Determinação espectrofotométrica de dipirona em produtos farmacêuticos por injeção em fluxo pela geração de íons triiodeto

A flow injection spectrophotometric procedure was developed for the determination of metamizol in pharmaceutical formulations. The system is based on the reaction between metamizol and triiodide generated in the system by mixing iodate and iodide-starch solutions. The absorbance of triiodide-starch complex giving a steady-state baseline value which was monitored at 580 nm. The inverse peaks caused by metamizol samples were measured and there was a direct relationship between absorbance decreasing and metamizol concentration from 1.4 x 10-4 to 7.0 x 10-4 mol L-1. The RSD was 0.45 % for a metamizol solution 4.2 x 10-4 mol L-1 (n = 10) with a detection limit (three-fold blank standard deviation/slope) of 6.0 x 10-5 mol L-1 The feasibility of the system was demonstrated for the determination of metamizol in commercial samples with sixty results obtained per hour. The results obtained for metamizol in pharmaceutical formulations using the proposed flow procedure and those obtained using an iodimetric procedure are in agreement at the 95% confidence level and within an acceptable range of error.

Danos ao DNA promovidos por ácido 5-aminolevulínico: possível associação com o desenvolvimento de carcinoma hepatocelular em portadores de porfiria aguda intermitente

5-Aminolevulinic acid (ALA) is a heme precursor accumulated in acute intermittent porphyria (AIP), which might be associated with hepatocellular carcinoma (HCC) in symptomatic patients. Under metal catalyzed oxidation, ALA and its cyclic dimerization product, 3,6-dihydropyrazine-2,5-dipropanoic acid, produce reactive oxygen species that damage plasmid and calf thymus DNA bases, increase the steady state level of 8-oxo-7,8-dihydro-2´-deoxyguanosine in liver DNA and promote mitochondrial DNA damage. The final product of ALA, 4,5-dioxovaleric acid (DOVA), is able to alkylate guanine moieties, producing adducts. ALA and DOVA are mutagenic in bacteria. This review shows an up-to-date literature data that reinforce the hypothesis that the DNA damage induced by ALA may be associated with the development of HCC in AIP patients.

Transferência de energia entre corantes catiônicos em sistemas homogêneos

In this work, the energy transfer by dipole-dipole interaction between cationic dyes in n-alcohols (methanol, ethanol, 1-propanol and 1-butanol) is studied by time resolved and steady state fluorescence measurements. The critical radii of energy transfer were determined by three independent methods; the spectral overlap, fluorescence decay profiles, and relative intensity measurements. In all solvents, R0 values of the dye pairs obtained from spectral overlap were between 40 to 90 Å. Steady state and time resolved fluorescence measurements resulted in values of R0 in the range of 50 - 80 Å, with good correlation of values.

Model-based study of a chemical-looping combustion process

Chemical-looping combustion (CLC) is a novel combustion technology with inherent separation of the greenhouse gas CO2. The technique typically employs a dual fluidized bed system where a metal oxide is used as a solid oxygen carrier that transfers the oxygen from combustion air to the fuel. The oxygen carrier is looping between the air reactor, where it is oxidized by the air, and the fuel reactor, where it is reduced by the fuel. Hence, air is not mixed with the fuel, and outgoing CO2 does not become diluted by the nitrogen, which gives a possibility to collect the CO2 from the flue gases after the water vapor is condensed. CLC is being proposed as a promising and energy efficient carbon capture technology, since it can achieve both an increase in power station efficiency simultaneously with low energy penalty from the carbon capture. The outcome of a comprehensive literature study concerning the current status of CLC development is presented in this thesis. Also, a steady state model of the CLC process, based on the conservation equations of mass and energy, was developed. The model was used to determine the process conditions and to calculate the reactor dimensions of a 100 MWth CLC system with bunsenite (NiO) as oxygen carrier and methane (CH4) as fuel. This study has been made in Oxygen Carriers and Their Industrial Applications research project (2008 – 2011), funded by the Tekes – Functional Material program. I would like to acknowledge Tekes and participating companies for funding and all project partners for good and comfortable cooperation.

