Investigations of Certain Organ Specific Toxic Effects of Titanium Dioxide Nnanoparticles by In Vivo and In Vitro Methods

The world of nanoparticles (NPs: particles with not more than 100 nm typical diameter at least in one dimension) has gained a great deal of attention in the last ca. 30 years in various fields of research, including life and health sciences. NPs can be cubical or spherical grains, but elongated structures: nano-rods, wires, tubes etc. also exist. This size lends some peculiar characteristics to the NPs, so properties and behavior of the same chemical substance in nano vs. more conventional states can be different. This is due to the high surface-to-volume ratio and to surface reactivity, and leads to biological, including toxicological, interactions not seen with traditional materials, resulting possibly in novel health risks. The relationship between elevated level of ambient airborne NPs and human morbidity and mortality has been generally accepted by now, and particulate air pollution has been recognized as an environmental carcinogenic agent. Among man-made NPs, by-products of various technological procedures, acting as pollutants, and purposefully produced nanomaterials are to be distinguished. Engineered nanomaterials are becoming part of everyday life, in form of NP-containing consumers’ products. The broad spectrum of application with concomitant human exposure raises the question of health risk. Here, a major problem is the lack of toxicity data for most manufactured NPs – and this is why nanotoxicology, an interdisciplinary field related to both environmental hygiene and nanotechnology, emerged. In case of exposure by NPs, the most likely entrance in the (human or animal) organism is, first of all for pollutants, but partly also for nanotechnological NPs, inhalation of air containing a nano-aerosol. NPs, deposited either in the nasopharynx or in the alveoli, are not held back by barriers like the alveolar and capillary wall, and reach other target organs by being phagocyted and transferred along the lymphatic system, or by different mechanisms including transcytosis, and finally are distributed throughout the body via the circulation. In case of consumers’ products, gastrointestinal and dermal uptake may also be of interest. In the aqueous microenvironment of living tissues, surface reactivity of NPs leads to generation of reactive oxygen species (ROS). The resulting oxidative stress can induce damage to biomolecules, primarily lipids and proteins, and finally induce inflammation and/or cytotoxicity. Titanium dioxide (TiO2) is a white, odorless, water insoluble soluble solid of high chemical stability and high melting temperature. It major crystal forms are anatase and rutile. TiO2 as white pigment is used also in the food and pharmaceutical industry. TiO2 NPs of various shapes (grains, rods, wires, tubes) have a broad range of application. Human exposure to TiO2 NPs may occur during manufacturing, processing, and use; in form of aerosols, suspensions or emulsions. The most health relevant routes of exposure in workplaces are inhalation and dermal exposure, while non-occupational exposure is most likely dermal or oral. Ill effects – increased oxidative stress, inflammation, lung damage – due to airborne TiO2 in humans suffering occupational exposure have been in fact documented and successfully modeled in animals. Nervous system effects would also be expected for an agent able to cross the blood-brain barrier and to cause oxidative stress. However, human data to this point are scarce. Animal experiments, done predominantly in mice and less in rats, showed various central nervous alterations including cell damage, altered synaptic transmission and plasticity, memory impairment and increased anxiety. Other organs, including the kidneys, also showed signs of damage – activation of inflammatory mediators, histological damage, decreased function – in rats and mice on TiO2 NP administration. These effects could be deduced to cellular uptake of nano-TiO2, followed by ROS generation, engulfment by lysosomes, and release of enzymes from the latter initiating inflammation and cell death. Exposure of humans to TiO2 NPs can take place both in occupational settings, in the residential environment, or during free-time activities, and certain properties of the TiO2 NPs suggest harmful effects on various organs and organ systems of humans or animals but the available reports on such effects are not yet conclusive. Based on the experience gained at the Department of Public Health in examining the toxicity of metal oxide NPs for over 10 years, and on the properties and possible effects of TiO2 NPs outlined above, it was decided to investigate in the present PhD work the alterations evoked by TiO2 NPs with a complex approach..

Possible neurotoxicity of titanium dioxide nanoparticles in a subacute rat model

Titanium dioxide nanoparticles (TiO2 NPs) have many industrial applications and also appear in various consumers’ goods including foods and medicines. This widespread application raises the question of a potential occupational, environmental and/or intentional human exposure and health hazard. Motility of NPs within the organism and surface reactivity of TiO2 NPs suggests, among others, potential nervous system tixicity. In the present work, rats were intratracheally exposed to TiO2 NPs and functional changes in the nervous system were examined using electrophysiological, behavioural and biochemical methods. The results verified to some extent the neurotoxicity of nano-titanium but also underlined the need for further investigations

