Effect of photodynamic therapy on the extracellular matrix and associated components

In many countries, photodynamic therapy (PDT) has been recognized as a standard treatment for malignant conditions (for example, esophageal and lung cancers) and non-malignant ones such as age-related macular degeneration and actinic keratoses. The administration of a non-toxic photosensitizer, its selective retention in highly proliferating cells and the later activation of this molecule by light to form reactive oxygen species that cause cell death is the principle of PDT. Three important mechanisms are responsible for the PDT effectiveness: a) direct tumor cell kill; b) damage of the tumor vasculature; c) post-treatment immunological response associated with the leukocyte stimulation and release of many inflammatory mediators like cytokines, growth factors, components of the complement system, acute phase proteins, and other immunoregulators. Due to the potential applications of this therapy, many studies have been reported regarding the effect of the treatment on cell survival/death, cell proliferation, matrix assembly, proteases and inhibitors, among others. Studies have demonstrated that PDT alters the extracellular matrix profoundly. For example, PDT induces collagen matrix changes, including cross-linking. The extracellular matrix is vital for tissue organization in multicellular organisms. In cooperation with growth factors and cytokines, it provides cells with key signals in a variety of physiological and pathological processes, for example, adhesion/migration and cell proliferation/differentiation/death. Thus, the focus of the present paper is related to the effects of PDT observed on the extracellular matrix and on the molecules associated with it, such as, adhesion molecules, matrix metalloproteinases, growth factors, and immunological mediators.

Comparative effects of organic and inorganic mercury on in vivo dopamine release in freely moving rats

The present study was carried out in order to compare the effects of administration of organic (methylmercury, MeHg) and inorganic (mercury chloride, HgCl 2 ) forms of mercury on in vivo dopamine (DA) release from rat striatum. Experiments were performed in conscious and freely moving female adult Sprague-Dawley (230-280 g) rats using brain microdialysis coupled to HPLC with electrochemical detection. Perfusion of different concentrations of MeHg or HgCl 2 (2 µL/min for 1 h, N = 5-7/group) into the striatum produced significant increases in the levels of DA. Infusion of 40 µM, 400 µM, or 4 mM MeHg increased DA levels to 907 ± 31, 2324 ± 156, and 9032 ± 70% of basal levels, respectively. The same concentrations of HgCl 2 increased DA levels to 1240 ± 66, 2500 ± 424, and 2658 ± 337% of basal levels, respectively. These increases were associated with significant decreases in levels of dihydroxyphenylacetic acid and homovallinic acid. Intrastriatal administration of MeHg induced a sharp concentration-dependent increase in DA levels with a peak 30 min after injection, whereas HgCl 2 induced a gradual, lower (for 4 mM) and delayed increase in DA levels (75 min after the beginning of perfusion). Comparing the neurochemical profile of the two mercury derivatives to induce increases in DA levels, we observed that the time-course of these increases induced by both mercurials was different and the effect produced by HgCl 2 was not concentration-dependent (the effect was the same for the concentrations of 400 µM and 4 mM HgCl 2 ). These results indicate that HgCl 2 produces increases in extracellular DA levels by a mechanism differing from that of MeHg.

Synaptic vesicle pool size, release probability and synaptic depression are sensitive to Ca2+ buffering capacity in the developing rat calyx of Held

The calyx of Held, a specialized synaptic terminal in the medial nucleus of the trapezoid body, undergoes a series of changes during postnatal development that prepares this synapse for reliable high frequency firing. These changes reduce short-term synaptic depression during tetanic stimulation and thereby prevent action potential failures during a stimulus train. We measured presynaptic membrane capacitance changes in calyces from young postnatal day 5-7 (p5-7) or older (p10-12) rat pups to examine the effect of calcium buffer capacity on vesicle pool size and the efficiency of exocytosis. Vesicle pool size was sensitive to the choice and concentration of exogenous Ca2+ buffer, and this sensitivity was much stronger in younger animals. Pool size and exocytosis efficiency in p5-7 calyces were depressed by 0.2 mM EGTA to a greater extent than with 0.05 mM BAPTA, even though BAPTA is a 100-fold faster Ca2+ buffer. However, this was not the case for p10-12 calyces. With 5 mM EGTA, exocytosis efficiency was reduced to a much larger extent in young calyces compared to older calyces. Depression of exocytosis using pairs of 10-ms depolarizations was reduced by 0.2 mM EGTA compared to 0.05 mM BAPTA to a similar extent in both age groups. These results indicate a developmentally regulated heterogeneity in the sensitivity of different vesicle pools to Ca2+ buffer capacity. We propose that, during development, a population of vesicles that are tightly coupled to Ca2+ channels expands at the expense of vesicles more distant from Ca2+ channels.

