dietary bioactive peptides in maintaining intestinal integrity and function
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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.
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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.
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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
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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