Proefschrift Universiteit Maastricht. / Met bibliogr., lit. opg. - Met een samenvatting in het Nederlands.

Orientador: Claudio Saddy Rodrigues Coy / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-03T16:26:48Z (GMT). No. of bitstreams: 1 Leal_VilmarMoura_M.pdf: 1606636 bytes, checksum: 7b12d0641f97608e38b55b8cc93da306 (MD5) Previous issue date: 2003 / Resumo: A fisiologia da evacuação e a fisiopatologia dos distúrbios evacuatórios ainda hoje não são bem compreendidas. A ocorrência destes distúrbios vem aumentando progressivamente, implica em limitações, compromete a qualidade de vida e tem custos significativos. A incontinência fecal acomete cerca de 2% da população, com predomínio em mulheres e que tenham tido partos normais. Com relação à constipação, em 30 a 50% dos casos, a causa é funcional. Os testes para o estudo da fisiologia anorretal têm sido bastante utilizados, especialmente a manometria. No entanto, algumas variáveis deste exame ainda apresentam dúvidas quanto sua interpretação. Dentre estas, destaca-se o Reflexo Inibitório Retoanal (RIRA), freqüentemente descrito como presente, ausente ou inconclusivo. Apenas recentemente vem sendo realizada uma abordagem mais pormenorizada deste. Sendo a pesquisa deste reflexo comumente realizada com cateter axial e considerando a assimetria anatômica do canal anal, seu estudo na zona de mais alta pressão (ZAP) com cateter radial poderia adicionar informações não disponíveis. Objetivo: estudar os parâmetros do reflexo inibitório retoanal em multíparas, com cateter radial. No período entre 2001 e 2002, foram estudadas 36 pacientes, com quatro a seis partos vaginais, com média de idade de 40,7 (30 a 50) anos, Grupo 1 e 10 pacientes, com um a três partos vaginais, com média de idade de 38,5 (31 a 50) anos, Grupo 2. Com relação à função evacuatória do Grupo 1, 63,9% das pacientes encontravam-se assintomáticas, 33,3% apresentavam como queixa constipação e 2,8% incontinência fecal. Dentre as pacientes do Grupo 2, 50% eram assintomáticas e as demais referiam constipação. Todas as pacientes são oriundas do Hospital Getúlio Vargas ¿ Teresina - PI - Universidade Federal do Piauí (UFPI). Foram analisados na ZAP a pressão anal média de repouso (PAM) e os seguintes valores por quadrante: pressão média de repouso pré-relaxamento (PREP), porcentagem de relaxamento (%RELAX), pressão no ponto de máximo relaxamento (PRELAX), tempo de relaxamento (TRELAX) e o tempo de recuperação (TREC). Não houve diferença significante entre as médias de idades dos pacientes dos Grupos 1 e 2 (p = 0,43), assim como entre as médias da pressão anal média de repouso (p = 0,053). Os valores das médias da PREP nos quadrantes apresentaram diferença com significância estatística, no Grupo 2. A comparação dos valores desta variável entre os Grupos 1 e 2 foi estatisticamente diferente nos quadrantes com exceção do anterior. Os valores das médias de PRELAX foram mais baixos e com significância estatística no Grupo 1, a comparação entre os grupos evidenciou diferença estatisticamente significante nos quadrantes 1 e 4. Não foram evidenciadas diferenças significativas entre os valores das médias de %RELAX no Grupo 1 ou Grupo 2, assim como entre os grupos. Também não ocorreu diferença significativa com relação aos valores dos tempos de relaxamento e de recuperação nos dois grupos, assim como a comparação destas variáveis entre os grupos nos diferentes quadrantes. Os dados obtidos nesta casuística permitem concluir que: 1- a PREP nos quadrantes, tende a uma simetria nas pacientes multíparas, provavelmente decorrente de comprometimento global da função esfincteriana; 2- o Reflexo Inibitório Retoanal(RIRA), contrariamente a PREP, pode ter os parâmetros que o compõe manifestados de maneira irregular nos diferentes quadrantes na ZAP, da mesma forma, em