dietary bioactive peptides in maintaining intestinal integrity and function

1
985 Dietary bioactive peptides in maintaining intestinal integrity and function Paul D. Thomas 1 , Trent W. Nichols 1 * and Angie R. Angstadt 1 . 1 CNDD, Hanover, PA, United States. Purpose: Dietary peptides are known to have biological importance bey- ound their nutritive value as protein, influencing structural, hormonal, immune, and neurological functions. Alterations in the state of phosphor- ylation of tight junctions (TJ) protein occludin in the colonic epithelia of Crohn’s and UC patients have been demonstrated. Protein balance studies performed in patients with IBD indicated better nitrogen balance with peptide-based diets than with whole food diets, which are in turn better than amino acid-based diets; however, no studied have examined the use of supplemental peptides in improving gut epithelial permeability and asso- ciated symptom relief. Methods: Twenty patients assessed to have gut hyperpermeability by a urine test utilizing lactulose to mannitol ratio were given either 3g per day of a peptide supplement from hydrolyzed fish protein or a control for 6 weeks, followed by a second permeability test and symptoms assessment scoring. Results: Preliminary results with the first 13 patients show improvement to normal permeability in 6 of 7 patients on peptide supplement, and no change or a progression to worse in 4 of 6 patients on control. Symptoms improved in 4 of 7 peptide patients and 5 of 6 control patients remained the same of worsened. Conclusions: These particular peptides appear to act as trophic factors that help heal the lining of the gut and may energize TJ via increased protein synthesis. Sponsored by Proper Nutrition, Inc. 986 Infliximab (Remicade®) in the management of ulcerative colitis Peter Tomaiolo, MD*. Saint Vincent Hospital, Worcester, MA, United States. Purpose: Case Study. Methods: Infliximab, a chimeric monoclonal antibody that binds to and neutralizes tumor necrosis factor-alpha (TNF-a), is under investigation for the management of ulcerative colitis (UC). Infliximab is currently approved for the treatment of active and fistulizing Crohn’s disease (CD), a condition that shares many similar pathologic and clinical features with UC. In both conditions, TNF-a is believed to be a key mediator in the inflammatory response. Thus, infliximab’s proven efficacy in CD makes it a promising therapy for UC. In this report, we describe a UC patient who demonstrated a remarkable response to infliximab. One day after receiving a single 5 mg/kg dose of infliximab the patient had complete resolution of his symp- toms. Results: The patient is an 85-year-old male with a history of UC as well as a past medical history of colon cancer and hypothyroidism. His disease had been well controlled on low doses of prednisone and mesalamine until approximately 1 month prior to the hospital admission described in this report, when he was admitted for a UC exacerbation. This admission was the result of persistent and worsening abdominal pain and bloody diarrhea following the previous admission. On examination the patient was found to have an elevated temperature of 101.5°F. His abdomen was diffusely tender and mildly distended with no bowel sounds. A KUB revealed dilated loops of bowel and a CAT scan revealed inflammatory changes from the splenic flexure to the rectum with no signs of peritonitis. His laboratory studies were significant for a hemoglobin of 14 g/dL, hematocrit of 41%, and white blood cell count of 12,000 mm3. The blood and stool cultures were negative. The patient’s physical exam and laboratory findings were con- sistent with the previous admission colonoscopy findings of pancolitis. A consultation from the surgical team was obtained for possible bowel obstruction/megacolon and the patient was treated with intravenous sol- umedrol, antibiotics and bowel rest. The patient was not considered a good candidate for treatment with cyclosporine. Despite these standard treat- ments, the patient’s symptoms worsened and surgery was feared to be inevitable. As a last resort, the patient agreed to treatment with infliximab. One day after receiving a single 5 mg/kg infliximab infusion, the patient reported complete resolution of his symptoms and was able to tolerate oral intake of food. The patient was discharged 4 days later and has continued to be assymptomatic to this date. Conclusions: Infliximab is a promising treatment for UC. This patient’s remarkable response to the drug is a case in point. Despite his age and poor prognosis at admission, the patient did remarkably well after a single dose of infliximab. 987 Bone mineral density measured by dual X-ray absorptiometry and quantitative ultrasonography in patients with ulcerative colitis Miklos Toth 1 , Pal Miheller 1 , Tamas Zagoni 1 , Andrea Nemetz 1 , Laszlo Pronai 1 , Laszlo Herszenyi 1 , Mark Juhasz 1 , Agota Kovacs 2 and Zsolt Tulassay 1 *. 1 2nd Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary; and 2 Department of Gastroenterology, Erzse ´bet Hospital, Budapest, Hungary. Purpose: To investigate the degree of decrease in bone mineral density (BMD) measured by dual X-ray absorption (DEXA) and of the sensitivity of quantitative ultrasonography (QUS) in patients with ulcerative colitis treated without and with glucocorticoids. Methods: BMD was measured by DEXA at the lumbar spine (LS), left femoral neck (FN), and the distal 1/3 of radius (1/3R) using a Hologic QDR 4500C in 71 patients with UC and 188 healthy controls (HC). Quantitative ultrasonography (QUS) was performed by Lunar Achilles. The disease duration was 8.1 6.6 years (mean SD) and we found the frequency of lifetime steroid usage 75%. Results: For comparison of DEXA and QUS results of UC patients and healthy controls see Table below. Steroid-never treated UC patients did not show statistically significant differences in BMD at any site compared to HC. The 56 steroid-ever users had significantly lower z-scores at LS (0.89 1.26 vs. 0.12 1.05) and at FN (0.47 1.02 vs. 0.23 1.04) compared to that of steroid-ever users. There were no significant differences in 1/3R z-scores and in QUS parameters between steroid-ever vs. steroid-never users. There was no correlation between disease duration and z-scores of any site. Conclusions: Steroid-ever treated UC patients have lower BMD values compared to that of steroid-never treated patients. The lack of association between disease duration and BMD suggests that low bone mass might be already present at the onset of UC. Radial BMD measurements and cal- caneal QUS do not have enough sensitivity to detect steroid-induced low bone mass of UC patients. Ulcerative colitis Healthy controls Statistics Lumbar spine z-score 0.64 1.26 0.18 1.19 p 0.01 Femoral neck z-score 0.29 1.04 0.10 1.05 p 0.05 Radial z-score 0.58 1.24 0.35 1.00 NS Calcaneal SOS (m/sec) 1560.8 43.8 1567.3 42.5 NS Calcaneal BUA (dB/MHz) 112.1 12.8 109.6 17.3 NS Calcaneal stiffness 98.6 15.1 89.0 19.1 NS Calcaneal stiffness z-score 0.29 1.41 0.35 1.83 NS 988 Treatment of mildly to moderately active ulcerative colitis with a tryptase inhibitor (APC 2059): an open-label pilot study William J Tremaine 1 *, Aaron Brzezinski 2 , Jeffry A Katz 3 , Douglas C Wolf 4 , Joyce Mordenti 5 and Matthias C Kurth 5 . 1 Gastroenterology, Cleveland Clinic, Cleveland, OH, United States; 2 Gastroenterology, Mayo Clinic, Rochester, MN, United States; 3 Gastroenterology, University Hospitals of Cleveland, Cleveland, OH, United States; 4 Atlanta Gastroenterology Associates, Atlanta, GA, United States; and 5 Axys Pharmaceuticals, Inc, S. San Francisco, CA, United States. S311 AJG – September, Suppl., 2001 Abstracts

