Browsing by Subject "RELEASE"

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  • Germini, Giorgia; Peltonen, Leena (2021)
    The aim of the study was to prepare indomethacin nanocrystal-loaded, 3D-printed, fast-dissolving oral polymeric film formulations. Nanocrystals were produced by the wet pearl milling technique, and 3D printing was performed by the semi-solid extrusion method. Hydroxypropyl methyl cellulose (HPMC) was the film-forming polymer, and glycerol the plasticizer. In-depth physicochemical characterization was made, including solid-state determination, particle size and size deviation analysis, film appearance evaluation, determination of weight variation, thickness, folding endurance, drug content uniformity, and disintegration time, and drug release testing. In drug nanocrystal studies, three different stabilizers were tested. Poloxamer F68 produced the smallest and most homogeneous particles, with particle size values of 230 nm and PI values below 0.20, and was selected as a stabilizer for the drug-loaded film studies. In printing studies, the polymer concentration was first optimized with drug-free formulations. The best mechanical film properties were achieved for the films with HPMC concentrations of 2.85% (w/w) and 3.5% (w/w), and these two HPMC levels were selected for further drug-loaded film studies. Besides, in the drug-loaded film printing studies, three different drug levels were tested. With the optimum concentration, films were flexible and homogeneous, disintegrated in 1 to 2.5 min, and released the drug in 2-3 min. Drug nanocrystals remained in the nano size range in the polymer films, particle sizes being in all film formulations from 300 to 500 nm. When the 3D-printed polymer films were compared to traditional film-casted polymer films, the physicochemical behavior and pharmaceutical performance of the films were very similar. As a conclusion, 3D printing of drug nanocrystals in oral polymeric film formulations is a very promising option for the production of immediate-release improved- solubility formulations.
  • Nurkhametova, Dilyara; Kudryavtsev, Igor; Guselnikova, Valeriia; Serebryakova, Maria; Giniatullina, Raisa R.; Wojciechowski, Sara; Tore, Fatma; Rizvanov, Albert; Koistinaho, Jari; Malm, Tarja; Giniatullin, Rashid (2019)
    Extracellular ATP activates inflammasome and triggers the release of multiple cytokines in various immune cells, a process primarily mediated by P2X7 receptors. However, the expression and functional properties of P2X7 receptors in native mast cells in tissues such as meninges where migraine pain originates from have not been explored. Here we report a novel model of murine cultured meningeal mast cells and using these, as well as easily accessible peritoneal mast cells, studied the mechanisms of ATP-mediated mast cell activation. We show that ATP induced a time and dose-dependent activation of peritoneal mast cells as analyzed by the uptake of organic dye YO-PRO1 as well as 4,6-diamidino-2-phenylindole (DAPI). Both YO-PRO1 and DAPI uptake in mast cells was mediated by the P2X7 subtype of ATP receptors as demonstrated by the inhibitory effect of P2X7 antagonist A839977. Consistent with this, significant YO-PRO1 uptake was promoted by the P2X7 agonist 2',3'-O-(benzoyl-4-benzoyl)-ATP (BzATP). Extracellular ATP-induced degranulation of native and cultured meningeal mast cells was shown with Toluidine Blue staining. Taken together, these data demonstrate the important contribution of P2X7 receptors to ATP-driven activation of mast cells, suggesting these purinergic mechanisms as potential triggers of neuroinflammation and pain sensitization in migraine.
  • Yu, Nancy Y.; Bieder, Andrea; Raman, Amitha; Mileti, Enrichetta; Katayama, Shintaro; Einarsdottir, Elisabet; Fredholm, Bertil B.; Falk, Anna; Tapia-Paez, Isabel; Daub, Carsten O.; Kere, Juha (2017)
    Caffeine is a widely consumed psychoactive substance, but little is known about the effects of caffeine stimulation on global gene expression changes in neurons. Here, we conducted gene expression profiling of human neuroepithelial stem cell-derived neurons, stimulated with normal consumption levels of caffeine (3 mu M and 10 mu M), over a period of 9 h. We found dosage-dependent activation of immediate early genes after 1 h. Neuronal projection development processes were up-regulated and negative regulation of axon extension processes were down-regulated at 3 h. In addition, genes involved in extracellular matrix organization, response for wound healing, and regulation of immune system processes were down-regulated by caffeine at 3 h. This study identified novel genes within the neuronal projection guidance pathways that respond to acute caffeine stimulation and suggests potential mechanisms for the effects of caffeine on neuronal cells.
