Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 5 uppsatser.

Comprendre comment les facteurs génétiques et environnementaux interagissent au cours du développement est une question fondamentale en biologie. Je me suis intéressée à cette question en utilisant le réseau de développement de la vulve du nématode C. elegans comme système modèle. L’objectif de mon projet était une étude quantitative de la modulation par l’environnement des voies de signalisation impliquées dans ce processus telles que, Ras, Delta-Notch et Wnt. J’ai tout d’abord analysé comment un facteur environnemental spécifique (la carence nutritionnelle) modifie les activités et les interactions entre les voies de signalisation sous-jacentes au développement vulvaire chez C. elegans. J’ai ainsi mis en évidence que l’augmentation de l’induction vulvaire par la carence passe par une augmentation de l’activité de la voie Ras et est indépendante de la voie Wnt. Cet effet de l’environnement est assuré par la détection de la diminution de l’apport en nutriments, probablement par l’action de la voie TOR, et affecte l’induction vulvaire en parallèle ou en amont du récepteur à l’EGF. J’ai ensuite examiné la sensibilité environnementale du système de développement de la vulve de Caenorhabditis dans une perspective évolutive et ce, grâce à l'analyse comparative de différents isolats. J’ai pu observer que l’exposition à des températures extrêmes induit des variants et des défauts de manière fortement dépendante de la souche et de l’espèce. L’occurrence de certains défauts développementaux induits par la température révèlent en outre que certaines cellules précurseurs de la vulve et les voies de signalisation associées présentent une sensibilité environnementale différente. / How genetic and environmental factors interact during development is a key question in current biology, yet little is known about how molecular and cellular processes integrate environmental information. In my PhD research I aimed to address this problem using the network of C. elegans vulval signalling pathways as a model system. The principal objective of my project was to quantitatively examine how involved major signalling pathways, EGF-Ras-MAPK, Wnt and Delta-Notch, are modulated by specific environmental signals. First, I analysed how a specific environmental factor (starvation) alters activities and interplay of signalling pathways underlying C. elegans vulval cell fate patterning. I found that starvation consistently increased vulval induction through upregulation of the EGF-Ras-MAPK pathway activity independent of the Wnt pathway. This environmental effect is mediated by internal sensing of nutrient deprivation, likely acting through the TOR pathway, and affects vulval induction at the level or upstream of the EGF receptor. Second, I examined the environmental sensitivity of the Caenorhabditis vulval developmental system from an evolutionary perspective through comparative analysis of different C. elegans and C. briggsae isolates. I found that extreme temperature induced diverse developmental variants and defects, which were strongly genotype- and species-dependent. The occurrence of certain developmental defects induced by temperature extremes further revealed that vulval precursor cells and associated fates differ in temperature sensitivity, and this cell-specific sensitivity shows evolutionary variation.

Orientador: Marlus Chorilli / Coorientador: Giovana Maria Fioravanti Calixto / Banca: Anderson Orzari Ribeiro / Banca: Denise Madalena Palomarim Spolidorio / Resumo: A candidíase vulvovaginal (CVV) é uma doença causada por espécies do gênero Candida spp. no trato genital inferior feminino que afeta um grande número de mulheres em todo mundo. Porém o uso sistêmico de fármacos causa muitas reações adversas e as formulações tópicas possuem um baixo tempo de retenção na mucosa vaginal devido à diluição dos sistemas na cavidade vaginal. Esse estudo propõe uma terapia antifúngica alternativa empregando sistemas precursores de cristais líquidos mucoadesivos (SPCLM) para a liberação de hipericina (HIP), um potente fotossensibilizador isolado de plantas do gênero Hipericum com e sem o emprego da terapia fotodinâmica (TFD). O sistema visa aumentar o tempo de permanência da formulação, bem como reduzir o número de aplicações e a quantidade de fármaco empregada. O emprego da TFD, por sua vez, se faz como uma forma de diminuir a resistência pelos microrganismos. Observou-se a formação de sistemas isotrópicos no sistema constituído por 30% da fase oleosa constituída por ácido oleico e colesterol na razão de 7:1, 40% de Procetyl AWS como tensoativo e 30% de uma dispersão de poloxamer à 16% empregando as técnicas de microscopia de luz polarizada e espalhamento de raios-X a baixo ângulo. Após a introdução de três diferentes concentrações de fluido vaginal simulado FVS (30, 50 e 100%), as formulações resultantes passaram a apresentar anisotropia e picos característicos de fase lamelar. Análises das propriedades mecânicas, reológicas e mucoadesivas das form... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Vulvovaginal candidosis (VVC) is a disease induced by Candida strains in the female genital tract that affects a great number of women worldwide. However, systemic drugs cause many adverse reactions. Also, currently employed topical dosage forms present low retention times due to their dilution in vaginal fluids. This study proposes an alternative antifungal therapy through the development of liquid crystalline precursor systems (LCPS) for hypericin release, a potent photosensitizer isolated from Hipericum plants with and without photodynamic inactivation (PDI). The developed system aims to increase the residence time of the formulations, as well as decrease the number of applications and the amount of drug. Photodynamic therapy was used to reduce microorganism resistance. Polarized light microscopy and Small-Angle X-Ray Scattering confirmed the formation of an isotropic system composed of 30% of oil phase containing oleic acid and cholesterol in (ratio of 7:1). After addition of three different concentrations of simulated vaginal fluid -SVF (30, 50 and 100%), the resultant formulations presented anisotropy and characteristic peaks of lamellar phases. Mechanical, rheological and mucoadhesive assays indicated the formation of long-range ordering systems as the amount of SVF increased. Drug validation assays indicated that the method is aceptable for hypericin quantification according to regulatory agencies. In vitro drug release assays exhibited a sustained release profile pro... (Complete abstract click electronic access below) / Mestre

Submitted by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-09-29T15:10:17Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação Livia Gusmao.pdf: 1628245 bytes, checksum: 42849e5f87bd042f59660a228ded7164 (MD5) / Approved for entry into archive by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-09-29T15:10:28Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação Livia Gusmao.pdf: 1628245 bytes, checksum: 42849e5f87bd042f59660a228ded7164 (MD5) / Made available in DSpace on 2017-09-29T15:10:28Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação Livia Gusmao.pdf: 1628245 bytes, checksum: 42849e5f87bd042f59660a228ded7164 (MD5) Previous issue date: 2013 / Hospital Icaraí / O líquen escleroso vulvar está envolvido em uma das vias da carcinogênse da vulva ligada à neoplasia intraepitelial vulvar diferenciada. A metilação da região promotora do DNA é a principal alteração epigenética pela qual um gene é inativado em seres humanos. A metilação do gene P16INK4a, que é um supressor de tumor e atua como inibidor da cinase dependente da ciclina, tem sido descrita como um evento precoce na carcinogênese vulvar. A metilação do gene TIMP-2, que atua como regulador de metaloproteinases, tem sido descrito como marcador de matriz extracelular. Esta pesquisa tem como objetivo estudar a presença da metilação dos genes P16INK4a e TIMP-2 no líquen escleroso vulvar e avaliar a associação das variáveis idade, doença de tireóide, tabagismo, uso de hormônio e prurido vulvar com a metilação dos referidos genes. Trata-se de um estudo transversal, onde foram analisadas 32 amostras obtidas por biópsia de pacientes com líquen escleroso vulvar. As amostras foram submetidas à extração do DNA por meio da técnica do fenol:clorofórmio e à avaliação da metilação dos genes P16INK4a e TIMP-2 pela modificação química do DNA pelo método do bissulfito. O DNA modificado foi submetido à PCR e a visualização do produto pelo gel de poliacrilamida. O estudo da associação de cada uma das variáveis com a metilação de ambos genes não mostrou significado estatístico. Notou-se que 39% (11/28) das amostras exibiram metilação somente para o gene TIMP-2, e nenhuma para o gene P16INK4a isoladamente, enquanto 32% (9/28) apresentaram metilação em ambos genes de forma simultânea. A análise da associação da metilação entre ambos genes mostrou significado estatístico (p=0,0292). Esses resultados sugerem que a associação da metilação entre os genes P16INK4a e TIMP-2 possa