Orientador: Mauro Mitsuuchi Tashima / Resumo: O modo como são dispostos os resíduos gerados pela indústria, pela agropecuária e pela sociedade gera uma preocupação crescente. Muitas pesquisas têm sido desenvolvidas com a finalidade de diminuir o impacto que estes causam a sociedade e ao meio ambiente. Diversos resíduos têm sido estudados como materiais cimentícios suplementares para substituição de parte da quantidade de cimento, contribuindo para a redução de áreas de aterro e também na diminuição da emissão de CO2 associada à produção de cimento Portland, que é responsável por cerca de 5% a 8% da emissão global de CO2. Um destes resíduos industriais é a cerâmica vermelha, proveniente do descarte de olarias. O objetivo geral dessa pesquisa é estudar a aplicação de resíduo cerâmico proveniente de olarias em misturas de solo-cimento para estabilização de um solo laterítico, avaliando a resistência à compressão, o efeito de expansão e contração, o potencial hidrogeniônico, a condutividade elétrica, a microestrutura e a proporção ideal de mistura (solo + resíduo cerâmico + cimento Portland). Os resultados mostram ganho de resistência e menor contração/expansão para as misturas com cimento, em relação ao solo puro. E que mesmo com a substituição de parte do cimento por resíduo cerâmico, a resistência praticamente não se altera, devido a reação pozolânica existente entre a cerâmica e o hidróxido de cálcio, o que é confirmado nos ensaios de pH e condutividade elétrica e por imagens obtidas por meio de microscopia eletrônica de... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The waste generated by industry, agriculture and society is a growing concern. Much research has been carried out to reduce the impact on society and the environment. Several residues have been studied as supplementary cementitious materials to replace part of the amount of cement, contributing to the reduction of landfill areas and also to the reduction of CO2 emissions associated with the production of Portland cement, which accounts for about 5% of 8% of global CO2 emissions. One of these industrial wastes is red ceramics from the disposal of potteries. The general objective of this research is to study the application of different percentages of the mixture of ceramic residue with Portland cement in the stabilization of a lateritic soil, evaluating the compressive strength, expansion and contraction effect, permeability, hydrogenation potential, electrical conductivity, the microstructure and the ideal mixing ratio (soil + ceramic residue + Portland cement). The results show increased strength and lower contraction / expansion for cement additions, relative to pure soil. And even with the replacement of part of the cement by ceramic waste, the strenght is practically unchanged due to the pozzolanic reaction between the ceramic and the calcium hydroxide, which is confirmed in the pH and electrical conductivity tests and the images of scanning electron microscopy. / Mestre

Dysregulation of the sodium-chloride cotransporter (NCC) is believed to significantly impact blood pressure. Recent studies have implicated overactivity of the sympathetic nervous system as a mechanism driving renal NCC dysregulation to evoke the development of salt-sensitive hypertension. It is proposed that the sympathetic nervous system accomplishes this by norepinephrine (NE)-mediated over-activation of the beta2-adrenergic receptors located in the distal tubules of the kidney. Beta2-adrenoreceptor activation is hypothesized to stimulate the protein kinases SPAK and OxSR1 to phosphorylate and thus activate NCC. This beta2-receptor-SPAK/OxSR1-NCC pathway was elucidated in studies that challenged salt-resistant mice with high-salt diets, bilateral adrenalectomies, and NE infusion. To expand the scope of these studies, we investigated the effects of elevated circulating NE on blood pressure, NCC activity, and expression of NCC proteins, SPAK, and OxSR1 in a different salt-resistant animal species (the Sprague-Dawley rat). In this study we implanted male Sprague-Dawley rats with osmotic minipumps delivering a subcutaneous infusion of either saline, NE, a 50:50 solution of DMSO/isotonic saline, a combination of NE and the NCC antagonist hydrochlorothiazide, or a combination of NE and the beta-adrenoreceptor antagonist propranolol. Following implantation of the pumps the rats were randomly assigned to either a standard diet (0.4% NaCl) or a high-salt diet (8% NaCl) for two weeks. After fourteen days all animals underwent acute femoral artery, vein, and bladder cannulation in order to monitor heart rate and blood pressure, administer drugs intravenously, and