Ulcerative Colitis: Altorjay I

Papp M, Altorjay I, Lakatos PL. · Debreceni Egyetem, Orvos- és Egészségtudományi Centrum Belgyógyászati Intézet, Gasztroenterológiai Tanszék, Debrecen. · Orv Hetil. · Pubmed #17478404 No free full text.

Abstract: The panel of serologic markers for inflammatory bowel diseases (IBDs) is rapidly expanding. Although anti- Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophil cytoplasmic antibodies (atypical P-ANCA) remain the most widely investigated, an increasing amount of experimental data is available on newly discovered antibodies directed against various microbial antigens. Such antibodies include anti-OmpC (outer membrane porin C), anti- Pseudomonas fluorescens (anti-I2) and antiglycan antibodies (anti-laminaribioside carbohydrate antibody [ALCA]), anti-chitobioside carbohydrate antibody [ACCA]), anti-mannobioside carbohydrate antibody [AMCA]) and anti-CBir1; this latter is the first bacterial antigen to induce colitis in animal models of IBD and also leads to a pathological immune response in IBD patients (anti-flagellin antibody). The role of assessment of various antibodies in the current diagnostic algorithm of IBD is rather questionable due to their limited sensitivity. In contrast, the association of serologic markers with disease behavior and phenotype is getting more into the focus of interest. An increasing number of observations confirm that patients with Crohn's disease expressing multiple serologic markers at high titers are more likely to have complicated small bowel disease (e.g. stricture and/or perforation) and are at higher risk for surgery than those without, or with low titer of antibodies. Creating homogenous disease sub-groups based on serologic response may help develop more standardized therapeutic approaches and may help in a better understanding of the pathomechanism of IBD. Further prospective clinical studies are needed to establish the clinical role of serologic tests in IBD.

Udvardy M, Altorjay I, Palatka K. · Debreceni Egyetem, Orvos- és Egészségtudományi Centrum, II. Belgyógyászati Klinika. · Orv Hetil. · Pubmed #11373889 No free full text.

Abstract: Anaemia, thrombocytosis are common secondary changes in inflammatory bowel disease (IBD), reflecting the clinical severity of the IBD cases, too. On the other hand, increased platelet function, fibrinolytic abnormalities, hypercoagulation of IBD patients predispose to thromboembolic events, and they may as well contribute to the local microcirculatory alterations leading to IBD itself. Reduced FXIII levels have been observed in IBD, which seems to be correlated with mucosal repair and might have therapeutic importance, too. Genetic thrombophilia received much attention recently, however, much less is known how frequent they are in IBD, what their clinical significance is, do they modify the clinical course itself. A short, concise review about links between haematology and IBD is given.

Papp M, Altorjay I, Lakos G, Tumpek J, Sipka S, Dinya T, Palatka K, Veres G, Udvardy M, Lakatos PL. · 2nd Department of Medicine, University of Debrecen, Hungary. · Clin Vaccine Immunol. · Pubmed #19193830 No free full text.

Abstract: No clear guidelines for indirect immunofluorescence (IIF) detection and interpretation of antineutrophil cytoplasmic antibodies (ANCA) have been proposed for inflammatory bowel diseases (IBD). We evaluated the reliability of the combined use of ethanol- and formalin-fixed neutrophil substrates to identify atypical perinuclear ANCA (P-ANCA) by IIF under routine laboratory circumstances. A total of 204 IBD patients were assessed with four different fluorescent substrates in two distinct laboratories. Antibodies against myeloperoxidase, proteinase-3, and other specific granule proteins (elastase, lactoferrin, cathepsin G, lysozyme, and bactericidal permeability-increasing protein) were measured by an enzyme-linked immunosorbent assay. The combined application of ethanol- and formalin-fixed slides to detect atypical P-ANCA resulted in a lack of agreement between assays (kappa, < or =0.39) in the interassay study and moderate agreement in the interobserver study (kappa, 0.42). After atypical and typical P-ANCA patterns were combined, the consensus improved greatly. A total of 26.9% of patients were P-ANCA positive by at least two tests (44.3% of ulcerative colitis [UC] and 13.1% of Crohn's disease [CD] patients; P < 0.0001), while overall ANCA positivity was 22.5% to 34.8%. The combined application of ethanol-fixed and formaldehyde-fixed neutrophil substrates did not facilitate differentiation between P-ANCA and atypical P-ANCA, and the results were not consistent when substrates from different sources were used. Combining all P-ANCA ensures the highest sensitivity and specificity in differentiating UC from CD.

