Vascular dysfunction by myofibroblast activation in patients with idiopathic pulmonary fibrosis and prognostic significance

In this study, we demonstrated the importance of telomerase protein expression and determined the relationships among telomerase, endothelin-1 (ET-1) and myofibroblasts during early and late remodeling of parenchymal and vascular areas in usual interstitial pneumonia (UIP) using 27 surgical lung biopsies from patients with idiopathic pulmonary fibrosis (IPF). Telomerase+, myofibroblasts α-SMA+, smooth muscle cells caldesmon+, endothelium ET-1+ cellularity, and fibrosis severity were evaluated in 30 fields covering normal lung parenchyma, minimal fibrosis (fibroblastic foci), severe (mural) fibrosis, and vascular areas of UIP by the point-counting technique and a semiquantitative score. The impact of these markers was determined in pulmonary functional tests and follow-up until death from IPF. Telomerase and ET-1 expression was significantly increased in normal and vascular areas compared to areas of fibroblast foci. Telomerase and ET-1 expression was inversely correlated with minimal fibrosis in areas of fibroblast foci and directly associated with severe fibrosis in vascular areas. Telomerase activity in minimal fibrosis areas was directly associated with diffusing capacity of the lung for oxygen/alveolar volume and ET-1 expression and indirectly associated with diffusing capacity of the lungs for carbon monoxide and severe fibrosis in vascular areas. Cox proportional hazards regression revealed a low risk of death for females with minimal fibrosis displaying high telomerase and ET-1 expression in normal areas. Vascular dysfunction by telomerase/ET-1 expression was found earlier than vascular remodeling by myofibroblast activation in UIP with impact on IPF evolution, suggesting that strategies aimed at preventing the effect of these mediators may have a greater impact on patient outcome.

Partial baroreceptor dysfunction and low plasma nitric oxide bioavailability as determinants of salt-sensitive hypertension: a reverse translational rat study

This study determined whether clinical salt-sensitive hypertension (cSSHT) results from the interaction between partial arterial baroreceptor impairment and a high-sodium (HNa) diet. In three series (S-I, S-II, S-III), mean arterial pressure (MAP) of conscious male Wistar ChR003 rats was measured once before (pdMAP) and twice after either sham (SHM) or bilateral aortic denervation (AD), following 7 days on a low-sodium (LNa) diet (LNaMAP) and then 21 days on a HNa diet (HNaMAP). The roles of plasma nitric oxide bioavailability (pNOB), renal medullary superoxide anion production (RMSAP), and mRNA expression of NAD(P)H oxidase and superoxide dismutase were also assessed. In SHM (n=11) and AD (n=15) groups of S-I, LNaMAP-pdMAP was 10.5±2.1 vs 23±2.1 mmHg (P<0.001), and the salt-sensitivity index (SSi; HNaMAP−LNaMAP) was 6.0±1.9 vs 12.7±1.9 mmHg (P=0.03), respectively. In the SHM group, all rats were normotensive, and 36% were salt sensitive (SSi≥10 mmHg), whereas in the AD group ∼50% showed cSSHT. A 45% reduction in pNOB (P≤0.004) was observed in both groups in dietary transit. RMSAP increased in the AD group on both diets but more so on the HNa diet (S-II, P<0.03) than on the LNa diet (S-III, P<0.04). MAP modeling in rats without a renal hypertensive genotype indicated that the AD*HNa diet interaction (P=0.008) increases the likelihood of developing cSSHT. Translationally, these findings help to explain why subjects with clinical salt-sensitive normotension may transition to cSSHT.

Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis

Because histopathological changes in the lungs of patients with systemic sclerosis (SSc) are consistent with alveolar and vessel cell damage, we presume that this interaction can be characterized by analyzing the expression of proteins regulating nitric oxide (NO) and plasminogen activator inhibitor-1 (PAI-1) synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and other clinical data, we studied these markers in 23 cases of SSc nonspecific interstitial pneumonia (SSc-NSIP). We used immunohistochemistry and morphometry to evaluate the amount of cells in alveolar septa and vessels staining for NO synthase (NOS) and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP, pulmonary function tests, and survival time until death. General linear model analysis demonstrated that staining for septal inducible NOS (iNOS) related significantly to staining of septal cells for interleukin (IL)-4 and to septal IL-13. In univariate analysis, higher levels of septal and vascular cells staining for iNOS were associated with a smaller percentage of septal and vascular cells expressing fibroblast growth factor and myofibroblast proliferation, respectively. Multivariate Cox model analysis demonstrated that, after controlling for SSc-NSIP histological patterns, just three variables were significantly associated with survival time: septal iNOS (P=0.04), septal IL-13 (P=0.03), and septal basic fibroblast growth factor (bFGF; P=0.02). Augmented NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4 staining in alveolar septa and vessels provides a possible independent diagnostic measure for the degree of pulmonary dysfunction and fibrosis with an impact on the survival of patients with SSc.

