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Les prématurés subissent un stress oxydant qui résulte d’une défense antioxydante faible et/ou d’une charge oxydante. Des données suggèrent qu’un stress oxydant peut affecter le métabolisme énergétique et mener au syndrome métabolique. Hypothèse: Une faible défense antioxydante tôt dans la vie est suffisante pour affecter le métabolisme énergétique à long terme. Méthodes: Quatre groupes de cobayes (n=21) ont reçu entre leurs 3e et 7e jours de vie une diète standard (C-1sem, C-14sem) ou une diète déficiente (DC-1sem, DC-14sem). À 7 jours, les groupes C-1sem et DC-1sem ont été sacrifiés, le plasma et le foie collectés. Les groupes C-14sem et DC-14sem ont reçu la diète standard jusqu’à 14sem de vie. La glycémie et les triglycérides plasmatiques ont été mesurés à 1, 3, 11, et 13-14sem. La tolérance au glucose a été évaluée à 13sem. Les antioxydants hépatiques et les protéines régulant le métabolisme énergétique ont été analysés à 1 et 14sem. Résultats: Un statut redox oxydé du glutathion était associé avec la diète déficiente et était maintenu oxydé au moins jusqu’à 14sem (p<0.01). Les faibles niveaux de triglycérides plasmatiques et de glycémies, ainsi qu’une meilleure tolérance au glucose à 14sem (p<0.05) étaient associés avec un statut redox plus oxydé. Conclusion: Le faible taux de glutathion observé chez les prématurés a été reproduit dans notre modèle. Puisque nos données suggèrent un rôle protecteur d’un redox plus oxydé et que l’environnement redox est un important régulateur métabolique influençant le développement, il faudrait faire attention avant d’initier des traitements antioxydants agressifs chez les prématurés. / Preterm infants are faced to oxidative stress resulting from a low antioxidant defence and/or a high oxidant load. Datas suggest that an oxidative stress may impair energy metabolism leading to metabolic syndrome development. Hypothesis: A weak antioxidant defence early in life such as observed in preterm newborns is sufficient to impair energy metabolism later in life. Methods: Four groups of guinea pigs (n=21) received between their 3rd and 7th days of life a control diet (C-1week, C-14weeks) or antioxidant deficient diet (DC-1week, DC-14weeks). At 7 day-old, 1week-groups were sacrificed for plasma and liver sampling whereas 14week-groups were fed with the control diet until 14 week-old. Blood glucose and plasma triacylglycerol were determined at 1, 3, 11 and 13-14 week-old. Glucose tolerance test was performed at 13 week-old. Hepatic antioxidant defences and key proteins regulating lipid and glucose metabolism were measured at 1 and 14 weeks. Results: The oxidized redox status of glutathione associated with the neonatal deficient diet was maintained until at least 14 week-old (p<0.01). The low plasma triacylglycerol, low blood glucose and better tolerance to glucose at 14 weeks (p<0.05) were associated with an oxidized redox status. Conclusion: The low glutathione observed in newborn preterm infants has been reproduced in our animal model. Since the oxidized redox state observed here seems to be protective against impaired energy metabolism and since the cellular redox environment is known to be an important rheostat of metabolism influencing development, it suggests being careful before adopting aggressive antioxidant treatments in preterm infants.

