| 1. |
- Andersson, Sven E, et al.
(författare)
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High NT-proBNP Is a Strong Predictor of Outcome in Elderly Heart Failure Patients.
- 2008
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Ingår i: American Journal of Geriatric Cardiology. - 1751-715X. ; 17:1, s. 13-20
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Tidskriftsartikel (refereegranskat)abstract
- All patients older than 65 years (184 men; mean age, 78+/-0.8 years/181 women; mean age, 82+/-0.6 years) seeking medical attention at the Lund University Hospital Emergency Clinic during a 2-year period who had an N-terminal prohormone brain natriuretic peptide (NT-proBNP) value >2000 pg/mL were followed up for survival. Mortality in the entire population was 21% after 3 months, 35% after 1 year, and 40% after 2 years. Multivariate analysis indicated that the NT-proBNP level and the New York Heart Association (NYHA) functional class were stronger predictors of mortality than were echocardiographic estimation of left ventricular ejection fraction or chest radiography. Patients who survived the first year were younger, had higher systolic blood pressure, had lower plasma creatinine, had lower inflammatory activity, and were treated with lower doses of furosemide. The results indicate that in this population, NT-proBNP level together with assessment of NYHA class gives the best prognostic information of 1-year mortality. (Am J Geriatr Cardiol. 2008;17:13-20).
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| 2. |
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| 3. |
- Andersson, Sven, et al.
(författare)
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Reduction of Homocysteine in Elderly with Heart Failure Improved Vascular Function and Blood Pressure Control but did Not Affect Inflammatory Activity.
- 2005
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843. ; 97:5, s. 306-310
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that hyperhomocysteinaemia is common in elderly heart failure patients, and is associated with endothelial dysfunction, impaired vasodilatory capacity and a low-grade inflammation. In the present study we examined if supplementation with B6, B12 and folate could normalize the hyperhomocysteinaemia and if so, in turn, would improve the associated parameters. This was an open study without placebo control on heart failure patients with plasma homocysteine > 15 microM. Measurements of cutaneous vascular reactivity, blood pressure, inflammatory activity and endothelial function were performed before and after intervention with intra-individual comparisons. The treatment reduced homocysteine to near normal values and enhanced the hyperaemic response to acetylcholine related to the response to heat. The mean arterial blood pressure and pulse rate was reduced. There was no effect on inflammatory activity, plasma levels of von Willebrand factor, subjective health quality or the hyperaemic responses to sodium nitroprusside or local warming. Hyperhomocysteinaemia in heart failure patients is multifactorial in origin. Folate deficiency, inflammatory activity and reduced renal function could be contributing. It is suggested that supplementation with B-vitamins can improve the vasodilatory capacity and reduce the blood pressure but additional studies are required to confirm this.
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| 4. |
- Bengtsson, Christine, et al.
(författare)
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Effect of Medication on Microvascular Vasodilatation in Patients with Systemic Lupus Erythematosus
- 2010
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 107:6, s. 919-924
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the microvascular responses in the skin, to local heat, iontophoretically administered acetylcholine and to sodium nitroprusside in relation to cardiovascular damage in patients with systemic lupus erythematosus (SLE) and matched controls. We also wanted to examine if the ongoing medication in SLE patients influenced this vascular response. We investigated 30 women with SLE and compared them with 20 age and sex-matched controls. The cutaneous blood flow response to local heat (+44 degrees C), iontophoretically administered endothelium-dependent (acetylcholine), as well as independent (sodium nitroprusside) vasodilatation, was measured by laser Doppler flowmetry. Clinical data and medication were retrieved from the clinical database and patient records. The cutaneous microvascular reactivity did not differ between SLE patients and a group of matched controls nor did it correlate with cardiovascular damage [assessed by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI)]. However, patients on antimalarial drugs (hydroxychloroquine n = 8 and chloroquine diphosphate n = 3) responded more strongly to sodium nitroprusside (endothelium-independent vasodilatation) compared with those without antimalarial drugs (p < 0.01). The response to acetylcholine was higher among patients on warfarin compared with those without (p < 0.05), whereas glucocorticoid use (>= 5 mg daily) was associated with reduced response to acetylcholine (p < 0.05). Smokers in general tended to have a lower response to acetylcholine (p = 0.064). Smoking SLE patients versus non-smoking SLE patients had a significantly lower response to acetylcholine (p = 0.01). Medication with antimalarial drugs-enhanced endothelium-independent vasodilatation, while glucocorticoid use was associated with reduction and warfarin-treatment with enhancement of endothelium-dependent vasodilatation. Therefore, despite there is no difference in microvascular endothelium-dependent vasodilatation, other factors such as medication and smoking may affect vasodilatation in SLE patients.
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| 5. |
- Bondesson, Susanne, et al.
(författare)
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Reduced peripheral vascular reactivity in refractory angina pectoris: Effect of enhanced external counterpulsation
- 2011
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Ingår i: Journal of geriatric cardiology : JGC. - 1671-5411. ; 8:4, s. 215-223
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Tidskriftsartikel (refereegranskat)abstract
- To examine if the skin microvascular bed is altered and can be modified by enhanced external counterpulsation (EECP) in patients with chronic refractory angina. Methods Twenty patients diagnosed with refractory angina were divided into EECP (n = 10) or no EECP (n = 10) groups. The data were compared to matched healthy subjects (n = 20). The cutaneous forearm microvascular blood flow was measured by Laser-Doppler flowmetry. The vascular responsiveness to iontophoretic administration of acetylcholine (ACh), sodium nitroprusside (SNP) and local skin warming were studied. Measurements of Canadian Cardiovascular Society (CCS)-class, blood pressure and plasma samples were registered. Results EECP patients showed reduced CCS-class compared to no EECP (P < 0.05). Both EECP and no EECP (P < 0.05) groups had decreased systolic blood pressure (SBP) as compared to SBP at baseline (P < 0.05). There was no difference in resting blood flow between the two refractory groups at baseline as well as after EECP and seven weeks of follow-up. Responses to heating, the responses to ACh and SNP in the cutaneous microcirculation were lower in both groups of refractory angina patients as compared to healthy subjects (P < 0.05). EECP patients corresponded positively to the treatment shown by reduced plasma level of soluble interleukin-2 receptor and CCS-class. Conclusions Refractory angina patients have reduced responsiveness in their cutaneous microcirculation to ACh, SNP and heat compared to healthy subjects. Although EECP reduced the CCS-class, this effect was not associated with improvements in responsiveness of the cutaneous microcirculation.
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| 6. |
- Cao, Lei, et al.
(författare)
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Secondhand cigarette smoke induces increased expression of contractile endothelin receptors in rat coronary arteries via a MEK1/2 sensitive mechanism
- 2021
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 55:1, s. 50-55
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Cigarette smoke, a strong risk factor for cardiovascular diseases, upregulates contractile endothelin (ET) receptors in coronary arteries. The present study examined the effects of second hand cigarette smoke exposure on the contractile endothelin receptors and the role of the MEK1/2 pathway in rat coronary arteries. Design: Rats were exposed to secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of a MEK1/2 inhibitor, U0126 daily for another 4 weeks. Contractile responses of isolated coronary arteries were recorded by a sensitive wire myograph. The receptor protein expression levels were examined by Western blotting. Results: The results showed that SHS in vivo caused increased expression of ET receptors ETA and ETB, and that the MEK1/2 blocker U0126 significantly reversed SHS exposure-increased ETA-mediated contractile responses and protein levels. Similar alterations were observed in ETB receptors. U0126 showed dose-dependent effects on SHS-induced response on contractile property and protein levels of the ETB receptor. However, only the higher dose U0126 (15 mg/kg) had inhibitory effects on the ETA receptor. Conclusions: Taken together, our data show that SHS increases contractile ET receptors and MEK1/2 pathway inhibitor offsets SHS exposure-induced ETA and ETB receptor upregulation in rat coronary arteries.