promover instabilidade genômica, podendo funcionar como marcador na evolução da doença. Estudos futuros sobre alterações moleculares da matriz extracelular, que por precederem as alterações morfológicas, talvez possam funcionar como sinalizador, individualizando as pacientes com maior risco de evolução do líquen escleroso vulvar para a NIV diferenciada e/ou câncer de vulva / The vulvar lichen sclerosus is involved in one of the pathways of vulvar carcinogenesis linked to differentiated vulvar intraepithelial neoplasia. The methylation of the promoter region of the DNA is the main epigenetic modification in humans in which a gene is inactivated. Methylation of P16INK4a gene, which is a tumor suppressor and acts as an inhibitor of cyclin-dependent kinase, has been described as an early event in carcinogenesis vulva. Methylation of TIMP-2 gene, which acts as a regulator of metalloproteinases, has been described as a marker of extracellular matrix. This research aims to study the presence of methylation of the P16INK4a gene and TIMP-2 in vulvar lichen sclerosus and evaluate the association of age, thyroid disease, smoking, hormone use and vulvar itching with methylation of these genes. It is a cross-sectional study, which analyzed 32 samples obtained by biopsy from patients with vulvar lichen sclerosus. The samples were subjected to DNA extraction by using the technique of phenol: chloroform and evaluation of methylation of the p16INK4a gene and TIMP-2 by chemical modification of DNA by the method of bisulfite. The modified DNA was subjected to PCR and visualization of the product by polyacrylamide gel electrophoresis. The association of each variable in the methylation of both genes showed no statistical significance. It was noted that 39% (11/28) samples showed methylation only to TIMP-2 gene, and none only for the P16INK4a gene, while 32% (9/28) exhibited methylation on both genes simultaneously. The analysis of the association between methylation of both genes showed statistical significance (p = 0.0292). These results suggest that the association between methylation of the P16INK4a gene and TIMP-2 can promote genomic instability, which can act as a marker in the evolution of the disease. Future studies on the molecular alterations of the extracellular matrix, which precede morphological changes, maybe they can function as a signal, separating the patients with higher risk of evolution of vulvar lichen sclerosus to differentiated VIN and / or cancer of the vulva

Submitted by (edna.saturno@ufrpe.br) on 2016-10-14T12:17:11Z No. of bitstreams: 1 Leopoldo Mayer de Freitas Neto.pdf: 829417 bytes, checksum: 20a0e805e8a2d62a9b139566d0ef9786 (MD5) / Made available in DSpace on 2016-10-14T12:17:11Z (GMT). No. of bitstreams: 1 Leopoldo Mayer de Freitas Neto.pdf: 829417 bytes, checksum: 20a0e805e8a2d62a9b139566d0ef9786 (MD5) Previous issue date: 2010-02-15 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / In this work, divided into three experiments, the aim was to verify the possibility to diagnose the pregnancy of does and ewes by different pathway access and diagnose the fetuses sex originated by natural mating and transfer of fresh and cryopreserved embryos. The examinations were carried out using an ultrasound scanner equipped with a linear transducer (6.0 and 8.0 MHz) used by transrectal and transabdominal via and a microconvex endocavitary (5.0 and 7.5 MHz) transducer used by transvaginal via. In the first experiment was verified the viability of the ultrasound examination by transretal, transabdominal and transvaginal via to diagnose pregnancy in goats (n = 240) and ewes (n = 320) at days 30th, 45th, 60th and 75th. In does and ewes the ultrasound examination was faster (P < 0.05) on days 30th and 45th of pregnancy, however by transabdominal via was faster on day 60th and 75th. In both species the time of pregnancy diagnose was greater (P < 0.05) on day 30th than the others days while this time was smallest (P < 0.05) at day 75th than day 45th and 60th. Independent of the examination via and the day of pregnancy the average time to diagnose the pregnancy was shorter (P < 0.05) in does than in ewes. Independing of the specie and the day of pregnancy the average time to diagnose the pregnancy by transrectal via was shorter (P < 0.05) than the other vias and the transvaginal via was shorter (P < 0.05) than the transabdominal one. In the second experiment, in order to improve the sexing of Boer fetuses (n = 123) by transrectal ultrasonography, the aim was to identify the migration period of the genital