Toxic effects of nitro-PAHs and amino-PAHs in human bronchial epithelial BEAS-2B cells: role of DNA-damage response.

I denne studien har vi evaluert og sammenlignet effektene av ulike nitro-polisykliske aromatiske hydrokarboner (nitro-PAH), som er mutagene og karsinogene forbindelser, og finnes på forurensningspartikler fra blant annet dieseleksos. Humane bronkiale epitelceller (BEAS-2B) ble eksponert for 1-nitropyren (1-NP), 3-nitrofluoranten (3-NF) og 3-nitrobenzantron (3-NBA), og deres korresponderende amino-former, 1-AP, 3-AF og 3-ABA, i tillegg til 2-nitrobenzantron (2-NBA) og benzo[a]pyren (B[a]P). Etter eksaminering med fluorescens mikroskopi viste det seg at 3-NBA var mest cytotoksisk, og at nitro-forbindelsene var mer potente enn sine korresponderende amino-former. Bedømt ut fra nukleær kondensering og kløyving av caspase 3 og PARP, induserte 3-NBA hovedsaklig apoptotisk celledød. Alle forbindelsene, med unntak av 2-NBA og B[a]P, førte til en signifikant økning i frigjøringen av cytokinet CXCL8 (IL-8). Generelt induserte nitro-forbindelsene CXCL8 i større grad enn amino-forbindelsene. Amino-formene derimot gav økt frigjøring av CCL5 (RANTES). B[a]P førte til økt ekspresjon av AhR/ARNT-regulerte gener som CYP1A1/1B1, mens 3-NBA, 3-NF og 1-NP alle reduserte disse genuttrykkene, noe som indikerer AhR/ARNT-antagonisme. 3-NBA forårsaket mest DNA-skade, bedømt ut fra mengden DNA-addukter, DNA enkelttrådbrudd og akkumulering av celler i S-fase. Videre analyse av DNA-skaderesponsen (DDR) viste at 3-NBA aktiverte ATM, Chk2 og p53. Aktiveringen av p53 ble vist ved økt fosforylering og translokasjon til kjernen. 2-NBA, 1-NP og B[a]P førte ikke til fosforylering av disse proteinene. p53-hemmeren, pifithrin-α, reduserte mengden 3-NBA-indusert celledød, hvilket tyder på at DNA-skade/DDR-signalisering og aktivering av p53 er sentrale komponenter i slik celledød. Studien illustrerer at de ulike PAH har svært forskjellige toksiske potensialer (målt i celledød og cytokindannelse), og små endringer i molekylstruktur, så som plassering av nitro-grupper eller substitusjon av nitro- med en aminogruppe, har dramatisk innvirkning på toksisiteten

Hverdagsmestring og aktiv alderdom i et fremtidsrettet og bærekraftig samfunn: Perspektiv fra Nord-Gudbrandsdalen

Tittel: Hverdagsmestring og aktiv alderdom i et fremtidsrettet og bærekraftig samfunn: perspektiv fra Nord-Gudbrandsdalen Dato: 10.05.2021 Forfattere: Elisabeth Tveiten Øya Johanne Liebig-Larsen Sofie Hagen Nilstad Veileder: Linda Stigen Nøkkelord: Aktiv alderdom, helse og omsorgstjenester, frivillig arbeid, personlige ressurser og bolig. Antall sider/ord: 10780 /54 Antall vedlegg: 5 Bakgrunn: Nord-Gudbrandsdalen møter utfordringer vedrørende fremtidens eldre grunnet økende fraflytting. Regionen gjennomfører prosjektet “Smart velferdsregion Nord-Gudbrandsdal", for å undersøke hvordan de eldre vil bo i fremtiden for å imøtekomme behovene og skape bærekraftig samfunn. Samfunnsutfordringen har behov for oppmerksomhet, planlegging og tilrettelegging, da det foreligger felles ønske om ressurskoordinering. Den avsluttende bacheloroppgaven i ergoterapi har utspring i dette prosjektet, og ferdigstilles 10. mai 2021. Hensikt: Hensikten med bacheloroppgaven er å identifisere hvordan mennesker 55+ kan benytte egne ressurser for lokalsamfunnets utvikling og hvordan de kan opprettholde hverdagsaktiviteter for en aktiv alderdom. Problemstilling: Hvordan beskriver mennesker 55+ at hverdagsmestring og en aktiv alderdom kan opprettholdes i fremtiden? Metode: Informasjonsinnhentingen ble utført gjennom en kvalitativ metode med semistrukturert intervju. Resultat: Regionen har gode aktivitetstilbud og frivillige organisasjoner for å leve aktive liv. Utfordringene er demografiske avstander, utilstrekkelige transporttilbud, boligtilpasninger og mangel på̊ sentrale leiligheter. Det fremkommer at ergoterapifaget ikke er tilstrekkelig belyst og krever ytterligere markedsføring. Konklusjon: Hverdagsmestring og en aktiv alderdom kan opprettholdes ved selvstendighet i hverdagen og utføringen av meningsfulle aktiviteter. Samfunnet må omorganiseres og tilrettelegges for at dette skal muliggjøres. Grunnet vanskene med å forutse hva hverdagsmestring vil innebære i fremtiden, ser bachelorgruppen det avgjørende å rette søkelyset mot ergoterapifaget