Lung hyperinflation stimulates the release of inflammatory mediators in spontaneously breathing subjects

Lung hyperinflation up to vital capacity is used to re-expand collapsed lung areas and to improve gas exchange during general anesthesia. However, it may induce inflammation in normal lungs. The objective of this study was to evaluate the effects of a lung hyperinflation maneuver (LHM) on plasma cytokine release in 10 healthy subjects (age: 26.1 ± 1.2 years, BMI: 23.8 ± 3.6 kg/m²). LHM was performed applying continuous positive airway pressure (CPAP) with a face mask, increased by 3-cmH2O steps up to 20 cmH2O every 5 breaths. At CPAP 20 cmH2O, an inspiratory pressure of 20 cmH2O above CPAP was applied, reaching an airway pressure of 40 cmH2O for 10 breaths. CPAP was then decreased stepwise. Blood samples were collected before and 2 and 12 h after LHM. TNF-α, IL-1β, IL-6, IL-8, IL-10, and IL-12 were measured by flow cytometry. Lung hyperinflation significantly increased (P < 0.05) all measured cytokines (TNF-α: 1.2 ± 3.8 vs 6.4 ± 8.6 pg/mL; IL-1β: 4.9 ± 15.6 vs 22.4 ± 28.4 pg/mL; IL-6: 1.4 ± 3.3 vs 6.5 ± 5.6 pg/mL; IL-8: 13.2 ± 8.8 vs 33.4 ± 26.4 pg/mL; IL-10: 3.3 ± 3.3 vs 7.7 ± 6.5 pg/mL, and IL-12: 3.1 ± 7.9 vs 9 ± 11.4 pg/mL), which returned to basal levels 12 h later. A significant correlation was found between changes in pro- (IL-6) and anti-inflammatory (IL-10) cytokines (r = 0.89, P = 0.004). LHM-induced lung stretching was associated with an early inflammatory response in healthy spontaneously breathing subjects.

Addressing conflicts of interest in the research paper: a societal demand in contemporary science?

In the last decade, dialogue between science and society has found a forum in an increasing number of publications on topics such as public engagement with science and public trust in science. Concerning the latter, issues that include cases of research misconduct, accountability in research, and conflicts of interest (COIs) have shaped global discussions on the communication of science. In the publication setting, the perception that hiding COIs and/or not managing them well may affect public trust in the research record has grown among editors. We conducted a search for editorials addressing COIs between 1989 and 2011, using four major databases: Medline/PubMed, Embase, Scopus, and Web of Knowledge. We explored the content of these editorials and the relationship they established between COIs and the public trust in science. Our results demonstrate that the relationship between disclosure of COIs and public trust in science has become a major concern among editors. We, thus, argue that COIs should be discussed more openly and frequently in graduate courses in the sciences, around the globe, not only in biomedical but also in non-biomedical areas. This is a critical issue in contemporary science, as graduate students are the future voices and decision-makers of the research community. Therefore, COIs, especially in the broader context of science and society, merit closer attention from policymakers, researchers, and educators. At times of great expectations for public engagement with science, mishandling of COIs may have undesirable consequences for public engagement with science and confidence in the scientific endeavor.

Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats

In cardiomyocytes, calcium (Ca2+) release units comprise clusters of intracellular Ca2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F0), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F0, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes.

Central release of nitric oxide mediates antinociception induced by aerobic exercise

Nitric oxide (NO) is a soluble gas that participates in important functions of the central nervous system, such as cognitive function, maintenance of synaptic plasticity for the control of sleep, appetite, body temperature, neurosecretion, and antinociception. Furthermore, during exercise large amounts of NO are released that contribute to maintaining body homeostasis. Besides NO production, physical exercise has been shown to induce antinociception. Thus, the present study aimed to investigate the central involvement of NO in exercise-induced antinociception. In both mechanical and thermal nociceptive tests, central [intrathecal (it) and intracerebroventricular (icv)] pretreatment with inhibitors of the NO/cGMP/KATP pathway (L-NOArg, ODQ, and glybenclamide) prevented the antinociceptive effect induced by aerobic exercise (AE). Furthermore, pretreatment (it, icv) with specific NO synthase inhibitors (L-NIO, aminoguanidine, and L-NPA) also prevented this effect. Supporting the hypothesis of the central involvement of NO in exercise-induced antinociception, nitrite levels in the cerebrospinal fluid increased immediately after AE. Therefore, the present study suggests that, during exercise, the NO released centrally induced antinociception.

