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  • 51.
    Helmersson, Johanna
    et al.
    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.
    Intra-day variation of in vivo prostaglandin F-2 alpha formation in healthy subjects2006In: Prostaglandins & other lipid mediators, ISSN 1098-8823, E-ISSN 2212-196X, Vol. 80, no 1-2, p. 93-99Article in journal (Refereed)
    Abstract [en]

    Prostaglandin F(2alpha) (PGF(2alpha)) is a major stable prostaglandin formed in vivo in physiological and pathophysiological situations and has mainly potent vasoconstrictive and pro-inflammatory properties. PGF(2alpha) is now used as an indicator of acute and chronic inflammation in human clinical settings but the extent of daily variation of PGF(2alpha)in vivo in healthy humans is unknown. We quantified levels of the PGF(2alpha) metabolite 15-keto-dihydro-PGF(2alpha) in 10 healthy males and females in spot urine samples during the day (including morning urine sample) and in 24-h urine during the same day. The intra-day coefficient of variation was 20.9%. However, the total mean value of 15-keto-dihydro-PGF(2alpha) in urine collected in the morning did not significantly differ from the mean level of 15-keto-dihydro-PGF(2alpha) in the 24-h urine samples in the 10 subjects. 15-Keto-dihydro-PGF(2alpha) levels in morning urine showed a positive linear correlation with levels of 15-keto-dihydro-PGF(2alpha) in 24-h urine (R=0.72, P<0.05). In conclusion, formation of PGF(2alpha) shows a biological variation within the day in healthy humans which should not be overlooked when planning a clinical study. Single morning urine samples can be used as an alternative to 24-h urine collections for quantification of PGF(2alpha) formation to simplify the sampling regime in larger clinical studies.

  • 52.
    Helmersson, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Active smoking and a history of smoking are associated with enhanced prostaglandin F(2alpha), interleukin-6 and F(2)-isoprostane formation in elderly men2005In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 181, no 1, p. 201-207Article in journal (Refereed)
    Abstract [en]

    The underlying mechanisms by which smoking induces cardiovascular diseases are largely unknown. The effect of smoking status on the cyclooxygenase (COX)-mediated inflammatory indicator prostaglandin F(2alpha) (PGF(2alpha)) has never been studied. Associations of cytokines and antioxidants and smoking status, have shown conflicting results. Urinary 15-keto-dihydro-PGF(2alpha) (a major metabolite of PGF(2alpha)), serum interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP), serum amyloid protein A (SAA), urinary 8-iso-PGF(2alpha) (an F(2)-isoprostane, indicator of oxidative stress), and serum alpha-tocopherol were quantified in a population-based sample (n = 642) of 77-year old men without diabetes. Fifty-five men were current smokers and 391 former smokers. Inflammatory indicators were increased in current smokers (15-keto-dihydro-PGF(2alpha), P < 0.001; IL-6, P = 0.01) than non-smokers. 8-iso-PGF(2alpha) was increased (P < 0.01) and alpha-tocopherol reduced (P < 0.001) in current smokers. Further, former smokers had increased formation of 15-keto-dihydro-PGF(2alpha), IL-6 and 8-iso-PGF(2alpha) compared non-smokers. This is the first study to show that smokers have increased PGF(2alpha) formation, thus enhanced COX-mediated inflammation, in addition to elevated levels of cytokines and isoprostanes. Subclinical COX- and cytokine-mediated inflammation and oxidative stress are ongoing processes not only in active smokers but also in former smokers which may contribute to the accelerated atherosclerosis associated with smoking.

  • 53.
    Helmersson, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, Bengt
    Larsson, Anders
    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.
    Association of type 2 diabetes with cyclooxygenase-mediated inflammation and oxidative stress in an elderly population2004In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 109, no 14, p. 1729-1734Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Involvement of cyclooxygenase (COX)-mediated inflammation in type 2 diabetes has not been studied, and the association between cytokine-mediated inflammation and diabetes is not fully clarified.

    METHODS AND RESULTS: 15-Keto-dihydro-prostaglandin F2alpha (a metabolite of prostaglandin F2alpha and an indicator of COX-mediated inflammation), high-sensitivity C-reactive protein (CRP), serum amyloid protein A (SAA), 8-iso-PGF2alpha (a nonenzymatic, free radical product of arachidonic acid and an indicator of oxidative stress), and alpha-tocopherol were measured in a population-based sample of 77-year-old men (n=765), in which 112 men had type 2 diabetes. The inflammatory indicators were increased in men with diabetes (urinary 15-keto-dihydro-PGF2alpha, P<0.001, CRP and SAA, P<0.05). However, when adjusted for body mass index, waist circumference, or fasting insulin, no association was found between diabetes and CRP or SAA. The oxidative stress indicator 8-iso-PGF2alpha in urine was increased (P<0.01) in men with diabetes. Patients who were newly diagnosed with diabetes (<7 years since diagnosis) had increased urinary 15-keto-dihydro-PGF2alpha and decreased alpha-tocopherol, but 8-iso-PGF2alpha was unaltered.

    CONCLUSIONS: This is the first study to show that type 2 diabetes in elderly men is related to COX-mediated inflammation, reflected by enhanced prostaglandin formation. The high levels of cytokine-mediated acute-phase proteins observed in men with diabetes appear to be related to obesity and increased fasting insulin. The results further suggest that the appearance of chronic inflammation is an early process in the pathogenesis of diabetes, whereas oxidative injury may be a later process, possibly related to inflammation.

  • 54.
    Helmersson, Johanna
    et al.
    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.
    Larsson, Anders
    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.
    Cyclooxygenase-mediated prostaglandin F2alpha is decreased in an elderly population treated with low-dose aspirin2005In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 72, no 4, p. 227-233Article in journal (Refereed)
    Abstract [en]

    Low-dose aspirin (acetylsalicylic acid) is used as prophylaxis against cardiovascular diseases. The effect of aspirin on inflammation and oxidative stress, processes known to be involved in cardiovascular diseases, are not fully known. Cyclooxygenase(COX)-mediated inflammatory indicator prostaglandin F2alpha(PGF2alpha (15-keto-dihydro-PGF2alpha), cytokine-mediated inflammatory indicators (interleukin-6, high sensitivity C-reactive protein, serum amyloid A protein), and oxidative stress indicators (8-iso-PGF2alpha, tocopherols) were quantified in men with daily 75 mg of aspirin (n = 175) and control men (n = 464), all of age 77, in a cross-sectional study. Men treated with aspirin had decreased levels of urinary 15-keto-dihydro-PGF2alpha than controls (P < 0.01), independent of possible cardiovascular risk factors. Aspirin-treated men had increased levels of alpha-tocopherol than controls (P<0.05). This is the first study to indicate that low-dose aspirin treatment is associated with decreased levels of PGF2alpha. This observation suggests a possible COX-mediated anti-inflammatory effect of low-dose aspirin, which should be further confirmed by intervention studies.

  • 55.
    Helmersson, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Alfthan, Georg
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Serum selenium predicts levels of F2-isoprostanes and prostaglandin F2alpha in a 27 year follow-up study of Swedish men2005In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 39, no 7, p. 763-770Article in journal (Refereed)
    Abstract [en]

    Low concentrations of selenium (Se) predict mortality and cardiovascular diseases in some populations. The effect of Se on in vivo indicators of oxidative stress and inflammation, two important features of atherosclerosis, in human populations is largely unexplored. This study investigated the longitudinal association between serum selenium (s-Se) and a golden standard indicator of oxidative stress in vivo (8-iso-prostaglandin F2, a major F2-isoprostane), an indicator of cyclooxygenase (COX)-mediated inflammation (prostaglandin F2), high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and serum amyloid A protein (SAA) in a follow-up study of 27 years. The s-Se was measured in 615 Swedish men at 50 years of age in a health investigation. The status of oxidative stress and inflammation was evaluated in a re-investigation 27 years later by quantification of urinary 8-iso-PGF2 and 15-keto-dihydro- PGF2 (a major metabolite of PGF2) and serum hsCRP, SAA and IL-6. Men in the highest quartile of s-Se at age 50 had decreased levels of 8-iso-PGF2 compared to all lower quartiles   and decreased levels of PGF2 compared to all lower quartiles   at follow-up. These associations were independent of BMI, diabetes, hyperlipidemia, hypertension, smoking, -tocopherol and β-carotene at baseline. The s-Se was not associated with hsCRP, SAA or IL-6 at follow-up. In conclusion, high concentrations of s-Se predict reduced levels of oxidative stress and subclinical COX-mediated (but not cytokine-mediated) inflammation in a male population. The associations between Se, oxidative stress and inflammation, respectively, might be related to the proposed cardiovascular protective property of Se.

