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  • 101.
    Smedman, Annika
    et al.
    Klinisk nutrition & metabolism.
    Vessby, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Isomer specific effects of conjugated linoleic acid on lipid peroxidation and its regulation by COX 2 inhibitor and vitamin E in humans.2001In: Eicosanoids & other bioactive lipids in cancer, inflammation and related diseases, Nashville USA 2001, 2001Conference paper (Refereed)
  • 102.
    Steer, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lithell, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Acute elevations of medium- and long-chain fatty acids have different impacts on endothelium-dependent vasodilation in humans2003In: Lipids, ISSN 0024-4201, E-ISSN 1558-9307, Vol. 38, no 1, p. 15-19Article in journal (Refereed)
    Abstract [en]

    It has previously been shown that acute elevation of long-chain fatty acids (LCFA) impairs endothelium-dependent vasodilation (EDV) in humans. In this study, we tested the hypothesis that an elevation of both medium-chain fatty acids (MCFA) and LCFA affects the endothelium differently from LCFA elevation alone. Ten healthy volunteers received an intravenous infusion of Structolipid (structured TG, MCFA/LCFA ratio 1:1) and heparin for 2 h, while another 10 subjects received an infusion of Intralipid (LCFA only) and heparin. EDV and endothelium-independent vasodilation (EIDV) were studied in the forearm after local administration of methacholine chloride (2 and 4 microg/min) and sodium nitroprusside (5 and 10 microg/min). Forearm blood flow was determined by venous occlusion plethysmography. Intralipid and heparin increased circulating FA levels from 0.2 +/- 0.1 to 1.4 +/- 0.5 mmol/L (P < 0.001) and reduced EDV by 20% (P < 0.01). Although Structolipid and heparin increased circulating FA levels to a similar extent (from 0.4 +/- 0.1 to 1.8 +/- 0.4 mmol/L after 2 h), EDV was not significantly changed. EIDV increased slightly during both interventions (P < 0.05). In conclusion, an acute elevation of LCFA attenuated EDV, whereas an elevation of both MCFA and LCFA did not influence EDV. Thus, FA composition seems to be of importance for EDV in healthy humans.

  • 103.
    Steer, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hulthe, Johannes
    Millgård, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sarabi, Dennis M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, Bengt
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Endothelial vasodilatory function is predicted by circulating apolipoprotein B and HDL in healthy humans2002In: Lipids, ISSN 0024-4201, E-ISSN 1558-9307, Vol. 37, no 12, p. 1135-1140Article in journal (Refereed)
    Abstract [en]

    Endothelium-dependent vasodilation (EDV), LDL particle size, and antibodies against oxidized LDL (oxLDLab) have been shown to be related to the development of atherosclerosis and cardiovascular disease. In this study, we investigated whether LDL particle size, oxLDLab, apolipoproteins, and lipoproteins are related to endothelial vasodilatory function in a population sample of 58 apparently healthy subjects aged 20 to 69 yr. EDV and endothelium-independent vasodilation (EIDV) were studied in the forearm during local administration of methacholine chloride (2 and 4 microg/min) or sodium nitroprusside (5 and 10 microg/min). Forearm blood flow was determined with venous occlusion plethysmography. In multiple stepwise regression analyses, neither oxLDLab nor small LDL particles were significantly predictive of endothelial vasodilatory function. Instead, a high level of apolipoprotein B (apoB) was an independent predictor of both attenuated EDV and EIDV (r = -0.43, P < 0.01, and r = -0.34, P < 0.05, respectively). HDL cholesterol, on the other hand, was the only lipid variable that was significantly related to the EDV to EIDV ratio, an index of endothelial vasodilatory function (r = 0.35, P < 0.01). The inverse associations between apoB and both EDV and EIDV indicate that apoB might be an early marker of structural vascular changes in healthy subjects, whereas HDL seems to be more specifically related to endothelial vasodilatory function.

