| 1. |
- Chen, Jie, et al.
(författare)
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Effects of autoantibodies removed by immunoadsorption from patients with dilated cardiomyopathy on neonatal rat cardiomyocytes
- 2006
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Ingår i: The European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 8:5, s. 460-467
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Immunoadsorption has been shown to improve cardiac performance and reduce mortality in patients with dilated cardiomyopathy. In this study, the underlying mechanism for these beneficial effects was investigated in cultured rat cardiomyocytes. METHODS AND RESULTS: Immunoadsorption was performed in patients with dilated cardiomyopathy (n=7). Antibody-induced complement-dependent cytotoxicity was investigated by colorimetric MTT. Autoantibodies against the beta(1)-adrenoceptor were detected by ELISA and purified. Column eluent from six patients exhibited a cytotoxic effect, three patients were positive for the beta(1)-adrenoceptor autoantibodies. The purified autoantibodies were able to visualize the beta(1)-adrenoceptors by immunocytofluorescence on rat cardiomyocytes, and also displayed partial agonist properties and induced a positive chronotropic effect, which were blocked by the beta(1)-selective antagonist bisoprolol and the peptide corresponding to the beta(1)-adrenoceptor. Column eluent from one patient induced apoptosis in nick end labelling test (8.1+/-1.7% vs. 2.9+/-1.2% in control, p<0.05). CONCLUSION: Autoantibodies removed by immunoadsorption from patients with dilated cardiomyopathy have a pathophysiological role, as shown by the complement-dependent cytotoxicity and chronotropic action on rat cardiomyocytes. This implies that removal of circulating autoantibodies might be part of the underlying mechanism for improved cardiac function.
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| 2. |
- Garcia-Ceja, Enrique, et al.
(författare)
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A Feature Importance Analysis for Soft-Sensing-Based Predictions in a Chemical Sulphonation Process
- 2020
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Ingår i: 2020 IEEE Conference on Industrial Cyberphysical Systems (ICPS). ; , s. 62-66
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Konferensbidrag (refereegranskat)abstract
- In this paper we present the results of a feature importance analysis of a chemical sulphonation process. The task consists of predicting the neutralization number (NT), which is a metric that characterizes the product quality of active detergents. The prediction is based on a dataset of environmental measurements, sampled from an industrial chemical process. We used a soft-sensing approach, that is, predicting a variable of interest based on other process variables, instead of directly sensing the variable of interest. Reasons for doing so range from expensive sensory hardware to harsh environments, e.g., inside a chemical reactor. The aim of this study was to explore and detect which variables are the most relevant for predicting product quality, and to what degree of precision. We trained regression models based on linear regression, regression tree and random forest. A random forest model was used to rank the predictor variables by importance. Then, we trained the models in a forward-selection style by adding one feature at a time, starting with the most important one. Our results show that it is sufficient to use the top 3 important variables, out of the 8 variables, to achieve satisfactory prediction results. On the other hand, Random Forest obtained the best result when trained with all variables.
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| 3. |
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| 4. |
- Haugen, Espen, 1973, et al.
(författare)
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Increased adiponectin level in parallel with increased NT-pro BNP in patients with severe heart failure in the elderly: A hospital cohort study.
- 2008
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 125:2, s. 216-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Adiponectin, which is a collagen-like plasma protein produced by adipose tissue, has in general anti-atherogenic and anti-inflammatory effects. Recently it was shown to be elevated in chronic heart failure patients. However whether this holds true in the elderly heart failure patients who are often associated with malnutrition remains unknown. MATERIALS AND METHODS: Patients with severe heart failure (n=92, average age >70 years, NYHA III-IV) and age-matched healthy volunteers (n=70) as control were enrolled in the present study. Serum levels of adiponectin and NT-pro BNP were measured. RESULTS: Adiponectin levels were significantly increased in heart failure patients for those >70 years old as compared with control group. There were higher adiponectin levels in non-ischemic heart failure as compared with those with ischemic cause. Serum adiponectin levels were positively associated with serum NT-pro BNP levels. There was a strong trend of higher adiponectin levels in those who died as compared with those who survived. CONCLUSION: Serum adiponectin levels were increased in the very elderly heart failure patients, and particularly in those with underlying non-ischemic origin. Adiponectin levels appear to be associated with increased mortality.
