BACKGROUND: Early identification of pediatric patients with Inflammatory Bowel Disease (IBD), including ulcerative colitis and Crohn disease, is important to help clinicians design optimal treatment regimens. Existing endoscopic techniques are effective in identifying disease activity. However, these methods are invasive, expensive, and less amenable to serial measurement. Recent studies have identified potential serologic and fecal biomarkers that may have the potential to provide clinicians with a more objective evaluation of disease activity. In the case of ulcerative colitis (UC), in which disease is confined to the large intestine, the information provided by fecal biomarkers is likely to be more specific than that provided by serologic biomarkers. Fecal lactoferrin (FLA) is one such biomarker that has shown to be useful not only in identifying levels of colonic inflammation, but also for use as a predictor of disease relapse and treatment efficacy. Measurement of fecal lactoferrin, in conjunction with information provided by other diagnostic modalities could expedite patient assessment and treatment. Additionally, it has been suggested that fecal lactoferrin levels may also provide prognostic information about response to treatment and disease outcome in pediatric patients with UC. The goal of this study is to explore the relationship between changes in FLA levels and response to medical therapy in hospitalized pediatric patients with UC. METHODS: Serial stool samples were collected daily from 10 patients admitted for management of severe active UC. Of these 10 patients, 3 responded favorably to standard treatment with intravenous corticosteroid therapy and were discharged to complete a course of oral steroids. 7 were unresponsive to steroid therapy and went on to require rescue (more intensive) medical therapy. Changes in FLA were correlated with steroid response and medical disposition at the time of discharge. RESULTS: A t-test was performed to determine the significance of the differences in percent change in FLA levels between patients discharged on steroids and patients discharged on rescue therapy. Patients discharged on steroids demonstrated a net decrease in FLA levels over the course of the first three days of steroid treatment while patients ultimately requiring rescue medical therapy demonstrated a net increase in FLA levels (mean values = -64.4% and +203.8%, respectively). A difference was found between the averages; however, this value did not reach statistical significance when analyzed with a t-test (p = 0.18). CONCLUSIONS: This study suggests that quantitative FLA levels may prove useful in predicting clinical course and discharge outcome in pediatric patients with ulcerative colitis. Future research in this field should seek larger sample sizes, increased longitudinal sample collection, and the potential for a composite assessment that will yield additional objective measures of disease activity.

The collection of microbes that inhabits the human gastrointestinal tract is known as intestinal microbiota, and an enormous body of work has shown that their activities contribute to health and disease. Ulcerative colitis (UC), which is a type of inflammatory bowel disease, is considered to arise due to a disruption in the balance between the immune system and microbiota. However, there is little consensus on the mechanism of action and microbes involved in the disease manifestation. In this work, I applied culture-enriched metagenomics (CEMG) to characterize the dynamics of gut microbiota in healthy individuals and UC patients. I showed that CEMG provides a higher resolution to study these microbial communities, and we used this approach to understand microbial colonization after fecal microbiota transplantation (FMT) therapy in UC patient. I showed that sequencing approaches alone did not reveal consistent engraftment across FMT responders. Using CEMG and a collection of bacterial whole-genome sequences, I showed patient-specific microbial strain transfer and a signature of commonly engrafted genes only in patients who responded to FMT. In this work, I also investigated the dynamics of a highly abundant bacteriophage, crAssphage, in an FMT donor and implemented a new method to detect bacteriophage engraftment post-FMT using SNP analysis. Finally, it has been suggested that antibiotic treatment before FMT may increase the efficacy of FMT. However, in this work, I show that while antibiotics alter the microbiome, there was no difference in the composition of the microbiome of antibiotic vs placebo group post-FMT. This is consistent with the randomized controlled trial results that shows pretreatment with antibiotics does not improve FMT outcome. Together, this work demonstrate the importance of in-depth microbiome analysis applied to culture-dependent and -independent sequencing to characterize microbial changes post-FMT. / Dissertation / Doctor of Philosophy (PhD) / Many bacteria reside in the human gut, and they are essential in our health and in disease. It is evident that these bacteria are associated with inflammatory bowel disease, but