A Novel Missense Mutation, I890T, in the Pore Region of Cardiac Sodium Channel Causes Brugada Syndrome

Brugada syndrome (BrS) is a life-threatening, inherited arrhythmogenic syndrome associated with autosomal dominant mutations in SCN5A, the gene encoding the cardiac Na₊ channel alpha subunit (Naᵥ1.5). The aim of this work was to characterize the functional alterations caused by a novel SCN5A mutation, I890T, and thus establish whether this mutation is associated with BrS. The mutation was identified by direct sequencing of SCN5A from the proband’s DNA. Wild-type (WT) or I890T Naᵥ1.5 channels were heterologously expressed in human embryonic kidney cells. Sodium currents were studied using standard whole cell patch-clamp protocols and immunodetection experiments were performed using an antibody against human Naᵥ1.5 channel. A marked decrease in current density was observed in cells expressing the I890T channel (from -52.0 ± 6.5 pA/pF, n=15 to 35.9 ± 3.4 pA/pF, n = 22, at -20 mV, WT and I890T, respectively). Moreover, a positive shift of the activation curve was identified (V½ =-32.0 ± 0.3 mV, n = 18, and -27.3 ± 0.3 mV, n = 22, WT and I890T, respectively). No changes between WT and I890T currents were observed in steady-state inactivation, time course of inactivation, slow inactivation or recovery from inactivation parameters. Cell surface protein biotinylation analyses confirmed that Nav1.5 channel membrane expression levels were similar in WT and I890T cells. In summary, our data reveal that the I890T mutation, located within the pore of Nav1.5, causes an evident loss-of-function of the channel. Thus, the BrS phenotype observed in the proband is most likely due to this mutation

Rhizodeposition of organic carbon by plants with contrasting traits for resource acquisition: responses to different fertility regimes

Background and aims Rhizodeposition plays an important role in mediating soil nutrient availability in ecosystems. However, owing to methodological difficulties (i.e., narrow zone of soil around roots, rapid assimilation by soil microbes) fertility-induced changes in rhizodeposition remain mostly unknown. Methods We developed a novel long-term continuous 13C labelling method to address the effects of two levels of nitrogen (N) fertilization on rhizodeposited carbon (C) by species with different nutrient acquisition strategies. Results Fertility-induced changes in rhizodeposition were modulated by root responses to N availability rather than by changes in soil microbial biomass. Differences among species were mostly related to plant biomass: species with higher total leaf and root biomass also had higher total rhizodeposited C, whereas species with lower root biomass had higher specific rhizodeposited C (per gram root mass). Experimental controls demonstrated that most of the biases commonly associated with this type of experiment (i.e., long-term steady-state labelling) were avoided using our methodological approach. Conclusions These results suggest that the amount of rhizodeposited C from plants grown under different levels of N were driven mainly by plant biomass and root morphology rather than microbial biomass. They also underline the importance of plant characteristics (i.e., biomass allocation) as opposed to traits associated with plant resource acquisition strategies in predicting total C rhizodeposition.

Formação de micelas mistas entre o sal biliar colato de sódio e o surfactante aniônico dodecanoato de sódio

Mixed-micelle formation between sodium chlolate (NaC) and the anionic surfactant sodium dodecanoate (SDoD) in Tris-HCl buffer solutions, pH 9.00, varying the molar fraction of the surfactants, was investigated by means of electrical conductivity and steady-state fluorescence of pyrene. The critical micelar concentration (cmc) was measured from the equivalent conductance versus the square root of the molar surfactant concentration plots and the regular solution theory (RST) was used to predict the mixing behavior. The I1/I3 pyrene ratio-surfactant concentration plots were used as an additional technique to follow the behavior and the changes in the micropolarity of the mixed micelles.

