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Luminal nitric oxide and epithelial expression of inducible and endothelial nitric oxide synthase in collagenous and lymphocytic colitis
Dept. of Medicine, Div. of Gastroenterol./Dept. of P., Örebro University Hospital, Örebro, Sweden and Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Dept. of Medicine, Div. of Gastroenterol./Dept. of P., Örebro University Hospital, Örebro, Sweden and Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Dept. of Medicine, Div. of Gastroenterol./Dept. of P., Örebro University Hospital, Örebro, Sweden and Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Dept. of Medicine, Div. of Gastroenterol./Dept. of P., Örebro University Hospital, Örebro, Sweden and Dept. of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden and Dept. of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
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2003 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 38, no 1, 66-72 p.Article in journal (Refereed) Published
Abstract [en]

Background: Colonic nitric oxide (NO) production in collagenous colitis (CC) has been studied in a small number of patients and found increased. The cellular source of NO is believed to be the colonic epithelial cells. The aim of this study was to investigate colonic NO levels in patients with CC and lymphocytic colitis (LC), to compare with the histopathological status and with the clinical activity, and to assess the epithelial expression of inducible and endothelial nitric oxide synthase (iNOS and eNOS).

Methods: We included 19 patients with CC, 8 patients with LC and 15 controls. During colonoscopy, luminal gas was sampled and NO levels were measured using the chemiluminescence technique. Mucosal biopsies were obtained for routine histopathologic examination and immunohistochemical studies of iNOS and eNOS. Clinical activity, as measured by the mean frequency of daily bowel movements during the week prior to colonoscopy, was assessed.

Results: Luminal NO levels, median (25-75 percentiles), in the patients with CC and LC were greatly increased compared to the controls, 1673 (145-8143) parts per billion (ppb) and 1838 (1065-2694) ppb versus 28 (20-46) ppb (P < 0.005, both). A positive association was seen between NO levels and histopathological status as well as clinical activity. Strong expression of iNOS was seen in the surface epithelium in 5 of 6 patients with CC and in 2 of 5 patients with LC.

Conclusions: The fact that luminal NO levels are related to histopathological status and correlate with clinical activity indicates that NO is involved in the pathophysiology of CC and LC. The epithelial cells are the most likely source of luminal NO.

Place, publisher, year, edition, pages
2003. Vol. 38, no 1, 66-72 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-33377DOI: 10.1080/00365520310000465PubMedID: 12608467Local ID: 19392OAI: oai:DiVA.org:liu-33377DiVA: diva2:254200
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-10-26Bibliographically approved
In thesis
1. Microscopic colitis: studies of epidemiology, clinical features and nitric oxide
Open this publication in new window or tab >>Microscopic colitis: studies of epidemiology, clinical features and nitric oxide
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lymphocytic colitis (LC) and collagenous colitis (CC) arc newly recognised inflammatory bowel diseases belonging to the group of microscopic colitides (MC). They are characterised clinically by chronic non-bloody and watery diarrhoea, and a macroscopically normal or near normal colonic mucosa where diagnostic histopathological abnormalities are found.

The aims of this thesis were to study the epidemiology of LC and CC in Örebro, the clinical features and outcome of treatment in a large Swedish cohort of patients with LC and the familial occurrence of MC. Further objectives were to study luminal levels of colonic nitric oxide (NO), plasma concentrations of the metabolites nitrate/nitrite and the epithelial expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in patients with MC and correlate to clinical and histopathological status.

Whereas previously thought to be rare diseases, our epidemiological study in Örebro 1993- 1998 showed that the annual incidence of LC and CC is close to the figures generally reported in Sweden in Crohn's disease. The combined rates of LC and CC are nearly as high as the incidence of ulcerative colitis. Microscopic colitis was diagnosed in 10% of all patients referred for a colonoscopy due to non-bloody diarrhoea, and in almost 20% of those older than 70 years.

The clinical features and outcome of treatment in LC were studied retrospectively in 199 Swedish patients. Diarrhoea was the predominant symptom, followed by abdominal pain and weight loss. Forty percent had at least one associated autoimmune or inflammatory disease; the most common were thyroid disorder and coeliac disease. A single attack occurred in 63% with a median disease duration of six months. In 1 0% a drug induced disease was suspected. A sudden onset of disease was noted in 25% and a non-significant peak of disease onset was seen in December-Janumy. The sudden onset, the single attack of limited duration, and the possible seasonality of the disease's onset may indicate an infectious etiology in some cases.

Corticosteroids, prednisolone as well as budesonide, were the most effective therapy in our retrospective LC study and more than 80% of the patients improved short-term. However, the relapse risk was high after withdrawal of therapy. A response rate of 50-70% was noted for loperamide, cholestyramine, metronidazole and mesalazine.

A family history of bowel disease- ulcerative colitis, Crohn's disease, CC or coeliac diseasewas reported in 12% of the 199 LC patients, and ulcerative colitis or Crohn's disease alone in 7%. We also report a familial occurrence of MC in five families, with two affected members in each family. In two families the members had different types of MC whereas in three families they all had CC.

Increased plasma levels of nitrate/nitrite and greatly enhanced levels of colonic luminal NO were found in MC patients. The NO levels were associated to the histopathological status and correlated with the clinical activity, indicating that NO is involved in the pathophysiology of MC. Expression of eN OS in the epithelium was not increased in patients with MC. An increased expression of iNOS was seen apically in the surface epithelium in MC patients, and a correlation between the staining intensity of iNOS and luminal NO levels, pointing towards the epithelial cells being the cellular source of the NO production.

Place, publisher, year, edition, pages
Linköpin: Linköping Universitet, 2004. 37 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 830
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24731 (URN)6982 (Local ID)91-7373-800-X (ISBN)6982 (Archive number)6982 (OAI)
Public defence
2004-01-23, Wilandersalen, Universitetssjukhuset, Örebro, 09:00 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-26Bibliographically approved

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