Reactive oxygen species in inflammation

Chronic inflammation is the underlying cause of many common disabling conditions such as rheumatoid arthritis (RA), multiple sclerosis, coeliac disease, type I diabetes and coronary artery disease. NOX2 complex derived reactive oxygen species (ROS) are known to regulate joint inflammation in rats and mice, and additionally recent genetic evidence associates phagocyte ROS and the development RA in humans. Ncf1mutated mice have lost the functionality of their NOX2 complex and thus have no phagocyte ROS production. These mice suffer from exacerbated arthritis. The immune suppressive effect of the NOX2 complex derived ROS is mediated by monocytes/macrophages that downregulate the activation of autoreactive T cells. The aim of this thesis was to study how ROS modulate immune responses in different arthritis models and in tumor development. Additionally, genome wide gene expression profiling was carried out to assess the global effects of NOX2 complex derived ROS. Firstly, these results confirmed the potent anti-inflammatory nature of phagocyte ROS in arthritis models that were driven by the adaptive immune system. Secondly, arthritis models with predominantly innate immunity induced pathophysiology were moderately enhanced by phagocyte, more specifically, neutrophil derived ROS. Thirdly, the ROS induced immune suppression mediated by the adaptive immune system allowed development of bigger implanted tumors, while phagocyte ROS production did not affect the development of spontaneously growing tumors. Lastly, genome wide gene expression analysis revealed that both humans and mice with abrogated phagocyte NOX2 complex ROS production had an enhanced type I interferon signature in blood, reflecting their hyperinflammatory immune status.

Do blood components affect the production of reactive oxygen species (ROS) by equine synovial cells in vitro?

Blood-derived products are commonly administered to horses and humans to treat many musculoskeletal diseases, due to their potential antioxidant and anti-inflammatory effects. Nevertheless, antioxidant effects have never been shown upon horse synovial fluid cells in vitro. If proved, this could give a new perspective to justify the clinical application of blood-derived products. The aim of the present study was to investigate the antioxidant effects of two blood-derived products - plasma (unconditioned blood product - UBP) and a commercial blood preparation (conditioned blood product - CBP)¹ - upon stimulated equine synovial fluid cells. Healthy tarsocrural joints (60) were tapped to obtain synovial fluid cells; these cells were pooled, processed, stimulated with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA), and evaluated by flow cytometry for the production of reactive oxygen species (ROS). Upon addition of any blood-derived product here used - UBP and CBP - there was a significant decrease in the oxidative burst of synovial fluid cells (P<0.05). There was no difference between UBP and CBP effects. In conclusion, treatment of stimulated equine synovial cells with either UBP or CBP efficiently restored their redox equilibrium.

Clinical and blood gasometric parameters during Vaquejada competition

ABSTRACT: Clinical and complementary analysis are good alternatives to evaluate physiological demand in performance horses. The aim of this study was to assess whether the physical effort variation of the three-day Vaquejada competition (a Brazilian form of bullfighting) reflected in clinical and blood gasometric changes. During the competition eight sprints have been performed on the first day (D1), eight on the second (D2) and three on the last one (D3). Ten horses were evaluated by checking heart and respiratory rates and collecting blood samples for use in portable chemistry analyzer. Through that, it was assessed potential of hydrogen ion (pH), carbon dioxide pressure (pCO2), bicarbonate (HCO3-) and titratable base concentration (cBase). Evaluations were carried with resting of at least twenty hours, before physical activity (D0), as control parameter, and up to thirty minutes after each sprint. Clinical parameters have increased on D1, D2 and D3, when compared to D0, which demonstrated the increased demand for substrate and oxygen to the cells.. Blood gasometric trial showed reductions of all variables, most marked between D1 and D2. It was verified less alteration of all clinical and blood gasometric parameters in D3 against D0. We concluded that the change effort between days of competition influenced the clinical and blood gas parameters, demonstrating appropriate physiological response. The data were presented as mean and standard error of the mean (mean ± SEM) obtained in different days. Normality was confirmed by the Kolmogorov-Sminov test and data were compared by one-way ANOVA, followed by post-test Holm-Sidak (GraphPad Prism 2.6 for Windows, GraphPad Software, San Diego, CA, USA). P≤0.05 was considered as statistically significant.