  • Harjuhaahto, Sandra; Rasila, Tiina S.; Molchanova, Svetlana M.; Woldegebriel, Rosa; Kvist, Jouni; Konovalova, Svetlana; Sainio, Markus T.; Pennonen, Jana; Torregrosa-Munumer, Ruben; Ibrahim, Hazem; Otonkoski, Timo; Taira, Tomi; Ylikallio, Emil; Tyynismaa, Henna (2020)
    Mitochondrial intermembrane space proteins CHCHD2 and CHCHD10 have roles in motor neuron diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy and axonal neuropathy and in Parkinson's disease. They form a complex of unknown function. Here we address the importance of these two proteins in human motor neurons. We show that gene edited human induced pluripotent stem cells (iPSC) lacking either CHCHD2 or CHCHD10 are viable and can be differentiated into functional motor neurons that fire spontaneous and evoked action potentials. Mitochondria in knockout iPSC and motor neurons sustain ultrastructure but show increased proton leakage and respiration, and reciprocal compensatory increases in CHCHD2 or CHCHD10. Knockout motor neurons have largely overlapping transcriptome profiles compared to isogenic control line, in particular for synaptic gene expression. Our results show that the absence of either CHCHD2 or CHCHD10 alters mitochondrial respiration in human motor neurons, inducing similar compensatory responses. Thus, pathogenic mechanisms may involve loss of synaptic function resulting from defective energy metabolism.
  • Penttinen, Kirsi; Swan, Heikki; Vanninen, Sari; Paavola, Jere; Lahtinen, Annukka M.; Kontula, Kimmo; Aalto-Setala, Katriina (2015)
    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly malignant inherited arrhythmogenic disorder. Type 1 CPVT (CPVT1) is caused by cardiac ryanodine receptor (RyR2) gene mutations resulting in abnormal calcium release from sarcoplasmic reticulum. Dantrolene, an inhibitor of sarcoplasmic Ca2+ release, has been shown to rescue this abnormal Ca2+ release in vitro. We assessed the antiarrhythmic efficacy of dantrolene in six patients carrying various RyR2 mutations causing CPVT. The patients underwent exercise stress test before and after dantrolene infusion. Dantrolene reduced the number of premature ventricular complexes (PVCs) on average by 74% (range 33-97) in four patients with N-terminal or central mutations in the cytosolic region of the RyR2 protein, while dantrolene had no effect in two patients with mutations in or near the transmembrane domain. Induced pluripotent stem cells (iPSCs) were generated from all the patients and differentiated into spontaneously beating cardiomyocytes (CMs). The antiarrhythmic effect of dantrolene was studied in CMs after adrenaline stimulation by Ca2+ imaging. In iPSC derived CMs with RyR2 mutations in the N-terminal or central region, dantrolene suppressed the Ca2+ cycling abnormalities in 80% (range 65-97) of cells while with mutations in or near the transmembrane domain only in 23 or 32% of cells. In conclusion, we demonstrate that dantrolene given intravenously shows antiarrhythmic effects in a portion of CPVT1 patients and that iPSC derived CM models replicate these individual drug responses. These findings illustrate the potential of iPSC models to individualize drug therapy of inherited diseases.