we do not yet know how and what bacteria are involved in this disease. In this work, I describe a method to study these bacteria from stool that relies on growing them and investigating their DNA. I showed that our approach helped us recover a greater diversity of these bacteria and their genetic content in healthy individuals and patients with inflammatory bowel disease compared to methods that use only DNA based approaches. Using this method, we could better understand why some patients responded to a treatment consisting of transferring stool content from healthy donor to patient. I also investigated a group of viruses that infect bacteria and implemented a new computational method based on DNA sequencing to test whether these viruses transfer to the patient after receiving the fecal therapy. We also found that antibiotic treatment before fecal therapy in patients with inflammatory bowel disease does not improve the patient’s recovery.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Orientadores: Zula Garcia Giglio, Juvenal Ricardo Navarro Goes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Educação / Made available in DSpace on 2018-08-06T15:30:21Z (GMT). No. of bitstreams: 1 Maldaun_Daisy_M.pdf: 580822 bytes, checksum: f5f1e583f2cc833273662dd98f503183 (MD5) Previous issue date: 2006 / Resumo: Desde a Antiguidade, sabe-se, através dos registros da História, que sentimentos e emoções apresentam uma ressonância no corpo. No decorrer dos séculos, o avanço da medicina permitiu o conhecimento da existência de mecanismos através dos quais as emoções podem dar origem ao processo do adoecer. O objetivo deste estudo foi compreender os aspectos emocionais como a ansiedade, o medo e a raiva de pacientes com idade entre 51 e 74 anos portadores de Retocolite Ulcerativa Inespecífica (RCUI) - doença inflamatória intestinal de etiologia desconhecida, bem como viabilizar os resultados desta pesquisa a familiares e profissionais da saúde, numa tentativa de mostrar sua relevância no surgimento e evolução da doença. Como método de pesquisa, optou-se pelo Clínico-Qualitativo. Foram estudados oito (08) casos de pacientes portadores de RCUI, de ambos os sexos, com idades entre 51 e 74 anos. Como procedimento de investigação, foram realizadas entrevistas semidirigidas de questões abertas, levando em consideração a verbalização dos doentes em relação às mudanças ocorridas em suas vidas após o surgimento da doença. Quanto aos resultados, o referencial teórico utilizado para a sua interpretação foi baseado nos conceitos usuais da Psicologia Médica e da Medicina Psicossomática. e da Psicologia Compreensiva Explicativa e Fenomenológica de JASPERS,K. Considerou-se, após a avaliação dos aspectos emocionais desses pacientes através de seus depoimentos, que sua influência é relevante no desencadear e na evolução da RCUI. A psicoterapia, como um instrumento de ajuda e suporte ao tratamento clínico, deve colocar-se a serviço deste Ser doente e em prol da possibilidade de elaboração de uma nova forma de ele vivenciar a doença e seus conflitos, sejam quais forem os recursos de que ele dispõe para manifestá-los / Abstract: Ever since the early Ages, it is common knowledge that feelings and emotions resonate in the body. Throughout the centuries, the advance of medicine has brought to light the knowledge of existing mechanisms through which emotions can give rise to the process of getting sick. The objective of this study was to understand the emotional aspects, such as anxiety, fear and rage of patients aged between 51 and 74 with Unspecified Ulcerative Colitis, an inflammatory intestinal disease of unknown etiology. We also aim to make the results of the present study available to patients¿ family members and health professionals as a means to raise their awareness of the relevance of emotional aspects to the rise and evolution of the illness. The Method chosen to carry out the study was the Qualitative-Clinical Method; eight (08) patients of both sexes were studied. The investigative procedure consisted of semi-direct interviews of open questions; taking into consideration the patients¿ accounts on the changes occurred in their lives before and after the illness manifested itself. The theoretical reference point used for the interpretation of the results was based on the usual concepts of Medical Psychology and Psychosomatic Medicine and of the Comprehensible Explanatory Psychology and Phenomenology of JASPERS, K. Following the evaluation of the emotional aspects these patients mentioned in their testimonials, we concluded that they have great influence on the manifestation of the illness, and that psychotherapy, as an instrument of support for the clinical treatment, should be applied to offer them a new means of understanding the causes of their suffering in the search for a way to deal with the disease and the conflicts it brings along, regardless of which resources they may have available to do so / Mestrado / Gerontologia / Mestre em Gerontologia

It was the purpose of this thesis to establish the functional level of the thyroid gland in patients with chronic ulcerative colitis.

