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The stress system comprises the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal-medullary (SAM) axes. The two operate synergistically to regulate metabolic and biological processes, maintain homeostasis, and manage physiological responses towards various environmental challenges, known as stressors. Numerous studies have observed impaired HPA response among White breast cancer survivors followed by an eventual normalization of the HPA axis, but little is known about SAM functioning, the complementary relationship between physiological and psychological stress, and the influence of culturally related factors. This dissertation aims to address these gaps in the literature via three studies. In Study 1, we examined the diurnal and reactive patterns of salivary alpha-amylase, a SAM biomarker, in a sample of predominantly White women with and without a prior diagnosis of breast cancer. The purpose was to establish an initial understanding of SAM functioning in relation to the participants’ HPA activity as measured by cortisol responses (complementary to a previously published study in the laboratory). Results of Study 1 revealed no abnormal response to stress. Virtually identical alpha-amylase slopes were observed between breast cancer survivors and control participants, except that breast cancer survivors had elevated basal levels of alpha-amylase, thus suggesting a “heightened sympathetic tone”. In Study 2 acute and diurnal cortisol profiles and their accompanying psychological stress responses were examined in a sample of Chinese and White women with and without a prior diagnosis of breast cancer. In the same participants, we also examined chronic stress levels via hair cortisol concentrations which was the subject of Study 3. In both studies 2 and 3, we assessed the potential influences of cultural orientation and ethnocultural group membership on physiological and psychological stress patterns. For the most part, Study 2 supported previous findings from the literature and our laboratory: Breast cancer survivors displayed a blunted cortisol response and their diurnal profile was comparable to that of control participants. But contrary to our hypotheses, ethnocultural membership and cultural orientation did not influence physiological patterns of stress. However, an interaction between ethnocultural group, health status, and time (i.e., from baseline to one hour after stress induction) was observed in the subjective appraisal of an acute stressor. Specifically, White breast cancer survivors reported significantly lower levels of perceived stress than the other three groups. These results suggest that health-related stress may supersede the effects of culturally related stress and indicate the potential presence of posttraumatic growth among our sample of White breast cancer survivors only. Study 3 revealed no differences in hair cortisol concentrations between breast cancer survivors and control participants, nor between Chinese and White breast cancer survivors. However, it was observed that healthy Chinese women exhibited significantly higher levels of hair cortisol concentrations than their Western counterpart. Further analyses revealed that health status and cultural orientation did not significantly predict the observed patterns of physiological or psychological stress. Although non-significant, Study 3 results offered preliminary evidence that higher orientation towards both the dominant and non-dominant cultures is associated with higher levels of chronic physiological and psychological stress. Collectively, our studies may provide support for the long-term recovery of the HPA axis via the examination of acute, diurnal, and chronic patterns of cortisol, but further research will be required. The dissertation also highlights several important key points regarding culturally related factors, health, and stress: (1) The perception of stress is influenced by one’s degree of cultural orientation and (2) effects of health-related stress may supersede those of culturally related stress, but (3) among healthy women, ethnocultural minorities may have more stressful encounters than their Western counterpart, thus having important clinical implications for ethnocultural minorities who are newly diagnosed with a chronic condition. Together, results of the studies highlight the importance of further investigating the enduring and acute implications of psychosocial variables – particularly the influence of cultural orientation – on the experience and perception of stress.

