Aim To determine that carbon dioxide (CO2), instead of air, insufflated during colonoscopy reduces pain experienced by patients post colonoscopy. Method A randomised, double blinded, controlled trial with 205 consecutive consented patients referred for elective colonoscopy was undertaken at MidCentral Health Gastroenterology Department between July 2008 and January 2009. Patients were randomised to colonic insufflation with either air or CO2. A comparison of reported pain was undertaken using a 0 -10 point numeric rating scale at several time periods; intra procedure, 10, 30, and 60 minutes post procedure. Results The results were analysed using the SPSS programme. CO2 insufflation was used in 108 patients and air in 97 patients. Pain scores 10 minutes after were 0.43 ± 1.20 for CO2 and 1.61 ± 2.40 for air (P < .0001). 30 minutes after the procedure 90% of patients in the CO2 group reported no pain, compared to 61% of the air group. CO2 significantly reduced the amount of discomfort post colonoscopy at 10, 30 and 60 minutes. Conclusion Those receiving CO2 during colonoscopy experienced less post colonoscopy pain than those who received air insufflation. Carbon dioxide should be considered as the insufflating gas during colonoscopy.

Acute Upper Gastrointestinal Bleeding (AUGIB) accounts for 7000 deaths in the UK annually and is the single leading indication for transfusion of blood components. A large UK audit in 2007 reported high case fatality and rates of further bleeding. Since many deaths are determined by pre-existing co-morbidity, strategies to improve outcome should be targeted at preventable deaths and therefore focus upon improved control of haemorrhage and prevention of further bleeding, which are investigated in this thesis. Data for the analyses presented originate from the UK national audit of AUGIB, a laboratory study and a cross sectional survey. Five broad themes were investigated including service provision and timing of endoscopy, the use of transcatheter arterial embolisation (TAE) or surgery for refractory bleeding, the impact of coagulopathy on outcome, management of acute variceal haemorrhage (AVH) and haemostatic derangements after AVH, and the use of red blood cells (RBCs). Although there was no evidence of a “weekend effect” for mortality, earlier endoscopy (<12 hours) was associated with improved control of haemorrhage in higher risk patients compared to later endoscopy (>24 hours). TAE was an effective and safe modality for refractory bleeding, but the high post-surgical mortality (29%) raises questions about the appropriateness of case selection for surgery. Coagulopathy after non-variceal haemorrhage was associated with a 5-fold increase in risk-adjusted mortality. Further bleeding after AVH was strikingly high (26%) with notable deficiencies in the use of vasopressors, antibiotics and endotherapy. Global assessments of coagulation demonstrated that thrombin generation after AVH was normal, but clot strength was poor with excessive fibrinolysis. Platelets, fibrinogen and antifibrinolytics improved haemostasis ex vivo but coagulation factor transfusion had no effect. RBC transfusion practice is variable. This work on AUGIB provides new data highlighting areas of sub-optimal care, and informs both current practice and research questions for new interventional trials.