tubercle and its later differentiation into genital structures in fetuses derived from natural mating (TI) and fetus from fresh (TII), frozen (TIII) and vitrified (TIV) embryo transfer collected 7 days after breeding. Migration of the genital tubercle occurred earlier (P < 0.05) in TI (45.21 ± 3.31 days) than in TII (48.50 ± 3.70 days), TIII (48.93 ± 3.61 days) and TIV (48.85 ± 3.23 days). The visualization of the scrotum, prepuce and vulva occurred earlier (P < 0.05) in TI (51.20 ± 2.56; 50.35 ± 1.59; 49.75 ± 1.73 days) than in TII (53.25 ± 2.02; 53.37 ± 1.92; 51.76 ± 2.10 days),TIII (53.37 ± 1.92; 52.31 ± 2.00; 51 ± 78 ± 2.22 days) and TIV (54.06±1.75; 52.46 ± 1.95; 51.91 ± 2.06 days). In the third experiment, in order to improve fetal sexing by ultrasonography in Dorper ewe breed (n = 130), the objective was to identifythe migration period of the genital tubercle and the period of the visualization of external genital structures in fetuses derived from natural mating (TI) and from fresh (TII), frozen (TIII) and vitrified (TIV) embryos transfer collected 7 days after breeding. Migration of the genital tubercle occurred earlier (P < 0.05) in TI (42.21±2.86 days) than in TII (43.98±3.00 days), TIII (44.97±1.83 days) and TIV (44.58±1.97days). The visualization of scrotal bag, prepuce and vulva occurred, respectively, earlier (P < 0.05) in TI (45.22±1.25; 45.95±1.53; 45.01±.103 days) than in TII (48.91±1.92; 48.52±1.41; 47.41±1.41 days), TIII (49.97±1.08; 49.18±2.00; 47.64±1.82 days) and TIV(50.12±1.66; 49.27±1.1.61; 47.93±1.92 days). The results allow to conclude that the pregnancy diagnose may be performed by transrectal, transabdominal and transvaginal via, as well as, that is faster by transrectal via and hat the time for diagnosing is shorterin advanced pregnancy and in goat specie. Is also possible to conclude, taking into consideration the final position of the genital tubercle, that goat fetal sexing can be done from the 55th day onward in fetuses produced by natural mating and from the 60th day onward in fetuses derived from cryopreserved embryos. It can also be concluded that, real-time ultrasonography is a reliable tool for fetal sex determination in sheep after Day 50 of pregnancy taking into account both the location of the genital tubercle and the identification of external genital structures. In ovine species the fetal sexing can be done from the 50th day onward in fetuses produced by natural mating and from the 55th day onward in fetuses derived from cryopreserved embryos. Finally is possible to conclude that real-time ultrasonography is a reliable tool for early pregnancy diagnose in small ruminant as well as that to identify the sex on the first 60 days of pregnancy. / Com este trabalho, dividido em três experimentos, objetivou-se verificar a possibilidade de realizar o diagnóstico de prenhez em cabras e ovelhas por diferentes vias de acesso e sexar fetos originados de monta natural e da transferência de embriões frescos e criopreservados. Os exames foram realizados com um aparelho de ultrassom equipado com um transdutor linear (6,0 e 8,0 MHz) utilizado pelas vias transretal e transabdominal e outro microconvexo (5,0 e 7,5 MHz) endocavitário utilizado por via transvaginal. No primeiro experimento verificou-se a viabilidade do exame ultrassonográfico pelas vias transretal, transabdominal e transvaginal para diagnosticar a gestação de cabras (n = 240) e ovelhas (n = 320) no 30o, 45o, 60o e 75o dia. Nas cabras e ovelhas, o exame ultrassonográfico pela via transretal foi mais rápido (P < 0, 05) no 30o e no 45o dia da gestação, mas, pela via transabdominal foi mais rápido no 60o e no 75o dia. Em ambas as espécies, a duração do diagnóstico de gestação foi maior (P < 0,05) no 30o dia do que nos demais, enquanto que a duração do diagnóstico no 75o dia foi menor (P < 0,05) do que no 45o e 60o. Independentemente da via de exame e do dia da gestação, o tempo médio para diagnosticar a gestação foi menor (P < 0,05) nas cabras do que nas ovelhas. Independentemente da espécie e do dia da gestação, o tempo médio para diagnosticar a gestação pela via transretal foi menor (P < 0,05) do que as demais e o da transvaginal foi menor (P < 0,05) do que o da via transabdominal. No segundo experimento, com a finalidade de aperfeiçoar a sexagem de fetos (n = 123) caprinos da raça Boer por via transretal, procurou-se identificar o período de migração do tubérculo genital e sua diferenciação nas estruturas da genitália de fetos derivados de monta natural (TI) e da transferência de embriões frescos (TII), congelados (TIII) e vitrificados (TIV) colhidos 7 dias após a cobertura. A migração do tubérculo genital ocorreu mais cedo (P < 0,05) no TI (42,21±2,86 dias) do que no TII (43,98±3,00 dias), TIII (44,97±1,83 dias) e no TIV (44,58±1,97 dias). A visibilização da bolsa escrotal, prepúcio e vulva ocorreu precocemente (P < 0,05) no TI (45,22±1,25; 45,95±1,53;45,01±1,03 dias) do que no TII (53,25 ± 2,02; 53,37 ± 1,92; 51,76 ± 2,10 dias), TIII (53,25 ± 2,02; 53,37 ± 1,92; 51.76 ± 2,10 dias) e TIV (54,06±1,75; 52,46 ± 1,95;51,91 ± 2,06 dias). No terceiro experimento, com o propósito de aperfeiçoar a sexagem de fetos (n = 130) ovinos da raça Dorper por via transretal, procurou-se identificar o período de migração do tubérculo genital e sua diferenciação nas estruturas da genitália de fetos derivados de monta natural (TI) e da transferência de embriões frescos (TII), congelados (TIII) e vitrificados (TIV) colhidos 7 dias após a cobertura. A migração do tubérculo genital ocorreu mais cedo (P < 0,05) no TI (45,21 ± 3,31 dias) do que no TII (48,50 ± 3,70 dias), TIII (48.50 ± 3.70 dias) e no TIV (48,85 ± 3,23 dias). A visibilização da bolsa escrotal, prepúcio e vulva ocorreu precocemente (P < 0,05) no TI (51,20 ± 2,56; 50,35 ± 1,59; 49,75 ± 1,73 dias) do que no TII (53,25 ± 2,02; 53,37 ± 1,92; 51,76 ± 2,10 dias), TIII (53,25 ± 2,02; 53,37 ± 1,92; 51.76 ± 2,10 dias) e TIV (54,06±1,75; 52,46 ± 1,95; 51,91 ± 2,06 dias). Os resultados permitem concluir que o diagnóstico de gestação pode ser realizado pelas vias transretal, transabdominal etransvaginal, bem como que é mais rápido pela via transretal, na gestação avançada e na espécie caprina. É também permissível concluir que, com base no posicionamento final do tubérculo genital, é recomendável sexar fetos caprinos provenientes de monta natural somente a partir do 55o dia de prenhez e a partir do 60o dia naqueles derivados da transferência de embriões frescos e criopreservados. Nos ovinos a sexagem fetal já pode ser efetuada a partir do 50o dia de prenhez nos fetos oriundos de monta natural e a partir do 55o dia naqueles originados da transferência de embriões frescos e criopreservados. Ainda é possível concluir que a ultrassonografia em tempo real é uma ferramenta importante para diagnosticar precocemente a prenhez nos pequenos ruminantes, assim como identificar o sexo fetal nos primeiros 60 dias de gestação

Les cancers viro-induits dont le chef de file est le cancer du col utérin lié aupapillomavirus humain (HPV) représentent une cause importante de mortalité dans la Caraïbe. Ilsont récemment été désignés comme objectif de santé publique par les registres des cancers antillais.Pour autant, les données virologiques disponibles sont rares et concernent principalement lesantilles anglophones. Des études de répartition génotypique menées à Tobago, en Jamaïque et à laBarbade montrent, en population générale, une forte prévalence des infections par les HPV à hautrisque oncogène (HRHPV) et une prédominance de génotypes différents de ceux qui prévalent dansles pays du nord (i.e.: HPV16, HPV18) notamment les génotypes HPV45 et HPV58. Ces donnéessoulèvent la question de l’existence d’un profil de distribution génotypique particulier dans laCaraïbe et la nécessité, le cas échéant, d’adapter la stratégie de prévention vaccinale des infectionspar les HPV à haut risque oncogène car les vaccins actuels ne ciblent que les génotypes 16 et 18 .Objectifs : L’objectif principal du travail était de décrire la distribution génotypique (estimation dela prévalence des différents génotypes) des HPV oncogènes impliqués dans les infections de lasphère ano-génitale des femmes, en Guadeloupe. L’objectif secondaire était de préciser les facteursdémographiques, sociaux et cliniques associés à la présence d’une infection ano-génitale à HPVoncogène.Patients et méthodes : Trois études ont été envisagées : i) une étude rétrospective, en populationgénérale, à partir des données cytologiques et virologiques du cabinet de pathologie de Guadeloupedont l’activité est la plus intense dans le domaine ciblé, ii) deux études prospectives conduites chezdes femmes immunodéprimées, soit par une transplantation rénale, soit par une maladie systémiqueauto-immune. Cette population de femmes a été choisie car elle est caractérisée par une prévalenceélevée d’infections ano-génitales à HPV oncogènes et une fréquence importante de complicationscarcinologiques HPV-induites, documentée dans la littérature.8prévalence des HPV à haut risque oncogène de type ni 16 ni 18 comme en atteste la distributiongénotypique observée en population