Carcinomas de glândulas salivares são raros e seu tratamento de escolha é cirúrgico, seguido ou não de radioterapia. Até 50% dos casos apresentam recorrências neoplásicas e a maioria delas é local. O único tratamento de resgate com potencial curativo é o cirúrgico. No entanto, poucos estudos abordam o tema. O objetivo deste estudo é avaliar a ocorrência de complicações cirúrgicas e os fatores prognósticos clínicos e anatomopatológicos em pacientes portadores de carcinoma de glândulas salivares recidivado, submetidos à cirurgia de resgate. Foram avaliados 59 pacientes que preenchiam os critérios de elegibilidade do estudo: diagnóstico comprovado da recidiva de carcinoma de glândulas salivares e cirurgia de resgate realizada com intenção curativa. Trinta e 5 pacientes desta série (59,3%) foram tratados previamente em outra instituição. A cirurgia de resgate de todos os pacientes foi realizada no Hospital A. C. Camargo, em São Paulo, entre os anos de 1957 a 2000. O local do tumor primário foi parótida em 34 casos (57,6%); cavidade oral, em 13 (22,1%) e glândula submandibular, em 12 (20,3%). O tipo histológico mais freqüente foi o carcinoma adenocístico em 23 casos (39%), seguido pelo carcinoma mucoepidermóide, em 14 (23,7%). O tratamento prévio foi somente cirurgia em 47 casos, cirurgia e radioterapia adjuvante em 11 casos e cirurgia e quimioterapia em apenas um caso. A maioria dos pacientes apresentou recorrência local (39; 66%), em sete casos a recorrência foi regional (11,9%) e em treze foi locorregional (22,1%). O estádio clínico da recorrência foi inicial (rEC I e II) em 15 casos (25,5%) e avançado (rEC III e IV), em 44 (74,5%). O tratamento cirúrgico da recorrência foi ressecção local em 39 casos (66,1%), esvaziamento cervical isolado em 7 (11,9%) e cirurgias em monobloco (ressecção local associada a esvaziamento cervical) em 13 casos (22%). Em 5 pacientes foi realizada parotidectomia ampliada com temporalectomia. A taxa global de complicações cirúrgicas foi de 32,2%. A complicação mais comum foi a infecção da ferida operatória. Não houve mortalidade pós-operatória. Houve nova recorrência em 36 pacientes (61%). A recorrência mais freqüente foi a distância, em 16 casos (27%), sendo o pulmão o sítio mais acometido. Em 10 casos (17%) houve falha no controle local; em 5 (8,5%), falha locorregional e em 5, falha regional (8,5%). A sobrevida atuarial global, após a cirurgia de resgate, foi de 61,3% em 5 anos e 42% em 10 anos. O sexo, o tipo histológico, a topografia, o estadiamento clínico e a conservação do nervo facial (tumores parotídeos) não apresentaram associação com a sobrevida global. Em análise univariada a idade maior que 60 anos foi associada a pior prognóstico. Este estudo demonstra que o prognóstico de pacientes com carcinomas de glândulas salivares recidivados, selecionados para serem submetidos à cirurgia de resgate é aceitável. As taxas de complicações cirúrgicas foram geralmente locais e não houve mortalidade pós-operatória nesta série. / Salivary gland carcinomas are rare and the main treatment option is surgery with or without postoperative radiotherapy. Almost half of the cases present recurrences of tumors and the majority are local. The only potentially curative treatment for recurrent tumors is salvage surgery. However, few papers were published on this subject. The aim of this study is evaluate the surgical complications and clinical and pathologic prognostic factors in patients with recurrent salivary gland carcinoma submitted to salvage surgery. We reviewed the medical charts of 59 patients that fulfilled the eligibility critera of the study: proven diagnosis of locorregionally recurrent salivary gland carcinoma and surgery with curative intention. Thirty five patients (59,3%) had been previously treated at another institution. The salvage surgery in all the patients was performed at the A. C. Camargo Hospital in São Paulo, Brazil from 1957 to 2000. The site of the primary tumor was the parotid in 34 cases, the oral cavity in 13 and submandibular gland in 12 cases. The most frequent histopathologic type was adenoid cystic carcinoma (23 cases; 39%) and mucoepidermoid carcinoma (14 cases ;23.7%). The prior treatment was surgery alone in 47 cases, surgery with adjuvant radiotherapy in 11 cases and surgery and adjuvant chemotherapy in only one case. The majority of the patients presented local recurrence (39; 66%), in seven cases the recurrence was regional (11.9%) and in thirteen cases it was locorregional (22.1%). The clinical stage of the recurrences were initial (rCS I/II) in 15 patients (25.5%) and advanced (rCS III/IV) in 44 patients (74.5%). The surgical treatment of the recurrence was local ressection in 39 cases (66.1%), en bloc surgeries (local ressection and neck dissection) in thirteen cases (22%) and neck dissection alone in seven cases (11.9%). Wide parotidectomy with temporal bone ressection was performed in five cases. The overall rate of surgical complications was 32.2%. The most frequent complication was wound infection. There was no post-operative deaths. There was a new recurrence in 61% of the patients, and the majority were distant metastases (16 cases; 27%). The lung was the most frequent involved site. In ten cases (17%) the recurrence was local, in five cases it was locorregional (8.5%). The actuarial overall survival were 61.3% in 5 years and 42% in ten years and in five cases it was regional (8.5%). Gender, histopathology, site of the primary tumor, facial nerve preservation (parotid tumors), were not associated with overall survival. In the univariate analysis, only age older than 60 years was associate with a poor prognosis. This study shows that the prognosis of patients with recurrent salivary gland carcinoma treated to salvage surgery is acceptable. The rates of surgical complications are local and there was no post-operative mortality in this series.

