Câncer é a segunda causa de morte no mundo e foi responsável por 8,8 milhões de mortes em 2015, de acordo com a Organização Mundial da Saúde (OMS). Segundo o Instituto Nacional do Câncer (INCA), essa doença é um problema de utilidade pública. Em valores absolutos, o câncer de próstata, neoplasia maligna mais comum entre os homens, é o sexto tipo mais comum no mundo. Dentre os tratamentos para câncer de próstata estão a cirurgia, quimioterapia e radioterapia. Um dos principais tipos de radioterapia é a braquiterapia, realizada por meio de sementes radioativas de iodo-125, que são inseridas na próstata do paciente e liberam pequenas doses de radiação. Essas sementes podem ser introduzidas soltas ou em cordas poliméricas Quando introduzidas soltas, de acordo com a literatura, essas sementes podem migrar para outros órgãos. Para evitar essa migração, usa-se as sementes em cordas poliméricas. As cordas poliméricas são constituídas pelo poli(ácido lático-co-ácido glicólico), PLGA. O PLGA pode ser obtido por meio de seus dímeros cíclicos: glicolídeo e lactídeo. Esses dímeros, por sua vez, podem ser produzidos a partir de seus respectivos monômeros, os ácidos glicólico e lático. O objetivo desse trabalho foi analisar e discutir as condições favoráveis à síntese dos dímeros glicolídeo e lactídeo, dentre elas, etapas do processo e valores de temperatura e pressão. Foram executados sete experimentos com diferentes temperaturas e pressões nas três etapas da síntese: desidratação do ácido, formação do pré-polímero e despolimerização do pré-polímero. Na etapa intermediária da síntese, foi obtido o PLA quando foram utilizadas temperaturas acima de 150°C. A etapa final mostrou que temperaturas abaixo de 200°C não formam os dímeros. / Cancer is the second leading cause of world death and it was responsible for 8.8 million deaths in 2015, according to the World Health Organization (WHO). According to the National Cancer Institute (INCA), this disease is a public utility problem. In absolute values, prostate cancer, the most common cancer among men, is the sixth most common type in the world. Among prostate cancer treatments are surgery, chemotherapy and radiotherapy. One of the main radiotherapy types is brachytherapy, performed by iodine-125 radioactive seeds, which are inserted into the patient\'s prostate and release small radiation doses. These seeds can be introduced loose or such as stranded seeds. When introduced such as loose seeds, according to literature, these seeds can migrate to other organs. In order to avoid this migration, it is used stranded seeds. The stranded seeds are composed of PLGA, poly(lactic acid-co-glycolic acid). PLGA can be obtained by its cyclic dimers: glycolide and lactide. These dimers can be produced from their respective monomers, glycolic and lactic acids. The purpose of this study was to analyze and discuss the favorable conditions of the glycolide and lactide synthesis, such as process steps and temperature and pressure values. Seven experiments were performed at different temperatures and pressures in three synthesis steps: acid dehydration, prepolymer formation and depolymerization of prepolymer. In intermediary step, the PLA was obtained when temperatures were above 150°C. The final step showed that dimers are not formed at temperatures below 200°C.

