna, Svalbard
- 2002
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Ingår i: J.Geophys.Res.. ; 107:D4, s. ACL 1-14
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Tidskriftsartikel (refereegranskat)abstract
- In this work we examine the quality of the atmospherically deposited signals in an ice core taken from a periodically melting ice field, Lomonosovfonna on central Spitsbergen, Svalbard. The aim is to investigate how much the atmospheric deposited signals in the stratigraphy of ice pack are changed by periodic melting of the ice. To determine the impact of this melting on the stratigraphy found in the ice core, we use three diagnostics: 1) Association between peak values in the ice chemical and isotopic record and ice facies type; 2) Number of “annual” cycles in these records compared with independently-determined number of years represented in the ice core; 3) Statistical comparison between the isotopic record in the ice core and the isotope records from coastal stations from the same region. We find that during warm summers as much as 50% of the annual accumulation may melt and percolate into the firn, and in a median year this decreases to ca. 25 %. As a consequence of percolation the most mobile acids show upto 50 % higher concentrations in bubble poor ice facies compared with facies that are less affected by melt. Most of the other chemical species are less affected than the strong acids, and the stable water isotopes show little evidence of mobility Annual, or bi-annual cycles are detected in most parameters, and the water isotope record has a comparable statistical distribution to isotopic records from coastal stations. We conclude that ice cores from sites like Lomonosovfonna preserve an useful environmental record despite melt events and percolation, where most parameters displays an annual, or in poor cases a bi-annual atmospheric signal.
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| 5. |
- Pohjola, V, et al.
(författare)
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Reconstruction of three centuries of annual accumulation rates based on the record of stable isotopes of water from Lomonosovfonna, Svalbard
- 2002
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Ingår i: Annals of glaciology. ; 35, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- We use the upper 81 m of the record of stable isotopes of water from a 122 m long ice core from Lomonosovfonna, central Spitsbergen, to construct an ice core chronology and the annual accumulation rates over the ice field. The isotope cycles are counted in the ice core record using a model that neglects short wavelength and low amplitude cycles. We find approximately the same number of ä18O cycles as years between known reference horizons, and assume these cycles represent annual cycles. Testing the validity of this assumption using cycles in äD shows that both records give similar numbers of cycles. Using the ä18O chronology, and de-compressing the accumulation records using the Nye flow model, we calculate the annual accumulation for the ice core site back to 1715 AD. We find that the average accumulation rate from 1715 to 1950 o was on average 0.30 m w.e. Accumulation rates increased ca. 25% during the later part of the 20th century to an average of 0.41 m w.e. for the period 1950 – 1997. The accumulation rates show highly significant 2.1 and 21 year periodicities, which gives credibility to our time scale.
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| 10. |
- Isaksson, E, et al.
(författare)
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Ice cores from Svalbard :useful archives of past climate and pollution history.
- 2003
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Ingår i: Physics and chemistry of the earth. Part A. - : Elsevier BV. - 1464-1895 .- 1873-4642 .- 1474-7065. ; 28:28-32, s. 1217-1228
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Tidskriftsartikel (refereegranskat)abstract
- Ice cores from the relatively low-lying ice caps in Svalbard have not been widely exploited in climatic and environmental studies due to uncertainties about the effect of melt water percolation. However, results from two recent Svalbard ice cores, at Lomonosovfonna (1250 m asl) and Austfonna (750 m asl), have shown that with careful site selection, high-resolution sampling and multiple chemical analyses, it is possible to recover ice cores with partly preserved annual signals. These cores are estimated to cover at least the past 600 years and have been dated using a combination of known reference horizons and glacial modeling. The δ18O data from both Lomonosovfonna and Austfonna ice cores suggest that the 20th century was the warmest during the past 600 years. A comparison of the ice core and sea ice records from this period suggests that sea ice extent and Austfonna δ18O are linked over the past 400 years. This may reflect the position of the storm tracks and their direct influence on the relatively low altitude Austfonna. Lomonosovfonna may be less sensitive to such changes and primarily record atmospheric changes due to its higher elevation. The anthropogenic influence on Svalbard environment is illustrated by increased levels of non-sea-salt sulphate, nitrate, acidity, fly-ash and organic contaminants particularly during the second half of 1900s. Decreased concentrations of some components in recent decades most likely reflect emission and use restrictions. However, some current-use organic pesticide compounds show growing concentrations in near surface layers.
