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A study was performed to identify apoptotic cells in the equine intestine and to determine if the occurrence of apoptosis is affected by gastrointestinal disease and tissue layer of intestine. Samples of intestine were collected from 38 horses that underwent surgery or were humanely destroyed for small or large bowel obstruction, strangulation or distension. Samples were also taken from 9 horses which were humanely euthanized for reasons other than gastrointestinal disease or systemic disease. Specimens were collected at surgery from intestine involved in the primary lesion, distant to the primary lesion, or at necropsy from several sites including the primary lesion. Tissues were fixed, serially sectioned and stained with hematoxylin and eosin (H&E) and for apoptosis by the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) technique. The number of apoptotic cells per high power field were counted in the mucosa, circular muscle, longitudinal muscle and serosa for each sample of intestine. Apoptotic staining nuclei were seen in all layers of intestine. An increased number of apoptotic cells were found in the circular muscle of the intestine from horses with simple obstruction. Intestine distant from the primary strangulating lesion had higher numbers of apoptotic cells than intestine distant from a simple obstruction lesion or intestine taken at the site of a strangulating or simple obstructive lesion. Intestine from horses with obstructing or strangulating lesions in the small intestine and large colon has increased numbers of apoptotic cells. Further investigation is required to determine whether increased apoptosis affects intestinal function. / Master of Science

Humans harbour a diverse suite of microorganisms in and on their bodies. These microorganisms collectively amount to 10 times more cells than human cells in the body, and their combined genomes have more than 100 times more genes than the human genome does. Despite our understanding of the composition, diversity, and abundance of microorganisms of the human body, it is surprising how little we know about the structure and function of the human microbiome. Here, I use network structure to describe interactions among human-associated microbiota and the human body by exploring differences in structure of human microbiomes across five regions of the body and the robustness of these networks to perturbations. My results show that positive interactions among microbiota are extremely important in structuring microbiome networks and those structural aspects of microbiome networks play a major role in their response to perturbations.

Systemic hydration, plasma electrolytes, ingesta and fecal hydration and gastrointestinal passage of cobalt (after CoEDTA administration via nasogastric tube) in horses fed large grain meals or treated with enteral fluid therapy, IV fluid therapy and enteral laxatives were investigated. In the first study, 0.9% NaCl (10 L/h/8h) was administered slowly via a small-bore nasogastric tube or as 10 L boluses via a large-bore nasogastric tube to four normal horses. In the other studies, horses with a right dorsal colon fistula were used. To create the right dorsal colon fistula, a cannula with 5 cm internal diameter was implanted 2 to 6 weeks after a right dorsal colopexy had been created. Six horses with the right dorsal colostomy were alternately used to test three feeding regimes for 48 h: 1- hay free choice; 2- hay free choice plus 4.5 kg of sweet feed twice daily after a period of 5 days of adaptation; 3- sudden change from hay to hay plus sweet feed. Seven horses with the right dorsal colostomy were alternately used to test 6 experimental conditions while fasted for 24 h: 1- control (no treatment), 2- enteral MgSO4 (1 g/kg), 3- enteral Na2SO4 (1 g/kg), 4- IV lactated Ringer's solution (5 L/h/12 h), 5- enteral water (5 L/h/12 h), 6- enteral electrolyte solution (5 L/h/12 h). In the last study, four horses with the right dorsal colostomy were alternately treated with enteral electrolyte solution (10 L/h/6h) and enteral MgSO4 (1 g/kg) plus IV fluid therapy (10 L/h/6h). Despite the administration regimen, enteral administration of 0.9% NaCl produced diarrhea, hypernatremia and hyperchloremia. Colostomy allowed serial collection of large ingesta samples. Grain ingestion did not change PCV or plasma protein, but affected plasma electrolytes and produced dehydration of ingesta and formation of frothy ingesta. Fasting delayed gastrointestinal transit. Enteral fluid therapy was the most effective treatment in promoting ingesta hydration. Enteral water, MgSO4, Na2SO4, IV fluid therapy and enteral MgSO4 plus IV fluid therapy were either ineffective in promoting ingesta hydration or produced marked plasma electrolyte imbalance. These findings support the use of enteral fluid therapy in horses with gastrointestinal impaction. / Ph. D.

