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Pentadecapeptide BPC 157 Counteracts Failure of Lower Esophageal and Pyloric Sphincter Induced by NSAIDs in Rats
AGA Abstracts
of these patients had a normal response to multiple rapid swallow (MRS). Only 16% of the non-hypermobile patients with dysphagia had hypomotility (p<0.0005 vs JHS). 1 JHS patient (6%) had achalasia compared with 17% controls (p:0.24). 41% of the JHS patients had normal oesophageal motility and 6 of these had reflux studies: 50% had GORD. Only 2 JHS patients (12%) had hiatus hernias vs 20% in the control group (NS). Conclusion: This is the first study to characterise upper GI physiology in patients with JHS and non-obstructive dysphagia. Compared to dysphagia patients without hypermobility, the JHS patients had significantly more oesophageal hypomotility with half of them producing normal aftercontractions with MRS, suggesting muscle integrity. Those patients are likely to show the best response to prokinetics. The pathophysiology of hypomotility in these patients remains unknown. GORD was common in this population and will require antireflux therapy.
10 rats at least per group, assessed as described before (3). Results. NSAIDs (control). Regularly, fall of pressure occurred rapidly and persisted (i.e., DI, 12.5 mg: 30 mins: 45.0±2.5 PS, 55.0±2.5 LES - 3h: 43.8±2.5 PS, 56.0±2.5 LES -41.0±3.0 PS, 48.6±3.5 LES (3 days); PA 250 mg ig: 60.0±1.5 PS, 63.0±1.0 LES (15 mins); PA 5g ip: 35.0±5.5 PS, 40.0±3.5 LES (3h); IB, 4 weeks: 33.0±3.5 PS, 43.0±3.0 LES; AS 400mg ip, 3h: 60.0±1.5 PS, 62.0±0.5 LES (3h); AS 400mg ig, 3h: 58.0±1.5 PS, 61.0±1.0 LES; BPC 157. Regularly, initial fall of pressure was minimized and pressure values restored to normal values (i.e., DI, 12.5 mg: 30 mins: 66.0±2.5 PS, 70.0±2.5 LES - 3h: 62.8±2.5 PS, 69.0±3.5 LES - 62.2±3.0 PS, 72.6±5.5 LES (3 days); PA 250 mg ig: 70.0±1.5 PS, 73.0±1.0 LES (15 mins); PA 5g ip: 68.0±5.5 PS, 70.0±2.5 LES (3h); IB, 4 weeks: 70.0±5.5 PS, 73.0±6.0 LES; AS 400mg ip, 3h: 65.0±0.5 PS, 70.0±0.8 LES (3h); AS 400mg ig, 3h: 68.0±1.5 PS, 71.0±0.9 LES;; (vs. control p<0.05). Finally, these BPC 157 effects correlate with attenuated injuries of liver (PA+BPC157; IB+BPC157), stomach (AS+BPC 157, IB+BPC 157, DI+BPC157), and small intestine (DI+BPC157). Conclusion. All tested NSAIDs decrease pressure in LES and PS, whilst BPC 157 counteracts their effects and restored LES and PS function. Literature. 1.Curr Pharm Des. 2010;16:1224-34, 2. Dig Dis Sci. 2009;54:2070-83, 3. J Pharmacol Sci. 2008;108:7-17, 4. Dig Dis Sci. 2009;54:46-56, 5. J Pharmacol Sci. 2007;104:7-18. 6. J Physiol Pharmacol. 2010;61:241-50.