En février, 2009 un rapport de PHRMA (Pharmaceutical Research and Manufacturers of America) confirmait que plus de 300 médicaments pour le traitement des maladies cardiaques étaient en phase d’essais cliniques ou en révision par les agences règlementaires. Malgré cette abondance de nouvelles thérapies cardiovasculaires, le nombre de nouveaux médicaments approuvés chaque année (toutes indications confondues) est en déclin avec seulement 17 et 24 nouveaux médicaments approuvés en 2007 et 2008, respectivement. Seulement 1 médicament sur 5000 sera approuvé après 10 à 15 ans de développement au coût moyen de 800 millions $. De nombreuses initiatives ont été lancées par les agences règlementaires afin d’augmenter le taux de succès lors du développement des nouveaux médicaments mais les résultats tardent. Cette stagnation est attribuée au manque d’efficacité du nouveau médicament dans bien des cas mais les évaluations d’innocuité remportent la palme des causes d’arrêt de développement. Primum non nocere, la maxime d’Hippocrate, père de la médecine, demeure d’actualité en développement préclinique et clinique des médicaments. Environ 3% des médicaments approuvés au cours des 20 dernières années ont, par la suite, été retirés du marché suite à l’identification d’effets adverses. Les effets adverses cardiovasculaires représentent la plus fréquente cause d’arrêt de développement ou de retrait de médicament (27%) suivi par les effets sur le système nerveux. Après avoir défini le contexte des évaluations de pharmacologie de sécurité et l’utilisation des bio-marqueurs, nous avons validé des modèles d’évaluation de l’innocuité des nouveaux médicaments sur les systèmes cardiovasculaires, respiratoires et nerveux. Évoluant parmi les contraintes et les défis des programmes de développements des médicaments, nous avons évalué l’efficacité et l’innocuité de l’oxytocine (OT), un peptide endogène à des fins thérapeutiques. L’OT, une hormone historiquement associée à la reproduction, a démontré la capacité d’induire la différentiation in vitro de lignées cellulaires (P19) mais aussi de cellules souches embryonnaires en cardiomyocytes battants. Ces observations nous ont amené à considérer l’utilisation de l’OT dans le traitement de l’infarctus du myocarde. Afin d’arriver à cet objectif ultime, nous avons d’abord évalué la pharmacocinétique de l’OT dans un modèle de rat anesthésié. Ces études ont mis en évidence des caractéristiques uniques de l’OT dont une courte demi-vie et un profil pharmacocinétique non-linéaire en relation avec la dose administrée. Ensuite, nous avons évalué les effets cardiovasculaires de l’OT sur des animaux sains de différentes espèces. En recherche préclinique, l’utilisation de plusieurs espèces ainsi que de différents états (conscients et anesthésiés) est reconnue comme étant une des meilleures approches afin d’accroître la valeur prédictive des résultats obtenus chez les animaux à la réponse chez l’humain. Des modèles de rats anesthésiés et éveillés, de chiens anesthésiés et éveillés et de singes éveillés avec suivi cardiovasculaire par télémétrie ont été utilisés. L’OT s’est avéré être un agent ayant d’importants effets hémodynamiques présentant une réponse variable selon l’état (anesthésié ou éveillé), la dose, le mode d’administration (bolus ou infusion) et l’espèce utilisée. Ces études nous ont permis d’établir les doses et régimes de traitement n’ayant pas d’effets cardiovasculaires adverses et pouvant être utilisées dans le cadre des études d’efficacité subséquentes. Un modèle porcin d’infarctus du myocarde avec reperfusion a été utilisé afin d’évaluer les effets de l’OT dans le traitement de l’infarctus du myocarde. Dans le cadre d’un projet pilote, l’infusion continue d’OT initiée immédiatement au moment de la reperfusion coronarienne a induit des effets cardiovasculaires adverses chez tous les animaux traités incluant une réduction de la fraction de raccourcissement ventriculaire gauche et une aggravation de la cardiomyopathie dilatée suite à l’infarctus. Considérant ces observations, l’approche thérapeutique fût révisée afin d’éviter le traitement pendant la période d’inflammation aigüe considérée maximale autour du 3ième jour suite à l’ischémie. Lorsqu’initié 8 jours après l’ischémie myocardique, l’infusion d’OT a engendré des effets adverses chez les animaux ayant des niveaux endogènes d’OT élevés. Par ailleurs, aucun effet adverse (amélioration non-significative) ne fût observé chez les animaux ayant un faible niveau endogène d’OT. Chez les animaux du groupe placebo, une tendance à observer une meilleure récupération chez ceux ayant des niveaux endogènes initiaux élevés fût notée. Bien que la taille de la zone ischémique à risque soit comparable à celle rencontrée chez les patients atteints d’infarctus, l’utilisation d’animaux juvéniles et l’absence de maladies coronariennes sont des limitations importantes du modèle porcin utilisé. Le potentiel de l’OT pour le traitement de l’infarctus du myocarde demeure mais nos résultats suggèrent qu’une administration systémique à titre de thérapie de remplacement de l’OT devrait être considérée en fonction du niveau endogène. De plus amples évaluations de la sécurité du traitement avec l’OT dans des modèles animaux d’infarctus du