Browsing by Subject "Inflammation"

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Now showing items 21-40 of 83
  • Hanson, Linda L. Magnusson; Virtanen, Marianna; Rod, Naja H.; Steptoe, Andrew; Head, Jenny; Batty, G. D.; Kivimäki, Mika; Westerlund, Hugo (2019)
    Objective: Inflammation may underlie the association between psychological stress and cardiometabolic diseases, but this proposition has not been tested longitudinally. We investigated whether the circulating inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP) mediate the relationship between psychosocial work characteristics and diabetes. Methods: We used three phases of data at 5 years intervals from the Whitehall II cohort study, originally recruiting 10,308 civil service employees aged 35-55 years. The data included repeat self-reports of job demands, control and social support, IL-6 from plasma samples, CRP from serum samples, and diabetes, ascertained through oral glucose tolerance test, medications, and self-reports of doctor-diagnosed diabetes. Results: Structural equation models with age, sex and occupational position considering men and women combined, showed that low social support at work, but not high job demands or low job control, was prospectively associated with diabetes (standardized beta = 0.05, 95% confidence interval (CI) 0.01-0.09) and higher levels of IL-6 (beta = 0.03, CI 0.00-0.06). The inflammatory markers and diabetes were bidirectionally associated over time. A mediation model including workplace social support, IL-6 and diabetes further showed that 10% of the association between social support and diabetes over the three repeat examinations (total effect beta = 0.08, CI 0.01-0.15) was attributable to a weak indirect effect through IL-6 (beta = 0.01, CI 0.00-0.02). A similar indirect effect was observed for CRP in men only, while job control was prospectively associated with IL-6 among women. Conclusions: This study indicates an association between poor workplace support and diabetes that is partially ascribed to an inflammatory response.
  • Rossi, Heini; Raekallio, Marja; Määttä, Merita; Tapio, Heidi Anneli; Hanifeh, Mohsen; Junnila, Jouni; Rajamäki, Minna; Mykkänen, Anna (2019)
    Pneumonia is one of the potential complications of general anaesthesia in horses. Anaesthesia is known to increase neutrophils in bronchoalveolar lavage fluid (BALF) of horses after lateral recumbency, but studies after dorsal recumbency are lacking. Our primary aim was to determine when lung inflammation reaches its maximum and how rapidly BALF cytology returns to baseline after anaesthesia in dorsal recumbency. A secondary aim was to investigate the possible effect of vatinoxan, a novel drug, on the BALF cytology results. Six healthy experimental horses were enrolled in this observational crossover study. The horses were subject to repeated BALF and blood sampling for 7 days after general anaesthesia with two treatment protocols, and without anaesthesia (control). During the two treatments, the horses received either medetomidine-vatinoxan or medetomidine-placebo as premedication, and anaesthesia was induced with ketamine-midazolam and maintained with isoflurane for 1 h in dorsal recumbency. The differences in BALF and blood variables between the two anaesthesia protocols and control were analysed with repeated measures analysis of variance models. In this study, anaesthesia in dorsal recumbency resulted in no clinically relevant changes in airway cytology that could be differentiated from the effect of repeated BALF sampling. No differences in BALF matrix metalloproteinase gelatinolytic activity could be detected between the two treatments or the control series. Marked increase in serum amyloid A was detected in some animals. Vatinoxan as premedication did not consistently affect lung cytology or blood inflammatory markers after anaesthesia. (C) 2019 The Author(s). Published by Elsevier Ltd.