  • 56.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Björklund-Bodegard, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    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.
    24-Hour ambulatory blood pressure associates inversely with prostaglandin F-2 alpha, interleukin-6 and F-2-isoprostane formation in a Swedish population of older men2012In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 5, no 2, p. 145-153Article in journal (Refereed)
    Abstract [en]

    Vasoconstrictive prostaglandins (PGs), such as PGF(2 alpha), F-2-isoprostanes, and systemic inflammation may be involved in the physiological regulation of blood pressure (BP) and the pathophysiology leading to hypertension. However, studies evaluating these parameters and BP in human populations are sparse. We analysed the cross-sectional associations between 24-hour ambulatory BP and urinary 15-keto-dihydro-PGF(2 alpha) (indicator of PG-mediated vasoconstriction and inflammation), plasma interleukin-6 (IL-6), C-reactive protein (CRP), serum amyloid A (SAA) and urinary F-2-isoprostanes (indicator of vasoconstriction and oxidative stress) in 619 men in a Swedish older population (Uppsala Longitudinal Study of Adult Men, age 78 years). Both systolic and diastolic 24-hour BP correlated inversely with concentrations of 15-keto-dihydro-PGF(2 alpha) (P < 0.01) and F-2-isoprostanes (P< 0.01) independent on other cardiovascular risk factors. Additionally, diastolic 24-hour BP inversely correlated with plasma IL-6 (P< 0.05) and 24-hour pulse pressure showed a positive linear correlation with IL-6, CRP and SAA. In conclusion, high BP is associated with decreased formation of vasoconstrictive PGF(2 alpha) and F-2-isoprostanes in this population of older men. These findings, although unlike our original hypothesis, might have an important physiological function which needs to be further evaluated.

  • 57.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Miles, Elizabeth A
    Vlachava, Maria
    Kremmyda, Lefkothea-Stella
    Noakes, Paul S
    Diaper, Norma D
    Godfrey, Keith M
    Calder, Philip C
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Enhanced prostaglandin F(2α) formation in human pregnancy and the effect of increased oily fish intake: Results from the Salmon in Pregnancy Study2012In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 86, no 1-2, p. 35-38Article in journal (Refereed)
    Abstract [en]

    Oily fish intake during pregnancy may reduce the risk of allergic diseases in infancy possibly by shifts in the fatty acid balance and subsequent altered prostaglandin (PG) formation. This intervention is the first study to evaluate if increased oily fish intake affects in vivo PGF(2α) formation during pregnancy. British pregnant women were randomised to two portions of farmed salmon weekly (n=47), or maintenance of their normal diet low in fish (n=41), from pregnancy week 20 until parturition. The concentrations of eicosapentaenoic and docosahexaenoic acids in plasma phosphatidylcholine (PC) were higher and the concentration of arachidonic acid in plasma PC was lower in the salmon group than the control group at weeks 34 and 38 of pregnancy. PGF(2α) formation was evaluated by urinary measurement of 15-keto-dihydro-PGF(2α), a major PGF(2α) metabolite, at 20, 34 and 38 weeks. In both the salmon and control groups urinary 15-keto-dihydro-PGF(2α) concentrations increased significantly during pregnancy, which may be of physiological importance. Oily fish intervention altered fatty acid concentrations but did not affect urinary 15-keto-dihydro-PGF(2α) concentrations in pregnant women.

  • 58.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Prostaglandin F2α formation is associated with mortality in a Swedish community-based cohort of older males2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 4Article in journal (Refereed)
    Abstract [en]

    Aims

    An increasing number of clinical studies highlight the importance of the inflammatory mediator prostaglandin F2α (PGF). Prostaglandin F2α activity has been suggested to play pivotal roles in the development of cardiovascular diseases and cancer. However, whether systemic PGF concentrations may signal mortality is unknown. The aim was to evaluate in vivo PGF formation, by measuring urinary 15-keto-dihydro-PGF, and mortality risk in a community setting.                     

    Methods and results

    Urinary 15-keto-dihydro-PGF was measured in a Swedish population of 670 men (aged 77–78 years) and the participants were followed up for a median of 9.7 years (383 died, among them 156 of cardiovascular causes and 102 of cancer). In Cox regression models, urinary 15-keto-dihydro-PGF was significantly associated with cardiovascular mortality [multivariate hazard ratio (HR) for 1 SD increase of urinary 15-keto-dihydro-PGF: 1.18; 95% CI:1.04–1.34; P = 0.01) independent of established cardiovascular risk factors including C-reactive protein. Urinary 15-keto-dihydro-PGF was also independently associated with total mortality (multivariate HR for 1 SD increase of urinary 15-keto-dihydro-PGF: 1.11; 95% CI: 1.01–1.21; P = 0.03). The combination of 15-keto-dihydro-PGF concentrations above the median and high serum high-sensitive C-reactive protein (>3 mg/L) was independently associated with a two-fold increased risk of cancer and total mortality (P = 0.02 and P < 0.001, respectively).                     

    Conclusion

    This is the first study to show that the inflammatory mediator PGF was independently associated with mortality and specifically cardiovascular mortality 10 years later. The results are in line with the emerging evidence of the importance of the inflammatory mediator PGF in fatal cardiovascular disease.

  • 59.
    Ingelsson, Erik
    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. 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.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    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.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Low-grade albuminuria and the incidence of heart failure in a community-based cohort of elderly men2007In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 28, no 14, p. 1739-1745Article in journal (Refereed)
    Abstract [en]

    Aims To investigate associations of urinary albumin excretion rate (UAER) and heart failure (HF) incidence in a community-based sample.

    Methods and results In a prospective study of 70-year-old men free from HF at baseline (n = 1106), UAER (from timed overnight samples) was analysed with established risk factors for HF [acute MI before baseline, acute MI during follow-up (modelled as a time-dependent covariate), hypertension, diabetes, left ventricular hypertrophy, smoking, body mass index, and glomerular filtration rate] and more recently described risk factors [high-sensitive C-reactive protein and insulin sensitivity (clamp glucose disposal rate)] as predictors of HF incidence.

    Ninety-eight participants developed HF during a median follow-up of 9.0 years. In Cox proportional hazards models adjusted for established and novel risk factors for HF, a 1 SD increase in log UAER increased the risk of HF in individuals without anti-hypertensive treatment (hazard ratio 1.49; 95% CI 1.13–1.98; P = 0.005). Furthermore, UAER remained an independent predictor of HF, also in participants without diabetes at baseline or myocardial infarction at baseline or during follow-up. There were no significant associations between UAER and HF incidence in individuals with anti-hypertensive treatment.

    Conclusion Our observations support the notion that low-grade albuminuria is a marker for subclinical cardiovascular damage that predisposes to future HF in the community.

  • 60. Ishihara, O
    et al.
    Hayashi, M
    Osawa, H
    Kobayashi, K
    Takeda, S
    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.
    Isoprostanes, prostaglandins and tocopherols in pre-eclampsia, normal pregnancy and non-pregnancy.2004In: Free Radic Res, ISSN 1071-5762, Vol. 38, no 9, p. 913-8Article in journal (Refereed)
  • 61.
    Jobs, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Nerpin, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Jobs, Magnus
    Sundström, Johan
    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, Oxidative Stress and Inflammation.
    Larsson, Anders
    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.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Association Between Serum Cathepsin S and Mortality in Older Adults2011In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 306, no 10, p. 1113-1121Article in journal (Refereed)
    Abstract [en]

    Context: Experimental data suggest that cathepsin S, a cysteine protease, is involved in the complex pathways leading to cardiovascular disease and cancer. However, prospective data concerning a potential association between circulating cathepsin S levels and mortality are lacking.

    Objective: To investigate associations between circulating cathepsin S levels and mortality in 2 independent cohorts of elderly men and women.

    Design, Setting, and Participants: Prospective study using 2 community-based cohorts, the Uppsala Longitudinal Study of Adult Men (ULSAM; n=1009; mean age: 71 years; baseline period: 1991-1995; median follow-up: 12.6 years; end of follow-up: 2006) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n=987; 50% women; mean age: 70 years; baseline period: 2001-2004; median follow-up: 7.9 years; end of follow-up: 2010). Serum samples were used to measure cathepsin S.

    Main Outcome Measure: Total mortality.