  • Leino, Sakari; Koski, Sini K.; Hänninen, Raisa; Tapanainen, Tuukka; Rannanpää, Saara; Salminen, Outi (2018)
    Preclinical studies suggest the involvement of various subtypes of nicotinic acetylcholine receptors in the pathophysiology of Parkinson's disease, a neurodegenerative disorder characterized by the death of dopaminergic neurons in the substantia nigra pars compacta (SNC). We studied for the first time the effects of alpha 5 nicotinic receptor subunit gene deletion on motor behavior and neurodegeneration in mouse models of Parkinson's disease and levodopa-induced dyskinesia. Unilateral dopaminergic lesions were induced in wild-type and alpha 5-KO mice by 6-hydroxydopamine injections into the striatum or the medial forebrain bundle. Subsequently, rotational behavior induced by dopaminergic drugs was measured. A subset of animals received chronic treatments with levodopa and nicotine to assess levodopa-induced dyskinesia and antidyskinetic effects by nicotine. SNC lesion extent was assessed with tyrosine hydroxylase immunohistochemistry and stereological cell counting. Effects of alpha 5 gene deletion on the dopaminergic system were investigated by measuring ex vivo striatal dopamine transporter function and protein expression, dopamine and metabolite tissue concentrations and dopamine receptor mRNA expression. Hemiparkinsonian alpha 5-KO mice exhibited attenuated rotational behavior after amphetamine injection and attenuated levodopa-induced dyskinesia. In the intrastriatal lesion model, dopaminergic cell loss in the medial cluster of the SNC was less severe in alpha 5-KO mice. Decreased striatal dopamine uptake in alpha 5-KO animals suggested reduced dopamine transporter function as a mechanism of attenuated neurotoxicity. Nicotine reduced dyskinesia severity in wild-type but not alpha 5-KO mice. The attenuated dopaminergic neurodegeneration and motor dysfunction observed in hemiparkinsonian alpha 5KO mice suggests potential for alpha 5 subunit-containing nicotinic receptors as a novel target in the treatment of Parkinson's disease. (C) 2018 The Authors. Published by Elsevier Ltd.
  • Liu, Dongfei; Chen, Jian; Jiang, Tao; Li, Wei; Huang, Yao; Lu, Xiyi; Liu, Zehua; Zhang, Weixia; Zhou, Zheng; Ding, Qirui; Almeida Santos, Helder; Yin, Guoyong; Fan, Jin (2018)
    New treatment strategies for spinal cord injury with good therapeutic efficacy are actively pursued. Here, acetalated dextran (AcDX), a biodegradable polymer obtained by modifying vicinal diols of dextran, is demonstrated to protect the traumatically injured spinal cord. To facilitate its administration, AcDX is formulated into microspheres (approximate to 7.2 mu m in diameter) by the droplet microfluidic technique. Intrathecally injected AcDX microspheres effectively reduce the traumatic lesion volume and inflammatory response in the injured spinal cord, protect the spinal cord neurons from apoptosis, and ultimately, recover the locomotor function of injured rats. The neuroprotective feature of AcDX microspheres is achieved by sequestering glutamate and calcium ions in cerebrospinal fluid. The scavenging of glutamate and calcium ion reduces the influx of calcium ions into neurons and inhibits the formation of reactive oxygen species. Consequently, AcDX microspheres attenuate the expression of proapoptotic proteins, Calpain, and Bax, and enhance the expression of antiapoptotic protein Bcl-2. Overall, AcDX microspheres protect traumatically injured spinal cord by alleviating the glutamate-induced excitotoxicity. This study opens an exciting perspective toward the application of neuroprotective AcDX for the treatment of severe neurological diseases.
  • Popova, Dina; Castren, Eero; Taira, Tomi (2017)
    Recent studies demonstrate that chronic administration of the widely used antidepressant fluoxetine (FLX) promotes neurogenesis, synaptogenesis and synaptic plasticity in the adult hippocampus, cortex and amygdala. However, the mechanisms underlying these effects and how are they related to the clinical antidepressant efficacy are still poorly understood. We show here that chronic FLX administration decreases hippocampus-associated neophobia in naive mice. In parallel, electrophysiological recordings in hippocampal CA3-CA1 circuitry revealed that the FLX treatment resulted in increased short and long-term plasticity likely attributed to changes in presynaptic function. These changes were accompanied by enhancement in the expression of proteins related to vesicular trafficking and release, namely synaptophysin, synaptotagmin 1, MUNC 18 and syntaxin 1. Thus, chronic FLX administration is associated with enhanced synaptic dynamics atypical of mature CA1 synapses, elevated hippocampal plasticity, improved hippocampus-dependent behavior as well as altered expression of synaptic proteins regulating neurotransmitter trafficking and release. The results support the idea that antidepressants can promote neuronal plasticity and show that they can increase the functional dynamic range and information processing in synaptic circuitries. (C) 2017 Elsevier Ltd. All rights reserved.
