| 1. |
- Andersson, Agneta, et al.
(författare)
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Whole-grain foods do not affect insulin sensitivity or markers of lipid peroxidation and inflammation in healthy, moderately overweight subjects
- 2007
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Ingår i: Journal of Nutrition. - 0022-3166 .- 1541-6100. ; 137:6, s. 1401-1407
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Tidskriftsartikel (refereegranskat)abstract
- High intakes of whole grain foods are inversely related to the incidence of coronary heart diseases and type 2 diabetes, but the mechanisms remain unclear. Our study aimed to evaluate the effects of a diet rich in whole grains compared with a diet containing the same amount of refined grains on insulin sensitivity and markers of lipid peroxidation and inflammation. In a randomized crossover study, 22 women and 8 men (BMI 28 +/- 2) were given either whole-grain or refined-grain products (3 bread slices, 2 crisp bread slices, 1 portion muesli, and 1 portion pasta) to include in their habitual daily diet for two 6-wk periods. Peripheral insulin sensitivity was determined by euglycemic hyperinsulinemic clamp tests. 8-Iso-prostaglandin F(2alpha) (8-iso PGF(2alpha)), an F(2)-isoprostane, was measured in the urine as a marker of lipid peroxidation, and highly sensitive C-reactive protein and IL-6 were analyzed in plasma as markers of inflammation. Peripheral insulin sensitivity [mg glucose . kg body wt(-1) . min(-1) per unit plasma insulin (mU/L) x 100] did not improve when subjects consumed whole-grain products (6.8 +/- 3.0 at baseline and 6.5 +/- 2.7 after 6 wk) or refined products (6.4 +/- 2.9 and 6.9 +/- 3.2, respectively) and there were no differences between the 2 periods. Whole-grain consumption also did not affect 8-iso-PGF(2alpha) in urine, IL-6 and C-reactive protein in plasma, blood pressure, or serum lipid concentrations. In conclusion, substitution of whole grains (mainly based on milled wheat) for refined-grain products in the habitual daily diet of healthy moderately overweight adults for 6-wk did not affect insulin sensitivity or markers of lipid peroxidation and inflammation.
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| 2. |
- Basu, Samar, et al.
(författare)
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Association between oxidative stress and bone mineral density
- 2001
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 288:1, s. 275-9
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Tidskriftsartikel (refereegranskat)abstract
- Free radicals have been shown to be involved in bone resorption in vitro and in rodents. We studied the effect of oxidative stress on bone mineral density (BMD) in 48 women and 53 men from a population-based study. The levels of 8-iso-PGF(2alpha) (a major F(2)-isoprostane and a biomarker of oxidative stress) and a control, 15-keto-dihydro-PGF(2alpha) (a biomarker of inflammatory response), were measured in urinary samples and their association with BMD and quantitative ultrasound (QUS) measurements were examined. In multivariate linear regression analyses, 8-iso-PGF(2alpha) levels were negatively associated with both BMD and QUS. In contrast, no association was found for 15-keto-dihydro-PGF(2alpha). Our findings establish a biochemical link between increased oxidative stress and reduced bone density and provide a rational for further studies investigating the role of pro- and antioxidants in osteoporosis. Copyright 2001 Academic Press.
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| 3. |
- Basu, Samar
(författare)
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Bioactive eicosanoids : Role of prostaglandin F-2 alpha and F-2-isoprostanes in inflammation and oxidative stress related pathology
- 2010
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Ingår i: Molecules and Cells. - : Springer Science and Business Media LLC. - 1016-8478 .- 0219-1032. ; 30:5, s. 383-391
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Forskningsöversikt (refereegranskat)abstract
- Oxidative stress and inflammation are supposed to be the key players of several acute and chronic diseases, and also for progressive aging process. Eicosanoids, especially prostaglandin F-2 alpha (PGF(2 alpha)) and F-2-isoprostanes are endogenous compounds that are involved both in physiology and the above mentioned pathologies. These compounds are biosynthesized mainly from esterified arachidonic acid through both enzymatic and non-enzymatic free radical-catalysed reactions in vivo, respectively. They have shown to possess potent biological activities in addition to their application as biomarkers of oxidative stress and inflammation. Recent advancement of methodologies has made it possible to quantify these compounds more reliably and apply them in various in vivo studies successfully. Today, experimental and clinical studies have revealed that both PGF(2 alpha) and F-2-isoprostanes are involved in severe acute or chronic inflammatory conditions such as rheumatic diseases, asthma, risk factors of atherosclerosis, diabetes, ischemia-reperfusion, septic shock and many others. These evidences promote that assessment of bioactive PGF(2 alpha) and F-2-isoprostanes simultaneously in body fluids offers unique non-invasive analytical opportunity to study the function of these eicosanoids in physiology, oxidative stress-related and inflammatory diseases, and also in the determination of potency of various radical scavengers, anti-inflammatory compounds, drugs, antioxidants and diet.
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| 4. |
- 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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| 5. |
- Basu, Samar, et al.
(författare)
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Biomarkers of free radical injury during spinal cord ischemia
- 2001
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Ingår i: FEBS Letters. - 0014-5793 .- 1873-3468. ; 508:1, s. 36-38
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Tidskriftsartikel (refereegranskat)abstract
- Plasma and urinary levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) were analysed at baseline and during the ischemia-reperfusion period in experimental spinal cord ischemia. A significant and immediate increase of 8-iso-PGF(2alpha) in plasma at the start and up to 60 min, and in the urine at 90-150 min following ischemia indicate an association of oxidative injury. The inflammatory response indicator 15-keto-dihydro-PGF(2alpha) in plasma increased significantly at the start and up to 60 min after ischemia. No such increase was seen in animals with no spinal cord ischemia. Thus, free radical mediated and cyclooxygenase catalysed products of arachidonic acid are increased during spinal cord ischemia as a consequence of oxidative injury and inflammation.
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| 6. |
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| 7. |
- Basu, Samar, et al.