track renal function, respectively. Following surgical recovery, blood pressure and heart rate were measured continuously, and urine was collected in ten-minute intervals in order to assess peak natriuretic responses to amiloride and hydrochlorothiazide. Following this protocol the rats received an intravenous bolus of hexamethonium (30 mg/kg), and their peak drops in blood pressure were recorded. Afterwards both kidneys were harvested and frozen at -80 °C for measurement of NCC proteins, SPAK, and OxSR1 expression. This study demonstrates that increased circulating NE induces salt-sensitive hypertension in the naturally salt-resistant Sprague-Dawley rat. Chronic infusion of NE raised the blood pressure of the rats, and a high-salt diet exacerbated this effect. Furthermore, NE prevented salt-evoked suppression of NCC activity and NCC, SPAK, and OxSR1 protein expression. Co-infusion of hydrochlorothiazide with NE attenuated NE-mediated hypertension and caused no variance in the blood pressures between the standard salt and high-salt groups. This indicates that chronically antagonizing NCC eliminated the salt-sensitive component of NE-mediated hypertension. Beta-receptor antagonism combined with NE infusion completely eliminated the hypertensive influence of NE and downregulated the expression of NCC proteins, SPAK, and OxSR1. However, NCC activity still remained at a level comparable with that observed in the NE-infused rats, demonstrating dissociation between protein expression and function. These data, the first report in a rat model of an interaction of NE and a high salt intake that impairs NCC function, demonstrate that increased levels of NE in combination with a high dietary salt intake result in NCC dysregulation and the development of NE-mediated salt-sensitive hypertension. To an extent the data also support the proposition that NE activates the beta-adrenergic receptors to influence the activity of NCC and the expression of NCC proteins, SPAK, and OxSR1. Beta-antagonism combined with NE infusion attenuated the effects of NE on blood pressure and the expression of NCC proteins, SPAK, and OxSR1. However, the NE-mediated elevation of NCC activity still remained high. We propose that the beta-receptors are not the only adrenergic receptors that can influence NCC activity. The presence of alpha-adrenergic receptors in the distal tubules suggests that they may be able to keep NCC activity elevated through a pathway independent of the beta-receptors, SPAK, and OxSR1.

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Dans le but de mieux comprendre le fonctionnement du cerveau nous devons examiner les domaines structuraux qui le composent, de la simple cellule à des régions entières du cerveau interconnectées. Cependant, bien que le fonctionnement d’une ou plusieurs cellules soit relativement bien connu, il n’y a que peu d’informations concernant les groupements de neurones interagissant fonctionnellement dans une même tâche, les réseaux neuronaux. De plus, l'activité équilibrée et concertée des réseaux excitateurs et inhibiteurs joue un rôle clé pour les intégrations corticales appropriées. Par ailleurs, il existe plusieurs outils afin d’enregistrer l’activité des réseaux excitateurs, ce qui n’est pas le cas pour les réseaux inhibiteurs. L’imagerie du colorant sensible au voltage (VSDI) est une technique permettant l’enregistrement de l’activité neuronale au moyen d’une émission de fluorescence proportionnelle au changement de potentiel de membrane. Par rapport aux autres techniques employant des électrodes, le VSDI permet l’enregistrement non invasif de l’activité de centaines de sites en même temps. Au cours des dernières décennies, le VSDI a été largement utilisé tant in vitro qu’in vivo pour étudier l’activité d’une cellule et des réseaux excitateurs. Néanmoins, en utilisant le VSDI, les recherches quant à l’activité des réseaux excitateurs ont été principalement réalisées par quantification d’émission de fluorescence en définissant des régions d’intérêts à des temps fixes, alors que l’activité inhibitrice n’a été évaluée qu’à l’échelle cellulaire. La première approche ne permet pas l’obtention de toutes les informations de la dynamique de propagation de la transmission glutamatergique du fait qu’elle ne prend en considération ni la vitesse ni la direction de propagation du signal. En revanche, la seconde approche n’offre pas la possibilité d’étudier l’activité du réseau inhibiteur ce qui serait toutefois important de définir du fait de la propagation spatiale extensive des interneurones au sein des aires corticales. Durant mon doctorat, le but de mon travail a été d’étudier en détail les