Assessment of particulate exposure and surface characteristics in association with urinary levels of 8-hydroxy-2'-deoxyguanosine, considered as marker of oxidative stress

Epidemiological studies have demonstrated that exposure to fine particles is associated to adverse health effects, including cancer, respiratory and cardiovascular diseases. However, mechanisms by which particles induce health effects remain unclear. According to one of the most investigated hypotheses, particles cause adverse effects through the production of reactive oxygen species (ROS), which are very hazardous compounds able to attack directly biological structures, including the DNA strand or the lipid bilayer of the cells. If the defense mechanisms, constituted of antioxidants, are not able to counter ROS, then these compounds will cause in the body a range of oxidation reactions called "oxidative stress". The aim of the present research project was to better understand mechanisms by which exposure to fine particles induces oxidative stress. The first point of this project was to check whether exposure to high levels of fine particles is directly linked to oxidative stress, and whether this oxidative stress is accompanied by the activation of the defense mechanisms (antioxidants). The second point was to study the role played by the particle surface characteristics in the oxidative stress process. For that purpose, a study was conducted in bus depots with the participation of 40 mechanics. First, occupational exposure to particles (PM4) and to other pollutants (NOx, O3) was measured over a two-day period. Then, urine samples of mechanics were collected in order to measure levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) and antioxidants. 8OHdG is a molecule formed by the oxidation of DNA and allowing to assess the oxidative stress status of the mechanics. Finally, particles were collected on filters, and functional groups located on the particle surface were analyzed in the laboratory using a Knudsen flow reactor. This technique allows not only to quantify functional groups on the particle surface, but also to measure the reaction kinetics. Results obtained during the field campaign in bus depots showed that mechanics were exposed to rather low levels of PM4 (20-85 μg/m3) and of pollutants (NOx: 100-1000 ppb; O3: <15 ppb). However, despite this low exposure, urinary levels of the oxidative stress biomarker (8OHdG) increased significantly for non-smoking workers over a two-day period of shift. This oxidative stress was accompanied by an increase of antioxidants, indicating the activation of defense mechanisms. On the other hand, the analysis of functional groups on the particle surface showed important differences, depending on the workplace, the date and the activities of workers. The particle surface contained simultaneously antagonistic functional groups which did not undergo internal reactions (such as acids and bases), and was usually characterized by a high density of carbonyl functions and a low density of acidic sites. Reaction kinetics measured using the Knudsen flow reactor pointed out fast reactions of oxidizable groups and slow reactions of acidic sites. Several exposure parameters were significantly correlated with the increase of the oxidative stress status: the presence of acidic sites, carbonyl functions and oxidizable groups on the particle surface; reaction kinetics of functional groups on the particle surface; particulate iron and copper concentrations; and NOx concentration.

Intermittent atrial tachycardia promotes repolarization alternans and conduction slowing during rapid rates, and increases susceptibility to atrial fibrillation in a free-behaving sheep model.

INTRODUCTION: Paroxysmal atrial fibrillation (AF) may be triggered by intermittent atrial tachycardia, and ultimately lead to persistent AF. However, the mechanisms by which intermittent atrial tachycardia promotes sustained AF are not well understood. METHODS AND RESULTS: Eight sheep were chronically implanted with 2 pacemakers for the recording of broadband right atrial unipolar electrograms, and for the delivery of electrophysiological stimulation protocols and intermittent right atrial tachycardia. Right atrial kinetics of activation recovery interval (ARI) as a surrogate for action potential duration, of conduction time and velocity, and of repolarization alternans were analyzed at incremental pacing rates during the remodeling process induced by weeks of intermittent atrial tachycardia until the development of sustained AF. Intermittent atrial tachycardia decreased ARI and blunted its rate adaptation, facilitated atrial capture, and slowed conduction at high rates, and increased susceptibility to pacing-induced AF. In spite of blunted ARI rate adaptation, right atrial repolarization alternans was maintained during remodeling, and further increased in magnitude just before rapid pacing-induced AF. CONCLUSION: This study suggests that weeks of intermittent right atrial tachycardia result in a gradual electrical remodeling favorable for wavebreaks and reentry that may facilitate fibrillation.