Influência dos Íons Mg, Ca, Fe, Cu e Zn sobre a tensão superficial estática de soluções contendo surfatante

O objetivo do estudo foi avaliar a influência da presença de cinco íons em uma calda de pulverização contendo o surfatante Aterbane. A tensão superficial foi analisada por meio da medição da massa de um conjunto de 25 gotas, com quatro repetições constituindo um tratamento. O trabalho foi dividido em duas etapas. Na primeira, os tratamentos foram combinados em esquema fatorial 9x5x2, sendo nove concentrações do surfatante Aterbane (0,01; 0,025; 0,05; 0,1; 0,2; 0,5; 1; 2; e 3%), cinco íons (Mg++, Ca++, Fe+++, Cu+++ e Zn+++) e duas concentrações desses elementos (10 e 100 ppm). Na segunda etapa, os tratamentos foram combinados em esquema fatorial 5x5x1, utilizandose os mesmos cinco elementos (Mg++, Ca++, Fe+++, Cu+++ e Zn+++), em cinco concentrações (1, 5, 20, 50 e 200 ppm), com apenas uma concentração do surfatante Aterbane (0,025%). Outros nove tratamentos permitiram avaliar as tensões superficiais das concentrações do surfatante (0,01; 0,025; 0,05; 0,1; 0,2; 0,5; 1; 2; e 3%) sem a adição dos íons. Os resultados mostraram que houve interferência dos íons sobre as soluções, já que, com exceção do Fe+++ (na concentração de 10 e 100 ppm) e do Cu+++ (na concentração de 100 ppm), todos os íons reduziram a tensão mínima alcançada e aumentaram a eficiência do surfatante, implicando benefícios à ação do surfatante e sobre as características de possíveis soluções de aplicação. Todos os íons avaliados promoveram reduções nas tensões superficiais de soluções do surfatante na concentração de 0,025%.

Mannen som objekt och problem : Heikki Waris och betydelsen av kön i vetenskaplig socialpolitik, ca 1930-1970

I avhandlingen analyseras betydelsen av kön i den vetenskapliga socialpolitiken vid 1900-talets mitt, i synnerhet med fokus på Heikki Waris (1901–1989) produktion. Waris var Finlands första professor i socialpolitik, som efter andra världskriget etablerades som ett akademiskt ämne vid de finländska universiteten, och Waris blev känd som en av tidens främsta auktoriteter på den finländska socialpolitiken. Vid en tid då välfärdsstaten etablerades och samhället genomgick en snabb moderniseringsprocess, fokuserade den socialpolitiska forskningen på problem och frågor som främst ansågs beröra den manliga delen av befolkningen, såsom alkoholkonsumtion och relationer inom det industriella arbetet. Detta trots att de nordiska staterna senare skulle bli kända som så kallade kvinnovänliga välfärdsstater, där frågor om kvinnors position och jämställdhet beaktades. I avhandlingen belyses hur de texter Waris skrev, samt den forskning som han initierade, skapade ideal baserade på sundhet, ekonomiskt ansvarstagande, aktivitet och medvetenhet samt hur dessa ideal var kopplade till män och manlighet. Förutom att visa hur ideal konstruerades, studeras även de olika formerna och funktionerna av kön i den socialpolitiska litteraturen. Behandlades kön endast som demografisk kategori eller fanns det ett djupare intresse för mäns och kvinnors positioner och roller? Vilka förhållanden ville Waris och de andra socialpolitikerna belysa med att lyfta fram frågor om kön i sina texter? Waris var även en auktoritet på den snabba moderniseringsprocess som Finland hade genomgått sedan industrialiseringen vid 1800-talets slut. I avhandlingen argumenteras för att män och kvinnor på varierande sätt blev symboler för samhällelig förändring. ------------------------ Väitöskirjassa tutkitaan sukupuolen merkitystä sosiaalipolitiikan tutkimuksessa 1900-luvun puolivälissä. Lähtökohtana on Heikki Wariksen (1901–1989) tieteellinen tuotanto. Waris toimi Suomen ensimmäisenä sosiaalipolitiikan professorina ja kehitti sosiaalipolitiikkaa akateemisena aiheena Suomessa toisen maailmansodan jälkeen. Waris tunnettiin yhtenä aikansa merkittävimpänä suomalaisen sosiaalipolitiikan asiantuntijana. Hyvinvointivaltion rakentumisaikana sosiaalipolitiikan tutkimus keskittyi miehiin liittyviin ongelmiin ja kysymyksiin, kuten alkoholin kulutukseen. Väitöskirjassa osoitetaan miten Wariksen teksteissä, ja Wariksen ohjaamissa väitöskirjoissa rakennettiin terveellisyydelle, elättäjyydelle, aktiivisuudelle sekä tietoisuudelle pohjautuva ihanne, joka oli kytketty miehiin ja miehuuteen. Lisäksi tutkitaan sukupuolen muotoja ja funktioita sosiaalipoliittisessa kirjallisuudessa. Oliko sukupuoli pelkkä väestöllinen kategoria vai osoittivatko sosiaalipolitiikan tutkijat syvällisempää mielenkiintoa miesten ja naisten asemaa sekä rooleja kohtaan? Mitkä asiat huomioitiin sukupuolen avulla? Waris oli myös industrialismin aiheuttaman yhteiskuntamuutoksen asiantuntija. Väitöskirjassa osoitetaan miten miehiä ja naisia käsiteltiin eri tavalla muutoksen symboleina.