decorrência das alterações estruturais mais prováveis nas pacientes do Grupo 1; 3- a utilização do cateter radial no estudo do Reflexo Inibitório Retoanal (RIRA) pode fornecer dados não obtidos com o cateter axial / Abstract: Physiology of evacuation and physiopathology of evacuatories disturbs still today aren¿t well understood. The occurrence of this disturbs has been rising progressively, it implies in limitation, affects the quality of life and has significant costs. Fecal incontinence occurs at about 2% of population, more in women, especially in those who had vaginal delivery history. In relation to constipation, 30 ¿ 50% of the cases, the cause is functional. Physiologies tests have been used more and more frequently, among these tests the pioneer manometry has gain more attention. Therefore same variables of this test have still doubt about its interpretation. Among this doubts there is the inhibitory recto anal reflex (RIRA), frequently described as present, absent or inconclusive. Only recently a more detailed approach of this complex phenomena has been realized. Once the research of this reflex is commonly made with axial catheter, and considering that anatomy of the anal canal is not symmetric, the study of the RIRA in the high pressure zone (HPZ), with radial catheter could add more information that were not available. Aim: to study parameters of inhibitory recto anal reflex in multiparous, with radial catheter. In the period of 2001 to 2002, 36 patients with 4 to 6 vaginal delivery were studied, with average age 40,7 (30 ¿ 50) years old, belong to Group 1 and 10 patients with 0 to 3 vaginal delivery, with average age 38,5 (31 ¿ 50) years old, belong to Group 2. In relation to evacuation function in Group 1, 63,9% of the patients were asymptomatic, 33,3% had constipation and 2,8% had fecal incontinence. Among the patients of Group 2, 50% were asymptomatic and 50% were constipated. All patients were from Hospital Getúlio Vargas ¿ Teresina ¿ PI ¿ Federal University of Piauí ¿ UFPI. This study was approved by Ethical Committee of this university. In HPZ, anal resting pressure (ARP) and the follow values for quadrant: average of resting anal pressure before relaxation (PREP), percentage of relaxation (%RELAX), pressure at the point of maximum relaxation (PRELAX), relaxation time (TRELAX) and recovery time (TREC) were analyzed. There weren't significant difference between average age of the patients in the two groups (p = 0,43) as far as average of resting anal pressure (p = 0,053). The average values of PREP among quadrants had statistics significant differences in Group 2. The comparison of the values of this variable in two groups was statistically different in the quadrants except in the anterior. The values of PRELAX average were smaller and with statistics difference in Group 1, the comparison between groups shows statistics significant differences in quadrants 1 and 4. No significant differences were observed in the values of %RELAX in Group 1 or Group 2, as far as between the groups there were. Also no differences with relaxation and recovery time among quadrants in the groups as far as between groups. The data obtained in this study permit the following conclusion: 1- PREP among quadrants tend to a lack of symmetry in multiparous patient, probably because of global involvement of sphincter function; 2- RIRA in opposition of PREP, can have its parameters manifested of irregular way among quadrants of HPZ, the same way because of structural alterations more probably in patients of Group 1; 3- Use of radial catheter in study of RIRA can produce data that can not be obtained with axial catheter / Mestrado / Medicina Interna / Mestre em Ciências Médicas

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010. / Härtill 4 uppsatser.

