1
AGA Abstracts emanate from a patient's urine or faecal sample. We have previously demonstrated the ability of the electronic nose (E-nose) to separate patients with inflammatory bowel disease (IBD) from healthy controls by shifts in the patterns of VOCs that emanate from urine samples. Here, we have extended our work by analysing a new IBD cohort from the USA as well as additional normal controls from the UK without any digestive disease Methods - Urine samples from Crohn's disease [11] and ulcerative patients [5] with varying degrees of activity, duration and extent of disease and healthy controls [5] were collected and immediately frozen to -800C. Samples were coded and sent on dry ice to Warwick University for analysis. An additional 20 healthy control urines from the UK were collected and analysed with the USA samples. The samples were heated to 40C +/- 0.1 C in standard containers. The head space gas was then sampled by the e nose device. We used a field asymmetric ion mobility spectroscopy [FAIMS] device as the e nose. When a sample is presented to the sensor array in this device, it produces a unique response. By combining the sensor responses, we can create a ‘bio-odorant fingerprint' for that sample. When the instrument is presented with the same type of sample again, it is able to recognise the sample (or disease), mimicking the manner by which the human olfactory system can learn. Analysis of the patterns was performed by linear discriminant analysis. The study was approved by the Institutional Review Boards at UMass and University Hospital in Warwick Results The E-nose was able to separate those with IBD from healthy controls with a sensitivity of 85% and specificity of 84%. (Figure 1). Conclusion This pilot study suggests that the E-nose can be used to distinguish effectively between patients with IBD and healthy people from two different continents. Further work is needed to expand the number of patients tested, and examine if subtypes of disease can be defined by this methodology. Tu1256 Partially Hydrolyzed Guar Gum (PHGG), a Water-Soluble Dietary Fiber, Improves Corticotropin-Releasing Hormone (CRH)-Induced Intestinal Dysmotility in Rats Kentaro Suzuki, Yuji Naito, Kazuhiro Kamada, Katsura Mizushima, Yusuke Horii, Kazuhiro Katada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Nobuaki Yagi, Zenta Yasukawa, Makoto Tokunaga, Tsutomu Okubo, Lekh R. Juneja, Yoshito Itoh Background and aim: The pathophysiological mechanism of irritable bowel syndrome (IBS) is complex and still unclear. The brain-gut axis, especially associated with a response to stress, has been thought to be involved the mechanism of IBS and corticotropin-releasing hormone (CRH) is a key role of the stress response. We have shown partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber produced by guar gum beans, improve the castor oil induced diarrhea (DDW2013). The aim of this study was to investigate the effect of PHGG on CRH-induced intestinal dysmotility in a rat stress model. Materials and methods: Six-week-old male Wistar rats were used in this study. Under anesthesia, each rat was implanted stainless steel cannula which was held in place with dental acrylic bonded towards the lateral cerebral ventricle. Animals were allowed to acclimate to the environment for 7 days before initiating the study. Rats were then divided into two groups of 8 animals each, (1) control group: diet without PHGG, (2) PHGG group: diet with 5% PHGG for 7 days. After icv (intracerebroventricular) injection of CRH (10 μg/rat) or saline in each group, the condition of stools was checked with a 2-hour fecal pellets output count. Rats were sacrificed, and colon was dissected out for histopathological assessment. The expression of substance P was measured in colon tissue in each group. Results: After the icv injection of CRH, the numbers of stools excreted were increased in rats in the control group compared with vehicle-treated animals. However, in rats in PHGG group with icv of CRH, the number of stools excreted was not increased within 2-hr. No significance differences were found in colon histopathologically between groups. The level of colon substance P expression was increased in control with icv of CRH and this increase was attenuated by PHGG pretreatment. Conclusions: PHGG improved CRH-induced bowel dysmotility via the inhibition of substance P expression in an animal model. Tu1257 Evaluation of Capsule Endoscopy As a Diagnostic Method Before Treatment of Gastrointestinal Follicular Lymphoma Sadahisa Okuhara, Yasuhiro Maruyama, Tadanobu Nagaya [Aim] Gastrointestinal follicular lymphoma (GIFL) is typically detected in the small intestine using double-balloon endoscopy (DBE) or capsule endoscopy (CE). As there is uncertainty about the optimal method of diagnosis before treatment, we evaluated the diagnostic ability S-796 AGA Abstracts of CE as a gold standard for GIFL instead of DBE. [Methods ] A total of 23 patients (12 men, median age : 60 years) with GI-FL were selected retrospectively. All patients underwent both DBE and CE before treatment. [Results] Among our patients, 82.6% were classified as having GIFL stage I and all patients were considered to have GIFL pathological grade 1. Duodenum lesion was found in all patients (23/23) by DBE. Small intestine lesion was found in 60.9% (14/23) of patients, and terminal ileum lesion was found in 43.5% (10/23). Duodenum lesion, small intestine lesion, and terminal