myocarde seront nécessaires avant de considérer l’utilisation d’OT dans une population de patients atteint d’un infarctus du myocarde. En contre partie, les niveaux endogènes d’OT pourraient posséder une valeur pronostique et des études cliniques à cet égard pourraient être d’intérêt. / In february 2009, a report from PHRMA (Pharmaceutical Research and Manufacturers of America) confirmed that more than 300 drugs for treatment of cardiovascular diseases were in clinical trials or under review by regulatory agencies. Despite the abundance of new cardiovascular therapies, the number of new drugs approved each year (all indications combined) is declining steadily with only 17 and 24 new drugs approved in 2007 and 2008, respectively. Only 1 drug out of 5000 candidates will be approved after 10 to 15 years of development with an average cost of $800 millions. Several initiatives have been launched by regulatory agencies to increase the success rate in drug development but results are still awaited. This stagnation is attributed to the lack of efficacy of several drug candidates but safety assessments are the leading cause of drug development discontinuation. Primum non nocere, the maxim from Hippocrate, father of medicine, remains of major relevance in preclinical and clinical drug development. Over the past 20 years, approximately 3% of approved drugs were subsequently withdrawn from the market due to adverse effects. Cardiovascular adverse effects represent the most frequent cause of drug development discontinuation or withdrawal (27%) followed by effects on the nervous system. After defining the context of safety pharmacology evaluations and the use of biomarkers in drug development, we validated safety pharmacology models to investigate drug-induced cardiovascular, respiratory and neurological effects. As we progressed within constraints and challenges of drug development, we evaluated the efficacy and safety of oxytocin, an endogenous peptide with therapeutic potential. Oxytocin (OT), a hormone historically associated with reproduction, demonstrated the ability to induce in vitro differentiation of cell lines (P19) but also embryonic stem cells into beating cardiomyocytes. These observations lead us to consider the use of OT as a treatment for myocardial infarct. To achieve this ultimate goal, we first evaluated the pharmacokinetic of OT in an anesthetized rat model. These investigations highlighted the unique characteristics of OT including a very short half-life and a non-linear pharmacokinetic profile in response to the dose. Cardiovascular effects of OT in healthy animals were then evaluated in various species. In preclinical research, the use of various animal species and state of consciousness (conscious or anesthetized) is recognized as one of the best strategies to increase the predictive value of results obtained in animals to the human response. Our initial investigations of OT treatment regimens used various animal models including conscious and anesthetized rats, anesthetized pigs, conscious dogs with indirect blood pressure monitoring and diuresis and conscious monkeys with cardiovascular telemetry monitoring. These studies confirmed OT to have significant hemodynamic effects with variable responses depending on the state of consciousness (conscious or anesthetized), the dose, the administration protocol (bolus or infusion) and the species that were used. These screening studies enabled selection of a treatment regimen and dose without adverse effects that could subsequently be tested in efficacy studies. A porcine myocardial infarct (MI) model with reperfusion was used to evaluate the effects of OT following myocardial ischemia. In a pilot project, continuous infusion of OT initiated immediately at coronary reperfusion induced cardiovascular adverse effects in all treated animals including a reduction of left ventricular fraction shortening and worsening of dilated cardiomyopathy which is typical following MI. Considering these observations, the therapeutic strategy was revised to avoid OT treatment during the inflammatory phase which was considered maximal around day 3 post-ischemia. When initiated 8 days after MI, OT infusion induced adverse effects in animals with elevated endogenous levels of OT. In contrast, no significant effects (not statistically significant improvement) were observed in animals with low endogenous OT baseline. In placebo treated animals, a trend to observe a better recovery was noted in animals with high endogenous OT baseline. While the size of the ischemic zone was comparable to human patients with MI, the use of juvenile animals and the absence of coronary disease are important limitations of the porcine model. The potential of OT for treatment of MI remains but our results suggest that systemic administration of OT by continuous infusion as part of a replacement therapy should be investigated further in relation to endogenous levels. Further investigations on safety of the treatment with OT on animal MI models are warranted before the use of OT can be considered in the patient population after myocardial infarct. On the other hand, endogenous levels of OT may have a prognostic value and clinical trials to investigate this hypothesis may be of interest.