  • Danielsen, Pernille Høgh; Knudsen, Kristina Bram; Štrancar, Janez; Umek, Polona; Koklič, Tilen; Garvas, Maja; Vanhala, Esa; Savukoski, Sauli; Ding, Yaobo; Madsen, Anne Mette; Jacobsen, Nicklas Raun; Weydahl, Ingrid Konow; Berthing, Trine; Poulsen, Sarah Søs; Schmid, Otmar; Wolff, Henrik; Vogel, Ulla (2020)
    Nanomaterial (NM) characteristics may affect the pulmonary toxicity and inflammatory response, including specific surface area, size, shape, crystal phase or other surface characteristics. Grouping of TiO2 in hazard assessment might be challenging because of variation in physicochemical properties. We exposed C57BL/6 J mice to a single dose of four anatase TiO2 NMs with various sizes and shapes by intratracheal instillation and assessed the pulmonary toxicity 1, 3, 28, 90 or 180 days post-exposure. The quartz DQ12 was included as benchmark particle. Pulmonary responses were evaluated by histopathology, electron microscopy, bronchoalveolar lavage (BAL) fluid cell composition and acute phase response. Genotoxicity was evaluated by DNA strand break levels in BAL cells, lung and liver in the comet assay. Multiple regression analyses were applied to identify specific TiO2 NMs properties important for the pulmonary inflammation and acute phase response. The TiO2 NMs induced similar inflammatory responses when surface area was used as dose metrics, although inflammatory and acute phase response was greatest and more persistent for the TiO2 tube. Similar histopathological changes were observed for the TiO2 tube and DQ12 including pulmonary alveolar proteinosis indicating profound effects related to the tube shape. Comparison with previously published data on rutile TiO2 NMs indicated that rutile TiO2 NMs were more inflammogenic in terms of neutrophil influx than anatase TiO2 NMs when normalized to total deposited surface area. Overall, the results suggest that specific surface area, crystal phase and shape of TiO2 NMs are important predictors for the observed pulmonary effects of TiO2 NMs.
  • Leppänen, Jonna; Randell, Kaisa; Schwab, Ursula; Pihlajamäki, Jussi; Romppanen, Jarkko; Keski-Nisula, Leea; Heinonen, Seppo; Laitinen, Tomi (2021)
    We examined possible changes in endothelial function during a long agonist in vitro fertilization (IVF) protocol. We measured flow-mediated dilatation (FMD) and FMD percent (FMD%) from the brachial artery and plasma levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-〈). We studied longitudinally three time points in 27 women undergoing a long agonist IVF treatment at Kuopio University Hospital. The first visit was at the beginning of their period (low estradiol). The other two visits were during gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was used as the reference, and the women served as their own controls. During the stimulation protocol, FMD and FMD% remained. Toward the end of stimulation, hsCRP (P = 0.003), IL-6 (P = 0.04), and TNF-〈 (P = 0.008) concentrations all decreased, while estradiol levels increased (P < 0.001). Correlations between estradiol and proinflammatory factors or FMD were, however, non-significant. The only significant correlation appeared between FMD% and hsCRP at Visit 2 (r = 0.485, P = 0.01). In conclusion, IVF stimulation promoted no change in endothelial function, whereas hsCRP, IL-6, and TNF-〈 decreased. These findings indicate that estrogen may improve the cytokine profile among healthy women undergoing IVF, but this is not reflected in endothelial function.
  • Karppinen, Sanna-Maria; Heljasvaara, Ritva; Pihlajaniemi, Taina; Lagus, Heli; Järveläinen, Hannu (2020)
    Krooniset haavat ja haavan paranemisen pitkittyminen ovat merkittäviä kliinisiä ongelmia. Haavan paraneminen on monimutkainen biologinen prosessi, joka voidaan jakaa neljään vaiheeseen: verenvuodon tyrehtymiseen sekä sitä seuraaviin tulehdus-, korjaus- ja kypsymisvaiheisiin, joita säätelevät paikalliset olosuhteet. Haavan paranemiseen vaikuttaa myös yksilön yleistila kaikkine sairauksineen ja lääkityksineen. Paikallisista tekijöistä muun muassa tulehdusreaktiovaiheen pitkittyminen ja huono verenkierto edistävät haavojen kroonistumista. Diabetekseen liittyy huonontunut haavojen paranemistaipumus. Hyperglykemia heikentää haavan paranemista useilla eri mekanismeilla, joista yksi keskeinen perustuu hyperglykemian seurauksena kudoksiin ylimäärin kertyneiden, ei-entsymaattisesti liikaglykosyloituneiden molekyylien (advanced glycosylation end-products, AGE) käynnistämiin solubiologisiin häiriöihin. Paras keino estää hyperglykemian haitallinen vaikutus on tavoitella suositusten mukaista verenglukoosipitoisuutta.
