Novas estratégias terapêuticas para o tratamento da depressão: uma visão da química medicinal

Depression is a widespread humor disturbance promoted mainly by depletion of biogenic neurotransmitter amines involved in the CNS synapses. Effective drug treatments for depression have been available for more than forty years. Despite its remarkable structural diversity, this paper discuss under the medicinal chemistry point of view, all different classes of "monoamine based" antidepressant drugs, emphasizing the rational design, structure-activity relationships (SAR), biotransformation and physico-chemical properties related with antidepressant activity and molecular mechanism of action.

Simulations of 3D Stripixel Detectors

Large Hadron Collider (LHC) is the main particle accelerator at CERN. LHC is created with main goal to search elementary particles and help science investigate our universe. Radiation in LHC is caused by charged particles circular acceleration, therefore detectors tracing particles in existed severe conditions during the experiments must be radiation tolerant. Moreover, further upgrade of luminosity (up to 1035 cm-2s-1) requires development of particle detector’s structure. This work is dedicated to show the new type 3D stripixel detector with serious structural improvement. The new type of radiation-hard detector has a three-dimensional (3D) array of the p+ and n+ electrodes that penetrate into the detector bulk. The electrons and holes are then collected at oppositely biased electrodes. Proposed 3D stripixel detector demonstrates that full depletion voltage is lower that that for planar detectors. Low depletion voltage is one of the main advantages because only depleted part of the device is active are. Because of small spacing between electrodes, charge collection distances are smaller which results in high speed of the detector’s response. In this work is also briefly discussed dual-column type detectors, meaning consisting both n+ and p+ type columnar electrodes in its structure, and was declared that dual-column detectors show better electric filed distribution then single sided radiation detectors. The dead space or in other words low electric field region in significantly suppressed. Simulations were carried out by using Atlas device simulation software. As a simulation results in this work are represented the electric field distribution under different bias voltages.

Cyclin-dependent kinases 4 and 6 control tumor progression and direct glucose oxidation in the pentose cycle

Cyclin-dependent kinases CDK4 and CDK6 are essential for the control of the cell cycle through the G1 phase. Aberrant expression of CDK4 and CDK6 is a hall- mark of cancer, which would suggest that CDK4 and CDK6 are attractive targets for cancer therapy. Herein, we report that calcein AM is a potent specific inhibitor of CDK4 and CDK6 in HCT116 human colon adenocarcinoma cells, inhibiting retinoblastoma protein (pRb) phosphorylation and inducing cell cycle arrest in the G1 phase. The metabolic effects of calcein AM (the calcein acetoxymethyl-ester) on HCT116 cells were also evaluated and the flux between the oxidative and non-oxidative branches of the pentose phos-phate pathway was significantly altered. To elucidate whe-ther these metabolic changes were due to the inhibition of CDK4 and CDK6, we also characterized the metabolic profile of a CDK4, CDK6 and CDK2 triple knockout of mouse embryonic fibroblasts. The results show that the metabolic profile associated with the depletion of CDK4, CDK6 and CDK2 coincides with the metabolic changes induced by calcein AM on HCT116 cells, thus confirming that the inhibition of CDK4 and CDK6 disrupts the balance between the oxidative and non-oxidative branches of the pentose phosphate pathway. Taken together, these results indicate that low doses of calcein can halt cell division and kill tumor cells. Thus, selective inhibition of CDK4 and CDK6 may be of greater pharmacological interest, since inhibitors of these kinases affect both cell cycle progression and the robust metabolic profile of tumors.

Tempo de vida útil de propelentes base-simples

The purpose of this work was to determine the safe shelf life of single-base propellants. The kinetic parameters relative to the consumption of the stabilizer diphenylamine (DPA) added to the propellant were determined as a function of the storage and ageing time. High Performance Liquid Chromatography (HPLC) with spectrophotometric detection was used to determine the DPA percentage before and after the artificial ageing at 60, 70 and 80 ºC. The experimental data were very well adjusted to a pseudo-first order kinetic model and the respective kinetic constants are 8.0-10-3 day-1 (60 ºC); 1.9-10-2 day-1 (70 ºC); 1.2-10-1 day-1 (80 ºC). The activation energy was calculated as 130 kJ mol-1 and the half-time for depletion of the DPA at the hypothetical temperature of 40 ºC of storage was estimated as being 6 years.