Made available in DSpace on 2015-05-14T12:56:01Z (GMT). No. of bitstreams: 1 parte 1.pdf: 286274 bytes, checksum: 680b6739458bd32bbb943941a13dc712 (MD5) Previous issue date: 2007-12-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Diabetes mellitus is an endocrine disease, which causes alteration in assimilation, metabolism and balance of the blood glucose concentration. It is believed that the high level of blood glucose is linked to the development of buccal alterations; however, there is some controversy in the studies that aim to compare the concentration of blood and salivary glucose in diabetic patients. The objective of this paper is to comparatively evaluate the concentration of blood and salivary glucose as well as the salivary flow and xerostomia in type 2 diabetic and non-diabetic patients. Eighty adult subjects of both sexes have been selected, being 40 adults diabetic of the experimental type and 40 adults non-diabetic belonging to control. The total in-rest and stimulated salivary flow has been determined as well as the concentration of peripheral blood and salivary glucose. Descriptive analysis was carried out and Mann-Whitney and qui-square tests were applied considering significant values of p<0,05. The average value of salivary glucose in diabetic patients was 14,03±16,76 mg/dl and in the control group, 6,35±6,02 mg/dl, with p= 0,036. The capillary blood glucose in diabetic patients presented an average value equivalent to 213,23±87,98 mg/dl and, in non-diabetic patients it was equivalent to 99,15±13,72 mg/dl, with p= 000. The average value for the in-rest salivary flow was 0,21±0,16 ml/min in diabetic patients and 0,33±0,20 ml/min in the control group with p= 0,002. The stimulated salivary flow was lower in the group of diabetic patients, with an average of 0,63±0,43 ml/min, in relation to the control group, which presented an 1,20±0,70 ml/min average, with p= 0,00. Out of the diabetic patients, 45% had hyposalivation contrasting to 2,5% out of the non-diabetic patients, with p=0,00. Xerostomia was reported in 12,5% of diabetic patients and 5% of non-diabetic patients, with p=0,23. We can conclude that the salivary glucose concentration was significantly higher in the experimental group and that there was no correlation between the salivary and blood glucose concentration in diabetic patients. The total salivary flows were significantly reduced in diabetic patients and there was no significant difference as to the presence of xerostomia in both groups. / O diabetes mellitus é uma doença endócrina que causa alteração na assimilação, metabolismo e equilíbrio da concentração da glicose sanguínea. Acredita-se que o elevado nível de glicose sangüínea esteja associado ao desenvolvimento de alterações bucais, porém, existe controvérsia nos estudos que objetivam comparar a concentração de glicose sanguínea e salivar em pacientes diabéticos. O objetivo do presente estudo foi avaliar comparativamente a concentração de glicose salivar e sanguínea, o fluxo salivar e a xerostomia em pacientes diabéticos tipo 2 e não diabéticos. Foram selecionados 80 indivíduos adultos, de ambos os sexos, sendo 40 adultos diabéticos pertencentes ao experimental e 40 adultos não diabéticos pertencentes ao controle. Determinou-se o fluxo salivar total em repouso e estimulado, a concentração de glicose salivar e sanguínea periférica. Realizou-se análise descritiva e aplicaram-se testes de Mann-Whitney e qui-quadrado, considerando significantes valores de p<0,05. O valor médio de glicose salivar nos diabéticos foi 14,03±16,76 mg/dl e, no grupo controle, 6,35±6,02 mg/dl, com p= 0,036. A glicose sanguínea capilar nos diabéticos apresentou valor médio equivalente a 213,23±87,98 mg/dl e, nos não diabéticos, a 99,15±13,72 mg/dl, com p= 000. O valor médio para o fluxo salivar em repouso foi de 0,21±0,16 ml/min nos diabéticos e 0,33±0,20 ml/min no grupo controle, com p= 0,002. O fluxo salivar estimulado foi inferior no grupo dos diabéticos, com média de 0,63±0,43 ml/min, em relação ao grupo controle que apresentou média 1,20±0,70 ml/min, com p= 0,00. Entre os diabéticos, 45% apresentaram hipossalivação, contrastando com os 2,5% entre os não diabéticos, com p=0,00. A xerostomia foi referida em 12,5% dos diabéticos e 5% dos não diabéticos, com p=0,23. Pode-se concluir que concentração de glicose salivar foi significativamente maior no grupo experimental e que não houve correlação entre a concentração da glicose salivar e glicose sanguínea nos indivíduos diabéticos. Os fluxos salivares totais mostraram-se significativamente reduzidos nos pacientes diabéticos e não houve diferença significativa quanto à presença de xerostomia em ambos os grupos.