  • Koivuniemi, Raili; Hakkarainen, Tiina; Kiiskinen, Jasmi; Kosonen, Mika; Vuola, Jyrki; Valtonen, Jussi; Luukko, Kari; Kavola, Heli; Yliperttula, Marjo (2020)
    Objective: Skin graft donor site management is a concern particularly for elderly patients and patients with poor wound healing competence, and also because donor sites are a source of pain and discomfort. Although different types of dressings exist, there is no consensus regarding optimal dressing type on donor site care to promote healing, reduce pain, and improve patients' comfort. Approach: This prospective, single-center clinical trial evaluated the performance of nanofibrillar cellulose (NFC) wound dressing (FibDex (R) by UPM-Kymmene Corporation) for treatment of donor sites compared with a polylactide-based copolymer dressing. The study enrolled 24 patients requiring skin grafting with mean age of 49 +/- 18. The primary outcome measure was wound healing time. Secondary outcomes, the epithelialization, subjective pain, the scar appearance assessed using the Patient and Observer Scar Assessment Scale (POSAS), and skin elasticity and transepidermal water loss (TEWL), were evaluated at 1 and 6 months postoperatively. Results: No statistically significant differences were observed between NFC and copolymer dressings regarding wound healing time, epithelialization, experience of pain, or TEWL. Significant differences were observed in the POSAS results for thickness and vascularity in the Observer score, in the favor of NFC over copolymer dressing. Moreover, skin elasticity was significantly improved with NFC dressing in terms of viscoelasticity and elastic modulus at 1 month postoperatively. Innovation: NFC dressing is a new, green sustainable product for wound treatment without animal or human-origin components. Conclusion: NFC dressing provides efficient wound healing at skin graft donor sites and is comparable or even preferable compared with the copolymer dressing.
  • Liu, Zehua; Li, Yunzhan; Li, Wei; Lian, Wenhua; Kemell, Marianna; Hietala, Sami; Figueiredo, Patricia; Li, Li; Mäkilä, Ermei; Ma, Ming; Salonen, Jarno; Hirvonen, Jouni T.; Liu, Dongfei; Zhang, Hongbo; Deng, Xianming; Santos, Helder A. (2019)
    Here, an oxidation/acid dual-responsive nanohybrids/ark system was produced. The microfluidics-produced nanohybrids endow the system with an orchestrated cascade from wound detection, reactive oxygen species scavenging, drug release to hydrogel formation. The drug release behavior imitates the dynamic wound healing process, thus rendering an enhanced bio-mimetic regeneration.
  • Prisle, Nonne L.; Lin, Jack J.; Purdue, Sara; Lin, Haisheng; Meredith, J. Carson; Nenes, Athanasios (2019)
    The role of surfactants in governing water interactions of atmospheric aerosols has been a recurring topic in cloud microphysics for more than two decades. Studies of detailed surface thermodynamics are limited by the availability of aerosol samples for experimental analysis and incomplete validation of various proposed Kohler model frameworks for complex mixtures representative of atmospheric aerosol. Pollenkitt is a viscous material that coats grains of pollen and plays important roles in pollen dispersion and plant reproduction. Previous work suggests that it may also be an important contributor to pollen water uptake and cloud condensation nuclei (CCN) activity. The chemical composition of pollenkitt varies between species but has been found to comprise complex organic mixtures including oxygenated, lipid, and aliphatic functionalities. This mix of functionalities suggests that pollenkitt may display aqueous surface activity, which could significantly impact pollen interactions with atmospheric water. Here, we study the surface activity of pollenkitt from six different species and its influence on pollenkitt hygroscopicity. We measure cloud droplet activation and concentration-dependent surface tension of pollenkitt and its mixtures with ammonium sulfate salt. Experiments are compared to predictions from several thermodynamic models, taking aqueous surface tension reduction and surfactant surface partitioning into account in various ways. We find a clear reduction of surface tension by pollenkitt in aqueous solution and evidence for impact of both surface tension and surface partitioning mechanisms on cloud droplet activation potential and hygroscopicity of pollenkitt particles. In addition, we find indications of complex nonideal solution effects in a systematic and consistent dependency of pollenkitt hygroscopicity on particle size. The impact of pollenkitt surface activity on cloud microphysics is different from what is observed in previous work for simple atmospheric surfactants and more resembles recent observations for complex primary and secondary organic aerosol, adding new insight to our understanding of the multifaceted role of surfactants in governing aerosol-water interactions. We illustrate how the explicit characterization of pollenkitt contributions provides the basis for modeling water uptake and cloud formation of pollen and their fragments over a wide range of atmospheric conditions.