    Results: During follow-up, 413 participants died in the ULSAM cohort (incidence rate: 3.59/100 person-years at risk) and 100 participants died in the PIVUS cohort (incidence rate: 1.32/100 person-years at risk). In multivariable Cox regression models adjusted for age, systolic blood pressure, diabetes, smoking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease, higher serum cathepsin S was associated with an increased risk for mortality (ULSAM cohort: hazard ratio [HR] for 1-unit increase of cathepsin S, 1.04 [95% CI, 1.01-1.06], P=.009; PIVUS cohort: HR for 1-unit increase of cathepsin S, 1.03 [95% CI, 1.00-1.07], P=.04). In the ULSAM cohort, serum cathepsin S also was associated with cardiovascular mortality (131 deaths; HR for quintile 5 vs quintiles 1-4, 1.62 [95% CI, 1.11-2.37]; P=.01) and cancer mortality (148 deaths; HR for 1-unit increase of cathepsin S, 1.05 [95% CI, 1.01-1.10]; P=.01).

    Conclusions: Among elderly individuals in 2 independent cohorts, higher serum cathepsin S levels were associated with increased mortality risk. Additional research is needed to delineate the role of cathepsin S and whether its measurement might have clinical utility.

  • 62.
    Jobs, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jobs, Magnus
    University of Dalarna.
    Nerpin, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Iggman, David
    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.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lars, Lind
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Serum cathepsin S is associated with decreased insulin sensitivity and the development of diabetes type 2 in a community-based cohort of elderly men2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 1, p. 163-165Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes.

    RESEARCH DESIGN AND METHODS:

    Serum cathepsin S, insulin sensitivity (euglycemic-hyperinsulinemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up.

    RESULTS:

    After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase -0.09 [95% CI -0.14 to -0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08-2.01], P = 0.01).

    CONCLUSIONS:

    Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.

  • 63.
    Johansson, Jakob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ridefelt, Peter
    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.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Antithrombin administration during experimental cardiopulmonary resuscitation2004In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 62, no 1, p. 71-78Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine whether antithrombin (AT) administration during cardiopulmonary resuscitation (CPR) increased cerebral circulation and reduced reperfusion injury.

    METHODS: Ventricular fibrillation was induced in 24 anaesthetised pigs. After a 5-min non-intervention interval, CPR was started. The animals were randomised into two groups. The treatment group received AT (250 U/kg) and the control group received placebo, after 7 min of CPR. Defibrillation was attempted after 9 min of CPR. If restoration of spontaneous circulation (ROSC) was achieved, the animals were observed for 4 h. Cortical cerebral blood flow was measured using laser-Doppler flowmetry. Cerebral oxygen extraction was calculated to reflect the relation between global cerebral circulation and oxygen demand. Measurements of eicosanoids (8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha)), AT, thrombin-antithrombin complex (TAT) and soluble fibrin in jugular bulb plasma were performed to detect any signs of cerebral oxidative injury, inflammation and coagulation.

    RESULTS: There was no difference between the groups in cortical cerebral blood flow, cerebral oxygen extraction, or levels of eicosanoids, TAT or soluble fibrin in jugular bulb plasma after ROSC. In the control group reduction of AT began 15 min after ROSC and continued throughout the entire observation period (P < 0.05). Eicosanoids and TAT were increased compared to baseline in all animals (P < 0.01).

    CONCLUSIONS: In this experimental model of CPR, AT administration did not increase cerebral circulation or reduce reperfusion injury after ROSC.

  • 64. Kadiiska, M B
    et al.
    Gladen, B C
    Baird, D D
    Germolec, D
    Graham, L B
    Parker, C E
    Nyska, A
    Wachsman, J T
    Ames, B N
    Basu, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Brot, N
    Fitzgerald, G A
    Floyd, R A
    George, M
    Heinecke, J W
    Hatch, G E
    Hensley, K
    Lawson, J A
    Marnett, L J
    Morrow, J D
    Murray, D M
    Plastaras, J
    Roberts, L J
    Rokach, J
    Shigenaga, M K
    Sohal, R S
    Sun, J
    Tice, R R
    Van Thiel, D H
    Wellner, D
    Walter, P B
    Tomer, K B
    Mason, R P
    Barrett, J C
    Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning?2005In: Free Radic Biol Med, ISSN 0891-5849, Vol. 38, no 6, p. 698-710Article in journal (Refereed)
  • 65. Kadiiska, M B
    et al.
    Gladen, B C
    Baird, D D
    Graham, L B
    Parker, C E
    Ames, B N
    Basu, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Fitzgerald, G A
    Lawson, J A
    Marnett, L J
    Morrow, J D
    Murray, D M
    Plastaras, J
    Roberts, L J
    Rokach, J
    Shigenaga, M K
    Sun, J
    Walter, P B
    Tomer, K B
    Barrett, J C
    Mason, R P
    Biomarkers of oxidative stress study III. Effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in CCl4 poisoning.2005In: Free Radic Biol Med, ISSN 0891-5849, Vol. 38, no 6, p. 711-8Article in journal (Refereed)
  • 66. Kadiiska, Maria B.
    et al.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Brot, Nathan
    Cooper, Christopher
    Csallany, A. Saari
    Davies, Michael J.
    George, Magdalene M.
    Murray, Dennis M.
    Roberts, L. Jackson, II
    Shigenaga, Mark K.
    Sohal, Rajindar S.
    Stocker, Roland
    Van Thiel, David H.
    Wiswedel, Ingrid
    Hatch, Gary E.
    Mason, Ronald P.
    Biomarkers of oxidative stress study V: Ozone exposure of rats and its effect on lipids, proteins, and DNA in plasma and urine2013In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 61, p. 408-415Article in journal (Refereed)
    Abstract [en]

    Ozone exposure effect on free radical-catalyzed oxidation products of lipids, proteins, and DNA in the plasma and urine of rats was studied as a continuation of the international Biomarker of Oxidative Stress Study (BOSS) sponsored by NIEHS/NIH. The goal was to identify a biomarker for ozone-induced oxidative stress and to assess whether inconsistent results often reported in the literature might be due to the limitations of the available methods for measuring the various types of oxidative products. The time- and dose-dependent effects of ozone exposure on rat plasma lipid hydroperoxides, malondialdehyde, F-2-isoprostanes, protein carbonyls, methionine oxidation, and tyrosine- and phenylalanine oxidation products, as well as urinary malondialdehyde and F-2-isoprostanes were investigated with various techniques. The criterion used to recognize a marker in the model of ozone exposure was that a significant effect could be identified and measured in a biological fluid seen at both doses at more than one time point. No statistically significant differences between the experimental and the control groups at either ozone dose and time point studied could be identified in this study. Tissue samples were not included. Despite all the work accomplished in the BOSS study of ozone, no available product of oxidation in biological fluid has yet met the required criteria of being a biomarker. The current negative findings as a consequence of ozone exposure are of great importance, because they document that in complex systems, as the present in vivo experiment, the assays used may not provide meaningful data of ozone oxidation, especially in human studies. 

  • 67. Kadiiska, Maria B.
    et al.
    Peddada, Shyamal
    Herbert, Ronald A.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Hensley, Kenneth
    Jones, Dean P.
    Hatch, Gary E.
    Mason, Ronald P.
    Biomarkers of oxidative stress study VI. Endogenous plasma antioxidants fail as useful biomarkers of endotoxin-induced oxidative stress2015In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 81, p. 100-106Article in journal (Refereed)
    Abstract [en]

    This is the newest report in a series of publications aiming to identify a blood-based antioxidant biomarker that could serve as an in vivo indicator of oxidative stress. The goal of the study was to test whether acutely exposing Gottingen mini pigs to the endotoxin lipopolysaccharide (LPS) results in a loss of antioxidants from plasma. We set as a criterion that a significant effect should be measured in plasma and seen at both doses and at more than one time point Animals were injected with two doses of LPS at 2.5 and 514/kg iv. Control plasma was collected from each animal before the LPS injection. After the LPS injection, plasma samples were collected at 2, 16, 48, and 72 h. Compared with the controls at the same time point, statistically significant losses were not found for either dose at multiple time points in any of the following potential markers: ascorbic acid, tocopherols (alpha, delta, gamma), ratios of GSH/GSSG and cysteine/cystine, mixed disulfides, and total antioxidant capacity. However, uric acid, total GSH, and total Cys were significantly increased, probably because LPS had a harmful effect on the liver. The leakage of substances from damaged cells into the plasma may have increased plasma antioxidant concentrations, making changes difficult to interpret Although this study used a mini-pig animal model of LPS-induced oxidative stress, it confirmed our previous findings in different rat models that measurement of antioxidants in plasma is not useful for the assessment of oxidative damage in vivo.