This thesis examines the cytochrom P450 (CYP) drug metabolizing enzyme inhibition and antimicrobial properties of 46 common food plants available in the Canadian Market and the inhibitory properties of 17 traditional Cree antidiabetic medicines on aldose reductase. Inhibitory activity profiles of CYP 3A4, 3A5, 3A7 and 2D6 were created for the 46 samples. The most active plants in the CYP inhibition assay were the spices, belonging to the Apiaceae and Lamiaceae. Similarly, the most active plants in the antimicrobial assay were also the Apiaceae and Lamiaceae. Swine lens homogenate was tested as a novel model for the aldose reductase inhibition assay. Several Cree plants selected for the aldose reductase study showed a high activity, primarily in samples which also contained high levels of phenolics. A positive correlation was observed between total phenolics content and aldose reductase inhibition r2=0.44, p=0.05. Crude extracts of Rhododendron groenlandicum exhibited inhibitory activities of 35.11 ± 0.16 %. The subfractionation and HPLC analysis of R. groenlandicum revealed high levels of phenolics compounds including, catechin, epicatechin, quercetin and quercetin glycosides. This study found that medicinal and food plants contain phytochemicals that may have both beneficial and detrimental biological effects. / Nous avons étudié dans cette thèse les capacités de 46 plantes comestibles, disponibles sur le marché canadien, à inhiber le cytochrome P450 (CYP), enzyme responsable du métabolisme des médicaments, les propriétés antimicrobiennes, et les propriétés inhibitrices de l'aldose réductase à partir de 17 médicaments antidiabétiques traditionnellement utilisés par les Cris. Les profils de l'activité inhibitrice du CYP 3A4, 3A5, 3A7 et 2D6 ont été réalisés pour les 46 plantes à l'étude. Les plantes les plus actives dans le test d'inhibition du CYP furent les épices, plantes appartenant aux familles des Apiaceae et Lamiaceae. De même, les plantes les plus actives dans le bioessai antimicrobien furent aussi les plantes de ces deux mêmes familles. Un homogénat de cristallin de porc a été utilisé comme modèle nouveau pour le test d'inhibition de l'aldose réductase. Plusieurs plantes, utilisées par la nation Cri, qui ont été sélectionnées pour l'étude ont montré une forte activité inhibitrice de l’aldose réductase, principalement dans les échantillons qui contenaient des teneurs élevées en composés phénoliques. Une corrélation positive a été observée entre la teneur totale en composés phénoliques et l'inhibition de l'aldose réductase (r2 = 0.44, p = 0.05). Des extraits bruts de Rhododendron groenlandicum ont montré des activités inhibitrices de 35.11 ± 0.16%. Le sous-fractionnement et l'analyse HPLC de R. groenlandicum ont aussi révélé des teneurs élevées des composés phénoliques, incluant la catéchine, l'épicatéchine, la quercétine et les glycosides de quercétine. Cette étude a montré que les plantes médicinales et alimentaires contiennent des composés phytochimiques qui peuvent avoir à la fois des effets biologiques bénéfique et préjudiciable.

En aquest treball s'ha dissenyat un mètode ràpid i fiable de tinció amb fluorocroms per a l'anàlisi de la integritat i viabilitat espermàtiques a partir del marcatge de la beina mitocondrial amb MitoTracker®Green FM, de l'acrosoma amb la lectina Trypsin inhibitor from Soybean (SBTI) conjugada amb el fluorocrom Alexa Fluor®488 específic per la proacrosina i del nucli amb els fluorocroms bis-benzimida (específic per a cèl·lules viables) i iodur de propidi (específic per a cèl·lules no viables). També s'ha determinat l'efecte de la filtració de dosis seminals de mascles astentoteratonecrospèrmics en columnes de Sephadex neutre i de dosis de mascles amb baixa qualitat espermàtica per filtració en columnes de Sephadex iònic, llana de vidre i glass beads sobre la qualitat espermàtica dels diferents grups de mascles analitzats. Els resultats obtinguts han mostrat que diversos paràmetres de qualitat espermàtica milloren després de la filtració en les diferents reïnes segons la patologia que presentin. / In this work, a quick and reliable method of staining with fluorochromes was designed for the assessment of the sperm integrity and vitality by marking the mitochondrial sheath with MitoTracker®Green FM, the acrosome with the lectine Trypsin inhibitor from Soybean (SBTI) conjugated with the fluorochrome Alexa Fluor ® 488m, specific for the proacrosine, and the nucleus with the fluorochromes bis-benzimida (specific for viable cells) and propidium iodide (specific for non-viable cells).Moreover, in this work, the effects of filtration of seminal doses from asthenoteratonecrospermic boars through columns of Sephadex neuter and seminal doses from boars with low sperm quality through ionic Sephadex, glass wool and glass beads columns on sperm quality were tested. The results obtained showed that some sperm quality parameters improved after filtration through the different matrixes depending on the pathology that the males presented before filtration.