générale et en population immunodéprimée (i.e. prévalenceforte du type HPV52 et à moindre degré des types HPV39 et HPV51 chez les patientestransplantées et des types HPV31, HPV58, HPV39, HPV45 chez les patientes présentant unemaladie systémique auto-immune). Ces résultats confortent les données des études précédemmentconduites dans l’arc antillais et constituent un argument pour élargir la protection vaccinale anti-HPV aux types non 16 non 18, dans le but d’ optimiser la prévention primaire du cancer du colutérin, aux Antilles.Le vaccin anti-HPV nonavalent, de commercialisation récente, semble représenter une optionintéressante. En effet, les 5 types supplémentaires de HRHPV qu’il cible par rapport aux vaccins de1ère génération (i.e.: HPV31, HPV33, HPV45, HPV52, HPV58) correspondent aux types despapillomavirus humains à haut risque oncogène ni 16 ni 18 qui circulent activement dans laCaraïbe, y compris deux types impliqués dans les cancers invasifs du col utérin aux antillesfrançaises: HPV33 et HPV45.Les facteurs de risque d’infection par les HPV oncogènes identifiés dans notre travailcorrespondent aux facteurs largement documentés dans la littérature comme le début précoce desrapports sexuels ou le statut de célibataire. Une étude de plus grande envergure est nécessaire pourinvestiguer l’association avec la sclérodermie systémique. / Of the virus-related cancers, cervical cancer linked to the human papillomavirus(HPV), is one of the leading causes of mortality in the Caribbean. These cancers have recently beenidentified as an important public health problem by Caribbean cancer registries. However,virological data available are limited and related primarily to the English-speaking Caribbean.Genotypic distribution studies in Tobago, Jamaica and Barbados show a high HPV prevalence ofhigh-risk HPV types (HR HPV) infections in the general population and a predominance ofgenotypes different from those of northern countries (i.e.: HPV16 and HPV18) in particular typesHPV45 and HPV58. These data raise the question of the existence of a specific genotypicdistribution profile in the Caribbean and the need, if required, to adapt vaccine prevention strategyagainst HRHPV infections because current vaccines only target genotypes 16 and 18.Objectives: The main objective of this study was to describe the distribution of carcinogenic HPVtypes involved in anogenital infections of women in Guadeloupe. The second objective was toidentify the demographic, social and clinical factors associated with the presence of oncogenic HPVinfection of the anogenital area.Patients and methods: Three studies were conducted: (i) a retrospective study concerning thegeneral population based on cytological and virological data from the Guadeloupe pathologylaboratory whose activity is the most intense in the targeted field; (ii) two prospective studies inwomen immunocompromised (i.e.: kidney transplant recipients, autoimmune systemic disease).This population of women was chosen because it is characterized by a high prevalence of HPVanogenital infections with frequent HPV-induced mucosal cancer complications reported in theliterature.Our 3 studies show a high prevalence of anogenital infections with carcinogenic HPVin women on the island of Guadeloupe. This high prevalence appears to be directly linked to theprevalence of high-risk, oncogenic HPVs of type non 16 and non 18, as evidenced by the genotypicdistribution observed in the general population and the immunocompromised population (i.e. HPV52 , HPV39, HPV51 in kidney transplant recipients and HPV31, HPV58, HPV39, HPV45 inpatients with autoimmune systemic disease). These results are in accordance with data from studiespreviously carried-out in Caribbean. They constitute an argument for extending the protectionagainst non-16 and non-18 HPV types infections with the aim of optimizing the basic prevention ofcervical cancer in the caribbean countries. The nonavalent new HPV vaccine seems to constitute aninteresting option. The 5 additional types of HR HPV that it targets compared to first generationvaccines (i.e.: HPV31, HPV33, HPV45, HPV52, HPV58) correspond to high risk HPV types nor16nor18 that are actively marketed in the Caribbean, including two types involved in invasive cervical11cancer in the French West Indies: HPV33 and HPV45.Risk factors for HPV infection identified in our study correspond to factors widely documented inthe literature such as early onset of sexual intercourse or unmarried status. A larger study is neededto investigate the association with systemic sclerosis.