Carboidratos como fonte de compostos para a indústria de química fina

Coal, oil, natural gas, and shale gas are biomass that is formed millions of years ago. These are non-renewable and depleting, even considering the recent discovery of new sources of oil in the presalt and new technologies for the exploitation of shale deposits. Currently, these raw materials are used as a source of energy production and are also important for the production of fine chemicals. Since these materials are finite and their (oil) price is increasing, it is clear that there will be a progressive increase in the chemical industry to use renewable raw materials as a source of energy, an inevitable necessity for humanity. The major challenge for the society in the twenty first century is to unite governments, universities, research centers, and corporations to jointly act in all areas of science with one goal of finding a solution to global problems, such as conversion of biomass into compounds for the fine chemical industry.Non-renewable raw materials are used in the preparation of fuels, chemical intermediates, and derivatives for the fine chemical industry. However, their stock in nature has a finite duration, and their price is high and will likely increase with their depletion. In this scenario, the alternative is to use renewable biomass as a replacement for petrochemicals in the production of fine chemicals. As the production of biomass-based carbohydrates is the most abundant in nature, it is judicious to develop technologies for the generation of chain products (fuels, chemical intermediates, and derivatives for the fine chemicals industry) using this raw material. This paper presents some aspects and opportunities in the area of carbohydrate chemistry toward the generation of compounds for the fine chemical industry.

3D Stripixel Detectors Simulation

Solid-state silicon detectors have replaced conventional ones in almost all recent high-energy physics experiments. Pixel silicon sensors don't have any alternative in the area near the interaction point because of their high resolution and fast operation speed. However, present detectors hardly withstand high radiation doses. Forthcoming upgrade of the LHC in 2014 requires development of a new generation of pixel detectors which will be able to operate under ten times increased luminosity. A planar fabrication technique has some physical limitations; an improvement of the radiation hardness will reduce sensitivity of a detector. In that case a 3D pixel detector seems to be the most promising device which can overcome these difficulties. The objective of this work was to model a structure of the 3D stripixel detector and to simulate electrical characteristics of the device. Silvaco Atlas software has been used for these purposes. The structures of single and double sided dual column detectors with active edges were described using special command language. Simulations of these detectors have shown that electric field inside an active area has more uniform distribution in comparison to the planar structure. A smaller interelectrode space leads to a stronger field and also decreases the collection time. This makes the new type of detectors more radiation resistant. Other discovered advantages are the lower full depletion voltage and increased charge collection efficiency. So the 3D stripixel detectors have demonstrated improved characteristics and will be a suitable replacement for the planar ones.

Amperometric biosensor for ascorbic acid

A L-ascorbic acid biosensor based on ascorbate oxidase has been developed. The enzyme was extracted from the mesocarp of cucumber (Cucumis sativus) by using 0.05 mol L-1 phosphate buffer, pH 5.8 containing 0.5 mol L-1 NaCl. After the dialysis versus phosphate buffer 0.05 mol L-1 pH 5.8, the enzyme was immobilized onto nylon net through glutaraldehyde covalent bond. The membrane was coupled to an O2 electrode and the yielding reaction monitored by oxygen depletion at -600 mV using flow injection analysis optimized to 0.1 mol L-1 phosphate buffer pH 5.8, as the carrier solution and flow-rate of 0.5 mL min-1. The ascorbic acid calibration curve was linear from 1.2x10-4 to 1.0x10-3 mol L-1. The evaluation of biosensor lifetime leads to 500 injections. Commercial pharmaceutical samples were analyzed with the proposed method and the results were compared with those obtained by high-performance liquid chromatography (HPLC).