Colorectal cancer (CRC) is defined as a cancer appearing in the colon or in the rectum. In Sweden, ~ 6300 individuals were diagnosed with the disease in 2014 and ~ 2550 individuals diagnosed with CRC die each year due to their cancer. Surgery is the main treatment option of CRC and a survival rate of ~ 10 % is estimated if distant metastases have developed. It is therefore of importance to find factors that may be useful together with tumour, node, metastasis (TNM) stage to establish early CRC diagnosis, prognosis and follow-up of CRC patients. The aim of this thesis was to study the possible association of CD93, PLA2G4C, PDGF-D and inflammatory cytokines with CRC disease progression. In a prospective study approach CD93 and PLA2G4C single nucleotide polymorphisms (SNPs) were of potential importance in CRC prognosis. The T/T genotype of CD93 was associated with an increased CD93 expression in CRC tissue. Further, CRC patients carrying this genotype were associated with disseminated CRC at diagnosis and a lower recurrence-free survival after surgery. The A allele of a SNP of PLA2G4C was a stronger predictor for CRC-specific mortality than the conventional risk factors used in the clinic for selection of TNM stage II patients for adjuvant treatment. This indicates that the T/T genotype of CD93 and the A allele of PLA2G4C may be potential genetic factors related to disease severity and spread. Furthermore, they distinguish CRC patients that may benefit from a more comprehensive follow-up and adjuvant treatment. To study the putative involvement of PDGF-D in CRC the effects of PDGF-D signalling was studied in vitro. PDGF-D signalling altered the expression of genes of importance in CRC carcinogenesis and proliferation which was blocked by imatinib, a tyrosine kinase inhibitor. This indicates that PDGF-D signalling may be an important pathway in CRC progression and a potential target in CRC treatment. The analysis of various inflammatory cytokines in plasma at diagnosis showed an association between high levels and increased total- or CRC-specific mortality two years after surgery. High levels of CCL1 and CCL24 was the only cytokines strongly correlated with a worse CRC prognosis after statistical adjustments and may be of interest for further evaluation. In conclusion, this thesis presents circulating and genetic factors such as CD93, PLA2G4C, PDGF-D, CCL1 and CCL24 that may be of importance in CRC progression and may be of clinical value together with TNM stage in establishing prognosis. / Kolorektal cancer är en tumör i kolon eller rektum. I Sverige diagnosticerades år 2014 ca6300 individer med denna cancertyp och ca 2550 personer dör årligen till följd av kolorektalcancer. Operation är det huvudsakliga behandlingsalternativet för kolorektal cancer och vidfjärrmetastaser är överlevnaden &lt; 10 %. Det är därför viktigt att hitta markörer somtillsammans med TNM-stadium kan ge tidig information om sjukdomens prognos och lämpliguppföljning av patienter. Utveckling av kolorektal cancer sker genom ackumulering av genetiska mutationer ochepigenetisk nedreglering av tumörsuppressorgener. Därutöver spelar interaktionen mellantumören och dess närmaste omgivning, innehållande tillväxt- och inflammatoriska faktorer,en viktig roll i tumörens utveckling och metastasering. Syftet med avhandlingen var att studera associationen mellan CD93, PLA2G4C, PDGF-D samtinflammatoriska cytokiner och kolorektal cancer progression. En prospektiv studie visade att CD93 och PLA2G4C SNP var potentiellt viktiga förbedömningav kolorektal cancer prognos. T/T genotypen av SNP rs2749817 i CD93 var associerad medhögre uttryck av CD93 i kolorektal cancer vävnad, främst bland patienter i stadium IV.Därutöver observerades fler återfall efter operation hos patienter med T/T genotypen. Aallelen hos PLA2G4C SNP rs1549637 är en möjligtvis bättre markör för cancerspecifiköverlevnad vid stadium II än faktorer som idag används för att selektera patienter tilladjuvant behandling. Sammantaget antyder detta att T/T genotypen av CD93 och A allelenav PLA2G4C kan vara genetiska markörer relaterade till allvarlig tumörsjukdom ochspridning. Därutöver kan de eventuellt selektera patienter som kräver tätare uppföljning ochadjuvant behandling. För att studera den förmodade inblandningen av PDGF-D i kolorektal cancer undersöktesdess effekt på PDGF-D signalering in vitro. PDGF-D signaleringen förändradegenexpressionen av gener involverade i tumörutveckling och spridning, vilken kundeblockeras av tyrosinkinashämmaren imatinib. Det antyder att PDGF-D signalering kan vara enviktig faktor vid kolorektal cancer progression och ett potentiellt mål för behandling. Analysen av ett flertal inflammatoriska cytokiner visade en korrelation mellan högacytokinnivåer och ökad cancerspecifik och total dödlighet två år efter operation. Höga CCL1och CCL24 nivåer var de enda faktorerna som förblev signifikant associerade medcancerspecifik mortalitet vid fördjupad statistisk analys och bör studeras vidare. Sammanfattningsvis presenterar denna avhandling cirkulerande och genetiska faktorersåsom CD93, PLA2G4C, PDGF-D, CCL1 and CCL24 som eventuellt är viktiga vid bedömning avkolorektal cancer progression tillsammans med TNM stadium.

