INTRODUÇÃO: O tratamento das doenças decorrentes das deficiências quantitativa ou qualitativa do surfactante pulmonar consiste na reposição exógena, porém, esta terapêutica é de alto custo devido, basicamente, à metodologia sofisticada de produção do surfactante e à necessidade de importação. Com o propósito de reduzir os custos deste tratamento, o Instituto Butantan, em São Paulo, Brasil, desenvolveu uma nova tecnologia de produção, que demanda menor custo, através da extração orgânica de macerado de pulmão de suínos acoplada à adsorção em um derivado de celulose (DEAE-celulose). MÉTODOS: Com o objetivo de testar a eficácia deste novo produto, 74 coelhos prematuros de 27 dias de gestação foram randomizados em três grupos de estudo, de acordo com o tipo de tratamento realizado: Grupo Controle (n = 28, sem tratamento), Grupo Butantan (n = 22, Surfactante Butantan 50 mg/kg) e Grupo Survanta (n = 24, Survanta® 50 mg/kg). Os animais foram submetidos à ventilação mecânica com freqüência respiratória de 60 ciclos/ minuto, pressão expiratória positiva final de zero, tempo inspiratório de 0,5 segundo e fração inspirada de oxigênio de 21%, durante 20 minutos. O volume-corrente foi ajustado manualmente em 8 ml/kg durante o período da ventilação e a pressão ventilatória (pressão inspiratória - pressão expiratória final positiva) atingida foi registrada através de um pletismógrafo a cada 5 minutos. A complacência dinâmica foi determinada pela relação entre o volume-corrente e a pressão ventilatória. Ao final da ventilação, os animais foram divididos em dois grupos, um para a realização da curva pressão-volume e o outro para o estudo histopatológico. A análise histopatológica foi realizada com a determinação do tamanho alveolar médio, através da estimativa do intercepto linear médio (Lm); e com o cálculo do índice de distorção (ID) que indica a heterogeneidade do parênquima pulmonar. RESULTADOS: O volume-corrente alvo de 8 ml/kg foi atingido nos três grupos de estudo. Quanto a pressão ventilatória, foi observado menores pressões nos animais dos grupos Survanta® e Butantan durante todo o período da ventilação em relação ao grupo Controle. Melhor complacência dinâmica foi observada, não havendo diferença significante entre os grupos Survanta® e Butantan. Em relação à curva pressão-volume, volumes pulmonares maiores foram observados nos grupos Butantan e Survanta® comparados aos do grupo Controle; houve, também, melhor estabilização dos volumes pulmonares na fase expiratória entre os animais dos grupos tratados em relação ao grupo Controle. A análise histopatológica mostrou maior quantidade de alvéolos normais e menor de alvéolos hiperdistendidos ou colapsados nos animais do grupo que recebeu o novo surfactante e o grupo Survanta. No grupo controle, além de apresentar mais alvéolos colapsados e hiperdistendidos, houve também maior ocorrência de áreas com edema alveolar e derrame de material hialino na luz alveolar em relação aos outros dois grupos. CONCLUSÕES: Baseado nos resultados acima, concluiu-se que a administração do novo surfactante, produzido a partir da extração orgânica acoplada à adsorção em derivado de celulose, uma tecnologia de menor custo desenvolvida no Brasil, leva a melhora significativa das propriedades mecânicas pulmonares e da histerese na curva pressão-volume, além de apresentar melhor aeração do parênquima pulmonar e de forma mais homogênea, em coelhos prematuros. Estes efeitos foram semelhantes aos produzidos com a administração de um surfactante disponível no mercado para o uso clínico rotineiro / INTRODUCTION: Pulmonary diseases related to quantitative or qualitative surfactant deficiency are well described, mainly in neonatology. The treatment with surfactant replacement is effective although costly, due to the complexity of surfactant production and imports costs. Aiming the reduction of the cost associated with this therapy, the Butantan Institute, São Paulo, Brazil, developed a new technology based in organic extraction coupled with adsorption on a cellulose derivative, resulting in lower final cost. METHODS: In order to test the in vivo efficacy of this new product, 27 days gestation preterm rabbits were randomized after tracheostomy into 3 study groups, according to the type of treatment received: Control Group (n = 28, no treatment), Butantan Group (n = 22, Butantan surfactant, 50 mg/kg) or Survanta Group (n = 24, Survanta® 50 mg/kg). Mechanical ventilation was initiated with respiratory rate, 60 cycles/min; positive end expiratory pressure, zero and inspiratory time, 0.5 sec; FiO2, 21%. Inspiratory pressure and tidal volume was continuosly evaluated using a pletismograph, and set according to the necessary in order to ventilate with a preset target tidal volume of 8 ml/kg. Respiratory parameters were recorded each five min until the end of ventilation, after 20 min. Ventilatory pressure was defined as inspiratory pressure - positive end expiratory pressure (cmH2O); dynamic compliance (DC) was calculated as DC = {[Tidal volume (ml) / (Body weight (g)/1000)] / ventilatory pressure (cmH2O)}. After the end of ventilation period the animals were divided into two groups: the first for PV curve evaluation and the second for histopathological analysis. The histopathological analysis was performed with determination of mean alveolar size, using mean linear intercept (Lm) and the distortion index, to evaluate the heterogeneity of pulmonary parenchyma. Statistical analysis was by ANOVA ONE WAY, with Student-Newman-Keuls as post hoc test. Significance level was set at p = 0.05. RESULTS: The target tidal volume was achieved in all groups. We found lower ventilatory pressures, higher dynamic compliances and pulmonary volumes in both surfactant treated groups compared to the Control group, with no difference between them. Butantan surfactant and Survanta resulted in increased Lm and lower alveoli asymmetry, as evaluated by distortion index. CONCLUSION: We conclude that the new surfactant produced by Butantan Institute resulted in improvement of lung mechanics and histhopatological findings similar to the obtained with a clinicaly available surfactant, with no differences between them

