Browsing by Subject "BIOAVAILABILITY"

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  • Gu, Ying; Lee, Hsi-Ming; Napolitano, Nicole; Clemens, McKenzie; Zhang, Yazhou; Sorsa, Timo; Zhang, Yu; Johnson, Francis; Golub, Lorne M. (2013)
  • Li, Xia; Frechen, Sebastian; Moj, Daniel; Lehr, Thorsten; Taubert, Max; Hsin, Shih-hsuan; Mikus, Gerd; Neuvonen, Pertti J; Olkkola, Klaus; Saari, Teijo; Fuhr, Uwe (2020)
    Background Voriconazole, a first-line antifungal drug, exhibits nonlinear pharmacokinetics (PK), together with large interindividual variability but a narrow therapeutic range, and markedly inhibits cytochrome P450 (CYP) 3A4 in vivo. This causes difficulties in selecting appropriate dosing regimens of voriconazole and coadministered CYP3A4 substrates. Objective This study aimed to investigate the metabolism of voriconazole in detail to better understand dose- and time-dependent alterations in the PK of the drug, to provide the model basis for safe and effective use according to CYP2C19 genotype, and to assess the potential of voriconazole to cause drug-drug interactions (DDIs) with CYP3A4 substrates in more detail. Methods In vitro assays were carried out to explore time-dependent inhibition (TDI) of CYP3A4 by voriconazole. These results were combined with 93 published concentration-time datasets of voriconazole from clinical trials in healthy volunteers to develop a whole-body physiologically based PK (PBPK) model in PK-Sim(R). The model was evaluated quantitatively with the predicted/observed ratio of the area under the plasma concentration-time curve (AUC), maximum concentration (C-max), and trough concentrations for multiple dosings (C-trough), the geometric mean fold error, as well as visually with the comparison of predicted with observed concentration-time datasets over the full range of recommended intravenous and oral dosing regimens. Results The result of the half maximal inhibitory concentration (IC50) shift assay indicated that voriconazole causes TDI of CYP3A4. The PBPK model evaluation demonstrated a good performance of the model, with 71% of predicted/observed aggregate AUC ratios and all aggregateC(max)ratios from 28 evaluation datasets being within a 0.5- to 2-fold range. For those studies reporting CYP2C19 genotype, 89% of aggregate AUC ratios and all aggregateC(max)ratios were inside a 0.5- to 2-fold range of 44 test datasets. The results of model-based simulations showed that the standard oral maintenance dose of voriconazole 200 mg twice daily would be sufficient for CYP2C19 intermediate metabolizers (IMs; *1/*2, *1/*3, *2/*17, and *2/*2/*17) to reach the tentative therapeutic range of > 1-2 mg/L to <5-6 mg/L forC(trough), while 400 mg twice daily might be more suitable for rapid metabolizers (RMs; *1/*17, *17/*17) and normal metabolizers (NMs; *1/*1). When the model was integrated with independently developed CYP3A4 substrate models (midazolam and alfentanil), the observed AUC change of substrates by voriconazole was inside the 90% confidence interval of the predicted AUC change, indicating that CYP3A4 inhibition was appropriately incorporated into the voriconazole model. Conclusions Both the in vitro assay and model-based simulations support TDI of CYP3A4 by voriconazole as a pivotal characteristic of this drug's PK. The PBPK model developed here could support individual dose adjustment of voriconazole according to genetic polymorphisms of CYP2C19, and DDI risk management. The applicability of modeling results for patients remains to be confirmed in future studies.
  • Figueroa, D.; Rowe, O. F.; Paczkowska, J.; Legrand, C.; Andersson, A. (2016)
    Heterotrophic bacteria are, in many aquatic systems, reliant on autochthonous organic carbon as their energy source. One exception is low-productive humic lakes, where allochthonous dissolved organic matter (ADOM) is the major driver. We hypothesized that bacterial production (BP) is similarly regulated in subarctic estuaries that receive large amounts of riverine material. BP and potential explanatory factors were measured during May-August 2011 in the subarctic RAyenne Estuary, northern Sweden. The highest BP was observed in spring, concomitant with the spring river-flush and the lowest rates occurred during summer when primary production (PP) peaked. PLS correlations showed that similar to 60 % of the BP variation was explained by different ADOM components, measured as humic substances, dissolved organic carbon (DOC) and coloured dissolved organic matter (CDOM). On average, BP was threefold higher than PP. The bioavailability of allochthonous dissolved organic carbon (ADOC) exhibited large spatial and temporal variation; however, the average value was low, similar to 2 %. Bioassay analysis showed that BP in the near-shore area was potentially carbon limited early in the season, while BP at seaward stations was more commonly limited by nitrogen-phosphorus. Nevertheless, the bioassay indicated that ADOC could contribute significantly to the in situ BP, similar to 60 %. We conclude that ADOM is a regulator of BP in the studied estuary. Thus, projected climate-induced increases in river discharge suggest that BP will increase in subarctic coastal areas during the coming century.