  • 68. Kirkhus, Bente
    et al.
    Lamglait, Amandine
    Eilertsen, Karl-Erik
    Falch, Eva
    Haider, Trond
    Vik, Hogne
    Hoem, Nils
    Hagve, Tor-Arne
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Olsen, Elisabeth
    Seljeflot, Ingebjorg
    Nyberg, Lena
    Elind, Elisabeth
    Ulven, Stine M.
    Effects of similar intakes of marine n-3 fatty acids from enriched food products and fish oil on cardiovascular risk markers in healthy human subjects2012In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 107, no 9, p. 1339-1349Article in journal (Refereed)
    Abstract [en]

    There is convincing evidence that consumption of fish and fish oil rich in long-chain (LC) n-3 PUFA (n-3 LCPUFA), EPA (20 : 5n-3) and DHA (22 : 6n-3) reduce the risk of CHD. The aim of the present study was to investigate whether n-3 LCPUFA-enriched food products provide similar beneficial effects as fish oil with regard to incorporation into plasma lipids and effects on cardiovascular risk markers. A parallel 7-week intervention trial was performed where 159 healthy men and women were randomised to consume either 34 g fish pate (n 44), 500 ml fruit juice (n 38) or three capsules of concentrated fish oil (n 40), all contributing to a daily intake of approximately 1 g EPA and DHA. A fourth group did not receive any supplementation or food product and served as controls (n 37). Plasma fatty acid composition, serum lipids, and markers of inflammation and oxidative stress were measured. Compared with the control group, plasma n-3 LCPUFA and EPA: arachidonic acid ratio increased equally in all intervention groups. However, no significant changes in blood lipids and markers of inflammation and oxidative stress were observed. In conclusion, enriched fish pate and fruit juice represent suitable delivery systems for n-3 LCPUFA. However, although the dose given is known to reduce the risk of CVD, no significant changes were observed on cardiovascular risk markers in this healthy population.

  • 69.
    Krenn, Claus G.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Marklund, Stefan L
    Hjoberg, Josephine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Maintaining nitric oxide-induced airway relaxation with superoxide dismutase2007In: Nitric oxide, ISSN 1089-8603, E-ISSN 1089-8611, Vol. 16, no 4, p. 419-424Article in journal (Refereed)
    Abstract [en]

    Background

    We have previously shown that the protective effect of inhaled nitric oxide (iNO) against methacholine-induced bronchoconstriction is negated in airways subjected to hyperosmotic stress. In this study, hypothesizing that the impaired efficiency of iNO was caused by release of reactive oxygen radicals, we examined the effect of the radical scavenging enzyme superoxide dismutase (SOD).

    Methods

    Hemodynamic and respiratory measurements were performed on anesthetized rabbits after (1) inhalation of methacholine (MCh), (2) iNO (80 ppm), followed by MCh, (3) inhalation of hypertonic saline (HS), followed by iNO and MCh and (4) pre-treatment with inhalation of SOD, followed by HS, iNO and MCh. We analyzed plasma for a marker of oxidative stress, 8-iso-prostaglandin (PG)F and for a marker of activation of COX-mediated inflammatory cascades, PGF metabolite.

    Results

    Pre-treatment with SOD restored the bronchoprotective response to iNO in hyperosmotic airways. No direct effect was seen by SOD treatment on levels of 8-iso-PGF, but this marker of oxidative stress correlated positively with increased bronchoconstriction. Hyperosmotic challenge elevated levels of PGF metabolite, and pre-treatment with SOD protected against this activation of the inflammatory cascade.

    Conclusion

    SOD pre-treatment restores the relaxant effects of iNO in hyperosmotically challenged airways by attenuating oxidative stress and activation of COX-mediated inflammatory cascades.

  • 70. Kuhnt, Katrin
    et al.
    Wagner, Andreas
    Kraft, Jana
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Jahreis, Gerhard
    Dietary supplementation with 11trans- and 12trans-18:1 and oxidative stress in humans2006In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 84, no 5, p. 981-988Article in journal (Refereed)
    Abstract [en]

    Background: High consumption of trans fat has been associated with high oxidative stress in humans, which could increase the risk of the development or acceleration of several diseases, such as atherosclerosis, cancer, and type 2 diabetes.

    Objective: Several urinary and blood biomarkers of oxidative stress [8-iso-prostaglandin-F2(alpha) (PGF(2 alpha)), 15-keto-dihydro-PGF(2 alpha), and 7,8-dihydro-8-oxo-2'-deoxy-guanosine in urine and alpha-, beta, gamma-, delta-tocopherol, and retinol in plasma] were monitored to evaluate the oxidative stress induced by dietary supplementation of 11trans- and 12trans-18:1 isomers in humans during a 6-wk intervention.

    Design: After a 14-d adaptation period free of trans fatty acid supplementation (baseline), the test group (n = 12) received 3.0 g 11trans-18:1/d and 3.0 g 12trans-18:1/d (Sigma 6.0 g/d), and the control group (n = 12) consumed a control oil free of trans fatty acids and conjugated linoleic acids for 6 wk.

    Results: The postintervention concentration of urinary 8-iso-PGF(2 alpha) (free radical-induced lipid peroxidation) in the test group was significantly higher than baseline and significantly higher than that observed in the control group. The concentrations of 15-ketodihydro-PGF(2 alpha) (cyclooxygenase-mediated inflammatory response indicator) and 7,8-dihydro-8-oxo-2'-deoxy-guanosine (oxidative DNA damage) were not affected by the 11trans- and 12trans-18:1 supplementation.

    Conclusions: Although an increase in urinary 8-iso-PGF(2 alpha) was observed and the effects of prolonged high (ie, > 5.0 g/d) consumption of trans fat could be relevant to the development of disease, the mean intakes of 11trans- and 12trans-18:1 in Europeans are estimated to be significantly below the amounts administered in this study (ie, 6.0 g/d); such low intakes could minimize the possible risk of detrimental effects on human health.

  • 71.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Hansson, Lars-Olof
    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.
    Increased serum cyststin C is associated with increased mortality in elderly men2005In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 65, no 4, p. 301-305Article in journal (Refereed)
    Abstract [en]

    Renal dysfunction measured by serum creatinine is associated with increased cardiovascular morbidity and mortality. Plasma cystatin C has been shown in several studies to be superior to plasma creatinine for the estimation of glomerular filtration rate (GFR). The aim of the present study was to investigate the relationship between cystatin C and mortality in elderly men. Serum cystatin C was analyzed by nephelometry in a group of 77-year-old men (n=792) and correlated cystatin C levels with mortality during a follow-up period of 1-4 years. The cystatin C values were significantly correlated with overall mortality (p=0.013). Mortality was three times higher in the highest cystatin C quintile in relation to the lowest quintile.

  • 72.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Palm, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Insulin-like growth factor binding protein-1 (IGFBP-1) during normal pregnancy2013In: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 29, no 2, p. 129-132Article in journal (Refereed)
    Abstract [en]

    Background:

    Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is the main binder of IGFs in secretory endometrium and decidualized stromal endometrial cells and IGFBP-1 has been shown to modulate IGF bioactivities and influence fetal growth. To be able to evaluate IGFBP-1 values during pregnancy it is important to establish normal values in pregnant women.

    Materials & Methods:

    We have studied IGFBP-1 concentrations in maternal plasma from 52 healthy women with normal singleton pregnancies. Several plasma samples were collected from each woman and the samples were grouped according to gestational age into the following periods: week 7-17; week 17-24; week 24-28; week 28-31; week 31-34; week 34-38; -2 to 0 weeks prior to delivery and postpartum (>6 weeks after delivery).

    Results:

    The 2.5 and 97.5 percentiles for IGFBP-1 were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values.

    Conclusions:

    IGFBP-1 is increased during pregnancy compared to postpartum. Two peaks, at week 17-24 and just before delivery, were observed.