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| 5. |
- Haugen, Espen, 1973, et al.
(författare)
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Increased interleukin-6 but not tumour necrosis factor-alpha predicts mortality in the population of elderly heart failure patients.
- 2008
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Ingår i: Experimental and clinical cardiology. - 1205-6626. ; 13:1, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increased proinflammatory cytokines have mainly been studied in younger patients with heart failure and are regarded as prognostic markers. However, whether this holds true in elderly patients with heart failure remains uncertain. OBJECTIVES: To determine whether inflammation is equally important in the progression of heart failure in the elderly as has been previously reported in younger patients, and whether cytokine level can predict mortality in this population of elderly heart failure patients. METHODS: The cytokine profile in an elderly patient group with severe heart failure (n=54, mean [+/- SD] age of 80.1+/-5.0 years, New York Heart Association class III or IV) was compared with that of age-matched healthy individuals (n=70). Of the 54 study patients, 46% were hypertensive, 54% had coronary artery disease, 43% had atrial fibrillation and 24% had a previous stroke. One-year mortality was 24%. RESULTS: The results showed increased levels of interleukin-6 (IL-6), tumour necrosis factor-alpha and epidermal growth factor in the heart failure patients compared with those in the control group. Moreover, IL-6, tumour necrosis factor-alpha and vascular endothelial growth factor were significantly increased in patients who died within one year. Further logistic regression analyses showed that IL-6 was the only significant predictor of one-year mortality. In a subgroup of heart failure patients with atrial fibrillation, there were significant cytokine activations, whereas in a subgroup with ischemia or diabetes, cytokines were less activated. CONCLUSIONS: In the present octogenarian group with heart failure, there were significant increases of inflammatory cytokines that were associated with mortality, and IL-6 was the only cytokine to predict one-year mortality. Cytokine activation was more pronounced in the subgroup of patients with heart failure and concomitant atrial fibrillation.
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| 6. |
- Haugen, Espen, 1973, et al.
(författare)
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Parallel gene expressions of IL-6 and BNP during cardiac hypertrophy complicated with diastolic dysfunction in spontaneously hypertensive rats.
- 2007
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 115:1, s. 24-8
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Tidskriftsartikel (refereegranskat)abstract
- There is increasing evidence showing that inflammation is involved in heart failure. However, heart failure may differ greatly due to different aetiologies. The role of inflammation in hypertensive heart failure, particularly in the early stage of cardiac dysfunction, has not been studied completely. This study aims at finding out whether inflammation is involved in the early stage of heart dysfunction due to hypertension. METHODS: Ten spontaneously hypertensive rats (SHR) and ten age-matched Wistar rats were used. Cardiac morphology and function, as well as coronary flow reserve, were examined by echocardiography. mRNAs for cytokines and brain natriuretic peptide were determined by RT-PCR. RESULTS: The results demonstrate cardiac hypertrophy with increased heart/body weight ratio in SHR. Echocardiographic examination has shown that SHR developed diastolic heart dysfunction as determined by tissue Doppler without decrease in systolic function. In heart biopsies, there were increased mRNA levels for interleukin-6 and brain natriuretic peptide whereas decreased mRNA for interleukin-2, beta adrenergic receptor, interferon and NFkb in SHR as compared to WKY group. Coronary flow remained unchanged in both groups. CONCLUSION: SHR developed cardiac hypertrophy complicated with diastolic heart dysfunction with increased expression of brain natriuretic peptide, down-regulation of beta adrenergic receptors and simultaneous up-regulation of IL-6, which indicates active proinflammatory process as, at least partly, underlying mechanism during the early stage when cardiac hypertrophy associated with diastolic dysfunction occurs.