Sa1128 What Are the Symptoms and Risk Factors for Candida Esophagitis? Naoyoshi Nagata, Naoki Asayama, So Nishimura, Takuro Shimbo, Shinichi Oka, Naomi Uemura Background and Aims: Candida esophagitis (CE) is one of the most gastointestinal infection in the esophagus.The clinical symtoms and risk factors in CE has not been fully studied yet. Our aims are to identify the clinical symptoms and risk factors for CE. Materials and Methods: We prospectively enrolled 1,855 patients who underwent upper endoscopy and answered questionnaires in 2009-2010. We investigated with regard to the following items. 1) Gastrointestinal (GI) symptoms: epigastric pain, hurtburn, reflux, hunger cramps, nausea, dysphagia, and odynophagia. Each symptoms were assessed using the GI Symptom Rating Scale (GSRS). 2) Lifestyle: history of smoking and alcohol, 3) Digestive disorder: postoperative stomach, reflux esophagitis, 4) Underlying diseases: HIV infection, diabetes mellitus, hyperlipidemia, chronic renal failure, and liver cirrhosis, 5) Drugs: steroids, proton pomp inhibitor (PPI), and H2 blocker. CE was diagnosed by gross appearance at endoscopy. Results: Of the 1,855 patients, 71 patients (3.8%) were diagnosed with CE. No significant difference was observed in upper GI symptoms between CE + and CE - (CE- 53% vs CE+ 58%, p= 0.42). Among GI symptoms, odynophagia (odds ratio (OR), 1.30; 95% confidence interval (CI), 1.03-1.1.64; p=0.03) is found to be associated with CE (multivariate analysis). Atthached table shows the risk factors (Univariate analysis). Multivariate analysis revealed that age (OR, 1.03; 95% CI, 1.00-1.04; p=0.02), chronic renal failure (OR, 4.23; 95%CI, 1.82-10.1; p<0.01), HIV infection (OR, 8.77; 95%CI, 4.39-17.5; p<0.01), and steroid user (OR, 11.4; 95%CI, 6.02-19.8; p<0.01) were the independent risk factors. Conclusions: The characteristics of GI symotoms with CE is odynophagia. Age, chronic renal failure, HIV infection,and steroid user are independent risk factors. This study presents new information on the risk factors and GI symptoms for CE. Risk factors for Candida Esophagitis (CE) by univariate analysis (n=1,855)
Sa1130 Prevalence of Pathologic Reflux Disease in Patients With Spastic Motility Disorders Lauren B. Gerson, Sami R. Achem Background: Spastic esophageal motility disorders should be considered in patients presenting with dysphagia, chest pain, or gastroesophageal reflux (GERD) symptoms that are not responding to proton pump inhibitor (PPI) therapy. The co-existence of pathologic GERD in this patient population deserves further study. Methods: We performed a retrospective analysis of patients undergoing esophageal manometry from 2000-2010 in order to identify patients diagnosed with a spastic motility disorder. Nutcracker esophagus (NE) was defined as the presence of mean distal esophageal amplitude ≥ 180 mm Hg with preserved peristalsis. Hypertensive lower esophageal sphincter was present if the mean lower esophageal sphincter pressure exceeded 45 mm Hg. Diffuse esophageal spasm (DES) was present if there were simultaneous contractions occurring more than 20% of the time with a minimum esophageal amplitude of 30 mm Hg and otherwise preserved peristalsis. In order to be included into the study, we required that patients also underwent ambulatory pH monitoring off of PPI therapy. Patients with abnormal pH studies on PPI therapy were also included. We recorded percentage time pH< 4% for total time, upright and supine values and considered a patient to have GERD if one or more of the values were abnormal, including total time pH<4 greater than 4.5%, upright pH more than 8%, or supine pH<4 for more than 3% of the time. For patients undergoing 48-hour pH analysis, the 24-hour period with the highest pH values was included. Results: We identified 261 patients who underwent esophageal motility studies between 2000-2010 and were diagnosed with a spastic esophageal motility disorder. 