The inflammatory bowel diseases (IBDs) are a group of chronic conditions affecting the gastrointestinal tract, often presenting with non-specific clinical features such as abdominal pain, weight loss and diarrhoea. Approximately 25% of patients are diagnosed with IBD in childhood. For epidemiological studies, previously collected (1990-1995) and original (2003-2008) Scottish incidence data were used to determine national trends in newly diagnosed paediatric IBD (PIBD). A smaller, geographically defined, prospective 14-year cohort (1997- 2011) in South-East Scotland (SES) was used to assess regional trends in incidence, point prevalence, disease extent, medication use and PIBD surgery rates in 326 children. For the detailed analysis of the role of ICOSLG and CRP in Scottish children with PIBD, haplotype-tagging of both genes in 448 children (and their parents) registered on the Paediatric Inflammatory bowel disease Cohort and Treatment Study (PICTS) database was performed. Further clinical information from this database and previously gathered adult mRNA microarray data were also used to inform the analysis. For the faecal calprotectin (FC) case-control study, all PIBD patients diagnosed in SES between 01.01.05 and 31.12.10 (aged 1- 17yrs) with a FC performed during initial workup were identified; controls were matched non- IBD patients who had similarly undergone endoscopy with a referral FC level available. The systematic review and meta-analysis of FC case-control studies was performed with keywords relating to IBD and calprotectin in electronic resources from 1946 to May 2012. Inclusion criteria were studies that reported FC levels prior to the endoscopic investigation of IBD in children less than 18 years old. Laboratory work used newly derived HEK293 and HCT116 cell lines stably expressing wild-type NOD2 and the CD-associated NOD2 frameshift mutant, as well as utilising previously derived HEK293 and HCT116 cells stably expressing green fluorescent-labelled protein LC3 during the assessment of autophagy. Western blot, immunofluorescent microscopy and flow cytometry were used for analysis. There was a significant rise in PIBD incidence in Scotland since the early 1990s, with 260 new cases between 1990-1995 (4.45/100,000/year) and 436 in the 2003-2008 epoch (7.82/100,000/year) (p<0.001). A five-fold increase in Crohn's disease (CD) in the last 40 years was also demonstrated. SES was shown to have the highest recorded PIBD incidence rate in the UK for the six-year epoch from 2006-2011 (9.50/100,000/year) with a significant rise in ulcerative colitis (UC) to 2.67/100,000/year (p=0.010). Point prevalence rates for PIBD in SES had also risen significantly to 41.2/100,000 between the 2000-2005 and 2006-2011 epochs (p=0.016). With a follow up of 1577 patient years, the severe phenotype in children with PIBD was confirmed; 34% of children with CD presented with pan-enteric disease (44% at follow up), and 76% of children with UC had pancolonic disease at diagnosis (81% at follow up). 26% of patients required methotrexate and 18% were exposed to infliximab/adalimumab, with the time to first exposure of both significantly lower in children diagnosed between 2006-2011 (p=0.001 and p<0.001 respectively). A total of 70% of children were exposed to azathioprine and 20% underwent IBD-related surgery. Using a haplotype-tagging approach and transmission disequilibrium testing (TDT) in 230 PIBD case-parent trios there was significant overtransmission of the rs8126734-A single nucleotide polymorphism (SNP) in ICOSLG following correction (p=0.0467). In the CD TDT analysis the same SNP was overtransmitted (p=0.0084). The strongest susceptibility signal was evident across the two marker haplotype rs762421-A / rs8126734-G (p=0.0072), suggesting that the 3-prime untranslated region in ICOSLG may be targeted for deep sequencing. mRNA microarray data from adult patients showed downregulation of ICOSLG expression in the ascending colon (p=0.023) and upregulation in the descending colon (p=0.0351) in uninflamed biopsies from CD patients and non-IBD controls; no difference in gene expression was shown in UC patients. Using a similar approach, the A allele of two SNPs tagging CRP showed significant over-transmission to affected IBD patients after correction (rs1417938, p=0.006; rs1130864, p=0.015). The six-marker haplotype (ACACAC) showed significant distortion of transmission to affected individuals (p=8x10-4). CD and UC patients demonstrated differences in rs1205 genotype (p=0.0085) and CRP haplotype (p=0.0024), with the influence of the rs1205 SNP on response to anti-tumour necrosis factor-alpha therapy also shown (p=0.021). During the FC case-control study significantly elevated FC levels at diagnosis were demonstrated compared to controls (1265 μg/g vs 65 μg/g; p<0.001). FC also outperformed commonly used blood parameters (e.g. CRP, ESR, platelets), with an area under the curve of 0.93 (95% CI 0.89-0.97) and good sensitivity (0.93 [95% CI 0.86-0.98]) and specificity (0.74 [95% CI 0.64-0.82]) when values above 200μg/g were used. FC