Brodifacoum is a highly effective anticoagulant rodenticide that presents a secondary hazard to some non-target wildlife. The high acute toxicity of brodifacoum to mammals and birds, and its prolonged persistence in liver predicates secondary risk to predators and scavengers of poisoned rodents. Hence there is a need to improve ability to monitor and predict hazards of brodifacoum to non-targets, and optimise use patterns accordingly. Use of a less persistent anticoagulant rodenticide, diphacinone, is an alternative approach currently under investigation in New Zealand. This thesis describes a series of laboratory and pen studies that address information gaps relevant to the assessment of non-target hazards in continued use of brodifacoum, and of using diphacinone as an alternative. Non-lethal techniques for determining sublethal brodifacoum exposure in birds was investigated in chickens. Elevation of prothrombin time was a less reliable index than residual concentrations in tissues. Samples requiring less invasive procedures, such as dried blood spots or faeces, have potential to detect recent sublethal brodifacoum exposure and refinement of these indices could be useful in proactive monitoring of avian wildlife. Residual brodifacoum in eggs of sublethally-exposed hens raised further questions regarding wider non-target hazard and adverse effects on development of fertile eggs or chicks. A laboratory trial with rats found a positive correlation between residual brodifacoum concentrations in liver and the amount of brodifacoum ingested as bait. An estimated 14-22% of ingested brodifacoum was excreted in rat faeces in the period between ingestion of a lethal dose and death, indicating another potentially significant environmental pathway for brodifacoum transfer. In considering diphacinone as a less persistent alternative rodenticide to brodifacoum, evaluation of residual concentrations and persistence in pig tissues was required to estimate secondary hazard to human consumers and adequate with-holding periods for hunting feral pigs in areas where diphacinone was applied. A pen trial showed that domestic pigs were more susceptible to diphacinone toxicity, and thus primary poisoning risk, than previously estimated. Hepatic half-life of diphacinone in pigs was approximately 14 days, indicating reduced persistence in comparison to brodifacoum and enabling estimates of with-holding periods for hunting feral pigs from areas where diphacinone baits were applied. To investigate potential hazards of diphacinone use to invertebrates a trial using tree weta, a native New Zealand invertebrate, was undertaken. Weta readily ate diphacinone wax block baits with no mortality or weight loss evident, indicating low susceptibility. Residual whole-body diphacinone concentrations did not increase with the amount of diphacinone bait eaten. A simple, deterministic risk assessment suggested that, as a single secondary exposure, the maximum diphacinone concentration measured in weta would present a low risk to non-target birds. Given international recognition of the high secondary hazard and corresponding restrictions on use of brodifacoum, continued availability of brodifacoum to non-licensed users and sustained field applications for possum and rodent control in New Zealand is an exceptional use pattern. New data in this thesis suggest that baiting strategies that minimise the amount of brodifacoum available in the environment are important and regulatory review of some New Zealand brodifacoum applications should address this. In parallel, development of diphacinone as an alternative to brodifacoum should continue, as new data here confirms lower persistence in mammalian liver than brodifacoum, and also indicates low toxicity to invertebrates. However further investigation of multiple-exposure hazard and potential sublethal effects of diphacinone on non-target mammals and birds is warranted before extensive and sustained field applications of diphacinone are undertaken.

