ER stress in Alzheimer's disease: a novel neuronal trigger for inflammation and Alzheimer's pathology

The endoplasmic reticulum (ER) is involved in several crucial cellular functions, e.g. protein folding and quality control, maintenance of Ca2+ balance, and cholesterol synthesis. Many genetic and environmental insults can disturb the function of ER and induce ER stress. ER contains three branches of stress sensors, i.e. IRE1, PERK and ATF6 transducers, which recognize the misfolding of proteins in ER and activate a complex signaling network to generate the unfolded protein response (UPR). Alzheimer's disease (AD) is a progressive neurodegenerative disorder involving misfolding and aggregation of proteins in conjunction with prolonged cellular stress, e.g. in redox regulation and Ca2+ homeostasis. Emerging evidence indicates that the UPR is activated in neurons but not in glial cells in AD brains. Neurons display pPERK, peIF2α and pIRE1α immunostaining along with abundant diffuse staining of phosphorylated tau protein. Recent studies have demonstrated that ER stress can also induce an inflammatory response via different UPR transducers. The most potent pathways are IRE1-TRAF2, PERK-eIF2α, PERK-GSK-3, ATF6-CREBH, as well as inflammatory caspase-induced signaling pathways. We will describe the mechanisms which could link the ER stress of neurons to the activation of the inflammatory response and the evolution of pathological changes in AD

A refined in vitro model to study inflammatory responses in organotypic membrane culture of postnatal rat hippocampal slices

BACKGROUND: Propagated tissue degeneration, especially during aging, has been shown to be enhanced through potentiation of innate immune responses. Neurodegenerative diseases and a wide variety of inflammatory conditions are linked together and several anti-inflammatory compounds considered as having therapeutic potential for example in Alzheimer's disease (AD). In vitro brain slice techniques have been widely used to unravel the complexity of neuroinflammation, but rarely, has the power of the model itself been reported. Our aim was to gain a more detailed insight and understanding of the behaviour of hippocampus tissue slices in serum-free, interface culture per se and after exposure to different pro- and anti-inflammatory compounds. METHODS: The responses of the slices to pro- and anti-inflammatory stimuli were monitored at various time points by measuring the leakage of lactate dehydrogenase (LDH) and the release of cytokines interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) and nitric oxide (NO) from the culture media. Histological methods were applied to reveal the morphological status after exposure to stimuli and during the time course of the culture period. Statistical power analysis were made with nQuery Advisor(®), version 5.0, (Statistical Solutions, Saugus, MA) computer program for Wilcoxon (Mann-Whitney) rank-sum test. RESULTS: By using the interface membrane culture technique, the hippocampal slices largely recover from the trauma caused by cutting after 4–5 days in vitro. Furthermore, the cultures remain stable and retain their responsiveness to inflammatory stimuli for at least 3 weeks. During this time period, cultures are susceptible to modification by inflammatory stimuli as assessed by quantitative biochemical assays and morphological characterizations. CONCLUSION: The present report outlines the techniques for studying immune responses using a serum-free slice culture model. Statistically powerful data under controlled culture conditions and with ethically justified use of animals can be obtained as soon as after 4–5 DIV. The model is most probably suitable also for studies of chronic inflammation