Teollisuuden sivutuotteiden hyödyntäminen ekstruusion raaka-aineena

Ilmaston lämpeneminen ja luonnonvarojen ehtyminen ovat nostaneet ympäristöasiat erittäin ajankohtaisiksi ja kierrättämisen merkitys korostuu entisestään. Tässä diplomityössä on käsitelty teollisuuden jätteiden ja sivutuotteiden kierrättämistä puumuovikomposiitin raaka-aineeksi. Työssä on tutkittu Kaakkois-Suomessa olevia tärkeimpiä teollisuuden sivuainevirtoja puumuovikomposiitin kannalta sekä valmistettu puumuovikomposiittia hyödyntämällä kahta kaatopaikalle päätyvää jätettä. Kaakkois-Suomen teollisuuden jätteitä selvitettäessä löytyi paljon puumuovikomposiitin valmistamiseen soveltuvia jätteitä. Mekaanisen metsäteollisuuden sivutuotteita käytetään yleisesti puumuovikomposiitin valmistamiseen. Muita potentiaaliseksi havaittuja raakaaineita ovat mm. lentotuhka, lasikuitujäte, pakkauskartonki, muovijätteet ja vuorivillan valmistuksessa syntyvät jätteet. Koemateriaaleiksi valittiin puunpoltosta peräisin oleva lentotuhka ja vuorivillan valmistamisessa syntyvä vuorivillapöly. Materiaaleilla korvattiin puuta puumuovikomposiitissa ja valmistetulle komposiitille suoritettiin kokeita mekaanisten ominaisuuksien selvittämiseksi. Molempien materiaalien kohdalla ominaisuuksien havaittiin parantuneen ilman täyteainetta valmistettuun komposiittiin verrattuna.

Nuclear Matrix in Apoptotic Cell Death and Cell Proliferation. The role of Nuclear Mitotic Apparatus (NuMA) Protein

The nucleus is a membrane enclosed organelle containing most of the genetic information of the cell in the form of chromatin. The nucleus, which can be divided into many sub-organelles such as the nucleoli, the Cajal bodies and the nuclear lamina, is the site for several essential cellular functions such as the DNA replication and its regulation and most of the RNA synthesis and processing. The nucleus is often affected in disease: the size and the shape of the nucleus, the chromatin distribution and the size of the nucleoli have remained the basis for the grading of several cancers. The maintenance of the vertebrate body shape depends on the skeleton. Similarly, in a smaller context, the shape of the cell and the nucleus are mainly regulated by the cytoskeletal and nucleoskeletal elements. The nuclear matrix, which by definition is a detergent, DNase and salt resistant proteinaceous nuclear structure, has been suggested to form the nucleoskeleton responsible for the nuclear integrity. Nuclear mitotic apparatus protein, NuMA, a component of the nuclear matrix, is better known for its mitotic spindle organizing function. NuMA is one of the nuclear matrix proteins suggested to participate in the maintenance of the nuclear integrity during interphase but its interphase function has not been solved to date. This thesis study concentrated on the role of NuMA and the nuclear matrix as structural and functional components of the interphase nucleus. The first two studies clarified the essential role of caspase-3 in the disintegration of the nuclear structures during apoptosis. The second study also showed NuMA and chromatin to co-elute from cells in significant amounts and the apoptotic cleavage of NuMA was clarified to have an important role in the dissociation of NuMA from the chromatin. The third study concentrated on the interphase function of NuMA showing NuMA depletion to result in cell cycle arrest and the cytoplasmic relocalization of NuMA interaction partner GAS41. We suggest that the relocalization of the transcription factor GAS41 may mediate the cell cycle arrest. Thus, this study has given new aspects in the interactions of NuMA, chromatin and the nuclear matrix.

PET and MR imaging in Parkinson’s disease patients with cognitive impairment. A study of dopaminergic dysfunction, amyloid deposition, cortical hypometabolism and brain atrophy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. It is characterized by a severe loss of substantia nigra dopaminergic neurons leading to dopamine depletion in the striatum. PD affects movement, producing motor symptoms such as rigidity, tremor and bradykinesia. Non-motor symptoms include autonomic dysfunction, neurobehavioral problems and cognitive impairment, which may lead to dementia. The pathophysiological basis of cognitive impairment and dementia in PD is unclear. The aim of this thesis was to study the pathophysiological basis of cognitive impairment and dementia in PD. We evaluated the relation between frontostriatal dopaminergic dysfunction and the cognitive symptoms in PD patients with [18F]Fdopa PET. We also combined [C]PIB and [¹⁸F]FDG PET and magnetic resonance imaging in PD patients with and without dementia. In addition, we analysed subregional striatal [¹⁸F]Fdopa PET data to find out whether a simple ratio approach would reliably separate PD patients from healthy controls. The impaired dopaminergic function of the frontostriatal regions was related to the impairment in cognitive functions, such as memory and cognitive processing in PD patients. PD patients with dementia showed an impaired glucose metabolism but not amyloid deposition in the cortical brain regions, and the hypometabolism was associated with the degree of cognitive impairment. PD patients had atrophy, both in the prefrontal cortex and in the hippocampus, and the hippocampal atrophy was related to impaired memory. A single 15-min scan 75 min after a tracer injection seemed to be sufficient for separating patients with PD from healthy controls in a clinical research environment. In conclusion, the occurrence of cognitive impairment and dementia in PD seems to be multifactorial and relates to changes, such as reduced dopaminergic activity, hypometabolism, brain atrophy and rarely to amyloid accumulation.