ileum lesion were found in 21.7% (5/23), 56.5% (13/23), and 17.4% (4/23) of patients by CE. The detection rate for duodenum and terminal ileum lesions by CE was significantly lower than that by DBE (p<0.01). However, CE and DBE detection rates did not differ significantly for small intestine lesions (p=0.76).The histological grade of all intestinal lesions was 1 as determined by biopsy. [Conclusion] For diagnosis of disease stage and the decision to treat GIFL, CE together with biopsy of the duodenum by esophagogastroduodenoscopy and of the terminal ileum by colonoscopy may be sufficient Tu1258 Exhaled Pentane May Identify Disease Activity in Patients With Inflammatory Bowel Diseases Martin Bortlik, Kseniya Dryahina, Dana. Duricova, Nadezda Machkova, Patrik Spanel, Milan Lukas Background: The current diagnostic methods used for assessment of disease activity in patients with ulcerative colitis (UC) and Crohn s disease (CD) are either invasive, or have limited sensitivity and specificity. Among biological markers, C-reactive protein (CRP) and faecal calprotectin (FC) are most frequently used for this purpose. However, identification of new sensitive and non-invasive biomarkers may be of great value in routine clinical practice. Methods: One hundred and eighty patients with inflammatory bowel diseases (IBD; 129 CD and 51 UC) were recruited and participated in an ongoing study. Clinical activity indices (Harvey Bradshaw (HB) and Simple Clinical Colitis Activity Index (SCCAI)), biological markers (CRP, FC), and colonoscopy were used for assessment of disease activity. Patients were divided into 3 groups: complete remission (G1), partial remission (G2), and disease activity (G3). Fourteen volatile organic compounds (VOCs) were quantified in the exhaled breath of all patients using selected ion flow tube mass spectrometry (SIFT-MS), and results (expressed in parts per billion by volume; ppbv) in each group were compared. Results: Among all VOCs assessed, pentane concentrations in G1 and G3 were significantly different: median concentrations in CD patients were 51 ppbv (range: 29-86), and 37 ppbv (18-68) in G1 and G3, respectively. In UC patients, concentrations were 57 ppbv (41-88), and 39 ppbv (21-54) in G1 and G3, respectively. Significant correlation of exhaled pentane concentration with HBI/SCCAI was observed (Pearson correlation coefficient p=0.41 for CD, and 0.46 for UC, resp.). Exhaled pentane also showed good sensitivity and specificity as a marker of disease activity (AUC 0.776 for CD and 0.837 for UC patients). The median values of other VOCs were not significantly different. Conclusions: Pentane concentrations in exhaled breath of IBD patients correlate with disease activity, and may help to differentiate between patients with active and non-active disease. This work was supported by IBD- Comfort Foundation. Tu1259 Novel Synergistic Efficacy of Atovaquone and Diclazuril Against Severe Gastrointestinal Syndrome in Fetal Maternal Toxoplasmosis Helieh S. Oz, Thomas Tobin Toxoplasmosis is the 3rd most common cause of foodborne GI hospitalization and congenital syndromes in U.S.A. In the event of stressors like pregnancy, dormant cysts are reactivated to trigger life-threatening clinical disease. There is no safe and effective therapy against chronic or congenital Toxoplasmosis. Due to large global burden and shortcomings of current therapies, there is urgent need for effective anti-Toxoplasma drugs. We proposed that combined Atovaquone (current therapy) and Diclazuril (targets plant chlorophyll) to be safe and synergistically to protect GI against Toxoplasma (with remnant of chloroplast organelles) in pregnancy. Methods: Programmed pregnant mice were infected with Type II strain high dose Tachyzoites and treated with Atovaquone, Diclazuril monotherapy or combined therapy. Dams were monitored for pain, distress, abortion and samples collected at the end of study. Results: Infected dams developed severe GI related complications and gained excess pathologic weight (60%) due to ascities. Combined therapy (Diclazuril+Atovaquone P<0.01) and to a lesser extent Diclazuril monotherapy (P<0.05) protected dams from excess weight. Infected dams showed severe splenomegaly (3 fold), with distorted microstructure and significant increases in weight and length of splenic tissues compared with those normalized with combined therapy. Infected dams exhibited hepatomegaly and severe hepatitis with dysplastic hepatocytes, multinucleated giant cells transformation, influx of inflammatory cells, and necrosis. Combined therapy synergistically normalized (p<0.001) and to a lesser extent monotherapy (Diclazuril p<0.01, Atovaquone p<0.05) protected dams from severe hepatitis. Colonic tissues significantly shortened in length (p<0.001) with microabscess formation in cryptic structures, and infiltration of macrophages and lymphocytes, which were normalized with synergistic effects of combined therapy. Additionally, behavioral response to abdominal pain stimuli and fetal weight and fetal numbers were significantly preserved in treated dams. Conclusions: Combined Atovaquone and Diclazuril therapy synergistically protected dams' gastrointestinal structure as well as nested fetuses against severe Toxoplasmosis. This is the first report describing 1) synergistic effects of Atovaquone+Diclazuril 2) safety in pregnancy and 3) efficacy against severe Toxoplasmosis. Supported by NIH-NIDCR (HO) and KSTC (TT).