Crohn’s disease (CD), a chronic inflammatory condition of the gut affecting 1:1000 of western populations, is thought to arise from a dysregulated immune response in a genetically susceptible individual. Polymorphisms in the ligand recognition domain of an intracellular pattern recognition receptor (PRR), NOD2, remain the strongest genetic risk factor for the development of CD. NOD2 directs autophagy in human DCs to facilitate bacterial destruction and antigen presentation; the CD-variant-NOD2 shows defects in this pathway. Recent work in the laboratory has demonstrated NOD2 signals to control expression induction of microRNA-29, which is impaired in cells from CD patients expressing CD NOD2-variants, and among other immunoregulatory effects, microRNA-29 suppresses IL-12p40/IL-23. Thus NOD2 directs key anti-microbe and immunoregulatory functions whose breakdown in the presence of CD-variant-NOD2 could act as a trigger for inflammation in this disease. In comparison with other PRRs, relatively little is understood of the hardwiring of NOD2 signalling, the mechanism of NOD2-mediated autophagy induction, the means by which NOD2 recruits a signalling platform within the cytosol and the mechanism of synergy with other PRRs and the inflammasome. In this work I used quantitative proteomics to map the NOD2 signalling cascade and its cross-talk with TLR2, demonstrating novel mediators: LCP1, a plastin, reduced phagocytosis of bacteria but did not alter bacterial killing, and aided control of the release of MCP1 and may be involved in IL-12p40 release. SHP1, a phospho-tyrosine phosphatase, is required for the propagation of signalling cascades via p38, p44/42 MAPK and NF-κB. It controls release of MIP1β and IL-12p40. HMGB1, an alarmin, is dephosphorylated on NOD2 stimulation and would result in changes to cellular location of HMGB1. Lastly, DAPK1, a serine/threonine kinase, is associated with HLA-DM loading compartment on NOD2 triggering, but does not alter CLIP levels on the surface of the cells. Thus, defining the hard wiring of NOD2 signalling in healthy donors, in comparison with CD donors expressing variant NOD2, is important to define targets amenable to drug design within this pathway.

During the course of infection with chronic pathogens such as Hepatitis C virus (HCV), Hepatitis B virus (HBV) and HIV, virus-specific CD8^&plus; T cells differentiate into heterogeneous dysfunctional subpopulations. Advances in multi-parameter flow cytometry have allowed these subpopulations to be further classified into classes of exhausted T cells, primarily by their expression of multiple inhibitory receptors. However, the exact phenotype of CD8^&plus; T cells during exhaustion is an area of great interest as many inhibitory receptors are also expressed on functional CD8^&plus; T cells. Discovering novel and specific markers of T cell exhaustion is fundamental in developing strategies to restore CD8^&plus; T cell function in chronic viral infections. Recently, genome wide expression profiles have identified broad molecular phenotypes in exhausted T cells that could not have been discovered by flow cytometry alone. I show how similar genomic approaches identify and further characterise the ectonucleotidase CD39 as a novel marker of CD8^&plus; T cell exhaustion in chronic viral infection. I show that CD39 is highly expressed in HCV and HIV-specific CD8^&plus; T cells and that CD39^&plus; CD8^&plus; T cells are enriched with gene signatures of exhaustion. CD39 is highly co-expressed with multiple inhibitory receptors including PD-1, enzymatically active on CD8^&plus; T cells in HCV infection and positively correlated with viral load in both HCV and HIV. I also demonstrate the discovery of a novel CD39^High population of cells in the mouse model of chronic Lymphocytic Choriomenigitis Virus (LCMV) infection, which express the highest degrees of PD-1, LAG3 and 2B4 in the CD39^&plus; fraction. Thus, CD39 is a novel and specific marker of severe CD8^&plus; T cell exhaustion in human and animal models of chronic viral infection.