Les roches argileuses sont considérées comme de potentielles roches-hôtes pour le stockage en profondeur des déchets radioactifs de Haute Activité et de Moyenne Activité à Vie Longue (déchets HA-MAVL). L’iode 129 et le sélénium 79, issus des déchets nucléaires, sont considérés comme deux des radio-éléments les plus pénalisants en termes de sûreté. Cependant, l’iode et le sélénium présentent, vis-à-vis des conditions d’oxydo-réduction, des propriétés qui nécessitent une attention particulière quant à leur état d’oxydation. Une étude comparative sur la migration du sélénium et de l’iode au travers de roches argileuses a donc été réalisée afin de déterminer, dans un premier temps l’effet des conditions redox sur la migration du sélénium et de l’iode, et dans un second temps l’influence de la minéralogie sur le comportement de ces éléments. A cet effet, deux roches argileuses ont été étudiées, à savoir les argilites toarciennes de Tournemire (France) et les Argiles à Opalines (OPA) du Mont Terri (Suisse). L’étude des iodures dans les roches argileuses indurées a permis de confirmer le rôle de la pyrite oxydée et de la MON dans la rétention des iodures. On soupçonne notamment que la rétention des iodures serait contrôlée cinétiquement. Lors de l’étude de la migration du sélénium, nous nous sommes intéressé aux formes les plus oxydées de cet élément, à savoir le Se(IV) et le Se(VI). La migration du Se(IV) est fortement liée à des processus d’oxydo-réduction. En effet, lors de la diffusion de cet élément dans le Toarcien supérieur et l’OPA, une fraction importante du Se(IV) est réduite. Cette réduction semble fortement associée à la présence de fer dans la roche. L’étude du Se(VI) nous a permis de mettre en évidence un comportement dépendant de la concentration initiale : la rétention est significative aux plus faibles concentrations et non aux fortes concentrations. Les analyses spectroscopiques montrent une faible réduction du Se(VI) au contact du fer dans la roche. Néanmoins, nous ne pouvons pas exclure que cette réduction soit d’origine microbienne. / Deep argillaceous formations are considered as potential host rock for high-level radioactive waste repository. Based on safety assessment calculations, active selenium (79Se) and iodine (129I) from high level radioactive waste might be ones of the major dose contributors due to their longevity and their anionic character. However, because of their high sensitivity to redox condition, a special attention to the oxidation state of these elements is required. A comparative study on the diffusion properties of selenium and iodine through argillaceous rocks was realized with the aim to determine the effects of both the redox conditions and the mineralogy on the migration of these two elements. For these purposes, we have studied two argillaceous rocks: Toarcian argillite from Tournemire (France) and Opalinus clay (OPA) from the Mont-Terri (Switzerland). The study of the iodide migration allowed to confirm the control on the iodide retention of both oxidized pyrite and natural organic matter. A kinetic control of the iodide sorption is also suspected. We focus the selenium study on the more oxidized species, Se(IV) and Se(VI). The Se(IV) migration is strongly dependant from oxydo-reduction processes. Indeed, the Se(IV) diffusion experiments through Tournemire argillite and OPA indicated a significant reduction associated to Fe(II). The Se(VI) study evidenced a behavior dependant from the initial concentration : at the highest concentration, no significant retention was observed while the retention is significant at the lowest concentration. Futhermore, spectroscopic analyses tend to show a low Se(VI) reduction at the Fe contact. However, biotic origin cannot be excluded

As infecções adquiridas durante cirurgias oftalmológicas podem ter efeitos devastadores. O objetivo do presente estudo foi de comparar a proporção de culturas bacterianas negativas no fundo de saco conjuntival inferior após uma ou três gotas sequenciais de iodopovidona a 5% (PVPI). Os voluntários foram aleatoriamente designados para receber uma gota de PVPI (grupo PVPI) (no tempo 28 minutos) ou três gotas de PVPI (grupo PVPI+) (nos tempos 0, 20 e 28 minutos) no saco conjuntival inferior em olhos selecionados aleatoriamente. Um cotonete conjuntival foi identicamente obtido cinco minutos antes e 30 minutos após o tempo 0. A espessura corneana central foi medida da mesma maneira antes do tempo 0 e após o tempo 30 minutos. Os esfregaços conjuntivais foram incubados aerobicamente em meio líquido de tioglicolato enriquecido (caldo de carne) e em três meios de cultura sólidos (ágar chocolate, ágar de tripticase-soja com 5% de sangue de ovelha e ágar Sabouraud). No grupo PVPI (n=59), a proporção de olhos com culturas bacterianas negativas após o uso do PVPI (79,7%) não diferiu significativamente do valor basal (76,3%; p=0,7539). No grupo PVPI+ (n=61), a proporção de olhos com culturas bacterianas negativas após instilação de PVPI (85,3%) foi significativamente maior do que antes da intervenção (70,5%) (p=0,0177). No entanto, a análise estatística intergrupos não detectou esta diferença. Não houve diferença significativa na média da espessura corneana central antes e após a intervenção em ambos os grupos. A instilação de três gotas sequenciais de PVPI foi associada ao aumento na proporção de olhos com culturas conjuntivais negativas, enquanto que a instilação de uma única gota de PVPI não demonstrou este aumento. É necessário um estudo mais aprofundado para determinar se a diferença entre os regimes de administração da PVPI está associada a diferentes taxas de infecções oculares pós-operatórias. / Infections acquired during ophthalmic surgery can be devastating. The purpose of the current study is to compare the proportion of negative bacterial cultures after one versus three sequential drops of povidone-iodine (PI) 5% into the inferior conjunctival fornix. Patients were randomly assigned to receive 1 (PI group) drop (at time 28 minutes) or three (PI plus group) sequential drops (at time 0, 20 and 28 minutes) of PI 5% into the inferior conjunctival sac of one randomly selected eye. A conjunctival swab was identically obtained 5 minutes before and 30 minutes after time 0. Central corneal thickness (CCT) was measured in the same way before time 0 and after time 30. Conjunctival swabs were incubated aerobically in enriched Thioglycolate liquid medium (meat broth) and in three solid culture media (chocolate agar, trypticase soy agar with 5% sheep blood, and Sabouraud agar). In the PI group (n=59), the proportion of eyes with negative bacterial cultures after PI (79.7%) did not differ significantly from baseline (76.3%; p=0.7539). In the PI plus group (n=61), the proportion of eyes with negative bacterial cultures after PI (85.3%) was significantly higher than before PI (70.5%) (p=0.0177). However, the intergroup statistical analysis did not detect this difference.There was no significant difference in mean CCT before and after the intervention in both groups. Instillation of three sequential drops of PI was associated with an increase in the proportion of eyes with negative conjunctival cultures, while instillation of a single drop of PI did not demonstrate this increase.Further study is warranted to determine whether the difference between the PI administration regimens is also associated with differences in the rates of postoperative ocular infections.