Hot spots in density fingering of exothermic autocatalytic chemical fronts

A light field is commonly described by a two-plane representation with four dimensions. Refocused three-dimensional contents can be rendered from light field images. A method for capturing these images is by using cameras with microlens arrays. A dense sampling of the light field results in large amounts of redundant data. Therefore, an efficient compression is vital for a practical use of these data. In this paper, we propose a displacement intra prediction scheme with a maximum of two hypotheses for the compression of plenoptic contents from focused plenoptic cameras. The proposed scheme is further implemented into HEVC. The work is aiming at coding plenoptic captured contents efficiently without knowing underlying camera geometries. In addition, the theoretical analysis of the displacement intra prediction for plenoptic images is explained; the relationship between the compressed captured images and their rendered quality is also analyzed. Evaluation results show that plenoptic contents can be efficiently compressed by the proposed scheme. Bit rate reduction up to 60 percent over HEVC is obtained for plenoptic images, and more than 30 percent is achieved for the tested video sequences

Detection of exhaled methane levels for monitoring trauma-related haemorrhage following blunt trauma: study protocol for a prospective observational study

Early recognition and effective treatment of internal bleeding impose a cardinal challenge for trauma teams. The reduction of the superior mesenteric artery (SMA) blood flow is among the first compensatory responses to blood loss, thus being a promising candidate as a diagnostic tool for occult haemorrhage. Unfortunately, methods for monitoring the SMA flow have not been elaborated to date. Nevertheless, animal experiments suggest that exhaled methane (CH4) levels correspond to the SMA perfusion. We hypothesise that real-time detection of CH4 concentrations in the exhaled air is an applicable technique for the early recognition of haemorrhage in severely injured patients. We also hypothesise that exhaled CH4 levels reflect the volume of blood loss more accurately than conventional markers of blood loss and shock such as shock index, haemoglobin, base deficit, lactate, end-tidal carbon dioxide and sublingual microcirculatory indices.One hundred and eleven severely injured (Injury Severity Score ≥16), intubated, bleeding patients sustaining blunt trauma will be included in this prospective observational study. Blood loss will be detected with CT and estimated with CT-linked radiologic software. Exhaled CH4 concentrations will be monitored by attaching a near-infrared laser technique-based photoacoustic spectroscopy apparatus to the exhalation outlet of the ventilator on patient arrival. The primary outcome is the volume of blood loss. Need for massive transfusion and 24-hour mortality will constitute secondary outcomes. The relation of exhaled CH4 to study outcomes and its performance in predicting blood loss in comparison with conventional shock markers and microcirculatory indices will be tested.Our protocol (ID: 5400/2021-SZTE) has been registered on ClinicalTrials.gov (NCT04987411) and complies with the Declaration of Helsinki and has been approved by the medical ethics committee at the University of Szeged (Ref.nr.:121/2021-SZTE RKEB). It is in data collection phase, theresults will be shared with the scientific community through publication in a peer-reviewed journal.NCT04987411; ClinicalTrials.gov, registered on 27 July 2021

Pohjoismansin peruskurssi

Tämä aineisto on suunnattu soveltuvin osin viiden opintopisteen laajuisen mansin kielen alkeiskurssin kurssimateriaaliksi. Kurssin tavoitteena on oppia pohjoismansin perussanastoa sekä morfologian ja syntaksin perusteet: aineiston avulla voi saavuttaa Eurooppalaisen viitekehyksen tason B1. Kurssin jälkeen opiskelija pystyy ymmärtämään ja tuottamaan yksinkertaista mansinkielistä tekstiä sekä käymään lyhyitä keskusteluja mansiksi. Opiskelija tuntee ja tunnistaa tavallisimmat morfologiset päätteet ja osaa käyttää niitä kielen rakenteissa. Opiskelija hallitsee mansin kielen perussanaston ja osaa tarvittaessa etsiä sanoja sanakirjoista ja verkkoaineistoista. Materiaali on alun perin koottu mansin kielen alkeiskurssille Helsingin yliopiston suomalais-ugrilaisen kielentutkimuksen oppinaineen piirissä keväällä 2019. Tuolloin FT Susanna Virtanen aloitti yksikössä mansin kielen opetuksen vaiheessa, jossa se oli ollut tauolla vuosia. Hän päätti tehdä kurssien oppimateriaalit itse, koska ajantasaisia valmiita materiaaleja ei ollut. Niin syntyi ensin irrallisia luentomonisteita, joita alettiin kehittää jäntevämmäksi ja yhtenäisemmäksi kurssimateriaaliksi mm. opiskelijapalautteen avulla. Keväällä 2020 työhön liittyivät myös maisteri Csilla Horváth ja mansin kielen opettajan tutkinnon suorittanut toimittaja Tamara Merova, joiden panos työn onnistumiseen on ollut korvaamaton. Aineiston on tarkoitus täyttää akuutti ajantasaisen opetusmateriaalin tarve ja tuoda osansa suomalais-ugrilaisen kielentutkimuksen alan yliopistopedagogiseen kehitykseen. Mansin kielen opetuksella on Helsingin yliopistossa pitkät perinteet, mutta oppimateriaalit eivät ole kehittyneet ajan mukana. Rautaesiripun aikana ainoa saatavilla oleva aineisto oli 1800–1900-lukujen taitteessa kerätyt kansanrunoustekstit. Niiden käyttöä jatkettiin vielä rajojen avauduttuakin, koska uutta kirjallista aineistoa oli edelleen niukasti saatavilla. Länsimaisen tradition mukaisia oppimateriaaleja ei ole juuri tuotettu yliopistotasoiseen opetukseen. Nyt kuitenkin tilanne on korjaantumassa: tämän materiaalin toimittajat ovat saaneet Koneen säätiöltä rahoituksen alkeisoppikirjan toimittamiseen. Oppikirjan odotetaan ilmestyvän Suomalais-Ugrilaisen Seuran kustantamana vuonna 2023. Materiaaliin on koottu teoreettinen selostus jokaisesta kielioppiaiheesta. Aiheita havainnollistetaan käytännön esimerkein. Samalla opitaan mansin kielen perussanastoa. Jokaisen teoriaosuuden jälkeen rakenteita ja sanastoa harjoitellaan havainnollisin tehtävin. Kielenainekset esitetään kyrillistä kirjaimistoa käyttäen, koska se on mansiyhteisön itse käyttämä kirjoitustyyli. Kirjan tekstikappaleet ja kieliesimerkit on poimittu mm. mansin kielen lukemistoista ja ajankohtaisista sanomalehtiartikkeleista (ks. lähdeluettelo). Osa esimerkeistä on toimittajien itse luomia. Aineiston kuvitus on Papunetin ilmaisesta kuvapankista. Aineistoa käyttävän opettajan suositellaan valitsemaan aineistosta kurssin laajuuteen soveltuvat aihealueet. Esim. kappaleiden 13, 14 ja 15 aiheet voi jättää myös myöhempien kurssien teemoiks

