| 1. |
- Basu, Samar, et al.
(författare)
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Bioaktiva isoprostaner : nya markörer för oxidativ stress och inflammationsrelaterade sjukdomar
- 2009
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 106:5, s. 274-278
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Tidskriftsartikel (refereegranskat)abstract
- Oxidativ stress (fria radikaler) tros vara orsaken till åldrande och flera sjukdomar, däri bland arterioskleros, men det har saknats en pålitlig metodik för att påvisa aktiviteten av fria radikaler in vivo. Här presenteras isoprostaner som nya och tillförlitliga markörer för mätning av oxidativ stress in vivo genom indirekt mätning av radikalreaktioner. Isoprostaner kan ses i ökad mängd vid flera sjukdomstillstånd som är associerade med oxidativ stress och inflammation, till exempel kardiovaskulära sjukdomar, sjukdomar som är associerade med en ökad kardiovaskulär risk samt lungsjukdomar. Mätning av isoprostaner kan vidare ge ökad kunskap om fria radikalers fysiologiska roll och antioxidanternas roll vid sjukdomar samt vara ett verktyg vid utveckling av nya läkemedel mot oxidativ stress.
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| 2. |
- Basu, Samar, et al.
(författare)
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Cytokine-mediated inflammation is independently associated with insulin sensitivity measured by the euglycemic insulin clamp in a community-based cohort of elderly men
- 2011
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Ingår i: International Journal of Clinical and Experimental Medicine. - : E-Century Publishing. - 1940-5901. ; 4:2, s. 164-168
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Tidskriftsartikel (refereegranskat)abstract
- Both clinical and experimental studies suggest a close relation between an inflammatory state and insulin resistance. We investigated the association between cytokine-mediated inflammation (high sensitivity C reactive protein [hsCRP] and interleukin [IL] 6) and insulin sensitivity (insulin-mediated glucose disposal rate, assessed by the euglycemic insulin clamp) in a community-based cohort, with subgroup analyses of normal weight individuals without diabetes mellitus and metabolic syndrome (NCEP). hsCRP and IL- 6 were inversely associated with insulin sensitivity (multivariable-adjusted regression coefficient for 1-SD increase of hsCRP -0.12 (-0.21-(-0.03), p=0.01) and of IL-6 - 0.11 (-0.21-(-0.02), p=0.01) in models adjusting for age and components of the metabolic syndrome (systolic and diastolic blood pressure, antihypertensive drugs, HDL-cholesterol, triglycerides, fasting plasma glucose, waist circumference). The multivariable-adjusted association between hsCRP, IL-6 and insulin sensitivity were of a similar magnitude in normal weight individuals without diabetes and without the metabolic syndrome. Our data show that cytokine -mediated subclinical inflammation is independently associated with decreased insulin sensitivity also in apparently metabolically healthy normal weight individuals, indicating that the interplay between inflammatory processes and insulin resistance is present already in the early stages of the development of glucometabolic disease. (IJCEM1012002).
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| 3. |
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| 4. |
- Basu, Samar, et al.
(författare)
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Regulatory factors of basal F(2)-isoprostane formation: population, age, gender and smoking habits in humans.
- 2009
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Ingår i: Free radical research. - : Informa UK Limited. - 1029-2470 .- 1071-5762. ; 43:1, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress is assumed to be the key underlying factor in the pathogenesis of many common diseases. This study describes the basal levels of 8-iso-PGF(2alpha ), a major F(2)-isoprostane and an in vivo oxidative stress biomarker in healthy subjects from three countries, namely Italy, Poland and Sweden, in relation to their smoking habits, age and gender. It studied urinary 8-iso-PGF(2alpha ) in 588 subjects from Sweden (n=220), Italy (n=203) and Poland (n=165). Polish subjects had the highest levels of F(2)-isoprostanes followed by the Swedish and Italians when adjusted for smoking, age, sex and creatinine and the inter-country differences were statistically significant. Smokers had significantly higher levels of 8-iso-PGF(2alpha ) compared to non-smokers in all countries and there was a moderate decrease with age. Women had only slightly lower 8-iso-PGF(2alpha ) than men. There is a difference in F(2)-isoprostane levels in vivo between countries. Smoking, age and gender affect isoprostane formation and should be taken into consideration in clinical studies of oxidative stress.