<p>Purpose: The aim of this thesis is to study the European (ESTRO/EAU/EORTC) and American (ABS) guidelines how to report the permanent seed implant and the most significant dosimetric parameters. It will also report on the permanent seed implant at Södersjukhuset, Karolinska University Hospital according to the guidelines. A large number of studies on pre- and post-implant dosimetry on permanent seed implants have recently been published but none is considered a standard. This makes it difficult, if not impossible, to compare data from different centres. The differences in reporting will also be discussed in this thesis. Another part of the study is to investigate how the morbidity correlates with the dose. The results in this report will give an overview of the experience at Södersjukhuset.</p><p>Matherials and Methods: This study includes 198 patients who received implants between 2004-2007 with I-125 seeds under transperineal ultrasound at Södersjukhuset (to a prescribed dose of 145 Gy). The dose-planning system VariSeed 7.1 was used with an online connection to the ultrasound system with real-time verification. Dose constraints for the planning system are V(100)>99%, V(150)>60%, V(200)>25%, UrD(10)<130% and UrD(30)<125%. Outer and inner wall of rectum was outlined for 55 patients as recommended by ESTRO/EAU/EORTC and doses to rectum were also computed.</p><p>Results: The median value for dosimetric parameters at Södersjukhuset, Karolinska University Hospital are for the prostate; D(90)=174Gy (153-194Gy), V(100)= 99% (93-100%), V(150)= 57% (40-74%), for the urethra; UrD(30) = 130% (112-147%), UrD(10) = 124% (107-142%) and for the rectum; RD2cc= 98Gy (73-128Gy), RD0.1cc=164Gy (119-240Gy), RV(100)=0.3cc (0.0-1.3cc), RV(150)=0.0cc (0.0-0.2cc). These values correspond to recommended data, except for the V(150) value. Regarding the clinically observed results, 3 patients had a relapse in their cancer, 2 patients had mild proctitis and 15 patients had urinary problems.</p><p>Discussion and Conclusions: The significant dosimetric parameters for reporting according to ESTRO/EAU/EORTC and ABS for prostate are D90[Gy], V(100)[%] and V(150)[%], for urethra are D(30) and D(10), and for rectum RD2cc and RD0.1cc. These parameters consider as a minimum to use and they further recommend secondary parameters to report. Other authors have also recommended to report RV(100) and RV(150) for rectum. This study did not show any relationship between UrD(10), UrD(30) and urinary morbidity. According to the recommendations every patient should undergo a CT-based evaluation. Further investigations are needed on whether a post-implant CT-study is necessary for real-time implantation, as there is not enough published data on this aspect.</p>

<p>Oscillator strengths and transition energies are calculated for several mono-substitutes of benzene and naphthalene molecules. The substituents investigated are chlorine, bromine and iodine. Calculations for these molecules are presented, at the Hartree-Fock and DFT level of theory. The functional used in DFT is CAM-B3LYP.</p>

Oscillator strengths and transition energies are calculated for several mono-substitutes of benzene and naphthalene molecules. The substituents investigated are chlorine, bromine and iodine. Calculations for these molecules are presented, at the Hartree-Fock and DFT level of theory. The functional used in DFT is CAM-B3LYP.