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| 7. |
- Haugen, Espen, 1973
(författare)
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Pathophysiological role and clinical relevance of cytokines in hypertensive heart failure. A combined clinical and experimental study
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although mortality due to heart failure has decreased significantly in the last decade since the introduction of ACE-inhibitors and ?-adrenergic receptor blockers in the management of heart failure, chronic heart failure is still one of the most important causes of morbidity and mortality and has a very high frequency for readmission to hospitalization because of the aggravation of heart failure. This accounts for a significantly higher health-care expenditure that is twice as much the cost for cancer. One of the most important reasons is that the present heart failure management is mostly directed at the restoration of neurohormonal imbalance, rather than targeting the primary mechanism of the disease. There is an increasing body of evidence showing that inflammation is involved in the pathophysiology of heart failure, particularly in the young. Moreover, one of the most frequently seen sub-sets of heart failure in daily clinical practice is heart failure due to hypertension, particularly in the elderly. Heart failure in the elderly is often characterized by predominance of diastolic dysfunction and comorbidity. Therefore, heart failure is heterogeneous and the underlying mechanism may differ greatly from one cause to another and between the young and the elderly. The portfolio of cytokines includes at least tumor necrosis factor ? and interleukin-6 in the cardiovascular system. These have been referred to as proinflammatory cytokines. These inflammatory mediators are known to be expressed by all nucleated cell types residing in the myocardium including myocytes, suggesting that these molecules may not only orchestrate an inflammatory response but also participate directly in the pathophysiological processes such as remodelling. Thus, it is very likely that the elaboration of cytokines represents not only the mechanism responsible for worsening of heart failure, but also the mechanism of initiating heart failure. In heart failure in younger patients, the circulating level of tumor necrosis factor ? has been shown to be elevated. However, whether this is similarly elevated in elderly heart failure patients remains poorly understood. Since majority of heart failure patients are over 65 years old, this issue becomes very important and clinically relevant. Furthermore, recent large randomized clinical trials of tumor necrosis factor antagonists in heart failure patients in the younger population showed disappointing results. Therefore, the significance of cytokine activation in heart failure remains controversial. Is cytokine activation important in heart failure? Is this equally important in heart failure irrespective of age? If so, why was tumor necrosis factor ? inhibition not effective in chronic heart failure in recent clinical trials? We hypothesize that proinflammatory cytokine activation is pathophysiologically important and clinically relevant in hypertensive heart failure. However, cytokine activation may differ between the young and the elderly. Moreover, suppression of a single cytokine in heart failure may not be a rational and effective treatment strategy because it may lead to the upregulation of other proinflammatory cytokines. In this PhD thesis, we studied cytokine mRNA expressions in myocardium in the early stage of hypertensive heart failure in Spontaneously Hypertensive Rats with or without treatment with tumor necrosis factor ? antagonist Etanercept. Moreover, we characterized circulating cytokine profile among heart failure patients in the elderly. We have shown that there were cardiac hypertrophy in Spontaneously Hypertensive Rats with increased heart/body weight ratio, diastolic heart dysfunction as determined by the tissue Doppler, increased mRNA levels for interleukin 6 and brain natriuretic peptide whereas a decreased mRNA for the ?-adrenergic receptor. Chronic treatment with etanercept in Spontaneously Hypertensive Rats resulted in decreased relative wall thickness as well as increased cardiac reserve and higher blood pressure. In addition, interleukin-6 was further upregulated compared with placebo treatment. In human studies, our results have shown increased interleukin-6 and tumor necrosis factor ? in heart failure patients compared with those in the control group. Moreover, interleukin-6, tumor necrosis factor ? and vascular endothelial growth factor were significantly increased in patients who died within one year. Further logistical regression analyses showed that interleukin-6 is the only significant predictor for one-year mortality. In a subgroup of heart failure with atrial fibrillation there were significant cytokine activations, whereas in subgroups such as those with ischemia or diabetes, cytokines were less activated. Furthermore, we have shown significantly increased adiponectin levels in these elderly heart failure patients. In conclusion, in hypertensive heart failure, both clinically and experimentally, there is increased cytokine activation. In case of heart failure in the elderly, there is different activated cytokine profile as compared with that in the younger. Moreover, it appears that it is not enough to suppress one single cytokine because the cytokine network is redundant. However, more fundamental studies are needed to understand this complex cytokine network before an appropriate anti-inflammatory therapy emerges. Key Words: hypertension, cardiac remodelling, heart failure, cytokines, interleukin 6, etanercept, adiponectin, elderly.