Hepatitis C virus (HCV) is a major global pathogen estimated to infect over 170 million people worldwide. A recent study has shown that vaccination with adenoviral vectors, based on rare human and simian serotypes encoding the non-structural (NS) proteins of HCV, induces highly potent, multi-specific and durable T cell responses in healthy human volunteers. In this thesis I assess the safety and immunogenicity of these vaccines (ChAd3–NSmut and Ad6-NSmut), for the first time in HCV infected patients. This work also explores whether vaccine-induced T cell responses target in vivo circulating HCV antigens and common naturally occurring epitope variants. Patients with treatment naive chronic genotype 1 HCV infection were vaccinated (i.m.) with ChAd3-NSmut and Ad6-NSmut in a heterologous prime boost schedule, either with or without current IFN and ribavirin (IFN/RBV). Epitope-specific T cell responses were defined by fine mapping using HCV peptides. Circulating viral genomic sequence was determined in vaccinated patients at baseline and at any point of viral relapse. Cross-reactivity of vaccine-induced T cell responses was determined in T cell assays, using peptides corresponding to both circulating host virus and common population HCV epitope variants. An in vitro dendritic cell /T cell priming model was used to identify possible candidates for a cross-reactive vaccine immunogen at the most immunodominant epitope, NS3₁₄₀₆. 33 patients were vaccinated. Vaccination was well tolerated. At the highest vaccine dose (2.5 x 10¹⁰vp) vaccine-induced T cell responses were detectable in 11/20 patients receiving concurrent IFN/RBV and 2/4 patients receiving vaccination alone. In total 14 antigenic targets were identified, 2 of which have not previously been described. However, T cell responses were of lower magnitude and more narrowly focused than those observed in healthy volunteers vaccinated with the same regimen. Analysis of viral sequence showed that in many cases vaccine-induced T cells did not target the circulating virus. At the most immunodominant epitope (NS3₁₄₀₆), T cells induced by vaccination failed to target common circulating genotype 1 HCV variants. An in vitro model suggested that in order to target all genotype 1 sequences at this epitope, it would be necessary to insert both a genotype 1a and 1b version of this epitope into a vaccine immunogen. Vaccination with adenoviral vectors induces T cell responses in patients with chronic HCV infection, however immune responses are attenuated compared with healthy volunteers. Ultimately a successful therapeutic or prophylactic vaccine strategy will rely on inducing responses that target conserved or cross-reactive epitopes.