levels were not influenced by disease location in CD or UC. The systematic review and meta-analysis highlighted the often poor methodological quality of previous studies and concluded that across all studies FC had a pooled sensitivity of 0.98 (95% CI 0.95-1.00) and pooled specificity of 0.68 (95% CI 0.50-0.86) for PIBD at diagnosis. Characterisation of cells stably-expressing wild-type NOD2 or the CD-associated NOD2 frameshift mutation demonstrated increased cell proliferation compared to empty vector, and an accentuated apoptotic response to serum starvation. The NOD2 frameshift protein had a shorter half-life (at 11 hours) than the wild-type protein, with degradation of the NOD2 protein shown to be mediated through a proteasome-dependent pathway, possibly through lysine residues on the CARD domain. Following the establishment of a robust method of assessing autophagy in a cell culture system, experimental work showed that muramyl dipeptide-induced autophagy is unlikely to signal through the mammalian target of rapamycin, with the intermediate filament vimentin shown to be intimately involved in this pathway; the vimentin gene (Vim) was also shown to be a candidate susceptibility gene for CD. Using a panel of PIBD drugs azathioprine was shown to induce autophagy in a dose-dependent manner through an mTOR-dependent, ERK-independent pathway. It can be seen that with the increasing incidence and prevalence of PIBD in Scotland that a greater understanding of epidemiological trends, the role of genetic susceptibility, the optimal use of biomarkers and translational functional biology are all needed to understand further the aetiopathogenesis of PIBD. This future work will undoubtedly help to inform service design and the clinical care pathways utilised to provide the best care for children in addition to targeting pathways for potential drug development, with these measures helping to prepare for the increasing disease burden generated by PIBD.

Orientador: Alexandre Lima Andrade / Banca: Flávia de Almeida Lucas / Banca: Silvia Maria Caldeira Franco Andrade / Resumo: As ceratites ulcerativas são comuns na rotina do médico veterinário de pequenos animais, visto que a córnea é uma estrutura vulnerável devido sua exposição ao meio externo. Por compreender uma das estruturas responsáveis pela refração luminosa e participante do mecanismo de formação da imagem, é de extrema importância a integridade da anatomia e transparência da córnea para esta continuar desempenhando suas funções. Estudos ainda são realizados com o intuito de viabilizar opções terapêuticas cirúrgicas para o tratamento de úlceras de córnea complicadas, tentando alcançar uma cicatrização com um menor dano à estrutura corneal e menor opacidade cicatricial, devolvendo a transparência da córnea. Visto que os polímeros biodegradáveis tem se mostrado alvo de pesquisas atuais para aplicações médicas, com este estudo objetivou-se avaliar originalmente a biocompatibilidade da membrana do polímero poli(butileno adipato-co-tereftalato) (PBAT) na córnea e posterior aplicação clínica deste material nas ceratites ulcerativas profundas. Para tal, foi realizada avaliação clínica experimental e histopatológica após enxertia interlamelar do PBAT em córnea de coelhos, ao longo de 60 dias, e acompanhamento da evolução clínica do emprego da membrana de PBAT no tratamento de ceratites ulcerativas complicadas em cães, comparando ao uso do enxerto conjuntival, ao longo de 90 dias. Devido aos baixos sinais de inflamação corneal clínicos e histopatológicos nos coelhos e a cicatrização corneal em todo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Ulcerative keratitis are common in the routine of a small animals veterinary doctor, given that the cornea is a vulnerable structure due to its exposure to external environment. For containing one of the structures responsible for light refraction and participant in the mechanism of formation of images, it is of extreme importance the integrity and transparency of the cornea in order for it to continue to develop its functions. Studies are still performed with the intent of making feasible surgical therapeutic options for the treatment of complicated corneal ulcers, trying to reach cicatrization with less damage to the corneal structure and less scar opacity, seeking corneal transparency. Given that biodegradable polymers have been target of current research for medical applications, the objective of this study was to evaluate originally the biocompatibility of the poly (butylene adipate-co-terephthalate) polymer (PBAT) in the cornea and posterior clinical application of this material in deep ulcerative keratitis. It was performed clinical and histopathological evaluation after interlamellar grafting of PBAT in the cornea of rabbits, over 60 days, and follow-up of the clinical evolution of PBAT membrane in the treatment of complicated ulcerative keratitis in dogs, comparing to the use of conjunctival graft, over 90 days. Due to low levels of clinical and histopathological corneal inflammation found in rabbits and corneal cicatrization in all dogs, without occurence of visual ... (Complete abstract click electronic access below) / Mestre