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985

Dietary bioactive peptides in maintaining intestinal integrity andfunctionPaul D. Thomas1, Trent W. Nichols1* and Angie R. Angstadt1. 1CNDD,Hanover, PA, United States.

Purpose: Dietary peptides are known to have biological importance bey-ound their nutritive value as protein, influencing structural, hormonal,immune, and neurological functions. Alterations in the state of phosphor-ylation of tight junctions (TJ) protein occludin in the colonic epithelia ofCrohn’s and UC patients have been demonstrated. Protein balance studiesperformed in patients with IBD indicated better nitrogen balance withpeptide-based diets than with whole food diets, which are in turn better thanamino acid-based diets; however, no studied have examined the use ofsupplemental peptides in improving gut epithelial permeability and asso-ciated symptom relief.Methods: Twenty patients assessed to have gut hyperpermeability by aurine test utilizing lactulose to mannitol ratio were given either 3g per dayof a peptide supplement from hydrolyzed fish protein or a control for 6weeks, followed by a second permeability test and symptoms assessmentscoring.Results: Preliminary results with the first 13 patients show improvement tonormal permeability in 6 of 7 patients on peptide supplement, and nochange or a progression to worse in 4 of 6 patients on control. Symptomsimproved in 4 of 7 peptide patients and 5 of 6 control patients remained thesame of worsened.Conclusions: These particular peptides appear to act as trophic factors thathelp heal the lining of the gut and may energize TJ via increased proteinsynthesis. Sponsored by Proper Nutrition, Inc.

986

Infliximab (Remicade®) in the management of ulcerative colitisPeter Tomaiolo, MD*. Saint Vincent Hospital, Worcester, MA, UnitedStates.