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Denna uppsats syftar till att kritiskt undersöka de akademiska diskurserna kring den symboliska tolkningen av förhistoriska Komari-motiv på Rapa Nui (Påskön). Genom att undersöka ett antal olika källor kommer uppsatsen att ge en översiktlig genomgång av de aktuella akademiska diskurserna samt diskutera de olika tolkningarna av symboliken hos komari-motiven. Genom att kombinera diskursanalys med ett feministiskt arkeologiskt perspektiv och ett postkolonialt perspektiv är huvudsyftet med uppsatsen att bedöma i vilken utsträckning den sociala konstruktionen av kön och sexualitet samt koloniala idéer har påverkat tolkningarna av symbolerna. / This essay aims to critically examine the academic discourses surrounding the symbolic interpretation of prehistoric Komari-motifs in Rapa Nui (Easter Island). The analysis will draw on a variety of sources and will give a brief overview of the academic discourses in question and discuss the different interpretations of the symbolism behind the komari-motifs. Combining discourse analysis with a feminist archaeology perspective and a postcolonial perspective, the main aim of the essay is to assess to what extent the social construction of gender, sexuality and colonialist ideas influenced the development of theories regarding the symbols.

O líquen escleroso vulvar é uma doença crônica e benigna, porém apresenta um potencial de malignização para o carcinoma de células escamosas de vulva. Foram estudadas trinta doentes com líquen escleroso vulvar, divididas em três grupos, que fizeram uso tópico de propionato de clobetasol a 0,05%, testosterona a 2% e um placebo, para avaliar a evolução dos sintomas e o comportamento das células marcadas com o anticorpo Ki-67 e a proteína p53 antes e após os tratamentos. Observou-se melhora dos sintomas clínicos com o uso do clobetasol e da testosterona, que foi estatisticamente superior ao placebo (p<0,01). Observou-se diminuição significante das células marcadas com Ki-67 após o tratamento das doentes com o clobetasol (p<0,01) e com a testosterona (p<0,02). Enquanto, nas doentes que utilizaram placebo, observou-se um aumento do Ki-67. Em relação à análise das células marcadas com a proteína p53 também observou-se diminuição significante após o tratamento com o clobetasol (p<0,01) e com a testosterona (p<0,01). Enquanto no grupo placebo observou-se um aumento do p53. Quando se compara a variação do p53 entre os grupos clobetasol, testosterona e placebo observou-se uma diminuição do p53 estatisticamente superior (p<0,001) nas doentes que utilizaram clobetasol. Assim, os resultados mostram uma redução dos marcadores celulares após os tratamentos, e com o p53 a diminuição foi estatisticamente maior no grupo que utilizou clobetasol, sugerindo a eficácia desse tratamento / Vulvar Lichen Sclerosus consists of a benign chronic disease, however featuring a malignant potential for vulvar squamous cell carcinoma. The present study targeted 30 patients diagnosed Vulvar Lichen Sclerosus, divided in three groups, and who made topical use of clobetasol propionate at 0.05%, testosterone at 2% and a placebo, so as to assess the evolution of the symptoms and the behavior of the cells marked with antibody Ki-67 and protein p53, before and after the treatments. The administration of clobetasol and testosterone has proven effective in the management of the clinical symptoms, which turned out to be statistically higher than the placebo (p<0.01). The number of cells marked with Ki-67 decreased significantly patients treated with clobetasol (p<0.01) and testosterone (p<0.02), while the number of such cells increased in those patients who made use of the placebo. The number of cells marked with protein p53 also decreased significantly after the treatment with clobetasol (p<0.01) and testosterone (p<0.01), whereas the placebo group revealed an increased p53. When comparing the decrease of the p53 in the clobetasol, testosterone and placebo groups, we noted a decrease of the p53 statistically higher (p<0.001) in patients under clobetasol; suggesting a reduction in the cellular markers after the treatment. As for the p53, the decrease was statistically higher in the group under clobetasol, suggesting the efficacy of the treatment.