(författare)
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Cellular Expression of Cyclooxygenase, Aromatase, Adipokines, Inflammation and Cell Proliferation Markers in Breast Cancer Specimen
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Current evidences suggest that expression of Ki67, cyclooxygenase (COX), aromatase, adipokines, prostaglandins, free radicals, beta-catenin and alpha-SMA might be involved in breast cancer pathogenesis. The main objective of this study was to compare expression/localization of these potential compounds in breast cancer tissues with tissues collected adjacent to the tumor using immunohistochemistry and correlated with clinical pathology. The breast cancer specimens were collected from 30 women aged between 49 and 89 years who underwent breast surgery following cancer diagnosis. Expression levels of molecules by different stainings were graded as a score on a scale based upon staining intensity and proportion of positive cells/area or individually. AdipoR1, adiponectin, Ob-R, leptin, COX-1, COX-2, aromatase, PGF(2a), F-2-isoprostanes and alpha-SMA were localised on higher levels in the breast tissues adjacent to the tumor compared to tumor specimens when considering either score or staining area whereas COX-2 and AdipoR2 were found to be higher considering staining intensity and Ki67 on score level in the tumor tissue. There was no significant difference observed on beta-catenin either on score nor on staining area and intensity between tissues adjacent to the tumor and tumor tissues. A positive correlation was found between COX-1 and COX-2 in the tumor tissues. In conclusion, these suggest that Ki67, COXs, aromatase, prostaglandin, free radicals, adipokines, beta-catenin and alpha-SMA are involved in breast cancer. These further focus the need of examination of tissues adjacent to tumor, tumor itself and compare them with normal or benign breast tissues for a better understanding of breast cancer pathology and future evaluation of therapeutic benefit.
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| 8. |
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| 9. |
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| 10. |
- 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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| 11. |
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| 12. |
- Basu, Samar, et al.
(författare)
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Development of a novel biomarker of free radical damage in reperfusion injury after cardiac arrest
- 2000
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Ingår i: FEBS Letters. - 0014-5793 .- 1873-3468. ; 470:1, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- In a porcine model of cardiopulmonary resuscitation (CPR), we investigated changes in the plasma levels of 8-iso-PGF(2alpha), a marker for oxidative injury, and 15-keto-dihydro-PGF(2alpha), an inflammatory response indicator during the post-resuscitation period after cardiac arrest. Twelve piglets were subjected to either 2 or 5 min (VF2 and VF5 group) of ventricular fibrillation (VF) followed by 5 min of closed-chest CPR. Six piglets without cardiac arrest were used as controls. In VF5 group, 8-iso-PGF(2alpha) in the jugular bulb plasma (draining the brain) increased four-fold. Jugular bulb 8-iso-PGF(2alpha) in the control group remained unchanged. The 15-keto-dihydro-PGF(2alpha) also increased four-fold in the VF5 group. Thus, 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) measurements in jugular bulb plasma may be used as biomarkers for quantification of free radical catalyzed oxidative brain injury and inflammatory response in reperfusion injury
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| 13. |
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| 14. |
- Basu, Samar, et al.
(författare)
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Effects of melagatran, a novel direct thrombin inhibitor, during experimental septic shock
- 2000
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Ingår i: Expert Opinion on Investigational Drugs. - : Informa Healthcare. - 1354-3784 .- 1744-7658. ; 9:5, s. 1129-1137
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis and endotoxaemia initiate the generation of thrombin, which is responsible for the conversion of fibrinogen to fibrin, platelet aggregation and acts as an inflammatory mediator affecting numerous types of cells, including myocardial, smooth muscle and endothelial cells. Human Gram-negative septic shock, frequently seen in intensive care units, is a condition with high mortality. This condition can be replicated in the endotoxaemic pig. As many of the toxic effects of sepsis are due to thrombin generation, it was of interest to study, using this porcine experimental septic shock model, whether inhibition of thrombin could alleviate the effects of endotoxaemia. For this purpose melagatran, a direct synthetic thrombin inhibitor with a molecular weight of 429 Da, was employed. Melagatran does not significantly interact with any other enzymes in the coagulation cascade or fibrinolytic enzymes aside from thrombin. Furthermore, melagatran does not require endogenous co-factors such as antithrombin or heparin co-Factor II for its antithrombin effect, which is important, as these inhibitors are often consumed in septic patients. We have shown that melagatran exerts a beneficial effect on renal function, as evaluated by plasma creatinine and urinary output, during experimental septic shock. These effects were most pronounced during the later phase of the experimental period, after the infusion of melagatran had been discontinued. Prevention of intrarenal coagulation may be attributable to this finding. In addition, melagatran had beneficial effects on systemic haemodynamics (left ventricular stroke work index, pulmonary capillary wedge pressure and systemic vascular resistance index) in endotoxaemic pigs. This result may be explained by the ability of melagatran to inhibit thrombin, thereby counteracting thrombin's cellular effects. Thus, it can be seen, using this experimental model of septic shock, that melagatran may help to alleviate some of the damaging effects of endotoxaemia, although more research is required to test this further.
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| 15. |
- Basu, Samar, et al.
(författare)
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Eicosanoids and Adipokines in Breast Cancer : From Molecular Mechanisms to Clinical Considerations
- 2013
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:3, s. 323-360
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Forskningsöversikt (refereegranskat)abstract
- Chronic inflammation is one of the foremost risk factors for different types of malignancies, including breast cancer. Additional risk factors of this pathology in postmenopausal women are weight gain, obesity, estrogen secretion, and an imbalance in the production of adipokines, such as leptin and adiponectin. Various signaling products of transcription factor, nuclear factor-kappaB, in particular inflammatory eicosanoids, reactive oxygen species (ROS), and cytokines, are thought to be involved in chronic inflammation-induced cancer. Together, these key components have an influence on inflammatory reactions in malignant tissue damage when their levels are deregulated endogenously. Prostaglandins (PGs) are well recognized in inflammation and cancer, and they are solely biosynthesized through cyclooxygenases (COXs) from arachidonic acid. Concurrently, ROS give rise to bioactive isoprostanes from arachidonic acid precursors that are also involved in acute and chronic inflammation, but their specific characteristics in breast cancer are less demonstrated. Higher aromatase activity, a cytochrome P-450 enzyme, is intimately connected to tumor growth in the breast through estrogen synthesis, and is interrelated to COXs that catalyze the formation of both inflammatory and anti-inflammatory PGs such as PGE(2), PGF(2 alpha), PGD(2), and PGJ(2) synchronously under the influence of specific mediators and downstream enzymes. Some of the latter compounds upsurge the intracellular cyclic adenosine monophosphate concentration and appear to be associated with estrogen synthesis. This review discusses the role of COX- and ROS-catalyzed eicosanoids and adipokines in breast cancer, and therefore ranges from their molecular mechanisms to clinical aspects to understand the impact of inflammation.
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| 16. |
- Basu, Samar, et al.