Lannoitetehtaan prosessivesien käsittelyvaihtoehtojen soveltuvuuden arviointi

Phosphorus and nitrogen cause eutrophication of water bodies, causing severe damage to the ecosystem. Eutrophication of the waters causes oxygen depletion, which in turn increases fish mortality, releasing toxins in waters. The released toxins can cause damage to animals and humans, which is the reason in many countries to set emission limits for waste water. Nutrients exist naturally, but due to human activities there is high nutrient leaching to water bodies. Human activity is one of the main reasons to the eutrophication. The aim of this thesis was to estimate the suitability of different water treatment options for Yara Finland’s fertilizer plant’s process waters in Siilinjärvi. The fertilizer plant process waters are high concentrate and especially nitrogen concentrations are high, which bring challenge to the treatment. At the theoretical part was investigated conventional and as well advanced wastewater treatment methods like reverse osmosis, adsorption and ion exchange. Beside different treatment methods corporate environmental requirements, responsibility and strategies were researched. At the empirical part of the thesis the goal was to find out possibil-ities to intensify the efficiency of purification at lamella clarifier with chemical precipitation. In addition possibility to use already existing chemical purifying plant for process waters was estimated. As a result of the research Yara has a possibility to intensify lamella clarifier’s action by addi-tion of calcium hydroxide and thus to obtain the phosphorus and fluorine to precipitate out of the water. But in practice this would be too expensive. It is possible to eliminate nitrogen compounds by adsorption or ammonia stripping, both methods requires additional testing. It is possible to process waters in chemical purifying plant, if ammonium nitrogen has been reduced before. Reverse osmosis is possible to exploit for the phosphoric acid plant’s waters.

Establishment of anammox process in sludge samples collected from swine wastewater treatment system

The high load of nitrogen present in swine wastewater is one of the biggest management challenges of the activity. The Anammox process emerges as a good alternative for biological removal of nitrogen. This study aims to acclimate sludge collected from swine effluent treatment systems to establish the Anammox process. Two sludge samples were collected at Embrapa Swine and Poultry, Concordia - SC, Brazil, one from the bottom of an inactive anaerobic pond (inoculum A) and another from an aeration tank (inoculum B). Both were acclimated until the depletion of NO3-N, being subsequently inoculated in two reactors (Reactor A - Inoculum A and Reactor B - Inoculum B). The Reactor A showed activity after 110 days of operation, while the Reactor B needed 170 days. The difference in the start-up time could be explained by the different environmental conditions to which each sludge was submitted. FISH and PCR analyses confirmed the presence of microorganisms with Anammox activity, demonstrating that the sludge of swine wastewater treatment systems is a good source of inoculum for the development of the Anammox process.

Estenose arterial pós-transplante hepático: tratamento com angioplastia transluminal percutânea

Vascular complications after liver transplantation include oclusion or stenosis at the sites of anastomosis in the hepatic artery, portal vein, and vena cava. Balloon angioplasty of these stenosis carries little risk and is a useful procedure for the treatment of these problems. The purpose of this paper was to assess whether percutaneous transluminal angioplasty can help to prolong allograft survival and impruve allograft function in patient with hepatic artery stenosis after liver transplantation. We report a 43-year-old mate with stenosis of hepatic artery anastomosis after liver transplantation. An abrupt elevation of liver enzymes and serum bilirrubin levels was noted on the fifth postoperative month. The patient underwent percutaneous liver biopsy, which revealed important ductal depletion due to hypoperfusion, even though Doppler ultrasound examination demonstrated arterial flow. An angiogram confirmed severe stenosis of the arterial anastomosis with poor intraparenchymal arterial perfusion pattern. In an attempt to preserve the graft, a percutaneous transluminal angioplasty was performed using microballoons mounted on a hydrophylic micro guidewire. Intervention proceeded without complications. Liver enzimes and bilirrubin levels decreased within twenty-four hours of angioplasty. Normal levels were achieved after one week. Seven month after angioplasty, the patient is in a optimal clinical condition with no signs of graft impairment. We conclude that percutaneous transluminal angioplasty of hepatic artery stenosis after liver transplantation is relatively safe and may help decrease allograft loss.