Carcinomas de glândulas salivares são raros e seu tratamento de escolha é cirúrgico, seguido ou não de radioterapia. Até 50% dos casos apresentam recorrências neoplásicas e a maioria delas é local. O único tratamento de resgate com potencial curativo é o cirúrgico. No entanto, poucos estudos abordam o tema. O objetivo deste estudo é avaliar a ocorrência de complicações cirúrgicas e os fatores prognósticos clínicos e anatomopatológicos em pacientes portadores de carcinoma de glândulas salivares recidivado, submetidos à cirurgia de resgate. Foram avaliados 59 pacientes que preenchiam os critérios de elegibilidade do estudo: diagnóstico comprovado da recidiva de carcinoma de glândulas salivares e cirurgia de resgate realizada com intenção curativa. Trinta e 5 pacientes desta série (59,3%) foram tratados previamente em outra instituição. A cirurgia de resgate de todos os pacientes foi realizada no Hospital A. C. Camargo, em São Paulo, entre os anos de 1957 a 2000. O local do tumor primário foi parótida em 34 casos (57,6%); cavidade oral, em 13 (22,1%) e glândula submandibular, em 12 (20,3%). O tipo histológico mais freqüente foi o carcinoma adenocístico em 23 casos (39%), seguido pelo carcinoma mucoepidermóide, em 14 (23,7%). O tratamento prévio foi somente cirurgia em 47 casos, cirurgia e radioterapia adjuvante em 11 casos e cirurgia e quimioterapia em apenas um caso. A maioria dos pacientes apresentou recorrência local (39; 66%), em sete casos a recorrência foi regional (11,9%) e em treze foi locorregional (22,1%). O estádio clínico da recorrência foi inicial (rEC I e II) em 15 casos (25,5%) e avançado (rEC III e IV), em 44 (74,5%). O tratamento cirúrgico da recorrência foi ressecção local em 39 casos (66,1%), esvaziamento cervical isolado em 7 (11,9%) e cirurgias em monobloco (ressecção local associada a esvaziamento cervical) em 13 casos (22%). Em 5 pacientes foi realizada parotidectomia ampliada com temporalectomia. A taxa global de complicações cirúrgicas foi de 32,2%. A complicação mais comum foi a infecção da ferida operatória. Não houve mortalidade pós-operatória. Houve nova recorrência em 36 pacientes (61%). A recorrência mais freqüente foi a distância, em 16 casos (27%), sendo o pulmão o sítio mais acometido. Em 10 casos (17%) houve falha no controle local; em 5 (8,5%), falha locorregional e em 5, falha regional (8,5%). A sobrevida atuarial global, após a cirurgia de resgate, foi de 61,3% em 5 anos e 42% em 10 anos. O sexo, o tipo histológico, a topografia, o estadiamento clínico e a conservação do nervo facial (tumores parotídeos) não apresentaram associação com a sobrevida global. Em análise univariada a idade maior que 60 anos foi associada a pior prognóstico. Este estudo demonstra que o prognóstico de pacientes com carcinomas de glândulas salivares recidivados, selecionados para serem submetidos à cirurgia de resgate é aceitável. As taxas de complicações cirúrgicas foram geralmente locais e não houve mortalidade pós-operatória nesta série. / Salivary gland carcinomas are rare and the main treatment option is surgery with or without postoperative radiotherapy. Almost half of the cases present recurrences of tumors and the majority are local. The only potentially curative treatment for recurrent tumors is salvage surgery. However, few papers were published on this subject. The aim of this study is evaluate the surgical complications and clinical and pathologic prognostic factors in patients with recurrent salivary gland carcinoma submitted to salvage surgery. We reviewed the medical charts of 59 patients that fulfilled the eligibility critera of the study: proven diagnosis of locorregionally recurrent salivary gland carcinoma and surgery with curative intention. Thirty five patients (59,3%) had been previously treated at another institution. The salvage surgery in all the patients was performed at the A. C. Camargo Hospital in São Paulo, Brazil from 1957 to 2000. The site of the primary tumor was the parotid in 34 cases, the oral cavity in 13 and submandibular gland in 12 cases. The most frequent histopathologic type was adenoid cystic carcinoma (23 cases; 39%) and mucoepidermoid carcinoma (14 cases ;23.7%). The prior treatment was surgery alone in 47 cases, surgery with adjuvant radiotherapy in 11 cases and surgery and adjuvant chemotherapy in only one case. The majority of the patients presented local recurrence (39; 66%), in seven cases the recurrence was regional (11.9%) and in thirteen cases it was locorregional (22.1%). The clinical stage of the recurrences were initial (rCS I/II) in 15 patients (25.5%) and advanced (rCS III/IV) in 44 patients (74.5%). The surgical treatment of the recurrence was local ressection in 39 cases (66.1%), en