123 (47%) patients were excluded due to lack of pH monitoring studies; this cohort included 4 patients with failed Bravo studies and 8 patients with normal pH studies on PPI therapy. Subsequent analysis was performed on 138 patients who had undergone esophageal manometry and pH monitoring. The cohort included 58 patients with NE, 57 with DES, and 23 patients with hypertensive LES and/or more than one diagnosis. Esophageal pH monitoring included 24-hour pH studies in 58 (42%), 48-hour Bravo pH monitoring in 71 (51%) and esophageal pH-impedance in 4 patients. Results are demonstrated in the Table. Patients with NE were more likely to be younger compared to patients with DES and the entire cohort. 68% of the patients demonstrated abnormal pH monitoring values. NE patients were more likely to manifest co-existing pathologic GERD. Bravo probe failure or early dislodgement occurred in 9 (3%) of the patients. Conclusions: Over two-thirds of patients with spastic motility disorders manifested pathologic GERD. Abnormal pH studies were more common in patients with NE. Future studies should determine the impact of medical and endoscopic therapy for spastic motility disorders on underlying GERD. Demographic Data and Study Results
IQR, interquartile range. Sa1129 Pentadecapeptide BPC 157 Counteracts Failure of Lower Esophageal and Pyloric Sphincter Induced by NSAIDs in Rats Sandra Franjic, Domagoj Drmic, Lara Bauk, Mirjana Stupnisek, Tomislav Becejac, Bozo Radic, Spomenko Ilic, Alenka Boban Blagaic, Danijela Kolenc, Luka Brcic, Zeljko Romic, Sven Seiwerth, Predrag Sikiric Aim. The risks of aspirin/NSAIDs to induce esophageal and other GI tract lesions have been documented, whilst their effect on lower esophagea sphincter (LES) and pyloric sphincter (PS) pressure is far less studied. Thereby, we tested in rats various NSAIDs and a safe stable gastric pentadecapeptide BPC 157(GEPPPGKPADDAGLV, MW 1419), LD1 not achieved, since successful in inflammatory bowel disease trials, and counteracts esophagitis, sphincters failure, gastrointestinal ulcer and skin ulcer, gastro- or colo-cutaneous fistulas in rats, and particularly counteracts NSAIDs-lesions(1-6). Methods. Diclofenac (DI) (12.5 or 40 mg/kg ip, once daily, for 1, 2 or 3 days), ibuprofen (IB) (400 mg/day/kg for 4 weeks), paracetamol (PA) (150 mg/kg ip, 250 mg/kg ig, 5 g/kg ip once), aspirin (AS) (400 mg/kg i.p. or i.g.), BPC 157 immediately after NSAIDs (10 ug/kg i.p. or i.g.), LES and PS pressure (cm H2O),
AGA Abstracts
Values shown are mean ± standard deviation. NS= not significant. *ANOVA performed for continuous variables. Categorical variables analyzed with chi-square analysis.
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of these patients had a normal response to multiple rapid swallow (MRS). Only 16% of the non-hypermobile patients with dysphagia had hypomotility (p<0.0005 vs JHS). 1 JHS patient (6%) had achalasia compared with 17% controls (p:0.24). 41% of the JHS patients had normal oesophageal motility and 6 of these had reflux studies: 50% had GORD. Only 2 JHS patients (12%) had hiatus hernias vs 20% in the control group (NS). Conclusion: This is the first study to characterise upper GI physiology in patients with JHS and non-obstructive dysphagia. Compared to dysphagia patients without hypermobility, the JHS patients had significantly more oesophageal hypomotility with half of them producing normal aftercontractions with MRS, suggesting muscle integrity. Those patients are likely to show the best response to prokinetics. The pathophysiology of hypomotility in these patients remains unknown. GORD was common in this population and will require antireflux therapy.