  • 104.
    Steer, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Millgård, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lithell, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Vitamin C, diclophenac and L-arginine protect endothelium-dependent vasodilation against elevated circulating fatty acid levels in humans2003In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 168, no 1, p. 65-72Article in journal (Refereed)
    Abstract [en]

    An acute elevation of circulating non-esterified fatty acids (NEFAs) has previously been shown to impair endothelium-dependent vasodilation (EDV). In this study, we investigated if local administration of vitamin C (n=8, 18 mg/min), L-arginine (n=8, 12.5 mg/min), or the cyclooxygenase (COX) inhibitor diclophenac (n=8, 0.5 mg/min) can counteract the endothelial dysfunction seen during infusion of Intralipid plus heparin (n=10). EDV and endothelium-independent vasodilation (EIDV) were studied in the forearm after local administration of methacholine chloride (Mch; 2 and 4 microg/min) and sodium nitroprusside (SNP; 5 and 10 microg/min). Forearm blood flow (FBF) was determined with venous occlusion plethysmography. Intralipid and heparin increased circulating NEFA levels sevenfold and impaired EDV (P<0.001 vs baseline). Concomitant administration of L-arginine or diclophenac abolished the NEFA-induced impairment in EDV. Concomitant vitamin C administration actually improved EDV (P<0.05 vs baseline). NEFA elevation increased EIDV (P<0.01), but this effect was not significant after L-arginine or diclophenac infusions. In conclusion, an acute elevation of circulating NEFAs led to impaired EDV. Administration of L-arginine, vitamin C or COX inhibition abolished this effect, suggesting that NEFAs might interact with endothelial vasodilatory function through multiple mechanisms.

  • 105.
    Steer, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Millgård, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sarabi, Dennis M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Kahan, Thomas
    Edner, Magnus
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cardiac and vascular structure and function are related to lipid peroxidation and metabolism2002In: Lipids, ISSN 0024-4201, E-ISSN 1558-9307, Vol. 37, no 3, p. 231-236Article in journal (Refereed)
    Abstract [en]

    The present study investigated possible relationships between left ventricular mass, intima-media thickness of the carotid artery (IMT), total arterial compliance, and lipid status in a population sample of 58 apparently healthy subjects aged 20 to 69. By stepwise multiple regression analysis, including age, blood pressure, and smoking, left ventricular mass index, measured by M-mode echocardiography, increased by 13.0 g/m2 for each 1 standard deviation (SD = 0.11 microM, r = 0.60, P< 0.01) increase in plasma malondialdehyde and 9.50 g/m2 per SD increase in plasma 8-iso-prostaglandin F2alpha in women only (SD = 8.88 ng/L, r = 0.44, P = 0.01). Each 1-SD (SD = 0.27 g/L) increase in apolipoprotein B was associated with a 63 microm increase in IMT (r = 0.47, P = 0.014) and a 0.27 mL/min/m2/mm Hg (r = -0.60, P < 0.01) decrease in stroke index/pulse pressure ratio, reflecting total arterial compliance in women. In men, each 1-SD increase in the proportion of stearic acid (18:0) in serum cholesterol esters (SD = 0.12 percent units) reduced the transmitral E/A ratio, measured by Doppler echocardiography, reflecting left ventricular diastolic function, by 0.10 units (r = -0.29, P < 0.05). Thus, important cardiovascular characteristics, such as left ventricular mass, left ventricular diastolic function, carotid IMT, and total arterial compliance, were independently predicted by indices of lipid metabolism and peroxidation in apparently healthy subjects.