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| 5. |
- Carlsson, Axel C, et al.
(författare)
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Kidney injury molecule (KIM)-1 is associated with insulin resistance : results from two community-based studies of elderly individuals
- 2014
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 103:3, s. 516-21
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Insulin resistance has been shown to be closely associated with glomerular filtration rate and urinary albumin/creatinine ratio, even prior to the development of diabetes. Urinary kidney injury molecule 1 (KIM-1) is a novel, highly specific marker of kidney tubular damage. The role of insulin resistance in the development of kidney tubular damage is not previously reported. Thus, we aimed to investigate the associations between insulin sensitivity (assessed by HOMA) and urinary KIM-1.DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Two community-based cohorts of elderly individuals were investigated: Prospective Investigation of the vasculature in Uppsala seniors (PIVUS, n=701; mean age 75 years, 52% women); and Uppsala Longitudinal Study of adult men (ULSAM, n=533; mean age 78 years).RESULTS: Lower insulin sensitivity was associated with higher urinary KIM-1 in both cohorts after adjustments for age, BMI, blood pressure, antihypertensive treatment, glomerular filtration rate, and urinary albumin-creatinine ratio (PIVUS: regression coefficient for 1-SD higher HOMA-IR 0.11, 95% CI 0.03-0.20, p=0.009, and ULSAM: 0.13, 95% CI 0.04-0.22, p=0.007). Results were similar in individuals without diabetes, with normal kidney function and normo-albuminuria.CONCLUSIONS: Our findings in elderly individuals support the notion that the interplay between an impaired glucose metabolism and renal tubular damage is evident even prior to the development of diabetes and overt kidney disease.
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| 6. |
- Carlsson, Axel C, et al.
(författare)
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Soluble TNF receptors and kidney dysfunction in the elderly
- 2014
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 25:6, s. 1313-1320
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Tidskriftsartikel (refereegranskat)abstract
- The importance of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in the development of kidney disease is being unraveled. Yet, community-based data regarding the role of sTNFRs are lacking. We assessed serum sTNFRs and aspects of kidney damage cross-sectionally in two independent community-based cohorts of elderly participants: Prospective Investigation of the Vasculature in Uppsala Seniors (n=815; mean age, 75 years; 51% women) and Uppsala Longitudinal Study of Adult Men (n=778; mean age, 78 years). Serum sTNFR1 correlated substantially with different aspects of kidney pathology in the Uppsala Longitudinal Study of Adult Men cohort (R=-0.52 for estimated GFR, R=0.22 for urinary albumin-to-creatinine ratio, and R=0.17 for urinary kidney injury molecule-1; P<0.001 for all), with similar correlations in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. These associations remained significant after adjustment for age, sex, inflammatory markers, and cardiovascular risk factors and were also evident in participants without diabetes. Serum sTNFR2 was associated with all three markers in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort (P<0.001 for all). Our findings from two independent community-based cohorts confirm and extend results of previous studies supporting circulating sTNFRs as relevant biomarkers for kidney damage and dysfunction in elderly individuals, even in the absence of diabetes.
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| 7. |
- Carlsson, Axel C, et al.
(författare)
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Urinary kidney injury molecule 1 and incidence of heart failure in elderly men
- 2013
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Ingår i: European Journal of Heart Failure. - : Oxford University Press. - 1388-9842 .- 1879-0844. ; 15:4, s. 447-446
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: There is growing recognition of the clinical importance of cardiorenal syndrome-the bidirectional interplay between kidney and cardiac dysfunction. Yet, the role of kidney tubular damage in the development of heart failure is less studied. The objective of this study was to investigate whether urinary kidney injury molecule (KIM)-1, a specific marker of tubular damage, predisposes to an increased heart failure risk.METHODS AND RESULTS: This was a community-based cohort study [Uppsala Longitudinal study of Adult Men (ULSAM)] of 565, 77-year-old men free from heart failure at baseline. Heart failure hospitalizations were used as outcome. During follow-up (median 8.0 years), 73 participants were hospitalized for heart failure. In models adjusted for cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, LDL/HDL ratio, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, LV hypertrophy, and prevalent cardiovascular disease) and markers of kidney dysfunction and damage [cystatin C-based glomerular filtration rate (GFR) and urinary albumin/creatinine ratio], a higher urinary KIM-1/creatinine ratio was associated with higher risk for heart failure (hazard ratio upper vs. lower tertile, 1.81; 95% confidence interval 1.01-3.29; P < 0.05). Participants with a combination of low GFR (<60 mL/min/1.72 m(2)) and high KIM-1/creatinine (>128 ng/mmol) had a 3-fold increase in heart failure risk compared with participants with normal GFR and KIM-1 (P < 0.001).CONCLUSION: Our findings suggest that kidney tubular damage predisposes to an increased risk for heart failure in the community. Further studies are needed to clarify the causal role of KIM-1 in the development of heart failure, and to evaluate the clinical utility of urinary KIM-1 measurements.