Background The conventional ileostomy can be avoided. Many attempts have been performed. The first successful solution was the continent ileostomy- Kock pouch. The high rate of complications and revisions some experienced forced surgeon to try to restore the continence by the mechanism of the anus involving an ileal pouch. Both procedures afterwards documented excellent functional outcome, but the complication rates were not negligible and the long-term failure rate were increasing. Different surgical refinements were done and the risk factors for complications and failures were investigated as experience and materials increased. Restoring of the integrity of anal function and the succsess of the ileal pouch-anal anastomosis shadowed the practise of the forerunner: the continent ileostomy reservoir. This latter procedure was more demanding and seemed in the first year of ileal pouchanal anastomosis era to have significant more complications and revisional surgery. The worldwide adoption of the pelvic pouch decreased the need for the continent ileostomy and a vicious circle evolved. Today only few centres perform the procedure. Patients who are not suitable for ileal anal-pouch anastomosis are seldom offered the possibility of having a continent ileostomy. Aims The aims of the study was to investigate surgical load, complications and long-term functional outcome and to define factors which affect these subjects in patients operated with ileal pouch-anal anastomosis, continent ileostomy or both in one single surgical department during the same period and without any institutional learning curve, and furthermore, to compare and contrast the two options. Material and methods From 1984 to 2005(7) 304 (315) patients were operated with IPAA at St. Olavs Hospital (earlier: Regional Hospital of Trondheim). From 1983 to 2002(7) 50 (65) patients had a continent ileostomy constructed. This was an observational study in the scope of surveillance and quality assurance. All patients were offered a planed regularly annual outpatient clinic follow up programme including a prospective standardised interview on clinical outcome. This was a supplement to clinical investigation with endoscopy and consecutive documentation of complications and other factors affecting the patients’ health. Data were recorded in the medical chart. In this system, all patients had recorded dataset. However, the intervals between data recordings differ and the intervals increased by time. All inpatients data were included. Standard descriptive statistical analysis and simple associations were undertaken. Handling longitudinal data with limited cases, varying time intervals was done in a Times Series Cross Sectional data model, analysed, and adjusted for several factors affecting functional outcome. Multivariable analysis was done. Results The estimated failure rate at 20 years was 11.4% for ileal pouch-anal anastomosis and 11.6% for continent ileostomy. Salvage procedures rates were 31% vs. 38%, respectively (p=0.06). The salvage procedures in IPAA included local procedures and redoes with laparotomy. Salvage procedures in CI were related to the function of the nipple valve, mainly nipple valve sliding and less frequent stenosis or fistulas. Complications rates were high. In pelvic pouch surgery, half of the patients would need re-operations in 20 years. Ten percentages had early anastomotic separation without septic complications. Four percentages had early pelvic septic complications. Fistulas and sepsis at the anastomotic site were the main severe complications, often leading to pouch failure. Closing of the loop ileostomy was accompanied with complications in six percentages. In the patients (48) who did not have a covering stoma the overall complications rate did not differ from those with a loop ileostomy, although nine needed a secondary stoma. Covering stoma seems to postpone anastomotic complications. Handsewn anastomosis had more strictures, but otherwise the complications rates were similar to stapled anastomosis. Patients having the diagnosis changed to Crohn`s diseases had more complications and higher failure rate. Early anastomotic complications were associated with long-term complications. In patients with continent ileostomy the nipple valve sliding is the main cause of revision. One third needed revision once or several times. At 20 years follow-up, half of the patients would need surgery due to complications. Although many patients with CI need several revisions, all patients were continent at the last follow up with a stable intubation frequency of 3 – 5 per 24 hour. The failure of the pelvic pouch is the end of severe complications. Two third of the failures had the pouch excision or permanent ileostomy with the pouch in situ. One third underwent a conversion to CI, with equal surgical and functional outcome as other patients with CI. In IPAA, bowel movements at day were between 5-6 at day and 0-1 at night. The