Síntese, caracterização e estudos de interação de um análogo da antitoxina CcdA empregando fluorescência no estado estacionário

Toxin-antitoxin (TA) systems contribute to plasmid stability by a mechanism called post-segregational killing. The ccd was the first TA system to be discovered with CcdB being the toxin and CcdA the antitoxin. CcdA, an 8.3 kDa protein, interacts with CcdB (11.7 kDa), preventing the cytotoxic activity of CcdB on the DNA gyrase. As an approach to understanding this interaction, CcdA41, a polypeptide derived from CcdA, was synthesized by solid-phase methodology and its interaction with CcdB was analyzed by steady state fluorescence. CcdA41 formed a stable complex with CcdBET2, a peptide based on CcdB, the more recently described bacterial topoisomerase inhibitor.

Supressão das anomalias de fase e batimentos laterais em espectros de RMN 13c obtidos com a sequência de precessão livre no estado estacionário

The Steady-State Free Precession (SSFP) sequence has been widely used in low-field and low-resolution imaging NMR experiments to increase the signal-to-noise ratio (s/n) of the signals. Here, we analyzed the Scrambled Steady State - SSS and Unscrambled Steady State - USS sequences to suppress phase anomalies and sidebands of the 13C NMR spectrum acquired in the SSFP regime. The results showed that the application of the USS sequence allowed a uniform distribution of the time interval between pulses (Tp), in the established time range, allowing a greater suppression of phase anomalies and sidebands, when compared with the SSS sequence.

Electrochemical and physical characterization of Ni-Cu-Fe alloy for chlor-alkali hydrogen cathodes

This work describes the development of an alternative acetate bath for the electrochemical codeposition of Ni-Cu-Fe electrodes at low pH that is stable for several weeks and produces electrodes with good performance for chlor-alkali electrolysis. Physical characterization of the electrode surface was made using X ray absorption spectroscopy (XAS), scanning electron microscopy (SEM) and energy dispersive analysis (EDX). The evaluation of the material as electrocatalyst for the hydrogen evolution reaction (her) was carried out in brine solution (160 g L-1 NaCl + 150 g L-1 NaOH) at different temperatures through steady-state polarization curves. The Ni-Cu-Fe electrodes obtained with this bath have shown low overpotentials for the her, around 0.150 V at 353 K, and good stability under continuous long-term operation for 260 hours. One positive aspect of this cathode is that the polarization behavior of the material shows only one Tafel slope over the temperature range of 298 - 353 K.

Magnetic Resonance Experiments with Atomic Hydrogen

In this thesis three experiments with atomic hydrogen (H) at low temperatures T<1 K are presented. Experiments were carried out with two- (2D) and three-dimensional (3D) H gas, and with H atoms trapped in solid H2 matrix. The main focus of this work is on interatomic interactions, which have certain specific features in these three systems considered. A common feature is the very high density of atomic hydrogen, the systems are close to quantum degeneracy. Short range interactions in collisions between atoms are important in gaseous H. The system of H in H₂ differ dramatically because atoms remain fixed in the H₂ lattice and properties are governed by long-range interactions with the solid matrix and with H atoms. The main tools in our studies were the methods of magnetic resonance, with electron spin resonance (ESR) at 128 GHz being used as the principal detection method. For the first time in experiments with H in high magnetic fields and at low temperatures we combined ESR and NMR to perform electron-nuclear double resonance (ENDOR) as well as coherent two-photon spectroscopy. This allowed to distinguish between different types of interactions in the magnetic resonance spectra. Experiments with 2D H gas utilized the thermal compression method in homogeneous magnetic field, developed in our laboratory. In this work methods were developed for direct studies of 3D H at high density, and for creating high density samples of H in H₂. We measured magnetic resonance line shifts due to collisions in the 2D and 3D H gases. First we observed that the cold collision shift in 2D H gas composed of atoms in a single hyperfine state is much smaller than predicted by the mean-field theory. This motivated us to carry out similar experiments with 3D H. In 3D H the cold collision shift was found to be an order of magnitude smaller for atoms in a single hyperfine state than that for a mixture of atoms in two different hyperfine states. The collisional shifts were found to be in fair agreement with the theory, which takes into account symmetrization of the wave functions of the colliding atoms. The origin of the small shift in the 2D H composed of single hyperfine state atoms is not yet understood. The measurement of the shift in 3D H provides experimental determination for the difference of the scattering lengths of ground state atoms. The experiment with H atoms captured in H2 matrix at temperatures below 1 K originated from our work with H gas. We found out that samples of H in H2 were formed during recombination of gas phase H, enabling sample preparation at temperatures below 0.5 K. Alternatively, we created the samples by electron impact dissociation of H₂ molecules in situ in the solid. By the latter method we reached highest densities of H atoms reported so far, 3.5(5)x10¹⁹ cm^-3. The H atoms were found to be stable for weeks at temperatures below 0.5 K. The observation of dipolar interaction effects provides a verification for the density measurement. Our results point to two different sites for H atoms in H2 lattice. The steady-state nuclear polarizations of the atoms were found to be non-thermal. The possibility for further increase of the impurity H density is considered. At higher densities and lower temperatures it might be possible to observe phenomena related to quantum degeneracy in solid.