(författare)
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Evidence for Time-dependent Maximum Increase ofFree Radical Damage and Eicosanoid Formation in theBrain as Related to Duration of Cardiac Arrest andCardio-pulmonary Resuscitation
- 2003
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Ingår i: Free radical research. - : Informa UK Limited. - 1071-5762 .- 1029-2470. ; 37:3, s. 251-256
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Tidskriftsartikel (refereegranskat)abstract
- Recovery of neurological function in patients following cardiac arrest and cardiopulmonary resuscitation (CPR) is a complex event. Free radical induced oxidative stress is supposed to be involved in this process. We studied levels of 8-iso-PGF2alpha (indicating oxidative injury) and 15-keto-dihydro-PGF2alpha (indicating inflammatory response) in venous plasma obtained from the jugular bulb in a porcine model of experimental cardiopulmonary resuscitation (CPR) where 2, 5, 8, 10 or 12 min of ventricular fibrillation (VF) was followed by 5 or 8 min of closed-chest CPR. A significant increase of 8-iso-PGF2alpha was observed immediately following restoration of spontaneous circulation in all experiments of various duration of VF and CPR. No such increase was seen in a control group. When compared between the groups there was a duration-dependent maximum increase of 8-iso-PGF2alpha which was greatest in animals subjected to the longest period (VF12 min + CPR8 min) of no or low blood flow. In contrast, the greatest increase of 15-keto-dihydro-PGF2alpha was observed in the 13 min group (VF8 min + CPR5 min). Thus, a time-dependent cerebral oxidative injury occurs in conjunction which cardiac arrest and CPR.
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| 17. |
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| 18. |
- Basu, Samar
(författare)
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F2-isoprostane induced prostaglandin formation in the rabbit
- 2006
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Ingår i: Free radical research. - : Informa Healthcare. - 1071-5762 .- 1029-2470. ; 40:3, s. 273-277
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Tidskriftsartikel (refereegranskat)abstract
- F2-isoprostanes, non-enzymatic free radical mediated products of arachidonic acid, have shown to form during various oxidant stress status and have potent biological effects. This study investigates to what extent 8-iso-PGF2α (a major F2-isoprostane), a bioactive product of lipid peroxidation can modify endogenous prostaglandin F2α (PGF2α) formation since prostaglandins are inflammatory as well as potent vasoregulatory substances that modulate diverse important physiological functions, and also form during acute and chronic inflammation. An immediate appearance and disappearance of 8-iso-PGF2α was seen in both plasma and urine within a short interval after i.v. administration of 43 μg/kg of 8-iso-PGF2α to the rabbits. A successive but differential formation of PGF2α resulted in a rapid and pulsatile increase of plasma 15-keto-dihydro-PGF2α, a major metabolite of primary PGF2α. Later, this compound was excreted efficiently as intact compound into the urine during the 3 h of experiment. A 8-fold increase of PGF2α metabolite in plasma at 10 min and 12-fold increase in the urine at 30–60 after the i.v. administration of 8-iso-PGF2α was observed which continued throughout the 3 h of experiment. This observation suggests that pharmacologically administered or endogenously produced 8-iso-PGF2α during oxidant stress induces prostaglandin formation presumbly through the classical cyclooxygenase-catalysed arachidonic acid oxidation which might be inflammatory itself to the cells and exerts further vasoconstrictive effects.
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| 19. |
- Basu, Samar
(författare)
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F2-isoprostanes in human health and diseases : from molecular mechanisms to clinical implications
- 2008
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert. - 1523-0864 .- 1557-7716. ; 10:8, s. 1405-1434
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Forskningsöversikt (refereegranskat)abstract
- Oxidative stress is implicated as one of the major underlying mechanisms behind many acute and chronic diseases, and involved in normal aging. However, the measurement of free radicals or their end products is complicated. Thus, proof of association of free radicals in pathologic conditions has been absent. Isoprostanes are prostaglandin-like bioactive compounds that are biosynthesized in vivo independent of cyclooxygenases, principally through free-radical catalyzation of arachidonic acid. Isoprostanes are now considered to be reliable biomarkers of oxidative stress, as evidenced by an autonomous study organized recently by the National Institutes of Health (NIH) in the United States. A number of these compounds have potent biologic activities such as vasoconstrictive and certain inflammatory properties. Isoprostanes are involved in many human diseases. Additionally, elevated levels of F2-isoprostanes have been seen in normal human pregnancy and after intake of some fatty acids, but their physiologic assignments have not yet been distinctive. This evidence indicates that measurement of bioactive F2-isoprostanes in body fluids offers a unique noninvasive analytic utensil to study the role of free radicals in physiology, oxidative stress–related diseases, experimental acute or chronic inflammatory conditions, and also in the assessment of various antioxidants, radical scavengers, and drugs.
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| 20. |
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| 21. |
- Basu, Samar
(författare)
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Fatty acid oxidation and isoprostanes : oxidative strain and oxidative stress
- 2010
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Ingår i: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 0952-3278 .- 1532-2823. ; 82:4-6, s. 219-225
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress is implicated as one of the key causes underlying many diseases. Free radicals are important constituents of basal physiology. Assessment of free radicals or the end products of their action has proved to be difficult. Consequently, authentication of the contribution of free radicals to physiology and pathology has usually been equivocal. Isoprostanes are biosynthesized in vivo, predominantly through free radical attack on arachidonic acid and are now regarded as robust biomarkers of oxidative stress in vivo. Isoprostanes are associated with many human diseases, and their concentration is altered over the course of normal human pregnancy, but their (patho)physiological roles have not yet been clearly defined. Measurement of F-2-isoprostanes in body fluids could offer a unique analytical opportunity to study the role of free radicals in physiology and pathophysiology in order to comprehend both oxidative strain and oxidative stress.
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| 22. |
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| 23. |
- Basu, Samar, et al.
(författare)
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Inflammatory F2-isoprostane, prostaglandin F2α, pentraxin 3 levels and breast cancer risk : The Swedish Mammography Cohort
- 2016
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Ingår i: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 0952-3278 .- 1532-2823. ; 113, s. 28-32
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Breast cancer is a common cancer among women. Identifying cellular participation of F2-isoprostane, prostaglandin F2α (PGF2α) and pentraxin 3 (PTX3) in cancer we evaluated whether their prediagnostic systemic levels that originate from different inflammatory pathways were associated with breast cancer risk.METHODS: Seventy-eight breast cancer cases diagnosed after blood collection and 797 controls from the Swedish Mammography Cohort were analysed for urinary F2-isoprostane, PGF2α and plasma PTX3 levels.RESULTS: None of the biomarkers investigated were significantly associated with breast cancer risk. However, there was the suggestion of an inverse association with PTX3 with multivariable adjusted ORs (95% CI) of 0.56 (95% CI=0.29-1.06) and 0.67 (95% CI=0.35-1.28) for the second and third tertiles, respectively (ptrend=0.20). No associations were observed between F2-isoprostane (OR=0.87; 95% CI=0.48-1.57; ptrend=0.67) and PGF2α metabolite (OR=1.03; 95% CI=0.56-1.88; ptrend=0.91) comparing the top to bottom tertiles.CONCLUSIONS: The systemic levels of F2-isoprostane, PGF2α and PTX3 witnessed in women who later developed breast cancer may not provide prognostic information regarding tumor development in spite of their known involvement in situ cellular context. These observations may indicate that other mechanisms exist in controlling cellular formation of F2-isoprostane, PGF2α and PTX3 and their systemic availability in breast cancer patients.