The main objective of this thesis was to study (i) the effect of the fasting and lairage on carcass and technological meat quality and (ii) the inclusion of magnesium (MgCO3 and MgSO4) and/or tryptophan during 5 days before slaughtering pigs as a strategy to decrease stress levels and improve meat quality, with two different porcine RYR1 genotypes (NN and nn). An adequate combination of fasting and lairage period is recommended. A supplement of MgCO3 or Trp did not improve meat quality under minimal stressful ante mortem conditions; and MgSO4 had a laxative effect on pigs supplemented with it. When including nn pigs to the herd, it is recommended to consider the supplements’ combination of tryptophan and a source of Mg (avoiding MgSO4) to alleviate the negative effect of the stress and to improve technological meat quality. / L’objectiu principal d’aquest treball fou estudiar (i) l’efecte del dejuni i el temps d’espera a l’escorxador i (ii) l’efecte de l’addició de suplements de magnesi (MgCO3 o MgSO4) i/o triptòfan a la dieta durant els 5 dies previs al sacrifici com a estratègia per disminuir els nivells d’estrès i millorar la qualitat de la carn, en dos genotips porcins diferents respecte el gen RYR1 (NN i nn). Es recomana combinar correctament el dejuni i l’espera per millorar el benestar i la qualitat de la carn. El MgCO3 o el Trp no va millorar la qualitat de la carn en condicions de mínim estrès; i el MgSO4 provocà problemes digestius. En el cas d’optar per la utilització de genètiques nn, es recomana considerar la utilització de suplements de L-Trp amb fonts de magnesi (excloent el MgSO4) per pal•liar les conseqüències negatives de l’estrès i millorar la qualitat tecnològica de la carn.

No description available.

A preocupação com a exposição do Homem ao ruído excessivo data dos primórdios da civilização. Com a modernidade, os níveis de ruído têm sido crescentes não só nas atividades laborais, como também nas sociais e recreativas, levando a perda auditiva induzida por níveis de pressão sonora elevada (PAINPS) a ser considerada a segunda maior causa de surdez. Esses fatos nos levaram a realizar estudo experimental buscando avaliar o efeito do nível de pressão sonora elevada e do extrato seco de Ginkgo biloba EGb 761 na cóclea de cobaias albinas, fêmeas e adultas, pela avaliação de eventuais alterações da sua citoarquitetura, por meio de microscopia de luz e pela observação das alterações do epitélio sensorial com microscopia eletrônica de varredura / Human exposition to excessive sound levels has been a cause for preoccupation since the early stages of our civilization. In the Modern Era, sound levels have increased not only at work but also during social and leisure activities, leading the hearing loss induced by high levels of sound pressure to be considered the second most important cause of deafness. Bearing that in mind an experimental work was designed in an attempt to search for the effects of high sound pressure and Ginkgo biloba EGb 761 dry extract to the cochlea of albino adult female guinea pigs with the evaluation of cell architecture alterations by means of light microscopy and also by the evaluation of alterations to the sensory epithelium with the scanning electron microscopy (SEM) array

No description available.