Advanced welding technologies used for arctic metal structures

Rapid depletion of easy-to-access fossil fuel, predominantly, oil and gas resources has now necessitated increase in need to develop new oil and gas sources in ever more remote and hostile environments. This is necessary in order to explore more oil and gas resources to meet rapidly rising long-term energy demand in the world, both at present and in the nearest future. Arctic is one of these harsh environments, where enormous oil and gas resources are available, containing about 20% of the world total oil and gas, but the environmental conditions are very harsh and hostile. However, virtually all the facilities required for the exploration and development of this new energy source are constructed with metals as well as their alloys and are predominantly joined together by welding processes and technologies. Meanwhile, due to entirely different environment from the usual moderate temperate region, conventional welding technologies, common metals and their alloys cannot be applied as this Arctic environment demand metals structures with very high toughness and strength properties under extremely low temperature. This is due to the fact that metals transit from ductility to brittleness as the temperature moves toward extreme negative values. Hence, this research work investigates and presents the advanced welding technologies applicable to Arctic metal structures which can give satisfactory weldments under active Arctic service conditions. .

Talviaikainen happitilanne eräissä Pohjois-Savon järvissä vuosina 1997-2008

Pohjois-Savossa seurattiin talviaikaista happitilannetta vuosina 1997-2008. Seurannan kohteena oli neljä pienehköä järveä (Iso-Valkeinen, Kevätön, Kolmisoppi ja Vehmasjärvi), jotka ovat erityyppisiä syvyydeltään, rehevyystasoltaan ja humuspitoisuudeltaan. Näiden esimerkkijärvien oli tarkoitus antaa yleisemminkin viitteitä happitilanteen kehityksestä talven aikana. Alkutalven tulosten perusteella annettiin vuosittain tiedote, jossa arvioitiin happikatojen mahdollisuutta kevättalven kuluessa. Yleisöllä oli myös mahdollisuus seurata happi- ja lämpötilatuloksia Pohjois-Savon ympäristökeskuksen verkkopalvelun kautta. Hapenkulutusnopeus oli rehevimmässä seurantajärvessä kaksinkertainen verrattuna karumpiin ja syvyyden myötä ero vain korostui. Pohjanläheisessä vesikerroksessa 1 mg/l:n happipitoisuus kului karuissa järvissä noin kahdessa viikossa ja rehevässä noin kolmessa päivässä. Vuosien välinen vaihtelu oli kuitenkin hyvin suurta. Vaihtelu oli suurta myös karuissa järvissä. Veden jäätymisajankohdalla ja veden lämpötilalla on merkittävä vaikutus siihen, millainen kevättalven happitilanteesta muodostui. Seurantajärvien aineiston perusteella voidaan karkeasti arvioida, että kuukauden viivästyminen jäätymisessä tai vesipatsaan viilentyminen ennen jäätymistä asteen verran kylmemmäksi merkitsevät noin kolmanneksen korkeampaa happipitoisuutta kevättalvella. Vesipatsaan happitilanteen heikentymisen sekä ravinne- ja rautapitoisuuksien välillä todettiin vahvat yhteydet. Kaikkien järvien aineistossa happitilanteen heikkeneminen johti voimakkaimmin alusveden ammoniumtyppi-, kokonaisfosfori- ja rautapitoisuuksien kasvuun. Pitoisuusmuutokset olivat talven aikana suurimmat rehevimmässä kohdejärvessä, Kevättömässä, jossa kokonaisfosforipitoisuudet keskimäärin kymmenkertaistuivat, fosfaattifosforipitoisuudet kasvoivat keskimäärin 20-kertaisiksi ja rautapitoisuudet yli seitsenkertaisiksi.