| 1. |
- Moilanen, Lauri J., et al.
(författare)
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TRPA1 Contributes to the Acute Inflammatory Response and Mediates Carrageenan-Induced Paw Edema in the Mouse
- 2012
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Transient receptor potential ankyrin 1 (TRPA1) is an ion channel involved in thermosensation and nociception. TRPA1 is activated by exogenous irritants and also by oxidants formed in inflammatory reactions. However, our understanding of its role in inflammation is limited. Here, we tested the hypothesis that TRPA1 is involved in acute inflammatory edema. The TRPA1 agonist allyl isothiocyanate (AITC) induced inflammatory edema when injected intraplantarly to mice, mimicking the classical response to carrageenan. Interestingly, the TRPA1 antagonist HC-030031 and the cyclo-oxygenase (COX) inhibitor ibuprofen inhibited not only AITC but also carrageenan-induced edema. TRPA1-deficient mice displayed attenuated responses to carrageenan and AITC. Furthermore, AITC enhanced COX-2 expression in HEK293 cells transfected with human TRPA1, a response that was reversed by HC-030031. This study demonstrates a hitherto unknown role of TRPA1 in carrageenan-induced inflammatory edema. The results also strongly suggest that TRPA1 contributes, in a COX-dependent manner, to the development of acute inflammation.
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| 2. |
- Archer, Mari, et al.
(författare)
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The role of alcohol use and adiposity in serum levels of IL-1RA in depressed patients
- 2022
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Ingår i: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of Interleukin-1 Receptor antagonist (IL-1Ra), an innate antagonist to pro-inflammatory cytokine IL-1, has attracted increasing attention due to its potential pathogenic and therapeutic implications in depression. However, the role of alcohol and adiposity in modulating IL-1Ra cytokine pathway in depressed patients has remainned unknown. The aim of this study was to follow the changes in IL-1Ra serum levels in depressed patients with or without simultaneous alcohol use disorder (AUD) and different degrees of adiposity during 6 months of follow-up.MATERIALS AND METHODS: A total of 242 patients with depression were followed for 6 months. At baseline 99 patients had simultaneous AUD. Levels of serum IL-1Ra and common mediators of inflammation (IL-6, hs-CRP) were measured. Clinical assessments included Body Mass Index (BMI), Montgomery-Asberg Depression Rating Scale (MADRS) and Alcohol Use Disorders Identification Test (AUDIT) scores.RESULTS: Significant reductions in clinical symptoms and IL-1Ra were observed during 6-month follow-up. In hierarchical linear regression analysis, the effect of MADRS score, age, gender, and smoking had a combined effect of 2.4% in the model. The effect of AUDIT score increased the effect to 4.2% of variance (p = 0.08), whereas adding BMI increased the effect to 18.5% (p < 0.001).CONCLUSION: Adiposity may influence the IL-1Ra anti-inflammatory response in depressed patients, whereas the effect of alcohol consumption in these patients seems insignificant. These findings should be considered in studies on the role of IL-1Ra in depression.
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| 3. |
- Flinkman, Ella, et al.
(författare)
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Association Between Blood Eosinophils and Neutrophils With Clinical Features in Adult-Onset Asthma.
- 2023
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Ingår i: The journal of allergy and clinical immunology. In practice. - : Elsevier BV. - 2213-2198 .- 2213-2201. ; 11:3, s. 811-821
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is a disease that can be separated into different phenotypes and endotypes based on the clinical characteristics and the molecular mechanisms of the condition, respectively.To assess the association between blood eosinophil and neutrophil counts with clinical and molecular features in patients with adult-onset asthma.Blood eosinophil and neutrophil counts were measured from 203 patients who took part in the Seinäjoki Adult Asthma Study and attended the 12-year follow-up visit. The patients were then divided into four groups (paucigranulocytic [n= 108], neutrophilic [n= 60], eosinophilic [n= 21], and mixed granulocytic [n= 14]), according to eosinophil and neutrophil levels. The cutoff values used to define the groups were 0.30× 109 · L-1 for blood eosinophils and 4.4× 109 · L-1 for blood neutrophils.The neutrophilic group had highest body mass index. It was dispensed the highest doses of inhaled corticosteroids during the 12-year follow-up and made the most unplanned respiratory visits. The neutrophilic, eosinophilic, and mixed granulocytic groups had more severe asthma compared with the paucigranulocytic group. The neutrophilic and eosinophilic groups were associated with higher dispensed antibiotics. The eosinophilic group had more nasal polyps, more suspected sinusitis, a greater decline in lung function, and increased levels of periostin, FeNO, and IgE. The neutrophilic group had increased high-sensitivity C-reactive protein, matrix metalloproteinase-9, IL-6, leptin, and soluble urokinase plasminogen activator receptor levels. The mixed granulocytic group showed increased resistin levels together with the neutrophilic group.In addition to blood eosinophils, the blood neutrophil count reflects underlying inflammatory patterns and indicates important differences in asthma clinical features and outcomes.