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| 7. |
- Dimitrijevic, Ivan, et al.
(författare)
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Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease
- 2009
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Endothelin-1 and angiotensin II are strong vasoconstrictors. Patients with ischemic heart disease have elevated plasma levels of endothelin-1 and angiotensin II and show increased vascular tone. The aim of the present study was to examine the endothelin and angiotensin II receptor expression in subcutaneous arteries from patients with different degrees of ischemic heart disease. Methods: Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG) surgery because of ischemic heart disease (n = 15), patients with angina pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A ( ETA) and type B (ETB), and angiotensin type 1 (AT(1)) and type 2 (AT(2)) receptors expression and function were examined using immunohistochemistry, Western blot and in vitro pharmacology. Results: ETA and, to a lesser extent, ETB receptor staining was observed in the healthy vascular smooth muscle cells. The level of ETB receptor expression was higher in patients undergoing CABG surgery (250% +/- 23%; P < 0.05) and in the patients with angina pectoris (199% +/- 6%; P < 0.05), than in the healthy controls (100% +/- 28%). The data was confirmed by Western blotting. Arteries from CABG patients showed increased vasoconstriction upon administration of the selective ETB receptor agonist sarafotoxin S6c, compared to healthy controls (P < 0.05). No such difference was found for the ETA receptors. AT(1) and, to a lesser extent, AT(2) receptor immunostaining was seen in the vascular smooth muscle cells. The level of AT(1) receptor expression was higher in both the angina pectoris (128% +/- 25%; P < 0.05) and in the CABG patients (203% +/- 41%; P < 0.05), as compared to the healthy controls (100% +/- 25%). The increased AT(1) receptor expression was confirmed by Western blotting. Myograph experiment did however not show any change in vasoconstriction to angiotensin II in CABG patients compared to healthy controls (P = n.s). Conclusion: The results demonstrate, for the first time, upregulation of ETB and AT(1) receptors in vascular smooth muscle cells in ischemic heart disease. These receptors may play a role in the pathophysiology of ischemic heart disease and could provide important targets for pharmaceutical interventions.
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| 8. |
- Edvinsson, Marie-Louise, et al.
(författare)
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Characterization of Relaxant Responses to Natriuretic Peptides in the Human Microcirculation In Vitro and In Vivo
- 2016
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Ingår i: Microcirculation. - : Wiley. - 1073-9688. ; 23:6, s. 438-446
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We characterized the vasodilatory effects of ANP, BNP, and CNP in human subcutaneous arterioles in vitro and the cutaneous microcirculation in vivo. Methods: The in vitro experiments were performed using wire myography and the responses were characterized by the use of inhibitors for nitric oxide (L-NAME), prostaglandin synthesis (indomethacin), or the endothelium-derived hyperpolarization factor. In vivo, the vasorelaxant effect of iontophoretically administrated BNP or CNP was measured with a noninvasive laser Doppler technique. Involvement of nitric oxide or prostaglandins was assessed by L-NAME or indomethacin given by iontophoresis. Results: In vitro all three peptides showed significant vasodilatation with the efficacy order: CNP > BNP = ANP. The BNP-induced vasodilatation, but not that of ANP or CNP, was significantly reduced by pretreatment with indomethacin or L-NAME. In vivo administration of BNP induced a marked vasodilatory response that was attenuated by local pretreatment of L-NAME. Indomethacin by itself resulted in increased cutaneous perfusion. Conclusions: NPs are potent vasodilators in the human subcutaneous circulation. The response to BNP differs from that of the other peptides as it seems dependent on cyclooxygenase products and nitric oxide.
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| 9. |
- Lindstedt, Isak H., et al.
(författare)
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Reduced responsiveness of cutaneous microcirculation in essential hypertension - A pilot study
- 2006
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 15:5, s. 275-280
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Our hypothesis states that the reactivity of the cutaneous microcirculation is reduced in patients with hypertension compared with healthy subjects. The objective was to verify the hypothesis by measuring microvascular function in hypertensive patients. Design. The study was a controlled trial with two arms: 15 hypertensives and 15 normotensives were enrolled, aged 30-60 years, and in hypertensives, a diastolic blood pressure of > 90 mmHg. The hypertensive patients were compared with gender- and age-matched controls having a diastolic blood pressure < 90 mmHg. The patients were kept on their medication. Method. The local cutaneous forearm blood flow was measured by Laser-Doppler flowmetry. The blood flow response to local warming (44 degrees C), to the endothelium-dependent vasodilator acetylcholine (ACh), or to the endothelium-independent dilators sodium nitroprusside (SNP) and calcitonin gene-related peptide (CGRP) administered by iontophoresis were determined. Inflammatory markers and NT-pro brain natriuretic peptide (NT-proBNP) levels in plasma was also measured. Electrocardiograms (ECG) were evaluated and the subjects answered a lifestyle questionnaire. Results. The percentage change in vasodilator response to CGRP was significantly lower in the hypertensives compared with normotensives, 285% (95% CI 86-484) vs 764% (95% CI 366-1162) of baseline, p < 0.05. The change to local warming was 2191% (95% CI 1574-2807) in normotensives vs 1384% (95% CI 852-1917) in the hypertensives, p < 0.05. The vasodilator response to ACh was 1249% (95% CI 895-1602) in the normotensives and 873% (95% CI 610-1136) in the hypertensives. The vasodilator response to SNP in the normotensives was 771% (95% CI 436-1107) and 682% (95% Cl 416-948) in the hypertensive group. Plasma level of NT-proBNP was 90 ng/l (95% CI 35-145) in normotensives vs 285 ng/l (95% CI 70-499) in hypertensives (p=0.06). The ECGs showed a tendency towards left ventricular hypertrophy (LVH) in hypertensives. Conclusion. Patients with essential hypertension had significantly reduced microvascular dilator responses to CGRP and to local warming. Also, there was a tendency towards reduced responses to ACh. This points towards a generally weaker responsiveness of the cutaneous microvessels in hypertensives and could be a contributing factor to the development of high blood pressure. Patients with essential hypertension also had a tendency of higher plasma levels of NT-proBNP, which could be seen as an early sign of organ damage.
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| 10. |
- Rehnström, Mimmi, et al.
(författare)
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Ovariectomy Reduces Vasocontractile Responses of Rat Middle Cerebral Arteries After Focal Cerebral Ischemia
- 2022
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Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 79:1, s. 122-128
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Effects of sex hormones on stroke outcome are not fully understood. A deleterious consequence of cerebral ischemia is upregulation of vasoconstrictor receptors in cerebral arteries that exacerbate stroke injury. Here, we tested the hypothesis that female sex hormones alter vasocontractile responses after experimental stroke in vivo or after organ culture in vitro, a model of vasocontractile receptor upregulation. Female rats with intact ovaries and ovariectomized (OVX) females treated with 17β-estradiol, progesterone, or placebo were subjected to transient, unilateral middle cerebral artery occlusion followed by reperfusion (I/R). The maximum contractile response, measured my wire myography, in response to the endothelin B receptor agonist sarafotoxin 6c was increased in female arteries after I/R, but the maximum response was significantly lower in arteries from OVX females. Maximum contraction mediated by the serotonin agonist 5-carboxamidotryptamine was diminished after I/R, with arteries from OVX females showing a greater decrease in maximum contractile response. Contraction elicited by angiotensin II was similar in all arteries. Neither estrogen nor progesterone treatment of OVX females affected I/R-induced changes in endothelin B- and 5-carboxamidotryptamine-induced vasocontraction. These findings suggest that sex hormones do not directly influence vasocontractile alterations that occur after ischemic stroke; however, loss of ovarian function does impact this process.