A study of combustion phenomena in circulating fluidized beds by developing and applying experimental and modelling methods for laboratory-scale reactors

The results shown in this thesis are based on selected publications of the 2000s decade. The work was carried out in several national and EC funded public research projects and in close cooperation with industrial partners. The main objective of the thesis was to study and quantify the most important phenomena of circulating fluidized bed combustors by developing and applying proper experimental and modelling methods using laboratory scale equipments. An understanding of the phenomena plays an essential role in the development of combustion and emission performance, and the availability and controls of CFB boilers. Experimental procedures to study fuel combustion behaviour under CFB conditions are presented in the thesis. Steady state and dynamic measurements under well controlled conditions were carried out to produce the data needed for the development of high efficiency, utility scale CFB technology. The importance of combustion control and furnace dynamics is emphasized when CFB boilers are scaled up with a once through steam cycle. Qualitative information on fuel combustion characteristics was obtained directly by comparing flue gas oxygen responses during the impulse change experiments with fuel feed. A one-dimensional, time dependent model was developed to analyse the measurement data Emission formation was studied combined with fuel combustion behaviour. Correlations were developed for NO, N2O, CO and char loading, as a function of temperature and oxygen concentration in the bed area. An online method to characterize char loading under CFB conditions was developed and validated with the pilot scale CFB tests. Finally, a new method to control air and fuel feeds in CFB combustion was introduced. The method is based on models and an analysis of the fluctuation of the flue gas oxygen concentration. The effect of high oxygen concentrations on fuel combustion behaviour was also studied to evaluate the potential of CFB boilers to apply oxygenfiring technology to CCS. In future studies, it will be necessary to go through the whole scale up chain from laboratory phenomena devices through pilot scale test rigs to large scale, commercial boilers in order to validate the applicability and scalability of the, results. This thesis shows the chain between the laboratory scale phenomena test rig (bench scale) and the CFB process test rig (pilot). CFB technology has been scaled up successfully from an industrial scale to a utility scale during the last decade. The work shown in the thesis, for its part, has supported the development by producing new detailed information on combustion under CFB conditions.

Studies on Neuromuscular Blocking Agents and Their Antagonists During Anaesthesia