  • 73.
    Lindström, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Persson, Lars-Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Raqib, Rubhana
    El Arifeen, Shams
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Ekström, Eva-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Associations between oxidative parameters in pregnancy and birth anthropometry in a cohort of women and children in rural Bangladesh: The MINIMat-cohort2012In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 46, no 3, p. 253-264Article in journal (Refereed)
    Abstract [en]

    Oxidative stress is suggested as a potential mechanism in impaired foetal growth, smaller birth size and thus subsequently adult chronic diseases. We have investigated associations between oxidative stress in pregnancy and birth anthropometry (weight, height, head and chest circumferences). In the MINIMat-trial (Maternal and Infant Nutrition Interventions, Matlab) in rural Bangladesh, free 8-iso-prostaglandin P-2 alpha (lipid peroxidation) was analysed in pregnancy week 14 and 30 and 8-Hydroxy-2 '-Deoxyguanosine (DNA oxidation) in week 19. We found that higher levels of lipid peroxidation in early pregnancy were associated with larger infant size (birth length and chest circumference). In late pregnancy, no clear pattern of associations was found. Increasing level of DNA oxidation was associated with lower birth length in girls but no other associations were found. In conclusion, a higher level of lipid peroxidation in early (but not late) pregnancy was associated with a favourable larger birth size suggesting that timing of lipid peroxidation is of importance.

  • 74.
    Michaëlsson, Karl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wolk, Alicja
    Langenskiöld, Sophie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Economics.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Warensjö Lemming, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Milk intake and risk of mortality and fractures in women and men: cohort studies2014In: British Medical Journal, ISSN 1756-1833, Vol. 349, p. g6015-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine whether high milk consumption is associated with mortality and fractures in women and men.

    DESIGN: Cohort studies.

    SETTING: Three counties in central Sweden.

    PARTICIPANTS: Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997.

    MAIN OUTCOME MEASURE: Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture.

    RESULTS: During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker).

    CONCLUSIONS: High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.

  • 75.
    Miclescu, Adriana
    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, Clinical Nutrition and Metabolism.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Cardio-cerebral and metabolic effects of methylene blue in hypertonic sodium lactate during experimental cardiopulmonary resuscitation2007In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 75, no 1, p. 88-97Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Methylene blue (MB) administered with a hypertonic-hyperoncotic solution reduces the myocardial and cerebral damage due to ischaemia and reperfusion injury after experimental cardiac arrest and also increases short-term survival. As MB precipitates in hypertonic sodium chloride, an alternative mixture of methylene blue in hypertonic sodium lactate (MBL) was developed and investigated during and after cardiopulmonary resuscitation (CPR). METHODS: Using an experimental pig model of cardiac arrest (12 min cardiac arrest and 8 min CPR) the cardio-cerebral and metabolic effects of MBL (n=10), MB in normal saline (MBS; n=10) or in hypertonic saline dextran (MBHSD; n=10) were compared. Haemodynamic variables and cerebral cortical blood flow (CCBF) were recorded. Biochemical markers of cerebral oxidative injury (8-iso-PGF2alpha), inflammation (15-keto-dihydro-PGF2alpha), and neuronal damage (protein S-100beta) were measured in blood from the sagittal sinus, whereas markers of myocardial injury, electrolytes, and lactate were measured in arterial plasma. RESULTS: There were no differences between groups in survival, or in biochemical markers of cerebral injury. In contrast, the MBS group exhibited not only increased CKMB (P<0.001) and troponin I in comparison with MBHSD (P=0.019) and MBL (P=0.037), but also greater pulmonary capillary wedge pressure 120 min after return of spontaneous circulation (ROSC). Lactate administration had an alkalinizing effect started 120 min after ROSC. CONCLUSIONS: Methylene blue in hypertonic sodium lactate may be used against reperfusion injury during experimental cardiac arrest, having similar effects as MB with hypertonic saline-dextran, but in addition better myocardial protection than MB with normal saline. The neuroprotective effects did not differ.

  • 76.
    Miclescu, Adriana
    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.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Methylene blue added to a hypertonic-hyperoncotic solution increases short-term survival in experimental cardiac arrest2006In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 34, no 11, p. 2806-2813Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Methylene blue (MB), a free-radical scavenger inhibiting the production and actions of nitric oxide, may counteract excessive vasodilatation induced by nitric oxide during cardiac arrest. Effects of MB in cardiac arrest and cardiopulmonary resuscitation were investigated. DESIGN: Randomized, prospective, laboratory animal study. SETTING: University animal research laboratory. SUBJECTS: A total of 63 piglets of both sexes. INTERVENTIONS: A pig model of extended cardiac arrest (12 mins of untreated cardiac arrest and 8 mins of cardiopulmonary resuscitation) was employed to assess the addition or no addition of MB to a hypertonic saline-dextran solution. These two groups (MB and hypertonic saline-dextran group [MB group] and hypertonic saline-dextran-only group) of 21 animals were each compared with a group receiving isotonic saline (n = 21). MEASUREMENTS AND MAIN RESULTS: Although the groups were similar in baseline values, 4-hr survival in the MB group was increased (p = .02) in comparison with the isotonic saline group. Hemodynamic variables were somewhat improved at 15 mins after restoration of spontaneous circulation in the MB group compared with the other two groups. The jugular bulb levels of 8-isoprostane-prostaglandin F2alpha and 15-keto-dihydro-prostaglandin F2alpha (indicators of peroxidation and inflammation) were significantly decreased in the MB group compared with the isotonic saline group. Significant differences were recorded between the three groups in levels of protein S-100beta (indicator of neurologic injury), with lower levels in the MB group compared with the isotonic saline and hypertonic saline-dextran-only groups. Troponin I and myocardial muscle creatine kinase isoenzyme arterial concentrations (indicators of myocardial damage) were also significantly lower in the MB group. CONCLUSIONS: MB co-administered with a hypertonic-hyperoncotic solution increased 4-hr survival vs. saline in an experimental porcine model of cardiac arrest and reduced oxidative, inflammatory, myocardial, and neurologic injury.

  • 77.
    Miclescu, Adriana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nordquist, Lena
    Uppsala University.
    Hysing, Eva-Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Butler, Stephen
    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.
    Lind, Anne-Li
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Targeting oxidative injury and citokines activity in the treatment with anti-TNF alpha antibodies against CRPS 12013In: Pain Practice, ISSN 1530-7085, E-ISSN 1533-2500, Vol. 13, no 8, p. 641-648Article in journal (Refereed)
    Abstract [en]

    Cytokines and oxygen free radicals have been implicated in the potential pathogenic development of complex regional pain syndrome (CRPS). We aimed to analyze the relationship between clinical status, circulating levels of cytokines, and markers of oxidative damage during the treatment with anti-TNFα antibodies. The patient chosen for treatment had not had improvement through a number of conventional therapies and fulfilled the current diagnostic criteria for CRPS-1. We investigated the clinical variables before and after systemic administration of 1.4 mg/kg anti-TNFα antibody (infliximab), repeated after 1 month in a dose of 3 mg/kg. Blood samples were collected before and after anti-TNFα antibodies administration, and plasma was analyzed for 8-isoprostane-prostaglandin F2α (8-iso-PGF2α, a marker of oxidative injury) and cytokines (TNF-α, IL-4, IL-6, IL-7, IL-8, IL-10, IL-17A). Plasma concentrations of 8-iso-PGF2α were measured with radioimmunoassay (RIA), and the kinetics of cytokines were detected in plasma by antibody-based proximity ligation (PLA). Pathologically high levels of 8-iso-PGF2α were found in the patient. Immediately after each administration of infliximab, the levels of 8-iso-PGF2α decreased. Although the patient showed an improvement of the cutaneous dystrophic symptoms and diminished pain associated with these lesions, the levels of circulating TNFα increased after the administration of anti-TNFα antibodies. In a patient with CRPS-1 treated with anti-TNFα antibodies, we report increased levels of circulating TNFα and a temporary mitigation of oxidative stress as measured by plasma F2-isoprostane. This case report provides evidence 2 supporting the indication of monitoring the oxidative stress biomarkers during treatment with anti-TNFα antibodies in CRPS 1.

  • 78. Miles, Elizabeth A
    et al.
    Noakes, Paul S
    Kremmyda, Lefkothea-Stella
    Vlachava, Maria
    Diaper, Norma D
    Rosenlund, Grethe
    Urwin, Heidi
    Yaqoob, Parveen
    Rossary, Adrien
    Farges, Marie-Chantal
    Vasson, Marie-Paule
    Liaset, Bjørn
    Frøyland, Livar
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Garcia, Erika
    Olza, Josune
    Mesa, Maria D
    Aguilera, Concepcion M
    Gil, Angel
    Robinson, Sian M
    Inskip, Hazel M
    Godfrey, Keith M
    Calder, Philip C
    The Salmon in Pregnancy Study: study design, subject characteristics, maternal fish and marine n-3 fatty acid intake, and marine n-3 fatty acid status in maternal and umbilical cord blood2011In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 94, no 6, p. 1986S-1992SArticle in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Oily fish provides marine n-3 (omega-3) fatty acids that are considered to be important in the growth, development, and health of the fetus and newborn infant.