Deoxygenation of fatty acids for production of fuels and chemicals

The decreasing fossil fuel resources combined with an increasing world energy demand has raised an interest in renewable energy sources. The alternatives can be solar, wind and geothermal energies, but only biomass can be a substitute for the carbon–based feedstock, which is suitable for the production of transportation fuels and chemicals. However, a high oxygen content of the biomass creates challenges for the future chemical industry, forcing the development of new processes which allow a complete or selective oxygen removal without any significant carbon loss. Therefore, understanding and optimization of biomass deoxygenation processes are crucial for the future bio–based chemical industry. In this work, deoxygenation of fatty acids and their derivatives was studied over Pd/C and TiO2 supported noble metal catalysts (Pt, Pt–Re, Re and Ru) to obtain future fuel components. The 5 % Pd/C catalyst was investigated in semibatch and fixed bed reactors at 300 °C and 1.7–2 MPa of inert and hydrogen–containing atmospheres. Based on extensive kinetic studies, plausible reaction mechanisms and pathways were proposed. The influence of the unsaturation in the deoxygenation of model compounds and industrial feedstock – tall oil fatty acids – over a Pd/C catalyst was demonstrated. The optimization of the reaction conditions suppressed the formation of by–products, hence high yields and selectivities towards linear hydrocarbons and catalyst stability were achieved. Experiments in a fixed bed reactor filled with a 2 % Pd/C catalyst were performed with stearic acid as a model compound at different hydrogen–containing gas atmospheres to understand the catalyst stability under various conditions. Moreover, prolonged experiments were carried out with concentrated model compounds to reveal the catalyst deactivation. New materials were proposed for the selective deoxygenation process at lower temperatures (~200 °C) with a tunable selectivity to hydrodeoxygenation by using 4 % Pt/TiO2 or decarboxylation/decarbonylation over 4 % Ru/TiO2 catalysts. A new method for selective hydrogenation of fatty acids to fatty alcohols was demonstrated with a 4 % Re/TiO2 catalyst. A reaction pathway and mechanism for TiO2 supported metal catalysts was proposed and an optimization of the process conditions led to an increase in the formation of the desired products.

Influence of body mass and environmental oxygen tension on the oxygen consumption rates of an enteropneust, Glossobalanus crozieri

The present study deals with a species of enteropneust, Glossobalanus crozieri, focusing on two aspects of its respiration: a) oxygen consumption and body mass, and b) the influence of environmental oxygen tension on the respiratory rate. Preliminarily, the body water content was shown to be 85% of the whole body weight. The regression coefficient of the oxygen consumption on the wet body mass (0.578) seems to agree with the view that in enteropneusts respiration is mainly cutaneous. The respiratory rate was significantly reduced at O2 tensions from 76 mmHg downwards, suggesting conformity rather than regulation

Precipitated immune complexes of IgM induce the generation of reactive oxygen species by rabbit polymorphonuclear leucocytes

We report that immune complexes of IgM (ICIgM) antibodies and ovalbumin in the form of a precipitate from the equivalence zone induce the generation of reactive oxygen species by rabbit blood polymorphonuclear leucocytes (PMN), as measured by the chemiluminescence (CL) production in the presence of luminol. The kinetics of CL generation induced by ICIgM is quite different from that induced by precipitated immune complexes of IgG (ICIgG): the maximum rate of CL production for ICIgM occurs around 14 min, whereas for ICIgG it occurs about 5 min after incubation with the cells. Also the triggering of the process requires a higher concentration of ICIgM than of ICIgG. Evidence is presented that these effects are not mediated by interaction of the antigen (ovalbumin) with the cell, since immune precipitates of ovalbumin and the F(ab')2 fragment had no effect. Our observations that precipitated ICIgM can also be an effective stimulus for CL generation and thus for O2- production reveal a new functional capability of PMN. These results may have implications for the understanding of the participation of ICIgM (as well as of ICIgG) in inflammatory reactions mediated by PMN in immune complex diseases, and in the mechanisms of defense against microbes and other non-self agents.