  • Tiedje, James M.; Wang , Fang; Manaia, Celia M.; Virta, Marko; Sheng, Hongjie; Ma, Liping; Zhang , Tong; Topp, Edward (2019)
    Antibiotic resistance and its environmental component are gaining more attention as part of combating the growing healthcare crisis. The One Health framework, promulgated by many global health agencies, recognizes that antimicrobial resistance is a truly inter-domain problem in which human health, animal agriculture, and the environment are the core and interrelated components. This prospectus presents the status and issues relevant to the environmental component of antibiotic resistance, namely, the needs for advancing surveillance methodology: the environmental reservoirs and sources of resistance, namely, urban wastewater treatment plants, aquaculture production systems, soil receiving manure and biosolid, and the atmosphere which includes longer range dispersal. Recently, much work has been done describing antibiotic resistance genes in various environments; now quantitative, mechanistic, and hypothesis-driven studies are needed to identify practices that reduce real risks and maintain the effectiveness of our current antibiotics as long as possible. Advanced deployable detection methods for antibiotic resistance in diverse environmental samples are needed in order to provide the surveillance information to identify risks and define barriers that can reduce risks. Also needed are practices that reduce antibiotic use and thereby reduce selection for resistance, as well as practices that limit the dispersal of or destroy antibiotic-resistant bacteria or their resistance genes that are feasible for these varied environmental domains.
  • Toropainen, Elisa; Fraser-Miller, Sara J.; Novakovic, Dunja; Del Amo, Eva M.; Vellonen, Kati-Sisko; Ruponen, Marika; Viitala, Tapani; Korhonen, Ossi; Auriola, Seppo; Hellinen, Laura; Reinisalo, Mika; Tengvall, Unni; Choi, Stephanie; Absar, Mohammad; Strachan, Clare; Urtti, Arto (2021)
    Eye drops of poorly soluble drugs are frequently formulated as suspensions. Bioavailability of suspended drug depends on the retention and dissolution of drug particles in the tear fluid, but these factors are still poorly understood. We investigated seven ocular indomethacin suspensions (experimental suspensions with two particle sizes and three viscosities, one commercial suspension) in physical and biological tests. The median particle size (d(50)) categories of the experimental suspensions were 0.37-1.33 and 3.12-3.50 mu m and their viscosity levels were 1.3, 7.0, and 15 mPa center dot s. Smaller particle size facilitated ocular absorption of indomethacin to the aqueous humor of albino rabbits. In aqueous humor the AUC values of indomethacin suspensions with different particle sizes, but equal viscosity, differed over a 1.5 to 2.3-fold range. Higher viscosity increased ocular absorption 3.4-4.3-fold for the suspensions with similar particle sizes. Overall, the bioavailability range for the suspensions was about 8-fold. Instillation of larger particles resulted in higher tear fluid AUC values of total indomethacin (suspended and dissolved) as compared to application of smaller particles. Despite these tear fluid AUC values of total indomethacin, instillation of the larger particles resulted in smaller AUC levels of indomethacin in the aqueous humor. This suggests that the small particles yielded higher concentrations of dissolved indomethacin in the tear fluid, thereby leading to improved ocular bioavailability. This new conclusion was supported by ocular pharmacokinetic modeling. Both particle size and viscosity have a significant impact on drug concentrations in the tear fluid and ocular drug bioavailability from topical suspensions. Viscosity and particle size are the key players in the complex interplay of drug retention and dissolution in the tear fluid, thereby defining ocular drug absorption and bioequivalence of ocular suspensions.