Tu1259 Novel Synergistic Efficacy of Atovaquone and Diclazuril Against Severe Gastrointestinal Syndrome in Fetal Maternal Toxoplasmosis

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Page 1: Tu1259 Novel Synergistic Efficacy of Atovaquone and Diclazuril Against Severe Gastrointestinal Syndrome in Fetal Maternal Toxoplasmosis

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semanate from a patient's urine or faecal sample. We have previously demonstrated the abilityof the electronic nose (E-nose) to separate patients with inflammatory bowel disease (IBD)from healthy controls by shifts in the patterns of VOCs that emanate from urine samples.Here, we have extended our work by analysing a new IBD cohort from the USA as well asadditional normal controls from the UK without any digestive disease Methods - Urinesamples from Crohn's disease [11] and ulcerative patients [5] with varying degrees of activity,duration and extent of disease and healthy controls [5] were collected and immediatelyfrozen to -800C. Samples were coded and sent on dry ice to Warwick University for analysis.An additional 20 healthy control urines from the UK were collected and analysed with theUSA samples. The samples were heated to 40C +/- 0.1 C in standard containers. The headspace gas was then sampled by the e nose device. We used a field asymmetric ion mobilityspectroscopy [FAIMS] device as the e nose. When a sample is presented to the sensor arrayin this device, it produces a unique response. By combining the sensor responses, we cancreate a ‘bio-odorant fingerprint' for that sample. When the instrument is presented withthe same type of sample again, it is able to recognise the sample (or disease), mimickingthe manner by which the human olfactory system can learn. Analysis of the patterns wasperformed by linear discriminant analysis. The study was approved by the InstitutionalReview Boards at UMass and University Hospital in Warwick Results The E-nose was ableto separate those with IBD from healthy controls with a sensitivity of 85% and specificityof 84%. (Figure 1). Conclusion This pilot study suggests that the E-nose can be used todistinguish effectively between patients with IBD and healthy people from two differentcontinents. Further work is needed to expand the number of patients tested, and examineif subtypes of disease can be defined by this methodology.

