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Diabetic gastroenteropathy is a common complication, which develops in patients with long-term diabetes. The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide known for its cytoprotective properties and plays an important role in neuronal development, neuromodulation and neuroprotection. The present study was designed to elucidate, for the first time, the impact of prolonged hyperglycaemia conditions on a population of PACAP-like immunoreactive neurons in selected parts of the porcine gastrointestinal tract. The experiment was conducted on 10 juvenile female pigs assigned to two experimental groups: The DM group (pigs with streptozocin-induced diabetes) and the C group (control pigs). Diabetes conditions were induced by a single intravenous injection of streptozocin. Six weeks after the induction of diabetes, all animals were euthanised and further collected, and fixed fragments of the stomach, duodenum, jejunum, ileum and descending colon were processed using the routine double-labelling immunofluorescence technique. Streptozotocin-induced hyperglycaemia caused a significant increase in the population of PACAP-containing enteric neurons in the porcine stomach, small intestines and descending colon. The recorded changes may result from the direct toxic effect of hyperglycaemia on the ENS neurons, oxidative stress or inflammatory conditions accompanying hyperglycaemia and suggest that PACAP is involved in regulatory processes of the GIT function in the course of diabetes.

Black bears are omnivorous, and tend to be opportunistic feeders, in that they will eat what is readily abundant or available. The end-products of intestinal digestion are absorbed by the body through the action of transporter proteins expressed on the brushborder membrane of small intestinal epithelial cells. The goal of this study was to increase the understanding of the physiological processes associated with nutrient assimilation by black bears. Distribution and relative abundance of mRNA of a peptide transporter (PepT1), a glucose transporter (SGLT1), two AA transporters (NBAT, bo,+AT), and a digestive enzyme, aminopeptidase N (APN), in the intestinal tract of black bears were investigated. Ten bears were used for this study. For tissue collection, the intestine was removed from the animal and divided into five sections. Each collected section was opened longitudinally, rinsed in ice-cold PBS, and the mucosal scrapings were stored at -80&#61616;C. Total RNA was extracted and quantified by spectrophotometry. Abundance of PepT1, SGLT1, NBAT, bo,+AT, and APN mRNA was determined by performing Northern blots, using bear cDNA probes. Northern blot data were quantified by densitometric analysis, with the abundance of each gene expressed relative to GAPDH. Abundance of PepT1 (P < 0.05), APN (P < 0.05), and SGLT1 (P < 0.0001) changed quadratically from the proximal to the distal intestine with abundance being greatest in the midregion. Abundance of bo,+AT mRNA increased linearly (P < 0.05) from the proximal to distal intestine. Abundance of NBAT mRNA did not change among intestinal segments.The absolute number of molecules of mRNA/ng of total RNA for each gene was determined using Real-Time PCR. Similar to the Northern results, abundance of PepT1 (P < 0.0003), SGLT1 (P < 0.0003), and APN (P < 0.02) changed quadratically from the proximal to distal intestine with abundance being greatest in the mid-region, and bo,+AT mRNA increased linearly (P < 0.0001) from the proximal to distal intestine. NBAT mRNA abundance also increased linearly (P < 0.0001) from proximal to distal intestine. PepT1 mRNA was present at tenfold or greater levels than AA transporter mRNA in all segments of the intestine, suggesting that di- and tripeptides constitute the major form in which AAs are absorbed. NBAT and bo,+AT mRNA abundance was greater towards the distal portion of the intestine, suggesting their importance in salvaging remaining unabsorbed AAs.These results indicate that the mRNA of nutrient transporters examined and APN are differentially expressed throughout the gastrointestinal tract of black bears, suggesting their involvement in nutrient assimilation. / Master of Science

Diss. (sammanfattning) Umeå : Umeå universitet, 2008. / Härtill 4 uppsatser.

bgbrady@hotmail.com / The primary intestinal follicular lymphoma is a rare disease described in the last classification of lymphomas from WHO. It is a localized disease with excellent prognosis. We describe in this article ,a 64 year-old Peruvian female with abdominal pain and delayed vomiting for the last two years, has undergone a partial intestinal resection due to bowel obstruction. There was a well-circumscribed annular tumor. A diagnosis of non-polypoid primary intestinal follicular lymphoma was made. We report the case and review the literature in this article. / El linfoma folicular primario intestinal es un desorden raro descrito en la última clasificación de linfomas de la WHO. Es una entidad localizada con excelente pronóstico. En el presente artículo, reportamos una mujer peruana de 64 años de edad diagnosticada con linfoma folicular primario intestinal. Ella tuvo dos años con dolor abdominal y vómitos tardíos. Ella desarrolló una obstrucción intestinal y tuvo una resección completa del tumor. Se describe el caso y se realiza una revisión de la literatura de esta entidad.