  • 106. Stockfelt, Leo
    et al.
    Sallsten, Gerd
    Almerud, Pernilla
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Barregard, Lars
    Short-term chamber exposure to low doses of two kinds of wood smoke does not induce systemic inflammation, coagulation or oxidative stress in healthy humans2013In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 25, no 8, p. 417-425Article in journal (Refereed)
    Abstract [en]

    Introduction: Air pollution increases the risk of cardiovascular diseases. A proposed mechanism is that local airway inflammation leads to systemic inflammation, affecting coagulation and the long-term risk of atherosclerosis. One major source of air pollution is wood burning. Here we investigate whether exposure to two kinds of wood smoke, previously shown to cause airway effects, affects biomarkers of systemic inflammation, coagulation and lipid peroxidation. Methods: Thirteen healthy adults were exposed to filtered air followed by two sessions of wood smoke for three hours, one week apart. One session used smoke from the start-up phase of the wood-burning cycle, and the other smoke from the burn-out phase. Mean particle mass concentrations were 295 mu g/m(3) and 146 mu g/m(3), and number concentrations were 140 000/cm(3) and 100 000/cm(3), respectively. Biomarkers were analyzed in samples of blood and urine taken before and several times after exposure. Results after wood smoke exposure were adjusted for exposure to filtered air. Results: Markers of systemic inflammation and soluble adhesion molecules did not increase after wood smoke exposure. Effects on markers of coagulation were ambiguous, with minor decreases in fibrinogen and platelet counts and mixed results concerning the coagulation factors VII and VIII. Urinary F-2-isoprostane, a consistent marker of in vivo lipid peroxidation, unexpectedly decreased after wood smoke exposure. Conclusions: The effects on biomarkers of inflammation, coagulation and lipid peroxidation do not indicate an increased risk of cardiovascular diseases in healthy adults by short-term exposure to wood smoke at these moderate doses, previously shown to cause airway effects.

  • 107. Tholstrup, Tine
    et al.
    Hellgren, Lars I
    Petersen, Martin
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Straarup, Ellen Marie
    Schnohr, Peter
    Sandström, Brittmarie
    A solid dietary fat containing fish oil redistributes lipoprotein subclasses without increasing oxidative stress in men.2004In: J Nutr, ISSN 0022-3166, Vol. 134, no 5, p. 1051-7Article in journal (Refereed)
  • 108. Tholstrup, Tine
    et al.
    Raff, Marianne
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Nonboe, Pernille
    Sejrsen, Kristen
    Straarup, Ellen M
    Effects of butter high in ruminant trans and monounsaturated fatty acids on lipoproteins, incorporation of fatty acids into lipid classes, plasma C-reactive protein, oxidative stress, hemostatic variables, and insulin in healthy young men.2006In: Am J Clin Nutr, ISSN 0002-9165, Vol. 83, no 2, p. 237-43Article in journal (Refereed)
  • 109. Turpeinen, A. M.
    et al.
    von Willebrand, E.
    Salminen, I.
    Lindén, J.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Rai, D.
    Effects of cis-9,trans-11 CLA in rats at intake levels reported for breast-fed infants2006In: Lipids, ISSN 0024-4201, E-ISSN 1558-9307, Vol. 41, no 7, p. 669-677Article in journal (Refereed)
    Abstract [en]

    CLA intake in exclusively breast-fed infants is close to levels found to have physiological effects in animals. However, in the majority of studies mixtures of CLA isomers have been used and the independent effects of the major CLA isomer in human milk, cis-9, trans-11 CLA, at the intake level in exclusively breast-fed infants have hardly been studied. We therefore studied the effects of cis-9,trans-11 CLA on plasma lipids and glucose, immune function, and bone metabolism in growing rats. Thirty male Sprague-Dawley rats (n = 10/group) were fed either 20 mg/kg/d cis-9,trans-11 CLA and 20 mg/kg/d sunflower oil (CLA20), 40 mg/kg/d cis-9,trans-11 CLA (CLA40), or 40 mg/kg/d sunflower oil (placebo) for 8 wk. No significant differences between groups were found in plasma lipids, glucose, insulin, C-reactive protein, or lipid peroxidation. Liver fat content was lowest in the CLA20 group. In vitro interleukin 2 (IL-2) production increased, and tumor necrosis factor alpha, IL-1 beta, prostaglandin E-2, and leukotriene 134 production decreased in the CLA20 group. No differences between groups were detected in IL-4, IL-6, or interferon gamma production, plasma osteocalcin, insulin-like growth factor, or urinary deoxypyridinoline crosslinks. Plasma tartrate-resistant acid phosphatase 5b activity was significantly increased in the CLA40 group. The results indicate anti-inflammatory effects and enhanced T-cell function for the CLA20 group. No adverse effects were seen in the CLA20 group, whereas indications of increased bone resorption rate were observed in the CLA40 group.