  • Haraguchi, Lumi; Asmala, Eero; Jakobsen, Hans H.; Carstensen, Jacob (2019)
    Dissolved organic matter (DOM) is an important component of nutrient cycling, but the role of different organisms controlling the processing of autochthonous DOM remains poorly understood. Aiming to characterize phytoplankton-derived DOM and the effects of complex pelagic communities on its dynamics, we incubated natural plankton communities from a temperate mesohaline estuary under controlled conditions for 18 days. The incubations were carried out in contrasting seasons (spring and autumn) and changes in the planktonic community (phytoplankton, bacteria and microzooplankton), nutrients and DOM were assessed. Our results highlight the complexity of DOM production and fate in natural planktonic communities. Small changes in DOM composition were observed in the experiments relative to the orders-of-magnitude variations experienced in the phytoplankton assembly. We argue that the tight coupling between microbial processing and DOM production by phytoplankton and grazers stabilizes variations in quantity and characteristics of autochthonous DOM, resulting in apparently homogeneous semi-labile DOM pool throughout the experiments. However, seasonal differences in the production and processing of DOM were observed, reflecting differences in the nutrient regimes and initial DOM characteristics in each experiment, but also likely influenced by changes in the successional status of the pelagic community. Acknowledging that characteristics of the DOM derived from phytoplankton growth can vary broadly, heterotrophic processing and successional status of the community are synergistically important factors for shaping those characteristics, and thus affecting the seasonal signature of the semi-labile autochthonous DOM pool.
  • Elovaara, Samu; Eronen-Rasimus, Eeva; Asmala, Eero; Tamelander, Tobias; Kaartokallio, Hermanni (2021)
    Microbial consumption of phytoplankton-derived organic carbon in the pelagic food web is an important component of the global C cycle. We studied C cycling in two phytoplankton-bacteria systems (non-axenic cultures of a dinoflagellate Apocalathium malmogiense and a cryptophyte Rhodomonas marina) in two complementary experiments. In the first experiment we grew phytoplankton and bacteria in nutrient-replete conditions and followed C processing at early exponential growth phase and twice later when the community had grown denser. Cell-specific primary production and total community respiration were up to 4 and 7 times higher, respectively, in the A. malmogiense treatments. Based on the optical signals, accumulating dissolved organic C (DOC) was degraded more in the R. marina treatments, and the rate of bacterial production to primary production was higher. Thus, the flow of C from phytoplankton to bacteria was relatively higher in R. marina treatments than in A. malmogiense treatments, which was further supported by faster C-14 transfer from phytoplankton to bacterial biomass. In the second experiment we investigated consumption of the phytoplankton-derived DOC by bacteria. DOC consumption and transformation, bacterial production, and bacterial respiration were all higher in R. marina treatments. In both experiments A. malmogiense supported a bacterial community predominated by bacteria specialized in the utilization of less labile DOC (class Bacteroidia), whereas R. marina supported a community predominated by copiotrophic Alphaand Gammaproteobacteria. Our findings suggest that large dinoflagellates cycle relatively more C between phytoplankton biomass and the inorganic C pool, whereas small cryptophytes direct relatively more C to the microbial loop.