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| 24. |
- Basu, Samar, et al.
(författare)
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Is There any Role for Serum Cathepsin S, CRP levels on Prognostic Information in Breast Cancer? : The Swedish Mammography Cohort
- 2015
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 23:16, s. 1298-1302
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is the most common cancer among women, and both low-grade inflammation and cathepsins might have important roles in breast cancer. We questioned whether prediagnostic circulating levels of C-reactive protein (CRP), cathepsin B and cathepsin S were associated with breast cancer risk. Sixty-nine incident breast cancer cases diagnosed after blood collection and 719 controls from the Swedish Mammography Cohort were analysed for systemic CRP, cathepsin B and cathepsin S. Cathepsin S and inflammation (hsCRP) adjusted cathepsin S were inversely associated with breast cancer risk (cathepsin S: OR for top vs. bottom tertile = 0.46; 95% CI = 0.23-0.92; Ptrend = 0.02; hsCRP adjusted cathepsin S: OR of 0.44; 95% CI = 0.22-0.87; Ptrend = 0.02). hsCRP was significantly associated with increased breast cancer risk (OR for top vs. bottom tertile= 2.01; 95% CI = 1.02-3.95; Ptrend = 0.04). No significant association was observed between cathepsin B and breast cancer risk (OR for top vs. bottom tertile= 0.67; 95% CI = 0.32-1.40; Ptrend = 0.30). These observations lead to hypothesis that levels of cathepsin S and hsCRP observed in women who later developed breast cancer may provide prognostic information regarding tumor development and need to be evaluated in prospective studies.
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| 25. |
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| 26. |
- Basu, Samar, et al.
(författare)
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Lipid peroxidation induced by an early inflammatory response in endotoxaemia
- 2000
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 44:1, s. 17-23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Endotoxaemic challenge promptly causes lipid peroxidation. Porcine endotoxaemia can be used to replicate severe human septic shock. This model was used to evaluate non-enzymatic [8-Iso-prostaglandin F2alpha (8-Iso-PGF2alpha)] and enzymatic [15-keto-13,14-dihydro-prostaglandin F2alpha (15-K-DH-PGF2alpha)] lipid peroxidation, respectively, in relation to survival. The aim of this study was to correlate, if possible, pathophysiologic events during endotoxaemia to the levels of these arachidonic acid metabolites. METHODS: Nineteen pigs were anaesthetised, monitored (circulatory and respiratory variables in relation to lipid peroxidation) and given a continuous 6 h E. coli endotoxin (10 microg x kg(-1) x h(-1)) infusion. All animals were mechanically ventilated at constant tidal volumes and the inspired oxygen fraction was kept constant during the experimental period. RESULTS: This endotoxin infusion caused expressed derangements in all pigs and death in 9 of them. The levels of 8-Iso-PGF2alpha, indicating oxidative injury, were different in time course, magnitude and fashion between survivors and non-survivors. The levels of 15-K-DH-PGF2alpha, indicating inflammatory response, showed a similar pattern. At 1 h the CO2 partial pressure in arterial blood was significantly higher in non-surviving pigs and correlated (r: 0.7; P<0.05) to the levels of 15-K-DH-PGF2alpha. Prostaglandin F2alpha is mainly metabolised in the lung. The lung weights were significantly (P<0.05) higher in non-surviving than in surviving animals. Both free radical and cyclooxygenase catalysed oxidative modification occurs during endotoxaemia. CONCLUSION: Increased metabolism and inflammation, as evaluated by 15-K-DH-PGF2alpha, in the group of non-survivors may mediate the increase in arterial CO2. Thus, increased lipid peroxidation seems to be associated with endotoxaemic organ dysfunction and increased mortality.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Basu, Samar
(författare)
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Novel cyclooxygenase-catalyzed bioactive prostaglandin F-2 alpha from physiology to new principles in inflammation
- 2007
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Ingår i: Medicinal research reviews (Print). - : Wiley. - 0198-6325 .- 1098-1128. ; 27:4, s. 435-468
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Forskningsöversikt (refereegranskat)abstract
- Prostaglandin F2 (PGF2), a foremost stable vasoactive cyclooxygenase (COX)-catalyzed prostaglandin, regulates a number of key physiological functions such as luteolysis, ovarian function, luteal maintenance of pregnancy, and parturition as a constitutive part of ongoing reproductive processes of the body. It has recently been implicated in the regulation of intricate pathophysiological processes, such as acute and chronic inflammation, cardiovascular and rheumatic diseases. Since the discovery of a second isoform of COXs, it has been shown that PGF2 can be formed in vivo from arachidonic acid through both isoforms of COXs, namely cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Being synthesized in various parts of the body, it metabolizes instantly to a number of rather inactive metabolites mainly in the lungs, liver, kidney, and efficiently excretes into the urine. 15-Keto-dihydro-PGF2, a major stable metabolite of PGF2 that reflects in vivo PGF2 biosynthesis, is found in larger quantities than its parent compound in the circulation and urine in basal physiological conditions, with short-lived pulses during luteolysis, induced termination of pregnancy and parturition, and is increased in tissues and various body fluids during acute, sub-chronic, and severe chronic inflammation. Further, the close relationship of PGF2 with a number of risk factors for atherosclerosis indicates its major role in inflammation pathology. This review addresses multiple aspects of PGF2 in addition to its emerging role in physiology to inflammation.
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| 31. |
- Basu, Samar, et al.
(författare)
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Oxidative injury and survival during endotoxemia
- 1998
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Ingår i: FEBS Letters. - 0014-5793 .- 1873-3468. ; 438:3, s. 159-160
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the plasma levels of 8-iso-PGF2alpha, a non-enzymatic, and 15-K-DH-PGF2alpha, a cyclooxygenase catalyzed oxidation product of arachidonic acid in an experimental porcine endotoxemic shock model. A significant (P < 0.001) and rapid appearance and disappearance of PGF2alpha metabolite after endotoxin infusion was very similar in both non-survival and survival groups indicating an acute progression and recession of inflammation. When oxidative injury was assessed by measuring free 8-iso-PGF2alpha the levels in plasma increased significantly up to 2 h and remained at this level until death among the non-survivors. This was apparently different from the survivors where the 8-iso-PGF2alpha levels increased to its height at 1 h, then decreased to the basal levels after 5 h. Thus, free radical and cyclooxygenase catalyzed oxidation of arachidonic acid occurs during endotoxemia. Free radical dependent oxidative injury following endotoxin induced inflammation may be the major cause of organ failure and increased mortality.