10 rats at least per group, assessed as described before (3). Results. NSAIDs (control). Regularly, fall of pressure occurred rapidly and persisted (i.e., DI, 12.5 mg: 30 mins: 45.0±2.5 PS, 55.0±2.5 LES - 3h: 43.8±2.5 PS, 56.0±2.5 LES -41.0±3.0 PS, 48.6±3.5 LES (3 days); PA 250 mg ig: 60.0±1.5 PS, 63.0±1.0 LES (15 mins); PA 5g ip: 35.0±5.5 PS, 40.0±3.5 LES (3h); IB, 4 weeks: 33.0±3.5 PS, 43.0±3.0 LES; AS 400mg ip, 3h: 60.0±1.5 PS, 62.0±0.5 LES (3h); AS 400mg ig, 3h: 58.0±1.5 PS, 61.0±1.0 LES; BPC 157. Regularly, initial fall of pressure was minimized and pressure values restored to normal values (i.e., DI, 12.5 mg: 30 mins: 66.0±2.5 PS, 70.0±2.5 LES - 3h: 62.8±2.5 PS, 69.0±3.5 LES - 62.2±3.0 PS, 72.6±5.5 LES (3 days); PA 250 mg ig: 70.0±1.5 PS, 73.0±1.0 LES (15 mins); PA 5g ip: 68.0±5.5 PS, 70.0±2.5 LES (3h); IB, 4 weeks: 70.0±5.5 PS, 73.0±6.0 LES; AS 400mg ip, 3h: 65.0±0.5 PS, 70.0±0.8 LES (3h); AS 400mg ig, 3h: 68.0±1.5 PS, 71.0±0.9 LES;; (vs. control p<0.05). Finally, these BPC 157 effects correlate with attenuated injuries of liver (PA+BPC157; IB+BPC157), stomach (AS+BPC 157, IB+BPC 157, DI+BPC157), and small intestine (DI+BPC157). Conclusion. All tested NSAIDs decrease pressure in LES and PS, whilst BPC 157 counteracts their effects and restored LES and PS function. Literature. 1.Curr Pharm Des. 2010;16:1224-34, 2. Dig Dis Sci. 2009;54:2070-83, 3. J Pharmacol Sci. 2008;108:7-17, 4. Dig Dis Sci. 2009;54:46-56, 5. J Pharmacol Sci. 2007;104:7-18. 6. J Physiol Pharmacol. 2010;61:241-50.
Sa1128 What Are the Symptoms and Risk Factors for Candida Esophagitis? Naoyoshi Nagata, Naoki Asayama, So Nishimura, Takuro Shimbo, Shinichi Oka, Naomi Uemura Background and Aims: Candida esophagitis (CE) is one of the most gastointestinal infection in the esophagus.The clinical symtoms and risk factors in CE has not been fully studied yet. Our aims are to identify the clinical symptoms and risk factors for CE. Materials and Methods: We prospectively enrolled 1,855 patients who underwent upper endoscopy and answered questionnaires in 2009-2010. We investigated with regard to the following items. 1) Gastrointestinal (GI) symptoms: epigastric pain, hurtburn, reflux, hunger cramps, nausea, dysphagia, and odynophagia. Each symptoms were assessed using the GI Symptom Rating Scale (GSRS). 2) Lifestyle: history of smoking and alcohol, 3) Digestive disorder: postoperative stomach, reflux esophagitis, 4) Underlying diseases: HIV infection, diabetes mellitus, hyperlipidemia, chronic renal failure, and liver cirrhosis, 5) Drugs: steroids, proton pomp inhibitor (PPI), and H2 blocker. CE was diagnosed by gross appearance at endoscopy. Results: Of the 1,855 patients, 71 patients (3.8%) were diagnosed with CE. No significant difference was observed in upper GI symptoms between CE + and CE - (CE- 53% vs CE+ 58%, p= 0.42). Among GI symptoms, odynophagia (odds ratio (OR), 1.30; 95% confidence interval (CI), 1.03-1.1.64; p=0.03) is found to be associated with CE (multivariate analysis). Atthached table shows the risk factors (Univariate analysis). Multivariate analysis revealed that age (OR, 1.03; 95% CI, 1.00-1.04; p=0.02), chronic renal failure (OR, 4.23; 95%CI, 1.82-10.1; p<0.01), HIV infection (OR, 8.77; 95%CI, 4.39-17.5; p<0.01), and steroid user (OR, 11.4; 95%CI, 6.02-19.8; p<0.01) were the independent risk factors. Conclusions: The characteristics of GI symotoms with CE is odynophagia. Age, chronic renal failure, HIV infection,and steroid user are independent risk factors. This study presents new information on the risk factors and GI symptoms for CE. Risk factors for Candida Esophagitis (CE) by univariate analysis (n=1,855)