  • Verni, Michela; Pontonio, Erica; Krona, Annika; Jacob, Sera; Pinto, Daniela; Verardo, Vito; Díaz-de-Cerio, Elixabet; Coda, Rossana; Rizzello, Carlo (2020)
    Brewers' spent grain (BSG) is the major by-product of the brewing industry which remain largely unutilized despite its nutritional quality. In this study, the effects of fermentation on BSG antioxidant potential were analyzed. A biotechnological protocol including the use of xylanase followed by fermentation withLactiplantibacillus plantarum (Lactobacillus plantarum)PU1, PRO17, and H46 was used. Bioprocessed BSG exhibited enhanced antioxidant potential, characterized by high radical scavenging activity, long-term inhibition of linoleic acid oxidation and protective effect toward oxidative stress on human keratinocytes NCTC 2544. Immunolabelling and confocal laser microscopy showed that xylanase caused an extensive cell wall arabinoxylan disruption, contributing to the release of bound phenols molecules, thus available to further conversion through lactic acid bacteria metabolism. To clarify the role of fermentation on the antioxidant BSG potential, phenols were selectively extracted and characterized through HPLC-MS techniques. Novel antioxidant peptides were purified and identified in the most active bioprocessed BSG.
  • Peltonen, Leena; Strachan, Clare J. (2020)
    Poor aqueous solubility is currently a prevalent issue in the development of small molecule pharmaceuticals. Several methods are possible for improving the solubility, dissolution rate and bioavailability of Biopharmaceutics Classification System (BCS) class II and class IV drugs. Two solid state approaches, which rely on reductions in order, and can theoretically be applied to all molecules without any specific chemical prerequisites (compared with e.g. ionizable or co-former groups, or sufficient lipophilicity), are the use of the amorphous form and nanocrystals. Research involving these two approaches is relatively extensive and commercial products are now available based on these technologies. Nevertheless, their formulation remains more challenging than with conventional dosage forms. This article describes these two technologies from both theoretical and practical perspectives by briefly discussing the physicochemical backgrounds behind these approaches, as well as the resulting practical implications, both positive and negative. Case studies demonstrating the benefits and challenges of these two techniques are presented.
  • Manninen, Noora Johanna; Soinne, Helena Susanna; Lemola, Riitta; Hoikkala, Laura Kristiina; Turtola, Eila (2018)
    Dissolved organic carbon (DOC) load in discharges from cultivated soils may have negative impacts on surface waters. The magnitude of the load may vary according to soil properties or agricultural management practices. This study quantifies the DOC load of cultivated mineral soils and investigates whether the load is affected by agricultural practices. Discharge volumes and concentrations of DOC and dissolved organic nitrogen (DON) were continually measured at three sites from surface runoff and artificial subsurface drainage or from combined total discharge over a two-year period (2012-2014). Two experimental sites in South-West Finland had clayey soils (with soil carbon contents of 2.7-5.9% in the topmost soil layer), and the third site in West-Central Finland had sandy soil (soil carbon contents of 4.3-6.2%). Permanent grassland, organic manure application, mineral fertilization, and conventional ploughing or no-till activities were studied. Furthermore, the biodegradable DOC pool of surface runoff and subsurface drainage water from no-till and ploughed fields was estimated in a 2-month incubation experiment with natural bacterial communities collected from the Baltic Sea seawater. The annual DOC and DON loads were affected by discharge volume and seasonal weather conditions. The loads varied between 25-52 kg ha(-1) and 0.8-3.2 kg ha(-1), respectively, and were comparable to those from boreal forests with similar soil types. The DOC load increased with increasing topsoil carbon content at all sites. There were slightly higher DOC concentrations and DOC load from permanent grassland, but otherwise we could not distinguish any clear management-induced differences in the total DOC loads. While only 6-17% of the DOC in discharge water was biologically degraded during the 2-month incubation, the proportion of biodegradable (labile) DOC in surface runoff appeared to increase when soil was ploughed compared to no-till. (c) 2017 Elsevier B.V. All rights reserved.