Purpose: The aim of this thesis is to study the European (ESTRO/EAU/EORTC) and American (ABS) guidelines how to report the permanent seed implant and the most significant dosimetric parameters. It will also report on the permanent seed implant at Södersjukhuset, Karolinska University Hospital according to the guidelines. A large number of studies on pre- and post-implant dosimetry on permanent seed implants have recently been published but none is considered a standard. This makes it difficult, if not impossible, to compare data from different centres. The differences in reporting will also be discussed in this thesis. Another part of the study is to investigate how the morbidity correlates with the dose. The results in this report will give an overview of the experience at Södersjukhuset. Matherials and Methods: This study includes 198 patients who received implants between 2004-2007 with I-125 seeds under transperineal ultrasound at Södersjukhuset (to a prescribed dose of 145 Gy). The dose-planning system VariSeed 7.1 was used with an online connection to the ultrasound system with real-time verification. Dose constraints for the planning system are V(100)&gt;99%, V(150)&gt;60%, V(200)&gt;25%, UrD(10)&lt;130% and UrD(30)&lt;125%. Outer and inner wall of rectum was outlined for 55 patients as recommended by ESTRO/EAU/EORTC and doses to rectum were also computed. Results: The median value for dosimetric parameters at Södersjukhuset, Karolinska University Hospital are for the prostate; D(90)=174Gy (153-194Gy), V(100)= 99% (93-100%), V(150)= 57% (40-74%), for the urethra; UrD(30) = 130% (112-147%), UrD(10) = 124% (107-142%) and for the rectum; RD2cc= 98Gy (73-128Gy), RD0.1cc=164Gy (119-240Gy), RV(100)=0.3cc (0.0-1.3cc), RV(150)=0.0cc (0.0-0.2cc). These values correspond to recommended data, except for the V(150) value. Regarding the clinically observed results, 3 patients had a relapse in their cancer, 2 patients had mild proctitis and 15 patients had urinary problems. Discussion and Conclusions: The significant dosimetric parameters for reporting according to ESTRO/EAU/EORTC and ABS for prostate are D90[Gy], V(100)[%] and V(150)[%], for urethra are D(30) and D(10), and for rectum RD2cc and RD0.1cc. These parameters consider as a minimum to use and they further recommend secondary parameters to report. Other authors have also recommended to report RV(100) and RV(150) for rectum. This study did not show any relationship between UrD(10), UrD(30) and urinary morbidity. According to the recommendations every patient should undergo a CT-based evaluation. Further investigations are needed on whether a post-implant CT-study is necessary for real-time implantation, as there is not enough published data on this aspect.

Im Rahmen der vorliegenden Arbeit wurden zentrale Aspekte der Schilddrüsenphysiologie am Beispiel von Iod, TSHR und IGF-IR untersucht. Der Pathologie der Schilddrüsenautonomie liegen konstitutiv aktivierende Mutationen des TSHR zugrunde. Die Prävalenz der Schilddrüsenautonomie ist in Iod armen Regionen deutlich erhöht. Als Ursache für Mutationen im TSHR wird vermehrter oxidativer Stress unter Iodmangel angenommen (Krohn et al. 2007; Maier et al. 2007). Die genauen molekularen Mechanismen konnten bisher noch nicht hinreichend aufgeklärt werden. In diesem Zusammenhang interessierte uns inwiefern eine ausreichende Iodversorgung die Entwicklung bereits autonomer Zellen beeinflussen kann. Das verwendete in vitro Modell der Schilddrüsenautonomie mit konstitutiv aktivierenden Mutationen im TSHR wurde bereits in früheren Arbeiten charakterisiert (Führer et al. 2003). Mit Hilfe von Microarray Untersuchungen und Funktionsanalysen, konnten wir deutliche Genregulationen durch Iod an Hand von normalen und autonomen Thyreozyten erkennen. Besonders auffällig war die differentielle Regulation von Genen, die z.B. in der Proliferation, dem Zellzyklus und metabolischen Prozessen involviert sind. Wesentlich ist, dass trotz einer konstitutiven Aktivierung des TSHR Iod dennoch die Proliferation und Funktion einer frühzeitigen Schilddrüsenautonomie herabsetzt. Die physiologische Rolle des IGF-IR in der Schilddrüsenphysiologie in vivo wurde noch nicht systematisch erforscht. Um die Rolle des IGF-IR in der Schilddrüse im Hinblick auf deren Entwicklung und Metabolismus näher zu untersuchen, wurde ein Mausmodell generiert bei dem der IGF-IR schilddrüsenspezifisch über eine durch den TG Promoter regulierte Cre Rekombinase (Igf1rTgCre) ausgeschaltet wurde. Ziel war es nun zu untersuchen, welche Folgen ein thyreoidaler Igf1r Knockout auf die Funktion, Morphologie und Entwicklung der murinen Schilddrüse und metabolischer Parameter hat. Dieser Knockout zeigte in den Mäusen keine Veränderungen des Schilddrüsengewichtes und der Serum T3 Werte, wobei das Serum T4 nach 8 Wochen leicht absank, nach 4 Monaten aber wieder Normalwerte zeigte. Allerdings waren die Serum TSH Werte bis zu 9fach erhöht. Die Histologie der Igf1r-/- Mäuse zeigten mit einer Rate von 86% papilläre Schilddrüsenhyperplasien sowie eine starke Heterogenität der Follikelstruktur, die auch bei den Igf1r-/- Mäuse zu finden war. Die molekulare Kompensation des Igf1r Knockouts in der Schilddrüse besonders durch TSH konnte durch unsere Untersuchungen nicht hinreichend geklärt werden. Die Daten aus unseren Ergebnissen und eines reversen Mausmodells (Überexpression des IGF-IR und IGF-I) (Clement et al. 2001) weisen daraufhin, dass das IGF-IR Signal weniger essentiell für die Schilddrüsenhormonsynthese ist als für das Aufrechterhalten einer Homöostase und normaler Schilddrüsenmorphogenese.