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- Nyström, Fredrik, 1963-, et al.
(författare)
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Less difference between office and ambulatory blood pressure in women than in men both before and during antihypertensive treatment
- 2000
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 9:6, s. 340-345
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Tidskriftsartikel (refereegranskat)abstract
- In 199 subjects (56% women) with a diastolic blood pressure (BP) of 95-115 mmHg, 5 mg of either amlodipine or felodipine extended release (ER) was given for 4 weeks following 4 weeks of placebo-treatment. BP was measured by conventional clinic BP technique and by 24-h ambulatory BP monitoring (Spacelab 90202/90207). Men and women had identical clinic BP at baseline and it was lowered equally much by 4 weeks of treatment (men: 158/101 and 147/93, women: 159/102 and 149/93 mmHg, respectively). However, ambulatory BP was higher in women than in men both before and after treatment (men: 145/91 and 134/85, women: 149/95 and 140/89 mmHg, respectively, p < 0.05 for both comparisons). The difference between clinic BP and daytime ambulatory BP was higher in men than in women (systolic men: 8.1 +/- 14, women: 3.7 +/- 15 mmHg, respectively, p = 0.04, diastolic men: 5.5 +/- 8.0, women: 2.1 +/- 8.3 mmHg, p = 0.004). The correlation between the treatment effect measured by ambulatory and clinic BP was poor (systolic r = 0.26, p < 0.0001, diastolic r = 0.17, p = 0.03) and was unaffected by exclusion of subjects with normal ambulatory BP. The poor correlation between treatment effects measured as clinic and ambulatory BP is intriguing, and suggests that using ambulatory BP instead of clinic BP for monitoring the treatment of hypertension could affect the clinical outcome.
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| 16. |
- Samuelsson, A, et al.
(författare)
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Clustering of enterococcal infections in a general intensive care unit
- 2003
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Ingår i: Journal of Hospital Infection. - 0195-6701 .- 1532-2939. ; 54:3, s. 188-195
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Tidskriftsartikel (refereegranskat)abstract
- This is a retrospective study comparing patients' characteristics, antibiotic consumption and environmental contamination before the impact of a new regimen of intensified infection control measures in a general intensive care unit (ICU) at a university-affiliated tertiary-care teaching hospital. The new regimen consisted of (1) reorganization of patient rooms (2) improved hygienic measures including strict hygiene barrier nursing (3) more isolated patient care and (4) more restrictive use of antibiotics. The regimen was introduced after a cluster of enterococcal infections. All patients admitted to the ICU from 1 March 1995 to 28 february 1997 were included. A study period of 12 months after reorganization of the ward was compared with the 12 months immediately before it. The antibiotic consumption, the individual patient's severity of disease (APACHE score), and the extent of therapeutic interventions (TISS score) were recorded. Enterococci were typed biochemically, antibiograms were established and the relation between the isolates was investigated with pulsed-field gel electrophoresis. The bacteriological results and the patient data suggested a hospital-acquired spread as the cause of the ICU enterococcal outbreak. After implementation of the new regimen, we observed a reduction in the rate of enterococcal bloodstream infections from 3.1 to 1.8%. The consumption of antibiotics fell from 6.11 to 4.24 defined daily doses per patient.The introduction of strict hygiene and barrier nursing, more restrictive use of antibiotics, isolation of infected patients, thorough cleaning and disinfection of the unit was followed by an absence of enterococcal infection clustering and reduction in incidence of enterococcal bacteraemia. We were not able to determine whether the reduction in antibiotic consumption was due to the intervention programme. ⌐ 2003 The Hospital Infection Society. Published by Elsevier Science Ltd. All rights reserved.