This dissertation collects four essays on banks, firms and real effects of bank lending. Owing to the appliance of different econometric methods on several datasets, insights in the behav-ior of and the impacts from financial markets and market participants are generated. In the first chapter, our results uncover a so far undocumented ability of the interbank market to distinguish between banks of different quality in times of aggregate distress. We show empirical evidence that during the 2007 financial crisis the inability of some banks to roll over their interbank debt was not due to a failure of the interbank market per se but rather to bank-specific shocks affecting banks’ capital, liquidity and credit quality as well as revised bank-level risk perceptions. Relationship banking is not capable of containing these frictions, as hard information seems to dominate soft information. In detail, we explore determinants of the formation and resilience of interbank lending relationships by analyzing an extensive da-taset comprising over 1.9 million interbank relationships of more than 3,500 German banks between 2000 and 2012. The second chapter examines the relationship between central bank funding and credit risk-taking. Employing bank-firm-level data from the German credit registry during 2009:Q1-2014:Q4, we find that banks borrowing from the central bank rebalance their portfolios to-wards ex-ante riskier firms. We further establish that this effect is driven by the ECB’s maturi-ty extensions and that the risk-taking sensitivity of banks borrowing from the ECB is inde-pendent of idiosyncratic bank characteristics. Finally, we show that these shifts in bank lend-ing are associated with an increase in firm-level investment and employment, but also with a deterioration of bank balance sheet quality in the following year. Once we analyze the relationship of banks as lenders vis-à-vis banks as borrowers and banks as lenders vis-à-vis non-financial companies as borrowers, we enlarge the understand-ing of non-financial companies not only in terms of being simply borrowers, respectively sub-jects exhibiting of credit risks. Instead, we try to understand the inner working of those com-panies more generally and analyze their quality not only in terms of a bank’s risk assessment but also in terms of the overall market assessment. However, this in turn can generate infor-mation useable to assess the quality of a bank’s credit portfolio in dimensions that so far are not taken into account by the current regulatory framework. Moreover, a better understanding of banks and non-banks beyond the standard lens of the banking and corporate finance litera-ture might promote new scopes for future research connecting those discrete subjects. In this regard, the third chapter analyzes the dependence of price reactions to corporate insider trad-ing on several measures of corporate governance quality. Our results strongly support the view that first, higher corporate governance levels seem to prevent or discourage insiders from engaging in insider trading as means of opportunistic rent extraction. Second, results confirm the notion of buy and sell trades not being just two sides of the same coin. That is, a higher level of corporate governance leads to a better pre-event information environment which results in less positive abnormal returns after insider buy trades as the incremental posi-tive information revealed by the trade is smaller. In contrast, sell trades in firms with better corporate governance are perceived to convey more valuable and most importantly negative information to the capital market so that prices adjust more for companies with better govern-ance schemes. Third, we show that institutional ownership even on an aggregate level is a sufficient measure to proxy a company’s corporate governance level. Hence, as information on companies’ bylaws and on investors’ investment dedication and type for example are scarce, respectively associated with higher costs because one has to gather that information one can refrain from that and instead proxy the governance level with the aggregate measure of institutional ownership. The latter result is important for carrying out future analyses merg-ing and extending the findings of the first two chapters. Last, the fourth chapter abstracts from borrowers as subjects of credit risk, as well, and most importantly extends the analysis of banks, firms and their interactions effecting each other by a macroeconomic perspective of the real effects of bank lending. That is, as capital flows and real estate are pro-cyclical, and real estate has a substantial weight in economies’ income and wealth Chapter 4 studies the role of real estate markets in the transmission of bank flow shocks to output growth across German cities. In this regard, real sector firms play a central role in the transmission mechanism we uncover. More specifically, the empirical analysis relies on a new and unique matched data set at the city level and the bank-firm level. To measure bank flow shocks, we show that changes in sovereign spreads of Southern Eu-ropean countries (the so-called PIGS spread) can predict German cross-border bank flows. To achieve identification by geographic variation, in addition to a traditional supply-side varia-ble, we use a novel instrument that exploits a policy assigning refugee immigrants to munici-palities on an exogenous basis. We find that output growth responds more to bank flow shocks in cities that are more exposed to tightness in local real estate markets. We estimate that, during the 2009-2014 period, for every 100-basis point increase in the PIGS spread, the most exposed cities grow 15-2 basis points more than the least exposed ones. Moreover, the differential response of commercial property prices can explain most of this growth differen-tial. When we unpack the transmission mechanism by using matched bank-firm-level data on credit, employment, capital expenditure and TFP, we find that firm real estate collateral as measured by tangible fixed assets plays a critical role. In particular, bank flow shocks in-crease the credit supply to firms and sectors with more real estate collateral. Higher credit supply then leads firms to hire and invest more, without evidence of capital misallocation.