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| 8. |
- Haugen, Espen, 1973, et al.
(författare)
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TNFalpha antagonist upregulates interleukin-6 in rats with hypertensive heart failure.
- 2008
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 130:1, s. 64-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tumor necrosis factor alpha (TNFalpha) has been shown to be a prognostic marker in heart failure, but recent clinical trials using TNFalpha antagonists in patients with severe heart failure have been disappointing. Hypertension is one of most common causes to chronic heart failure in humans. HYPOTHESIS: Suppression of a single cytokine in CHF is not an effective treatment strategy because it leads to the upregulation of other proinflammatory cytokines. OBJECTIVES: The aim of the present study was to investigate the effect of chronic treatment with a TNFalpha antagonist in a rat model of the early stage of heart failure due to hypertension. METHODS: Spontaneously hypertensive rats (SHR, n=30) and healthy Wistar Kyoto rats (WKY, n=30) were treated with either the TNFalpha antagonist etanercept or placebo for 12 weeks. At the end of the study, the rats were 26 weeks old and indices of cardiac structure, function and cytokines were analyzed. RESULTS: SHR displayed early stage of heart failure as shown by increased heart weight/body weight ratio and relative wall thickness by echocardiography, downregulated myocardial beta(1)-adrenoceptor, and upregulated myocardial brain natriuretic peptide and interleukin-6 (IL6). Chronic treatment with etanercept in SHR resulted in decreased relative wall thickness but also increased cardiac reserve and higher blood pressure. In addition, IL6 was further upregulated compared with placebo treatment. CONCLUSION: Chronic treatment with etanercept in SHR resulted in favorable cardiac remodeling, but also had a positive inotropic effect and was associated with an upregulation of IL6. These findings indicate that chronic treatment with TNFalpha antagonists is not an effective treatment strategy and may aggravate heart failure in the long term.
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| 9. |
- Heggelund, Julie E., et al.
(författare)
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Both El Tor and classical cholera toxin bind blood group determinants
- 2012
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - San Diego : Elsevier. - 0006-291X .- 1090-2104. ; 418:4, s. 731-735
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Tidskriftsartikel (refereegranskat)abstract
- Cholera is a disease which shows a clear blood group profile, with blood group 0 individuals experiencing the most severe symptoms. For a long time, the cholera toxin has been suspected to be the main culprit of this blood group dependence. Here, we show that both El Tor and classical cholera toxin B-pentamers do indeed bind blood group determinants (with equal affinities), using Surface Plasmon Resonance and NMR spectroscopy. Together with previous structural data, this confirms our earlier hypothesis as to the molecular basis of cholera blood group dependence, with an interesting twist: the shorter blood group H-determinant characteristic of blood group 0 individuals binds with similar binding affinity compared to the A-determinant, however, with different kinetics. (C) 2012 Elsevier Inc. All rights reserved.
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| 10. |
- Isic, Azra, 1979, et al.
(författare)
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TNFalpha-antagonist neither improve cardiac remodelling or cardiac function at early stage of heart failure in diabetic rats.