    OBJECTIVES:

    The objectives were to increase salmon consumption among pregnant women and to determine the effect on maternal and umbilical cord plasma marine n-3 fatty acid content.

    DESIGN:

    Women (n = 123) with low habitual consumption of oily fish were randomly assigned to continue their habitual diet or were provided with 2 portions of farmed salmon/wk to include in their diet from week 20 of pregnancy until delivery.

    RESULTS:

    Median weekly consumption frequency of study salmon in the salmon group was 1.94 portions, and total fish consumption frequency was 2.11 portions/wk in the salmon group and 0.47 portions/wk in the control group (P < 0.001). Intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from the diet, from seafood, and from oily fish were higher in the salmon group (all P < 0.001). Percentages of EPA and DHA in plasma phosphatidylcholine decreased during pregnancy in the control group (P for trend = 0.029 and 0.008, respectively), whereas they increased in the salmon group (P for trend for both < 0.001). EPA and DHA percentages were higher in maternal plasma phosphatidylcholine at weeks 34 and 38 of pregnancy and in umbilical cord plasma phosphatidylcholine in the salmon group (P < 0.001 for all).

    CONCLUSION:

    If pregnant women, who do not regularly eat oily fish, eat 2 portions of salmon/wk, they will increase their intake of EPA and DHA, achieving the recommended minimum intake; and they will increase their and their fetus' status of EPA and DHA. This trial was registered at clinicaltrials.gov as NCT00801502.

  • 79.
    Mutscher, Diana K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Gustafsson, Urban
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Anders O
    Department of Medical Sciences.
    Eriksson, Mats
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Ropivacaine may have advantates cmpared to bupivacaine in porcine endotoxemic shock2005Other (Other (popular scientific, debate etc.))
  • 80.
    Mutschler, Diana K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eriksson, M. B.
    Wikström, B. G.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berggren-Kiiski, Ritva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lagrange, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nordgren, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Microdialysis-evaluated myocardial cyclooxygenase-mediated inflammation and early circulatory depression in porcine endotoxemia2003In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 31, no 6, p. 1780-1785Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the early myocardial biochemical inflammatory response with the microdialysis technique during porcine endotoxemia and to simultaneously monitor systemic hemodynamics.

    DESIGN: Prospective, randomized, placebo-controlled trial with parallel groups.

    SETTING: Animal research laboratory at the University Hospital of Uppsala, Sweden.

    SUBJECTS: Thirteen piglets aged 12-14 wks receiving general anesthesia.

    INTERVENTIONS: After thoracotomy and the insertion of microdialysis probes in standardized locations in the left ventricle of the heart and in the quadriceps muscle, seven pigs received a continuous infusion of endotoxin, initiating a severe endotoxemic shock. Six pigs received saline instead of endotoxin.

    MEASUREMENTS AND MAIN RESULTS: Endotoxemia caused a rapid and pronounced elevation of a metabolite obtained from prostaglandin degradation, 15-keto-dihydro-PGF(2alpha), in myocardial microdialysate fluid being specific of cyclooxygenase (COX)-mediated inflammation (p <.001 vs. saline-infused controls). Simultaneously, we observed a decrease in left ventricular stroke work index in the endotoxemic pigs (p <.01 vs. saline-infused controls). Endotoxemia did not alter 15-keto-dihydro-PGF(2alpha) levels in quadriceps muscle. Endotoxemia caused increases in taurine, hypoxanthine, and magnesium in myocardial microdialysate (p <.05 vs. saline-infused controls), whereas the contents of pyruvate, lactate, inosine, adenosine, and calcium were not significantly changed.

    CONCLUSION: Endotoxemia induced a myocardial COX-mediated inflammation without signs of ischemia. In parallel, a depletion of myocardial energy substrates and a deterioration in myocardial performance were seen.

  • 81.
    Mutschler, Diana K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gustafsson, Urban
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, Anders O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Eriksson, Mats B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ropivacaine may have advantages compared to bupivacaine in porcine endotoxemic shock2006In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 111, no 2, p. 189-199Article in journal (Refereed)
    Abstract [en]

    Patients that undergo major abdominal surgery often receive epidural postoperative analgesia. Septic complications are frequently seen in this cohort. In a porcine model of endotoxemic shock, resembling human gram-negative septic shock, we evaluated the effects of two widely used local anaesthetics, bupivacaine and ropivacaine given intravenously. In the endotoxin-ropivacaine group mixed venous saturation and platelet count were higher as compared to endotoxemic controls. Mean arterial blood pressure and platelet count were higher in ropivacaine-endotoxin pigs than in bupivacaine-endotoxin ones. Bupivacaine augmented endotoxin-mediated decrease in left ventricular stroke work index. Ropivacaine displays pathophysiological advantages compared to bupivacaine in septic shock, which may be explained by improved tissue perfusion by ropivacaine.

  • 82. Nachat-Kappes, R.
    et al.
    Pinel, A.
    Combe, K.
    Lamas, B.
    Farges, M. -C
    Rossary, A.
    Goncalves-Mendes, N.
    Caldefie-Chezet, F.
    Vasson, M. -P
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Effects of Enriched Environment on COX-2, Leptin and Eicosanoids in a Mouse Model of Breast Cancer2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 12, p. e51525-Article in journal (Refereed)
    Abstract [en]

    Cyclooxygenase-2 (COX-2) and adipokines have been implicated in breast cancer. This study investigated a possible link between COX-2 and adipokines in the development of mammary tumors. A model of environmental enrichment (EE), known to reduce tumor growth was used for a syngeneic murine model of mammary carcinoma. 3-week-old, female C57BL/6 mice were housed in standard environment (SE) or EE cages for 9 weeks and transplanted orthotopically with syngeneic EO771 adenocarcinoma cells into the right inguinal mammary fat pad. EE housing influenced mammary gland development with a decrease in COX-2 expressing cells and enhanced side-branching and advanced development of alveolar structures of the mammary gland. Tumor volume and weight were decreased in EE housed mice and were associated with a reduction in COX-2 and Ki67 levels, and an increase in caspase-3 levels. In tumors of SE mice, high COX-2 expression correlated with enhanced leptin detection. Non-tumor-bearing EE mice showed a significant increase in adiponectin levels but no change in those of leptin, F2-isoprostanes, PGF2α, IL-6, TNF-α, PAI-1, and MCP-1 levels. Both tumor-bearing groups (SE and EE housing) had increased resistin, IL-6, TNF-α, PAI-1 and MCP-1 levels irrespective of the different housing environment demonstrating higher inflammatory response due to the presence of the tumor. This study demonstrates that EE housing influenced normal mammary gland development and inhibited mammary tumor growth resulting in a marked decrease in intratumoral COX-2 activity and an increase in the plasma ratio of adiponectin/leptin levels.

  • 83.
    Nerpin, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Jobs, Elisabeth
    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, Oxidative Stress and Inflammation.
    Ingelsson, Erik
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Inflammation, oxidative stress, glomerular filtration rate, and albuminuria in elderly men: a cross-sectional study2012In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 5, no 1, p. 537-Article in journal (Refereed)
    Abstract [en]

     BACKGROUND: The role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied. Accordingly, we aimed at investigating the associations between estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and markers of different inflammatory pathways and oxidative stress in a community based cohort of elderly men.

    FINDINGS: Cystatin C-based GFR, ACR, and biomarkers of cytokine-mediated inflammation (interleukin-6, high-sensitivity C-reactive protein[CRP], serum amyloid A[SAA]), cyclooxygenase-mediated inflammation (urinary prostaglandin F2alpha [PGF2alpha]), and oxidative stress (urinary F2 isoprostanes) were assessed in the Uppsala Longitudinal Study of Adult Men(n = 647, mean age 77 years).

    RESULTS: In linear regression models adjusting for age, BMI, smoking, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and treatment with statins, ACE-inhibitors, ASA, and anti-inflammatory agents, eGFR was inversely associated with CRP, interleukin-6, and SAA (beta-coefficient -0.13 to -0.19, p < 0.001 for all), and positively associated with urinary F2-isoprostanes (beta-coefficient 0.09, p = 0.02). In line with this, ACR was positively associated with CRP, interleukin-6, and SAA (beta- coefficient 0.09-0.12, p < 0.02 for all), and negatively associated with urinary F2-isoprostanes (beta-coefficient -0.12, p = 0.002). The associations were similar but with lower regression coefficients in a sub-sample with normal eGFR (>60 ml/min/1.73 m2, n = 514), with the exception that F2-isoprostane and SAA were no longer associated with eGFR.