  • Asmala, Eero; Osburn, Christopher L.; Paerl, Ryan W.; Paerl, Hans W. (2021)
    Estuaries regulate transport of dissolved organic carbon (DOC) from land to ocean. Export of terrestrial DOC from coastal watersheds is exacerbated by increasing major rainfall and storm events and human activities, leading to pulses of DOC that are shunted through rivers downstream to estuaries. Despite an upward trend of extreme events, the fate of the pulsed terrestrial DOC in estuaries remains unclear. We analyzed the effects of seven major tropical cyclones (TC) from 1999 to 2017 on the quantity and fate of DOC in the Neuse River Estuary (NC, USA). Significant TC-induced increases in DOC were observed throughout the estuary; the increase lasting from around 50 d at head-of-tide to over 6 months in lower estuary. Our results suggest that pulsed terrestrial DOC associated with TCs temporarily overwhelms the estuarine filter's abiotic and biotic degradation capacity under such high flow events, enhancing the shunt of terrestrial carbon to the coastal ocean.
  • Chamlagain, Bhawani; Sugito, Tessa Ayuningtyas; Deptula, Paulina; Edelmann, Minnamari; Kariluoto, Susanna; Varmanen, Pekka; Piironen, Vieno (2018)
    The in situ production of active vitamin B12 was investigated in aqueous cereal-based matrices with three strains of food-grade Propionibacterium freudenreichii. Matrices prepared from malted barley flour (33% w/v; BM), barley flour (6%; BF), and wheat aleurone (15%; AM) were fermented. The effect of cobalt and the lower ligand 5,6-dimethylbenzimidazole (DMBI) or its natural precursors (riboflavin and nicotinamide) on active B12 production was evaluated. Active B12 production was confirmed by UHPLC-UV-MS analysis. A B12 content of 12-37 mu was produced in BM; this content increased 10-fold with cobalt and reached 940-1,480 mu with both cobalt and DMBI. With riboflavin and nicotinamide, B12 production in cobalt-supplemented BM increased to 712 mu Approximately, 10 mu was achieved in BF and AM and was increased to 80 mu in BF and 260 mu in AM with cobalt and DMBI. The UHPLC and microbiological assay (MBA) results agreed when both cobalt and DMBI or riboflavin and nicotinamide were supplemented. However, MBA gave ca. 20%-40% higher results in BM and AM supplemented with cobalt, indicating the presence of human inactive analogues, such as pseudovitamin B12. This study demonstrates that cereal products can be naturally fortified with active B12 to a nutritionally relevant level by fermenting with P. freudenreichii.
  • Semjonov, Kristian; Salm, Maia; Lipiäinen, Tiina; Kogermann, Karin; Lust, Andres; Laidmäe, Ivo; Antikainen, Osmo; Strachan, Clare J.; Ehlers, Henrik; Yliruusi, Jouko; Heinämäki, Jyrki (2018)
    Solid dispersions (SDs) hold a proven potential in formulating poorly water-soluble drugs. The present paper investigates the interfacial phenomena associated with the bulk powder flow, water sorption, wetting and dissolution of the SDs prepared by a modified melt and quench-cooling (QC) method. Poorly water-soluble indomethacin (IND) was QC molten with solubilizing graft copolymer (Soluplus (R)) or polyol sugar alcohol (xylitol, XYL). The interfacial interactions of SDs with air/water were found to be reliant on the type (amorphous/crystalline) and amount of the carrier material used. The final SDs were composed of fused agglomerates (SOL) or large jagged particles (XYL) with good wetting and powder flow properties. The initial dissolution of IND was accelerated by both carrier materials studied. The QC molten SDs with amorphous Soluplus (R) significantly improved the dissolution rate of IND at pH 6.8 (79.9 +/- 0.2% at 30 min) compared to that of pure crystalline drug. The substantial improvement in the dissolution rate of IND was in connection with the amorphous state of the drug being stabilized by Soluplus (R) in the QC molten SDs. However, it is evident that a strong H-bond formation between the components in some regions of the QC molten SDs can limit the dissolution of IND. The QC molten two-phase SDs with a polyol carrier (XYL) showed rapid and continuous drug release without reaching a plateau.