Cette étude archéozoologique porte sur les variations morphologiques de différents éléments du squelette porcin (Sus scrofa domesticus) et s’appuie sur deux présupposés majeurs : (1) les changements morphologiques de l’animal sont le reflet des évolutions du contexte socio-économique ; (2) il existe une grande diversité des formes porcines, conditionnée par différents facteurs d’influence (environnement, stratégies agropastorales, habitudes culturelles, etc.). L’analyse menée, sur la base de tels postulats, tend à mesurer puis décrire ces changements et cette diversité pour tenter d’en comprendre l’origine et les mécanismes de progression. Pour cela il a fallu observer les restes dentaires et osseux de plus de 600 sites archéologiques, situés sur les territoires gaulois, français et italien, datés de La Tène moyenne à la période moderne, à l’aide de différentes méthodes de morphométrie géométrique et traditionnelle. De cette manière, il a été possible de constituer un solide référentiel ostéométrique pour le porc et d’atteindre ici une meilleure compréhension des pratiques d’élevage aux périodes gauloise, romaine et médiévale / This archaeozoological study investigates morphological variations in different skeletal parts of the pig (Sus scrofa domesticus) according to two main assumptions: (1) the morphological changes of the animal reflect socio-economic changes; (2) there is a great diversity of pig’s forms, driven by different factors (environment, agropastoral strategies, cultural habits, etc.). Our analysis, based on these assumptions, tends to quantify and describe these changes and this diversification to try to understand their origin and mechanisms. For this we have observed the dental and skeletal remains of more than 600 archaeological sites, located on the Gallic, French and Italian territories, dated from La Tène moyenne to the modern period, using different methods of geometric and traditional morphometrics. In this way, we were able to build a strong osteometric framework for pigs and get new clues to a better understanding of farming practices for Gallic, Roman and medieval periods

Submitted by Morgana Andrade (morgana.andrade@ufes.br) on 2016-06-30T18:24:36Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Emanuel Maretto Effgen.pdf: 1064710 bytes, checksum: 9bafee2156d00099d000b0c4a1fea7a1 (MD5) / Approved for entry into archive by Patricia Barros (patricia.barros@ufes.br) on 2016-07-04T12:56:16Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Emanuel Maretto Effgen.pdf: 1064710 bytes, checksum: 9bafee2156d00099d000b0c4a1fea7a1 (MD5) / Made available in DSpace on 2016-07-04T12:56:16Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Emanuel Maretto Effgen.pdf: 1064710 bytes, checksum: 9bafee2156d00099d000b0c4a1fea7a1 (MD5) / No estado do Espírito Santo, estima-se que existem pouco mais de 226 mil cabeça de suínos, gerando cerca de 730.000 m³ de dejetos ricos em nutriente anualmente. Dessa forma, partindo do pressuposto que a aplicação da Água Residuária de Suinocultura (ARS) pode promover alterações nos teores de potássio do solo, promovendo incremento desse nutriente, bem como propiciar aumento da produção de massa seca do Panicum maximum cv. Mombaça, sem que haja desbalanceamento nutricional da planta, objetivou-se avaliar os teores de potássio no solo e na planta, bem como a produção de massa seca do Capim Mombaça (Panicum maximum cv. Mombaça) decorrentes de diferentes doses de ARS em comparação com a adução mineral. Esta pesquisa foi realizada em uma propriedade rural, localizada no município de Jerônimo Monteiro – ES. Para o K e a relação K/CTC, utilizou-se o esquema de parcelas subsubdivididas com três repetições. As parcelas receberam cinco tratamentos sendo: adubação mineral (200 kg ha-1 K) via Cloreto de Potásio; e doses de ARS 50, 100, 150 e 200, equivalentes a 100, 200, 300 e 400 kg ha-1 K, calculados a partir da recomendação agronômica. Nas subparcelas, teve-se às profundidades do solo, sendo: 0 a 10; 10 a 20; 20 a 40 e 40 a 60 centímetros. Nas subsubparcelas, a situação representada pelo tempo antes da aplicação da ARS foi denominada AAARS, e dez dias após cada aplicação da ARS, denominada DAARS. Para a Massa Seca e o teor de K na planta, teve-se um esquema de parcelas subdivididas com três repetições. As parcelas receberam os tratamentos: adubação mineral e doses de ARS 50, 100, 150 e 200% da dosagem recomendada de potássio. As subparcelas foram os períodos de avaliação das aplicações da ARS aos dias 10, 130, 210 e 270 decorridos do início do experimento. Depois dos resultados obtidos, procedeu-se a análise estatística por meio de análise de variância adotando 5% significância F, sendo realizado o contraste entre os valores médios obtidos para adubação mineral e a ARS ao nível de 5 % de probabilidade, pelo teste de Tukey. Posteriormente, para as variáveis quantitativas foi realizada a análise de regressão a 5% de significância, sendo os modelos foram escolhidos pela utilização o teste t de Student, e pelos coeficientes de determinação R2, utilizando-se o software