réseaux neuronaux excitateurs et inhibiteurs de l’aire CA1 de l’hippocampe de souris à l’aide du VSDI. Pour les étudier de façon plus compréhensive, en collaboration avec une équipe de mathématicien, nous avons développé un algorithme permettant de mesurer la vitesse et la direction de propagation du signal VSDI, ce qui représente une nouvelle méthode pour analyser le flux optique. Après la validation réussie de l’algorithme avec des données de substitution pour tester sa précision, nous avons analysé deux séries d’expériences dans lesquelles l’activité des réseaux excitateurs a été manipulée soit par augmentation de l’intensité de stimulation passant de 10 à 30 Volts ou en bloquant la transmission GABAergique avec la picrotoxine, un antagoniste du récepteur GABAA. Les résultats de ces manipulations montrent une diminution significative de la vitesse alors que l’application de picrotoxine modifie de façon significative la direction de propagation, ce qui rend le signal de dépolarisation médié par le VSDI moins dispersé par rapport au contrôle. L’utilisation du VSDI a permis l’entière caractérisation des signaux hyperpolarisants médiés par les récepteurs GABAA dans toutes les sous-couches de CA1 (champ IPSP), offrant ainsi une nouvelle façon d’étudier les événements inhibiteurs à l’échelle d’un réseau. De plus, j’ai montré qu’en activant les récepteurs mGluR5, j’étais capable d’augmenter de façon durable le champ IPSP du VSDI, avec la durée et l’ampleur au niveau des sous-couches spécifiques de CA1. Globalement, je présente dans cette thèse de nouvelles méthodes et nouveaux résultats qui peuvent représenter une avancée dans la quête d’une meilleure compréhension des réseaux neuronaux, excitateurs et inhibiteurs, ce qui, espérons-le, pourra contribuer à réduire l’écart de connaissance entre l’activité d’une seule cellule et celle du comportement. / In order to better understand brain functioning we need to investigate all the structural domains present in it, from single cell to interconnected entire brain regions. However, while our knowledge in terms of single/few cells functioning is vast, very little is known about neuronal networks, which are interacting collections of neurons functionally related to the same task. Moreover, the balanced and concerted activity of excitatory and inhibitory networks plays a key role for proper cortical computations. However, while exist several tools to record excitatory networks activity, this is not the case for inhibitory networks. Voltage sensitive dye imaging (VSDI) is a technique that allows the recording of neuronal activity by mean of proportional emission of fluorescence according to changes in membrane potential. The advantage of using VSDI over other recording techniques using electrodes is that VSDI allows not invasive recording of neuronal activity from hundreds of sites at the same time. During my doctoral course I aimed at studying in detail excitatory and inhibitory neuronal networks in the CA1 area of mouse hippocampus with VSDI. To study excitatory networks more comprehensively, in collaboration with a team of mathematicians, we developed a mathematical algorithm that allowed measuring the velocity and the direction of spreading of the VSDI signal and it represents a new method to determine an optical flow. After successful validation of the algorithm with surrogate data to test its accuracy, we analysed two set of experiments in which network excitatory activity has been manipulated either by increasing Schaffer’s collaterals stimulation intensity or by blocking GABAergic transmission with the GABAA receptor antagonist picrotoxin in order to increase the depolarization in the CA1 region of the hippocampus. The results of these manipulations significantly decreased signal velocity whereas picrotoxin application significantly modified the direction of spreading, making the depolarization-mediated VSDI signal less dispersed compared to control. Using VSDI I was able to fully characterize GABAA receptor-mediated hyperpolarizing signals in all the CA1 sublayers (field IPSPs), thus providing a new way of monitoring inhibitory events at network level. Moreover, I found that the activation of mGluR5 receptors induced an increase in a long-lasting manner of the VSDI-recorded field IPSPs, with duration and magnitude that relied on the specific CA1 sublayer considered. Overall, my work shows new methodologies and new findings that may represent a step forward in the quest for a better understanding of neuronal networks, both excitatory as well as inhibitory, which hopefully can contribute to reduce the gap of knowledge between single cell activity and behaviour.