O objetivo deste estudo foi analisar os efeitos da suplementação com ácido ascórbico (AA) sobre os aspectos morfológicos do plexo mioentérico de camundongos mdx jovens. Foram utilizados camundongos mdx e controles C57BL/10 machos divididos em seis grupos (n=5): GC30 (Grupo controle com 30 dias de idade); GC60 (Grupo controle com 60 dias de idade); GCS60 (Grupo controle suplementado com ácido ascórbico, com 60 dias de idade); GD30 (Grupo distrófico com 30 dias de idade); GD60 (Grupo distrófico com 60 dias de idade) e GDS60 (Grupo distrófico suplementado com AA, com 60 dias de idade). Após a eutanásia, os segmentos orais do jejuno (SOJ) foram coletados e submetidos a técnicas histoquimicas de evidenciação neuronal: NADH-diaforase, NADPH-diaforase e AChE. Os resultados demonstraram um aumento significativo do peso corporal para os animais distróficos (grupos GD30 e GD60) quando comparados aos seus respectivos controles (grupos GC30 e GC60). A análise quantitativa demonstrou que os animais do grupo GD60 possui área total do intestino delgado significativamente maior que os animais do grupo GC60; Não houve diferenças significativas entre os grupos GCS60 e GDS60. Em todos os grupos de animais com 60 dias, exceto para a densidade de neurônios nitrérgicos que se apresentou maior no grupo GCS60, todos os demais parâmetros (densidade e área do perfil neuronal) foram semelhantes entre os grupos, tanto controle (GC60 e GCS60) como distrófico (GD60 E GDS60), nas duas metodologias de coloração utilizadas (NADH-d e NADPH-d). A análise qualitativa demonstrou que componentes do plexo mioentérico dos animais distróficos suplementados com AA (GDS60) evidenciados positivos a NADPH-d e AChE apresentaram manutenção dos aspectos normais do plexo mioentérico quando comparados aos animais do grupo GD60. / The aim of this study was assessment of the effects of ascorbic acid (AA) supplementation on morphoquantitative aspects of myenteric plexus of jejunum young mdx mice. Dystrophic mdx and control C57BL/10 animals were used and divided in six groups (n = 5): GC30 (control group with 30 days of age); GC60 (control group with 60 days of age); GCS60 (control group supplemented with ascorbic acid, 60 days of age); GD30 (dystrophic group 30 days of age); GD60 (dystrophic group 60 days of age) and GDS60 (dystrophic group supplemented with AA, 60 days of age). After euthanasia, the oral segments of the jejunum (SOJ) were collected and submitted to the histochemical techniques of neuronal evidencing: NADH-diaphorase, NADPHdiaphorase and AChE. The results showed a significant increase of weight in dystrophic mice (groups GD30, GD60 and GDS60) compared to its controls (groups GC30, GC60 and GCS60). The quantitative analysis showed that the GD60 group had a significantly higher small intestine total area than the GC60; no differences significant between GCS60 and GDS60 groups. All groups of animals with 60 days of age, except for the density of nitrergic neurons showed higher in GCS60 group, in all other parameters (the neuronal density and neuronal profile area) were similar between groups, controls (GC60 and GCS60) and dystrophic (GD60 e GDS60), for techniques of the NADH-d e NADPH-d.Morphological analysis of the components of myenteric plexus of dystrophic animals supplemented with AA (group GDS60) and evidenced by the techniques of NADPH-d and AChE, showed repair of the myenteric plexus aspects compared to animals of group no supplemented (GD60).