bloc surgeries (local ressection and neck dissection) in thirteen cases (22%) and neck dissection alone in seven cases (11.9%). Wide parotidectomy with temporal bone ressection was performed in five cases. The overall rate of surgical complications was 32.2%. The most frequent complication was wound infection. There was no post-operative deaths. There was a new recurrence in 61% of the patients, and the majority were distant metastases (16 cases; 27%). The lung was the most frequent involved site. In ten cases (17%) the recurrence was local, in five cases it was locorregional (8.5%). The actuarial overall survival were 61.3% in 5 years and 42% in ten years and in five cases it was regional (8.5%). Gender, histopathology, site of the primary tumor, facial nerve preservation (parotid tumors), were not associated with overall survival. In the univariate analysis, only age older than 60 years was associate with a poor prognosis. This study shows that the prognosis of patients with recurrent salivary gland carcinoma treated to salvage surgery is acceptable. The rates of surgical complications are local and there was no post-operative mortality in this series.

Le suivi et la compréhension des états de stress et de récupération des sportifs est un enjeu majeur, notamment dans le cadre de périodisations complètes de l’entraînement. Un déséquilibre mal maîtrisé entre le stress et la récupération peut induire une fatigue voire un épuisement psychologique et physiologique du sportif. Il en découlera des conséquences néfastes sur le bien-être et la santé de la personne mais également sur la performance individuelle et collective. Ces conséquences sont complexes et impliquent des dimensions environnementales, sociales, psychologiques et physiologiques non-spécifiques. Enfin, ces symptômes sont soumis à des variations intra et interindividuelles importantes rendant le diagnostic d’autant plus complexe à établir. En s’appuyant sur plusieurs suivis de sportifs en pôle « Espoir », ce travail de recherche montre l’évolution de variables psychologiques et physiologiques intervenant dans la réponse au stress chez le sportif. Ces travaux permettent également de mettre en évidence des variables prédictives des états de stress et de récupération. Enfin, nous démontrons que les états de stress et de récupération des sportifs impactent les états émotionnels au niveau intra et interindividuel. / Monitoring stress and recovery states is a key issue, especially in high performance sport. An imbalance between stress and recovery can induce fatigue, psychological and physiological exhaustion. Thus, negative consequences on well-being, health and individual and collective performance can be experienced. These consequences are complex as they stem from non-specific environmental, social, psychological and physiological dimensions. These phenomena are subject to important intra-individual and inter-individual variations, which make a diagnosis hard to establish. Based on a several followings of athletes from high performance structures, this research shows the evolution of psychological and physiological variables intervening as a response to stress. From these studies, some predictive variables also showed up in predicting stress and recovery states. Finally, we made evidence of the impact of athletes’ stress and recovery states on emotional states, on the intra and inter-individual levels.

v anglickém jazyce The possible assessments of unprofessional exposures of low frequency noise Introduction: Along with technical development, the number of sources of low frequency noise increases in the human environment and the number of complaints from people exposed to noise from these sources increases as well. The statutory limit for non-professional exposure to low frequency noise has not yet been established (due to the limited amount of data on low frequency noise exposure risks) in the EU countries (USA) and no WHO recommendations have been issued in this area. For these reasons, the hygienic limit for municipal/non-professional exposure to low frequency noise was not specified in the Czech Republic. Objecticve: The present dissertation thesis was to investigate whether the short-term experimental exposure to low frequency noise with the tonic component induces significant changes in the circadian rhythm of cortisol and alpha-amylase in saliva in the experimental set of volunteers. Saliva is a biological material that allows low-invasiveness collection. The work was supposed to assess whether possible changes could be used as objective indicators of the presence of the stress response to the noise exposure. Material and metods: An experimental study was conducted on a set of 100...