  • Joutsi-Korhonen, Lotta; Helin, Tuukka; Lassila, Riitta (2020)
    Hyytymishäiriöissä verenkiertoon vapautuu fibriinin D-dimeeriä, kun sekä hyytymisaktivaatio että fibrinolyysi kiihtyvät. COVID-19-taudissa hoitojakson aikana nousujohteinen FiDD-pitoisuus on yhteydessä inflammaation vaikeusasteeseen, tukostapahtumiin ja kuoleman riskiin. Jopa neljäsosalla tehohoitoon joutuvista potilaista on todettu alaraajojen laskimotukos, joka voi johtaa keuhkoemboliaan.
  • Mattila, Kalle; Mäkelä, Siru; Hernberg, Micaela; Vihinen, Pia (2018)
    Immuuniaktivaation vapauttajat ovat uusia syöpälääkkeitä, joiden haittavaikutuksena voi ilmaantua tulehduksia. Jos päivystyspotilasta on hoidettu näillä lääkkeillä, hänen oireitaan tulee epäillä lääkkeen haittavaikutuksiksi, kunnes toisin on osoitettu. Samanaikainen infektio on mahdollinen.
  • Pussinen, Pirkko J.; Malle, Ernst; Sattler, Wolfgang (2018)
  • Rydman, Elina M.; Ilves, Marit; Koivisto, Antti J.; Kinaret, Pia A. S.; Fortino, Vittorio; Savinko, Terhi S.; Lehto, Maili T.; Pulkkinen, Ville; Vippola, Minnamari; Hämeri, Kaarle J.; Matikainen, Sampsa; Wolff, Henrik; Savolainen, Kai M.; Greco, Dario; Alenius, Harri (2014)
  • Kaye, Sanna; Heinonen, Sini; Pietiläinen, Kirsi (2020)
    Vertailemalla harvinaisia identtisiä mutta eripainoisia kaksosia voidaan selvittää lihavuuden vaikutusta aineenvaihduntaan DNA-sekvenssin samankaltaisuudesta riippumatta. Hankinnainen lihavuus vaikuttaa epäedullisesti veren rasvoihin, hyytymistekijöiden pitoisuuksiin ja tulehdusvälittäjäaineisiin sekä huonontaa endoteelitoimintaa ja altistaa ateroskleroosille. Tutkimusten perusteella rasvakudos on keskeisessä asemassa siinä, miten lihavuuden havaitut haitalliset aineenvaihdunnan muutokset syntyvät. Hankinnainen lihavuus liittyy rasvakudoksessa mitokondriotoiminnan heikentymiseen ja lievään tulehdukseen sekä insuliiniresistenssiin. Nämä muutokset heikentävät rasvakudoksen laajenemiskapasiteettia, jolloin ylimääräinen rasva alkaa varastoitua muihin kudoksiin, kuten maksaan, haimaan ja lihakseen, ja aiheuttaa aineenvaihdunnan laaja-alaisen häiriötilan. Erityisesti maksaan kertyvä rasva näyttää määrittävän lihavuuden haitallista metaboliaa.
  • Myntti, Tarja; Rahkonen, Leena; Paavonen, Jorma; Stefanovic, Vedran (2018)
    • Korioamnioniitti on yleisempi piilevänä kuin kliinisenä. • Tilan varhainen tunnistaminen mahdollistaa hoidon kohdentamisen ja synnytyksen ajankohdan optimoinnin. • Äidin kuume ja CRP-arvo ovat epäherkkiä ja epätarkkoja menetelmiä korioamnioniitin diagnostiikassa. • Lapsiveden mikrobi-inflammaatio on yhtä yleinen raskauksissa, joissa sikiökalvot ovat ehjät, kuin niissä, joissa sikiökalvot ovat puhjenneet.