INTRODUÇÃO: O câncer de vulva representa entre 3 a 5% dos cânceres do trato genital feminino e aproximadamente 0,6% dos cânceres da mulher. Existem poucos estudos na literatura sobre fatores prognósticos incluindo avaliação molecular, relacionados a esta doença. Este estudo foi realizado para avaliar fatores prognósticos clínicos, epidemiológicos, patológicos e moleculares de pacientes portadores de câncer de vulva submetidos a tratamento cirúrgico. Avaliamos também uma classificação de prognóstico com base na pontuação do risco relativo dos fatores encontrados. MÉTODOS: Foram selecionadas as pacientes portadoras de carcinoma escamocelular de vulva, submetidas a tratamento cirúrgico no Departamento de Cirurgia Pélvica e Serviço de Ginecologia do Hospital Aristides Maltez entre o período de Junho de 1993 e Junho de 2011. Avaliamos as características clínicas, epidemiológicas, de anatomia patológica e molecular, em relação ao prognóstico das pacientes. A avaliação molecular estudou a expressão da proteína p53 e metaloproteinase 2 de matriz por exame de imunohistoquímica pela técnica de arranjo em matriz de amostras teciduais (TMA). Com base no banco de dados realizado através de consulta aos prontuários e com os resultados de anatomia patológica e testes imunohistoquímicos realizamos análise estatística em relação à sobrevida global das pacientes.RESULTADOS: Setenta e cinco pacientes foram elegíveis para o estudo. A análise univariada mostra como fatores relacionados à sobrevida foram a presença de linfonodo suspeito de metástase ao exame clínico (p=0,004), o tamanho maior de 4 centímetros (p=0,001), a presença de linfonodo com metástase (p=0,026), o estadiamento por grupos (p=0,001), a localização mediana (p=0,011), a profundidade de infiltração maior de 2 milímetros (p=0,012), a expressão da MMP 2 em mais de 50% das células (p=0,009). Na análise multivariada os fatores relacionados à sobrevida foram o tamanho maior de 4 centímetros (p=0,014), a profundidade de invasão maior de 2 milímetros (p=0,023) e a expressão de MMP2 em mais de 50% das células (p=0,046). De acordo ao risco relativo dos fatores identificados como relacionados ao prognóstico pela análise multivariada, foi elaborada a contagem de pontos para uma classificação prognóstica. Essa pontuação classifica em três categorias conforme a presença ou ausência dos fatores identificados na análise multivariada e pode corresponder a três expectativas de sobrevida. CONCLUSÕES: Os fatores tamanho maior de 4 centímetros, profundidade de invasão maior de 2 milímetros e expressão em mais de 50% das células tumorais de metaloproteinase 2 parecem estar relacionados a menor taxa de sobrevida global de pacientes portadores de câncer de vulva submetidas a tratamento cirúrgico. Pode ser realizada uma classificação para o prognóstico de acordo com uma contagem de pontos atribuídos ao risco relativo destes fatores / INTRODUCTION: Vulvar cancer accounts for 3-5% of all cancers of the female genital tract and approximately 0.6% of women\'s cancers. There are few studies on prognostic factors including molecular evaluation related to this disease. This study was conducted to evaluate clinical, epidemiological, pathological and molecular prognostic factors of patients with vulvar cancer, undergoing surgical treatment. A classification based on prognostic risk score related to the factors found was also evaluated. METHODS: Patients were selected with squamous cell carcinoma of the vulva who underwent surgical treatment at the Department of Pelvic Surgery and Department of Gynecology, Hospital Aristides Maltez between the period of June 1993 and June 2011. Clinical, epidemiological, and molecular and pathological anatomy characteristics were evaluated in relation to the prognosis of patients. Molecular assessment studied the expression of p53 protein and metalloproteinase 2 by immunohistochemical examination through the technical arrangement on matrix tissue samples (TMA). Based on the database performed on medical records held and the results of pathological anatomy and immunohistochemical tests, the statistical analysis was performed with respect to overall survival of patients. RESULTS: Seventy-five patients were eligible for the study. Univariate analysis shows how factors related to survival were the presence of lymph node metastasis suspected on clinical examination (p = 0.004), the larger size of 4 cm (p = 0.001), presence of lymph node metastasis (p = 0.026), staging groups (p = 0.001), the location median (p = 0.011), the depth of infiltration larger than 2 millimeters (p = 0.012), the expression of MMP 2 in more than 50% of the cells (p = 0.009). In multivariate analysis, factors related to survival were larger size than 4 cm (p = 0.014), depth of invasion greater than 2 mm (p = 0.023) and MMP2 expression in more than 50% of cells (p = 0.046). According to the relative risk of factors identified as related to prognosis by multivariate analysis, a score was developed for a prognostic classification. This score classifies into three categories, according to the presence or absence of the factors identified in the multivariate analysis and may correspond to three survival expectations. CONCLUSIONS: Prognostic factors as the size larger than 4 centimeters, depth of invasion greater than 2 mm and expression in more than 50% of tumor cells of metalloproteinase 2 may be related to lower overall survival rate of patients with cancer of the vulva undergoing surgery. Classification may be performed for the prognostic according to a count point attributed to the relative risk of these factors