Impairment of Mesenteric Perfusion as a Marker of Major Bleeding in Trauma Patients

The majority of potentially preventable mortality in trauma patients is related to bleeding; therefore, early recognition and effective treatment of hemorrhagic shock impose a cardinal challenge for trauma teams worldwide. The reduction in mesenteric perfusion (MP) is among the first compensatory responses to blood loss; however, there is no adequate tool for splanchnic hemodynamic monitoring in emergency patient care. In this narrative review, (i) methods based on flowmetry, CT imaging, video microscopy (VM), measurement of laboratory markers, spectroscopy, and tissue capnometry were critically analyzed with respect to their accessibility, and applicability, sensitivity, and specificity. (ii) Then, we demonstrated that derangement of MP is a promising diagnostic indicator of blood loss. (iii) Finally, we discussed a new diagnostic method for the evaluation of hemorrhage based on exhaled methane (CH4) measurement. Conclusions: Monitoring the MP is a feasible option for the evaluation of blood loss. There are a wide range of experimentally used methodologies; however, due to their practical limitations, only a fraction of them could be integrated into routine emergency trauma care. According to our comprehensive review, breath analysis, including exhaled CH4 measurement, would provide the possibility for continuous, non-invasive monitoring of blood loss

Methane Admixture Protects Liver Mitochondria and Improves Graft Function after Static Cold Storage and Reperfusion

Mitochondria are targets of cold ischemia-reperfusion (IR), the major cause of cell damage during static cold preservation of liver allografts. The bioactivity of methane (CH4) has recently been recognized in various hypoxic and IR conditions as having influence on many aspects of mitochondrial biology. We therefore hypothesized that cold storage of liver grafts in CH4-enriched preservation solution can provide an increased defence against organ dysfunction in a preclinical rat model of liver transplantation. Livers were preserved for 24 h in cold histidine–tryptophan–ketoglutarate (HTK) or CH4-enriched HTK solution (HTK-CH4) (n = 24 each); then, viability parameters were monitored for 60 min during normothermic isolated reperfusion and perfusate and liver tissue were collected. The oxidative phosphorylation capacity and extramitochondrial Ca2+ movement were measured by high resolution respirometry. Oxygen and glucose consumption increased significantly while hepatocellular damage was decreased in the HTK-CH4 grafts compared to the HTK group. Mitochondrial oxidative phosphorylation capacity was more preserved (128.8 ± 31.5 pmol/s/mL vs 201.3 ± 54.8 pmol/s/mL) and a significantly higher Ca2+ flux was detected in HTK-CH4 storage (2.9 ± 0.1 mV/s) compared to HTK (2.3 ± 0.09 mV/s). These results demonstrate the direct effect of CH4 on hepatic mitochondrial function and extramitochondrial Ca2+ fluxes, which may have contributed to improved graft functions and a preserved histomorphology after cold IR