  • Paasela, Monika; Kolho, Kaija-Leena; Vaarala, Outi; Honkanen, Jarno (2014)
  • Pohjolainen, Timo; Karppinen, Jaro; Malmivaara, Antti; Niinimäki, Jaakko; Salmenkivi, Jyrki (2018)
    Lannenikamavälilevylle ja sen rappeumaperäisille muutoksille tarvitaan yhtenäinen nimikkeistö. Termien tulisi olla niin ymmärrettäviä ja johdonmukaisia, jotta muutosten luonne selviää toiselle lääkärille. Yhtenäinen nimikkeistö on perusta varsinkin kliinikoiden ja radiologien yhteistyölle. Välilevyrappeuman morfologisille muutoksille ehdotamme termejä välilevyn kuivuminen, fibroosi, välilevytilan madaltuminen, välilevyn pullistuminen, halkeamat, syyrustoisen renkaan rappeutuminen, välilevyn sisäinen kaasu, nikamasolmun apofyysin reunakerrostumat, sytokiinien välittämät inflammaatiomuutokset ja päätelevyn kalkkeutuminen.
  • Nyberg, Rosa (Helsingfors universitet, 2016)
    Parodontiitti on biofilmi-infektio, joka rappeuttaa hampaan kiinnityskudosta ja voi hoitamattomana johtaa hampaan menetykseen. Lipopolysakkaridi on gram-negatiivisten bakteerien pinnalla esiintyvä molekyyli, jonka vuorovaikutus isäntäyksilön kanssa käynnistää isännän immuunivasteen. Parodontiitin ja lipopolysakkaridin yhteyttä systeemisiin sairauksiin on tutkittu runsaasti. Tämän tutkielman tarkoitus on kirjallisuuskatsauksen muodossa selventää lipopolysakkaridin paikallista merkitystä ihmisen parodontaalitulehduksessa. Kirjallisuuskatsaukseen sisällytetyt tutkimukset valittiin PubMed-tietokannasta määrätyin hyväksymis- ja poissulkukriteerein. Kirjallisuuden perusteella lipopolysakkaridin rooli tulehduksessa on moninainen; se on osallisena tulehduksen käynnistymisessä ja tulehdusvälittäjäainetuotannossa sekä aktivoi isäntäyksilön omia soluja tuhoamaan ienkudosta. Hyväksymiskriteerit täyttävä tutkimusaineisto oli rajallinen ja jatkotutkimusta aiheesta tarvitaan, jotta lipopolysakkaridin paikallinen toimintamekanismi ihmisen parodontaalitulehduksessa ymmärretään kunnolla. Tämän kirjallisuuskatsauksen perusteella voidaan kuitenkin todeta, että lipopolysakkaridi on huomattava tulehdusta edistävä, säätelevä ja kudostuhoa aiheuttava tekijä ihmisen parodontaalitulehduksessa.
  • Salmenkari, Hanne; Issakainen, Tomi; Vapaatalo, Heikki; Korpela, Riitta (2015)
    AIM: To investigate local corticosterone production and angiotensin- I converting enzyme (ACE) protein expression and their interaction in healthy and inflamed intestine. METHODS: Acute intestinal inflammation was induced to six weeks old male Balb/c mice by administration of either 3% or 5% dextran sodium sulfate (DSS) in drinking water for 7 d (n = 12 in each group). Healthy controls (n = 12) were given tap water. Corticosterone production and ACE protein shedding were measured from ex vivo incubates of the small and large intestine using EIA and ELISA, respectively. Morphological changes of the intestinal wall were assessed in hematoxylin-eosin stained tissue preparations of jejunum and distal colon. Effects of angiotensin II, captopril and metyrapone on corticosterone production was assessed by incubating pieces of small intestine of healthy mice in the presence of 0.1, 1 or 10 mu mol/L angiotensin II, 1, 10 or 100 mu mol/L captopril or 1, 10 or 100 mu mol/L metyrapone solutions and measuring corticosterone released to the incubation buffer after 90 min (n = 5 in each group). RESULTS: Both concentrations of DSS induced inflammation and morphological changes in large intestines but not in small intestines. Changes were observed as distortions of the crypt structure, mucosal erosion, immune cell infiltration to the mucosa and submucosal edema. Ex vivo corticosterone production (2.9 +/- 1.0 ng/mL vs 2.0 +/- 0.8 ng/mL, P = 0.034) and ACE shedding (269.2 +/- 97.1 ng/mL vs 175.7 +/- 52.2 ng/mL, P = 0.016) were increased in small intestines in 3% DSS group compared to the controls. In large intestine, corticosterone production was increased compared to the controls in both 3% DSS (229 +/- 81 pg/mL vs 158 +/- 30 pg/mL, P = 0.017) and 5% DSS groups (366 +/- 163 pg/mL vs 158 +/- 30 pg/mL, P = 0.002). Large intestine ACE shedding was increased in 5% DSS group (41.5 +/- 9.0 ng/mL vs 20.9 +/- 5.2 ng/mL, P = 0.034). Angiotensin II treatment augmented corticosterone production in small intestine at concentration of 10 mu mol/L (0.97 +/- 0.21 ng/mg protein vs 0.40 +/- 0.09 ng/mg protein, P = 0.036). CONCLUSION: Intestinal ACE shedding is increased by DSS-induced intestinal inflammation and parallels local corticosterone production. ACE product angiotensin. stimulates corticosterone formation in healthy intestine.