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| 4. |
- Hyysalo, Jenni, et al.
(författare)
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A population-based study on the prevalence of NASH using scores validated against liver histology.
- 2014
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Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278. ; 60:4, s. 839-846
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Tidskriftsartikel (refereegranskat)abstract
- Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. Diagnosis of NASH requires a liver biopsy. We estimated the prevalence of NASH non-invasively in a population-based study using scores validated against liver histology.
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| 5. |
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| 6. |
- Kiiski, Heikki, et al.
(författare)
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Increased plasma UCH-L1 after aneurysmal subarachnoid hemorrhage is associated with unfavorable neurological outcome
- 2016
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 361, s. 144-149
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Aneurysmal subarachnoid hemorrhage (aSAH) is a common cause of long-term disability and death. After primary hemorrhage, secondary brain injury is the main cause of mortality and morbidity. Despite extensive research, reliable prognostic biomarkers are lacking. We measured ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) levels in aSAH patients to evaluate its prognostic potential. This is the first time that plasma UCH-L1 has been studied as a potential prognostic biomarker in patients with aSAH. Methods: In this prospective population-based study, UCH-L1 levels were measured in aSAH patients (n = 47) for up to five days. UCH-L1 was measured at 0, 12 and 24 h after the admission to the intensive care unit (ICU) and daily thereafter until the patient was transferred from the ICU. Only patients whose UCH-L1 was measured within 24 h from aSAH were included in the study. The patients' neurological outcome was evaluated with the modified Rankin Scale (mRS) at six months after aSAH. Results: UCH-L1 levels during the first 24 h after aSAH were not significantly different between the groups with favorable (mRS 0-2) and unfavorable (mRS 3-6) neurological outcome. In 22 patients, UCH-L1 levels were obtained for up to five days. In this subgroup, UCH-L1 measured at day five showed significant elevation from baseline levels in patients with unfavorable outcome (p = 0.026). Elevated UCH-L1 levels at day five were higher in patients with unfavorable outcome than in patients with favorable outcome (p = 0.001). Conclusions: Elevated UCH-L1 levels during the five-day follow-up were associated with unfavorable neurological outcome. Repetitive measurements of UCH-L1 concentrations with an emphasis on change relative to the individual baseline could be the optimal approach for future clinical studies.
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| 7. |
- Kiiski, Heikki, et al.
(författare)
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Plasma soluble Urokinase-Type Plasminogen activator receptor is not associated with neurological Outcome in Patients with aneurysmal subarachnoid hemorrhage
- 2017
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Ingår i: Frontiers in Neurology. - : FRONTIERS MEDIA SA. - 1664-2295. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Object: Aneurysmal subarachnoid hemorrhage (aSAH) is a common cause of death or long-term disability. Despite advances in neurocritical care, there is still only a very limited ability to monitor the development of secondary brain injury or to predict neurological outcome after aSAH. Soluble urokinase-type plasminogen activator receptor (suPAR) has shown potential as a prognostic and as an inflammatory biomarker in a wide range of critical illnesses since it displays an association with overall immune system activation. This is the first time that suPAR has been evaluated as a prognostic biomarker in aSAH. Methods: In this prospective population-based study, plasma suPAR levels were measured in aSAH patients (n = 47) for up to 5 days. suPAR was measured at 0, 12, and 24 h after patient admission to the intensive care unit (ICU) and daily thereafter until he/ she was transferred from the ICU. The patients' neurological outcome was evaluated with the modified Rankin Scale (mRS) at 6 months after aSAH. Results: suPAR levels (n = 47) during the first 24 h after aSAH were comparable in groups with a favorable (mRS 0-2) or an unfavorable (mRS 3-6) outcome. suPAR levels during the first 24 h were not associated with the findings in the primary brain CT, with acute hydrocephalus, or with antimicrobial medication use during 5-days' follow-up. suPAR levels were associated with generally accepted inflammatory biomarkers (C-reactive protein, leukocyte count). Conclusion: Plasma suPAR level was not associated with either neurological outcome or selected clinical conditions. While suPAR is a promising biomarker for prognostication in several conditions requiring intensive care, it did not reveal any value as a prognostic biomarker after aSAH.
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| 8. |
- Kiiski, Heikki, et al.