In vertebrates, the urogenital sinus and the hindgut are connected at a hollow region called cloaca. A midline mesenchymal structure known as urorectal septum (urs) descends from the ventral body wall to separate the urogenital sinus from the hindgut before the formation of an anal opening. Subsequent cloaca membrane regression at the ventral midline of the genital tubercle (GT) is crucial for the formation of an anal opening. These two events are important during cloaca septation in urorectal development. Mice with defective Shh or Wnt signaling displayed similar urorectal defects such as GT agenesis, un-partitioned cloaca (persistent cloaca) and proximal urethral opening that are attributable to increased cell apoptosis. Furthermore, Shh and Wnt signal transduction coordinate with each other and regulate cell survival of the developing urorectum. However, the molecular mechanisms by which these two signaling pathways coordinate in urorectal development remain unclear. We previously identified Wnt inhibitory factor1 (Wif1) from Affymetrix array analysis for genes/pathways that is implicated in urorectal development. Wif1 is a secreted protein that binds directly to Wnt ligands preventing Wnts from binding to receptors. This leads to -catenin degradation and thereby inhibits their activities. It is known that Wif1 binds to Wnt3a and Wnt5a with high affinity and deletion of Wnt3a, Wnt5a and -catenin in mice caused GT agenesis, persistent cloaca and proximal hypospadias. Using ETU-induced anorectal malformations model, I found out that Wif1 is ectopically expressed in the un-tubularized and un-septated urorectum. Wif1 is mainly expressed at the fusing endoderm that associates with programmed cell death during cloaca septation. Exogenous addition of Wif1 protein in urorectum culture also caused cloaca membrane disintegration, and proximal urethral opening that may be due to aberrant apoptosis. Shh and Wif1 are differentially expressed at the cloaca endoderm. In normal mice, Shh is highly expressed at the cloaca endoderm except those Wif1-expressing endodermal cells. Blockage of Shh pathway by cyclopamine in urorectum culture induced ectopic expression of Wif1, concomitant with genital tubercle hypoplasia and un-septated cloaca. More importantly, deletion of Shh in mice hastened Wif1 expression at the cloaca membrane endoderm and elicited increased cell death in the Wif1 expressing endoderm. Wif1-/- embryos display urorectal defects including delayed genital outgrowth and proximal hypospadias. Therefore, disruption of spatiotemporal expression of Wif1 could lead to defective Wnt signaling and contributes to abnormal urorectal development in Shh-/- mutant. Current study revealed that Wif1 is involved in urorectal development and is implicated in urorectal defects. It may function as a pro-apoptotic factor to regulate endodermal cell death which is essential for the septation process. Its specific expression is restricted at the midline cloaca endoderm by Shh signaling to inhibit local Wnt--catenin activities during cloaca septation. I proposed novel hypothetical models to explain (1) the significance of the tempo-spatial expression of Wif1; (2) the significance of cell death; and (3) the molecular mechanism that Shh signaling regulates Wnt signaling activities through Wif1 in urorectal development. / published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

In mammals, the external genitalia, urinary tract and anorectal tract are developed from a common embryonic primordium, the urorectum. Cloaca is the hollow space inside the urorectum that connects the hindgut and the urogenital sinus. During the urorectal development, the external genitalia is formed from the outgrowth of genital tubercle (GT) protruding from the urorectum, while the future urinary tract and anorectal tract are formed by the partition of cloaca during cloacal septation. GT outgrowth and cloacal septation are important developmental events for the formation of genitourinary and anorectal system. In human, dysregulation of these developmental events results in congenital anorectal malformations (ARM). Wnt signaling is one of the key signaling pathways that regulates urorectal development. The activity of Wnt signaling is initiated by the binding of Wnt ligands to cell surface receptors, which can be antagonized by secretory Wnt inhibitors. Dickkopf1 (Dkk1) and Wnt inhibitory factor 1 (Wif1) are secretory Wnt inhibitors implicated in urorectal development. However, the functions of other secretory Wnt inhibitors during urorectal developments remain to