Osteopaattisen hoidon vaikuttavuus niska- ja hartiaperäisissä kiputiloissa : arviointi NDI-mittarilla

Selvitimme opinnäytetyössämme osteopaattisen hoidon vaikuttavuutta niska- ja hartiaperäisissä kiputiloissa Neck Disability Index (NDI) -mittarilla arvioituna kokeellisessa tutkimusasetelmassa. Tutkimushenkilöt valittiin Stadian sosiaali- ja terveysalalle huhtikuussa 2006 lähetetyn sähköpostikutsun vastausten perusteella. Tutkimukseen osallistumisen valintakriteerejä olivat niska- tai hartiakipu, jännityspäänsärky sekä 18-40 vuoden ikä. Halukkaista valitsimme 12 tutkimushenkilön tutkimusjoukon. Lopullisissa tutkimustuloksissa on huomioitu 11 tutkimushenkilön tulokset. Artikulaatiotekniikoita käytettiin kaula- ja rintarangan fasettinivelten mobilisointiin. Pehmytkudostekniikoita käytettiin CES (cervical erector spinae)- ja DES (dorsal erector spinae) -alueiden esihoitona. Manipulaatiotekniikoilla hoidettiin rintarangan aliliikkuvia segmenttejä. MET-tekniikoilla pyrittiin vaikuttamaan CES-alueen lihasten tonukseen ja kaularangan kokonaisliikelaajuut een. Tutkimushenkilö täytti NDI-mittarin ennen ensimmäistä tutkimus- ja hoitokertaa sekä kolme päivää viimeisen hoitokerran jälkeen. NDI-mittareiden vastaukset pisteytettiin erillisiksi tuloksiksi ennen ja jälkeen hoitojen. Saatuja tuloksia vertailtiin keskenään yksittäisen tutkimushenkilön kohdalla. Tuloksia tarkasteltiin NDI-arvon prosentuaalisena muutoksena suhteessa alkutilanteeseen. NDI-mittarin osoittama niskahaitta-arvo laski yhdeksällä ja nousi kahdella tutkimushenkilöllä. Koko tutkimukseen osallistuneen ryhmän prosentuaalisen muutoksen keskiarvo oli -58,68 Tutkimustulosta voidaan pitää merkittävänä, mutta otannan ollessa näin pieni, emme pysty yleistämään tehtyjen hoitojen vaikuttavuutta. Tutkimuksen perusteella näyttäisi siltä, että DES-alueen lihaskivuista valitetaan vähän verrattuna saman alueen nikamatason löydöksiin. Löydösten pohjalta on mahdollista ajatella, että DES-alueen ylä- ja keskiosan segmentaariset dysfunktiot kompensoituvat CES-alueen lihaskipuin a. Sen vuoksi ehdotamme rintarangan käsittelyn olevan hyväksyttävä vaihtoehto kaularangan manipulaatiolle sen samankaltaisten vaikutusten takia. Tämä ajattelumalli on myös käypähoitosuositusten mukainen. Jatkotutkimuksia kyseisestä aiheesta tarvitaan. Ehdotuksenamme jatkotutkimusten tutkimusasetelmalle on hoitaa ainoastaan rintarangan alueen dysfunktioita ja seurata sen suoria vaikutuksia kaularangan alueelle.

Totuuden tuntomerkit : tosi-TV:tä ja "totuus"-elokuvaa

Opinnäytetyön kirjallinen osa pohtii dokumentaarisen elokuvan ja tosi-TV:n eroja ja yhtäläisyyksiä. Kysymys on rajattu koskemaan näiden kahden lajityypin keinoja autenttisen vaikutelman luomiseksi muodon ja teknisen toteutuksen tasolla. Dokumentaarisella elokuvalla ja tosi-TV:llä on osittain samanlaiset lähtökohdat, mutta niiden keinoissa on enemmän eroja kuin yhtäläisyyksiä. Keskityn tutkimuksessani erityisesti tosi-TV:n muotoon. Lähtökohtana pohdinnalle olen käyttänyt Veijo Hietalan ja Ari Honka-Hallilan esittämää teoriaa televisio-ohjelman autenttisuuden vaikutelmaa lisäävistä indekseistä eli "mittareista". Ohjelman autenttisuutta voidaan Hietalan ja Honka-Hallilan mukaan mitata visuaalisilla, temporaalisilla ja interaktiivisilla indekseillä. Käyn läpi tosi-TV:n kuvan, äänen, rakenteen, leikkauksen ja käsikirjoituksen keinoja autenttisuuden vaikutelman tehostamisessa ja vertaan niitä dokumentaarisen elokuvan vastaaviin keinoihin. Käsittelen myös joitain vain televisiolle ominaisia keinoja luoda autenttisuuden vaikutelmaa, kuten suoran lähetyksen illuusio ja vuorovaikutus katsojan kanssa. Pohdin myös "toisen sukupolven" tosi-TV:lle ominaista tapaa tuoda "tavallisen" ihmisen tunteet televisiodraaman keskiöön. Vaikka tosi-TV:llä ja dokumentaarisella elokuvalla on joitain yhtymäkohtia, ovat ne lajityyppeinä etääntyneet kauas toisistaan. Tämä ei kuitenkaan välttämättä tarkoita sitä, että niiden sisältöjen erot olisivat tarkkarajaiset. Myöskään ei ole aina yksiselitteisen selvää, onko jokin tietty ohjelma dokumentti vai tosi-TV-ohjelma. Opinnäytetyöni teososan muodostavat Laulua kauniiden lasten saarelta -nimisen teatterikappaleen videoprojisoinnit. Teatterikappaleessa tehtäväni oli ohjata tosi-TV:tä jäljittelevä kuvaustilanne koko näytelmän ajaksi. Teososan tekeminen on ollut lähtökohtana kirjallisen osan pohdinnoille.