Objetivou-se avaliar a efetividade da ventilação forçada associada à nebulização sobre as respostas comportamentais e fisiológicas de suínos mantidos dentro do veículo transportador antes do descarregamento na indústria frigorífica. Durante 6 semanas de transporte, 2 veículos pot-belly (PB) transportaram 191 suínos cada até a mesma planta frigorífica. Na chegada, ambos veículos permaneceram estacionados por 30 minutos antes da descarga. Um dos veículos PB foi posicionado ao lado do sistema de ventilação e nebulização (PBVM), enquanto o outro PB não teve acesso ao sistema de resfriamento (PBC). O tratamento (PBVM) consistiu em 10 minutos de ventilação (Espera 1); seguido de 10 minutos de ventilação e nebulização (Espera 2) e 10 minutos finais de ventilação (Espera 3). A temperatura do ar (T) e a umidade relativa (RH) foram monitorados. A frequência de suínos deitados e a frequência de acesso ao bebedouro foram calculadas. Temperaturas do trato gastrointestinal (GTT), lactato sanguíneo, hematócrito, creatina quinase e concentrações de cortisol foram avaliados. Durante a Espera 1, a ventilação forçada reduziu a temperatura do ar e o índice de temperatura e umidade no tratamento PBVM. Na Espera 3, a temperatura e o índice de temperatura e umidade foram menores (P &lt; 0.001) no tratamento PBVM comparado ao PBC, contudo a umidade relativa do ar foi maior (P &lt; 0.001). Suínos oriundos do compartimento 4 do PBVM apresentaram maior atividade durante o tempo de Espera 2 e 3, e reduzido tempo de latência para se deitar na baia do frigorífico (P &lt; 0.05). Redução no GTT dos suínos oriundos do PBC foi observada após 1 hora de período de descanso comparada ao PBVM. O percentual de hematócrito tendeu a ser maior nos suínos PBC comparado ao PBVM. O sistema de ventilação e nebulização utilizado na indústria frigorifica antes do descarregamento melhora de forma eficiente as condições internas térmicas do caminhão e consequentemente o conforto térmico dos suínos mantidos no veículo transportador, com redução na temperatura dentro dos compartimento e baixo nível de desidratação no abate. / The aim of this study was to evaluate the effectiveness of water misting with forced ventilation on a stationary trailer on internal vehicle ambient conditions, behavioral and physiological response of market pigs. During 6 weekly shipments, two identical tri-axle pot-belly (PB) trailers transported 191 pigs each (126 ± 5 kg BW) to the same slaughter plant. On arrival, both trailers were kept stationary in the yard for 30 min before unloading. One PB trailer was pulled over along a fan-misters bank (PBVM), while the other PB trailer had no access to this cooling system (PBC). The PBVM treatment consisted in 10 min of fan-assisted ventilation (wait 1) followed by 10 min of ventilation and water misting (wait 2) and final 10 min of ventilation (wait 3). The air temperature (T) and relative humidity (RH) were monitored. The frequency of lying pigs, the latency to rest and the frequency of drinking bouts were calculated. Gastrointestinal tract temperature (GTT) and exsanguination blood lactate, hematocrit, creatine kinase and cortisol concentrations were assessed. In wait 1, the application of the fan-assisted ventilation resulted in lower (P &lt; 0.05) T and THI in the PBVM. In wait 3, T and THI were still lower (P &lt; 0.001) in PBVM compared to PBC, but the RH was higher (P &lt; 0.001). Pigs from compartment 4 of PBVM had a greater (P &lt; 0.001) activity during waits 2 and 3, and a reduced latency to lie down in the lairage pen compared to the same compartment in the PBC (P &lt; 0.05). A higher (P &lt; 0.05) GTT drop was recorded until 1 h after lairage in pigs located in PBC compared to those transported in PBVM. At slaughter, hematocrit tended to be higher (P = 0.08) in blood of PBC pigs compared to PBVM. The fan-misters bank used on the PBVM vehicle sitting at the slaughter plant before unloading efficiently improves internal trailer thermal conditions and consequently thermal comfort of pigs kept in a stationary trailer, with reduced temperature within the compartments and lower dehydration condition at slaughter.