Characterization and pro‐inflammatory potential of indoor mold particles

A number of epidemiological studies find an association between indoor air dampness and respiratory health effects. This is often suggested to be linked to enhanced mold growth. However, the role of mold are obviously difficult to disentangle from other dampness related exposure including microbes as well as non‐biological particles and chemical pollutants. The association may partly be due to visible mycelial growth and a characteristic musty smell of mold. Thus, the potential role of mold exposure should be further explored by evaluating information from experimental studies elucidating possible mechanistic links. Such studies show that exposure to spores and hyphal fragments may act as allergens and pro‐inflammatory mediators, and that they may damage airways by the production of toxins, enzymes and volatile organic compounds. In the present review, we hypothesizes that continuous exposure to mold particles may result in chronic low‐grade pro‐inflammatory responses contributing to respiratory diseases. We summarize some of the main methods for detection and characterization of fungal aerosols and highlight in vitro research elucidating how molds may induce toxicity and pro‐inflammatory reactions in human cell models relevant for airway exposure. Data suggest that the fraction of fungal hyphal fragments in indoor air is much higher than that of airborne spores, and the hyphal fragments often have a higher pro‐inflammatory potential. Thus, hyphal fragments of prevalent mold species with strong pro‐inflammatory potential may be particularly relevant candidates for respiratory diseases associated with damp/mold‐contaminated indoor air. Future studies linking of indoor air dampness with health effects should assess the toxicity and pro‐inflammatory potential of indoor air particulate matter, and combined this information with a better characterization of biological components including hyphal fragments from both pathogenic and non‐pathogenic mold species. Such studies may increase our understanding of the potential role of mold exposure

Characterization and pro‐inflammatory potential of indoor mold particles

A number of epidemiological studies find an association between indoor air dampness and respiratory health effects. This is often suggested to be linked to enhanced mold growth. However, the role of mold are obviously difficult to disentangle from other dampness related exposure including microbes as well as non‐biological particles and chemical pollutants. The association may partly be due to visible mycelial growth and a characteristic musty smell of mold. Thus, the potential role of mold exposure should be further explored by evaluating information from experimental studies elucidating possible mechanistic links. Such studies show that exposure to spores and hyphal fragments may act as allergens and pro‐inflammatory mediators, and that they may damage airways by the production of toxins, enzymes and volatile organic compounds. In the present review, we hypothesizes that continuous exposure to mold particles may result in chronic low‐grade pro‐inflammatory responses contributing to respiratory diseases. We summarize some of the main methods for detection and characterization of fungal aerosols and highlight in vitro research elucidating how molds may induce toxicity and pro‐inflammatory reactions in human cell models relevant for airway exposure. Data suggest that the fraction of fungal hyphal fragments in indoor air is much higher than that of airborne spores, and the hyphal fragments often have a higher pro‐inflammatory potential. Thus, hyphal fragments of prevalent mold species with strong pro‐inflammatory potential may be particularly relevant candidates for respiratory diseases associated with damp/mold‐contaminated indoor air. Future studies linking of indoor air dampness with health effects should assess the toxicity and pro‐inflammatory potential of indoor air particulate matter, and combined this information with a better characterization of biological components including hyphal fragments from both pathogenic and non‐pathogenic mold species. Such studies may increase our understanding of the potential role of mold exposure

Pro-Inflammatory Responses in Human Bronchial Epithelial Cells Induced by Spores and Hyphal Fragments of Common Damp Indoor Molds