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| 32. |
- Basu, Samar, et al.
(författare)
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Ozone exposure effect on systemic prostaglandin F-2 alpha in rat plasma and urine may not reveal pulmonary damage through inflammation
- 2017
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Ingår i: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 0952-3278 .- 1532-2823. ; 126, s. 79-83
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Tidskriftsartikel (refereegranskat)abstract
- The acute ozone induced lung injury model has been widely used to explore injury and repair processes induced by oxidant overload. The current study evaluated acute ozone exposure effects on prostaglandin F-2 alpha (PGF(2 alpha)) in male Fischer rat plasma and urine with the hypothesis that ozone may induce an inflammatory response in the body that can be measured by the induction of PGF2 alpha. That might then lead to the identification of potential marker for acute lung injury through systemic inflammation. The time and dose-dependent effects of ozone exposure on the plasma and urinary levels of a major PGF(2 alpha) metabolite15-keto-dihydro-PGF(2 alpha) were determined using a radioimmunoassay. No statistically significant differences in the PGF(2 alpha) metabolite were found between the control and the experimental groups at either ozone exposure dose (2 ppm and 5 ppm) or any time point (2 h, 7 h and 16 h) post exposure for plasma and at 7 different post exposure time points (between 2 and 80 h) for urine. It is concluded that acute ozone exposure does not cause changes in plasma and urinary PGF(2 alpha), and therefore their measurement in plasma and urine may not be used to reveal pulmonary inflammation and damage by ozone.
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| 33. |
- Basu, Samar, et al.
(författare)
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Propofol (Diprivan-EDTA) counteracts oxidative injury and deterioration of the arterial oxygen tension during experimental septic shock
- 2001
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Ingår i: Resuscitation. - 0300-9572 .- 1873-1570. ; 50:3, s. 341-348
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Human septic shock can be replicated in the endotoxaemic pig. Endotoxaemia causes a multitude of events, including reduced PaO(2) and increased lipid peroxidation. This study was designed to evaluate the possible effects of a commonly used anaesthetic drug with known antioxidant properties (propofol) during porcine endotoxaemia.METHODS: Ten pigs were anaesthetised and given a 6 h E. coli endotoxin infusion. The animals received, randomly, a supplementary continuous infusion of propofol emulsion (containing 0.005% EDTA) or the corresponding volume of vehicle (controls). Pathophysiologic responses were determined. Non-enzymatic (by measuring plasma 8-iso-PGF(2 alpha) and enzymatic (by measuring plasma 15-keto-dihydro-PGF(2 alpha)) lipid peroxidations were evaluated. Plasma levels of the endogenous antioxidants alpha- and gamma-tocopherols, were also analysed.RESULTS: Endotoxaemia increased plasma levels of 8-iso-PGF(2 alpha) (1st-4th h) and 15-keto-dihydro-PGF(2 alpha) (1st-4th h) significantly more in controls than in the propofol+endotoxin group. PaO(2) was significantly less affected by endotoxin in the propofol treated animals (2nd-4th h). Mean arterial pressure (4th-6th h) and systemic vascular resistance (6th h) were reduced significantly more by endotoxin among the propofol-treated animals. Vitamin E (alpha-tocopherol) increased in all animals, significantly more in the propofol+endotoxin group (1/2-6th h) than in the control group.CONCLUSIONS: Propofol reduced endotoxin-induced free radical mediated and cyclooxygenase catalysed lipid peroxidation significantly. The implication is that propofol counteracts endotoxin-induced deterioration of PaO(2).
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| 34. |
- Basu, Samar, et al.
(författare)
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Propofol mitigates systemic oxidative injury during experimental cardiopulmonary cerebral resuscitation
- 2011
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Ingår i: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 0952-3278 .- 1532-2823. ; 84:5-6, s. 123-130
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Tidskriftsartikel (refereegranskat)abstract
- Effects of propofol, an intravenous anesthetic agent that exerts potent antioxidant properties, were investigated in an experimental model of cardiac arrest and cardiopulmonary resuscitation. An extended cardiac arrest with 15 randomized piglets was studied to assess the effect of propofol or its solvent intralipid as the control group. Oxidative stress (as measured by a major F(2)-isoprostane) and inflammation (a major metabolite of PGF(2α)) were evaluated in addition to the hemodynamic evaluation, protein S-100β and in situ tissue brain damage by immunochemistry at sacrifice after 3h of reperfusion following cardiac arrest and restoration of spontaneous circulation (ROSC). ROSC increased jugular bulb plasma levels of F(2)-isoprostane and PGF(2α) metabolite significantly more in controls than in the propofol-treated group. In situ tissue damage after ischemia-reperfusion was variable among the pigs at sacrifice, but tended to be greater in the control than the propofol-treated group. Propofol significantly reduced an ROSC-mediated oxidative stress in the brain.
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| 35. |
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| 36. |
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| 37. |
- 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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| 38. |
- Basu, Samar, et al.
(författare)
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Retinol palmitate counteracts oxidative injury during experimental septic shock
- 2001
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Ingår i: Annals of the Academy of Medicine, Singapore. - 0304-4602. ; 30:3, s. 265-269
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Retinols seem to be of clinical importance in ameliorating the clinical consequences of septic shock. These beneficial effects of retinols are suggested to be due to an antioxidant property. The present study was undertaken in order to confirm or rule out such an effect of retinol palmitate (RP) in experimental septic shock by measuring F2-isoprostanes and a major prostaglandin F2 alpha metabolite as indicators of oxidative injury and inflammatory response, respectively. MATERIALS AND METHODS: Fourteen anaesthetised pigs were randomly given an injection of RP (2.300 IU x kg-1) or the corresponding volume of vehicle. All pigs received a continuous infusion of E. coli endotoxin (10 micrograms x kg-1 x h-1). Blood samples were analysed for lipid peroxidation products (8-iso-PGF2 alpha), indicating free radical induced oxidative injury and 15-keto-dihydro-PGF2 alpha indicating cyclooxygenase-mediated inflammatory response). RESULTS: Significantly elevated levels of 8-iso-PGF2 alpha were seen at 3, 5 and 6 hours of endotoxaemia in the vehicle + endotoxin group as compared to RP + endotoxin group. Endotoxin induced cyclooxygenase-mediated inflammatory response was not affected by RP. CONCLUSIONS: This study is the first one to show that RP counteracts oxidative injury rather than inflammatory response in experimental septic shock. These results may be of importance for the understanding of some beneficial effects of RP during endotoxaemia (i.e. improved systemic haemodynamics and reduced serum levels of endotoxin). Our results may explain the therapeutic effects of nutrients rich in caroten/retinols used in some clinical studies.