be elucidated. In this study, expression analyses showed that Dkk1, Dickkopf2 (Dkk2), Dickkopf4 (Dkk4), Secreted Frizzled-related Protein 1 (Sfrp1) and Wif1 were expressed in the developing urorectum. The dynamic, overlapping and restricted expression patterns of these Wnt inhibitors were closely associated with the GT outgrowth and the cloacal septation events, implying that these Wnt inhibitors functioned in a coordinated manner in defining the field of Wnt signaling activities in the developing urorectum. Wif1 knockout mice (〖Wif1〗^(-/-)) was used as the model to investigate the functions of and the interplay between secretory Wnt inhibitors in urorectal development. GT outgrowth and cloacal septation defects were observed in 〖Wif1〗^(-/-) embryos. Most of the 〖Wif1〗^(-/-) embryos displayed varying degrees of GT outgrowth defects, while septation defects were only occasionally observed. This suggested that GT outgrowth and cloacal septation were regulated by Wif1 via different regulatory mechanisms. In the urorectum of 〖Wif1〗^(-/-) embryos, Dkk1 was significantly upregulated in the peri-cloacal mesenchyme. Further expression analysis suggested that Dkk1 was sufficient to rescue cloacal septation defects but not GT outgrowth defects in 〖Wif1〗^(-/-)embryos. In the 〖Wif1〗^(-/-) embryos with severe GT outgrowth defects, the Fgf8-expressing distal urethral epithelium, the signaling center in the urorectum, was absent, suggesting that the GT outgrowth defects could be contributed by the loss of dUE-expressing signals such as Fgf8. This study demonstrated the importance of secretory Wnt inhibitors in the GT outgrowth and cloacal septation and suggested that secretory Wnt inhibitors played partially overlapping roles in urorectal development. A rescue mechanism for cloacal septation performed by Dkk1 upon Wif1 deletion was proposed. Such auto-regulatory mechanism within the Wnt signaling pathway indicated that Wnt inhibitors play essential regulatory roles in the urorectal development and a balanced Wnt signaling activity modulated by Wnt inhibitors is crucial to the development of urorectum. / published_or_final_version / Surgery / Master / Master of Philosophy

Lic.-avh. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 3 uppsatser.

Licentiatavhandling (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 3 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Made available in DSpace on 2015-12-06T23:44:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2006 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Objetivo: Estudar as células ganglionares e as células intersticiais de Cajal (CIC) no intestino terminal de ratos portadores de anomalia anorretal (AAR) induzida pela etilenotiouréia (ETU). Métodos: Os animais foram distribuídos em três grupos: Grupo A - fetos normais, obtidos de ratas grávidas às quais não foi administrada ETU; Grupo S - fetos não portadores de AAR obtidos de ratas grávidas às quais foi administrada ETU e Grupo C - fetos portadores de AAR obtidos de ratas grávidas às quais foi administrada ETU. A ETU foi administrada no décimo primeiro dia de gestação na dose de 125 mg/Kg, por gavagem. As ratas foram submetidas à laparotomia e histerotomia para retirada dos fetos no vigésimo primeiro dia de gestação. O intestino terminal dos fetos foi retirado e analisado por imunohistoquímica para pesquisa das CIC e células ganglionares. Resultados: Foram encontradas diferenças estatisticamente significantes entre os grupos A, S e C quanto à densidade de CIC e de células ganglionares. O grupo A apresentou a maior densidade, seguida pelo grupo S, e a menor densidade, de ambas as células, foi encontrada no Grupo C. Não se observou diferença estatisticamente significante entre os três tipos de anomalia anorretal obtidos, quanto à densidade de ambas as células. Conclusão: Existe uma menor densidade de CIC e de células ganglionares no intestino terminal de ratos portadores de AAR. / Objective: to study the ganglion cells and the interstitial cells of Cajal (ICC) in the terminal bowel of rats with ethylenethiourea (ETU)-induced anorectal malformations (ARM). Methods: the animals were divided into three groups: Group A – normal fetuses from pregnant rats that were not administered ETU; Group B – fetuses without ARM born from pregnant rats that were administered ETU and Group C - fetuses with ARM born from pregnant rats that received ETU. ETU was administered on the 11 th day of pregnancy at the dose of 125 mg/kg body weight by gastric gavage. The rats had cesarean section on the 21 st day of gestation. The fetuses’ terminal bowel tissue was analyzed by immunohistochemistry to demonstrate ICC and ganglion cells. Results: statistically significant differences were found between groups A, B and C regarding ICC and ganglion cell densities. Group A had the highest cell density, followed by Group B and the lowest density of both cells was found in Group C. There were no statistically significant differences between the three types of ARM regarding the density of either cell. Conclusion: ICC and ganglion cell densities are decreased in the terminal bowel of rats with ARM / BV UNIFESP: Teses e dissertações