SAEG. Verificou-se que, mesmo com a aplicação de doses de K superior à recomendação agronômica através da ARS, ocorreu a redução linear dos teores de K no perfil solo, assim como ocorre o acréscimo linear desses teores com o aumento da dose. A aplicação ARS mostrou-se mais eficiente para incrementar K no solo, quando comparada à Adubação Mineral. A dose que se mostrou mais eficiente na manutenção dos teores K no solo é ARS 150 %. A maior produção de biomassa deu-se na dose 50%, todavia culminando com os menores teores de K na planta do capim Mombaça, e os maiores teores na planta foram obtidos nas maiores doses de ARS. Verifica-se que os atributos químicos do solo são influenciados pela aplicação de ARS, o que denota a necessidade de periodicidade na avaliação desses atributos em áreas com aplicação contínua de ARS. / In Espírito Santo state, it is estimated that there are just over 226 000 head of pigs, therefore, these generate about 730.000m³ nutrient-rich waste annually. Thus, assuming that the application of the swine wastewater can promote changes in the potassium soil, promoting increment this nutrient as well as provide increased dry matter yield of Panicum maximum cv. Mombasa, without nutritional unbalance the plant, it was aimed to evaluate the levels of potassium in the soil and plant, and the dry mass of Mombasa Grass (Panicum maximum cv. Mombasa) resulting from different doses of ARS compared to mineral adduction. This research was conducted in a rural property located in the municipality of Jeronimo Monteiro - ES. For K and K/CEC was used a scheme split-split-plot portion with three replications. The plots received five treatments being: mineral fertilizer (200 kg ha-1 K) via potassium chloride; ARS and doses of 50, 100, 150 and 200, corresponding to 100, 200, 300 and 400 kg ha-1 K, calculated from the agronomic recommendation. Subplots, it was taken to the depths of the soil, being: 0-10; 10 to 20; 20 to 40 and 40 to 60 centimeters. In the sub-subplots, the situation represented by time before the application of ARS was named AAARS, and ten days after each application of ARS, called DAARS. For Dry mass and K content in the plant, had become a split plot arrangement with three replications. The plots received treatments: mineral fertilizer and doses of ARS 50, 100, 150 and 200% of the recommended dosage of potassium. The subplots periods of evaluation of the applications of ARS 10 days, 130, 210 and 270 elapsed from the beginning of the experiment. After the results, it was proceeded to statistical analysis using analysis of variance adopting 5% significance F, the contrast between the mean values obtained for mineral fertilizer and the ARS at 5% probability being performed by Tukey test. Subsequently, for quantitative variables regression analysis the 5% significance level was conducted, and the models were chosen by using the Student t test, and the coefficient of determination R2, using the SAEG software. It was found that, even with the application of higher doses of K recommendation the agronomic via ARS occurred linear reducing of the content K in the soil profile as well as linear increase these levels with increasing dose occurs. The ARS application was more efficient to increase soil K compared to mineral fertilization. The more effective dose in maintaining levels of K in the soil was ARS 150%.The highest biomass yield was given at a dose 50%, however culminating with the lowest levels of K in the plant grass Mombasa, and the highest levels in the plant were obtained at higher doses of ARS. It appears that the soil chemical properties are influenced by the application of ARS, which indicates the need for periodicity in the evaluation of these attributes in areas with continuous application of ARS.

Orthognatic surgery deals with congenital and acquired dentoalveolar or skeletal deformities of the face. An unfavourable downward rotation of a mandible and posterior vertical maxillary excess cause an anterior open bite, which is characterized by excessive anterior facial height in the lower third, a gap between the incisors in maximal occlusion and a large mandibular angle. Osteotomy (mainly Le Fort I osteotomy or bilateral sagittal split osteotomy of the mandibular ramus - BSSO), ostectomy or distraction osteogenesis are performed to correct the orthognatic deformities. Osteosynthetic materials based on titanium or bioresorbable materials are used in the form of miniplates with monocortical screws, or bicortical screws are utilized to fix the bony fragments. Stability of the new jaws position is the main criterion for success. Relapse causes a loss of occlusion and consequently functional and aesthetic disorders. Relapse consists of skeletal and dental factors. Skeletal relapse is usually divided into early and long-term relapse. BSSO with counter-clockwise (CCW) rotation of the occlusal plane alone was traditionally considered to be the least stable treatment method. Some authors suggest the use of two miniplates on each side of the osteotomy, but we have not found scientific proof of the...