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| 39. |
- Basu, Samar
(författare)
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The enigma of in vivo oxidative stress assessment: isoprostanes as an emerging target
- 2007
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Ingår i: Scandinavian Journal of Food & Nutrition. - : Informa UK Limited. - 1748-2984 .- 1748-2976. ; 51:2, s. 48-61
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress is believed to be one of the major factors behind several acute and chronic diseases, and may also be associated with ageing. Excess formation of free radicals in miscellaneous body environment may originate from endogenous response to cell injury, but also from exposure to a number of exogenous toxins. When the antioxidant defence system is overwhelmed, this leads to cell damage. However, the measurement of free radicals or their endproducts is tricky, since these compounds are reactive and short lived, and have diverse characteristics. Specific evidence for the involvement of free radicals in pathological situations has been difficult to obtain, partly owing to shortcomings in earlier described methods for the measurement of oxidative stress. Isoprostanes, which are prostaglandin-like bioactive compounds synthesized in vivo from oxidation of arachidonic acid, independently of cyclooxygenases, are involved in many human diseases, and their measurement therefore offers a way to assess oxidative stress. Elevated levels of F2-isoprostanes have also been seen in the normal human pregnancy, but their physiological role has not yet been defined. Large amounts of bioactive F2-isoprostanes are excreted in the urine in normal basal situations, with a wide interindividual variation. Their exact role in the regulation of normal physiological functions, however, needs to be explored further. Current understanding suggests that measurement of F2-isoprostanes in body fluids provides a reliable analytical tool to study oxidative stress-related diseases and experimental inflammatory conditions, and also in the evaluation of various dietary antioxidants, as well as drugs with radical-scavenging properties. However, assessment of isoprostanes in plasma or urine does not necessarily reflect any specific tissue damage, nor does it provide information on the oxidation of lipids other than arachidonic acid.
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| 40. |
- Basu, Samar, et al.
(författare)
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Time course and attenuation of ischaemia-reperfusion induced oxidative injury by propofol in human renal transplantation
- 2007
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Ingår i: Redox report. - 1351-0002 .- 1743-2928. ; 12:4, s. 195-202
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Tidskriftsartikel (refereegranskat)abstract
- Ischaemia-reperfusion injury resulting from interruption and restoration of blood flow might be related to free radical mediated oxidative stress and inflammation, and subsequently to post-surgery related complications. We studied the impact of renal transplantation on oxidative stress and inflammation by measuring F2-isoprostanes and prostaglandin F2α, respectively, during transplantation and post-surgery. Additionally, due to earlier observations, two dissimilar anaesthetic agents (thiopentone and propofol) were compared to determine their antioxidative capacity rather than their anaesthetic properties. Blood samples were collected before, post-intubation, immediately, 30, 60,120, 240 min, and 12 and 24 h after reperfusion. Oxidative stress and inflammatory response were detected by measuring 8-iso-PGF2α (a major F2-isoprostane and a biomarker of oxidative stress) and 15-keto-dihydro-PGF2α (a major metabolite of PGF2α and a biomarker of COX-mediated inflammatory response), respectively. Reperfusion of the transplanted graft significantly increased plasma levels of 8-iso-PGF2α. PGF2α metabolite levels, although elevated, did not reach statistical significance. In addition, significantly lower levels of 8-iso-PGF2a were observed in the propofol group compared to the thiopentone group. Together, these findings underline an augmented oxidative stress activity following an inflammatory response after human renal transplantation. Furthermore, propofol a well-known anaesthetic, counteracted oxidative stress by lowering the formation of a major F2-isoprostane.
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| 41. |
- Basu, Samar, et al.
(författare)
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Type 1 diabetes is associated with increased cyclooxygenase- and cytokine-mediated inflammation
- 2005
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 28:6, s. 1371-1375
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The extent of involvement of cyclooxygenase (COX)-mediated inflammation in type 1 diabetes is unknown, and the association between the COX- and cytokine-mediated inflammatory responses in type 1 diabetes is not fully understood. RESEARCH DESIGN AND METHODS: Plasma high-sensitivity C-reactive protein (CRP), 24-h urinary and plasma 15-keto-dihydro-prostaglandin F(2alpha) (a metabolite of prostaglandin F(2alpha) [PGF(2alpha)] and an indicator of COX-mediated inflammation), serum amyloid protein A (SAA), and interleukin (IL)-6 (indicators of inflammation) were measured in 38 subjects with type 1 diabetes and 41 healthy age- and sex-matched control subjects. RESULTS: The inflammatory indicators (urinary 15-keto-dihydro-PGF(2alpha), P < 0.01; IL-6, P < 0.04) were increased in men with diabetes. CRP and SAA did not show any significant difference between the diabetic and the control subjects. Urinary levels of 15-keto-dihydro-PGF(2alpha) correlated with the degree of glycemic control, HbA(1c) (r = 0.42, P < 0.0005). No correlation was found between the duration of diabetes and the inflammatory biomarkers or metabolic measurements. CONCLUSIONS: These results suggest that an early low-grade inflammatory process reflected by elevated levels of PGF(2alpha) and IL-6 is involved in type 1 diabetes. Thus, both COX- and cytokine-mediated inflammatory pathways are significantly related to type 1 diabetes.
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| 42. |
- Basu, Samar, et al.
(författare)
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Vitamin E in relation to lipid peroxidation in experimental septic shock
- 2000
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Ingår i: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 0952-3278 .- 1532-2823. ; 62:3, s. 195-199
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Tidskriftsartikel (refereegranskat)abstract
- Lipid peroxidation and antioxidant balance in the body is a crucial factor in the pathophysiology of various diseases. This study investigates the circulatory alpha-tocopherol levels and its relationship with 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a non-enzymatic and, 15-keto-13,14-dihydro-PGF2alpha (15-K-DH-PGF2alpha), a cyclooxygenase catalysed oxidation product of arachidonic acid in experimental septic shock in pigs. A steady decrease in alpha-tocopherol levels in plasma was observed in both survivor and non-survivor animals. A simultaneous increase of oxidative injury indicator, plasma 8-iso-PGF2alpha was seen in both groups but with a different fashion. 8-Iso-PGF2alpha levels increased steadily in the animals that died during the experiment. An early and rapid increase of plasma 15-K-DH-PGF2alpha, an inflammatory response indicator, was also observed in all animals. There was a significant difference in the kinetics of decrement of alpha-tocopherol levels and a concomitant increase in 15-K-DH-PGF2alpha levels among the non-survivors. Thus, a successive disappearance of circulatory vitamin E in conjunction with the surge of plasma isoprostanes and prostaglandins impairs the oxidant-antioxidant balance in favour of the former and may possibly have an effect on the survivality during experimental porcine septicaemia.