  • Tamene, Aynadis; Baye, Kaleab; Kariluoto, Susanna; Edelmann, Minnamari; Bationo, Fabrice; Leconte, Nicolas; Humblot, Christele (2019)
    Folate deficiencies are widespread around the world. Promoting consumption of folate-rich foods could be a sustainable option to alleviate this problem. However, these foods are not always available. Cereals, being a staple food, could contribute to folate intake. They are fermented prior to consumption in many African countries, and fermentation can modify the folate content. In Ethiopia, injera is a widely consumed fermented flat bread. The main drivers of its fermentation are lactic acid bacteria (LAB). The aim of this work was to isolate and identify folate-producing LAB from injera fermented dough and to evaluate their ability to increase folate status after depletion in a rat model. Among the 162 strains isolated from 60 different fermentations, 19 were able to grow on a folate-free culture medium and produced 1 to 43 mu g/L (24 h, 30 degrees C incubation). The four highest folate producers belonged to the Lactobacillus plantarum species. The most productive strain was able to enhance folate status after depletion in a rat model, despite the relatively low folate content of the feed supplemented with the strain. Folate-producing L. plantarum strain has potential use as a commercial starter in injera production.
  • Duong, TT; Isomaki, A; Paaver, U; Laidmae, I; Tonisoo, A; Yen, TTH; Kogermann, K; Raal, A; Heinamaki, J; Pham, TMH (2021)
    Berberine (BBR) is a poorly water-soluble quaternary isoquinoline alkaloid of plant origin with potential uses in the drug therapy of hypercholesterolemia. To tackle the limitations associated with the oral therapeutic use of BBR (such as a first-pass metabolism and poor absorption), BBR-loaded liposomes were fabricated by ethanol-injection and thin-film hydration methods. The size and size distribution, polydispersity index (PDI), solid-state properties, entrapment efficiency (EE) and in vitro drug release of liposomes were investigated. The BBR-loaded liposomes prepared by ethanol-injection and thin-film hydration methods presented an average liposome size ranging from 50 nm to 244 nm and from 111 nm to 449 nm, respectively. The PDI values for the liposomes were less than 0.3, suggesting a narrow size distribution. The EE of liposomes ranged from 56% to 92%. Poorly water-soluble BBR was found to accumulate in the bi-layered phospholipid membrane of the liposomes prepared by the thin-film hydration method. The BBR-loaded liposomes generated by both nanofabrication methods presented extended drug release behavior in vitro. In conclusion, both ethanol-injection and thin-film hydration nanofabrication methods are feasible for generating BBR-loaded oral liposomes with a uniform size, high EE and modified drug release behavior in vitro.
  • Chamlagain, Bhawani; Rautio, Saija; Edelmann, Minnamari; Ollilainen, Velimatti; Piironen, Vieno (2020)
    The niacin content of cereal raw materials reported in food-composition databases often differs considerably. One major reason for this discrepancy is the analytical method used for its measurement is that a significant part of the niacin in cereals exists in bound form. In this study, we compared the niacin content of some representative cereal raw materials analysed with a sensitive and validated ultra-high performance liquid chromatography-fluorescence method against the values found in five national food-composition databases. We used established extraction methods that are assumed to liberate niacin available for absorption (acid hydrolysis mimicking human digestion) or total niacin (strong acid-alkaline hydrolysis). The niacin content (mg/100 g dry weight) obtained with acid hydrolysis ranged from a low level in corn flour (0.26), white wheat flour (0.45) and oat flakes (0.48), to a higher level in wholegrain flours (rye: 0.79, barley: 0.99, wheat: 0.88), wheat bran (2.7) and wheat germ (2.7). The niacin content with the acid-alkaline hydrolysis, however, was 1.9-11-fold the value measured after extraction with acid hydrolysis. In general, the niacin content found in the databases is closer to the results obtained after the acid-alkaline extraction, suggesting that the niacin values reported in the databases may not reflect actual bioaccessible niacin but total niacin.
  • Kakaei Lafdani, Elham; Laurén, Ari; Cvetkovic, Jovana; Pumpanen, Jukka; Saarela, Taija; Palviainen, Marjo (2021)
    Forest regeneration operations increase the concentration of nitrogen (N) in watercourses especially outside the growing season when traditional biological water protection methods are inefficient. Biochar adsorption-based water treatment could be a solution for nutrient retention. We studied the total nitrogen (TN) and nitrate-nitrogen (NO3--N) adsorption-desorption properties of spruce and birch biochar. The adsorption test was performed under four different initial concentrations of TN (1, 2, 3, and 4 mg L-1) using forest runoff water collected from ditch drains of boreal harvested peatland. The results showed that the TN adsorption amount increased linearly from the lowest to the highest concentration. The maximum adsorption capacity was 2.4 and 3.2 times greater in the highest concentration (4 mg L-1) compared to the lowest concentration (1 mg L-1) in spruce and birch biochar, respectively. The NO3--N adsorption amount of birch biochar increased linearly from 0 to 0.15 mg NO3--N g biochar(-1) when the initial concentration of NO3--N increased from 0.2 to 1.4 mg L-1. However, in spruce biochar, the initial concentration did not affect NO3--N adsorption amount. The results indicate that concentration significantly affects the biochar's capacity to adsorb N from water. The desorption test was performed by adding biochar extracted from the adsorption test into the forest runoff water with low TN concentration (0.2 or 0.35 mg L-1). The desorption results showed that desorption was negligibly small, and it was dependent on the TN concentration for birch biochar. Therefore, biochar can be a complementary method supporting water purification in peatland areas.