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| 11. |
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| 12. |
- Ahnstedt, Hilda, et al.
(författare)
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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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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708. ; 205:2, s. 266-278
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Tidskriftsartikel (refereegranskat)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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| 13. |
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| 14. |
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| 15. |
- Borgström, Emilie W., et al.
(författare)
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Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors
- 2023
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Ingår i: Journal of Clinical Immunology. - : Springer. - 0271-9142 .- 1573-2592. ; 43, s. 136-150
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Tidskriftsartikel (refereegranskat)abstract
- Purpose; The aim of this study was to characterize clinical effects and biomarkers in three patients with chronic mucocutaneous candidiasis (CMC) caused by gain-of-function (GOF) mutations in the STAT1 gene during treatment with Janus kinase (JAK) inhibitors.Methods: Mass cytometry (CyTOF) was used to characterize mononuclear leukocyte populations and Olink assay to quantify 265 plasma proteins. Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA) was used to quantify the reactivity against Candida albicans.Results: Overall, JAK inhibitors improved clinical symptoms of CMC, but caused side effects in two patients. Absolute numbers of neutrophils, T cells, B cells, and NK cells were sustained during baricitinib treatment. Detailed analysis of cellular subsets, using CyTOF, revealed increased expression of CD45, CD52, and CD99 in NK cells, reflecting a more functional phenotype. Conversely, monocytes and eosinophils downregulated CD16, consistent with reduced inflammation. Moreover, T and B cells showed increased expression of activation markers during treatment. In one patient with a remarkable clinical effect of baricitinib treatment, the immune response to C. albicans increased after 7 weeks of treatment. Alterations in plasma biomarkers involved downregulation of cellular markers CXCL10, annexin A1, granzyme B, granzyme H, and oncostatin M, whereas FGF21 was the only upregulated marker after 7 weeks. After 3 months, IFN-gamma and CXCL10 were downregulated.Conclusions: The clinical effect of JAK inhibitor treatment of CMC is promising. Several biological variables were altered during baricitinib treatment demonstrating that lymphocytes, NK cells, monocytes, and eosinophils were affected. In parallel, cellular reactivity against C. albicans was enhanced.
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| 16. |
- Brändström, Anders, et al.
(författare)
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Clustering across generations : a comparative analysis of infant mortality in 19th century Sweden
- 2007
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Ingår i: ESSHC Conference in Lisbon, 26 February-1 March, 2008.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Many studies in the past have emphasized the positive correlation between infant mortality and fertility, but how this operates remain unclear. In this paper, we investigate these interdependent processes using data from the Demographic Data base at Ume{\aa} University. More specifically, we have data from regions in the northern part of Sweden, starting in the fifteenth century and ending around the year 1900. In an earlier paper, we have studied the intergenerational aspects of infant mortality and in this paper we incorporate fertility. We investigate the interaction between the two processes and how patterns are tranferred from generation to generation.
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| 17. |
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| 18. |
- Deen, Marie, et al.
(författare)
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Blocking CGRP in migraine patients – a review of pros and cons
- 2017
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Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 18, s. 1-9
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Forskningsöversikt (refereegranskat)abstract
- Migraine is the most prevalent neurological disorder worldwide and it has immense socioeconomic impact. Currently, preventative treatment options for migraine include drugs developed for diseases other than migraine such as hypertension, depression and epilepsy. During the last decade, however, blocking calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for prevention of migraine attacks. CGRP has been shown to be released during migraine attacks and it may play a causative role in induction of migraine attacks. Here, we review the pros and cons of blocking CGRP in migraine patients. To date, two different classes of drugs blocking CGRP have been developed: small molecule CGRP receptor antagonists (gepants), and monoclonal antibodies, targeting either CGRP or the CGRP receptor. Several trials have been conducted to test the efficacy and safety of these drugs. In general, a superior efficacy compared to placebo has been shown, especially with regards to the antibodies. In addition, the efficacy is in line with other currently used prophylactic treatments. The drugs have also been well tolerated, except for some of the gepants, which induced a transient increase in transaminases. Thus, blocking CGRP in migraine patients is seemingly both efficient and well tolerated. However, CGRP and its receptor are abundantly present in both the vasculature, and in the peripheral and central nervous system, and are involved in several physiological processes. Therefore, blocking CGRP may pose a risk in subjects with comorbidities such as cardiovascular diseases. In addition, long-term effects are still unknown. Evidence from animal studies suggests that blocking CGRP may induce constipation, affect the homeostatic functions of the pituitary hormones or attenuate wound healing. However, these effects have so far not been reported in human studies. In conclusion, this review suggests that, based on current knowledge, the pros of blocking CGRP in migraine patients exceeds the cons.
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| 19. |
- Edvinsson, Emma, et al.
(författare)
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Hur beskrivs psykiskt status?
- 2019. - 1
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Ingår i: Handbok i barn- och ungdomspsykiatriskt utredningsarbete. - Lund : Studentlitteratur AB. - 9789144126807 ; , s. 151-156
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 20. |
- Edvinsson, Marie, et al.
(författare)
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Bartonella spp. seroprevalence in tick-exposed Swedish patients with persistent symptoms
- 2021
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Ingår i: Parasites & Vectors. - : BioMed Central (BMC). - 1756-3305. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bartonella spp. are emerging pathogens transmitted by arthropod vectors, possibly including ticks. We have investigated signs of bartonellosis in Swedish patients with presumed tick-bite exposure and symptom duration of at least 6 months.Methods: Serological testing for Bartonella henselae and Bartonella quintana was performed in 224 patients. Symptoms, tick exposure, evidence of co-infection and previous treatments were evaluated. Seropositive patients were compared to a matched group (twofold larger and negative serology) from the same study cohort.Results: Seroprevalence was 7% for B. henselae and 1% for B. quintana, with one patient testing positive to both agents. Tick bites were reported by 63% of the patients in the seropositive group and 88% in the seronegative group and presumed tick exposure was more common in the seronegative group. Animal contact was equally common in both groups, along with reported symptoms. The most common symptoms were fatigue, muscular symptoms, arthralgia and cognitive symptoms. Exposure to co-infections was evenly distributed in the seropositive and seronegative groups.Conclusions: Antibodies to Bartonella were more common in this cohort of patients than in cohorts of healthy Swedish blood donors in previous studies but lower than those in blood donors from southern Europe. Positive Bartonella serology was not linked to any specific symptom, nor to (suspected) tick-bite exposure.
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| 21. |
- Edvinsson, Marie, et al.
(författare)
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Chlamydophila pneumoniae changes iron homeostasis in infected tissues
- 2008
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1438-4221 .- 1618-0607. ; 298:7-8, s. 635-44
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Tidskriftsartikel (refereegranskat)abstract
- Many bacteria, including Chlamydophila pneumoniae (C. pneumoniae), are dependent on iron (Fe) for their growth. However, it is not known whether bacterial infections affect gastrointestinal uptake and uptake of trace elements in infected tissues. A human C. pneumoniae strain adapted to C57BL/6J mice was used to study hepcidin gene expression in the liver and divalent metal transporter 1 (DMT1) content in the liver and intestine and whether Fe is concomitantly changed in serum, liver, and intestine. The copper/zinc (Cu/Zn) ratio in the serum was used as a marker for infection. Bacterial DNA, mRNA, and hepcidin were measured by real-time PCR, DMT1 by Western blot, and trace elements by ICP-MS on days 2, 5, and 8 of the infection. C. pneumoniae DNA was found in the liver on all days but the number of viable bacteria peaked on day 8. Hepcidin expression increased on days 2 and 5, whereas DMT1 content in the liver increased on day 8. Fe decreased in serum, increased in the liver but was not changed in the intestine during the disease. In the serum, the Cu/Zn ratio peaked on day 5. The peak of viable bacteria in the liver was associated with increased DMT1 and Fe contents and increased hepcidin expression, but this did not affect intestinal Fe uptake. Thus, growth of C. pneumoniae in tissues parallels a redistribution of Fe to those tissues resulting in a changed body homeostasis of Fe.