Tu1256

Partially Hydrolyzed Guar Gum (PHGG), a Water-Soluble Dietary Fiber,Improves Corticotropin-Releasing Hormone (CRH)-Induced IntestinalDysmotility in RatsKentaro Suzuki, Yuji Naito, Kazuhiro Kamada, Katsura Mizushima, Yusuke Horii,Kazuhiro Katada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Nobuaki Yagi,Zenta Yasukawa, Makoto Tokunaga, Tsutomu Okubo, Lekh R. Juneja, Yoshito Itoh

Background and aim: The pathophysiological mechanism of irritable bowel syndrome (IBS)is complex and still unclear. The brain-gut axis, especially associated with a response tostress, has been thought to be involved the mechanism of IBS and corticotropin-releasinghormone (CRH) is a key role of the stress response. We have shown partially hydrolyzedguar gum (PHGG), a water-soluble dietary fiber produced by guar gum beans, improve thecastor oil induced diarrhea (DDW2013). The aim of this study was to investigate the effectof PHGG on CRH-induced intestinal dysmotility in a rat stress model. Materials and methods:Six-week-old male Wistar rats were used in this study. Under anesthesia, each rat wasimplanted stainless steel cannula which was held in place with dental acrylic bonded towardsthe lateral cerebral ventricle. Animals were allowed to acclimate to the environment for 7days before initiating the study. Rats were then divided into two groups of 8 animals each,(1) control group: diet without PHGG, (2) PHGG group: diet with 5% PHGG for 7 days.After icv (intracerebroventricular) injection of CRH (10 μg/rat) or saline in each group, thecondition of stools was checked with a 2-hour fecal pellets output count. Rats were sacrificed,and colon was dissected out for histopathological assessment. The expression of substanceP was measured in colon tissue in each group. Results: After the icv injection of CRH, thenumbers of stools excreted were increased in rats in the control group compared withvehicle-treated animals. However, in rats in PHGG group with icv of CRH, the number ofstools excreted was not increased within 2-hr. No significance differences were found incolon histopathologically between groups. The level of colon substance P expression wasincreased in control with icv of CRH and this increase was attenuated by PHGG pretreatment.Conclusions: PHGG improved CRH-induced bowel dysmotility via the inhibition of substanceP expression in an animal model.

Tu1257

Evaluation of Capsule Endoscopy As a Diagnostic Method Before Treatment ofGastrointestinal Follicular LymphomaSadahisa Okuhara, Yasuhiro Maruyama, Tadanobu Nagaya

[Aim] Gastrointestinal follicular lymphoma (GIFL) is typically detected in the small intestineusing double-balloon endoscopy (DBE) or capsule endoscopy (CE). As there is uncertaintyabout the optimal method of diagnosis before treatment, we evaluated the diagnostic ability

S-796AGA Abstracts

of CE as a gold standard for GIFL instead of DBE. [Methods ] A total of 23 patients (12men, median age : 60 years) with GI-FL were selected retrospectively. All patients underwentboth DBE and CE before treatment. [Results] Among our patients, 82.6% were classified ashaving GIFL stage I and all patients were considered to have GIFL pathological grade 1.Duodenum lesion was found in all patients (23/23) by DBE. Small intestine lesion was foundin 60.9% (14/23) of patients, and terminal ileum lesion was found in 43.5% (10/23).Duodenum lesion, small intestine lesion, and terminal ileum lesion were found in 21.7%(5/23), 56.5% (13/23), and 17.4% (4/23) of patients by CE. The detection rate for duodenumand terminal ileum lesions by CE was significantly lower than that by DBE (p<0.01). However,CE and DBE detection rates did not differ significantly for small intestine lesions (p=0.76).Thehistological grade of all intestinal lesions was 1 as determined by biopsy. [Conclusion] Fordiagnosis of disease stage and the decision to treat GIFL, CE together with biopsy of theduodenum by esophagogastroduodenoscopy and of the terminal ileum by colonoscopy maybe sufficient

Tu1258

Exhaled Pentane May Identify Disease Activity in Patients With InflammatoryBowel DiseasesMartin Bortlik, Kseniya Dryahina, Dana. Duricova, Nadezda Machkova, Patrik Spanel,Milan Lukas