Doctor of Philosophy / Department of Entomology / Marcelo Ramalho-Ortigao / The emergence and reemergence of vector-borne diseases pose significant threats to humans and other animals worldwide. Although vector control relies mostly on insecticides, the emergence of insecticide resistance urges for the development of new strategies to control the spread of such diseases. For sand fly-transmitted leishmaniasis, Transmission Blocking Vaccines (TBV) may constitute a feasible strategy to impair Leishmania transmission from infected to uninfected vertebrate hosts. Moreover, sand fly saliva-based vaccines represent an alternative or complementary approach as these vaccines protect different mammalian hosts against Leishmania. Based on the potential use of sand fly molecules as vaccines against leishmaniasis, we assessed the potential of Phlebotomus papatasi midgut secreted proteins as TBV candidates and the expression variability of sand fly salivary gland genes. Regarding the TBV approach, we took advantage of the RNA interference (RNAi) technique to evaluate the effects of knocking down P. papatasi midgut-specific genes on Leishmania major development within the sand fly midgut. Whereas peritrophin 1 (PpPer1) knock down led to increased Le. major load by 39%, knocking down chitinase 1 (PpChit1) reduced Le. major load in P. papatasi midguts by 63%. Thus, our data strongly suggest that PpChit1 constitutes a potential target for TBV approaches against Leishmania transmission in endemic areas. Concerning protective vaccines based on salivary gland secreted proteins, we searched for expression polymorphism in selected salivary gland genes in natural and colonized populations of P. papatasi. Significant differences in salivary gland gene expression were not only exhibited in P. papatasi specimens collected in different geographic habitats but also seasonal difference in gene expression was displayed by specimens belonging to the same population. As antigen dose is an important component of immune responses, different doses of salivary protein inoculated into host skin may interfere with vaccine protection. Thus, the efficacy of sand fly saliva-based vaccine upon exposure to different salivary protein doses must be evaluated before deployment in endemic areas. Our data also ruled out some biotic factors as responsible for fine-tuning the expression of such genes. Overall, this dissertation makes significant contribution to the development of sand fly-based vaccines against leishmaniasis.

L’astringence est une sensation de sécheresse ressentie en bouche lors de la dégustation des vins rouges, qui résulte de la complexation entre les polyphénols du vin et les protéines de la salive, provoquant une diminution de lubrification en bouche. Parmi les protéines salivaires, les protéines riches en prolines (PRP) sont connues pour leur capacité à se lier aux polyphénols et à précipiter avec eux. Une meilleure connaissance de ce phénomène au niveau moléculaire est nécessaire pour le comprendre et le maîtriser. Il a été montré qu’un peptide de quatorze acides aminés, IB714, dont la séquence est conservée au sein des protéines riches en proline, était un mime représentatif des PRP. Un travail préliminaire par spectrométrie de masse résolue en énergie a permis de caractériser les interactions entre des polyphénols et le peptide IB714. Une échelle d’affinité en phase gazeuse a ainsi été déterminée. Cependant, cette méthodologie d’analyse d’un système modèle ne permet pas de s’accommoder de la complexité du vin. C’est pourquoi nous avons conçu une nouvelle stratégie reposant sur l'utilisation de sondes moléculaires immobilisée sur des billes magnétiques. Dans un premier temps nous avons élaboré une sonde peptidique, en greffant le peptide IB714 sur des billes magnétiques portant des fonctions carboxylates. Cette sonde peptidique a ensuite été étudiée avec des polyphénols modèles. Après sédimentation des billes magnétiques, les polyphénols non captés par la sonde ont été dosés par spectrométrie de masse en utilisant un étalon interne. Une échelle d'affinité en phase liquide a été établie de cette manière. Les positions relatives des polyphénols modèles sur cette échelle sont similaires à celles qui ont été établies en phase gazeuse. Dans un second temps, nous avons construit sur le même principe une sonde polyphénolique. Pour cela, un polyphénol modifié chimiquement a été immobilisé sur des billes magnétiques portant des fonctions amines. Cette sonde polyphénolique a été utilisée pour étudier l'interaction avec le