Tato diplomová práce se zabývá zhodnocením zavedení nového výrobku společnosti Henkel na český trh. V úvodu je přestavena společnost Henkel, její historie a finanční výsledky posledních dvou let, dále historie značky Persil. Druhá část je zaměřena obecně na východiska marketingové teorie a na její aplikaci ve firmě Henkel ČR. Stěžejní část práce se zabývá samotným zavedením výrobku Persil Sensitive na český trh, analýzou trhu, strategií a vyhodnocením prodejů Persilu Sensitive. Poslední kapitoly jsou věnovány dokreslení trhu pracích prostředků, poskytují informace o způsobech praní, složení pracího prostředku a testech, které se objevily v médiích.

A capacidade do Staphylococcus aureus escapar do sistema imune do hospedeiro é atribuída à existência de algumas exotoxinas, as quais são codificadas por genes acessórios. A expressão de genes codificadores de exotoxinas é controlada por reguladores, tais como o agr (acessory gene regulator), sendo identificados 4 tipos polimórficos deste regulador. Neste estudo, foram utilizadas 37 isolados de Staphylococcus aureus, sensíveis à oxacilina, originados de laboratórios e hospitais públicos e privados brasileiros. Utilizou-se a técnica de PCR para a amplificação dos genes codificadores dos fatores de virulência estudados e do tipo de agr presente em cada cepa. A técnica da eletroforese em campo pulsado (PFGE) foi utilizada para se verificar a existência clonal entre os isolados. Observou-se que o gene codificador de enterotoxina mais freqüentemente isolado foi o gene sea, todos relacionados com o tipo III de agr. Observou-se, também, alguns pontos divergentes com publicações anteriores como a presença dos genes seb e tst na mesma cepa (33%), cuja relação julgava-se não ser muito freqüente, o mesmo acontecendo com os genes tst e lukElukD. Não se encontrou isolado portador dos genes codificadores das toxinas esfoliatinas. Segundo a técnica de PFGE, não houve relação clonal entre os isolados. Conclui-se, portanto, que as bases moleculares da patogenicidade do S. aureus são multi-fatoriais, dependendo não somente da presença como também da expressão de alguns genes acessórios como também do tipo de agr presente. / The capacity of the Staphylococcus aureus to escape from the immune system of the host is conferred to the existence of some exotoxins, which are codified by accessory genes. The expression of the genes of exotoxins is controlled by regulators, such as agr (acessory gene regulator), being identified four different types of this regulator. In this study, it had been used 37 strains of Staphylococcus aureus, sensible to the oxacillin, proceeding from public and private Brazilians laboratories. It had been used the PCR technique for detention of the genes of the virulence factors and the agr type present in each strain. The PFGE had been used for detectation of clonal relationship between the strains. Thus, it was observed that the most frequently determined gene coder of enterotoxin was sea (100% were related as type of agr III). it was observed divergent points to the studies carried through in other countries, like strains with coders genes of seb and tst (33%).This correlation, the literature judged not to be frequent, the same happening for the simultaneous presence of tst and lukE-lukD. It was not found in this study strains carrying of exfoliatin toxins. According to PFGE, there wasn\' t evidence of clonal relationship between the strains. It is concluded, therefore, that the molecular bases of the pathogenicity of the S. aureus are multifactorial, depending not only on the presence, as also of the expression of some accessory genes and the agr type present.