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| 22. |
- Edvinsson, Marie, 1976-
(författare)
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Chlamydophila pneumoniae in Cardiovascular Diseases : Clinical and Experimental Studies
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chlamydophila pneumoniae (C. pneumoniae) has been suggested as a stimulator of chronic inflammation in atherosclerosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 50% of patients with stable angina pectoris or acute coronary syndrome undergoing coronary artery bypass grafting. C. pneumoniae mRNA, a marker of replicating bacteria, was demonstrated in 18% of the aortic biopsies. Inflammation may have a role in the pathogenesis of thoracic aortic aneurysm, aortic dissection and aortic valve stenosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 26% of thoracic aortic aneurysm patients and in 11% of aortic dissection patients undergoing thoracic surgery and in 22% of stenotic aortic heart valves from patients undergoing aortic valve replacement. No bacterial mRNA was demonstrated in these aortic biopsies, nor in the valves, suggesting that the infection has passed into a persistent state. C. pneumoniae DNA was demonstrated in peripheral blood mononuclear cells in only 5% of aortic valve stenosis patients and not in thoracic aortic aneurysm or aortic dissection patients, suggesting that the bacterium disseminated to the cardiovascular tissue long before the patient required surgery. The copper/zinc ratio in serum, a marker of infection/inflammation, was significantly elevated in thoracic aortic aneurysm patients, supporting an inflammatory pathogenesis. Patients positive for C. pneumoniae in the aortic valve had more advanced coronary atherosclerosis, further supporting a possible role for C. pneumoniae in atherosclerosis. Mice were infected with C. pneumoniae that disseminated to all organs investigated (i.e. lungs, heart, aorta, liver and spleen). Trace element concentrations were altered in infected animals with an increased copper/zinc ratio in serum, a progressively increased iron concentration in the liver and a progressively decreased iron concentration in serum. Iron is important for C. pneumoniae metabolism, and a changed iron homeostasis was noted in infected mice by alterations in iron-regulating proteins, such as DMT1 and hepcidin.
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| 23. |
- Edvinsson, Marie, et al.
(författare)
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Chlamydophila pneumoniae in chronic rhinosinusitis
- 2006
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 126:9, s. 952-957
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Tidskriftsartikel (refereegranskat)abstract
- CONCLUSIONS: The intracellular bacterium Chlamydophila pneumoniae (Cp) was infrequently found in nasopharynx and lacking in biopsies from the middle turbinate in chronic rhinosinusitis (CRS) patients. Compared with healthy controls, patients suffering from CRS had significantly higher and more prevalent antibody titers to Cp. However, an association between CRS and Cp could not be established. OBJECTIVES: To study the prevalence of Cp in CRS patients and in healthy controls to determine if an association exists between Cp and CRS. MATERIALS AND METHODS: PCR against Cp was run on middle turbinate biopsies and on throat and nasopharyngeal swabs from 25 CRS patients and from 10 healthy controls. Serum samples were tested for Cp-specific antibodies by the microimmunofluorescence method. Patients that tested positive for Cp or had high antibody titers were treated with antibiotics. RESULTS: Cp was found in nasopharyngeal samples from two patients but from none of the controls. Neither patients nor controls had Cp in biopsies from the middle turbinate. Antibody titers against Cp were significantly higher and more prevalent in patients than in controls. Seventeen patients were treated with antibiotics but only four of them recovered from sinusitis symptoms during the 2-year follow-up.
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| 24. |
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| 25. |
- Edvinsson, Marie, et al.
(författare)
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Cholesterol uptake in the mouse aorta increases during Chlamydia pneumoniae infection
- 2017
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Ingår i: Pathogens and Disease. - : OXFORD UNIV PRESS. - 2049-632X. ; 75:1
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia pneumoniae has been suggested as a stimulator of the atherosclerotic process. Mice fed a normal diet were infected intranasally with C. pneumoniae and given one intraperitoneal injection of C-14-cholesterol tracer per day for 12 days. Bacteria were demonstrated in the aorta in the early phase of infection and in lungs and liver throughout the study period of 20 days. C-14-cholesterol was not affected in the heart but increased in the blood, liver and aorta on day 4 when the infection was clinically most severe. Furthermore, on day 20 C-14-cholesterol tended to be increased in the aorta. Accordingly, copper-and zinc levels and expressions of the infection biomarkers Cxcl2 and Ifng increased in the liver on day 4 with a tendency of increased of copper, zinc and Ifng on day 20. In mice where bacteria could be cultivated from the lungs, expressions of cholesterol transporters Abca1 and Idol were both increased in the liver on day 4. The increased levels of C-14-cholesterol in blood and aorta together with increased Abca1 and Idol in the liver during C. pneumoniae infection in mice fed a normal diet suggest that this pathogen may have a role in the initiation of the atherosclerotic process.
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| 26. |
- Edvinsson, Marie, et al.
(författare)
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Iron Homeostasis in Tissues Is Affected during Persistent Chlamydia pneumoniae Infection in Mice
- 2017
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Ingår i: BioMed Research International. - : Hindawi Publishing Corporation. - 2314-6133 .- 2314-6141.
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia pneumoniae (C. pneumoniae) may be a mediator in the pathogenesis of atherosclerosis. For its growth C. pneumoniae depends on iron (Fe), but how Fe changes in tissues during persistent infection or affects bacterial replication in tissues is unknown. C. pneumoniae-infected C57BL/6J mice were sacrificed on days 4, 8, 20, and 40. Mice had bacteria in the lungs and liver on all days. Inflammatory markers, chemokine Cxcl2 and interferon-gamma, were not affected in the liver on day 40. The copper (Cu)/zinc (Zn) ratio in serum, another marker of infection/inflammation, increased on day 4 and tended to increase again on day 40. The Fe markers, transferrin receptor (TfR), Hepcidin (Hamp1), and ferroportin 1 (Fpn1), increased in the liver on day 4 and then normalized except for TfR that tended to decrease. TfR responses were similar to Fe in serum that increased on day 4 but tended to decrease thereafter. In the liver, Fe was increased on day 4 and also on day 40. The reappearing increases in Cu/Zn on day 40 concomitant with the increase in liver Fe on day 40, even though TfR tended to decrease, and the fact that viable C. pneumoniae was present in the lungs and liver may indicate the early phase of activation of recurrent infection.
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| 27. |
- Edvinsson, Marie-Louise, et al.
(författare)
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Deteriorated function of cutaneous microcirculation in chronic congestive heart failure
- 2011
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Ingår i: Journal of geriatric cardiology : JGC. - 1671-5411. ; 8:2, s. 82-87
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Tidskriftsartikel (refereegranskat)abstract
- Background Chronic congestive heart failure is a complex condition that leads to dysfunction in the peripheral microcirculation. We have previously shown that vascular reactivity is reduced with increasing age. In this study, we examined a group of very old patients with severe chronic heart failure to test the hypothesis that vascular function is further compromised by a combination of heart failure and aging. Methods Cutaneous forearm blood flow was measured by laser Doppler flowmetry and compared among three groups: Group 1 (n = 20, mean +/- SE: 85.5 +/- 4 years), heart failure patients with New York Heart Association class IV (NYHA IV) and with a NT-proBNP level >= 5000 ng/L; Group 2 (n = 15, mean +/- SE: 76.5 +/- 2 years), heart failure patients with NYHA II and NT-proBNP <= 2000 ng/L, and Group 3 (n = 10, mean +/- SE: 67.6 +/- 3.0 years), healthy controls with no clinical signs of heart failure. The vasodilator response to the iontophoretic administration of acetylcholine (ACh), acting via an endothelial mechanism, and sodium nitroprusside (SNP), acting via a smooth muscle cell mechanism, were studied. Results All patients with heart failure had significantly reduced vascular reactivity independent of the mode of stimulation (ACh, SNP or heat) when compared to healthy controls. However, the responses did not differ between the two groups of heart failure patients. Conclusions Cutaneous vascular reactivity is reduced in heart failure patients and does not correlate with the severity of the condition or age of patients.
