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- Ahnstedt, Hilda, et al.
(author)
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Cytokines and growth factors modify the upregulation of contractile endothelin ET(A) and ET(B) receptors in rat cerebral arteries after organ culture.
- 2012
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In: Acta Physiologica. - : Wiley. - 1748-1708. ; 205:2, s. 266-278
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Journal article (peer-reviewed)abstract
- Aim: Experimental cerebral ischemia and organ culture of cerebral arteries induce an increased endothelin ET(B) receptor-mediated contraction. The aim of the present study was to examine if cytokines and growth factors, known to be activated in ischemia, can influence the expression and function of endothelin receptors after organ culture. Methods: Rat middle cerebral arteries were cultured for 24 h at 37°C in humidified 5% CO(2) and air in culture medium alone, or with tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), platelet-derived growth factor (PDGF), epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF). Concentration-response curves were obtained for sarafotoxin 6c (ET(B) receptor agonist) and endothelin-1 (here ET(A) receptor agonist, because of ET(B) receptor desensitization). The receptor mRNA expression was examined by real-time PCR and the protein expression by immunohistochemistry and Western blot. Results: TNF-α (100 ng/ml) and EGF (20 ng/ml) potentiated the ET(B) receptor-mediated contraction (increase in pEC(50) without change in E(max) ). bFGF (10 ng/ml) and IL-1β (10 ng/ml) induced an enhanced ET(A) receptor-mediated contraction. bFGF (10 ng/ml) significantly increased the ET(B) mRNA level, and EGF (20 ng/ml) increased the ET(A) receptor protein. Increased ET(B) receptor mRNA and protein level also were observed after treatment with IL-1β (10 ng/ml). Conclusion: The present study show that TNF-α, IL-1β, EGF and bFGF can modify the expression and function of endothelin receptors during organ culture. Since there is similar receptor upregulation in experimental stroke, the effect of cytokines and growth factors on endothelin receptor upregulation is an interesting aspect to study in vivo.
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| 5. |
- Henriksson, Marie, et al.
(author)
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MEK1/2 inhibition attenuates vascular ET(A) and ET (B) receptor alterations after cerebral ischaemia.
- 2007
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In: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 178:4, s. 470-476
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Journal article (peer-reviewed)abstract
- Cerebral ischaemia is associated with elevated levels of endothelin B (ETB) receptors in the ipsilateral middle cerebral artery (MCA). This up-regulation of ET receptors occurs via de novo transcription involving mitogen-activated protein kinases (MAPK). The aim of this study was to examine the effect of inhibition of the MAP kinase/ERK kinase (MEK)1/2 on ET receptor alteration, brain damage, and neurology in experimental cerebral ischaemia. Transient middle cerebral artery occlusion (MCAO) was induced in male Wistar rats by the intraluminal filament technique. The animals received 100 mg/kg intraperitoneally of the MEK1/2 inhibitor U0126 or vehicle in conjunction with the occlusion. After 24 h, the rats were decapitated and the brains removed. The middle cerebral arteries were dissected out and examined with myographs or immunohistochemistry. The ischaemic areas of the brains were compared. After the MCAO, the contractile responses of the ETA and ETB receptors were augmented in the ipsilateral MCA. U0126 decreased this alteration in ET receptor response. Furthermore, treatment with U0126 significantly decreased the brain damage and improved neurological scores. Immunohistochemistry showed that there were lower protein levels of phosphorylated extracellular signal-regulated kinases (ERK)1/2 and phosphorylated transcription factor Elk-1 in the U0126-treated rats compared to control. The results show that treatment with the MEK1/2 inhibitor U0126 in ischaemic stroke decreases brain damage, neurological symptoms, and ET receptor alteration. The vascular effects of U0126 provide new perspective on possible mechanisms of actions of MAPK inhibition in cerebral ischaemia.
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| 6. |
- Henriksson, Marie, et al.
(author)
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Protein kinase C inhibition attenuates vascular ETB receptor upregulation and decreases brain damage after cerebral ischemia in rat.