Combined aliskiren and L-arginine treatment has antihypertensive effects and prevents vascular endothelial dysfunction in a model of renovascular hypertension

Angiotensin II is a key player in the pathogenesis of renovascular hypertension, a condition associated with endothelial dysfunction. We investigated aliskiren (ALSK) and L-arginine treatment both alone and in combination on blood pressure (BP), and vascular reactivity in aortic rings. Hypertension was induced in 40 male Wistar rats by clipping the left renal artery. Animals were divided into Sham, 2-kidney, 1-clip (2K1C) hypertension, 2K1C+ALSK (ALSK), 2K1C+L-arginine (L-arg), and 2K1C+ALSK+L-arginine (ALSK+L-arg) treatment groups. For 4 weeks, BP was monitored and endothelium-dependent and independent vasoconstriction and relaxation were assessed in aortic rings. ALSK+L-arg reduced BP and the contractile response to phenylephrine and improved acetylcholine relaxation. Endothelium removal and incubation with N-nitro-L-arginine methyl ester (L-NAME) increased the response to phenylephrine in all groups, but the effect was greater in the ALSK+L-arg group. Losartan reduced the contractile response in all groups, apocynin reduced the contractile response in the 2K1C, ALSK and ALSK+L-arg groups, and incubation with superoxide dismutase reduced the phenylephrine response in the 2K1C and ALSK groups. eNOS expression increased in the 2K1C and L-arg groups, and iNOS was increased significantly only in the 2K1C group compared with other groups. AT1 expression increased in the 2K1C compared with the Sham, ALSK and ALSK+L-arg groups, AT2 expression increased in the ALSK+L-arg group compared with the Sham and L-arg groups, and gp91phox decreased in the ALSK+L-arg group compared with the 2K1C and ALSK groups. In conclusion, combined ALSK+L-arg was effective in reducing BP and preventing endothelial dysfunction in aortic rings of 2K1C hypertensive rats. The responsible mechanisms appear to be related to the modulation of the local renin-angiotensin system, which is associated with a reduction in endothelial oxidative stress.

Overexpression of myeloid differentiation protein 88 in mice induces mild cardiac dysfunction, but no deficit in heart morphology

Cardiac remodeling involves changes in heart shape, size, structure, and function after injury to the myocardium. The proinflammatory adaptor protein myeloid differentiation protein 88 (MyD88) contributes to cardiac remodeling. To investigate whether excessive MyD88 levels initiate spontaneous cardiac remodeling at the whole-organism level, we generated a transgenic MyD88 mouse model with a cardiac-specific promoter. MyD88 mice (male, 20-30 g, n=∼80) were born at the expected Mendelian ratio and demonstrated similar morphology of the heart and cardiomyocytes with that of wild-type controls. Although heart weight was unaffected, cardiac contractility of MyD88 hearts was mildly reduced, as shown by echocardiographic examination, compared with wild-type controls. Moreover, the cardiac dysfunction phenotype was associated with elevation of ANF and BNP expression. Collectively, our data provide novel evidence of the critical role of balanced MyD88 signaling in maintaining physiological function in the adult heart.

Från ung till vuxen i omställningens tid : en longitudinell studie av värderingar med utgångspunkt i Ingleharts teori om den tysta revolutionen

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Oroliga inför framtiden : en studie av folkligt politiskt agerande bland bruksarbetarna i Billnäs ca 1900–1920