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| 28. |
- Edvinsson, Marie Louise, et al.
(författare)
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Improved outcome with standardized plan for clinical management of acute decompensated chronic heart failure
- 2019
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Ingår i: Journal of Geriatric Cardiology. - 1671-5411. ; 16:1, s. 12-18
-
Tidskriftsartikel (refereegranskat)abstract
- Background Our overall goal is to improve clinical care for inpatients with chronic heart failure (CHF). A retrospective assessment of CHF patients admitted to our hospital over the past decade (2005 vs. 2014) indicated a need for better strategies to evaluate clinical treatment, implement best practices and achieve optimal patient outcome. To that purpose, we developed a standardized plan to improve in-hospital treatment of acute decompensated CHF patients. Methods & Results Retrospective chart reviews were conducted to compare three cohorts of CHF patients admitted to the University Hospital of Lund at different time points over a 12-year period: 2005 (365 patients), 2014 (172 patients) and 2017–2018 (57 patients). Little improvement was seen between 2005 and 2014 with respect to one-year mortality (35% vs. 34%) and adequate treatment with recommended medications, e.g., use of renin-angiotensin system blockers (45% vs. 51%). A standardized treatment plan was devised to improve outcomes. A third cohort, treated under the plan (2017–2018), was compared with the 2014 cohort. One-year mortality (18% vs. 34%) and 30-day readmission (5% vs. 30%) were dramatically decreased, and adherence to medication guidelines was achieved. Key elements of the plan included well-defined treatment procedures, enhanced communication and teamwork, education, adequate time for treatment (5 days) and post-discharge follow-up as necessary. Natriuretic peptide (NT-proBNP) levels were useful for assessing patient status, prognosis and response to treatment. Conclusion Development of a standard plan for clinical management of acute decompensated CHF patients resulted in significant improvements in patient outcome, as reflected in decreased rates of 30-day readmission and one-year mortality.
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| 29. |
- Edvinsson, Marie, et al.
(författare)
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No evidence of Chlamydia pneumoniae in the synovia of patients with osteoarthritis
- 2019
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Ingår i: Journal of international medical research. - : Sage Publications. - 0300-0605 .- 1473-2300. ; 47:2, s. 635-640
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Osteoarthritis (OA) is a common cause of disability affecting millions of people of all ages worldwide. The pathogenesis involves an inflammatory component, but the cause of the inflammation remains incompletely understood. The intracellular bacteria Chlamydia trachomatis and C. pneumoniae have been demonstrated in patients with reactive arthritis. Both of these microorganisms can cause chronic and persistent infections, with C. trachomatis being the most common cause of reactive arthritis. This study was performed to investigate the presence of C. pneumoniae in a large number of patients with primary OA.METHODS: The study included 75 patients who underwent total knee arthroplasty. During surgery, a synovial biopsy was performed and synovial fluid drawn. Real-time polymerase chain reaction (PCR) of C. pneumoniae was run on all patients, and real-time PCR of bacterial 16S rDNA was conducted on 30 of the 75 patients to screen for the presence of other bacteria.RESULTS: Real-time PCR showed no evidence of the presence of C. pneumoniae in the patients' specimens, nor were other bacteria detected.CONCLUSIONS: Although an inflammatory component is part of the pathogenesis of OA, we found no evidence indicating that C. pneumoniae is a stimulator of that inflammation.
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| 30. |
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| 31. |
- Edvinsson, Marie, et al.
(författare)
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Persistent Chlamydophila pneumoniae infection in thoracic aortic aneurysm and aortic dissection?
- 2010
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 115:3, s. 181-186
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Chlamydophila pneumoniae (C. pneumoniae) has been associated with atherosclerosis and abdominal aortic aneurysm and is probably disseminated by peripheral blood mononuclear cells (PBMC). Viable and metabolically active bacteria can be demonstrated by the presence of bacterial mRNA and on-going dissemination by the presence of bacteria in PBMC. The aim of this study was to determine the prevalence of C. pneumoniae DNA and mRNA in aortic biopsies and C. pneumoniae DNA in PBMC in thoracic aortic aneurysm and aortic dissection patients. Design. Real-time PCR was used to detect C. pneumoniae DNA and mRNA in biopsies and C. pneumoniae DNA in PBMC. Results. C. pneumoniae DNA was found in biopsies in 26% (6/23) of aneurysm patients and 11% (2/18) of dissection patients but in none of the forensic autopsy controls. C. pneumoniae mRNA was not found in any biopsy, and all PBMC were C. pneumoniae-negative. Conclusions. Presence of C. pneumoniae DNA but not mRNA in aortic biopsies and no evidence of C. pneumoniae in PBMC suggest that the infection in the aorta has passed into a state of persistence.
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| 32. |
- Edvinsson, Marie, et al.
(författare)
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Presence of Chlamydophila pneumoniae DNA but not mRNA in stenotic aortic heart valves
- 2010
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 143:1, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- Background: The pathogenesis of aortic valve stenosis may involve inflammation and we have previously demonstrated Chlamydophila pneumoniae (C. pneumoniae) DNA in stenotic aortic heart valves. Dissemination of these bacteria is probably mediated by alveolar macrophages. Bacterial DNA alone does not indicate whether the bacteria are viable and replicating. This study aimed to investigate the presence of C. pneumoniae mRNA, a marker of replicating bacteria, and C. pneumoniae DNA in stenotic aortic valves and the prevalence of C. pneumoniae in peripheral blood mononuclear cells (PBMC).Methods: DNA was extracted from heart valves and PBMC and mRNA from heart valves from 76 patients undergoing aortic valve replacement surgery. C. pneumoniae DNA and mRNA were measured by real-time PCR targeting the ompA gene.Results: C. pneumoniae DNA was demonstrated in 22% of heart valves and in 5% of PBMC. C. pneumoniae mRNA was not detected in any valve. Patients positive for C. pneumoniae in the valve underwent coronary artery by-pass grafting more often (p = 0.01) and suffered from angina pectoris (p = 0.02) and arterial hypertension (p = 0.03) more often than patients negative for C. pneumoniae in the valve.Conclusions: These findings support a role for C. pneumoniae in the pathogenesis of aortic valve stenosis and indicate that the bacteria disseminate from the respiratory tract long before the patients were in need of surgery and that the valve infection thereafter entered into a persistent and non-replicative state. Moreover, patients positive for C. pneumoniae in the valve more often needed by-pass grafting because of more advanced coronary disease.
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| 33. |
- Edvinsson, Marie, et al.