O presente estudo tem por objetivo avaliar as características clinicopatológicas, imunoistoquímicas e moleculares de 513 casos brasileiros de tumor estromal gastrintestinal, incluindo o estudo da expressão imunoistoquímica de CD117, CD34, proteína DOG1, actina de músculo liso, desmina, proteína S-100, antígeno Ki-67, proteína p53, molécula de adesão CD44v3, receptor para fator de crescimento epidérmico, proteína HER2 e receptor para fator de crescimento derivado de plaqueta alfa, além da análise molecular de mutações envolvendo os genes KIT e receptor para fator de crescimento derivado de plaqueta alfa e da pesquisa de amplificação dos genes receptor para fator de crescimento epidérmico e HER2 por hibridização \"in situ\" fluorescente. As características clínicas e morfológicas dos casos estudados não foram diferentes das referidas pela literatura. Houve expressão de CD117 (KIT) em 95,7% dos casos. A proteína DOG1 foi expressa em 85,9% dos tumores, sendo capaz de diagnosticar 20% dos casos com ausência de expressão de CD117 (KIT). O índice de proliferação celular determinado pelo antígeno Ki-67 foi superior nos casos classificados como de alto risco para comportamento biológico agressivo segundo critérios do \"National Institutes of Health\". A expressão da proteína p53 esteve restrita aos casos classificados como de alto risco. Não se observou expressão imunoistoquímica da molécula de adesão CD44v3. A proteína receptora para fator de crescimento epidérmico foi expressa em 84,4% dos casos, porém não se observou superexpressão da proteína HER2. A expressão imunoistoquímica da proteína receptora para fator de crescimento derivado de plaqueta alfa foi observada em 94,4% dos casos estudados, não apresentando relação com o tipo de mutação encontrado. As mutações do gene KIT foram as mais frequentemente observadas, principalmente do éxon 11. Mutações do gene receptor para fator de crescimento derivado de plaqueta alfa foram observadas em 8,1% dos casos, sendo que 54,5% dos casos com ausência de expressão imunoistoquímica de CD117 (KIT) apresentavam mutações nesse gene. A hibridização \"in situ\" fluorescente não demonstrou amplificação dos genes receptor para fator de crescimento epidérmico e HER2 nos tumores estromais gastrintestinais. / The present study presents the clinicopathologic, immunohistochemical and molecular genetic features of 513 Brazilian cases of gastrointestinal stromal tumor, including the immunohistochemical expression of CD117, CD34, DOG1 protein, smooth muscle actin, desmin, S-100 protein, Ki-67 antigen, p53 protein, CD44v3 adhesion molecule, epidermal growth factor receptor, HER2 protein and platelet derived growth factor receptor alpha, the mutation analysis of KIT and platelet-derived growth factor receptor alpha genes, and the investigation of amplification of HER2 and epidermal growth factor receptor genes by fluorescence \"in situ\" hybridization. The clinicopathologic features of Brazilian gastrointestinal stromal tumors do not differ from those published from other countries. CD117 (KIT) was expressed by immunohistochemistry in 95.7% of cases. DOG1 protein was expressed in 85.9% of tumors, being able to establish the diagnosis of GIST in 20% of those cases that were negative for CD117 (KIT). Ki-67 proliferation index was higher in those cases classified as high-risk of aggressive behavior by the National Institutes of Health consensus approach. The immunohistochemical expression of p53 protein was restricted to cases classified as high-risk of aggressive behavior. The adhesion molecule CD44v3 was not expressed in any of the cases. The epidermal growth factor receptor protein was overexpressed in 84.4% of cases, and HER2 protein was not expressed in all cases. The platelet-derived growth factor receptor alpha protein was detected by immunohistochemistry in 94.4% of tumors, and there was no relationship between its expression and the mutation status. KIT mutations were the most frequent, mainly of exon 11. Plateletderived growth factor receptor alpha mutations were found in 8.1% of the cases, and 54.5% of those cases that were negative for CD117 (KIT) had mutations in platelet-derived growth factor receptor alpha gene. Fluorescence \"in situ\" hybridization revealed no amplification of epidermal growth factor receptor and HER2 genes in gastrointestinal stromal tumors.