Åren 1901, 1905–1906 och 1917–1918 gjorde bruksarbetarna i Billnäs uppror mot bruksledningen och den lokala makteliten. Det lugna och harmoniska brukssamhället i Västnyland drabbades av djupgående konfrontationer som ledde till uppsägningar, vräkning av arbetarfamiljer och att slutligen 54 bruksarbetare miste livet till följd av deras upproriskhet. I den här avhandlingen undersöker jag med ett mikrohistoriskt angreppssätt folkligt politiskt agerande i det tidiga 1900-talets Finland. Genom att närma vanliga människors vardag och deras politiska föreställningar om samhället omkring dem, avser jag med den här avhandlingen skapa nya förståelser för politiskt agerande bland samhällets underordnade. För att kunna genomföra detta har jag i avhandlingen kombinerat olika slags källor: jag använder arkivmaterial, tidningar och intervjuer. Avhandlingens teoretiska ram utgörs av socialhistorisk forskning som studerar folkligt politiskt agerande på olika håll i världen och av nyare kulturhistorisk forskning som tar i beaktande hur klass, genus, språk och religion fungerade i människors vardag. Med den här avhandlingen vill jag bidra till att försöka skapa förståelse för vår tids politiska agerande (alltifrån upplopp till vardagligt motstånd) bland människor vars vardag påverkas av sociala och politiska omvälvningar. Kan olika former av folkligt politiskt agerande förstås som uttryck för att allt flera idag, liksom bruksarbetarna i början av 1900-talet, är oroliga inför framtiden?

Att lindra ett lidande : en kvalitativ studie om lindrande av den mobbade elevens lidande

The study's aim is to achieve knowledge of how to relieve the suffering of the bullied student. The methodology in this study is hermeneutics. The theoretical perspective is the caritative theory. The questions in the study are: 1) What does it mean to relieve a suffering? 2) What can caregivers do to relieve the suffering of the young bullied pupil? 3) How do the caregivers experience their role in relieving the suffering? The review of previous research shows that bullying is a phenomenon that causes great harm to the health of young people. There are varying developed strategies to deal with bullying in the schools. Only one article studied the counsellor role in fighting bullying. There is a need to examine how a suffering can be relieved, how the caregiver experience handling bullying, and how caregivers can be involved in relieving the suffering the bullied youngster is going through. The empirical part of the study was conducted through qualitative semi-structured interviews with counsellors who work with high school students. The study was conducted in close collaboration with the project "Analys av ungdomsenkäten" conducted by the youth researchers at Åbo Akademi and the Swedish Ostrobothnia Youth foundation (SOU). The collected material was analyzed according to Elo and Kyngäs (2007) guidelines for inductive content analysis. The result shows that caregivers play an important role in relieving a suffering. Counsellors emphasize the importance of a mutual relationship in order to relieve the victims suffering. Lack of time was the main culprit. The core of alleviating a suffering can be compared with those factors the informants take into account in the caring encounter with the bullied pupil.