- 2007
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In: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 8, s. 7-7
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Journal article (peer-reviewed)abstract
- Background: Protein kinase C (PKC) is known to be involved in the pathophysiology of experimental cerebral ischemia. We have previously shown that after transient middle cerebral artery occlusion, there is an upregulation of endothelin receptors in the ipsilateral middle cerebral artery. The present study aimed to examine the effect of the PKC inhibitor Ro-32-0432 on endothelin receptor upregulation, infarct volume and neurology outcome after middle cerebral artery occlusion in rat. Results: At 24 hours after transient middle cerebral artery occlusion (MCAO), the contractile endothelin B receptor mediated response and the endothelin B receptor protein expression were upregulated in the ipsilateral but not the contralateral middle cerebral artery. In Ro-32-0432 treated rats, the upregulated endothelin receptor response was attenuated. Furthermore, Ro-32-0432 treatment decreased the ischemic brain damage significantly and improved neurological scores. Immunohistochemistry showed fainter staining of endothelin B receptor protein in the smooth muscle cells of the ipsilateral middle cerebral artery of Ro-32-0432 treated rats compared to control. Conclusion: The results suggest that treatment with Ro-32-0432 in ischemic stroke decreases the ischemic infarction area, neurological symptoms and associated endothelin B receptor upregulation. This provides a new perspective on possible mechanisms of actions of PKC inhibition in cerebral ischemia.
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| 7. |
- Memon, Ashfaque A., et al.
(author)
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Quantification of mitochondrial DNA copy number in suspected cancer patients by a well optimized ddPCR method
- 2017
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In: Biomolecular Detection and Quantification. - : Elsevier BV. - 2214-7535. ; 13, s. 32-39
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Journal article (peer-reviewed)abstract
- Changes in mitochondrial DNA (mtDNA) content is a useful clinical biomarker for various diseases, however results are controversial as several analytical factors can affect measurement of mtDNA. MtDNA is often quantified by taking ratio between a target mitochondrial gene and a reference nuclear gene (mtDNA/nDNA) using quantitative real time PCR often on two separate experiments. It measures relative levels by using external calibrator which may not be comparable across laboratories. We have developed and optimized a droplet digital PCR (ddPCR) based method for quantification of absolute copy number of both mtDNA and nDNA gene in whole blood. Finally, the role of mtDNA in suspected cancer patients referred to a cancer diagnostic center was investigated.Analytical factors which can result in false quantification of mtDNA have been optimized and both target and reference have been quantified simultaneously with intra- and inter-assay coefficient variances as 3.1% and 4.2% respectively. Quantification of mtDNA show that compared to controls, solid tumors (but not hematologic malignancies) and other diseases had significantly lower copy number of mtDNA. Higher mtDNA (highest quartile) was associated with a significantly lower risk of both solid tumors and other diseases, independent of age and sex. Receiver operating curve demonstrated that mtDNA levels could differentiate controls from patients with solid tumors and other diseases.Quantification of mtDNA by a well optimized ddPCR method showed that its depletion may be a hallmark of general illness and can be used to stratify healthy individuals from patients diagnosed with cancer and other chronic diseases.
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- Milos Nymberg, Veronica, et al.
(author)
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Lifestyle and cardiovascular risk factors in a Swedish primary care population with self-reported psychiatric symptoms
- 2024
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In: Preventive Medicine Reports. - Amsterdam : Elsevier. - 2211-3355. ; 37
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Journal article (peer-reviewed)abstract
- ObjectiveIndividuals with psychiatric illness suffer from poorer physical health compared with the general population and have a higher risk of developing cardiovascular and metabolic diseases. This cross-sectional study aims to describe the prevalence of lifestyle and cardiovascular risk factors and the association with self-reported psychiatric symptoms in a population of 40-year-old individuals screened with targeted Health Dialogues in southern Sweden.MethodsAll 40-year-old individuals registered at 99 primary healthcare centers in southern Sweden were invited to participate. Self-reported lifestyle habits on a web questionnaire, anthropometric measurements, blood pressure, and blood tests were collected. The Health Dialogue resulted in a risk level assessment for different lifestyle habits and a meeting with a trained coach.ResultsA total of 1831 individuals completed a Health Dialogue between 1st January 2021 and 30th June 2022. There were more individuals with high-risk levels for several lifestyle habits in the group with self-reported psychiatric illness compared with the rest of the study population. The analysis showed that physical inactivity, unhealthy diet, high-risk alcohol intake, tobacco use, psychosocial strain, higher BMI, and waist-hip ratio were associated with increased levels of psychiatric symptoms after adjustment for sex and socioeconomic factors.ConclusionUnhealthy lifestyle habits were associated with self-reported psychiatric symptoms in 40-year-old individuals assessed with targeted Health Dialogues in a primary care context. Organized screening might contribute to early detection of modifiable risk factors for cardiovascular disease. Individuals with psychiatric symptoms should be prioritized for screening of unhealthy lifestyle behaviors. © 2023 The Author(s)
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| 9. |
- Nymberg, Peter, et al.