  • Drago, Salvatore E.; Craparo, Emanuela F.; Luxenhofer, Robert; Cavallaro, Gennara (2021)
    In this paper, two amphiphilic graft copolymers were synthesized by grafting polylactic acid (PLA) as hydrophobic chain and poly(2-methyl-2-oxazoline) (PMeOx) or poly(2-methyl-2-oxazine) (PMeOzi) as hydrophilic chain, respectively, to a backbone of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA). These original graft copolymers were used to prepare nanoparticles delivering Zileuton in inhalation therapy. Among various tested methods, direct nanoprecipitation proved to be the best technique to prepare nanoparticles with the smallest dimensions, the narrowest dimensional distribution and a spherical shape. To overcome the size limitations for administration by inhalation, the nano-into-micro strategy was applied, encapsulating the nanoparticles in water-soluble mannitol-based microparticles by spray-drying. This process has allowed to produce spherical microparticles with the proper size for optimal lung deposition, and, once in contact with fluids mimicking the lung district, able to dissolve and release non-aggregated nanoparticles, potentially able to spread through the mucus, releasing about 70% of the drug payload in 24hours.
  • Lehtoranta, Jouni; Bendtsen, Jorgen; Lannergren, Christer; Saarijarvi, Erkki; Lindström, Magnus; Pitkanen, Heikki (2022)
    We studied the effects of pumping surface water down through the pycnocline (i.e. artificial ventilation) on hydrodynamics, oxygen concentrations, hydrogen sulfide, and nutrients in two anoxic coastal basins (Lannerstasundet and Sandofjarden). In addition, in a corresponding laboratory aquarium experiment, pumping of less saline surface water entrained dense bottom water with a mixing ratio of 6.8 and illustrated dispersal below the pycnocline. Oxygen saturation increased from 0 to 20%; oxygen penetrated poorly into the sediment of the aquarium. In the salinity-stratified Lannerstasundet basin, ventilation also oxidized the anoxic bottom water. The ventilation removed hydrogen sulfide and decreased the sub-pycnocline water pools of phosphorus and ammonium, which was not observed in a neighboring reference basin. The summertime ventilation warmed and made the sub-pycnocline water less saline. In the autumn, the inflows of cooled water from the surroundings with equal or higher salinity promoted its sinking in the relatively warm ventilated basin. The inflows maintained oxygen concentrations between 4 and 8 mg L-1 for months after the ventilation ended. In contrast to Lannerstasundet, ventilation did not prevent formation of anoxia and release of nutrients in the temperature stratified Sandofjarden. Here, the ventilation capacity was less than that in Lannerstasundet and ventilation expanded the sub-thermocline bottom area, warmed the bottom sediments, and probably displaced oxic water from the experimental area. The ventilation did not promote density conditions for inflows and no marked inflow-induced oxidation was observed after midsummer. We conclude that a significant amount of anoxic water was entrained into the ascending plume which reduced the oxygen content below the pycnocline ventilation in aquarium experiment. Additionally, summertime ventilation may improve the status of the salinity-stratified basins for further oxidation. The improvement occurs due to autumn cooling and favorable basin topography, which promote inflows of oxic water with larger density and thereby, renewal of bottom water in the pumped basin. The semi-enclosed and temperature-stratified basin cannot form such favorable density conditions for inflows and thus ventilation is less efficient.
  • Koskenpato, K.; Ainola, M.; Przybyla, B.; Kouri, V-P; Virkki, L.; Koskenpato, J.; Ristimaki, A.; Konttinen, Y. T. (2016)
    Objectives: Healthy human labial salivary glands produce epidermal growth factor (EGF). In Sjogren's syndrome (SS), EGF staining is diminished. SS is also associated with chronic autoimmune corpus gastritis. We therefore hypothesized that EGF secretion would be diminished in SS and that this could affect gastric target cells.Methods: Salivary EGF secretion in SS was compared to that in healthy controls using an enzyme-linked immunosorbent assay (ELISA). EGF receptor (EGFR) immunoreactive cells in the gastric corpus of healthy human subjects were analysed using immunostaining.Results: Salivary secretion of EGF was diminished in SS patients (232.4, range 52.6-618.4, vs. 756.6, range 105.3-1631.6 pg/min, p=0.002). Proton-pump positive parietal cells were mostly EGFR immunoreactive whereas very few pepsinogen I (PGI)-positive cells were EGFR positive.Conclusions: As EGF is relatively acid resistant, salivary gland-derived EGF might participate in an exo/endocrine mode of parietal cell maintenance in the gastric corpus. Deficiency of salivary gland-derived EGF in SS patients may cause impairment of gastric parietal cells resulting in exposure of immunogenic cryptic antigens and loss of immunological self-tolerance.