  • 110. Turpeinen, Anu M
    et al.
    Ylönen, Niina
    von Willebrand, Eva
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Aro, Antti
    Immunological and metabolic effects of cis-9, trans-11-conjugated linoleic acid in subjects with birch pollen allergy2008In: Br J Nutr, ISSN 0007-1145, p. 1-8Article in journal (Refereed)
    Abstract [en]

    Animal studies suggest that conjugated linoleic acid (CLA) may modulate the immune response, while studies in healthy human subjects have shown little effect and results are controversial. However, the effects of CLA may be more prominent in situations of immune imbalance, such as allergy. We studied the effects of the natural CLA isomer, cis-9, trans-11-CLA, on allergy symptoms and immunological parameters in subjects with birch pollen allergy. In a randomised, placebo-controlled study, forty subjects (20-46 years) with diagnosed birch pollen allergy received 2g CLA/d in capsules, which contained 65.3 % cis-9, trans-11-CLA and 8-5 % trans-10, cis-12-CLA (n 20), or placebo (high-oleic acid sunflower-seed oil) (n 20) for 12 weeks. The supplementation began 8 weeks before the birch pollen season and continued throughout the season. Allergy symptoms and use of medication were recorded daily. Lymphocyte subsets, cytokine production, immunoglobulins, C-reactive protein, lipid and glucose metabolism and lipid peroxidation were assessed before and after supplementation. The CLA group reported a better overall feeling of wellbeing (P< ;0.05) and less sneezing (P< ;0.05) during the pollen season. CLA supplementation decreased the in vitro production of TNF-alpha (P< ;0.01), interferon-gamma (P< ;0.05) and IL-5 (P< ;0.05). Total plasma IgE and birch-specific IgE concentrations did not differ between groups, whereas plasma IgA (P< ;0.05), granulocyte macrophage colony-stimulating factor (P< ;0.05) and eosinophil-derived neurotoxin (P< ;0.05) concentrations were lower after CLA supplementation. Urinary excretion of 8-iso-PGF(2 alpha), a major F-2-isoprostane (P< ;0.01), and 15-keto-dihydro-PGF(2 alpha), a primary PGF(2 alpha) metabolite (P< ; 0.05), increased in the CLA group. The results suggest that cis-9, trans-11-CLA has modest anti-inflammatory effects in allergic subjects.

  • 111. Ulus, A T
    et al.
    Aksoyek, A
    Ozkan, M
    Katircioglu, S F
    Vessby, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Basu, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Oxidative stress and changes in alpha- and gamma-tocopherol levels during coronary artery bypass grafting.2004In: Ann N Y Acad Sci, ISSN 0077-8923, Vol. 1031, p. 352-6Article in journal (Refereed)
  • 112.
    Vessby, Bengt
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Smedman, Annika
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Risérus, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Basu, Samar
    Conjugated linoleic acid (CLA) reduces body fat and increases lipid peroxidation in humans2000In: Proceedings of ISSFAL, Japan 2000, 2000Conference paper (Refereed)
  • 113. Wang, Huifen
    et al.
    Steffen, Lyn M.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Steinberger, Julia
    Moran, Antoinette
    Jacobs, David R., Jr.
    Hong, Ching-Ping
    Sinaiko, Alan R.
    Obesity Modifies the Relations Between Serum Markers of Dairy Fats and Inflammation and Oxidative Stress Among Adolescents2011In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 19, no 12, p. 2404-2410Article in journal (Refereed)
    Abstract [en]