La famille des composés halogènes et inter-halogènes représentent des solides moléculaires adoptant des phases denses communes avec des solides moléculaires diatomiques comme l’azote et l’hydrogène. Parmi les transformations structurales et électroniques induites sous haute pression et observées dans ces solides, on note, entre autres, la dissociation moléculaire et la métallisation. De plus, l’étude des phases denses de l’iode a permis récemment l’observation d’une structure cristalline possédant une modulation dite incommensurable, c’est-à-dire une modulation possédant une périodicité différente de celle de la structure cristalline, jetant ainsi une lumière nouvelle sur le processus de dissociation moléculaire dans les solides halogènes. Dans ce mémoire, on propose d’étudier les changements structuraux dans monobromure d’iode (IBr), un composé inter-halogène possédant des propriétés structurales semblables à celles de deux composés halogènes, soit l’iode (I2) et le brome (Br2) sous leur forme solide. Des expériences de diffraction des rayons X de poudres en utilisant un rayonnement synchrotron ont été réalisées à température ambiante sur l’IBr en variant la pression jusqu’aux environs de 60 GPa. La nature chimique particulière du composé IBr a nécessité la mise au point de techniques de chargement d’échantillon destinées à préserver l’intégrité chimique de la substance utilisée. On rapporte également l’observation d’une phase de l’IBr présentant une modulation incommensurable. Les phases observées dans l’IBr permettent d’établir des parallèles avec les phases denses rapportées dans I2 et Br2 par le biais d’un modèle phénoménologique décrivant la séquence structurale des solides halogènes sous forme condensée.

La famille des composés halogènes et inter-halogènes représentent des solides moléculaires adoptant des phases denses communes avec des solides moléculaires diatomiques comme l’azote et l’hydrogène. Parmi les transformations structurales et électroniques induites sous haute pression et observées dans ces solides, on note, entre autres, la dissociation moléculaire et la métallisation. De plus, l’étude des phases denses de l’iode a permis récemment l’observation d’une structure cristalline possédant une modulation dite incommensurable, c’est-à-dire une modulation possédant une périodicité différente de celle de la structure cristalline, jetant ainsi une lumière nouvelle sur le processus de dissociation moléculaire dans les solides halogènes. Dans ce mémoire, on propose d’étudier les changements structuraux dans monobromure d’iode (IBr), un composé inter-halogène possédant des propriétés structurales semblables à celles de deux composés halogènes, soit l’iode (I2) et le brome (Br2) sous leur forme solide. Des expériences de diffraction des rayons X de poudres en utilisant un rayonnement synchrotron ont été réalisées à température ambiante sur l’IBr en variant la pression jusqu’aux environs de 60 GPa. La nature chimique particulière du composé IBr a nécessité la mise au point de techniques de chargement d’échantillon destinées à préserver l’intégrité chimique de la substance utilisée. On rapporte également l’observation d’une phase de l’IBr présentant une modulation incommensurable. Les phases observées dans l’IBr permettent d’établir des parallèles avec les phases denses rapportées dans I2 et Br2 par le biais d’un modèle phénoménologique décrivant la séquence structurale des solides halogènes sous forme condensée.