INTRODUCTION: The techniques currently in practice to diagnose and assess interval disease activity in patients with inflammatory bowel disease (IBD) are costly and invasive. Physicians typically rely on information derived from a combination of endoscopic, radiologic, and histologic studies to diagnose and determine the extent and severity of the two most common forms of IBD, Crohn disease (CD) and ulcerative colitis (UC). The development of noninvasive methods of assessing response to therapy is of increasing importance to pediatric healthcare providers. Previous studies have demonstrated that serum and fecal biomarkers are reliable measures of inflammation in the gastrointestinal tract. However, existing biomarkers are non-specific and their levels can be elevated in the context of either acute and chronic inflammation (IBD) or infection. As such, further studies are required to develop newer and novel biomarkers that have greater specificity for use in the diagnosis and interval assessment in children and adults with IBD. OBJECTIVES: The goal of this study is to further assess the relationship between biomarkers in the stool and serum of patients with IBD that are being treated with the anti-TNF therapy, infliximab (Remicade). To accomplish this, we will assess the changes in serum and fecal biomarker levels over the course of treatment and correlate the changes in fecal and serum biomarker levels with clinical, biochemical, and endoscopic outcome variables. METHODS: We conducted a prospective longitudinal cohort study in pediatric patients with IBD receiving long-term immunosuppressive therapy with Remicade. Pediatric patients diagnosed with either CD or UC who receive Remicade at Boston Children’s Hospital were recruited. Patients were drawn from subsets of patients that were either naïve to Remicade, had received Remicade for less than 6 months, or had received Remicade for more than one year at the time of enrollment. We collected longitudinal data over the course of their first 6 consecutive infusions following enrollment, including blood and stool samples, disease activity indexes, as well as a patient-reported outcome measure (IMPACT-III Questionnaire) at each infusion session. RESULTS: A total of 33 patients with IBD who fit our eligibility criteria and provided informed consent were enrolled to date. Of these, 20 had a CD diagnosis and 13 had a UC diagnosis. We collected baseline serum, fecal, and IMPACT-III score data and followed enrolled patients over the course of subsequent infusions. Mean baseline fecal ASCA levels from 8 CD and 6 UC patients were 0.08±0.021 OD and 0.02±0.0015 OD, respectively. At baseline, serum lactoferrin (p<0.10), calprotectin (p<0.10), ESR (p<0.05), and CRP (p<0.10) were significantly higher among CD patients. CONCLUSION: Our data demonstrate the potential for serum and fecal biomarkers to evaluate therapeutic response to Remicade. Completion of study enrollment and data collection will be necessary to determine if individual or combinations of fecal and serum biomarkers yield the most robust measures for use in the diagnosis and interval assessment of children and adults with IBD.

Com o objetivo de estudar os possíveis efeitos da administração sistêmica de glutamina ou da associação de hidrocortisona, dimetilsulfóxido, ácido ascórbico e pentoxifilina nas lesões de isquemia e reperfusão no cólon maior, foram utilizados dezoito equinos. Sob anestesia geral e controle da oximetria de pulso e pressão arterial, os equinos foram submetidos a laparotomia e em um segmento do cólon maior foi induzida isquemia venosa total. Após uma hora de isquemia, seis equinos do Grupo G receberam glutamina (25mg/Kg IV), seis equinos do Grupo A receberam uma associação de hidrocortisona (4mg/Kg IV), dimetilsulfóxido (20mg/Kg IV), ácido ascórbico (50mg/Kg IV), e pentoxifilina (10mg/Kg IV) e os seis equinos do Grupo C receberam apenas solução de Ringer com lactato e constituíram o Grupo controle. Após duas horas de isquemia o fluxo sanguíneo local foi restabelecido. Decorridas duas horas de reperfusão foi realizada a laparorrafia e permitiu-se a recuperação anestésica. Seis horas após o início da reperfusão os equinos do Grupo G receberam novamente 25mg/Kg de glutamina, enquanto os equinos dos Grupos A e C receberam apenas solução de Ringer com lactato. Doze horas após o início da reperfusão os equinos foram eutanasiados. Foram colhidas amostras de cólon antes da indução da isquemia, após duas horas de isquemia e após duas e doze horas de reperfusão, que foram submetidas a avaliação histomorfológica, ultra-estrutural e determinação da atividade de mieloperoxidase. Os resultados para todas as variáveis estudadas foram semelhantes entre os grupos, permitindo concluir que os tratamentos, nas condições em que foram empregados neste estudo, não foram eficazes em atenuar as alterações decorrentes de isquemia e reperfusão no cólon maior de equinos. / This study was designed to evaluate the effects of intravenous administration of glutamine or the association of hydrocortisone, dimethyl sulphoxide, ascorbic acid and pentoxifylline on ischemia reperfusion lesions of the large colon. A segment of the large colon was isolated in 18 horses under inhalant general anesthesia and total venous ischemia was induced. One hour after the onset of ischemia, glutamine (25mg/Kg IV) was administered to six horses (G group), an association of hydrocortisone (4mg/Kg IV), dimethyl sulphoxide (20mg/Kg IV), ascorbic acid (50mg/Kg IV) and pentoxifylline (10mg/Kg IV) was administered to six horses, and the others received only isotonic fluids and remained as the control group (C). After 2 hours of ischemia and 2 hours of reperfusion the abdomen was closed and the horses were allowed to recover from anesthesia. After 6 hours of reperfusion, horses of group G received another dose of glutamine (25mg/Kg IV) whereas groups A and C received only isotonic fluids. Horses were euthanatized 12 hours after reperfusion. Biopsies were taken from the large colon before and after 2 hours of ischemia and after 2 and 12 hours of reperfusion. Alterations were evaluated under light and scanning electronic microscopy and scored. Additionally, mieloperoxidase (MPO) activity was measured. Results showed that scores for mucosal lesion, edema, hemorrhage, neutrophil infiltration and MPO activity during IR were similar between groups G, A and C. It was concluded that treatments were not effective in attenuating effects of ischemia and reperfusion in the equine large colon.