Sa1130 Prevalence of Pathologic Reflux Disease in Patients With Spastic Motility Disorders Lauren B. Gerson, Sami R. Achem Background: Spastic esophageal motility disorders should be considered in patients presenting with dysphagia, chest pain, or gastroesophageal reflux (GERD) symptoms that are not responding to proton pump inhibitor (PPI) therapy. The co-existence of pathologic GERD in this patient population deserves further study. Methods: We performed a retrospective analysis of patients undergoing esophageal manometry from 2000-2010 in order to identify patients diagnosed with a spastic motility disorder. Nutcracker esophagus (NE) was defined as the presence of mean distal esophageal amplitude ≥ 180 mm Hg with preserved peristalsis. Hypertensive lower esophageal sphincter was present if the mean lower esophageal sphincter pressure exceeded 45 mm Hg. Diffuse esophageal spasm (DES) was present if there were simultaneous contractions occurring more than 20% of the time with a minimum esophageal amplitude of 30 mm Hg and otherwise preserved peristalsis. In order to be included into the study, we required that patients also underwent ambulatory pH monitoring off of PPI therapy. Patients with abnormal pH studies on PPI therapy were also included. We recorded percentage time pH< 4% for total time, upright and supine values and considered a patient to have GERD if one or more of the values were abnormal, including total time pH<4 greater than 4.5%, upright pH more than 8%, or supine pH<4 for more than 3% of the time. For patients undergoing 48-hour pH analysis, the 24-hour period with the highest pH values was included. Results: We identified 261 patients who underwent esophageal motility studies between 2000-2010 and were diagnosed with a spastic esophageal motility disorder. 123 (47%) patients were excluded due to lack of pH monitoring studies; this cohort included 4 patients with failed Bravo studies and 8 patients with normal pH studies on PPI therapy. Subsequent analysis was performed on 138 patients who had undergone esophageal manometry and pH monitoring. The cohort included 58 patients with NE, 57 with DES, and 23 patients with hypertensive LES and/or more than one diagnosis. Esophageal pH monitoring included 24-hour pH studies in 58 (42%), 48-hour Bravo pH monitoring in 71 (51%) and esophageal pH-impedance in 4 patients. Results are demonstrated in the Table. Patients with NE were more likely to be younger compared to patients with DES and the entire cohort. 68% of the patients demonstrated abnormal pH monitoring values. NE patients were more likely to manifest co-existing pathologic GERD. Bravo probe failure or early dislodgement occurred in 9 (3%) of the patients. Conclusions: Over two-thirds of patients with spastic motility disorders manifested pathologic GERD. Abnormal pH studies were more common in patients with NE. Future studies should determine the impact of medical and endoscopic therapy for spastic motility disorders on underlying GERD. Demographic Data and Study Results
IQR, interquartile range. Sa1129 Pentadecapeptide BPC 157 Counteracts Failure of Lower Esophageal and Pyloric Sphincter Induced by NSAIDs in Rats Sandra Franjic, Domagoj Drmic, Lara Bauk, Mirjana Stupnisek, Tomislav Becejac, Bozo Radic, Spomenko Ilic, Alenka Boban Blagaic, Danijela Kolenc, Luka Brcic, Zeljko Romic, Sven Seiwerth, Predrag Sikiric Aim. The risks of aspirin/NSAIDs to induce esophageal and other GI tract lesions have been documented, whilst their effect on lower esophagea sphincter (LES) and pyloric sphincter (PS) pressure is far less studied. Thereby, we tested in rats various NSAIDs and a safe stable gastric pentadecapeptide BPC 157(GEPPPGKPADDAGLV, MW 1419), LD1 not achieved, since successful in inflammatory bowel disease trials, and counteracts esophagitis, sphincters failure, gastrointestinal ulcer and skin ulcer, gastro- or colo-cutaneous fistulas in rats, and particularly counteracts NSAIDs-lesions(1-6). Methods. Diclofenac (DI) (12.5 or 40 mg/kg ip, once daily, for 1, 2 or 3 days), ibuprofen (IB) (400 mg/day/kg for 4 weeks), paracetamol (PA) (150 mg/kg ip, 250 mg/kg ig, 5 g/kg ip once), aspirin (AS) (400 mg/kg i.p. or i.g.), BPC 157 immediately after NSAIDs (10 ug/kg i.p. or i.g.), LES and PS pressure (cm H2O),
AGA Abstracts
Values shown are mean ± standard deviation. NS= not significant. *ANOVA performed for continuous variables. Categorical variables analyzed with chi-square analysis.
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