Two research paths for probing the roles of oxygen in metabolic regulation

Tissues such as skeletal and cardiac muscles must sustain very large-scale changes in ATP turnover rate during equally large changes in work. In many skeletal muscles these changes can exceed 100-fold. Examination of a number of cell and whole-organism level systems identifies ATP concentration as a key parameter of the interior milieu that is nearly universally 'homeostatic'; it is common to observe no change in ATP concentration even while change in its turnover rate can increase or decrease by two orders of magnitude or more. A large number of other intermediates of cellular metabolism are also regulated within narrow concentration ranges, but none seemingly as precisely as is [ATP]. In fact, the only other metabolite in aerobic energy metabolism that is seemingly as 'homeostatic' is oxygen - at least in working muscles where myoglobin serves to buffer oxygen concentrations at stable and constant values at work rates up to the aerobic maximum. In contrast to intracellular oxygen concentration, a 1:1 relationship between oxygen delivery and metabolic rate is observed over biologically realistic and large-magnitude changes in work. The central regulatory question is how the oxygen delivery signal is transmitted to the intracellular metabolic machinery. Traditional explanations assume diffusion as the dominant mechanism, while proponents of an ultrastructurally dominated view of the cell assume an intracellular perfusion system to account for the data which have been most perplexing to metabolic biochemistry so far: the striking lack of correlation between changes in pathway reaction rates and changes in concentrations of pathway substrates, including oxygen and pathway intermediates.

Pancreatic nitric oxide and oxygen free radicals in the early stages of streptozotocin-induced diabetes mellitus in the rat

The objective of the present study was to explore the regulatory mechanisms of free radicals during streptozotocin (STZ)-induced pancreatic damage, which may involve nitric oxide (NO) production as a modulator of cellular oxidative stress. Removal of oxygen species by incubating pancreatic tissues in the presence of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) (1 U/ml) produced a decrease in nitrite levels (42%) and NO synthase (NOS) activity (50%) in diabetic but not in control samples. When NO production was blocked by N G-monomethyl-L-arginine (L-NMMA) (600 µM), SOD activity increased (15.21 ± 1.23 vs 24.40 ± 2.01 U/mg dry weight). The increase was abolished when the NO donor, spermine nonoate, was added to the incubating medium (13.2 ± 1.32). Lipid peroxidation was lower in diabetic tissues when PEG-SOD was added (0.40 ± 0.02 vs 0.20 ± 0.03 nmol/mg protein), and when L-NMMA blocked NOS activity in the incubating medium (0.28 ± 0.05); spermine nonoate (100 µM) abolished the decrease in lipoperoxide level (0.70 ± 0.02). We conclude that removal of oxygen species produces a decrease in pancreatic NO and NOS levels in STZ-treated rats. Moreover, inhibition of NOS activity produces an increase in SOD activity and a decrease in lipoperoxidation in diabetic pancreatic tissues. Oxidative stress and NO pathway are related and seem to modulate each other in acute STZ-induced diabetic pancreas in the rat.

Oxygen consumption of rats with broad intestinal resection

The study was performed to investigate possible alterations in oxygen consumption in an animal model with broad intestinal resection. Oxygen consumption and the thermal effect of a short meal were measured in rats subjected to short bowel syndrome. Four groups of rats were used. Group I was the control group, group II was sham operated, group III was submitted to 80% jejunum-ileum resection, and group IV was submitted to 80% jejunum-ileum resection with colon interposition. Ninety days after surgery, oxygen consumption was measured over a period of 6 h with the animals fasted overnight. The thermal effect of feeding was determined in another session of oxygen consumption measurement in animals fasted for 12 h. A 12-kcal meal was then introduced into the animal chamber and oxygen consumption was measured for a further 4 h. No differences in fasting oxygen consumption or in the thermal effect of the meal were detected among the groups studied. It is concluded that short bowel syndrome does not affect the overall energy expenditure of rats.