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| 43. |
- Bendsen, Nathalie T., et al.
(författare)
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Effect of industrially produced trans fat on markers of systemic inflammation : evidence from a randomized trial in women
- 2011
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 52:10, s. 1821-1828
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Tidskriftsartikel (refereegranskat)abstract
- Consumption of industrially produced trans fatty acids (IP-TFA) has been positively associated with systemic markers of low-grade inflammation and endothelial dysfunction in cross-sectional studies, but results from intervention studies are inconclusive. Therefore, we conducted a 16 week double-blind parallel intervention study with the objective to examine the effect of IP-TFA intake on bio-markers of inflammation, oxidative stress, and endothelial dysfunction. Fifty-two healthy overweight postmenopausal women (49 completers) were randomly assigned to receive either partially hydrogenated soybean oil (15.7 g/day IP-TFA) or control oil without IP-TFA. After 16 weeks, IP-TFA intake increased baseline-adjusted serum tumor necrosis factor (TNF) alpha by 12% [95% confidence interval (CI): 5-20; P = 0.002] more in the IP-TFA group compared with controls. Plasma soluble TNF receptors 1 and 2 were also increased by IP-TFA [155 pg/ml (CI: 63-247); P < 0.001 and 480 pg/ml (CI: 72-887); P = 0.02, respectively]. Serum C-reactive protein, interleukin (IL) 6 and adiponectin and subcutaneous abdominal adipose tissue mRNA expression of IL6, IL8, TNF alpha, and adiponectin as well as ceramide content were not affected by IP-TFA, nor was urinary 8-iso-prostaglandin-F(2 alpha). In conclusion, this dietary trial indicates that the mechanisms linking dietary IP-TFA to cardiovascular disease may involve activation of the TNF alpha system.
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| 44. |
- Berg, Kirsti, et al.
(författare)
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Acetylsalicylic acid treatment until surgery reduces oxidative stress and inflammation in patients undergoing coronary artery bypass grafting
- 2013
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 43:6, s. 1154-1163
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Acetylsalicylic acid (ASA) is a cornerstone in the treatment of coronary artery disease (CAD) due to its antiplatelet effect. Cessation of aspirin before coronary artery bypass grafting (CABG) is often recommended to avoid bleeding, but the practice is controversial because it is suggested to worsen the underlying CAD. The aims of the present prospective, randomized study were to assess if ASA administration until the day before CABG decreases the oxidative load through a reduction of inflammation and myocardial damage, compared with patients with preoperative discontinuation of ASA. METHODS: Twenty patients scheduled for CABG were randomly assigned to either routine ASA-treatment (160 mg daily) until the time of surgery (ASA), or to ASA-withdrawal 7 days before surgery (No-ASA). Blood-samples were taken from a radial artery and coronary sinus, during and after surgery and analysed for 8-iso-prostaglandin (PG) F(2α); a major F(2)-isoprostane, high-sensitivity C-reactive protein (hs-CRP), cytokines and troponin T. Left ventricle Tru-Cut biopsies were taken from viable myocardium close to the left anterior descending artery just after connection to cardiopulmonary bypass, and before cardioplegia were established for gene analysis (Illumina HT-12) and immunohistochemistry (CD45). RESULTS: 8-Iso-PGF(2α) at baseline (t(1)) were 111 (277) pmol/l and 221 (490) pmol/l for ASA and No-ASA, respectively (P = 0.065). Area under the curve showed a significantly lower level in plasma concentration of 8-iso-PGF(2α) and hsCRP in the ASA group compared with the No-ASA group with (158 pM vs 297 pM, P = 0.035) and hsCRP (8.4 mg/l vs 10.1 mg/l, P = 0.013). All cytokines increased during surgery, but no significant differences between the two groups were observed. Nine genes (10 transcripts) were found with a false discovery rate (FDR) <0.1 between the ASA and No-ASA groups. CONCLUSIONS: Continued ASA treatment until the time of CABG reduced oxidative and inflammatory responses. Also, a likely beneficial effect upon myocardial injury was noticed. Although none of the genes known to be involved in oxidative stress or inflammation took a different expression in myocardial tissue, the genetic analysis showed interesting differences in the mRNA level. Further research in this field is necessary to understand the role of the genes.
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| 45. |
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| 46. |
- Berg, K., et al.
(författare)
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Oxidative stress during coronary artery bypass operations : Importance of surgical trauma and drug treatment
- 2006
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 40:5, s. 291-297
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate oxidative stress and myocardial injury at different stages of coronary artery bypass grafting (CABG). Design. Twenty patients underwent CABG with use of cardiopulmonary bypass (CPB) and with intermittent sampling of plasma and urine. Main markers were: 8-iso-PGF(2 alpha) (oxidative stress); troponin T (myocardial injury); and 15-keto-dihydro-PGF2 alpha and hsCRP (inflammation). Results. Plasma 8-iso-PGF2 alpha increased after start of surgery, but there was no further rise during CPB or after aortic cross-clamp release and no significant myocardial arterio-venous differences. An increase in troponin T was seen early after the operation, but no relationship was established between 8-iso-PGF2 alpha and troponin T. 8-iso-PGF2 alpha levels were elevated by preoperative withdrawal of acetylsalicylic acid (ASA) but reduced by intraoperative use of heparin. 15-keto-dihydro-PGF2 alpha was elevated during operation and hsCRP following operation. Conclusions. In the present study oxidative stress was multifactorial in origin with main impacts from surgical trauma, less from CPB and little if any from myocardial ischemia-reperfusion events. In addition, cardiovascular drugs in common use like ASA and heparin seemed to influence the pro- and antioxidant balance, a finding that has to be confirmed in future studies.
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| 47. |
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| 48. |
- Bjermo, Helena, et al.