(författare)
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Trace element balance is changed in infected organs during acute Chlamydophila pneumoniae infection in mice
- 2008
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Ingår i: Biometals. - : Springer Science and Business Media LLC. - 0966-0844 .- 1572-8773. ; 21:2, s. 229-237
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Tidskriftsartikel (refereegranskat)abstract
- Most infectious diseases are accompanied by changed levels of several trace elements in the blood. However, sequential changes in trace elements in tissues harbouring bacterial infections have not been studied. In the present study the respiratory pathogen Chlamydophila pneumoniae (C. pneumoniae), adapted to C57BL/6J mice, was used to study whether the balance of trace elements is changed in infected organs. Bacteria were quantitatively measured by real-time PCR in the blood, lungs, liver, aorta, and heart on days 2, 5, and 8 of the infection. Concentrations of 13 trace elements were measured in the liver, heart, and serum by inductively coupled plasma mass-spectrometry (ICP-MS). Infected mice developed expected clinical signs of disease and bacteria were found in lungs, liver, and heart on all days. The number of bacteria peaked on day 2 in the heart and on day 5 in the liver. The copper/zinc (Cu/Zn) ratio in serum increased as a response to the infection. Cu increased in the liver but did not change in the heart. Iron (Fe) in serum decreased progressively, whereas in the heart it tended to increase, and in the liver it progressively increased. C. pneumoniae may thus cause a changed trace element balance in target tissues of infection that may be pivotal for bacterial growth.
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| 34. |
- Edvinsson, Marie, et al.
(författare)
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Trace Element Changes in Thoracic Aortic Dissection
- 2016
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Ingår i: Biological Trace Element Research. - : Springer Science and Business Media LLC. - 0163-4984 .- 1559-0720. ; 169:2, s. 159-163
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Tidskriftsartikel (refereegranskat)abstract
- Thoracic aortic dissection is a life-threatening condition with an incompletely understood pathogenesis. Trace elements are essential for the functioning of different processes in the body, including the immune system and associated responses to infection/inflammation. Because inflammation may be part of the pathogenesis of thoracic aortic dissection, we investigated whether trace element changes associated with inflammation occur in serum and tissue samples during the disease. The study included 21 patients undergoing surgery for thoracic aortic dissection, 10 forensic autopsy specimens for tissue controls and 23 healthy blood donors for serum controls. Levels of magnesium (Mg), calcium (Ca), vanadium (V), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), cadmium (Cd) and mercury (Hg) were measured in the aortic tissue and serum by inductively coupled plasma-mass spectrometry (ICP-MS). In the serum, Ca, V, Cu and Zn decreased, whereas Fe increased. In the tissue, Cu and Zn decreased and Fe tended to increase. The Cu/Zn ratio in the serum, a marker of infection/inflammation, did not change in the patients. Concerning trace element changes in the serum and tissue, our data do not support the hypothesis that inflammation is involved in the pathogenesis of thoracic aortic dissection.
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| 35. |
- Edvinsson, Sören, 1953-, et al.
(författare)
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Wealth and health in 19th century Sweden : A study of social differences in adult mortality in the Sundsvall Region
- 2011
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Ingår i: Explorations in economic history. - New York : Academic P.. - 0014-4983 .- 1090-2457. ; 48:3, s. 376-388
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Tidskriftsartikel (refereegranskat)abstract
- The present article analyses social inequality in mortality in the 19th century Sundsvall region, an area that experienced rapid industrialization after 1850. The purpose of the study is to investigate whether there were social differences in mortality in this context and whether these differences increased during the industrial break-through. The expected advantages for higher social classes could not be confirmed in this environment. Instead, the best survival was found among those belonging to the agricultural sector. We found a strongly gendered pattern, with much higher mortality for and small health differences among men, while the results indicate increasing social inequality in female mortality during industrialization. The spatial pattern of mortality was pronounced and living with a partner had a strong impact on survival, particularly for men. We finally discuss the role of gender and class expectations in relation to lifestyles for the social patterning of mortality.
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| 36. |
- Faxén, Lisa, et al.
(författare)
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Persistent SARS-CoV-2 infection in patients with B-cell deficiency : a case series of successful antiviral treatment of four patients
- 2023
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Ingår i: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 128
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Tidskriftsartikel (refereegranskat)abstract
- Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immunocompromised patients remains a major medical challenge. Diagnosing the syndrome is difficult as symptoms may mimic other diseases and treatment guidelines are lacking. We describe a case series of four patients with persistent SARS-CoV-2 infection that all had an underlying B-cell deficiency due to rituximab treatment (in one case in combination with epcoritamab). In all four patients, it was initially difficult to recognize the persistent disease, leading to a duration of illness between 45 and 242 days. Two patients were only positive for SARS-CoV-2 by polymerase chain reaction (PCR) in the nasopharynx at the beginning of the disease but were later repeatedly negative. However, when bronchoalveolar lavage was performed, a positive SARS-CoV-2 PCR was revealed from the lower airways in both patients. The difficulties establishing diagnosis contributed to these two patients’ long disease course. The longest disease duration was in the patient treated with rituximab and epcoritamab, who also responded poorly to single standard antiviral treatment. This patient ultimately cleared the infection after administering a combination treatment with remdesivir and nirmatrelvir/ritonavir. After a confirmed diagnosis, the other three patients cleared the infection when they were finally treated with antivirals. Increasing clinicians’ awareness of this condition is important as it might be treatable once diagnosed. Further studies are warranted to define the condition and treatment strategy with greater precision.
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| 37. |
- Frederiksen, Simona D., et al.
(författare)
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Serotonin and Neuropeptides in Blood From Episodic and Chronic Migraine and Cluster Headache Patients in Case-Control and Case-Crossover Settings : A Systematic Review and Meta-Analysis
- 2020
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Ingår i: Headache. - : Wiley. - 0017-8748. ; 60:6, s. 1132-1164
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Forskningsöversikt (refereegranskat)abstract
- Objective: The aim of this systematic review and meta-analysis (SR-MA) was to identify signaling molecule profiles and blood-derived biomarkers in migraine and cluster headache (CH) patients. Background: Currently no migraine and CH valid biomarkers are available. Blood tests based on biomarker profiles have been used to gather information about the nervous system. Such tests have not yet been established within the primary headache field. Methods: Case-control and case-crossover studies investigating whole blood, plasma, and serum were identified worldwide. The qualitative synthesis focused on 9 signaling molecules (serotonin [5-HT], calcitonin gene-related peptide [CGRP], endothelin-1 [ET-1], neurokinin A, neurokinin B, neuropeptide Y, pituitary adenylate cyclase-activating peptide 38 [PACAP-38], substance P (SP), and vasoactive intestinal peptide) and the quantitative synthesis on 5-HT and CGRP (≥5 comparisons available). The meta-analysis was conducted using standard and 3-level random effect models. Results: Fifty-four eligible studies were identified (87.0% migraine, 9.3% CH, 3.7% migraine, and CH), and 2768 headache patients and 1165 controls included. Comparable fluctuations of 5-HT, CGRP, ET-1, PACAP-38, and SP in blood were generally observed between migraine and CH. Significant findings were observed for some subgroups and strata, for example, higher interictal and ictal 5-HT venous blood levels (ratio of means = 1.32, 95% CI: 1.08; 1.61; ratio of means = 1.23, 95% CI: 1.01; 1.49) in episodic migraine with aura with a female-dominated case group, higher interictal CGRP blood levels in episodic migraine (ratio of means = 1.63, 95% CI: 1.18; 2.26), and chronic migraine (ratio of means = 1.89, 95% CI: 1.33; 2.68), and higher ictal CGRP blood levels (ratio of means = 1.35, 95% CI: 1.09; 1.68) in episodic migraine were observed. In most subgroups, the quantitative synthesis revealed a high degree of heterogeneity between studies in part explained by the blood sampling site, specimen source, blood specimen, and sex distribution. Other potential confounders were age, aura, study quality, menstrual cycle, and methodology (eg, storage temperature). Conclusions: Potential migraine and CH signaling molecule profiles and biomarkers were revealed. Nevertheless, the high degree of heterogeneity between studies impedes identification of valid biomarkers but allowed us to assess the presence of confounders. Consideration of the potential confounders identified in this SR-MA might be of importance in the experimental planning of future studies. This consideration could be incorporated through establishment of specific guidelines.
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| 38. |
- Gidlöf, Olof, et al.