    Pentadecanoic acid (15: 0) and heptadecanoic acid (17: 0), the dairy-specific saturated fatty acids have been inversely, while inflammation and oxidative stress have been positively related to the risk of cardiovascular disease (CVD). Both fatty acid metabolism and inflammation and oxidative stress may be influenced by adiposity. In the current cross-sectional analyses among adolescents (mean age 15 years), we determined whether overweight status modified the associations between dairy fatty acids (pentadecanoic acid (15: 0) and heptadecanoic acid (17: 0)) represented in serum phospholipids (PL) and markers of inflammation and oxidative stress. Six biomarkers for inflammation and oxidative stress were analyzed, including circulating adiponectin, C-reactive protein (CRP), cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and urinary 15-keto-dihydro-PGF2 alpha (15-keto) and 8-iso-PGF2 alpha (F2-iso). Generalized linear regression analyses, adjusted for age, gender, race, tanner score, total energy intake and physical activity, revealed that PL dairy fatty acids were inversely associated with CRP, F2-iso and 15-keto in overweight, but not in normal weight adolescents (all P(interaction) < 0.05). However, higher level of PL dairy fatty acids was associated with lower IL-6 among all adolescents. Further adjustment for dietary intake of calcium, vitamin D, protein, total flavonoids, and omega-3 fatty acids did not materially change the findings. Dairy-specific saturated fats, i.e., 15: 0 and 17: 0 fatty acids, may contribute to the potential health benefits of dairy products, especially for overweight adolescents.

  • 114.
    Wiklund, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Miclescu, Adriana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wiklund, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Neuro- and cardioprotective effects of blockade of nitric oxide action by administration of methylene blue2007In: Neuroprotective agents: Eighth international neuroprotection society meeting / [ed] Slikker W; Andrew RJ; Trembly B, 2007, Vol. 1122, no 1, p. 231-244Conference paper (Refereed)
    Abstract [en]

    Methylene blue (MB), generic name methylthioninium (C16H18ClN3 S · 3H2O), is a blue dye synthesized in 1876 by Heinrich Caro for use as a textile dye and used in the laboratory and clinically since the 1890s, with well-known toxicity and pharmacokinetics. It has experimentally proven neuroprotective and cardioprotective effects in a porcine model of global ischemia–reperfusion in experimental cardiac arrest. This effect has been attributed to MB's blocking effect on nitric oxide synthase and guanylyl cyclase, the latter blocking the synthesis of the second messenger of nitric oxide. The physiological effects during reperfusion include stabilization of the systemic circulation without significantly increased total peripheral resistance, moderately increased cerebral cortical blood flow, a decrease of lipid peroxidation and inflammation, and less anoxic tissue injury in the brain and the heart. The last two effects are recorded as less increase in plasma concentrations of astroglial protein S-100β, as well as troponin I and creatine kinase isoenzyme MB, respectively.

  • 115.
    Wiklund, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Basu, Samar
    Circulatory arrest as a model for studies of global ischemic injury and neuroprotection2005In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1053, p. 205-219Article in journal (Refereed)
    Abstract [en]

    Despite many programs aimed at better immediate care of cardiac arrest victims, the subsequent mortality rate is high, with myocardial and central nervous system (CNS) injuries as the most common causes of death. Preclinical research is badly needed to produce a sound base for future clinical trials and possible improvements in clinical outcome. In our laboratory, we use piglets weighing approximately 25 kg. Ventricular fibrillation is produced by an AC current and left without treatment for 8-12 min, after which cardiopulmonary resuscitation according to current human guidelines is undertaken. The heart is then defibrillated and restoration of spontaneous circulation induced. During the procedure, blood pressure and flow measurements are obtained in the systemic, pulmonary, and cerebral circulation. Peroxidation and inflammation are monitored by systemic and cerebral venous plasma concentrations of isoprostane (8-iso-PGF(2alpha)), an indicator of oxidative damage, and prostaglandin F(2alpha) metabolite (15-keto-dihydro-PGF(2alpha)), an indicator of cyclooxygenase-2 activity, respectively. Neurocellular damage is monitored by the jugular plasma concentration of protein S-100beta. Neurological outcome is assessed at >24 h after the incident. Our results show that plasma concentrations of 8-iso-PGF(2alpha) are greater after more extended periods of ischemia. PBN (alpha-phenyl-N-tert-butyl nitrone), a so-called spin-trap scavenger, has a neuroprotective effect since neurological outcome is enhanced, and the 8-iso-PGF(2alpha) concentration is decreased during reperfusion. Use of water-soluble sulfonated PBN (S-PBN) results in better autoregulation of cerebral cortical blood flow and less peroxidation of CNS lipids during reperfusion. These observations suggest that our model can be used to explore neuroprotective effects of potential therapeutic agents.