peptide IB714. Par ailleurs, pour préparer une étude des interactions entre polyphénols et protéines salivaires avec des mélanges plus complexes que les systèmes modèles, une étude de fractionnement des protéines salivaires a été entreprise, permettant notamment de d’éliminer l’amylase, protéine majoritaire de la salive humaine. De même, un fractionnement d’un vin rouge a été entrepris pour disposer de fractions de tannins caractérisées par spectrométrie de masse. La sonde peptidique est l’outil moléculaire qui offre le plus de perspectives de développement ultérieur. / Astringency is a pucker or dry mouth sensation, typically experimented with red wine tasting, that finds its origin in the complexation of polyphenols with salivary proteins, producing a reduced lubrication of the oral cavity. Among salivary proteins, proline rich proteins (PRPs) are well known for their capacity to bind and precipitate dietary polyphenols. A better knowledge of this phenomenon at the molecular level is required in order to master it. A 14 amino acid stretch from the PRP IB7 has been synthesized and shown to be a representative mimic of PRPs. Previous work by Energy Resolved Mass Spectrometry (ERMS) allowed characterizing the keys parameters of the interactions between these polyphenols and the IB714 probe. An affinity scale in the gas phase was determined in this way. However, the ERMS approach was hardly compatible with the complexity of wine polyphenols, and a validation of the affinity scale in condensed phase was required. Thus, we designed a new strategy relying on the use of molecular probes immobilized on magnetic beads. A peptidic probe was obtained by grafting the synthetic IB714 peptide on magnetic beads bearing carboxylate functions, and used to study its interaction with model polyphenols. After magnetic precipitation of the beads, unbound polyphenols left in the supernatant were quantified by mass spectrometry using an internal standard. An affinity scale in liquid phase was established in this way. Relative positions of model polyphenols on this latter scale were similar to those determined by ERMS. A polyphenolic probe was obtained by grafting a model polyphenol on beads bearing amine functions. This probe has been used to study the interaction with IB714. To prepare further work on more complex mixtures, attempts were made to fractionate human saliva; this allowed eliminating amylase, the major salivary protein. Wine tannins were also fractionated, in order to isolate condensed polyphenols that are characterized by mass spectrometry. The peptidic probe is the molecular tool that offers the best perspectives for future work.

Zielstellung: Die Verwendung von Computertomographie und Magnetresonanzto-mographie zur Diagnostik von pathologischen Weichteilveränderungen, wie Läsionen der Speicheldrüsen, wird empfohlen. Diese begründet sich in Ihrer hohen Bildauflö-sung und dem guten Bildkontrast. Nach unserem Wissen gibt es aktuell keine publi-zierte Literatur, welche sich mit der CT- oder MRT-Anatomie der Speicheldrüsen der Katze beschäftigt. Ziel der vorliegenden Arbeit war es daher, Schnittbildmerkmale der Speicheldrüsen zu definieren und Landmarken für eine sichere Identifikation zu be-schreiben. Material und Methoden: Es wurden zwei Gruppen von Katzen untersucht. Die pros-pektiv untersuchten Tiere bestanden aus 16 Katzen, welche aus Gründen euthana-siert wurden, die nicht in Zusammenhang mit der Studie standen. Diese erfuhren ein CT (1 mm Schichtdicke) und 0,5 Tesla MRT (T2W, T2W SPIR, PDW, T1W) des Kop-fes. Im retrospektiven Anteil der Studie wurden CT-Untersuchungen (0,8-1 mm Schichtdicke) von 25 Katzen und MRT-Untersuchungen (T2W, T1W vor und nach Kontrastmittelgabe) von 21 Katzen verwendet. Diese Untersuchungen wurden zwi-schen 2005 und 2013 in unserer Klinik angefertigt. Dabei konnten keine Pathologien in Zusammenhang mit den Speicheldrüsen festgestellt werden. Alle Speicheldrüsen wurden bezüglich Identifizierbarkeit, Abgrenzbarkeit, Größe und Signalverhalten un-tersucht. Wenn vorhanden, wurden anatomische Landmarken die Speicheldrüsen umgebend notiert. Zusammenfassung 80 Ergebnisse: 94,3% der Glandulae parotidae, 90,7% der Glandulae mandibulares und 96,8% der Glandulae zygomaticae konnten mit dem CT identifiziert werden. Beim MRT waren es 94,1% der Glandulae parotidae, 99,2 % der Glandulae mandibulares, 88,9% der Glandulae zygomaticae und 51,4 % der Glandulae buccalis ventralis. In beiden Gruppen konnten keine der restlichen kleinen Speicheldrüsen identifiziert werden, dies galt für beide