Made available in DSpace on 2017-07-10T18:08:21Z (GMT). No. of bitstreams: 1 Denise A Zempulski.pdf: 2130382 bytes, checksum: 374994e9876ab99db94941e030ce4a28 (MD5) Previous issue date: 2013-02-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Cassava is a crop widely throughout the national territory. In 2011, the national production of cassava was estimated at 27.1 million tons, achieving an increase of 9.2% compared to the 2010 harvest. Among the liquid waste processing cassava, cites the Manipueira, it is the water content of the root mass extracted in pressing grated, in making flour. Manipueira residue is more problematic, because it has high pollution load and toxic potential due to the presence of cyanogenic glycosides, may cause serious problems to the environment and aquatic life if released into waterways. Other big environmental waste when discarded improperly, are waste dairy industries. The fractionation of milk constituents by ultrafiltration results in derivatives with great nutritional value and commercial, such as the retentate (concentrate fraction composed of protein and fat) and permeates (fraction diluted comprising lactose, minerals, electrolytes, nitrogen and water). Recently there is a higher quest for use of agro-industrial waste in order to recover substances and/or materials and thus increase economic efficiency of production processes. The application of agro-industrial residues in bioprocesses is used like alternative substrate, and a help to solve the problem of pollution in the processes of industrialization, where anaerobic digestion stands out due to its many favorable characteristics. One way to minimize environmental impacts and add value to the effluent is its use in the production of volatile fatty acids (VFA) production via anaerobic fermentation, which is the main objective of this work. All fermentations were performed at 30 ° C and 80 rpm with pig inoculum. Initially made up four fermentations, changing the substrate used (cassava, starchy hydrolyzate, whey permeate and synthetic medium) where obtained better results of VFA concentrations with cheese whey permeated and Manipueira. So, with these two substrates, was done the test without light (dark fermentation), and this new detail was responsible to increase the production of VFA in 38% for the manipueira and 20% for the permeate. Following an experimental design 22 was carried out with in quadruplicate central point for Manipueira, where they were tested three levels of glucose concentration (9, 19 e 29 g.L-1) and sodium bicarbonate (0.21, 1.71 and 3.21 g.L-1), and glucose concentrations of 29 g.L-1 and bicarbonate 3.21 g.L-1 that resulted in the increased production of VFA (1941,4 mg L-1 in 23 h) representing an increase of 77,3% in production. For the cheese whey permeate also was done test changing the glucose (75, 45 e 25 g.L-1) and alkalinity (7,7, 8,14, 9,2, 10,26 e 10,7 g.L-1). The best levels founded in this work for the permeate are 45 g.L-1 of glucose and 10,26 g.L-1 of alkalinity, resulting in 4115,16 mg.L-1 of VFA in 41 h. / A mandioca é uma cultura amplamente difundida por todo o território nacional. Em 2011, a produção nacional de mandioca foi estimada em 27,1 milhões de toneladas, obtendo uma variação positiva de 9,2% em relação à safra de 2010. Entre os resíduos líquidos do processamento da mandioca, cita-se a manipueira, que caracteriza a água de constituição da raiz, extraída na prensagem da massa ralada, na confecção da farinha. A manipueira é o resíduo mais problemático, por possuir elevada carga poluente e potencial tóxico devido à presença de glicosídeos cianogênicos, podendo causar sérios problemas ao meio ambiente e à vida aquática quando descartada inadequadamente. Outros resíduos de grande impacto ambiental quando descartados incorretamente, são os resíduos de indústrias de laticínio. O fracionamento dos constituintes do leite por ultrafiltração resulta em derivados de grande valor nutricional e comercial, como o retentado (fração concentrada composta por proteínas e gordura) e o permeado (fração diluída composta por lactose, sais minerais, eletrólitos, compostos nitrogenados e água). Recentemente há uma maior busca pelo uso de resíduos agroindustriais visando recuperar substâncias e/ou materiais e deste modo aumentar a eficiência econômica dos processos de produção. A aplicação de resíduos agroindustriais em bioprocessos é uma alternativa observada na forma de substratos, e uma ajuda para solucionar o problema da poluição nos processos de agroindustrialização, onde a digestão anaeróbia destaca-se devido as suas diversas características favoráveis. Uma das maneiras de minimizar os impactos ambientais e agregar valor ao efluente é a sua utilização na produção de ácidos