rates of more or less frequent incontinence were about 10%, and 41% and 55% had reported soling at day and night respectively. The long-term functional outcome did not deteriorate with time: ie. observational time, as an independent factor did not influence outcome. Factors influencing the outcome were found but the impact of gender, age, protective stoma, hand-sewn anastomosis and early complications were negligible. Pouchitis did significantly influence functional outcome negatively, but did not create deterioration over time. Estimated pouchitis rate in IPAA was 43% for more than 20 years. The onset of the first pouchitis appears mostly in the 5-6 first years after surgery. The crude rate was 35% and 6% of the patients had chronic pouchitis. Severe/chronic pouchitis was associated with primary sclerosing cholangitis, but not with pyoderma gangrenousum or diagnosed joint affections. Idiopathic pouchitis were absent among patients with familial adenomatous polyposis. In continent ileostomy the rate of pouchitis was 26%. Conclusion The complications in both the pelvic pouch surgery and the surgery of continent ileostomy are considerable. Although not similar the surgical load are in the same order of magnitude. For the continent ileostomy revisional surgery are to be expected. The failure rate of both procedures are high and in long-term similar. The long-term functional outcome are however stabile and excellent. The failed pelvic pouch can be converted to a continent ileostomy in selected and motivated patients. The entity of pouchitis is conflicting and has to be divided into several different entities both on clinical, constitutional and other differentiating features. Patients with PSC should be informed of a possible higher risk of severe and chronic pouchitis after IPAA.

Background and aim: Persistent stress and life events affect the course of ulcerative colitis (UC) by largely unknown mechanisms. Regulation of epithelial permeability to antigens is crucial for the balance between inflammation and immuno-surveillance, and increased intestinal permeability has been shown in patients with ulcerative colitis. Corticotropin releasing hormone (CRH) has been implicated as an important mediator of stress-induced abnormalities in intestinal mucosal function in animal models. Further cholinergic signalling during stress has been reported to increase bowel ion secretion in humans and uptake of HRP in rodents via activation of mast cells. The overall aim of this thesis was to examine the role of CRH-mediated and cholinergic signalling, and their interaction with mast cells and eosinophils, in the regulation of the mucosal barrier function in the normal human colon and in UC. In vivo studies or the use of surgical specimens for such studies have major shortcomings. Therefore a method with endoscopic biopsies in Ussing chambers was established for studies of protein antigen uptake and electrophysiology in human colonic biopsies, and used in subsequent investigations. Materials and methods: In the four studies a total of 91 healthy volunteers, 3 patients with rectal cancer, and 15 UC patients were included. Biopsies from the sigmoid colon were assessed for macromolecular permeability (Horseradish peroxidase (HRP), and 51Cr-EDTA), and electrophysiology during challenge with sodium caprate (C10), CRH or carbachol. Experiments were repeated with CRH receptor antagonists, carbachol receptor antagonists, mast cell stabilizers and nerve conductance blockers in Ussing chambers. The biopsies were examined by electron and light microscopy for endocytosis of HRP, morphological changes and receptor expression. Moreover, the human mast cell line, HMC-1; was used in studying expression of CRH receptors on mast cells. Results: Endoscopic biopsies of human colon were viable in Ussing chambers, and the technique was shown to be a reliable tool for studies of mucosal permeability to HRP. CRH stimulates transcellular uptake of HRP in human colon via CRH receptor subtypes R1 and R2 on subepithelial mast cells. Further, carbachol acts on muscarinic receptors, located on subepithelial eosinophils. Activated muscarinic M2 and M3 receptors on increased numbers of CRHproducing eosinophils in UC, lead to activation of mast cells and increased macromolecular uptake across the colonic mucosa. This signalling cascade is previously unrecognized, and may be involved in the inflammatory process in UC. Conclusions: In conclusion, we have demonstrated a chain of events leading to increased permeability to the protein antigen HRP in biopsies from healthy volunteers and patients with UC. The important steps begin with a cholinergic signal to muscarinic receptors on the CRH containing eosinophils. The next step includes activation of CRH receptors on mast cells leading to degranulation and increased macromolecular uptake across the epithelium. This explanatory model will have implications for understanding of the pathogenesis of UC and future treatment of the disease.

Thesis (M. Phil.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 112-126).