O presente estudo tem por objetivo avaliar as características clinicopatológicas, imunoistoquímicas e moleculares de 513 casos brasileiros de tumor estromal gastrintestinal, incluindo o estudo da expressão imunoistoquímica de CD117, CD34, proteína DOG1, actina de músculo liso, desmina, proteína S-100, antígeno Ki-67, proteína p53, molécula de adesão CD44v3, receptor para fator de crescimento epidérmico, proteína HER2 e receptor para fator de crescimento derivado de plaqueta alfa, além da análise molecular de mutações envolvendo os genes KIT e receptor para fator de crescimento derivado de plaqueta alfa e da pesquisa de amplificação dos genes receptor para fator de crescimento epidérmico e HER2 por hibridização \"in situ\" fluorescente. As características clínicas e morfológicas dos casos estudados não foram diferentes das referidas pela literatura. Houve expressão de CD117 (KIT) em 95,7% dos casos. A proteína DOG1 foi expressa em 85,9% dos tumores, sendo capaz de diagnosticar 20% dos casos com ausência de expressão de CD117 (KIT). O índice de proliferação celular determinado pelo antígeno Ki-67 foi superior nos casos classificados como de alto risco para comportamento biológico agressivo segundo critérios do \"National Institutes of Health\". A expressão da proteína p53 esteve restrita aos casos classificados como de alto risco. Não se observou expressão imunoistoquímica da molécula de adesão CD44v3. A proteína receptora para fator de crescimento epidérmico foi expressa em 84,4% dos casos, porém não se observou superexpressão da proteína HER2. A expressão imunoistoquímica da proteína receptora para fator de crescimento derivado de plaqueta alfa foi observada em 94,4% dos casos estudados, não apresentando relação com o tipo de mutação encontrado. As mutações do gene KIT foram as mais frequentemente observadas, principalmente do éxon 11. Mutações do gene receptor para fator de crescimento derivado de plaqueta alfa foram observadas em 8,1% dos casos, sendo que 54,5% dos casos com ausência de expressão imunoistoquímica de CD117 (KIT) apresentavam mutações nesse gene. A hibridização \"in situ\" fluorescente não demonstrou amplificação dos genes receptor para fator de crescimento epidérmico e HER2 nos tumores estromais gastrintestinais. / The present study presents the clinicopathologic, immunohistochemical and molecular genetic features of 513 Brazilian cases of gastrointestinal stromal tumor, including the immunohistochemical expression of CD117, CD34, DOG1 protein, smooth muscle actin, desmin, S-100 protein, Ki-67 antigen, p53 protein, CD44v3 adhesion molecule, epidermal growth factor receptor, HER2 protein and platelet derived growth factor receptor alpha, the mutation analysis of KIT and platelet-derived growth factor receptor alpha genes, and the investigation of amplification of HER2 and epidermal growth factor receptor genes by fluorescence \"in situ\" hybridization. The clinicopathologic features of Brazilian gastrointestinal stromal tumors do not differ from those published from other countries. CD117 (KIT) was expressed by immunohistochemistry in 95.7% of cases. DOG1 protein was expressed in 85.9% of tumors, being able to establish the diagnosis of GIST in 20% of those cases that were negative for CD117 (KIT). Ki-67 proliferation index was higher in those cases classified as high-risk of aggressive behavior by the National Institutes of Health consensus approach. The immunohistochemical expression of p53 protein was restricted to cases classified as high-risk of aggressive behavior. The adhesion molecule CD44v3 was not expressed in any of the cases. The epidermal growth factor receptor protein was overexpressed in 84.4% of cases, and HER2 protein was not expressed in all cases. The platelet-derived growth factor receptor alpha protein was detected by immunohistochemistry in 94.4% of tumors, and there was no relationship between its expression and the mutation status. KIT mutations were the most frequent, mainly of exon 11. Plateletderived growth factor receptor alpha mutations were found in 8.1% of the cases, and 54.5% of those cases that were negative for CD117 (KIT) had mutations in platelet-derived growth factor receptor alpha gene. Fluorescence \"in situ\" hybridization revealed no amplification of epidermal growth factor receptor and HER2 genes in gastrointestinal stromal tumors.

Syndromic craniosynostosis is most commonly associated with mutations in Fibroblast Growth Factor Receptor genes (FGFR)-1, 2 and 3. Clinical and animal reports suggest a link between FGFR-associated craniosynostosis and defects in the gastrointestinal tract (GIT). Objective: to determine whether GIT malformations occur more frequently in the craniosynostosis population with a known FGFR mutation when compared to the general population. Methods: A retrospective chart review of patients diagnosed with Crouzon, Pfeiffer or Apert syndromes between 1990 and 2011 was performed at the Hospital for Sick Children in Toronto. Thirty-two charts meeting inclusion criteria were analyzed for any history of GIT abnormalities. Results: Three out of 32 patients had documented intestinal/bowel malrotations while 7 had gastroesophageal reflux disease. All patients had documented FGFR2 mutations, a finding in line with previous studies and published case reports. Conclusions: Results suggest an association between FGFR-associated craniosynostosis and GIT malformations.