Effects of propofol on lipopolysaccharide-induced expression and release of HMGB1 in macrophages

This study aimed to determine the effects of different concentrations of propofol (2,6-diisopropylphenol) on lipopolysaccharide (LPS)-induced expression and release of high-mobility group box 1 protein (HMGB1) in mouse macrophages. Mouse macrophage cell line RAW264.7 cells were randomly divided into 5 treatment groups. Expression levels of HMGB1 mRNA were detected using RT-PCR, and cell culture supernatant HMGB1 protein levels were detected using enzyme-linked immunosorbent assay (ELISA). Translocation of HMGB1 from the nucleus to the cytoplasm in macrophages was observed by Western blotting and activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus was detected using ELISA. HMGB1 mRNA expression levels increased significantly in the cell culture supernatant and in cells after 24 h of stimulating RAW264.7 cells with LPS (500 ng/mL). However, HMGB1 mRNA expression levels in the P2 and P3 groups, which received 500 ng/mL LPS with 25 or 50 μmol/mL propofol, respectively, were significantly lower than those in the group receiving LPS stimulation (P<0.05). After stimulation by LPS, HMGB1 protein levels were reduced significantly in the nucleus but were increased in the cytoplasm (P<0.05). Simultaneously, the activity of NF-κB was enhanced significantly (P<0.05). After propofol intervention, HMGB1 translocation from the nucleus to the cytoplasm and NF-κB activity were inhibited significantly (each P<0.05). Thus, propofol can inhibit the LPS-induced expression and release of HMGB1 by inhibiting HMGB1 translocation and NF-κB activity in RAW264.7 cells, suggesting propofol may be protective in patients with sepsis.

Methylmercury inhibits prolactin release in a cell line of pituitary origin

Heavy metals, such as methylmercury, are key environmental pollutants that easily reach human beings by bioaccumulation through the food chain. Several reports have demonstrated that endocrine organs, and especially the pituitary gland, are potential targets for mercury accumulation; however, the effects on the regulation of hormonal release are unclear. It has been suggested that serum prolactin could represent a biomarker of heavy metal exposure. The aim of this study was to evaluate the effect of methylmercury on prolactin release and the role of the nitrergic system using prolactin secretory cells (the mammosomatotroph cell line, GH3B6). Exposure to methylmercury (0-100 μM) was cytotoxic in a time- and concentration-dependent manner, with an LC50 higher than described for cells of neuronal origin, suggesting GH3B6 cells have a relative resistance. Methylmercury (at exposures as low as 1 μM for 2 h) also decreased prolactin release. Interestingly, inhibition of nitric oxide synthase by N-nitro-L-arginine completely prevented the decrease in prolactin release without acute neurotoxic effects of methylmercury. These data indicate that the decrease in prolactin production occurs via activation of the nitrergic system and is an early effect of methylmercury in cells of pituitary origin.

Structural dynamics in the global pulp and paper industry

The pulp and paper industry is currently facing broad structural changes due to global shifts in demand and supply. These changes have significant impacts on national economies worldwide. Planted forests (especially eucalyptus) and recovered paper have quickly increased their importance as raw material for paper and paperboard production. Although advances in information and communication technologies could reduce the demand for communication papers, and the growth of paper consumption has indeed flattened in developed economies, particularly in North America and Western Europe, the consumption is increasing on a global scale. Moreover, the focal point of production and consumption is moving from the Western world to the rapidly growing markets of Southeast Asia. This study analyzes how the so-called megatrends (globalization, technological development, and increasing environmental awareness) affect the pulp and paper industry’s external environment, and seeks reliable ways to incorporate the impact of the megatrends on the models concerning the demand, trade, and use of paper and pulp. The study expands current research in several directions and points of view, for example, by applying and incorporating several quantitative methods and different models. As a result, the thesis makes a significant contribution to better understand and measure the impacts of structural changes on the pulp and paper industry. It also provides some managerial and policy implications.