(författare)
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Complete discrimination of six individuals based on high-resolution melting of hypervariable regions I and II of the mitochondrial genome
- 2009
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Ingår i: BioTechniques. - : Future Science Ltd. - 0736-6205 .- 1940-9818. ; 47:2, s. 671-678
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of mitochondrial DNA in forensic samples is routinely carried out by direct sequencing of hypervariable regions within the non-coding displacement loop. Although the accuracy and sensitivity of this method cannot be questioned, it is both time-consuming and labor intensive. Finding a way to rapidly pre-screen forensic samples-prior to sequencing, to reduce the number of samples that need to be sequenced-would greatly benefit forensic laboratories. Herein, we describe an assay for discrimination of DNA from different individuals based on high-resolution melting analysis of the two hypervariable regions HVI and HVII of the mitochondrial genome. By clearly distinguishing the DNA melting curves of six different individuals, we show that this assay has the potential to function as a rapid and inexpensive pre-screening method for forensic samples prior to DNA sequencing.
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| 39. |
- Henriksson, Marie, et al.
(författare)
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Importance of ERK1/2 in upregulation of endothelin type B receptors in cerebral arteries
- 2004
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Ingår i: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 142:7, s. 1155-1161
-
Tidskriftsartikel (refereegranskat)abstract
- 1 This study examines the importance of mitogen-activated protein kinases (MAPKs) in upregulation of endothelin type B (ETB) receptors. 2 Rat middle cerebral arteries (MCAs) were incubated for 24 h with or without kinase inhibitors. Vessel segments were mounted in myographs and the contractile responses to endothelin-1 (ET-1; ETA and ETB receptor agonist) and sarafotoxin 6c (S6c; ETB receptor agonist) were studied. We used real-time PCR to measure the receptor mRNA levels. An ELISA assay showed the activation of ERK1/2 kinases after 3 h. Immunohistochemistry revealed the presence of ETB receptors on the vessels. 3 After organ culture, S6c induced vasoconstriction. Incubation with the MEK/ERK inhibitors U0126 and SB386023 diminished the contractile response to S6c. The p38 MAPK inhibitor SB239063 did not affect the S6c-induced contraction. 4 The ET-1-induced vasoconstriction was increased after incubation with SB386023 or SB239063, while unaffected by U0126. 5 The ETB receptor mRNA levels were diminished by SB386023 and U0126. The ETA receptor mRNA levels were unaffected. 6 The levels of activated ERK1/2 kinases were significantly higher after 3 h of organ culture as compared to fresh vessels. 7 The level of ETB receptor protein on the smooth muscle cells of the MCA, visualised by immunohistochemistry, was somewhat diminished by SB386023. 8 Our results show that the ERK1/2 MAPK is important in the upregulation of contractile ETB receptors in MCA after organ culture. Since there is a similar upregulation in models of focal ischaemia and subarachnoid haemorrhage, this may be an important pathophysiological event.
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| 40. |
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| 41. |
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| 42. |
- Henriksson, Marie, et al.
(författare)
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MEK1/2 inhibition attenuates vascular ET(A) and ET (B) receptor alterations after cerebral ischaemia.
- 2007
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Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 178:4, s. 470-476
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Tidskriftsartikel (refereegranskat)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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| 43. |
- Henriksson, Marie, et al.
(författare)
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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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Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 8, s. 7-7
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Tidskriftsartikel (refereegranskat)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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| 44. |
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| 45. |
- Lissau, Jonas Sandby, et al.
(författare)
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What Limits Photon Upconversion on Mesoporous Thin Films Sensitized by Solution-Phase Absorbers?
- 2015
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 119:9, s. 4550-4564
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Tidskriftsartikel (refereegranskat)abstract
- Photon upconversion by sensitized triplet-triplet annihilation (UC-STTA) is a promising strategy for breaking the Shockley-Queisser limit for efficiency of single-threshold solar cells, and in particular dye-sensitized solar cells (DSSCs). Here, we report on a heterogeneous UC system, where the annihilating dyes (emitters) are bound to a ZrO2 nanostructured film and the light absorbing dyes (sensitizers) are free in solution. A comparative study of four different emitter dyes was conducted, all of them derivatives of the well-known UC-STTA emitter dye 9,10-diphenylanthracene (DPA), and in every case, the sensitizer dye was platinum(II) octaethylporphyrin (PtOEP). The physical separation of emitter and sensitizer molecules in two different phases makes homogeneous triplet-triplet annihilation among sensitizers in solution a significant loss channel at high excitation intensity and low emitter surface coverage. For the studied emitter dyes, the number and type of anchor groups, and the solubility of the emitter dye in the employed solvents, are the determining factors of the UC output. The signal evolves in time and with light exposure due to emitter desorption and light-induced endoperoxide formation. These results can guide the way toward a better understanding of UC-STTA on nanocrystalline metal oxides and its development for solar energy applications.
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| 46. |
- Nilsson, Kenneth, Docent, 1953-, et al.
(författare)
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A comprehensive clinical and laboratory evaluation of 224 patients with persistent symptoms attributed to presumed tick-bite exposure
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Persistent symptoms attributed to presumed tick-bite exposure constitute an unresolved medical controversy. We evaluated whether Swedish adults who met the criteria for post-treatment Lyme disease syndrome (PTLDS) exhibited characteristics distinguishable from adults who did not, but who displayed similar symptoms and disease course after suspected previous tick-bite infection (TBI). Methods and findings During 2015-2018, 255 patients-referred to the Centre for Vector-borne Infections, Uppsala University Hospital, Sweden with symptoms lasting longer than six months-were recruited. Of this group, 224 completed the study. Each patient was examined by an infectious disease specialist and, besides a full medical history, underwent a panel of blood and cerebrospinal fluid laboratory tests including hematological, biochemical, microbiological and immunological analyses, and the RAND-36 scale to measure quality of life. For analysis purposes, patients were divided into five subgroups, of which one represented PTLDS. According to serological results indicating TBI and documented/ reported objective signs of Lyme disease, 85 (38%) patients fulfilled the criteria for PTLDS and were compared with the other 139 (62%) serologically classified patients. In the PTLDS group, erythema chronicum migrans (ECM) was documented/reported in 86% of patients, previous neuroborreliosis in 15%, and acrodermatitis chronica atroficans (ACA) in 3.5%. However, there were no significant differences regarding symptoms, laboratory results or disease course between patients with PTLDS and those without laboratory evidence of Borrelia exposition. Most reported symptoms were fatigue-related (70%), musculoskeletal (79%), neurological (82%) and neurocognitive (57%). Tick bites were recalled by 74%. The RAND-36 score was significantly below that of the general Swedish population. Signs of immunological/inflammatory reactivity with myositis antibodies were detected in 20% of patients, fibrinogen levels were moderately increased in 21% and elevated rheumatoid factor in 6%. Conclusions The PTLDS group did not differ exclusively in any respect from the other subgroups, which either lacked previously documented/reported evidence of borreliosis or even lacked detectable serological signs of exposure to Lyme disease. The results suggest that symptoms often categorized as Chronic-Lyme-Disease (CLD) in the general debate, cannot be uniquely linked to Lyme disease. However, approximately 20% of the total group of patients showed signs of autoimmunity. Further studies are needed to elucidate the underlying causes and mechanisms of PTLDS and there is reason to consider a multifactorial approach.
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| 47. |
- Nilsson, Kenneth, Docent, 1953-, et al.