  • Gul, Uzma; Khan, Muhammad Imran; Madni, Asadullah; Sohail, Muhammad Farhan; Rehman, Mubashar; Rasul, Akhtar; Peltonen, Leena (2022)
    In this article, formulation studies for terbinafine hydrochloride nanoemulsions, prepared by high-energy ultrasonication technique, are described. Pseudo-ternary phase diagram was constructed in order to find out the optimal ratios of oil and surfactant/co-solvent mixture for nanoemulsion production. Clove and olive oils were selected as oil phase. Based on the droplet size evaluation, maximum nanoemulsion region were determined for formulation development. Further characterization included polydispersity index (PDI), zeta potential, Fourier transform infrared (FT-IR) spectroscopy, morphology, pH, viscosity, refractive index, ex vivo skin permeation, skin irritation, and histopathological examination. Droplet sizes of optimized formulations were in colloidal range. PDI values below 0.35 indicated considerably homogeneous nanoemulsions. Zeta potential values were from 13.2 to 18.1 mV indicating good stability, which was also confirmed by dispersion stability studies. Ex vivo permeation studies revealed almost total skin permeation of terbinafine hydrochloride from the nanoemulsions (96-98%) in 6 hours whereas commercial product reached only 57% permeation at the same time. Maximum drug amounts were seen in epidermis and dermis layers. Skin irritation and histopathological examination demonstrated dermatologically safe formulations. In conclusion, olive oil and clove oil-based nanoemulsion systems have potential to serve as promising carriers for topical terbinafine hydrochloride delivery.
  • Voss, Maren; Asmala, Eero; Bartl, Ines; Carstensen, Jacob; Conley, Daniel J.; Dippner, Joachim W.; Humborg, Christoph; Lukkari, Kaarina; Petkuviene, Jolita; Reader, Heather; Stedmon, Colin; Vybernaite-Lubiene, Irma; Wannicke, Nicola; Zilius, Mindaugas (2020)
    Coastal waters have strong gradients in dissolved organic matter (DOM) quantity and characteristics, originating from terrestrial inputs and autochthonous production. Enclosed seas with high freshwater input therefore experience high DOM concentrations and gradients from freshwater sources to more saline waters. The brackish Baltic Sea experiences such salinity gradients from east to west and from river mouths to the open sea. Furthermore, the catchment areas of the Baltic Sea are very diverse and vary from sparsely populated northern areas to densely populated southern zones. Coastal systems vary from enclosed or open bays, estuaries, fjords, archipelagos and lagoons where the residence time of DOM at these sites varies and may control the extent to which organic matter is biologically, chemically or physically modified or simply diluted with transport off-shore. Data of DOM with simultaneous measurements of dissolved organic (DO) nitrogen (N), carbon (C) and phosphorus (P) across a range of contrasting coastal systems are scarce. Here we present data from the Roskilde Fjord, Vistula and Öre estuaries and Curonian Lagoon; four coastal systems with large differences in salinity, nutrient concentrations, freshwater inflow and catchment characteristics. The C:N:P ratios of DOM of our data, despite high variability, show site specific significant differences resulting largely from differences residence time. Microbial processes seemed to have minor effects, and only in spring did uptake of DON in the Vistula and Öre estuaries take place and not at the other sites or seasons. Resuspension from sediments impacts bottom waters and the entire shallow water column in the Curonian Lagoon. Finally, our data combined with published data show that land use in the catchments seems to impact the DOC:DON and DOC:DOP ratios of the tributaries most.