Feasibility of industrial implementation of laser cutting into paper making machine

Laser cutting implementation possibilities into paper making machine was studied as the main objective of the work. Laser cutting technology application was considered as a replacement tool for conventional cutting methods used in paper making machines for longitudinal cutting such as edge trimming at different paper making process and tambour roll slitting. Laser cutting of paper was tested in 70’s for the first time. Since then, laser cutting and processing has been applied for paper materials with different level of success in industry. Laser cutting can be employed for longitudinal cutting of paper web in machine direction. The most common conventional cutting methods include water jet cutting and rotating slitting blades applied in paper making machines. Cutting with CO2 laser fulfils basic requirements for cutting quality, applicability to material and cutting speeds in all locations where longitudinal cutting is needed. Literature review provided description of advantages, disadvantages and challenges of laser technology when it was applied for cutting of paper material with particular attention to cutting of moving paper web. Based on studied laser cutting capabilities and problem definition of conventional cutting technologies, preliminary selection of the most promising application area was carried out. Laser cutting (trimming) of paper web edges in wet end was estimated to be the most promising area where it can be implemented. This assumption was made on the basis of rate of web breaks occurrence. It was found that up to 64 % of total number of web breaks occurred in wet end, particularly in location of so called open draws where paper web was transferred unsupported by wire or felt. Distribution of web breaks in machine cross direction revealed that defects of paper web edge was the main reason of tearing initiation and consequent web break. The assumption was made that laser cutting was capable of improvement of laser cut edge tensile strength due to high cutting quality and sealing effect of the edge after laser cutting. Studies of laser ablation of cellulose supported this claim. Linear energy needed for cutting was calculated with regard to paper web properties in intended laser cutting location. Calculated linear cutting energy was verified with series of laser cutting. Practically obtained laser energy needed for cutting deviated from calculated values. This could be explained by difference in heat transfer via radiation in laser cutting and different absorption characteristics of dry and moist paper material. Laser cut samples (both dry and moist (dry matter content about 25-40%)) were tested for strength properties. It was shown that tensile strength and strain break of laser cut samples are similar to corresponding values of non-laser cut samples. Chosen method, however, did not address tensile strength of laser cut edge in particular. Thus, the assumption of improving strength properties with laser cutting was not fully proved. Laser cutting effect on possible pollution of mill broke (recycling of trimmed edge) was carried out. Laser cut samples (both dry and moist) were tested on the content of dirt particles. The tests revealed that accumulation of dust particles on the surface of moist samples can take place. This has to be taken into account to prevent contamination of pulp suspension when trim waste is recycled. Material loss due to evaporation during laser cutting and amount of solid residues after cutting were evaluated. Edge trimming with laser would result in 0.25 kg/h of solid residues and 2.5 kg/h of lost material due to evaporation. Schemes of laser cutting implementation and needed laser equipment were discussed. Generally, laser cutting system would require two laser sources (one laser source for each cutting zone), set of beam transfer and focusing optics and cutting heads. In order to increase reliability of system, it was suggested that each laser source would have double capacity. That would allow to perform cutting employing one laser source working at full capacity for both cutting zones. Laser technology is in required level at the moment and do not require additional development. Moreover, capacity of speed increase is high due to availability high power laser sources what can support the tendency of speed increase of paper making machines. Laser cutting system would require special roll to maintain cutting. The scheme of such roll was proposed as well as roll integration into paper making machine. Laser cutting can be done in location of central roll in press section, before so-called open draw where many web breaks occur, where it has potential to improve runability of a paper making machine. Economic performance of laser cutting was done as comparison of laser cutting system and water jet cutting working in the same conditions. It was revealed that laser cutting would still be about two times more expensive compared to water jet cutting. This is mainly due to high investment cost of laser equipment and poor energy efficiency of CO2 lasers. Another factor is that laser cutting causes material loss due to evaporation whereas water jet cutting almost does not cause material loss. Despite difficulties of laser cutting implementation in paper making machine, its implementation can be beneficial. The crucial role in that is possibility to improve cut edge strength properties and consequently reduce number of web breaks. Capacity of laser cutting to maintain cutting speeds which exceed current speeds of paper making machines what is another argument to consider laser cutting technology in design of new high speed paper making machines.