(författare)
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Protein biomarker profiles in serum and CSF in 158 patients with PTLDS or persistent symptoms after presumed tick-bite exposure compared to those in patients with confirmed acute neuroborreliosis
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11
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Tidskriftsartikel (refereegranskat)abstract
- Background Current diagnostics for patients with lingering symptoms categorized as post-treatment Lyme disease syndrome (PTLDS) have their limitations and may be difficult to interpret. The aim of this exploratory study was to evaluate the feasibility of protein biomarker profiling as a diagnostic platform for this category of patients and to compare these results with similarly obtained results from a group of patients with acute neuroborreliosis.Methods and findings Two groups of patient cohorts (Cohort 1 and 2) were analyzed for biomarkers in serum and cerebrospinal fluid (CSF); the results were used for group-level comparison. Cohort 1 comprised 158 adult patients selected from 224 previously diagnosed patients, who between October 2015 and December 2018, after referral, were enrolled and structurally investigated based on defined inclusion criteria. They displayed similar lingering symptoms, with a duration of at least 6 months, after presumed previous tick-borne infection (TBI) and are fully described in a previously published study originating from the Center for Vector-borne Infections (CVI), Uppsala University Hospital, Sweden. Cohort 2, comprised 30 patients diagnosed at Uppsala University Hospital between 2016 and 2019 with laboratory-confirmed acute neuroborreliosis. Their proteomic results, based on serum and CSF analyses, were compared with the 158 patients in Cohort 1. The expression and the concentration of potential biomarkers in each patient's serum and CSF samples were measured based on two multiplex protein panels enabling simultaneous analysis of 92 inflammatory and neurology biomarkers. The PTLDS patient subgroup showed no nominally significant proteins compared to the other CVI patients in Cohort 1. However, CVI patients with signs of inflammation, which were evenly distributed in Cohort 1, showed 16 significantly (p <0.05) different proteins in both CSF and serum, but no association was seen with laboratory-confirmed exposure to Borrelia spp or other TBIs. When comparing the two cohorts, different protein profiles were observed, with 125/148 significantly different proteins in CSF and 93/174 in serum, in patients with laboratory confirmed acute neuroborreliosis, of which 6 in CSF and 6 in serum were significant at the p <0.001 level.Conclusions In this first comprehensive inflammatory and neurological biomarker profile study no differences in biomarker profiles were detected between patients with PTLDS and patients with similar persisting symptoms but who did not meet the PTLDS criteria, regardless of whether laboratory verified previous exposure to Borrelia or other TBI's were present. However, the expressed markers differed from those found in patients with confirmed acute neuroborreliosis, which does not support the view that PTLDS reflects an ongoing Borrelia infection. Further studies are needed to understand and assess the usefulness of biosignatures of patients with PTLDS before they can be applied in a clinical setting.
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| 48. |
- Nyström-Rosander, Christina, et al.
(författare)
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Chlamydophila pneumonia : Specific mRNA in aorta ascendens in patients undergoing coronary artery by-pass grafting
- 2006
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 38:9, s. 758-763
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this prospective study was to investigate if Chlamydophila pneumoniae (Cp)-specific DNA and mRNA are present in tissue samples from the wall of aorta ascendens in patients undergoing by-pass surgery for coronary artery disease (CAD) that includes stable angina pectoris (SAP, 25 patients) and acute coronary syndrome (ACS, 19 patients). Viable Cp was detected in 8/44 (18%) patients using reversed transcriptase PCR (RT-PCR) against bacterial mRNA with detection of cDNA using real-time PCR against the MOMP gene. Cp DNA was detected by nested PCR in 22/44 (50%) patients and by real-time PCR in 13/44 (30%) patients. In total, 24/44 (55%) patients were positive for Cp nucleic acid in any PCR. Antibodies to Cp were detected in 13/24 (54%) Cp PCR-positive and in 15/20 (75%) Cp PCR-negative patients. Nested PCR was run on throat swabs from all patients. No significant differences were noted between SAP and ACS patients regarding PCR results or serology. It has been suggested that Cp may be a 'silent passenger' picked up by the atherosclerotic plaque. Our findings of viable and metabolically active bacteria in aortic tissue add further support to the hypothesis that Cp may have an active role in the pathogenesis of atherosclerosis.
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| 49. |
- Nyström-Rosander, Christina, et al.
(författare)
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Thoracic aortic aneurysm patients with Chlamydophila pneumoniae infection showed a shift in trace element levels in serum and diseased aortic tissue
- 2009
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Ingår i: Journal of Trace Elements in Medicine and Biology. - : Elsevier BV. - 0946-672X .- 1878-3252. ; 23:2, s. 100-106
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Tidskriftsartikel (refereegranskat)abstract
- Few studies have been performed on trace elements in tissues and serum in cardiovascular disease and none in aortic aneurysm. In this study the concentrations of 10 trace elements were determined in serum and aneurysmatic aortic tissue from 23 patients undergoing thoracic surgery. Macroscopically, normal thoracic aortic tissue specimens from 10 forensic autopsies and serum from 23 healthy blood donors served as controls. DNA from the intracellular respiratory pathogen Chlamydophila pneumoniae (C. pneumoniae), which may be involved in the pathogenesis of atherosclerosis, was found in 26% (6/23) of the patients but in none of the controls. The serum copper/zinc ratio, a well-known marker of ongoing infection and/or inflammation, was higher (26%, p<0.001) in aneurysm patients. C. pneumoniae requires iron for its growth. In our aneurysm patients iron was higher in serum (by 54%, p<0.001) and aneurysmal tissue (by 60%, p<0.001). Although calcium was lower in patient sera (by 8%, p<0.001), it tended to be higher (by 20%, ns) in aneurysmatic tissue. In addition, mercury concentrations in serum and aneurysmatic tissue were positively correlated (r=0.51, p<0.05). Moreover, C. pneumoniae-positive aneurysmatic tissues had lower concentrations of manganese (46%, p<0.05) and zinc (26%, ns) but a higher concentration of mercury (50%, p<0.05) than C. pneumoniae-negative aneurysmatic tissues. In conclusion, aneurysm patients showed a shift in trace element levels in serum and in the diseased part of the aorta, the pattern being partly different in C. pneumoniae-positive compared with C. pneumoniae-negative patients. The results are compatible with active infection and/or inflammation, possibly initiated by C. pneumoniae.
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| 50. |
- Rubio-Beltrán, Eloisa, et al.
(författare)
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PACAP38 and PAC1 receptor blockade : a new target for headache?
- 2018
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Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 19:1
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Forskningsöversikt (refereegranskat)abstract
- Pituitary adenylate cyclase activating polypeptide-38 (PACAP38) is a widely distributed neuropeptide involved in neuroprotection, neurodevelopment, nociception and inflammation. Moreover, PACAP38 is a potent inducer of migraine-like attacks, but the mechanism behind this has not been fully elucidated.Migraine is a neurovascular disorder, recognized as the second most disabling disease. Nevertheless, the antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor are the only prophylactic treatment developed specifically for migraine. These antibodies have displayed positive results in clinical trials, but are not effective for all patients; therefore, new pharmacological targets need to be identified.Due to the ability of PACAP38 to induce migraine-like attacks, its location in structures previously associated with migraine pathophysiology and the 100-fold selectivity for the PAC1 receptor when compared to VIP, new attention has been drawn to this pathway and its potential role as a novel target for migraine treatment. In accordance with this, antibodies against PACAP38 (ALD 1910) and PAC1 receptor (AMG 301) are being developed, with AMG 301 already in Phase II clinical trials. No results have been published so far, but in preclinical studies, AMG 301 has shown responses comparable to those observed with triptans. If these antibodies prove to be effective for the treatment of migraine, several considerations should be addressed, for instance, the potential side effects of long-term blockade of the PACAP (receptor) pathway. Moreover, it is important to investigate whether these antibodies will indeed represent a therapeutic advantage for the patients that do not respond the CGRP (receptor)-antibodies.In conclusion, the data presented in this review indicate that PACAP38 and PAC1 receptor blockade are promising antimigraine therapies, but results from clinical trials are needed in order to confirm their efficacy and side effect profile.
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