Upper gastrointestinal symptoms can be caused by many different diseases and can present themselves in many different forms and range in intensity depending on the person. In previous research, upper gastrointestinal symptoms have been correlated with stress, smoking, alcohol intake, and nonsteroidal anti-inflammatory drugs (NSAIDs), among others. The purpose of this study will be focusing on finding any association between these risk factors mention and symptoms of upper gastrointestinal disease among college students. The study will utilize an Izumo scale questionnaire for the assessment of abdominal symptoms and Quality of Life (QOL). The questionnaire was built using Survey Monkey and distributed via email to students at the University of Central Florida (UCF). The main hypothesis was that the more the student’s advancement in their college career, stress load, alcohol consumption, smoking, poor diet and a high consumption of some over the counter medication (specifically Non-Steroidal Anti Inflammatory Drugs), the more prone the students will be to present symptoms of upper gastrointestinal disease. The results were analyzed using Statistical Package for the Social Science (SPSS), and Analysis of Variance (ANOVA) were used to find any associations. The One-Way ANOVA tests showed an association between gender, ethnicity, student status, major, cigarette smoking habits, alcohol consumption, binge drinking, diet, stress, sleeping, and overall health. The results of this study present clear evidence that among college students, their demographics as well as lifestyle and school choices have significant associations to the amount of gastrointestinal symptoms they present with.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21667号 / 医博第4473号 / 新制||医||1035(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 小柳 義夫, 教授 中川 一路, 教授 長船 健二 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Microbial contaminants in water are a major public health concern. Pathogens have been identified as a primary threat to river water quality in the United States, potentially impacting drinking and irrigation water sources and recreational waters. Agricultural runoff, feedlot operations, wastewater effluents, swimming activities, domestic and wild animals are potential sources of microbial contamination. This thesis presents Massachusetts as a case study for linking public health data of waterborne gastrointestinal diseases with sources of drinking water, potential recreational exposures, as well as hydrologic, climatic, and land use data. Giardia sp. has been chosen as a model organism. Information of reported human Giardiasis cases has been synthesized. Using Geological Information system and statistical software (SPSS and SAS) relationships of confirmed Giardiasis have been compared with available climate and hydrologic data. In this thesis the research finding suggest that there is no visible difference in disease occurrence related with amount of precipitation or extreme rain event. However human giardiasis in Massachusetts has been found related with temperature thus shows a seasonal trend in disease occurrence. Seasonal water related human activity likely have played a role in disease occurrence.

Background: Nutritional deficiencies are frequent in celiac disease (CeD), and one of the most common is zinc (Zn) deficiency. Supplements are often prescribed to treat Zn deficiency; however, they have been associated with adverse events and reduced absorption of other minerals. Data collected in our clinic showed that 38% of CeD patients would opt for a diet to improve Zn, however, such a diet may be challenging due to food interactions with phytic acid, which blocks Zn absorption. Therefore, the feasibility and efficacy of a Zn-optimized diet compared to supplementation is unknown. Aims: To assess the feasibility of the protocol and collect data on estimated effect sizes for secondary outcomes to plan a properly powered randomized controlled trial (RCT). Methods: We conducted an open-label, pilot RCT. CeD patients were randomized to Zn supplementation (Zn gluconate 25mg) or a Zn-optimized diet for 3 months and followed up with a 3-month pragmatic approach. We evaluated enrollment rates and adherence to both interventions. Plasma and urine Zn, stool samples, and questionnaires were collected pre- and post-intervention. Results: We enrolled 28 participants and 16 of them have completed the study. Interim analysis shows an enrollment fraction of 26% (i.e. 28/108 eligible participants), and a dropout rate of 17.9%. Eighty-two % of participants allocated to the Zn-supplement intervention and 50% in the dietary intervention were compliant at 3 months. Based on the effect size for normalization of plasma Zn at 3 months, 142 participants are required for an adequately powered RCT in the future. There were no significant differences in gastrointestinal or extra-intestinal symptoms, quality of life, anxiety and depression or adverse events between interventions. Conclusion: Based on this preliminary analysis, recruitment of participants will take 6 months longer than expected. Assessment of reasons for diet non-adherence will allow implementation of strategies to improve feasibility. / Thesis / Master of Science in Medical Sciences (MSMS)

<p>Colorectal cancer leads to more than 600,000 deaths worldwide per year. An abundance of research has shown that several non-steroidal anti-inflammatory drugs (NSAIDs) can exert chemotherapeutic and chemo-preventative effects in colorectal cancer patients. It is important to note, that use of many different NSAIDs carries a significant risk for cardiovascular and gastrointestinal (GI) complications. A recently developed group of NSAIDs, which release hydrogen sulfide (H₂S), has been shown to have greatly reduced these side effects as compared to conventional NSAIDs. This is likely attributable to the ability of H₂S to increase the resistance of the GI mucosa to injury, as well as to accelerate repair of injury when it occurs. Moreover, H₂S has been shown to be a vasodilator, and therefore may offset some of the hypertensive effects of NSAIDs.</p> <p>We assessed the chemotherapeutic actions of two of these newly developed NSAIDs. ATB-346 is an H₂S-releasing derivative of naproxen and ATB-352 is an H₂S-releasing derivative of ketoprofen. These drugs were tested in the azoxymethane mouse model and in the APC^Min/+mouse model of Colorectal cancer.</p> <p>In the azoxymethane model of colorectal cancer ATB-346 caused a significant reduction in number aberrant crypt foci (ACF), which are pre-neoplastic lesions used as markers of colorectal cancer. The reduction was superior to naproxen at all doses tested. ATB-352 also caused a significant reduction in the number of ACF, however the reduction was not superior to that produced by ketoprofen. In APC^Min/+mice treated with ATB-346 for 14 days (14.5 mg/kg) we observed a complete inhibition of the formation of colonic polyps/tumours and a 97.5% reduction in total polyp score. Shorter treatment with ATB-346 also produced similar reduction in total polyp score. We found that ATB-346-treated mice had lower levels of b-catenin and cmyc without significant changes in APC or p53 levels. <strong></strong></p> <p>These results demonstrate ATB-346 can exert superior chemo-preventative effects in mice models of colon cancer while leading to no gastric or intestinal damage.</p> / Master of Science (MSc)