Purpose: Case Study.Methods: Infliximab, a chimeric monoclonal antibody that binds to andneutralizes tumor necrosis factor-alpha (TNF-a), is under investigation forthe management of ulcerative colitis (UC). Infliximab is currently approvedfor the treatment of active and fistulizing Crohn’s disease (CD), a conditionthat shares many similar pathologic and clinical features with UC. In bothconditions, TNF-a is believed to be a key mediator in the inflammatoryresponse. Thus, infliximab’s proven efficacy in CD makes it a promisingtherapy for UC. In this report, we describe a UC patient who demonstrateda remarkable response to infliximab. One day after receiving a single 5mg/kg dose of infliximab the patient had complete resolution of his symp-toms.Results: The patient is an 85-year-old male with a history of UC as wellas a past medical history of colon cancer and hypothyroidism. His diseasehad been well controlled on low doses of prednisone and mesalamine untilapproximately 1 month prior to the hospital admission described in thisreport, when he was admitted for a UC exacerbation. This admission wasthe result of persistent and worsening abdominal pain and bloody diarrheafollowing the previous admission. On examination the patient was found tohave an elevated temperature of 101.5°F. His abdomen was diffusely tenderand mildly distended with no bowel sounds. A KUB revealed dilated loopsof bowel and a CAT scan revealed inflammatory changes from the splenicflexure to the rectum with no signs of peritonitis. His laboratory studieswere significant for a hemoglobin of 14 g/dL, hematocrit of 41%, and whiteblood cell count of 12,000 mm3. The blood and stool cultures werenegative. The patient’s physical exam and laboratory findings were con-sistent with the previous admission colonoscopy findings of pancolitis. Aconsultation from the surgical team was obtained for possible bowelobstruction/megacolon and the patient was treated with intravenous sol-umedrol, antibiotics and bowel rest. The patient was not considered a goodcandidate for treatment with cyclosporine. Despite these standard treat-

ments, the patient’s symptoms worsened and surgery was feared to beinevitable. As a last resort, the patient agreed to treatment with infliximab.One day after receiving a single 5 mg/kg infliximab infusion, the patientreported complete resolution of his symptoms and was able to tolerate oralintake of food. The patient was discharged 4 days later and has continuedto be assymptomatic to this date.Conclusions: Infliximab is a promising treatment for UC. This patient’sremarkable response to the drug is a case in point. Despite his age and poorprognosis at admission, the patient did remarkably well after a single doseof infliximab.

987

Bone mineral density measured by dual X-ray absorptiometry andquantitative ultrasonography in patients with ulcerative colitisMiklos Toth1, Pal Miheller1, Tamas Zagoni1, Andrea Nemetz1, LaszloPronai1, Laszlo Herszenyi1, Mark Juhasz1, Agota Kovacs2 and ZsoltTulassay1*. 12nd Department of Internal Medicine, Faculty ofMedicine, Semmelweis University, Budapest, Hungary; and 2Departmentof Gastroenterology, Erzsebet Hospital, Budapest, Hungary.

Purpose: To investigate the degree of decrease in bone mineral density(BMD) measured by dual X-ray absorption (DEXA) and of the sensitivityof quantitative ultrasonography (QUS) in patients with ulcerative colitistreated without and with glucocorticoids.Methods: BMD was measured by DEXA at the lumbar spine (LS), leftfemoral neck (FN), and the distal 1/3 of radius (1/3R) using a Hologic QDR4500C in 71 patients with UC and 188 healthy controls (HC). Quantitativeultrasonography (QUS) was performed by Lunar Achilles�. The diseaseduration was 8.1 � 6.6 years (mean � SD) and we found the frequency oflifetime steroid usage 75%.Results: For comparison of DEXA and QUS results of UC patients andhealthy controls see Table below. Steroid-never treated UC patients did notshow statistically significant differences in BMD at any site compared toHC. The 56 steroid-ever users had significantly lower z-scores at LS(�0.89 � 1.26 vs. �0.12 � 1.05) and at FN (�0.47 � 1.02 vs. �0.23 �1.04) compared to that of steroid-ever users. There were no significantdifferences in 1/3R z-scores and in QUS parameters between steroid-evervs. steroid-never users. There was no correlation between disease durationand z-scores of any site.Conclusions: Steroid-ever treated UC patients have lower BMD valuescompared to that of steroid-never treated patients. The lack of associationbetween disease duration and BMD suggests that low bone mass might bealready present at the onset of UC. Radial BMD measurements and cal-caneal QUS do not have enough sensitivity to detect steroid-induced lowbone mass of UC patients.

Ulcerative colitis Healthy controls Statistics

Lumbar spine z-score �0.64 � 1.26 �0.18 � 1.19 p � 0.01Femoral neck z-score �0.29 � 1.04 �0.10 � 1.05 p � 0.05Radial z-score �0.58 � 1.24 �0.35 � 1.00 NSCalcaneal SOS (m/sec) 1560.8 � 43.8 1567.3 � 42.5 NSCalcaneal BUA (dB/MHz) 112.1 � 12.8 109.6 � 17.3 NSCalcaneal stiffness 98.6 � 15.1 89.0 � 19.1 NSCalcaneal stiffness z-score �0.29 � 1.41 �0.35 � 1.83 NS

988

Treatment of mildly to moderately active ulcerative colitis with atryptase inhibitor (APC 2059): an open-label pilot studyWilliam J Tremaine1*, Aaron Brzezinski2, Jeffry A Katz3, Douglas CWolf4, Joyce Mordenti5 and Matthias C Kurth5. 1Gastroenterology,Cleveland Clinic, Cleveland, OH, United States; 2Gastroenterology,Mayo Clinic, Rochester, MN, United States; 3Gastroenterology,University Hospitals of Cleveland, Cleveland, OH, United States;4Atlanta Gastroenterology Associates, Atlanta, GA, United States; and5Axys Pharmaceuticals, Inc, S. San Francisco, CA, United States.

S311AJG – September, Suppl., 2001 Abstracts