Neuromuscular blocking agents (NMBAs) are widely used in clinical anaesthesia and emergency medicine. Main objectives are to facilitate endotracheal intubation and to allow surgery by reducing muscle tone and eliminating sudden movements, which may otherwise lead to trauma and complications. The most commonly used NMBAs are non-depolarizing agents with a medium duration of action, such as rocuronium and cisatracurium. They bind to the acetylcholine receptors in the neuromuscular junction, thus inhibiting the depolarization of the postsynaptic (muscular) membrane, which is a prerequisite for muscle contraction to take place. Previously, it has been assumed that nitrous oxide (N2O), which is commonly used in combination with volatile or intravenous anaesthetics during general anaesthesia, has no effect on NMBAs. Several studies have since claimed that N2O in fact does increase the effect of NMBAs when using bolus administration of the relaxant. The effect of N2O on the infusion requirements of two NMBAs (rocuronium and cisatracurium) with completely different molecular structure and pharmacological properties was assessed. A closed-loop feedback controlled infusion of NMBA with duration of at least 90 minutes at a 90% level of neuromuscular block was used. All patients received total intravenous anaesthesia (TIVA) with propofol and remifentanil. In both studies the study group (n=35) received N2O/Oxygen and the control group (n=35) Air/Oxygen. There were no significant differences in the mean steady state infusion requirements of NMBA (rocuronium in Study I; cisatracurium in Study II) between the groups in either study. In Study III the duration of the unsafe period of recovery after reversal of rocuronium-induced neuromuscular block by using neostigmine or sugammadex as a reversal agent was analyzed. The unsafe period of recovery was defined as the time elapsed from the moment of no clinical (visual) fade in the train-of-four (TOF) sequence until an objectively measured TOF-ratio of 0.90 was achieved. The duration of these periods were 10.3 ± 5.5 and 0.3 ± 0.3 min after neostigmine and sugammadex, respectively (P < 0.001). Study IV investigated the possible effect of reversal of a rocuronium NMB by sugammadex on depth of anaesthesia as indicated by the bispectral index and entropy levels in thirty patients. Sugammadex did not affect the level of anaesthesia as determined by EEG-derived indices of anaesthetic depth such as the bispectral index and entropy.

Methods and Models for Accelerating Dynamic Simulation of Fluid Power Circuits

The objective of this dissertation is to improve the dynamic simulation of fluid power circuits. A fluid power circuit is a typical way to implement power transmission in mobile working machines, e.g. cranes, excavators etc. Dynamic simulation is an essential tool in developing controllability and energy-efficient solutions for mobile machines. Efficient dynamic simulation is the basic requirement for the real-time simulation. In the real-time simulation of fluid power circuits there exist numerical problems due to the software and methods used for modelling and integration. A simulation model of a fluid power circuit is typically created using differential and algebraic equations. Efficient numerical methods are required since differential equations must be solved in real time. Unfortunately, simulation software packages offer only a limited selection of numerical solvers. Numerical problems cause noise to the results, which in many cases leads the simulation run to fail. Mathematically the fluid power circuit models are stiff systems of ordinary differential equations. Numerical solution of the stiff systems can be improved by two alternative approaches. The first is to develop numerical solvers suitable for solving stiff systems. The second is to decrease the model stiffness itself by introducing models and algorithms that either decrease the highest eigenvalues or neglect them by introducing steady-state solutions of the stiff parts of the models. The thesis proposes novel methods using the latter approach. The study aims to develop practical methods usable in dynamic simulation of fluid power circuits using explicit fixed-step integration algorithms. In this thesis, twomechanisms whichmake the systemstiff are studied. These are the pressure drop approaching zero in the turbulent orifice model and the volume approaching zero in the equation of pressure build-up. These are the critical areas to which alternative methods for modelling and numerical simulation are proposed. Generally, in hydraulic power transmission systems the orifice flow is clearly in the turbulent area. The flow becomes laminar as the pressure drop over the orifice approaches zero only in rare situations. These are e.g. when a valve is closed, or an actuator is driven against an end stopper, or external force makes actuator to switch its direction during operation. This means that in terms of accuracy, the description of laminar flow is not necessary. But, unfortunately, when a purely turbulent description of the orifice is used, numerical problems occur when the pressure drop comes close to zero since the first derivative of flow with respect to the pressure drop approaches infinity when the pressure drop approaches zero. Furthermore, the second derivative becomes discontinuous, which causes numerical noise and an infinitely small integration step when a variable step integrator is used. A numerically efficient model for the orifice flow is proposed using a cubic spline function to describe the flow in the laminar and transition areas. Parameters for the cubic spline function are selected such that its first derivative is equal to the first derivative of the pure turbulent orifice flow model in the boundary condition. In the dynamic simulation of fluid power circuits, a tradeoff exists between accuracy and calculation speed. This investigation is made for the two-regime flow orifice model. Especially inside of many types of valves, as well as between them, there exist very small volumes. The integration of pressures in small fluid volumes causes numerical problems in fluid power circuit simulation. Particularly in realtime simulation, these numerical problems are a great weakness. The system stiffness approaches infinity as the fluid volume approaches zero. If fixed step explicit algorithms for solving ordinary differential equations (ODE) are used, the system stability would easily be lost when integrating pressures in small volumes. To solve the problem caused by small fluid volumes, a pseudo-dynamic solver is proposed. Instead of integration of the pressure in a small volume, the pressure is solved as a steady-state pressure created in a separate cascade loop by numerical integration. The hydraulic capacitance V/Be of the parts of the circuit whose pressures are solved by the pseudo-dynamic method should be orders of magnitude smaller than that of those partswhose pressures are integrated. The key advantage of this novel method is that the numerical problems caused by the small volumes are completely avoided. Also, the method is freely applicable regardless of the integration routine applied. The superiority of both above-mentioned methods is that they are suited for use together with the semi-empirical modelling method which necessarily does not require any geometrical data of the valves and actuators to be modelled. In this modelling method, most of the needed component information can be taken from the manufacturer’s nominal graphs. This thesis introduces the methods and shows several numerical examples to demonstrate how the proposed methods improve the dynamic simulation of various hydraulic circuits.