Background: The current diagnostic methods used for assessment of disease activity inpatients with ulcerative colitis (UC) and Crohn s disease (CD) are either invasive, or havelimited sensitivity and specificity. Among biological markers, C-reactive protein (CRP) andfaecal calprotectin (FC) are most frequently used for this purpose. However, identificationof new sensitive and non-invasive biomarkers may be of great value in routine clinicalpractice. Methods: One hundred and eighty patients with inflammatory bowel diseases (IBD;129 CD and 51 UC) were recruited and participated in an ongoing study. Clinical activityindices (Harvey Bradshaw (HB) and Simple Clinical Colitis Activity Index (SCCAI)), biologicalmarkers (CRP, FC), and colonoscopy were used for assessment of disease activity. Patientswere divided into 3 groups: complete remission (G1), partial remission (G2), and diseaseactivity (G3). Fourteen volatile organic compounds (VOCs) were quantified in the exhaledbreath of all patients using selected ion flow tube mass spectrometry (SIFT-MS), and results(expressed in parts per billion by volume; ppbv) in each group were compared. Results:Among all VOCs assessed, pentane concentrations in G1 and G3 were significantly different:median concentrations in CD patients were 51 ppbv (range: 29-86), and 37 ppbv (18-68)in G1 and G3, respectively. In UC patients, concentrations were 57 ppbv (41-88), and39 ppbv (21-54) in G1 and G3, respectively. Significant correlation of exhaled pentaneconcentration with HBI/SCCAI was observed (Pearson correlation coefficient p=0.41 for CD,and 0.46 for UC, resp.). Exhaled pentane also showed good sensitivity and specificity as amarker of disease activity (AUC 0.776 for CD and 0.837 for UC patients). The medianvalues of other VOCs were not significantly different. Conclusions: Pentane concentrationsin exhaled breath of IBD patients correlate with disease activity, and may help to differentiatebetween patients with active and non-active disease. This work was supported by IBD-Comfort Foundation.

Tu1259

Novel Synergistic Efficacy of Atovaquone and Diclazuril Against SevereGastrointestinal Syndrome in Fetal Maternal ToxoplasmosisHelieh S. Oz, Thomas Tobin

Toxoplasmosis is the 3rd most common cause of foodborne GI hospitalization and congenitalsyndromes in U.S.A. In the event of stressors like pregnancy, dormant cysts are reactivatedto trigger life-threatening clinical disease. There is no safe and effective therapy againstchronic or congenital Toxoplasmosis. Due to large global burden and shortcomings of currenttherapies, there is urgent need for effective anti-Toxoplasma drugs. We proposed thatcombined Atovaquone (current therapy) and Diclazuril (targets plant chlorophyll) to be safeand synergistically to protect GI against Toxoplasma (with remnant of chloroplast organelles)in pregnancy. Methods: Programmed pregnant mice were infected with Type II strain highdose Tachyzoites and treated with Atovaquone, Diclazuril monotherapy or combined therapy.Dams were monitored for pain, distress, abortion and samples collected at the end ofstudy. Results: Infected dams developed severe GI related complications and gained excesspathologic weight (60%) due to ascities. Combined therapy (Diclazuril+Atovaquone P<0.01)and to a lesser extent Diclazuril monotherapy (P<0.05) protected dams from excess weight.Infected dams showed severe splenomegaly (3 fold), with distorted microstructure andsignificant increases in weight and length of splenic tissues compared with those normalizedwith combined therapy. Infected dams exhibited hepatomegaly and severe hepatitis withdysplastic hepatocytes, multinucleated giant cells transformation, influx of inflammatorycells, and necrosis. Combined therapy synergistically normalized (p<0.001) and to a lesserextent monotherapy (Diclazuril p<0.01, Atovaquone p<0.05) protected dams from severehepatitis. Colonic tissues significantly shortened in length (p<0.001) with microabscessformation in cryptic structures, and infiltration of macrophages and lymphocytes, whichwere normalized with synergistic effects of combined therapy. Additionally, behavioralresponse to abdominal pain stimuli and fetal weight and fetal numbers were significantlypreserved in treated dams. Conclusions: Combined Atovaquone and Diclazuril therapysynergistically protected dams' gastrointestinal structure as well as nested fetuses againstsevere Toxoplasmosis. This is the first report describing 1) synergistic effects ofAtovaquone+Diclazuril 2) safety in pregnancy and 3) efficacy against severe Toxoplasmosis.Supported by NIH-NIDCR (HO) and KSTC (TT).