- 2008
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Ingår i: Autoimmunity. - : Informa UK Limited. - 1607-842X .- 0891-6934. ; 41:6, s. 473-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Despite tumor necrosis factor alpha (TNFalpha) has been shown to be a prognostic marker in patients with heart failure and previous preclinical study with TNFalpha-antagonist has been demonstrated to improve cardiac function in acute heart failure, recent clinical trials using TNFalpha-antagonist in patients with chronic severe heart failure have been disappointing. The aim was to study why TNFalpha-antagonist may not work during long-term treatment in chronic heart failure (CHF) in experimental model. METHODS: 49 rats were used at the age of 26 weeks: healthy Whistar Kyoto rats (WKY, n = 26) and diabetic (WKY+D, n = 23). Rats in each group received either a 12-week treatment with TNFalpha-antagonist (Etanercept) or NaCl injections. RESULTS: In diabetic rats, there were increased plasma glucose level and blood pressure. By use of echocardiography diabetic rats displayed not only enlarged and thinned left ventricles but also decreased both systolic and diastolic functions. Moreover, there are increased interleukin-6 (IL6) mRNA levels. However, TNFalpha-antagonist, etanercept, does not improve either cardiac remodelling or cardiac function. IL6 mRNA level remained unchanged after treatment of etanercept. CONCLUSION: Chronic treatment of TNFalpha-antagonist has no favourable effect on either cardiac remodelling or cardiac function. It is therefore inappropriate to use TNFalpha-antagonist in CHF in diabetes as underlying cause.
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| 11. |
- Kondziella, Daniel, 1976, et al.
(författare)
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Hypertension in spontaneously hypertensive rats occurs despite low plasma levels of homocysteine
- 2008
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Ingår i: Physiological Research. - 0862-8408. ; 57:3, s. 487-490
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Tidskriftsartikel (refereegranskat)abstract
- Hyperhomocysteinemia has been suggested to induce hypertension due to its role in endothelial dysfunction. However, it remains controversial whether homocysteine and hypertension are truly causally related or merely loosely associated. To test the hypothesis that hyperhomocysteinemia occurs in Spontaneously Hypertensive Rats (SHR) we measured plasma levels of homocysteine in 10 male adult SHR and in 10 normotensive controls using Ion Exchange Chromatography. In addition, plasma concentrations of the 22 most common amino acids were measured to explore the relation of homocysteine with amino acid metabolism. Plasma levels of homocysteine were significantly lower in SHR (4.1 micromol/L +/-0.1) than in controls (7.2 micromol/L +/- 0.3; p<0.00001). The amounts of aminobutyric acid (ABU), alanine, citrulline and valine were decreased as well, whereas we found increased levels of aspartate, glutamate, glutamine, histidine and ornithine. Thus, contrary to our hypothesis, hypertension in SHR occurs despite low plasma levels of homocysteine. We provide a new hypothesis whereby reduced conversion of arginine to citrulline is related to increased ornithine levels, but decreased bioavailability of nitric oxide, resulting in impaired blood vessel relaxation and hypertension. In conclusion, our findings do not necessarily exclude that homocysteine and hypertension might be pathophysiologically connected, but corroborate the notion that hypertension can arise due to mechanisms independent of high homocysteine levels.
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| 12. |
- Sandbakk, Øyvind, et al.