Laitosmittaukset turbiinilaitoksen suorituskyvyn seurantaan ydinvoimalaitoksen vuosihuoltojen yhteydessä

Työssä kehitettiin höyryvoimalaitosprosessin tilan seurantaan laitosmittausrutiini, jolla tarkastellaan erityisesti turbiinilaitoksen suorituskykyä ennen ja jälkeen vuosihuoltojen. Laitosmittaukset on kehitetty Teollisuuden Voima Oyj:n Olkiluodon ydinvoimalaitosyksikköjen OL1 ja OL2 tarpeisiin. Mittauksilla saadaan tietoa vuosihuollon kokonaisvaikutuksista prosessiin eli muuttuiko mikään vuosihuollon aikana ja mitkä syyt johtivat muutokseen. Lisäksi säännöllisillä mittauksilla tavoitellaan pitkän aikavälin referenssitietoa prosessin tilasta. Esimerkkimittaukset tehtiin kevään 2008 vuosihuolloissa, R108 ja R208. Työssä on esitetty mittausten suorittaminen, tulosten laskenta ja tarkastelu sekä raportointi. Luotu mittausrutiini pohjautuu höyryturbiinien ja lämmönsiirtimien vastaanottokokeita käsitteleviin standardeihin sekä laitosten viimeisimpiin prosessimuutosten yhteydessä toteutettuihin suorituskykymittauksiin. Laitosmittauksista tehtiin vastaanottokokeita kevyemmät ja yksinkertaisemmat mittaustapahtumat, joilla saadaan kuitenkin riittävän luotettavaa tietoa. Tunnuslukuja, joita ei käytettävissä olevien mittatietojen avulla saatu suoraan selville tai laskettua massa- ja energiataseilla, määritettiin stationaarisen tilan mallinnusohjelmalla TEMPO:lla. Esimerkkimittaukset sujuivat hyvin ja saadut tulokset antoivat kaivattua lisätietoa vuosihuollon vaikutuksesta prosessiin. Generaattorin bruttoteho aleni OL1:llä ja pysyi ennallaan OL2:lla. OL1:n tehon aleneminen selittyi syöttöveden virtausmäärän vähenemisellä, johon vaikutti virtausmittalaitteen lähettimen vaihto. OL2:lla ei havaittu turbiiniprosessissa muutoksia, mutta lauhduttimien suorituskyky parani. Lauhduttimien suorituskyvyn paraneminen ilmeni asteisuuksien pienentymisenä, johon vaikuttivat puhdistaminen ja ilmavuotojen väheneminen.