  • 116.
    Wiklund, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Zoerner, Frank
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Semenas, Egidijus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Miclescu, Adriana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Improved neuroprotective effect of methylene blue with hypothermia after porcine cardiac arrest2013In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, no 8, p. 1073-1082Article in journal (Refereed)
    Abstract [en]

    Background

    Induced mild hypothermia and administration of methylene blue (MB) have proved to have neuroprotective effects in cardiopulmonary resuscitation (CPR); however, induction of hypothermia takes time. We set out to determine if MB administered during CPR could add to the histologic neuroprotective effect of hypothermia.

    Methods

    A piglet model of extended cardiac arrest (12 min of untreated cardiac arrest and 8 min of CPR) was used to assess possible additional neuroprotective effects of MB when administered during CPR before mild therapeutic hypothermia induced 30 min after restoration of spontaneous circulation (ROSC). Three groups were compared: C group (n = 8) received standard CPR; PH group (n = 8) received standard CPR but 30 min after ROSC these piglets were cooled to 34°C; the PH+MB group (n = 8) received an MB infusion 1 min after commencement of CPR and the same cooling protocol as the PH group. Three hours later, the animals were killed. Immediately after death, the brains were harvested pending histological and immunohistological analysis.

    Results

    Circulatory variables were similar in the groups except that cardiac output was greater in the PH+MB group 2–3 h after ROSC. Cerebral cortical neuronal injury and blood–brain barrier disruption was greatest in the C group and least in the MB group. The neuroprotective effect of MB and hypothermia was significantly greater than that of delayed hypothermia alone.

    Conclusion

    Administration of MB during CPR added to the short term neuroprotective effects of induced mild hypothermia induced 30 min after ROSC.

  • 117.
    Wohlin, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Apolipoprotein E epsilon 4 genotype is independently associated with increased intima-media thickness in a recessive pattern2007In: Lipids, ISSN 0024-4201, E-ISSN 1558-9307, Vol. 42, no 5, p. 451-456Article in journal (Refereed)
    Abstract [en]

    Polymorphisms in the apolipoprotein E (Apo E) gene have been associated with lipid levels, carotid intima media thickness (CCA-IMT), inflammation and cardiovascular disease (CVD). Earlier findings suggested an association of the Apo E alleles with increased CCA-IMT following a recessive pattern. Whether associations might be independent of C-reactive protein (CRP), lipid levels and other CVD risk factors is not known. We investigated the relationships between Apo E (epsilon2, epsilon3 and epsilon4 alleles) and CCA-IMT, measured by B-mode ultrasound, in dominant and recessive models in a community-based sample of 437 men 75 years of age. In men homozygous for the epsilon4 allele CCA-IMT was significantly increased by 0.13 mm to 0.86 +/- 0.16 mm compared to 0.73 +/- 0.19 mm in non- epsilon4-carriers (P = 0.0012) and 0.73 +/- 0.21 mm in epsilon4 heterozygous (P = 0.0044) in unadjusted recessive models. The association between Apo E epsilon4 genotype and CCA-IMT was independent of Apo E epsilon2 and Apo E epsilon3 alleles, CRP, lipid variables (TG, LDL, HDL) and other CVD risk factors (smoking, hypertension, body mass index, diabetes) (P = 0.018). No relations between Apo E genotype and CCA-IMT were observed in dominant models. No significant associations between the Apo E epsilon2 and epsilon3 alleles and CCA-IMT were found. In this study, men homozygous with the ApoE epsilon4 allele had thicker CCA-IMT, independently of Apo E epsilon2 and epsilon3 alleles, CRP, lipid variables (TG, LDL, HDL) and other CVD risk factors (smoking, hypertension, body mass index, diabetes), suggesting CCA-IMT to be modified by the ApoE epsilon4 genotype in a recessive pattern.