    CONCLUSION: Our data indicate that cytokine-mediated inflammation is involved in the early stages of impaired kidney function in the elderly, but that cyclooxygenase-mediated inflammation does not play a role at this stage. The unexpected association between higher eGFR/lower albuminuria and increased F2-isoprostanes in urine merits further studies.

  • 84. Nerpin, Elisabet
    et al.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jobs, Magnus
    Larsson, Anders
    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.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Insulin sensitivity measured with euglycemic clamp is independently associated with glomerular filtration rate in a community-based cohort2008In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, no 8, p. 1550-1555Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR. RESEARCH DESIGN AND METHODS: We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C-based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1,070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years. RESULTS: Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19 [95% CI 0.69-1.68]; P < 0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, and 2-h glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, and smoking), and lifestyle factors (BMI, physical activity, and consumption of tea, coffee, and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR also remained statistically significant in participants with normal fasting plasma glucose, normal glucose tolerance, and normal GFR (n = 443; P < 0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR <50 ml/min per 1.73 m(2)) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58 [95% CI 0.40-0.84]; P < 0.004). CONCLUSIONS: Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, before the onset of diabetes or prediabetic glucose elevations. Further studies are needed in order to establish causality.

  • 85. Nitescu, N
    et al.
    Ricksten, SE
    Marcussen, N
    Haraldsson, B
    Nilsson, U
    Basu, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Guron, G
    N-acetylcysteine attenuates kidney injury in rats subjected to renal ischaemia-reperfusion2006In: Nephrol Dial Transplant, Vol. 21, no 5, p. 1240-7Article in journal (Refereed)
  • 86.
    Palm, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Involvement of inflammation in normal pregnancy2013In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 5, p. 601-605Article in journal (Refereed)
    Abstract [en]

    Objective.

    To study the role of inflammatory biomarkers of cytokine and cyclooxygenase origin throughout normal pregnancy and postpartum.

    Design.

    Longitudinal prospective study.

    Setting.

    One outpatient antenatal clinic in Uppsala, Sweden.

    Population.

    Thirty-seven healthy women with normal pregnancies and normal neonatal outcome were included. 

    Methods.

    Blood and urine samples were collected from each woman at least 6 times during pregnancy and postpartum. Plasma levels of IL-6 and TNF-α were measured by using ELISA kits and urine levels of PGF2α metabolite were measured by using RIA.

    Main outcome measures.

    Median plasma and urine levels, the 25:th to the 75:th percentile and the average change per gestational week of IL-6, TNF-α and PGF2α metabolite .

    Results.

    IL-6 levels increased significantly throughout pregnancy and postpartum levels remained high. No change in TNF-α could be seen with advancing gestational age or postpartum period. The PGF2α metabolite levels increased significantly throughout pregnancy and decreased in postpartum period.

    Conclusion.

    These results suggest that mild but significant inflammatory activity is involved in development of normal pregnancy and might have important physiological effects.

  • 87.
    Palm, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    A longitudinal study of plasma levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF), sFlt1: PlGF ratio and vascular endothelial growth factor (VEGF-A) in normal pregnancy2011In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 90, no 11, p. 1244-1251Article in journal (Refereed)
    Abstract [en]

    Objective: To describe plasma levels of angiogenic (PlGF, VEGF-A) and anti-angiogenic (sFlt1) factors as well as the sFlt1:PlGF ratio throughout normal pregnancy and postpartum.

    Design: Longitudinal prospective study.

    Setting: One outpatient antenatal clinic in Uppsala, Sweden.

    Population: Thirty-seven healthy women with normal pregnancies and normal neonatal outcome were included.

    Methods: Blood samples were collected from each woman at least six times. Plasma levels of sFlt1, PlGF and VEGF-A were measured using commercially available ELISA kits. Main outcome measures. Median plasma levels, the 25th to the 75th percentile and the average change per gestational week of sFlt1, PlGF and the sFlt1:PlGF ratio.

    Results: sFlt1 levels were relatively constant until weeks 29-30, when they increased, reaching a peak at week 40. An increase of 643pg/ml per week was observed from weeks 30 to 40. Postpartum levels were low. PlGF increased by 16pg/ml per week from early pregnancy until weeks 29-30 and thereafter decreased by 14pg/ml per week until week 40. The sFlt1:PlGF ratio decreased from weeks 9-12, was constantly low from weeks 19-20 to 37-38 and then increased to weeks 39-40. VEGF-A was detectable in only 8% of the samples during pregnancy and in 64% postpartum.

    Conclusion: This longitudinal study demonstrates how sFlt1, PlGF and the sFlt1:PlGF ratio fluctuate throughout normal pregnancy and postpartum and may serve as a reference against which these factors can be studied in complicated pregnancies. VEGF-A levels were more often detectable postpartum.

  • 88.
    Petersson, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Serum fatty acid composition and indices of stearoyl-CoA desaturase activity are associated with systemic inflammation: longitudinal analyses in middle-aged men2008In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 99, no 6, p. 1186-1189Article in journal (Refereed)
    Abstract [en]

    Altered fatty acid (FA) composition is related to insulin resistance and CVD. One possible mediator may be inflammation, but longitudinal data relating FA composition to inflammation taking insulin resistance into account are limited. We investigated the long-term association between FA composition and C-reactive protein (CRP) concentrations in a large population-based cohort study in 767 men followed for 20 years. The association between FA composition in serum cholesteryl esters at age 50 and CRP concentrations at age 70 was investigated using linear regression. In addition, desaturase activities (stearoyl-CoA desaturase-1 (SCD-1), Delta 5- and Delta 6-desaturase) were estimated using FA product-to-precursor ratios. Insulin resistance was measured directly at follow-up by euglycaemic clamp. After adjusting for confounders (smoking, physical activity, alcohol intake, obesity and erythrocyte sedimentation rate) CRP concentrations were inversely associated with the proportion of 18:2n-6 (P=0.002) and positively associated with 16:1n-7 (P=0.008), 18: 1n-9 (P=0.0003), 20:5n-3 (P=0.04) and estimated SCD-1 (P=0.005) and Delta 6-desaturase (P=0.02) activities. After adding insulin resistance to the model, 18: 1n-9, 18:2n-6 and SCD-1 remained significant predictors of CRP. A FA composition indicating low intake of 18:2n-6, high intake of SFA and high SCD-1 activity is, in a Swedish population of middle-aged men, associated with CRP concentrations 20 years later, even independently of obesity and insulin resistance.

  • 89.
    Risérus, U
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Smedman, A
    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.
    Vessby, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Metabolic effects of conjugated linoleic acid in humans: the Swedish experience.2004In: Am J Clin Nutr, ISSN 0002-9165, Vol. 79, no 6 Suppl, p. 1146S-1148SArticle in journal (Refereed)
  • 90.
    Risérus, U
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ärnlöv, J
    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.
    Effects of cis-9, trans-11 conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men2004In: Am J Clin Nutr, Vol. 80, no 2, p. 279-283Article in journal (Refereed)
  • 91.
    Risérus, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Sprecher, Dennis
    Johnson, Tony
    Olson, Eric
    Hirschberg, Sandra
    Liu, Aixue
    Fang, Zeke
    Hegde, Priti
    Richards, Duncan
    Sarov-Blat, Leli
    Strum, Jay C
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Cheeseman, Jane
    Fielding, Barbara A
    Humphreys, Sandy M
    Danoff, Theodore
    Moore, Niall R
    Murgatroyd, Peter
    O'Rahilly, Stephen
    Sutton, Pauline
    Willson, Tim
    Hassall, David
    Frayn, Keith N
    Karpe, Fredrik
    Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men2008In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 57, no 2, p. 332-339Article in journal (Refereed)
    Abstract [en]

    OBJECTIEVE-Pharmacological use of peroxisome proliferator-activated receptor (PPAR)delta agonists and transgenic overexpression of PPAR delta in mice suggest amelioration of features of the metabolic syndrome through enhanced fat oxidation in skeletal muscle. We hypothesize a similar mechanism operates in humans. RESEARCH DESIGN AND METHODS-The PPAR delta agonist (10 mg o.d. GW501516), a comparator PPAR alpha agonist (20 mu g o.d. GW590735)), and placebo were given in a double-blind, randomized, three-parallel group, 2-week study to six healthy moderately overweight subjects in each group. Metabolic evaluation was made before and after treatment including liver fat quantification, fasting blood samples, a 6-h meal tolerance test with stable isotope fatty acids, skeletal muscle biopsy for gene expression, and urinary isoprostanes for global oxidative stress. RESULTS-Treatment with GW501516 showed statistically significant reductions in fasting plasma triglycerides (-30%), apolipoprotein B (-26%), LDL cholesterol (-23%), and insulin (-11%), whereas HDL cholesterol was unchanged. A 20% reduction in liver fat content (P < 0.05) and 30% reduction in urinary isoprostanes (P = 0.01) were also observed. Except for a lowering of triglycerides (-30%, P < 0.05), none of these changes were observed in response to GW590735. The relative proportion of exhaled CO, directly originating from the fat content of the meal was increased (P < 0.05) in response to GW501516, and skeletal muscle expression of carnitine palmitoyl-transferase 1b (CPT1b) was also significantly increased. CONCLUSIONS-The PPAR delta agonist GW501516 reverses multiple abnormalities associated with the metabolic syndrome without increasing oxidative stress. The effect is probably caused by increased fat oxidation in skeletal muscle.