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A Knudsen flow reactor has been used to quantify functional groups on the surface of seven different types of combustion particle samples: 3 amorphous carbons (FS 101, Printex 60, FW 2), 2 flame soots (hexane soot generated from a rich and a lean diffusion flame), and 2 Diesel particles (SRM 2975, Diesel soot recovered from a Diesel particulate filter). The technique is based on a heterogeneous titration reaction between a probe gas and a specific functional group on the particle surface. Six probe gases have been selected for the quantification of important functional groups: N(CH3)3 for the titration of acidic sites, NH2OH for carbonyl functions of aldehydes and ketones, CF3COOH and HCl for basic sites of different strength, O3 and NO2 for oxidizable groups. The limit of detection was generally well below 1% of a formal monolayer of adsorbed probe gas. Results obtained with N(CH3)3 were higher for the FW 2 amorphous carbon (post-oxidized sample, according to the manufacturer) and the Diesel particles (between 5.2·10 13 and 5.8·10 13 molecule/cm2), indicating a higher state of oxidation than for the other samples (between 1.3·10 12 and 3.7·10 12 molecule/cm2). The ratio of uptakes of CF3COOH and HCl inferred the presence of basic oxides on the particle surface, owing to the larger stability of the acetate compared to the chloride counter ion in the resulting pyrylium salt. The reactivity of the FS 101 amorphous carbon (3.7·10 15 molecule/cm2) and the hexane flame soot (between 1.9·10 15 and 2.7·10 15 molecule/cm2) towards O3 was very high, indicating the presence of a huge amount of oxidizable or reduced groups on the surface of these samples. Besides the quantification of surface functional groups, the kinetics of reactions between particles and probe gases has also been studied. The uptake coefficient γ0 was roughly correlated with the amount of probe gas taken up by the samples. Indeed, the presence of a high density of functional groups led to fast uptake of the probe gas. These different findings indicate that the particle surface appeared multi-functional, with the simultaneous presence of antagonistic functional groups which do not undergo internal chemical reactions, such as acid-base neutralization. Results also point to important differences in the surface reactivity of the samples, depending on the combustion conditions. The relative distribution of the surface functional groups may be a useful indicator for the state of oxidation and the reactivity of the particle surface.

Assessment of diesel exhaust particulate exposure and surface characteristics in association with levels of oxidative stress biomarkers

Exposure to PM10 and PM2.5 (particulate matter with aerodynamic diameter smaller than 10 μm and 2.5 μm, respectively) is associated with a range of adverse health effects, including cancer, pulmonary and cardiovascular diseases. Surface characteristics (chemical reactivity, surface area) are considered of prime importance to understand the mechanisms which lead to harmful effects. A hypothetical mechanism to explain these adverse effects is the ability of components (organics, metal ions) adsorbed on these particles to generate Reactive Oxygen Species (ROS), and thereby to cause oxidative stress in biological systems (Donaldson et al., 2003). ROS can attack almost any cellular structure, like DNA or cellular membrane, leading to the formation of a wide variety of degradation products which can be used as a biomarker of oxidative stress. The aim of the present research project is to test whether there is a correlation between the exposure to Diesel Exhaust Particulate (DEP) and the oxidative stress status. For that purpose, a survey has been conducted in real occupational situations where workers were exposed to DEP (bus depots). Different exposure variables have been considered: - particulate number, size distribution and surface area (SMPS); - particulate mass - PM2.5 and PM4 (gravimetry); - elemental and organic carbon (coulometry); - total adsorbed heavy metals - iron, copper, manganese (atomic adsorption); - surface functional groups present on aerosols (Knudsen flow reactor). (Demirdjian et al., 2005). Several biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine and several aldehydes) have been determined either in urine or serum of volunteers. Results obtained during the sampling campaign in several bus depots indicated that the occupational exposure to particulates in these places was rather low (40-50 μg/m3 for PM4). Size distributions indicated that particles are within the nanometric range. Surface characteristics of sampled particles varied strongly, depending on the bus depot. They were usually characterized by high carbonyl and low acidic sites content. Among the different biomarkers which have been analyzed within the framework of this study, mean levels of 8- hydroxy-2'-deoxyguanosine and several aldehydes (hexanal, heptanal, octanal, nonanal) increased during two consecutive days of exposure for non-smokers. In order to bring some insight into the relation between the particulate characteristics and the formation of ROS by-products, biomarkers levels will be discussed in relation with exposure variables.