(författare)
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Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity : a randomized controlled trial
- 2012
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 95:5, s. 1003-1012
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Replacing SFAs with vegetable PUFAs has cardiometabolic benefits, but the effects on liver fat are unknown. Increased dietary n-6 PUFAs have, however, also been proposed to promote inflammation-a yet unproven theory. OBJECTIVE: We investigated the effects of PUFAs on liver fat, systemic inflammation, and metabolic disorders. DESIGN: We randomly assigned 67 abdominally obese subjects (15% had type 2 diabetes) to a 10-wk isocaloric diet high in vegetable n-6 PUFA (PUFA diet) or SFA mainly from butter (SFA diet), without altering the macronutrient intake. Liver fat was assessed by MRI and magnetic resonance proton (1H) spectroscopy (MRS). Proprotein convertase subtilisin/kexin type-9 (PCSK9, a hepatic LDL-receptor regulator), inflammation, and adipose tissue expression of inflammatory and lipogenic genes were determined. RESULTS: A total of 61 subjects completed the study. Body weight modestly increased but was not different between groups. Liver fat was lower during the PUFA diet than during the SFA diet [between-group difference in relative change from baseline; 16% (MRI; P < 0.001), 34% (MRS; P = 0.02)]. PCSK9 (P = 0.001), TNF receptor-2 (P < 0.01), and IL-1 receptor antagonist (P = 0.02) concentrations were lower during the PUFA diet, whereas insulin (P = 0.06) tended to be higher during the SFA diet. In compliant subjects (defined as change in serum linoleic acid), insulin, total/HDL-cholesterol ratio, LDL cholesterol, and triglycerides were lower during the PUFA diet than during the SFA diet (P < 0.05). Adipose tissue gene expression was unchanged. CONCLUSIONS: Compared with SFA intake, n-6 PUFAs reduce liver fat and modestly improve metabolic status, without weight loss. A high n-6 PUFA intake does not cause any signs of inflammation or oxidative stress. Downregulation of PCSK9 could be a novel mechanism behind the cholesterol-lowering effects of PUFAs.
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| 49. |
- Bräsen, Jan Hinrich, et al.
(författare)
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Extracellular superoxide dismutase accelerates endothelial recovery and inhibits in-stent restenosis in stented atherosclerotic Watanabe heritable hyperlipidemic rabbit aorta
- 2007
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 50:23, s. 2249-2253
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Tidskriftsartikel (refereegranskat)abstract
- This study examined whether local gene therapy with extracellular superoxide dismutase (EC-SOD) could inhibit in-stent restenosis in atherosclerotic Watanabe heritable hyperlipidemic rabbits. Background Stenting causes an acute increase in superoxide anion production and oxidative stress; EC-SOD is a major component of antioxidative defense in blood vessels and has powerful cardioprotective effects in ischemic myocardium. Methods Endothelial denudation and stenting were done in 36 adult (15 to 18 months old) rabbits. Catheter-mediated intramural delivery of clinical good manufacturing practice-grade adenoviruses encoding rabbit EC-SOD were done simultaneously with stenting. Control animals received adenovirus-encoding nuclear-targeted β-galactosidase (AdLacZ). Circulating markers for oxidative stress (nonesterified 8-iso-prostaglandin F2 alpha) were measured. Analysis of 6-day, 28-day, and 90-day vessel histology, radical production, oxidation-specific epitopes, and expression studies were performed. Results The EC-SOD treatment reduced oxidant production in stented vessels compared with control vessels. Early systemic recovery of total SOD activity was observed in the treated rabbits. The EC-SOD significantly accelerated endothelial recovery (67.4% ± 10.8% vs. 24.2.1% ± 4.6% at 6 days, p < 0.05; 89.3% ± 3.7% vs. 45.1% ± 9.6% at 28 days, p < 0.05), and the beneficial effect involved increased proliferation of regenerating endothelium. The EC-SOD group showed a 61.3% lower (p < 0.05) neointimal formation at 28 days, with a similar, albeit nonsignificant trend at 90 days (1.20 ± 0.32 mm2 vs. 1.88 ± 0.24 mm2, p = 0.06). Conclusions The results suggest a central pathogenetic role of oxidation sensitive signaling processes in endothelial recovery and developing in-stent restenosis in atherosclerotic vessels. Local therapy against oxidative stress represents a promising therapeutic strategy in stent-induced vascular injury. Extracellular Superoxide Dismutase Accelerates Endothelial Recovery and Inhibits In-Stent Restenosis in Stented Atherosclerotic Watanabe Heritable Hyperlipidemic Rabbit Aorta Jan Hinrich Bräsen, Olli Leppänen, Matias Inkala, Tommi Heikura, Max Levin, Fabian Ahrens, Juha Rutanen, Hubertus Pietsch, David Bergqvist, Anna-Liisa Levonen, Samar Basu, Thomas Zeller, Günter Klöppel, Mikko O. Laukkanen, Seppo Ylä-Herttuala Percutaneous coronary interventions induce oxidative stress in vessels that already have compromised antioxidative defenses. Extracellular superoxide dismutase (EC-SOD) is a major antioxidant in healthy arteries, and exogenous EC-SOD confers powerful vasculoprotective and cardioprotective effects. However, the effects of EC-SOD therapy on stent-induced vascular injury have not been assessed. We present evidence showing that local therapy with EC-SOD, delivered using clinical-grade adenoviruses, attenuated tissue oxidant production, suppressed developing in-stent restenosis, and accelerated endothelial recovery.
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| 50. |
- Bräuner, Elvira Vaclavik, et al.
(författare)
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Indoor particles affect vascular function in the aged: an air filtration-based intervention study.
- 2008
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Ingår i: American journal of respiratory and critical care medicine. - 1535-4970. ; 177:4, s. 419-25
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Exposure to particulate matter is associated with risk of cardiovascular events, possibly through endothelial dysfunction, and indoor air may be most important. OBJECTIVES: We investigated effects of controlled exposure to indoor air particles on microvascular function (MVF) as the primary endpoint and biomarkers of inflammation and oxidative stress as secondary endpoints in a healthy elderly population. METHODS: A total of 21 nonsmoking couples participated in a randomized, double-blind, crossover study with two consecutive 48-hour exposures to either particle-filtered or nonfiltered air (2,533-4,058 and 7,718-12,988 particles/cm(3), respectively) in their homes. MEASUREMENTS AND MAIN RESULTS: MVF was assessed noninvasively by measuring digital peripheral artery tone after arm ischemia. Secondary endpoints included hemoglobin, red blood cells, platelet count, coagulation factors, P-selectin, plasma amyloid A, C-reactive protein, fibrinogen, IL-6, tumor necrosis factor-alpha, protein oxidation measured as 2-aminoadipic semialdehyde in plasma, urinary 8-iso-prostaglandin F(2alpha), and blood pressure. Indoor air filtration significantly improved MVF by 8.1% (95% confidence interval, 0.4-16.3%), and the particulate matter (diameter < 2.5 mum) mass of the indoor particles was more important than the total number concentration (10-700 nm) for these effects. MVF was significantly associated with personal exposure to iron, potassium, copper, zinc, arsenic, and lead in the fine fraction. After Bonferroni correction, none of the secondary biomarkers changed significantly. CONCLUSIONS: Reduction of particle exposure by filtration of recirculated indoor air for only 48 hours improved MVF in healthy elderly citizens, suggesting that this may be a feasible way of reducing the risk of cardiovascular disease.
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