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| 17. |
- Stahlberg, J., et al.
(författare)
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Structural basis for enantiomer binding and separation of a common beta-blocker : Crystal structure of cellobiohydrolase Cel7A with bound (S)-propranolol at 1.9 angstrom resolution
- 2001
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 305:1, s. 79-93
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Tidskriftsartikel (refereegranskat)abstract
- Cellobiohydrolase Cel7A (previously called CBH 1), the major cellulase produced by the mould fungus Trichoderma reesei, has been successfully exploited as a chiral selector for separation of stereo-isomers of some important pharmaceutical compounds, e.g. adrenergic beta -blockers. Previous investigations, including experiments with catalytically deficient mutants of Cel7A, point unanimously to the active site as being responsible for discrimination of enantiomers. In this work the structural basis for enantioselectivity of basic drugs by Cel7A has been studied by X-ray crystallography. The catalytic domain of Cel7A was co-crystallised with the (S)-enantiomer of a common beta -blocker, propranolol, at pH 7, and the structure of the complex was determined and refined at 1.9 Angstrom resolution. Indeed, (S)-propranolol binds at the active site, in glucosyl-binding subsites -1/ + 1. The catalytic residues Glu212 and Glu217 make tight salt links with the secondary amino group of (S)-propranolol. The oxygen atom attached to the chiral centre of (S)-propranolol forms hydrogen bonds to the nucleophile Glu212 O-epsilon1 and to Gln175 N-epsilon2, whereas the aromatic naphthyl moiety stacks with the indole ring of Trp376 in site +1. The bidentate charge interaction with the catalytic glutamate residues is apparently crucial, since no enantioselectivity has been obtained with the catalytically deficient mutants E212Q and E217Q. Activity inhibition experiments with wild-type Cel7A were performed in conditions close to those used for crystallisation. Competitive inhibition constants for (R)- and (S)-propranolol were determined at 220 muM and 44 muM, respectively, corresponding to binding free energies of 20 kJ/ mol and 24 kJ/mol, respectively. The K-i value for (R)-propranolol was 57-fold lower than the highest concentration, 12.5 mM, used in co-crystallisation experiments. Still several attempts to obtain a complex with the (R)-enantiomer have failed. By using cellobiose as a selective competing ligand, the retention of the enantiomers of propranolol on the chiral stationary phase (CSP) based on Cel7A mutant D214N were resolved into enantioselective and non-selective binding. The enantioselective binding was weaker for both enantiomers on D214N-CSP than on wild-type-CSP.
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| 19. |
- Wallenius, Kristina, 1973, et al.
(författare)
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Liver-derived IGF-I regulates GH secretion at the pituitary level in mice.
- 2001
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Ingår i: Endocrinology. - 0013-7227. ; 142:11, s. 4762-70
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Tidskriftsartikel (refereegranskat)abstract
- We have reported that liver-specific deletion of IGF-I in mice (LI-IGF-I-/-) results in decreased circulating IGF-I and increased GH levels. In the present study, we determined how elimination of hepatic IGF-I modifies the hypothalamic-pituitary GH axis to enhance GH secretion. The pituitary mRNA levels of GH releasing factor (GHRF) receptor and GH secretagogue (GHS) receptor were increased in LI-IGF-I-/- mice, and in line with this, their GH response to ip injections of GHRF and GHS was increased. Expression of mRNA for pituitary somatostatin receptors, hypothalamic GHRF, somatostatin, and neuropeptide Y was not altered in LI-IGF-I-/- mice, whereas hypothalamic IGF-I expression was increased. Changes in hepatic expression of major urinary protein and the PRL receptor in male LI-IGF-I-/- mice indicated an altered GH release pattern most consistent with enhanced GH trough levels. Liver weight was enhanced in LI-IGF-I-/- mice of both genders. In conclusion, loss of liver-derived IGF-I enhances GH release by increasing expression of pituitary GHRF and GHS receptors. The enhanced GH release in turn affects several liver parameters, in line with the existence of a pituitary-liver axis.
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