Damp indoor environments contaminated with different mold species may contribute to the development and exacerbation of respiratory illnesses. Human bronchial epithelial BEAS-2B cells were exposed to X-ray treated spores and hyphal fragments from pure cultures of Aspergillus fumigatus, Penicillum chrysogenum, Aspergillus versicolor and Stachybotrys chartarum. Hyphal fragments of A. fumigatus and P. chrysogenum induced expression and release of the pro-inflammatory cytokine interleukin (IL)-6 and the chemokine IL-8, while none of the other hyphal preparations had effects. Hyphal fragments from A. fumigatus and P. chrysogenum also increased the expression of IL-1α, IL-1β and tumor necrosis factor (TNF)-α, but these cytokines were not released. X-ray treated spores had little or no inflammatory potential. Attenuating Toll-like receptor (TLR)-2 by blocking antibodies strongly reduced the A. fumigatus and P. chrysogenum hyphae-induced IL-6 and IL-8 release, whereas TLR4 antagonist treatment was without effects. Untreated A. fumigatus spores formed hyphae and triggered expression of pro-inflammatory genes with similarities to the effects of hyphal fragments. In conclusion, while X-ray treated spores induced no pro-inflammatory responses, hyphal fragments of A. fumigatus and P. chrysogenum enhanced a TLR2-dependent expression and release of IL-6 and IL-8

Pro-Inflammatory Responses in Human Bronchial Epithelial Cells Induced by Spores and Hyphal Fragments of Common Damp Indoor Molds

Damp indoor environments contaminated with different mold species may contribute to the development and exacerbation of respiratory illnesses. Human bronchial epithelial BEAS-2B cells were exposed to X-ray treated spores and hyphal fragments from pure cultures of Aspergillus fumigatus, Penicillum chrysogenum, Aspergillus versicolor and Stachybotrys chartarum. Hyphal fragments of A. fumigatus and P. chrysogenum induced expression and release of the pro-inflammatory cytokine interleukin (IL)-6 and the chemokine IL-8, while none of the other hyphal preparations had effects. Hyphal fragments from A. fumigatus and P. chrysogenum also increased the expression of IL-1α, IL-1β and tumor necrosis factor (TNF)-α, but these cytokines were not released. X-ray treated spores had little or no inflammatory potential. Attenuating Toll-like receptor (TLR)-2 by blocking antibodies strongly reduced the A. fumigatus and P. chrysogenum hyphae-induced IL-6 and IL-8 release, whereas TLR4 antagonist treatment was without effects. Untreated A. fumigatus spores formed hyphae and triggered expression of pro-inflammatory genes with similarities to the effects of hyphal fragments. In conclusion, while X-ray treated spores induced no pro-inflammatory responses, hyphal fragments of A. fumigatus and P. chrysogenum enhanced a TLR2-dependent expression and release of IL-6 and IL-8

Pro-Inflammatory Responses in Human Bronchial Epithelial Cells Induced by Spores and Hyphal Fragments of Common Damp Indoor Molds

Damp indoor environments contaminated with different mold species may contribute to the development and exacerbation of respiratory illnesses. Human bronchial epithelial BEAS-2B cells were exposed to X-ray treated spores and hyphal fragments from pure cultures of Aspergillus fumigatus, Penicillum chrysogenum, Aspergillus versicolor and Stachybotrys chartarum. Hyphal fragments of A. fumigatus and P. chrysogenum induced expression and release of the pro-inflammatory cytokine interleukin (IL)-6 and the chemokine IL-8, while none of the other hyphal preparations had effects. Hyphal fragments from A. fumigatus and P. chrysogenum also increased the expression of IL-1α, IL-1β and tumor necrosis factor (TNF)-α, but these cytokines were not released. X-ray treated spores had little or no inflammatory potential. Attenuating Toll-like receptor (TLR)-2 by blocking antibodies strongly reduced the A. fumigatus and P. chrysogenum hyphae-induced IL-6 and IL-8 release, whereas TLR4 antagonist treatment was without effects. Untreated A. fumigatus spores formed hyphae and triggered expression of pro-inflammatory genes with similarities to the effects of hyphal fragments. In conclusion, while X-ray treated spores induced no pro-inflammatory responses, hyphal fragments of A. fumigatus and P. chrysogenum enhanced a TLR2-dependent expression and release of IL-6 and IL-8