Submitted by Suzana Dias (suzana.dias@famerp.br) on 2018-11-05T17:34:59Z No. of bitstreams: 1 RenataAlmeida_dissert.pdf: 630010 bytes, checksum: bb2d40cdec2c3f3c54ca453ee7b1e73c (MD5) / Made available in DSpace on 2018-11-05T17:34:59Z (GMT). No. of bitstreams: 1 RenataAlmeida_dissert.pdf: 630010 bytes, checksum: bb2d40cdec2c3f3c54ca453ee7b1e73c (MD5) Previous issue date: 2017-08-11 / Introduction: Hepatitis C is one of the leading causes of chronic liver disease, reaching 170 million people. The joint treatment of Alfapeginterferone and Ribavirin associated with Telaprevir can eradicate the virus in more than 50% of patients. Objective: This study aims to investigate psychological symptoms, quality of life, fatigue and confronting strategies or style in patients treated with alfapeginterferone, ribavirin and telaprevir: before, during and after treatment; Methods: Ten patients (6 men and 4 women) started the treatment and for four of them (3 men and 1 woman) it was suspended due to the effects. Results: According to data relating to the quality of life, the participants presented reduction in all domains, especially emotional, physical, social and vitality aspects. The main confronting strategy used was religious practice/fanciful thinking and the symptoms of fatigue, depression, and anxiety throughout the treatment increased with subsequent decline. Discussion: Data from this study in relation to gender and age are compatible with the literature. However, regarding fatigue symptoms, the levels do not corroborate with the manufacturer's information, which considers tiredness as an unusual reaction. Conclusion: the results indicate a decline in quality of life, a need for weekly psychological and psychiatric support, psychiatric medication aid and greater assistance from the team. / Introdução: A hepatite C é uma das principais causas de doenças hepáticas crônicas, atingindo 170 milhões de pessoas. O tratamento conjunto de Alfapeginterferona e Ribavirina associado ao Telaprevir pode erradicar o vírus em mais de 50% dos pacientes. Objetivo: investigar sintomas psicológicos, qualidade de vida, fadiga e estilo/estratégias de enfrentamento em pacientes tratados com alfapeginterferona, ribavirina e telaprevir: antes, durante e pós-tratamento; Método: dez pacientes (6 homens e 4 mulheres) iniciaram o tratamento e, para quatro deles (3 homens e 1 mulher), foi suspenso em função dos efeitos. Resultados: nos dados relativos à qualidade de vida os participantes apresentaram redução em todos os domínios, especialmente aspectos emocionais, físicos, sociais e vitalidade. A principal estratégia de enfrentamento utilizada foi prática religiosa/pensamento fantasioso e os sintomas de fadiga, depressão e ansiedade ao longo do tratamento aumentaram com posterior declínio. Discussão: os dados deste estudo em relação a sexo e idade são compatíveis com a literatura. Entretanto, em relação aos sintomas de fadiga, os níveis não corroboram com a informação do fabricante, que enquadra cansaço como uma reação incomum. Conclusão: os resultados apontam declínio na qualidade de vida, necessidade de acompanhamento psicológico semanal, psiquiátrico, auxílio de medicação psiquiátrica e maior assistência da equipe.