Bisfenolijohdannaiset : altistuminen ja terveysriskit rakennusalalla

Työterveyslaitoksen toteuttamassa ja Työsuojelurahaston rahoittamassa tutkimushankkeessa selvitettiin rakennusalan työntekijöiden altistumista epoksihartseissa käytetyille bisfenoliyhdisteille. Tutkimukseen osallistui 15 miespuolista työntekijää kahdesta eri työpaikasta, jotka tekivät viemäriputkien sukitusta ja lattiapinnoitusta. Työntekijöiltä kerättiin virtsanäytteitä viitenä eri ajankohtana (nollanäyte vapaan jälkeen, aamunäyte ennen työvuoroa, työvuoron jälkeen, työpäivän iltanäyte ja aamunäyte ennen seuraavaa työvuoroa), jotta kemikaalien poistumista elimistöstä pystyttiin paremmin arvioimaan. Virtsanäytteistä mitattiin seuraavia kemikaaleja: bisfenoli A (BPA), bisfenoli F (BPF), bisfenoli A diglysidyylieetteri (BADGE) ja bisfenoli F diglysidyylieetteri (BFDGE) sekä kahden jälkimmäisen aineenvaihduntatuotteita [bisfenoli A (2,3-dihydroksipropyyli) glysidyylieetteri (BADGE·H2O), bisfenoli A bis(2,3-dihydroksipropyyli) eetteri (BADGE·2H2O), bisfenoli A (3-kloori-2-hydroksipropyyli) (2,3-dihydroksipropyyli) eetteri (BADGE·HCl·H2O), bisfenoli A (3-kloori-2-hydroksipropyyli) glysidyylieetteri (BADGE·HCl), ja bisfenoli A bis(3-kloori- 2-hydroksipropyyli) eetteri (BADGE·2HCl) sekä bisfenoli F bis(2,3-dihydroksipropyyli) eetteri (BFDGE·2H2O), ja bisfenoli F bis(3-kloori-2-hydroksipropyyli) eetteri (BFDGE·2HCl)]. Työntekijöiden mittaustuloksia verrattiin työssään altistumattoman vertailuryhmän mittaustuloksiin. Vertailuhenkilöiltä kerättiin yksi virtsanäyte, joka otettiin aamulla. Työntekijöiltä kerättiin myös hengitysvyöhykeilmanäytteitä sekä käsienpyyhintänäytteitä. Kaikki mittausmenetelmät kehitettiin tässä hankkeessa. Työpaikoilla käytetyissä epoksipohjaisissa aineissa ei ollut mukana BPA:ta eikä BPF:ä, vaan ne koostuivat BADGE- ja BFDGE-pohjaisista epoksihartseista. Näin ollen työntekijöiden virtsanäytteiden BPA- ja BPF-pitoisuudet olivat samaa luokkaa kuin vertailuväestön vastaavat pitoisuudet. Sen sijaan osasta työntekijöiden virtsanäytteistä löytyi korkeampia BADGE- ja BFDGE-aineenvaihduntatuotteiden pitoisuuksia kuin vertailuryhmän näytteistä. Tämä viittaa työperäiseen altistumiseen BADGE:lle ja BFDGE:lle. Myös seuraavana päivänä kerätyistä näytteistä mitattiin selkeästi koholla olevia kemikaalipitoisuuksia, mikä viittaa ihon kautta tapahtuneeseen altistumiseen. Molemmilla työpaikoilla käytettiin koostumukseltaan suurin piirtein samanlaisia epoksivalmisteita. Tämä näkyy myös mittaustuloksissa, sillä molempien työpaikkojen työntekijöiden mittaustulokset olivat hyvin saman suuntaisia. Koska kyse on ihoa pienillä pitoisuuksilla herkistävistä aineista, näiden aineiden pääsy iholle ja imeytyminen elimistöön ihon läpi tulisi estää. Nyt saadut tulokset korostavat ennestään ihon kunnollisen suojaamisen tärkeyttä epoksitöissä. Turvallisesta epoksituotteiden käytöstä pinnoitustyössä on Työterveyslaitos tuottanut aiemmin ns. Epoksikansion, josta löytyy ohjeistusta mm. käsineiden valintaan epoksityössä (www.ttl.fi/epoksikansio). Tässä tutkimuksessa mitatut virtsapitoisuudet olivat sen verran matalia, että muut terveyshaitat aineiden imeytymisestä johtuen eivät ole nykytiedon valossa todennäköisiä. Altistumisen seurantaan tulee jatkossakin kiinnittää huomiota jo pelkästään senkin takia, että tämän tutkimuksen otos oli varsin kapea. Biomonitorointi tarjoaa altistumisen arviointiin hyvän työkalun. Työntekijöiden hengitysvyöhykkeeltä kerätyistä ilmanäytteistä pystyttiin mittaamaan BADGE:a ja BFDGE:tä, mutta pitoisuudet olivat matalia. Käsienpyyhintänäytteistä löytyi myös BADGE:a ja BFDGE:tä, varsinkin lattiapinnoitustyöpaikan näytteistä, mikä viittaisi myös siihen, että altistuminen on tapahtunut ainakin osittain ihon kautta. Tässä tutkimushankkeessa saatuja tuloksia voidaan jatkossa hyödyntää työperäisen bisfenolialtistumisen lisäksi myös kemikaaliturvallisuuteen liittyvässä viranomaistyössä esim. uusia altistumisen raja-arvoja asetettaessa sekä harkittaessa mahdollisia rajoituksia näiden aineiden käytölle

