Sykevälivaihtelu eteisvärinäpotilailla

Tiivistelmä. Eteisvärinä on sydämen yleisin pitkäkestoinen rytmihäiriö. Se laskee potilaiden elämänlaatua, altistaa potilaat vakaville komplikaatioille ja aiheuttaa terveydenhuollolle merkittäviä kustannuksia. Eteisvärinän hoidon tehon ennakoiminen yksittäisen potilaan kohdalla on hankalaa nykyisillä menetelmillä. Terveenkään sydämen syke ei ole täysin tasainen, vaan siihen liittyy aina sykevälivaihtelua. Sykevälivaihtelua voidaan analysoida usein eri keinoin ja se antaa tietoa sydämeen vaikuttavasta autonomisen hermoston säätelystä. Tässä syventävien opintojen tutkielmassa tutkittiin sykevälivaihtelua 163:lla kohtauksittaista eteisvärinää sairastavalla potilaalla. Sykevälianalyysiin käytettiin sekä aika- että taajuuspohjaista analyysimenetelmää. Ei-normalisoiduista arvoista määritettiin keskisyke, SDNN, LF-, HF- ja LF/HF-arvot. Tutkimusasetelmassa verrattiin ennen rytminhallintahoitoa määritettyjen sykevälivaihteluparametrien ja seuranta-ajan relapsin välistä yhteyttä. Aineiston analysoitavat Holter-nauhoitukset jaettiin rytminhallintahoidon mukaan alaryhmiin, joissa potilaat saivat joko katetriablaatiohoitoa tai lääkkeellistä rytminhallintahoitoa. Aineiston Holter-nauhoitukset olivat MANTRA-PAF-tutkimuksen nauhoituksia. Tutkimuksesta poissuljettiin nauhoitukset, joissa editoinnin jälkeisen häiriöttömän syketallenteen osuus oli < 95 %. Aiempia julkaisuja sykevälivaihtelusta eteisvärinäpotilailla on niukasti. Ottaen huomioon eteisvärinän yleisyyden ja hoidon tehon ennakoimisen vaikeuden, uusia menetelmiä tehon arviontiin tarvitaan. Tähän tutkimukseen on koottu myös tärkeimpiä tutkimustuloksia aiemmista eteisvärinäpotilaiden sykevälivaihtelututkimuksista. Tutkimuksessa havaittiin uusi julkaisematon löydös: perustilanteen taajuuskenttäanalyysin korkeampien LF-arvojen ja lääkkeellisen rytminhallintahoidon tehon välillä havaittiin tilastollisesti merkittävä yhteys. Tämän löydöksen kliininen merkitys jää kuitenkin vielä epäselväksi ja lisää tutkimuksia aiheesta tarvitaan

Physiologically based modelling framework for prediction of pulmonary pharmacokinetics of antimicrobial target site concentrations

Prediction of antimicrobial target-site pharmacokinetics is of relevance to optimize treatment with antimicrobial agents. A physiologically based pharmacokinetic (PBPK) model framework was developed for prediction of pulmonary pharmacokinetics, including key pulmonary infection sites (i.e. the alveolar macrophages and the epithelial lining fluid).\nThe modelling framework incorporated three lung PBPK models: a general passive permeability-limited model, a drug-specific permeability-limited model and a quantitative structure-property relationship (QSPR)-informed perfusion-limited model. We applied the modelling framework to three fluoroquinolone antibiotics. Incorporation of experimental drug-specific permeability data was found essential for accurate prediction.\nIn the absence of drug-specific transport data, our QSPR-based model has generic applicability. Furthermore, we evaluated the impact of drug properties and pathophysiologically related changes on pulmonary pharmacokinetics. Pulmonary pharmacokinetics were highly affected by physiological changes, causing a shift in the main route of diffusion (i.e. paracellular or transcellular). Finally, we show that lysosomal trapping can cause an overestimation of cytosolic concentrations for basic compounds when measuring drug concentrations in cell homogenate.\nThe developed lung PBPK model framework constitutes a promising tool for characterization of pulmonary exposure of systemically administrated antimicrobials.Pharmacolog

Unexpectedly diverse forest dung beetle communities in degraded rain forest landscapes in Madagascar

Tropical forests, which harbor high levels of biodiversity, are being lost at an alarming speed. Madagascar, a biodiversity hotspot, has lost more than half of its original forest cover. Most of the remaining forests are small fragments of primary and secondary forest with differing degrees of human impact. These forests, as well as coffee and fruit plantations, may be important in supporting the forest-dependent biodiversity in Madagascar but this has been little studied. In Madagascar, dung beetles, which offer important ecosystem services, are largely restricted to forests. We examined the ability of fragmented and degraded forests to support dung beetle diversity, compared to the large areas of primary forest in eastern Madagascar. We found a general trend of a reduction of species with a loss of forest connectivity. In contrast, a higher level of forest disturbance was associated with higher species diversity. In several sites of low-quality forest as many or more species were found as in less disturbed and primary forests. The average size of dung beetles was smaller in the lower quality localities than in the primary forests. These findings suggest that many forest dung beetles in Madagascar are better adapted to forest disturbance than earlier expected, although they require some level of connectivity to surrounding forest. in Malagasy is available with online material.Peer reviewe

Occurrence, Distribution, and Ecological Risk of Fluoroquinolones in Rivers and Wastewaters

The use of fluoroquinolones for the treatment of infections in humans and animals has increased in Argentina, and they can be found in large amounts in water bodies. The present study investigated the occurrence and associated ecological risk of 5 fluoroquinolones in rivers and farm wastewaters of San Luis, Santa Fe, Córdoba, Entre Ríos, and Buenos Aires provinces of Argentina by high-performance liquid chromatography coupled to fast-scanning fluorescence detection and ultra–high-performance liquid chromatography coupled to triple quadrupole mass spectrometry detection. The maximum concentrations of ciprofloxacin, enrofloxacin, ofloxacin, enoxacin, and difloxacin found in wastewater were 1.14, 11.9, 1.78, 22.1, and 14.2 μg L–1, respectively. In the case of river samples, only enrofloxacin was found, at a concentration of 0.97 μg L–1. The individual risk of aquatic organisms associated with water pollution due to fluoroquinolones was higher in bacteria, cyanobacteria, algae, plants, and anurans than in crustaceae and fish, with, in some cases, risk quotients >1. The proportion of samples classified as high risk was 87.5% for ofloxacin, 63.5% for enrofloxacin, 57.1% for ciprofloxacin, and 25% for enoxacin. Our results suggest that the prevalence of fluoroquinolones in water could be potentially risky for the aquatic ecosystem, and harmful to biodiversity.Fil: Teglia, Carla Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; ArgentinaFil: Perez, Florencia Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; ArgentinaFil: Michlig, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Programa de Investigación y Análisis de Residuos y Contaminantes Químicos; ArgentinaFil: Repetti, María Rosa. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Programa de Investigación y Análisis de Residuos y Contaminantes Químicos; ArgentinaFil: Goicoechea, Hector Casimiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; ArgentinaFil: Culzoni, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; Argentin