Made available in DSpace on 2016-04-28T20:15:26Z (GMT). No. of bitstreams: 1 2007-Tiago Marques dos Santos.pdf: 2575604 bytes, checksum: e88af70c2740e40f39ed1fb8bd423ec5 (MD5) Previous issue date: 2007-02-26 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / This work aimed to evaluate gastrointestinal and systemic disturbances, and mucosa and gut contents of gastrointestinal tract of horses subjected to overload carbohydrate. Eight crossbreed mature horses were used with body weight (BW) average of 364kg, geldings, adapted to diet composed by grass hay and concentrate, in a 60:40 proportion. A complete randomized design was used with horses allocated in three treatments. Treatment I: (Control) (n=2) horses were slaughtered without overload carbohydrate; Treatment II (n=3) and III (n=3), horses subjected to overload carbohydrate, with gastric infusion of 17.6 g starch/kg BW, and slaughtered after 24 and 36 hours, respectively. Horses were subjected to clinical, hematological and fecal evaluations before the overload and 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36 hours after overload. Four hours after overload horses became depressed and keeping until the end of evaluation, and one horse presented lameness 36 hours after overload. Any difference (P>0.05) were observed in heart rate, respiratory rate, body temperature and hoof temperature. Increase in packed cell volume and plasma protein concentration were observed 24 hours after overload, varying from 26.7 to 32.0% and 7.1 to 8.1 g/dL, respectively (P<0.05). Differences were observed (P<0.05) in plasmatic lactate concentration in zero, 20 and 28 hours after overload, with values of 0.7, 1.04 and 1.22 mmol/L, respectively. Plasma endotoxin concentration didn't cross 0.1000 EU/mL and may be not present. There were any difference (P>0.05) in fecal and digesta water content, however, fecal pH reduced along 36 hours post-overload (P <0.01), varying from 6.09 to 4.46. Content of large intestine in horses subjected to overload presented whitish-green color, milk aspect, with gas bubbles and acid odor. There weren t difference (P>0.05) in water content of feces and digesta, however, fecal pH reduced along 36 hours post-overload (P <0.01), varying from 6.09 to 4.46. Buffering capacity of ceco-colon digesta and feces were reduced in horses subjected to overload. Right dorsal colon, transverse colon and descendent colon were segments, except stomach, that presented lower pH values, varying from 4.49 to 4.56. Eosinophils infiltration were presented in mucosa and submucosa of all horses, however, only horses submitted to overload presented neutrophils and eosinophils leucocitoestase with neutrophils predominance restricted to large intestine. Tract gastrointestinal circulatory alterations observed were congestion, edema and lymphatic vessels dilatation, more evident in submucosa, with larger inflammatory cells infiltration in horses subjected to overload. Intestinal mucosa 36 hours after overload presented larger degree of imunorreactivity anti-myeloperoxidase, followed by horses evaluated at 24 hours after overload and control horses, varying from 2.7 to 4.0, 1.0 to 3.7 and 1.0 to 2.5, respectively. Overload carbohydrate in horses promoted intensive fermentation in ceco-colon, predisposing clinical disturbances, digesta alterations and mucosa and submucosa lesions at gastrointestinal tract of horses with