  • Barreto, Goncalo; Senturk, B.; Colombo, L.; Brück, O.; Neidenbach, P.; Salzmann, G.; Zenobi-Wong, M.; Rottmar, M. (2020)
    Objective: Lumican (LUM) is a major extracellular matrix glycoprotein in adult articular cartilage and its expression is known to be upregulated upon cartilage degeneration. LUM is associated with the pathogen-associated molecular pattern (PAMP) activation of the TLR4 signalling cascade, with TLR4 being highly associated with inflammation in rheumatic diseases. However, the main role of the LUM structural molecule in osteoarthritis (OA) remains elusive. The aim of this study was, therefore, to understand the role of LUM during TLR4-mediated activation in OA. Methods: After measuring LUM levels in synovial fluid (SF) of OA patients and lipopolysaccharide (LPS)-induced TLR4 activation, the role of LUM in the expression of pro-inflammatory molecules and cartilage degradation was assessed in vitro and ex vivo in a cartilage explant model. Primary macrophage activation and polarization were studied upon LUM co-stimulation with LPS. Results: We demonstrate that LUM is not only significantly upregulated in SF from OA patients compared to healthy controls, but also that LUM increases lipopolysaccharide (LPS)-induced TLR4 activation. Furthermore, we show that a pathophysiological level of LUM augments the LPS-induced TLR4 activation and expression of downstream pro-inflammatory molecules, resulting in extensive cartilage degradation. LUM co-stimulation with LPS also provided a pro-inflammatory stimulus, upregulating primary macrophage activation and polarization towards the M1-like phenotype. Conclusions: These findings strongly support the role of LUM as a mediator of PAMP-induced TLR4 activation of inflammation, cartilage degradation, and macrophage polarization in the OA joint and potentially other rheumatic diseases. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
  • Haahtela, Tari; Hanski, Ilkka; Von Hertzen, Leena; Jousilahti, Pekka; Laatikainen, Tiina; Mäkelä, Mika J.; Puska, Pekka; Reijula, Kari; Saarinen, Kimmo; Vartiainen, Erkki; Vasankari, Tuula; Virtanen, Suvi (2017)
  • Kinnunen, K.; Piippo, N.; Loukovaara, S.; Hytti, M.; Kaarniranta, K.; Kauppinen, A. (2017)
    Inflammation is a crucial component in the pathogenesis of many vascular diseases, such as atherosclerosis and diabetes. Inflammasomes are intracellular signalling complexes whose activation promotes inflammation. Nucleotide-binding domain and Leucine-rich repeat Receptor containing a Pyrin domain 3 (NLRP3) is a pattern recognition receptor (PRR) forming the best-known inflammasome. Disturbances in NLRP3 have been associated with multiple diseases. The purpose of this study was to explore the lysosomal destabilizationrelated NLRP3 inflammasome signaling pathway in human endothelial cells. In order to prime and activate NLRP3, human umbilical vein cells (HUVECs) were exposed to TNF-alpha and the lysosomal destructive agent Leusine-Leusine-OMethylesther (Leu-Leu-OMe), respectively. A caspase-1 inhibitor was used to block caspase-1' s enzymatic function and an interleukin 1 receptor antagonist (IL-1RA) to prevent any possible secondary effects of IL-1 beta. Leu-Leu-OMe increased the expression of NLRP3, IL-1 beta, and IL-18 in HUVECs. Exposure to Leu-Leu-OMe significantly promoted the production of IL-6 and IL-8 in primed HUVECs; this effect was prevented by the pre-treatment of cells with an IL-1RA. Our results suggest that lysosomal destabilization activates the NLRP3 inflammasome pathway that promotes the production of IL-6 and IL-8 in an autocrine manner in HUVEC cells.