O objetivo desse estudo foi investigar a associação da inflamação com a resistência periférica à insulina (RI) na vigência de dietas obesogênicas, suplementação com óleo de peixe (SOP) e ausência de TLR-4. Os animais receberam dieta balanceada (DB), DB e leite condensado (DB+LC), hiperlipídica (HFD) ou HFD+LC. DB+LC e HFD levaram ao aumento: no ganho de massa corpórea (MC) e expressão de F4/80 e leptina no tecido adiposo (TA) em relação à DB. Em relação à HFD, HFD+LC provocou: aumento no HOMA-IR (4x), nos conteúdos de IL-6, IL-10, TNF-a, IL-1b, ICAM-1, VCAM-1 e leptina no TA. Comparada à DB+LC, HF+LC aumentou: a MC, HOMA-IR e expressão de F4/80 e reduziu a expressão de leptina no TA. A SOP nos animais em DB reduziu a expressão de F4/80, TNF-a e TLR-4 no fígado. A SOP em HFD reduziu o MC, HOMA-IR e aumentou o conteúdo de adiponectina no TA. A deleção de TLR-4 elevou o MC em DB+OP e a gordura mesentérica no HFD+OP. Assim, o consumo elevado de gordura ou açúcar causou obesidade e a associação de ambos potencializou a obesidade e induziu RI e inflamação no TA. A suplementação com OP atenuou a inflamação associada à DB e a obesidade e RI na vigência de HFD, sendo esses efeitos dependentes de TLR-4. / The aim of this study was to investigate the association between inflammation and insulin resistance (IR) under obesogenic diets, fish oil supplementation (FOS) and TLR-4-/-. The mice were fed a balanced diet (BD), BD and condensed milk (BD+CM), high-fat diet (HFD) or high-fat diet and condensed milk (HFD+CM). The BD+CM and HFD increased: body weight gain (BWG), F4/80 and leptin in adipose tissue (AT). The HFD+CM compared to HFD increased: HOMA-IR, the contents of IL-6, IL-10, TNF-a, IL-1b, ICAM-1, VCAM-1 and leptin in AT. As compared to BD+CM, HFD+CM increased: BWG, HOMA-IR, F4/80 and reduced the leptin in AT. The FOS+BD reduced F4/80, TNF-a and TLR-4 in the liver. The FOS+HFD reduced BWG, HOMA-IR and increased the adiponectin in AT. TLR-4 deletion increased BWG in the FOS+BD and mesenteric fat in the FOS+HFD groups. The high consumption of fat or sugar induced obesity and the association of both potentiated this effect leading to IR and inflammation in adipose tissue and perivascular fat. FO supplementation attenuated the inflammation when associated with BD and the obesity and IR induced by HFD in a TLR-4 dependent-manner.

Legal regulation of sensitive commodity advertising (such as pharmaceutical drugs, dietary supplements, alcoholic beverages, tobacco products, games of chance) The subject of this thesis is the legal regulation of sensitive commodity advertising, such as tobacco products and alcoholic beverages on which I have focused in my work. The thesis is mainly based on topics relevant to current legislation and case law, which are directly linked to the advertising regulation of these products, and is based on controversy with the views of other experts on the subject. In my work I have not only described the historical development of advertisement in general, but also the initial introduction of advertising regulations as such, and, at the same time, the legal instruments related to the private and public law regulation with a detailed breakdown of relevant case law - without omission of international law and European Union law. Simultaneously, I have thoroughly analysed the issue of advertising regulations and its collision with the constitutionally established rights such as freedom of expression and freedom of enterprise also in the light of the imperative judicature decisions. One of the main parts of the analysis of this topic was also the focus on the ethical component of advertising self-regulation,...

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