(author)
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Effect of mindfulness on physical activity in primary healthcare patients : a randomised controlled trial pilot study
- 2021
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In: Pilot and Feasibility Studies. - : Springer Science and Business Media LLC. - 2055-5784. ; 7:1
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Journal article (peer-reviewed)abstract
- Increased physical activity can have health benefits among inactive individuals. In Sweden, the healthcare system uses physical activity on prescription (PAP) to motivate patients to increase their physical activity level. Mindfulness may further heighten the internal motivation to engage in physical activity. However, previous research has not demonstrated clear evidence of such an association.AIM: Examine the feasibility of the study design as a preparation for a full-scale study, and examine the differences, between three interventions, in change over time in physical activity levels and in related variables.METHOD: Comparison between three different interventions in an ordinary primary health care setting: PAP, mindfulness, and a combination of PAP and mindfulness. Physical activity was measured with self-report and ACTi Graph GT1X activity monitor. Statistical analysis was performed with a mixed-effect model to account for repeated observations and estimate differences both within groups and between groups at 3- and 6-months follow-up.RESULTS: Between September 2016 and December 2018, a total of 88 participants were randomised into three groups. The total dropout rate was 20.4%, the attendance rate to the mindfulness courses (52% > 6 times) and the web-based mindfulness training (8% > 800 min) was low according to the stated feasibility criteria. Eleven participants were excluded from analysis due to low activity monitor wear time. Neither the activity monitor data nor self-reported physical activity showed any significant differences between the groups.CONCLUSION: The study design needs adjustment for the mindfulness intervention design before a fully scaled study can be conducted. A combination of PAP and mindfulness may increase physical activity and self-rated health more than PAP or mindfulness alone.TRIAL REGISTRATION: ClinicalTrials.gov, registration number NCT02869854 . Regional Ethical Review Board in Lund registration number 2016/404.
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| 10. |
- Nymberg, Peter, et al.
(author)
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Pilot study on increased adherence to physical activity on prescription (PAP) through mindfulness : Study protocol 11 Medical and Health Sciences 1117 Public Health and Health Services
- 2018
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In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 19:1
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Journal article (peer-reviewed)abstract
- Background: In the Swedish population aged between 50 and 64 years only 7.1% reach the recommended level of physical activity. Physical activity on prescription (PAP) has been used in Sweden since the beginning of the twenty-first century with moderate adherence of approximately 50%. Mindfulness seems to affect motivation to and satisfaction with physical activity. The aim is to test the feasibility of a study in routine care; i.e. to test if mindfulness can improve adherence to PAP, measured by changes in physical activity. Methods/design: We will include 90 sedentary individuals, aged 40-65 years, from primary health care centres in Sweden. Individuals will be randomised to only PAP, mindfulness and PAP or mindfulness only. The PAP group will be based on patients' preferences. The mindfulness groups will meet once a week for 8 weeks and practise 20 min of individual training per day. There will not be any motivational interview or physical activity on prescription in the group assigned to only mindfulness. The participants will complete the Five Facet Mindfulness Questionnaire, the Insomnia Severity Index and also answer questions concerning their lifestyle. Physical activity will be measured by ACTi Graph GT1X activity monitor at baseline and after 3 and 6 months. Patients with a severe psychological disease, unstable angina or a recent myocardial infarction will be excluded. The main outcome will be adherence to PAP in an ordinary primary health care setting. In this pilot study, we will also evaluate measures such as the recruitment rate, number of dropouts and adherence to mindfulness practice. Discussion: This study is the first to explore the effect of mindfulness on adherence to PAP and test the feasibility of the study design. Trial registration: ClinicalTrials.gov, NCT02869854. Registered on 26 August 2016.
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