  • Wang, Qin; Wurtz, Peter; Auro, Kirsi; Makinen, Ville-Petteri; Kangas, Antti J.; Soininen, Pasi; Tiainen, Mika; Tynkkynen, Tuulia; Jokelainen, Jari; Santalahti, Kristiina; Salmi, Marko; Blankenberg, Stefan; Zeller, Tanja; Viikari, Jorma; Kahonen, Mika; Lehtimaki, Terho; Salomaa, Veikko; Perola, Markus; Jalkanen, Sirpa; Jarvelin, Marjo-Riitta; Raitakari, Olli T.; Kettunen, Johannes; Lawlor, Debbie A.; Ala-Korpela, Mika (2016)
    Background: Pregnancy triggers well-known alterations in maternal glucose and lipid balance but its overall effects on systemic metabolism remain incompletely understood. Methods: Detailed molecular profiles (87 metabolic measures and 37 cytokines) were measured for up to 4260 women (24-49 years, 322 pregnant) from three population-based cohorts in Finland. Circulating molecular concentrations in pregnant women were compared to those in non-pregnant women. Metabolic profiles were also reassessed for 583 women 6 years later to uncover the longitudinal metabolic changes in response to change in the pregnancy status. Results: Compared to non-pregnant women, all lipoprotein subclasses and lipids were markedly increased in pregnant women. The most pronounced differences were observed for the intermediate-density, low-density and high-density lipoprotein triglyceride concentrations. Large differences were also seen for many fatty acids and amino acids. Pregnant women also had higher concentrations of low-grade inflammatory marker glycoprotein acetyls, higher concentrations of interleukin-18 and lower concentrations of interleukin-12p70. The changes in metabolic concentrations for women who were not pregnant at baseline but pregnant 6 years later (or vice versa) matched (or were mirror-images of) the cross-sectional association pattern. Cross-sectional results were consistent across the three cohorts and similar longitudinal changes were seen for 653 women in 4-year and 497 women in 10-year follow-up. For multiple metabolic measures, the changes increased in magnitude across the three trimesters. Conclusions: Pregnancy initiates substantial metabolic and inflammatory changes in the mothers. Comprehensive characterisation of normal pregnancy is important for gaining understanding of the key nutrients for fetal growth and development. These findings also provide a valuable molecular reference in relation to studies of adverse pregnancy outcomes.
  • Tian, Li; Hui, Chin Wai; Bisht, Kanchan; Tan, Yunlong; Sharma, Kaushik; Chen, Song; Zhang, Xiangyang; Tremblay, Marie-Eve (2017)
    Mounting evidence indicates the importance of microglia for proper brain development and function, as well as in complex stress-related neuropsychiatric disorders and cognitive decline along the aging trajectory. Considering that microglia are resident immune cells of the brain, a homeostatic maintenance of their effector functions that impact neuronal circuitry, such as phagocytosis and secretion of inflammatory factors, is critical to prevent the onset and progression of these pathological conditions. However, the molecular mechanisms by which microglial functions can be properly regulated under healthy and pathological conditions are still largely unknown. We aim to summarize recent progress regarding the effects of psychosocial stress and oxidative stress on microglial phenotypes, leading to neuroinflammation and impaired microglia-synapse interactions, notably through our own studies of inbred mouse strains, and most importantly, to discuss about promising therapeutic strategies that take advantage of microglial functions to tackle such brain disorders in the context of adult psychosocial stress or aging-induced oxidative stress. (c) 2017 Elsevier Inc. All rights reserved.