No description available.

No description available.

Muito se tem pesquisado sobre os efeitos adversos dos antidepressivos tricíclicos (p.e. imipramina) sobre o sistema respiratório, embora pouco ou quase nada se encontre com relação a tal aspecto na literatura médica sobre a fluoxetina (Prozac®)– um inibidor seletivo da recaptação de serotonina, até porque esta droga começou a ser utilizada somente há cerca de quinze anos. Ambas substâncias (fluoxetina e imipramina, ou seus congêneres) agem basicamente sobre quadros depressivos, fóbicos e obsessivo-compulsivos, obesidade, anorexia, e outras indicações de várias naturezas, indo desde a ansiedade até a sindrome do pânico. Nota-se entretanto, que na maioria dos pacientes com tais quadros (sob tratamento com a fluoxetina ou não), são muito frequentes as queixas de natureza respiratória, como tosse, falta de ar, “angústia" no peito etc. Alguns efeitos adversos da fluoxetina e seus derivados são descritos na literatura, embora raros. Entre eles, destaca-se o comprometimento do aparelho respiratório na forma de doença pulmonar intersticial, pneumonia de hipersensibilidade e fosfolipidose. Apresentamos a seguir um projeto de trabalho experimental em cobaias com intuito de verificar a ação da fluoxetina sobre o aparelho respiratório, com relação à mecânica pulmonar, influência sobre o óxido nítrico exalado e resposta histopatológica pulmonar frente a possíveis injúrias, comparados a animais controles sem efeito da droga. Nosso modelo descreve um protocolo em que os animais foram submetidos ao cloridrato de fluoxetina por via oral durante 30 dias consecutivos, sendo ainda submetidos a uma reação de estresse tipo pânico– a natação forçada. / Although high-affinity imipramine binding sites have been reported in both rat and human lung, the role of the lungs in the pharmacokinetics of antidepressants like fluoxetine has not received much attention. Imipramine and fluoxetine have their action in depression, obesity, panic and anxiety among other indications. However, accumulation of selective serotonin-reuptake inhibitors- like fluoxetine, in the human lungs has been reported. Besides, it is very frequent to most patients (under fluoxetine treatment or not) present respiratory symptoms and/or signs, just like dyspnea, cough, chest anguish and so on. There also have been some adverse effects of fluoxetine described in the literature, although being few and isolated ones, related to hypersensitivity pneumonitis, phospholipidosis and interstitial lung disease. The purpose of this project is to investigate the fluoxetine action in respiratory tract, more specifically over the pulmonary interstitium, using an experimental model in guinea-pigs. Our project comprehends an experimental model with the animals under treatment of fluoxetine so that we could evaluate the substance effects on the respiratory system, concerning the mechanics and the lung histopathological aspects, compared to the control animals. We created then a protocol where the animals were treated with fluoxetine for 30 consecutive days and submmited to the forced swimmig test, a kind of panic-like reaction.