Analysis and modelling of chemical looping combustion process with and without oxygen uncoupling

Effective control and limiting of carbon dioxide (CO₂) emissions in energy production are major challenges of science today. Current research activities include the development of new low-cost carbon capture technologies, and among the proposed concepts, chemical combustion (CLC) and chemical looping with oxygen uncoupling (CLOU) have attracted significant attention allowing intrinsic separation of pure CO₂ from a hydrocarbon fuel combustion process with a comparatively small energy penalty. Both CLC and CLOU utilize the well-established fluidized bed technology, but several technical challenges need to be overcome in order to commercialize the processes. Therefore, development of proper modelling and simulation tools is essential for the design, optimization, and scale-up of chemical looping-based combustion systems. The main objective of this work was to analyze the technological feasibility of CLC and CLOU processes at different scales using a computational modelling approach. A onedimensional fluidized bed model frame was constructed and applied for simulations of CLC and CLOU systems consisting of interconnected fluidized bed reactors. The model is based on the conservation of mass and energy, and semi-empirical correlations are used to describe the hydrodynamics, chemical reactions, and transfer of heat in the reactors. Another objective was to evaluate the viability of chemical looping-based energy production, and a flow sheet model representing a CLC-integrated steam power plant was developed. The 1D model frame was succesfully validated based on the operation of a 150 kWth laboratory-sized CLC unit fed by methane. By following certain scale-up criteria, a conceptual design for a CLC reactor system at a pre-commercial scale of 100 MWth was created, after which the validated model was used to predict the performance of the system. As a result, further understanding of the parameters affecting the operation of a large-scale CLC process was acquired, which will be useful for the practical design work in the future. The integration of the reactor system and steam turbine cycle for power production was studied resulting in a suggested plant layout including a CLC boiler system, a simple heat recovery setup, and an integrated steam cycle with a three pressure level steam turbine. Possible operational regions of a CLOU reactor system fed by bituminous coal were determined via mass, energy, and exergy balance analysis. Finally, the 1D fluidized bed model was modified suitable for CLOU, and the performance of a hypothetical 500 MWth CLOU fuel reactor was evaluated by extensive case simulations.

The antioxidant action of Polypodium leucotomos extract and kojic acid: reactions with reactive oxygen species

Two natural products Polypodium leucotomos extract (PL) and kojic acid (KA) were tested for their ability to scavenge reactive oxygen species (·OH, ·O2-, H2O2, ¹O2) in phosphate buffer. Hydroxyl radicals were generated by the Fenton reaction, and the rate constants of scavenging were 1.6 x 10(9) M-1 s-1 for KA and 1.0 x 10(9) M-1 s-1 for PL, similar to that of ethanol (1.4 x 10(9) M-1 s-1). With superoxide anions generated by the xanthine/hypoxanthine system, KA and PL (0.2-1.0 mg/ml) inhibited ·O2-dependent reduction of nitroblue tetrazolium by up to 30 and 31%, respectively. In the detection of ¹O2 by rose bengal irradiation, PL at 1.0 mg/ml quenched singlet oxygen by 43% relative to azide and KA by 36%. The present study demonstrates that PL showed an antioxidant effect, scavenging three of four reactive oxygen species tested here. Unlike KA, PL did not significantly scavenge hydrogen peroxide.

The effects of 2,3-diphosphoglycerate, adenosine triphosphate, and glycosylated hemoglobin on the hemoglobin-oxygen affinity of diabetic patients

The position of the oxygen dissociation curve (ODC) is modulated by 2,3-diphosphoglycerate (2,3-DPG). Decreases in 2,3-DPG concentration within the red cell shift the curve to the left, whereas increases in concentration cause a shift to the right of the ODC. Some earlier studies on diabetic patients have reported that insulin treatment may reduce the red cell concentrations of 2,3-DPG, causing a shift of the ODC to the left, but the reports are contradictory. Three groups were compared in the present study: 1) nondiabetic control individuals (N = 19); 2) insulin-dependent diabetes mellitus (IDDM) patients (on insulin treatment) (N = 19); 3) non-insulin-dependent diabetes mellitus (NIDDM) patients using oral hypoglycemic agents and no insulin treatment (N = 22). The overall position of the ODC was the same for the three groups despite an increase of the glycosylated hemoglobin fraction that was expected to shift the ODC to the left in both groups of diabetic patients (HbA1c: control, 4.6%; IDDM, 10.5%; NIDDM, 9.0%). In IDDM patients, the effect of the glycosylated hemoglobin fraction on the position of the ODC appeared to be counterbalanced by small though statistically significant increases in 2,3-DPG concentration from 2.05 (control) to 2.45 µmol/ml blood (IDDM). Though not statistically significant, an increase of 2,3-DPG also occurred in NIDDM patients, while red cell ATP levels were the same for all groups. The positions of the ODC were the same for control subjects, IDDM and NIDDM patients. Thus, the PO2 at 50% hemoglobin-oxygen saturation was 26.8, 28.2 and 28.5 mmHg for control, IDDM and NIDDM, respectively. In conclusion, our data question the idea of adverse side effects of insulin treatment on oxygen transport. In other words, the shift to the left reported by others to be caused by insulin treatment was not detected.