Kuvaus maputolaisen lapsen elämästä 7- 12 –vuotiaana : Opas Savonia-ammattikorkeakoulun Terveysalan kansainväliseen opiskelijavaihtoon lähteville opiskelijoille

Savonia-ammatikorkeakoulusta lähtee Mosambikin pääkaupunkiin Maputoon vuosittain eri terveys-alan opiskelijoita vaihtoon. Hoitotyön- ja ensihoidon koulutusohjelman opiskelijat suorittavat siellä usein lasten- ja nuorten sekä yhteisön terveyden edistämisen harjoittelut. Opinnäytetyömme oli kehit-tämistyö, jonka tarkoituksena oli tuottaa opas 7−12 -vuotiaan maputolaisen lapsen elämästä kan-sainväliseen opiskelijavaihtoon lähtijöille. Tavoitteena oli, että kansainväliseen vaihtoon lähtevät opiskelijat saavat ennen harjoittelun alkua tietoa lasten elämästä, heidän terveyteensä vaikuttavista tekijöistä ja Mosambikin kulttuurista. Opinnäytetyö toteutettiin projektityönä. Projekti eteni vaiheittain, ensin oli ideointi- ja esisuunnittelu-vaihe, sitten suunnittelu- ja toteutusvaihe sekä lopuksi päättämisvaihe. Opinnäytetyön raportti sisältää teoriaosuuden, kuvauksen opinnäytetyöprosessista sekä tuotoksen tekemisestä ja arvioinnista. Opas toteutettiin teoriatiedon, oman opiskelijavaihdon havainnoinnin ja maputolaisten haastattelujen avulla. Oppaan ydinasiat ovat lapsen asumisympäristön kuvaus, lapsen terveys ja siihen vaikuttavat tekijät sekä koulutus ja perhe. Jatkokehittämistyönä Maputon keskussairaalaan voisi tehdä perehdytyskansion tuleville vaihto- opis-kelijoille yhteistyössä paikallisten opiskelijoiden kanssa.Students from the healthcare in Savonia Polytechnic go to Maputo, the capital of Mosambik every year as exchange students. Students from nursing and paramedic degree programme often carry out their practical training for pediatric and community health care there. Our thesis was a work of development with a purpose of producing a guide for future students going to Maputo for their international student exchange trip about the life of a 7-12 -year old child's life living in Maputo. The aim was to give information about the lives of the children, their health and fac-tors contributing to that, and the culture of Mosambik, available for the students going to Maputo be-fore they actually are there. The thesis was conducted in the form of a project. The project progressed in stages. The first stage was brainstorming and pre-planning, the second stage was planning and executing, and finally the completion stage. The report of the thesis includes theory, a description of the thesis process and a product of the work and it's evaluation. The guide was created with the help of theory, our own perceptions from our student exchange trip and interviews of people living in Maputo. The main points of the guide are describing the living envi-ronment of a child in Maputo, the health of the children there, and the factors influencing the health of the children, and also education and family. As a future challenge, a directory of orientation placed in the central hospital of Maputo could be made for future exchange students in co-operation with the local students

The relationship of oxidative and glycolytic capacity of longissimus dorsi muscle to meat quality when different pig breeds and crossbreeds are compared

The oxidative and glycolytic capacities as well as the calcium release and uptake of sarcoplasmic reticulum and mitochondria of longissimus dorsi (LD) from seven pig breeds or crosses, i.e. Landrace, Yorkshire, Hampshire, Hampshire x (Yorkshire x Landrace), Duroc x (Yorkshire x Landrace), Landrace x (Yorkshire x Landrace), and Yorkshire x (Yorkshire x Landrace), were studied. These muscle properties were compared to meat quality. No studies concerning oxidative capacity or calcium metabolism of Finnish Landrace and Yorkshire pigs have been published before. To determine the oxidative capacity of the LD muscle, the activities of citrate synthase and 3-hydroxyacyl-CoA-dehydrogenase as well as the mitochondrial volume density were measured. To elucidate the glycolytic capacity of the LD muscle, lactate, glycogen, the glycolytic potential as well as activity of glycogen phosphorylase and lactate dehydrogenase (LDH) were measured. Also the content of LDH isoenzymes were determined. The muscle quality of Landrace and Yorkshire was similar. The LDH activity was lower in the Hampshire cross LD and higher in the Duroc cross LD than in either Landrace or Yorkshire. There were no other differences between breeds. Lower lactate and higher glycogen levels were noted in the Hampshire cross LD as compared to the Duroc cross LD. In Duroc cross and Hampshire muscle, the proportion of LDH-1 was higher and LDH-5 lower than in most other breeds. Higher glycolytic potential, but lower ultimate pH and LDH activity were noted in the Hampshire breed. In Hampshire and its cross, the ultimate pH was lower than in other breeds or crosses. The activities of 3-hydroxyacyl-CoA-dehydrogenase and citrate synthase were higher in Hampshire than in the other breeds. Calcium uptake of sarcoplasmic reticulum and mitochondria as well as mitochondrial calcium release were lower in crosses than in purebred pigs. The redder the meat color (measured instrumentally), the higher the oxidative capacity and the glycolytic potential was. There was no correlation between the glycolytic potential and the sensory quality of meat. The LD of Hampshire was the most oxidative. High muscle oxidative capacity seemed to improve meat flavor and juiciness. This study concerned only the pig LD, so the results can not be generalised to the whole pig. The muscle properties of Hampshire and Duroc crosses were quite similar to those of Landrace and Yorkshire in most of properties studied, but not in the LDH isoenzyme distribution. There was a great interindividual heterogeneity, in properties studied, in every breed and cross