light to moderate degree,36 hours after overload. / Este trabalho teve como objetivo avaliar as altera??es sist?micas, da mucosa e conte?do do trato gastrointestinal de eq?inos submetidos ? sobrecarga diet?tica com amido. Foram utilizados oito eq?inos adultos castrados, com peso vivo m?dio de 364 kg, adaptados a dieta composta por feno de Coastcross e concentrado, na propor??o de 60:40. Foi utilizado um delineamento experimental com tr?s tratamentos: Tratamento I (Controle) (n=2), eutan?sia dos animais sem sobrecarga com amido; Tratamentos II (n=3) e III (n=3), animais submetidos ? sobrecarga com amido, com infus?o g?strica de 17,6 g amido/kg de peso corporal e eutan?sia ap?s 24 e 36 horas, respectivamente. Os eq?inos foram submetidos a avalia??es cl?nicas, hematol?gicas e f?sico-qu?micas das fezes antes da sobrecarga e 2, 4, 8, 12, 16, 20, 24, 28, 32 e 36 horas p?s-sobrecarga. Os animais apresentaram-se ap?ticos quatro horas ap?s a sobrecarga permanecendo assim at? o final da avalia??o e apenas um animal apresentou claudica??o, 36 horas p?s-sobrecarga. N?o houve diferen?a (P>0,05) na freq??ncia card?aca, freq??ncia respirat?ria, temperatura corporal e temperatura dos cascos. Houve aumento (P<0,05) no volume globular e prote?na plasm?tica total, 24 horas p?s-sobrecarga, variando de 26,7 a 32,0% e de 7,1 e 8,1 g/dL, respectivamente. Houve diferen?a (P<0,05) na concentra??o plasm?tica de lactato no tempo zero, 20 e 28 horas p?s-sobrecarga, com valores de 0,7, 1,04 e 1,22 mmol/L, respectivamente. A concentra??o plasm?tica de endotoxinas n?o ultrapassou 0,1000 EU/mL, podendo estar at? mesmo ausente. O conte?do do intestino grosso nos eq?inos submetidos ? sobrecarga apresentou cor verde esbranqui?ada, aspecto leitoso, com bolhas de g?s e odor ?cido. N?o houve diferen?a (P>0,05) no teor de ?gua das fezes e do conte?do da digesta, no entanto, o pH fecal reduziu ao longo de 36 horas p?s-sobrecarga (P<0,01), variando de 6,09 a 4,46. Houve redu??o na capacidade de tamponamento das fezes nos eq?inos submetidos ? sobrecarga e, de forma similar, ocorreu no conte?do do ceco-c?lon. O c?lon dorsal direito, c?lon transverso e c?lon descendente foram os segmentos, com exce??o do est?mago, que apresentaram a digesta com menores valores de pH, variando de 4,49 a 4,56. ? histopatologia, a infiltra??o de eosin?filos esteve presente na mucosa e submucosa de todos os eq?inos, no entanto, somente em dois eq?inos submetidos ? sobrecarga, observou-se leucocitoestase de neutr?filos e eosin?filos, com predomin?ncia de neutr?filos no intestino grosso. As altera??es circulat?rias observadas no trato gastrointestinal foram congest?o, edema e dilata??o de vasos linf?ticos, sendo mais evidentes na submucosa, local de maior infiltra??o de c?lulas inflamat?rias nos eq?inos submetidos ? sobrecarga. A mucosa dos segmentos do trato gastrointestinal dos eq?inos eutanasiados 36 horas p?ssobrecarga apresentou maior grau de imunorreatividade anti-mieloperoxidase, seguido dos eq?inos avaliados 24 horas p?s-sobrecarga e dos eq?inos do tratamento controle, variando de 2,7 a 4,0, 1,0 a 3,7 e 1,0 a 2,5, respectivamente. A sobrecarga diet?tica com amido em eq?inos promove fermenta??o intensa no ceco-c?lon, predispondo ao aparecimento de dist?rbios cl?nicos, altera??es do conte?do da digesta e les?es de leve a moderada na mucosa e submucosa do trato gastrointestinal dos eq?inos, ap?s 36 horas da sobrecarga.