Schnittbildverfahren. Als hilfreiche anatomi-sche Landmarken konnten der äußere Gehörgang, der M. masseter, der M. pterygo-ideus medialis und der Bulbus oculi herangezogen werden. Die medianen Dichtewer-te lagen für die Glandula parotis, die Glandula mandibularis und die Glandula zygo-matica bei 65 HU, 62 HU und 57 HU. Die Parotis war überwiegend dezent hyperin-tens zur Muskulatur und hypointens zum Fett. Die Mandibularis, Zygomatica, und Glandula buccalis ventralis stellten sich hauptsächlich hyperintens zur Muskulatur und hypointens zu Fettgewebe dar. Dieses Signalverhalten war für T1W, T2W und T2W SPIR (fettunterdrückt) gewichtete Sequenzen gleich. Die Größe war für beide Gruppen und Modalitäten vergleichbar und lag bei circa 17 x 6 mm (gemessen von lateral nach medial und von dorsal nach ventral) bei der Glandula parotis, 8 x 17 mm bei der Glandula mandibularis, 10 x 7 mm bei der Glandula zygomatica und bei der Glandula buccalis ventralis 3 x 10 mm. Schlussfolgerungen: Landmarken und Aussagen über die Signalintensität bezie-hungsweise Dichte und die Größe der Glandula parotis, Glandula mandibularis, Glandula zygomatica und der Glandula buccalis ventralis konnten erhoben werden. Die mangelhafte Identifizierbarkeit der restlichen kleinen Speicheldrüsen, im Ver-gleich zu den oben genannten, kann vor allem mit dem unzureichenden Weichteil-kontrast zum umliegenden Gewebe im CT und der niedrigen Auflösung des Nieder-feld-MRTs erklärt werden. Neuere MRT-Techniken können detailliertere Bilder er-zeugen und so eine Beschreibung der kleinen Speicheldrüsen ermöglichen. / Objective: Due to their high resolution and useful contrast resolution, CT and MRI are recommended methods for diagnosing pathological changes of soft tissues such as lesions of the salivary glands. To our knowledge, no studies about the CT or MR anatomy of the feline salivary glands have been published yet. The aim of the study was to define anatomical characteristics of the salivary glands in cross-sectional im-ages and to describe landmarks for a reliable identification. Materials and methods: Two groups of cats where examined. In a prospective trial, 16 cats, euthanized for reasons unrelated to the study, underwent a head CT (1 mm slice thickness) and 0.5 Tesla MRI scans (T2W, T2W SPIR, PDW, T1W). In a retro-spective trial, the CT scans (0.8-1 mm slice thickness) of 25 cats and the MR scans (T2W, T1W, pre- and post-contrast) of 21 cats were used. These scans were per-formed at our clinic between 2005 and 2013. No signs of salivary-gland-related pa-thologies were visible. All images were reviewed with respect to the following criteria: the presence, delineation and size of the salivary glands as well as the signal intensi-ty. Anatomical landmarks surrounding the glands were also recorded. Results: 94.3% of the parotid glands, 90.7% of the mandibular glands and 96.8% of the zygomatic glands could be delineated using CT. With MRI, 94.1% of the parotid Summary 82 glands, 99.2 % of the mandibular glands, 88.9% of the zygomatic glands and 51,4 % of the ventral buccal glands could be identified. In both groups the other small salivary glands could not be visualized neither in CT nor in MRI. Anatomical landmarks such as the external ear canal, the M. masseter, the M. pterygoideus medialis and the Bulbus oculi facilitate the identification. The mean density of the parotid gland, the mandibular gland and the zygomatic gland was 65 HU, 62 HU and 57 HU, respectively. The parotid gland was mainly modestly hyperintense to muscle and hypointense to fat. The mandibular, zygomatic and ven-tral buccal glands were hyperintense to muscle and hypointense to fat. Signal intensi-ties were similar for T1W, T2W and T2W SPIR images. Sizes were comparable for both groups and modalities and measured about 17x6 mm (lateral to medial and dor-sal to ventral) for the parotid gland, 8 x 17 mm for the mandibular gland, 10x7 mm for the zygomatic gland and 3x10 mm for the ventral buccal gland. Conclusions: Landmarks were recorded and data regarding the density/signal in-tensity and the size of the parotid gland, the mandibular gland, the zygomatic gland and the ventral buccal gland could be gathered. The discrepancy between depicting the small glands and the above mentioned glands can be explained mainly by the lack of contrast to the surrounding tissue in CT and the low spatial resolution in low-field MRI. Advanced MRI techniques are expected to produce more detailed images and therefore those techniques could be used to also describe the small salivary glands.