(författare)
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The Evolution of World-Class Endurance Training: The Scientist's View on Current and Future Trends
- 2023
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Ingår i: International Journal of Sports Physiology and Performance. - : Human Kinetics. - 1555-0265 .- 1555-0273. ; 18:8, s. 885-889
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elite sport is continuously evolving. World records keep falling and athletes from a longer list of countries are involved.Purpose: This commentary was designed to provide insights into present and future trends associated with world-class endurance training based on the perspectives, experience, and knowledge of an expert panel of 25 applied sport scientists.Results: The key drivers of development observed in the past 10-15 years were related to (1) more accessible scientific knowledge for coaches and athletes combined with (2) better integration of practical and scientific exchange across multidisciplinary perspectives within professionalized elite athlete support structures, as well as (3) utilization of new technological advances. Based on these perspectives, we discerned and exemplified the main trends in the practice of endurance sports into the following categories: better understanding of sport-specific demands; improved competition execution; larger, more specific, and more precise training loads; improved training quality; and a more professional and healthier lifestyle. The main areas expected to drive future improvements were associated with more extensive use of advanced technology for monitoring and prescribing training and recovery, more precise use of environmental and nutritional interventions, better understanding of athlete- equipment interactions, and greater emphasis on preventing injuries and illnesses.Conclusions: These expert insights can serve as a platform and inspiration to develop new hypotheses and ideas, encourage future collaboration between researchers and sport practitioners, and, perhaps most important, stimulate curiosity and further collaborative studies about the training, physiology, and performance of endurance athletes.
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| 13. |
- Scharin Täng, Margareta, 1962, et al.
(författare)
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Influence of age, hypertension, and diabetes on cardiac reserve in a rat model
- 2007
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Ingår i: J Am Soc Echocardiogr. - : Elsevier BV. - 0894-7317. ; 20:6, s. 731-7
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Tidskriftsartikel (refereegranskat)abstract
- Background Assessment of cardiac reserve is used to disclose heart disease and to predict outcome in humans. Low-dose dobutamine stress echocardiography (DSE) was used to study the influence of age, hypertension, and diabetes on cardiac reserve in the rat model. Methods Low-dose DSE was performed in four groups: 10 young, 10 adult, and 10 diabetic Whistar Kyoto rats, and 10 spontaneously hypertensive rats. Results Cardiac reserve assessed by low-dose DSE was shown to decrease with age and was impaired both in rat models of hypertension and diabetes. Less information was provided by measuring cardiac function at rest. Conclusions Cardiac reserve in rats is similar to humans in that it decreases with age and is impaired both in severe heart disease and during progression of myocardial dysfunction. We have shown that low-dose DSE in rats is a feasible and reliable method that could be used to study the development of heart disease.
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| 14. |
- Sparv, David, et al.
(författare)
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The Analgesic Effect of Oxygen in Suspected Acute Myocardial Infarction : A Substudy of the DETO2X-AMI Trial
- 2018
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Ingår i: JACC: Cardiovascular Interventions. - : Elsevier BV. - 1936-8798 .- 1876-7605. ; 39, s. 546-546
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: In this substudy of the DETO2X-AMI (An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction) trial, the authors aimed to assess the analgesic effect of moderate-flow oxygen supplementation in patients with suspected acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI) and to study the effect of oxygen supplementation on the use of opiates and sedatives during PCI. Background: Routine oxygen in normoxemic patients with AMI does not provide clinical benefit. However, oxygen may relieve ischemic pain. Methods: Patients were randomly allocated to oxygen or ambient air according to the main study protocol. After PCI, peak level of pain during PCI was measured by the Visual Analogue Scale. The total amount of opiates and sedatives was reported. Results: A total of 622 patients were enrolled: 330 in the oxygen group and 292 in the ambient air group. There was no significant difference in peak level of pain (oxygen 4.0 [1.0 to 6.0] vs. air 3.0 [0.6 to 6.0]; p = 0.37), use of opiates (mg) (oxygen 0.0 [0.0 to 3.0] vs. air 0.0 [0.0 to 3.0]; p = 0.31), or use of sedatives between the groups (median [interquartile range]) (oxygen 2.5 [0.0 to 2.5] vs. air 2.5 [0.0 to 2.5]; p = 0.74). Conclusions: In the present study, the authors did not find any analgesic effect of routine oxygen as compared with ambient air, and no differences in the use of sedatives and opiates during PCI. Our results indicate that moderate-flow oxygen supplementation does not relieve pain in normoxemic patients with suspected AMI undergoing treatment with PCI and should thus not be used for this purpose.
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