(författare)
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S100B, NSE and MMP-9 fail to predict neurologic outcome while elevated S100B associates with milder initial clinical presentation after aneurysmal subarachnoid hemorrhage
- 2018
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Ingår i: Journal of the Neurological Sciences. - : ELSEVIER SCIENCE BV. - 0022-510X .- 1878-5883. ; 390, s. 129-134
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Despite advances in the treatment of aneurysmal subarachnoid hemorrhage (aSAH) one-year mortality remains approximately 50%. Making an accurate prognosis at the early phase of the disease is notoriously difficult. A clinically reliable biomarker that could be used for better prediction of prognosis and/or as a surrogate for developing complications after aSAH is still lacking. In this study, we evaluated the prognostic values of three promising biomarkers, i.e. S100B, NSE, and MMP-9 in aSAH.Methods: In this prospective population-based study, S100B, NSE, and MMP-9 levels were measured in 47 aSAH patients for up to five days. Blood samples were taken at 0, 12 and 24 h after the admission to the intensive care unit (ICU) and daily after that until the patient was transferred from the ICU. The patients' neurological outcome was evaluated with the modified Rankin Scale (mRS) at six months after aSAH.Results: Biomarker-levels measured during the first 24 h were not associated with neurological outcome. S100B levels during the first 24 h were elevated in patients with a non-severe initial clinical presentation. Otherwise, there was no association between selected clinical variables and the early biomarker levels. In 22 patients, whose ICU follow-up lasted for up to five days, the total release of biomarkers was not associated with the neurological outcome.Conclusions: None of the measured biomarkers were associated with the neurological outcome evaluated at six months after aSAH. Elevated levels of S100B in patients with non-severe initial presentation suggest an adaptive role of this biomarker in aSAH. Based on our findings it is not advisable to use these biomarkers to guide clinical decision-making in patients with aSAH.
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| 9. |
- Klemettilä, Jari-Pekka, et al.
(författare)
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Glucagon-like peptide-1 serum levels are associated with weight gain in patients treated with clozapine
- 2021
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Ingår i: Psychiatry Research. - : Elsevier. - 0165-1781 .- 1872-7123. ; 306
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic syndrome and related cardiovascular risk factors are well-known comorbidities among patients with schizophrenia. Biomarkers of these antipsychotic-associated metabolic adverse effects and antipsychotic-induced weight gain are needed. Glucagon-like peptide-1 (GLP-1) is involved in insulin secretion, regulation of satiety, inhibition of food intake, and inhibition of gastric emptying. GLP-1 also induces reduction in body weight. Visfatin/ NAMPT/ PBEF is an adipocytokine secreted by several cells and tissues. Increased plasma visfatin levels have been associated with overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases, low grade inflammation, and proinflammatory markers. Associations between antipsychotic-induced weight gain and serum visfatin and GLP-1 levels have been little studied in patients with schizophrenia. The aim of the present study was to test the possible role of serum GLP-1 and visfatin level alterations as markers of weight gain in association with metabolic and inflammatory markers in 190 patients (109 male, 81 female) with schizophrenia on clozapine treatment. High serum levels of GLP-1 correlated significantly with higher levels of visfatin, leptin, insulin, HOMA-IR, higher BMI, and weight change among men. Associations between serum visfatin levels and BMI or weight change were not found in the present patients. Serum GLP-1 level seems to be a marker of metabolic risk factors among men with schizophrenia on clozapine treatment. Female patients may be more sensitive to suppressive effects of clozapine on GLP-1 secretion. Patients on clozapine would benefit from GLP-1 agonists as preventive treatment.
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| 10. |
- Lammi, Mikko, 1961-, et al.
(författare)
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Nivelrikon välittäjäaineet [Mediators of osteoarthritis]
- 2008
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Ingår i: Duodecim. - 0012-7183. ; 124:16, s. 1876-1884
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Forskningsöversikt (refereegranskat)abstract
- Normaalissa rustossa vallitsee tasapainotila kudosta tuottavien ja hajottavien prosessien kesken, mutta nivelrikossa painopiste siirtyy katabolian suuntaan. Nivelrikon etiologiaa ei tunneta, mutta sen syntyyn liittyy joukko tekijöitä, jotka johtavat väliaineen lisääntyneeseen hajoamiseen ja vähentyneeseen väliainetuotantoon, rustosolujen apoptoosiin, muutoksiin rustonalaisessa luussa ja nivelkalvon tulehdukseen. Nivelrikkoa välittävistä liukoisista tekijöistä ovat parhaiten tunnettuja tulehdusta moduloivat sytokiinit ja niiden aktivoimat tekijät, kuten metalloproteinaasit ja aggrekanaasit. Myös typpioksidin ja eikosanoidien yhteys nivelrikkoon on hyvin osoitettu. Viimeaikaiset tutkimukset ovat tuoneet esiin myös monia uusia tekijöitä, joilla todennäköisesti on merkitystä nivelrikon patologiassa. Nämä löydökset antavat pohjaa uudenlaisille hoitostrategioille.
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