graxos voláteis (AGVs) via fermentação anaeróbia, sendo este o objetivo principal deste trabalho. Todas as fermentações foram realizadas a 30ºC e 80 rpm com inoculo suíno. Inicialmente fez-se 4 fermentações, variando o substrato utilizado (manipueira, hidrolisado amiláceo, permeado de soro de queijo e meio sintético) onde obteve-se maiores resultados de concentração de AGVs com a manipueira e o permeado. Seguiram-se os estudos com estes dois substratos, fazendo-se o teste de ausência de luminosidade (fermentação escura), sendo esta estratégia responsável pelo aumento de 38% na produção de AGVs para a manipueira e 20% para o permeado. A seguir foi realizado um planejamento experimental 22 com quadruplicata no ponto central para a manipueira, onde foram testados 3 níveis de concentração de glicose (9, 19 e 29 g.L-1) e bicarbonato de sódio (0,21, 1,51 e 3,21 g.L-1), sendo as concentrações de glicose de 29 g.L-1 e bicarbonato de 3,21 g.L-1 as que resultaram em maior produção de AGV (1941,4 mg.L-1 em 23 h) representando um acréscimo de 77,3% na produção. Para o permeado de soro de queijo também foram realizados testes variando níveis de glicose (75, 45 e 25 g.L-1) e alcalinidade do meio (7,7, 8,14, 9,2, 10,26 e 10,7 g.L-1). Os níveis que apresentaram melhor resultado foram 45 g.L-1 de glicose e 10,26 g.L-1 de alcalinidade, resultando em 4115,16 mg.L-1 de AGVs em 41h.

La transplantation rénale, thérapie de choix de l'insuffisance rénale chronique terminale, est limitée par une pénurie d'organes. Les greffons issus de donneurs décédés par arrêt cardiaque (DDAC) peuvent contribuer à pallier à cette pénurie au prix de stratégies thérapeutiques visant à améliorer l'issue de la transplantation. Les cellules souches mésenchymateuses (MSC) de l'organisme adulte ont des propriétés de sécrétion, d'immunomodulation et de différenciation intéressantes dans ce contexte.L'objectif de ce travail est d'évaluer, dans un modèle pré-clinique porcin de DDAC, le potentiel thérapeutique de deux populations cellulaires d'intérêt : les MSC issues du liquide amniotique (AFSC) et les cellules de la fraction vasculaire stromale du tissu adipeux (SVF). Les AFSC porcines injectées dans l'artère rénale 7 jours post-greffe, en raison de leur sensibilité à une séquence d'hypoxie réoxygénation (HR) in vitro, accélèrent la reprise de fonction et réduisent l'extension des lésions chroniques du greffon et sont détectées dans le rein 24h après injection. La SVF porcine, phénotypiquement proche de celle de l'Homme, est moins sensible à cette séquence d'HR et peut être injectée dans l'artère du greffon à sa reperfusion sans perturbation du flux sanguin rénal, avec une rétention des cellules dans le rein 24h post injection.Ce travail met en évidence le rôle bénéfique des AFSC dans la réparation des lésions ischémie-reperfusion des greffons issus des DDAC, ainsi que la faisabilité de l'injection de la SVF dans l'artère rénale après transplantation, et ouvre des pistes pour l'optimisation les protocoles d'administration de produits de thérapie cellulaire en transplantation. / Kidney transplantation is the best therapeutic option for end stage chronic kidney failure, but is limited by transplant shortage. Use of transplants from deceased after cardiac death donors (DCD) could represent an additional graft source, but there is a need for developing new therapeutic approaches like cell therapy to increase their recovery. Mesenchymal stem cells (MSC) potentially extracted from many adult tissues have interesting paracrine, immune-modulating, and differentiation properties in this context. This work aims to assess, in a preclinical porcine model DCD donor, the therapeutic potential of two cell populations of interest: amniotic fluid derived MSC (AFSC) and cells from stromal vascular fraction of adipose tissue (SVF). Delayed injection of AFSC 7 days following kidney transplantation because of their sensitivity to a specific Hypoxia Reoxygenation (HR) sequence in vitro, accelerates graft function recovery and limits chronic injuries to the transplanted organ. Cells are detectable into the transplanted kidney 24h after injection. Porcine SVF is phenotypically similar to human. Injected in renal artery simultaneously with organ reperfusion because of its resistance to the HR sequence, porcine SVF does not disturb renal blood flow and allow cell-retention within the organ 24h after injection. This work highlights the protective effect of AFSC against ischemia reperfusion lesions in grafts from DCD donors and the feasibility of SVF injection directly into the renal artery of the graft following kidney transplantation in DCD conditions. Moreover it opens new lines for optimizing injection protocols of cellular products in kidney transplantation.