  • 92. Selin, Jinjin Zheng
    et al.
    Lindblad, Birgitta Ejdervik
    Rautiainen, Susanne
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Morgenstern, Ralf
    Bottai, Matteo
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Wolk, Alicja
    Are Increased Levels of Systemic Oxidative Stress and Inflammation Associated with Age-Related Cataract?2014In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 21, no 5, p. 700-704Article in journal (Refereed)
    Abstract [en]

    Oxidative stress and inflammation may be involved in the etiology of age-related cataract. This study is the first to investigate the association between urinary levels of 8-iso-prostaglandin F-2 alpha (PGF(2 alpha); as a biomarker for systemic oxidative stress in vivo) and 15-keto-dihydro-PGF(2 alpha) (as a biomarker for systemic inflammation in vivo) and risk of age-related cataract. We observed in a nested case-control study, including 258 women with incident cataract diagnosis and/or cataract extraction and 258 women without cataract, matched on age and date of urine sample collection that, women with higher levels of urinary 8-iso-PGF(2 alpha) as compared with lower levels had an increased risk of age-related cataract. There was no difference in 15-keto-dihydro-PGF(2 alpha) levels between cases and controls. Our observations lead to the hypothesis that higher systemic oxidative stress increases the risk of developing age-related cataract.

  • 93.
    Semenas, Egidijus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sharma, Hari Shanker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nozari, Ala
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Neuroprotective effects of 17-beta-estradiol after hypovolemic cardiac arrest in immature piglets: the role of nitric oxide and peroxidation2011In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 36, no 1, p. 30-37Article in journal (Refereed)
    Abstract [en]

    We recently reported that cerebral and cardiac injuries are mitigated in immature female piglets after severe hemorrhage with subsequent cardiac arrest (CA) Female sex was also associated with a smaller increase in the cerebral expression of inducible and neuronal nitric oxide synthase (nNOS). In the current study, we tested the hypothesis that exogenously administered 17β-estradiol (E2) can improve neurological outcome by NOS modulation. Thirty nine sexually immature piglets were bled to a mean arterial pressure of 35 mmHg over 15 min. Fifty μg/kg of E2 was then administered to 10 male and 10 female animals (estradiol group), while control animals (n=10 males and 9 females) received equal volume of normal saline. The animals were then subjected to ventricular fibrillation (4 min) followed by up to 15 min of open chest CPR. Vasopressin 0.4 U/kg and amiodarone 0.5 mg/kg were given and 3 ml/kg of 7.5% saline with 6% dextran was administered over 20 min. All surviving animals were euthanized after 3hr and their brains examined for histological injury and NOS expression. No significant differences were observed in survival or hemodynamics between the groups. Compared with the control group, animals in the E2 group exhibited a significantly smaller increase in nNOS and iNOS expression, a smaller blood-brain-barrier disruption and a mitigated neuronal injury. There was a significant correlation between nNOS and iNOS levels and neuronal injury. Interestingly estradiol attenuated cerebral damage (including lower activation of nNOS and iNOS) both in male and female piglets. In conclusion, in our immature piglets model of hypovolemic cardiac arrest, E2 down-regulates iNOS and nNOS expression and results in decreased BBB permeability disruption and smaller neuronal injury.

  • 94. Sentman, Marie-Louise
    et al.
    Granström, Micael
    Jakobson, Håkan
    Reaume, Andrew
    Basu, Samar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Marklund, Stefan L
    Phenotypes of mice lacking extracellular superoxide dismutase and copper- and zinc-containing superoxide dismutase.2006In: J Biol Chem, ISSN 0021-9258, Vol. 281, no 11, p. 6904-9Article in journal (Refereed)
  • 95. Sinaiko, A R
    et al.
    Steinberger, J
    Moran, A
    Prineas, R J
    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.
    Tracy, R
    Jacobs, D R
    Relation of body mass index and insulin resistance to cardiovascular risk factors, inflammatory factors, and oxidative stress during adolescence.2005In: Circulation, ISSN 1524-4539, Vol. 111, no 15, p. 1985-91Article in journal (Refereed)
  • 96. Sjogren,
    et al.
    Basu, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Rosell,
    Silveira,
    de Faire,
    Vessby, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Hamsten,
    Hellenius,
    Fisher,
    Measures of Oxidized Low-Density Lipoprotein and Oxidative Stress Are Not Related and Not Elevated in Otherwise Healthy Men With the Metabolic Syndrome.2005In: Arterioscler Thromb Vasc Biol, ISSN 1524-4636Article in journal (Refereed)
  • 97.
    Sjögren, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Basta, Giuseppina
    de Caterina, Raffaele
    Rosell, Magdalena
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Silveira, Angela
    de Faire, Ulf
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Hamsten, Anders
    Hellenius, Mai-Lis
    Fisher, Rachel M
    Markers of endothelial activity are related to components of the metabolic syndrome, but not to circulating concentrations of the advanced glycation end-product N epsilon-carboxymethyl-lysine in healthy Swedish men2007In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 195, no 2, p. e168-e175Article in journal (Refereed)
    Abstract [en]

    Endothelial function is considered important in the development of cardiovascular diseases and type 2 diabetes. Circulating advanced glycation end-products (AGEs) and dietary components have been shown to affect endothelial function in type 2 diabetics, but determinants of endothelial function in a non-diabetic population are more poorly investigated. Therefore, we investigated relationships between dietary habits, AGEs and endothelial activation in men with isolated metabolic disturbances. Circulating markers of endothelial activation (soluble forms of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and von Willebrand factor) and plasma N epsilon-carboxymethyl-lysine (CML, the predominant AGE in human plasma) were analyzed in a cross-sectional study of 294 healthy men. Individuals completed a 7-day dietary record, and metabolic and inflammatory parameters were determined. NCEP/ATPIII-criteria were used to define the metabolic syndrome. Endothelial activation was higher in individuals with the metabolic syndrome, and was positively related to certain features of the syndrome (insulin, glucose, inflammation and obesity), but not to others (triacylglycerol and blood pressure). Dietary factors were related to endothelial activation, but CML was not. Multivariate analysis revealed energy and alcohol intake, along with insulin and markers of oxidative stress and inflammation, to be positive predictors of endothelial activation. In this cohort of otherwise healthy men, endothelial activation was increased in individuals with the full metabolic syndrome, but not in those with only some of the components of the metabolic syndrome. Insulin resistance, inflammation, oxidative stress, the dietary intake of energy and alcohol, but not plasma CML, predicted endothelial activation in these men.

  • 98.
    Smedman, Annika
    et al.
    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.
    Vessby, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Konjugerad linolsyra ökade lipidperoxidationen i friska människor2001In: Riksstämmans program, 2001Conference paper (Refereed)
  • 99.
    Smedman, Annika
    et al.
    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.
    Vessby, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. Klinisk nutrition & metabolism.
    Metabolic effects of CLA supplementation in human subjects1999Conference paper (Refereed)
  • 100.
    Smedman, Annika
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences. 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 (CLA) on Lipid Peroxidation and its Regulation by COX-2 Inhibitor and Vitamin E.2001In: Proceedings of the 8th Annual Meeting of the Oxygen Society 2001, North Carolina, 2001Conference paper (Refereed)
123 51 - 100 of 119
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