  • 118.
    Zethelius, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Use of multiple biomarkers to improve the prediction of death from cardiovascular causes2008In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 358, no 20, p. 2107-2116Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The incremental usefulness of adding multiple biomarkers from different disease pathways for predicting the risk of death from cardiovascular causes has not, to our knowledge, been evaluated among the elderly. METHODS: We used data from the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men, to investigate whether a combination of biomarkers that reflect myocardial cell damage, left ventricular dysfunction, renal failure, and inflammation (troponin I, N-terminal pro-brain natriuretic peptide, cystatin C, and C-reactive protein, respectively) improved the risk stratification of a person beyond an assessment that was based on the established risk factors for cardiovascular disease (age, systolic blood pressure, use or nonuse of antihypertensive treatment, total cholesterol, high-density lipoprotein cholesterol, use or nonuse of lipid-lowering treatment, presence or absence of diabetes, smoking status, and body-mass index). RESULTS: During follow-up (median, 10.0 years), 315 of the 1135 participants in our study (mean age, 71 years at baseline) died; 136 deaths were the result of cardiovascular disease. In Cox proportional-hazards models adjusted for established risk factors, all of the biomarkers significantly predicted the risk of death from cardiovascular causes. The C statistic increased significantly when the four biomarkers were incorporated into a model with established risk factors, both in the whole cohort (C statistic with biomarkers vs. without biomarkers, 0.766 vs. 0.664; P<0.001) and in the group of 661 participants who did not have cardiovascular disease at baseline (0.748 vs. 0.688, P=0.03). The improvement in risk assessment remained strong when it was estimated by other statistical measures of model discrimination, calibration, and global fit. CONCLUSIONS: Our data suggest that in elderly men with or without prevalent cardiovascular disease, the simultaneous addition of several biomarkers of cardiovascular and renal abnormalities substantially improves the risk stratification for death from cardiovascular causes beyond that of a model that is based only on established risk factors.

  • 119.
    Åsgård, Rikard
    et al.
    Department of Biosciences and Nutrition, Karolinska Institute.
    Rytter, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Abramsson-Zetterberg, Lilianne
    National Food Administration.
    Möller, Lennart
    Department of Biosciences and Nutrition, Karolinska Institute.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    High intake of fruit and vegetables is related to low oxidative stress and inflammation in a group of patients with type 2 diabetes2007In: Scandinavian Journal of Food and Nutrition, ISSN 1748-2976, E-ISSN 1748-2984, Vol. 51, no 4, p. 149-158Article in journal (Refereed)
    Abstract [en]

    Background : Patients with type 2 diabetes have increased levels of oxidative stress and inflammation. A high fruit and vegetable intake may be beneficial. Objective : To study whether fruit and vegetable intake and levels of plasma antioxidants relate to markers of oxidative stress and inflammation in a group of patients with type 2 diabetes. Further, to investigate whether plasma antioxidants are good biomarkers for intake of fruit and vegetables. Design : Patients with type 2 diabetes were studied. Their dietary intake and levels of plasma antioxidants, and markers of oxidative stress and inflammation were analysed. Results : Fruit and vegetable intake was inversely related to oxidative stress. Plasma carotenoids were negatively correlated with inflammation. The plasma levels of -carotene and β-carotene showed strongly positive associations with fruit and vegetable intake. Conclusions : The results suggest that fruit and vegetable intake may decrease oxidative stress and inflammation in this group of patients. An increased intake of fruit and vegetables can therefore be beneficial for patients with type 2 diabetes, since these patients are documented to have raised oxidative stress and inflammation. The study support the usefulness of plasma -carotene and β-carotene as biomarkers for fruit and vegetable intake.

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