  • Fransner, Filippa; Fransson, Agneta; Humborg, Christoph; Gustafsson, Erik; Tedesco, Letizia; Hordoir, Robinson; Nycander, Jonas (2019)
    Coastal seas receive large amounts of terrestrially derived organic carbon (OC). The fate of this carbon, and its impact on the marine environment, is however poorly understood. Here we combine underway CO2 partial pressure (pCO(2)) measurements with coupled 3-D hydrodynamical-biogeochemical modelling to investigate whether remineralization of terrestrial dissolved organic carbon (tDOC) can explain CO2 supersaturated surface waters in the Gulf of Bothnia, a subarctic estuary. We find that a substantial remineralization of tDOC and a strong tDOC-induced light attenuation dampening the primary production are required to reproduce the observed CO2 supersaturated waters in the nearshore areas. A removal rate of tDOC of the order of 1 year, estimated in a previous modelling study in the same area, gives a good agreement between modelled and observed pCO(2). The remineralization rate is on the same order as bacterial degradation rates calculated from published incubation experiments, suggesting that bacteria has the potential to cause this degradation. Furthermore, the observed high pCO(2) values during the ice-covered season argue against photochemical degradation as the main removal mechanism. All of the remineralized tDOC is outgassed to the atmosphere in the model, turning the northernmost part of the Gulf of Bothnia into a source of CO2 to the atmosphere.
  • EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA); Turck, Dominique; Heinonen, Marina (2021)
    Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of calcidiol monohydrate as a novel food (NF) pursuant to Regulation (EU) 2015/2283, including its bioavailability as a metabolite of vitamin D3 when added for nutritional purposes to food supplements. The NF is produced chemically. It is proposed in food supplements up to 10 lg/day for individuals > 11 years of age, including pregnant and lactating women and up to 5 lg/day in 3- to 10-year-old children. The production process, composition, specifications and stability of the NF do not raise safety concerns. Animal and human data indicate efficient absorption. The NF contains a fraction of nanoparticles, which are fat soluble and unlikely to reach systemic distribution. There are no concerns regarding genotoxicity. Human adult studies do not raise safety concerns. Combined intake estimates of calcidiol from the NF and calcidiol and vitamin D from the diet were below the tolerable upper intake level (UL) for vitamin D for subjects above 11 years of age. The achieved mean serum 25(OH)D concentration in adults supplemented with 10 lg NF per day remained below 200 nmol/L. The Panel concludes that the NF is safe under the proposed conditions of use and use levels for individuals > 11 years old, including pregnant and lactating women. The applicant did not provide data on the bioavailability and safety of the NF in children. The combined intake estimation in children (3-10 years) is close to the UL for vitamin D. Therefore, the Panel could not conclude on the safety of consumption of the NF in children (3-10 years) at the proposed daily intake. The NF is a bioavailable source of the biologically active metabolite of vitamin D, i.e. 1,25-dihydroxyvitamin D. (C) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.
  • Liu, Fengyuan; Edelmann, Minnamari; Piironen, Vieno; Kariluoto, Susanna (2022)
    Both the liberation and stability of endogenous folate are relevant to the bioaccessibility of folate. Since folates are unstable, in addition to studying the natural folate content in foods, bioaccessibility should be considered. To understand folate changes during digestion, a mixture of standard folate compounds was subjected to a static in vitro gastrointestinal digestion assay. Next, different types of bread were analysed to study how food matrices influence folate bioaccessibility. Folates were identified and quantitated by a UHPLC-PDA/FL method. Folic acid and 10-formylfolic acid were stable throughout the digestion, and the conversions among formyl folates and 5,10-methenyltetrahydrofolate were triggered at the gastric phase. Tetrahydrofolate began to degrade during the oral phase and was lost completely during the gastric phase. During the intestinal phase, 5-methyltetrahydrofolate began to degrade and suffered a 60% loss. With bread matrices, folate conversions and the decrease of reduced folates were also common, but the extent of changes varied. Generally, rye breads had the highest (80–120%) bioaccessibility of folate, while oat breads had the lowest (31–102%). The high proportion of 5-methyltetrahydrofolate could result in low bioaccessibility because of its relatively low stability during digestion in bread matrices. An increase in 10-formylfolic acid content was observed for all the breads, but 10-formyldihydrofolate seemed to be more stable in rye breads than in oat and wheat breads. The results showed that folates undergo significant changes during digestion and that food matrices could be modified to affect these changes towards better folate bioaccessibility.