Temporal and regional patterns in seal-induced catch and gear damage in the coastal trap-net fishery in the northern Baltic Sea: effect of netting material on damage

11 pages, 7 figures, 4 tablesSeal-induced damage in the traditional trap-net fishery increased dramatically during the 1990s in the northern Baltic Sea. Most damage is induced by a rapidly growing grey seal (Halichoerus grypus) population. We evaluated seal damage in the coastal trap-net fishery of the Gulf of Bothnia, where different gear constructions and netting materials are used. A total of 72 commercial fishermen with 136 trap-nets were involved in the study. Catch and gear-damage observations made by fishermen were consistent with our own. The largest catch losses of salmon (Salmo salar) were recorded in the Bothnian Sea, where seals damaged at least 37% of salmon catch (by number). In other regions, losses were notably smaller, at between 3 and 9%. The number of salmon caught in a trap on any one occasion correlated significantly with the number of damaged salmon. However, the more salmon were present in a trap, the smaller was the proportion damaged by seals. Observed catch losses in the whitefish (Coregonus sp.) fishery varied between regions from 5 to 7%. Gear damage was observed in 2-15% of trap-net emptyings, depending largely on region. The extent of gear damage followed the trend of catch damage in each region. Fish entanglement in trap-nets increased the amount of gear damage. The type of netting material significantly affected gear-damage frequencies and salmon entanglement. Seal-induced catch and gear damage could be reduced by gear modification and operational changes. The choice of suitable netting materials and the development of seal-safe fish-bags are essential in protecting the gear and catch from seals. © 2005 Elsevier B.V. All rights reservedPeer Reviewe

MECHANICAL PULPING: Effect of autohydrolysis on the lignin structure and the kinetics of delignification of birch wood

The first aim of this study was to investigate the delignification kinetics of alkaline cooking for autohydrolyzed birch wood (Betula pendula). A series of cooking trials, at temperatures ranging between 130°C and 170°C were performed on untreated (P-factor 0) and autohydrolyzed (P-factor 200) wood. The results of carbohydrate and lignin analyses were fitted to a kinetic model and it was observed that autohydrolysis doubles the delignification rate, during bulk delignification. However, a slight decrease was noticed in the delignification rate during residual pulping. Thus, the second aim of this study was to elucidate the reasons behind accelerated delignification. For this purpose two different autohydrolysis treatments (P-factors 200 and 750) were applied to birch wood. Lignin was isolated from both the native and autohydrolyzed wood and subjected to elemental analysis, methoxyl group determination, carbohydrate analysis and quantitative 1H, 13C and 31P nuclear magnetic resonance (NMR) spectroscopy. The results indicate that, during autohydrolysis, P-O-4 linkages were cleaved, the methoxyl group content was reduced and the syringyl/guaiacyl (S/G) ratio decreased. In addition, a decrease in primary and secondary aliphatic hydroxyl groups and an increase in phenolic hydroxyl groups were detected. It could be concluded that condensation reactions were also occurring during autohydrolysis. Although lignin reactions such as the cleavage of (i-O-4-cleavages and the increase in phenolic hydroxyl groups partly account for the pulping behaviour the reason behind the significantly accelerated bulk delignification is not entirely explained through this study. More research concerning reactions during autohydrolysis is needed.</p