Made available in DSpace on 2014-06-11T19:33:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-12-14Bitstream added on 2014-06-13T18:45:11Z : No. of bitstreams: 1 miranda_jegb_dr_botfm.pdf: 452583 bytes, checksum: e49feaadec832a47890a0269d2b98b50 (MD5) / O controle esfincteriano é um marco do desenvolvimento na vida de uma criança. É uma área do cuidado pediátrico que apresenta uma ótima oportunidade para prevenção, orientação e intervenção clínica. Avaliar a prática do treinamento do controle esfincteriano anal (TEA) em crianças saudáveis, na faixa etária de três a seis anos de idade, por meio de entrevista aplicada aos pais ou cuidadores. Estudo transversal observacional e descritivo que constou de inquérito baseado em entrevista, utilizando casos consecutivos de cem crianças entre 3 e 6 anos de idade no período de junho de 2005 a agosto de 2006. Resultados. A retirada das fraldas iniciou-se antes dos 18 meses em 31% das crianças, entre os 18 e 30 meses em 58% e após os 30 meses em 11%. Em relação à duração do treinamento, 43% das crianças foram treinadas em menos de 3 meses, 34% entre 3 e 6 meses e 23% em mais de 6 meses, não houve diferença entre a idade do início e a duração do TEA (p = 0,6489). Observou-se que não houve diferença estatisticamente significante entre os gêneros masculino e feminino tanto para a idade de início (p = 0,6181), quanto para a duração do TEA (p = 0,4709). Já para a escolaridade das mães com relação à idade de início, observou-se diferença estatisticamente significante entre a escolaridade menor ou igual a 11 anos ou maior que 11 anos (p = 0,0008), entretanto não houve diferença estatisticamente significante para a duração do TEA (p = 0,2001). Não houve diferença estatisticamente significante para o filho único e não único, tanto para a idade de início (p = 0,9285), quanto para o tempo de duração do TEA (p = 0,7318). Houve diferença estatisticamente significante entre as classes A-B bem e as classes C-D-E para a idade de início (p = 0,0032), entretanto, não houve diferença estatisticamente significante... / The control of the sphincter is a milestone in a child’s development. It’s an area of the pediatric care which stands a great opportunity for prevention, guidance and clinical intervention. To study the toilet training practice in children between three and six years old, by interviewing parents and caregivers. Observational and descriptive transversal study, consisting of an inquiry based on interviews using consecutives one hundred children, from June 2005 to August 2006. The removal of diapers started before 18 months in 31% of the children, between 18 and 30 months in 58% and after 30 months in 11%. As for the duration of the toilet training, 43% of the children had been trained for less than three months, 34% between three and six months and 22% over six months. There was no difference between the age of initiation and the duration of the toilet training (p = 0,6489). For male and female genders there was no statistically significant difference either for age of initiation (p = 0,6181), or duration of the toilet training (p = 0,4709). It has been observed that there was a statistically significant difference for schooling under or equal to 11 years or over 11 years for the age of initiation (p = 0,0008). However, there has been no statistically significant difference for the duration of the toilet training (p = 0,2001). Mothers of little schooling started training earlier, but this does not interfere with the duration of training. It has been observed that there was no statistically significant difference whether it was an only child or not, either for the age of initiation (p = 0,9285) or for the duration of the toilet training (p = 0,7318). It has been observed that there was a statistically significant difference between A-B and C-D-E social classes for the age of initiation (p = 0,0032). However there has been no statistically significant... (Complete abstract click electronic access below)