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| 8. |
- Carlsson, Axel C, et al.
(författare)
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Urinary kidney injury molecule-1 and the risk of cardiovascular mortality in elderly men
- 2014
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Ingår i: American Society of Nephrology. Clinical Journal. - 1555-9041 .- 1555-905X. ; 9:8, s. 1393-1401
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997-2001; median follow-up 8.1 years; end of follow-up, 2008).RESULTS: During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C-based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m(2)), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m(2)), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).CONCLUSIONS: These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.
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| 9. |
- Fall, Tove, 1979-, et al.
(författare)
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Reference Intervals for Fecal Calprotectin in Adults Using Two Different Extraction Methods in the Uppsala-SCAPIS Cohort
- 2017
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Ingår i: Clinical Laboratory. - 1433-6510. ; 63:9, s. 1493-1496
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fecal calprotectin measurement is generally recommended to exclude inflammatory bowel disease (IBD) in patients with suspected IBD. A problem with the fecal calprotectin assays so far has been the rather long test-turnaround times. Recently a particle enhanced turbidimetric immunoassay (PETIA) for fecal calprotectin with assay times of approximately 10 minutes has been introduced on the European market. The aim of this study was to define reference intervals for adults with this new fecal calprotectin PETIA using two different extraction methods. Methods: Samples were collected from 382 healthy individuals from the Swedish CArdioPulmonary bioImage Study (SCAPIS) Uppsala cohort in the age range 50 - 65 years. 202 samples were processed with CALEX® Cap extraction device (BÜHLMANN, Schönenbuch, Switzerland) and 180 samples were extracted using weighed samples. The extracted samples were analyzed on a Mindray BS-380 using the fCal Turbo PETIA reagent (BÜHLMANN). Results: The calculated reference values for the Calex device were < 199 µg/g for the whole cohort, < 184 µg/g for females, and < 215 µg/g for males, while the corresponding values for weighed samples were < 153 µg/g for the whole cohort, < 141 µg/g for females, and < 215 µg/g for males. There were no significant statistical differences for calprotectin levels in males and females. Conclusions: The CALEX device yielded slightly higher calprotectin values. As there were no significant gender differences, the study indicates gender independent reference intervals of < 199 µg/g feces for the CALEX device and < 153 µg/g feces for weighed samples in patients in the 50 - 65 year age range.
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| 10. |
- Fall, Tove, 1979-, et al.
(författare)
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Reference Intervals for Fecal Calprotectin in Pregnant Women Using a Particle Enhanced Turbidimetric Assay
- 2019
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Ingår i: Clinical Laboratory. - 1433-6510. ; 65:7, s. 1293-1297
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fecal calprotectin is widely used as a marker for inflammatory bowel diseases (IBD). IBD often affects women during their reproductive years, but there are no established reference intervals during pregnancy. The aim of the present study was to define reference values during pregnancy and in the postpartum period to allow comparisons between patient results and reference values.METHODS: Fecal samples were collected from 84 healthy females during pregnancy week 26 to 28 and a second sample was collected six months after delivery. The samples were weighed, extracted, and centrifugated to remove debris. The extracted samples were then analyzed on a chemistry analyzer using a particle enhanced turbidimetric immunoassay reagent.RESULTS: The calculated reference interval during pregnancy was < 127 μg/g (90% confidence interval, 90 - 164 μg/g) and the corresponding reference interval during the postpartum period was < 143 μg/g (60 - 226 μg/g). There were no significant statistical differences between F-calprotectin values analyzed at the two sampling times.CONCLUSIONS: The reference values are slightly higher than the cutoff values of 50 - 100 μg/g often used as General cutoff for fecal calprotectin.
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