  • Niemistö, Juha; Silvonen, Soila; Horppila, Jukka (2020)
    Effects of hypolimnetic aeration (pumping of epilimnetic water into the hypolimnion) on the quantity of settling material in eutrophied Lake Vesijarvi, Finland were studied by comparing spatially comprehensive gross sedimentation rates as dry and organic matter prior to aeration activity and during two aerated years. Possible changes in the organic matter (as loss on ignition, LOI), carbon (C) and nitrogen (N) contents and changes in the C/N ratio of the settling material and surface sediment were quantified. Thermal stratification broke up earlier due to aeration and was followed by sedimentation peaks. The absolute amount of dry and organic matter as well as C and N settling to the lake bottom were significantly higher in the aerated years. Increased sedimentation rates were especially pronounced in the deep zones indicating enhanced sediment focusing. Increased sedimentation of C and N reflected higher primary production during the aerated years, which most likely was associated with increased temperature and turbulence and the subsequent regeneration and recycling of nutrients in the water body. Aeration seemed to slightly enhance degradation, but contrary to its ultimate aim, it failed to decrease the phosphorus content of the water column and deposits of organic material in the deep zones of the lake.
  • JET Contributors; Widdowson, Anna; Likonen, Jari; Mizohata, Kenichiro (2021)
    An assessment of the tritium (T) inventory in plasma facing components (PFC) during JET T and deuterium-tritium (DT) operations is presented based on the most comprehensive ex situ fuel retention data set on JET PFCs from the 2015-2016 ILW3 operating period is presented. The global fuel retention is 4.19 x 10(23) D atoms, 0.19% of injected fuel. The inner divertor remains the region of highest fuel retention (46.5%). The T inventory in PFCs at the end of JET operations is calculated as 7.48 x 10(22) atoms and is informative for accountancy, clean-up efficacy and waste liability assessments. The T accumulation rate at the upper inner divertor during JET DT operations has been used to assess the requirements and frequency of operation of a new laser induced desorption diagnostic to be installed on JET for the final DT experiments in 2023.
  • Vesikansa, Aino; Sakha, Prasanna; Kuja-Panula, Juha; Molchanova, Svetlana; Rivera Baeza, Claudio; Huttunen, Henri J.; Rauvala, Heikki; Taira, Tomi; Lauri, Sari E. (2012)
  • Chen, Yan; Wen, Jian Guo; Feng, Jin Jin; Wang, Yi He; Li, Tian Fang; Nurmi, Katariina; Eklund, Kari K.; Xing, Dong (2019)
    BACKGROUND: The treatment of nucleotide-binding domain and leucine-rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome-mediated pediatric inflammatory diseases is challenging. Here we studied whether cyclic adenosine monophosphate (cAMP) elevator forskolin could attenuate the nigericin-induced NLRP3-inflammasome activation and interleukin-1 beta (IL-1 beta) secretion in human macrophages. METHODS: The proteins and messenger RNA (mRNA) levels of inflammasome structural proteins and proinflammatory cytokines were measured in forskolin-stimulated nigericin-activated human THP-1 macrophages and primary macrophages. RESULTS: Activation of THP-1 macrophages with nigericin increased the mRNA expression of NLRP3, IL-1 beta, and caspase-1 (P <0.01). Forskolin stimulation had no effect on the mRNA expression of NLRP3, caspase-1, or IL-1 beta in nigericin-activated cells (P> 0.05), while their protein levels were significantly decreased (P <0.05). Forskolin-mediated increase in cytoplasmic cAMP in non-activated cells was attenuated in nigericin-activated macrophages (P <0.05). Basal IL-1 beta secretion increased from 584 to 2696 pg/ml (P <0.01) in nigericin-activated macrophages; forskolin dose-dependently reduced the nigericin-induced secretion of mature IL-1 beta (P <0.01). Forskolin also inhibited the IL-1 beta secretion from activated human primary macrophages. CONCLUSIONS: Forskolin inhibits the NLRP3 inflammasome activation and the secretion of mature IL-1 beta, in human macrophages. Forskolin and other cAMP elevator drugs could represent a novel approach for treatment of diseases associated with excessive inflammasome activation, like pediatric inflammatory diseases.