Framåt med stöd av det förflutna : religiöst historiebruk hos Anders Svedberg

Att det förflutna spelar en avgörande roll vid såväl individers som kollektivs identitetsformering är snarast ett axiom inom historiefacket. Därför är det ingen överraskning att det förflutna brukas av grupper och deras ledare i syfte att befästa och vidmakthålla den egna identiteten. Forskningen kring detta – den så kallade historiebruksforskningen – har under de senaste decennierna upplevt ett starkt uppsving inom flera discipliner i Norden, framför allt inom historia och historiedidaktik. Historiebruksforskningen har ändå försummat att i någon högre grad ta i beaktande religiösa och teologiska aspekter, liksom också de teologiska ämnena har varit dåliga på att visa intresse för historiebruksfrågor. Avhandlingen kan därför ses som ett svar på denna ömsesidiga försummelse, och som ett bidrag till det aktuella och framväxande forskningsfältet kring historiebruk och kulturellt minne. Med utgångspunkt i den österbottniske mångsysslaren Anders Svedberg (1832–1889) undersöks mer konkret begreppet ”religiöst historiebruk”. Anders Svedberg växte upp, levde och verkade i det av väckelsen starkt präglade Munsala i svenska Österbotten. Han var en man av folket som kände till dess seder, bruk och historia. Därför kunde han ösa ur dess historia när han skrev sina tidningsartiklar och när han i lantdagen talade för allmogens demokratisering. Genom anspelningar på och hänvisningar till det förflutna refererade han ofta till kyrkohistoriska händelser i sin argumentation. Men vilka händelser använde han sig av? Varför hänvisade han till just de händelserna? Hur gjorde han det och i vilket syfte? Utifrån dessa konkreta frågor ger undersökningen förslag på vad som allmänt kan tänkas karakterisera ett religiöst historiebruk. Resultaten ger vid handen att ett religiöst historiebruk – särskilt när det bygger på en religiös minnesgemenskaps kulturella texter – har en förmåga att fungera legitimerande, mobiliserande och inkluderande/exkluderande. --------------------------------------------------------------------- Menneisyydellä on merkittävä osa sekä yksilön että yhteisön identiteetin muotoutumisessa. Tämä väittämä on yleisesti tunnustettu. Siksi ei ole yllättävää että eri yhteisöt ja niiden johtajat hyödyntävät menneisyyttä vahvistaakseen ja suojellakseen omaa identiteettiään. Niin kutsuttu historian käytön tutkimus on viime vuosikymmenillä vahvistanut asemaansa monilla tieteenaloilla pohjoismaissa, erityisesti historiatieteessä ja historian didaktiikassa. Historian käytön tutkimus ei kuitenkaan oleellisesti ole huomioinut uskonnollisia tai teologisia näkökulmia. Myöskään teologiset oppiaineet eivät ole osoittaneet suurempaa kiinnostusta historian käyttöä kohtaan. Väitöstutkimus vastaa siten näihin molempiin laiminlyönteihin ja se voidaan nähdä kirkkohistoriallisena panoksena historian käytön ja kulttuurisen muistin ajankohtaiseen ja kasvavaan tutkimusalaan. Tutkimus ottaa lähtökohdakseen pohjoismaalaisen monitaiturin Anders Svedbergin (1832–1889) ja tarkastelee hänen kautta käsitettä ”uskonnollinen historiankäyttö”. Anders Svedberg varttui, eli ja toimi Munsalassa aikaan jolloin herännäisyydellä ja muilla herätysliikkeillä oli vahva jalansija alueella. Svedberg tunsi pohjoismaalaisen maalaisväestön tavat ja tottumukset sekä alueen historian. Tämän takia hän osasi hyödyntää kyseistä historiaa kirjoittaessaan lehtiartikkeleita maalaisväestölle ja ajaessaan heidän etujaan säätyvaltiopäivillä. Kirjoituksissaan ja puheissaan hän viittasi usein historiallisiin ja kirkkohistoriallisiin tapahtumiin. Mutta mihin tapahtumiin hän viittasi? Miksi hän viittasi juuri näihin tapahtumiin, miten hän sen teki ja millä tavalla? Näiden konkreettisten kysymysten avulla tutkimus pyrkii tarkastelemaan miltä uskonnollinen historiankäyttö yleisellä tasolla voi näyttää. Tutkimustulos osoittaa että uskonnollisella historiankäytöllä – varsinkin perustuessaan uskonnollisen muistiyhteisön kulttuuriseen tekstiin – on kyky legitimoida, mobilisoida sekä sisällyttää ja sulkea pois ihmisiä.

Ekonomisk karta över Bergö och Malax socknar på grundval av lantmäterikartor från åren 1753-1801 uppgjord av Helmer Smeds

0-meridiaani : Helsinki.

Ekonomisk karta över Bergö och Malax socknar på grundval av lantmäterikartor från åren 1884-1920 uppgjord av Helmer Smeds

0-meridiaani : Helsinki.

Restoration of sensory dysfunction following peripheral nerve injury by the polysaccharide from culinary and medicinal mushroom, Hericium erinaceus (Bull.: Fr.) Pers. through its neuroregenerative action

Abstract Peripheral nerves have the unique capability to regenerate after injury. Insights into regeneration of peripheral nerves after injury may have implications for neurodegenerative diseases of the nervous system. We investigated the ability of polysaccharide from Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats by daily oral administration. In sensory functional recovery test, the time taken for the rats to withdraw its hind limb from contact with the hot plate was measured. The test revealed acceleration of sensory recovery in the polysaccharide group compared to negative controls. Further, peripheral nerve injury leads to changes at the remotely located DRG containing cell bodies of sensory neurons. Immunofluorescence studies showed that Akt and p38 MAPK were expressed in DRG and strongly upregulated in polysaccharide group after peripheral nerve injury. The intensity of endothelial cells antigen-1 that recognized endothelial cells in the blood vessels of distal segments in crushed nerves was significantly higher in the treated groups than in the negative control group. Our findings suggest that H. erinaceus is capable of accelerating sensory functional recovery after peripheral nerve injury and the effect involves the activation of protein kinase signaling pathways and restoration of blood-nerve barrier.