Paper- and membrane-based ion-modulated electronics

Avhandlingen handlar om pappers- och membranbaserad jonmodulerad elektronik. Målet med forskningen har varit att utveckla billig, miljövänlig och brännbar elektronik, som kan användas i vardagliga engångsprodukter. Baskomponenterna som utvecklas och presenteras i avhandlingen är transistorer och kondensatorer. Mer komplicerad logisk kretselektronik demonstreras också med hjälp av dessa komponenter. Substraten som utnyttjas vid framställningen av dessa elektroniska komponenter är papper och membran. Dessa substrat är flexibla, hållbara, billiga, miljövänliga, etc. och därför väl anpassade för befintliga tryckteknologier. Själva baskomponenterna framställs sedan på dessa substrat genom att trycka flera skikt på varandra, där varje enskilt skikt är ett individuellt material. Detta är möjligt eftersom de organiska materialen som används i dessa komponenter är upplösta i ett lösningsmedel och kan därmed tryckas på samma sätt som ett vanligt bläck. Ett tredimensionellt objekt kan på detta sätt framställas. I avhandlingen presenteras flera olika typer av transistorer, men den gemensamma nämnaren bland dessa är att isolatorn är en jonledare. Denna, ganska ovanliga, transistormodellen har den stora fördelen att lågspänningskomponenter kan relativt enkelt framställas. Det som är speciellt med våra transistorer är att vi har använt miljövänliga jonledare. Detta, bl.a., leder till att våra komponenter visar både god prestanda, tillika som de är miljövänliga. I avhandlingen demonstrerar vi även tryckta superkondensatorer, en motsvarighet till laddningsbara batterier, konstruerade på papper med aktiverat kol och miljövänliga jonledare. De mest komplicerade logiska kretsar som demonstreras i denna avhandling är ring-oscillatorer och 1-bits-minnen konstruerade på papper. --------------------------------------------- Väitöskirja käsittelee paperille ja polymeerikalvolle tulostettua ionimoduloitua elektroniikkaa. Tutkimuksen tavoitteena oli kehittää edullista, ympäristöystävällistä ja polttokelpoista elektroniikkaa, jota voidaan käyttää esim. tavanomaisissa kertakäyttötuotteissa. Väitöskirjassa esitellään erilaisia transistoreita ja kondensaattoreita. Näitä elektronisia peruskomponentteja käyttäen demonstroidaan myös monimutkaisempia loogisia piirejä. Komponenttien valmistuksessa alustana käytettiin paperia ja polymeerikalvoa. Valitut alustat ovat joustavia ja kestäviä, ja ovat siksi hyvin yhteensopivia olemassa olevien tulostusmenetelmien kanssa. Peruskomponentit valmistettiin tulostamalla eri materiaaleja päällekkäin. Komponenteissa käytettävät orgaaniset aineet ovat liuenneessa muodossa musteessa, joka voidaan tulostaa samalla periaatteella kuin mikä tahansa normaali muste. Tällä menetelmällä voidaan valmistaa myös kolmiulotteisia tuotteita. Väitöskirjassa esitellään useita erityyppisiä transistoreita, joissa yhdistävänä tekijänä on ionisesti johtava eriste. Tällaista suhteellisen harvinaista transistorityyppiä käyttämällä voidaan mahdollistaa matala-jännitteisten komponenttien yksinkertainen valmistus. Valmistettujen transistoreiden etu on ionisten nesteiden ympäristöystävällisyys. Elektroniset komponentit ovat täten hyviä suorituskyvyltään, mutteivät haitallisia ympäristölle. Väitöskirjassa demonstroidaan myös tulostettujen superkondensaattoreiden, eli ladattavien paristojen vastineiden, valmistus paperille aktiivihiiltä ja ionisia nesteitä käyttäen. Kaikkein monimutkaisimmat loogiset piirit, jotka tässä väitöskirjassa esitellään, ovat rengasoskillaattorit sekä 1-bittinen paperille valmistettu muisti.

Carbon footprint of recycled paper

Industrial production of pulp and paper is an intensive consumer of energy, natural resources, and chemicals that result in a big carbon footprint of the final product. At present companies and industries aspire to calculate their gas emissions into the atmosphere in order to afterwards reduce atmospheric contamination. One of the approaches allowing to increase carbon burden from the pulp and paper manufacture is paper recycling. The general purpose of the current paper is to establish methods of quantifying and minimizing the carbon footprint of paper. The first target of this research is to derive a mathematical relationship between virgin fibre requirements with respect to the amount of recycled paper used in the pulp. One more purpose is to establish a model to be used to clarify the contribution of recycling and transportation to decreasing carbon dioxide emissions. For this study sensitivity analysis is used to investigate the robustness of obtained results. The results of the present study show that an increasing of recycling rate does not always lead to minimizing the carbon footprint. Additionally, we derived that transportation of waste paper throughout distances longer than 5800 km has no sense because the use of that paper will only increase carbon dioxide emissions and it is better to reject recycling at all. Finally, we designed the model for organization of a new supply chain of paper product to a customer. The models were implemented as reusable MATLAB frameworks.