Lakatos PL, Altorjay I, Szamosi T, Palatka K, Vitalis Z, Tumpek J, Sipka S, Udvardy M, Dinya T, Lakatos L, Kovacs A, Molnar T, Tulassay Z, Miheller P, Barta Z, Stocker W, Papp J, Veres G, Papp M, Anonymous00019. · 1st Department of Medicine, Semmelweis University, Budapest, Hungary. · Inflamm Bowel Dis. · Pubmed #18972554 No free full text.

Abstract: BACKGROUND: Pancreatic autoantibodies (PAB) and goblet cell autoantibodies (GAB) are specific for Crohn's disease (CD) and ulcerative colitis (UC), but the sensitivity alone is low. Conventional antibodies and carbohydrates (glycans) are associated with disease phenotype and may be of diagnostic importance in inflammatory bowel disease (IBD). Our aim was to determine the accuracy of PAB and GAB autoantibodies as well as to study relevant phenotype-serotype associations. METHODS: A Hungarian study cohort of 1092 subjects, including 689 well-characterized, unrelated IBD patients (CD: 579, m/f ratio: 274/305, duration: 7.9 +/- 11.2 years; UC: 110, m/f ratio: 53/57, duration: 8.9 +/- 9.8 years), 139 celiac patients, 100 healthy, and 64 non-IBD gastrointestinal controls were investigated. Sera were assayed for PAB-GAB IgA/IgG, anti-Omp, anti-Saccharomyces cerevisiae antibodies (ASCA), and anti-glycans. TLR4 and NOD2/CARD15 was tested by polymerase chain reaction / restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined. RESULTS: The prevalence of PAB was significantly more frequent in CD (41.1%) versus UC (22.7%), celiac (22.3%), and controls (8% and 4.6%, P < 0.01 for each), while GAB detection was poor in all groups except UC (15.4%). In CD the combination of PAB and/or anti-glycans/ASCA increased the sensitivity to 72% and 59%, respectively, for isolated colonic disease. PAB was associated to gylcans (odds ratio [OR] 1.74,P = 0.002), ASCA IgG/IgA (OR 1.75, P = 0.002), Omp (OR 1.86, P = 0.001) as well as perforating, perianal disease, arthritis, ocular, and cutaneous manifestations (P = 0.002-0.032). In contrast, PAB and GAB antibodies were not associated with NOD2/CARD15 or TLR4, response to medical therapy, or need for surgery. No associations were found in UC. CONCLUSIONS: PAB autoantibodies in combination with ASCA or anti-glycan antibodies increase the sensitivity for detecting CD, especially isolated colonic CD. Antibody response to PAB was associated with complicated disease phenotype and extraintestinal manifestations in this Eastern European IBD cohort.

Szamosi T, Lakatos PL, Anonymous00057, Szilvasi A, Lakatos L, Kovacs A, Molnar T, Altorjay I, Papp M, Szabo O, Satori A, Tulassay Z, Miheller P, Horvath HC, Papp J, Tordai A, Andrikovics H. · 1st Department of Medicine, Semmelweis University, Koranyi st. 2/A, 1083, Budapest, Hungary. · Dig Dis Sci. · Pubmed #18716880 No free full text.

Abstract: PURPOSE: In previous studies the NFKBIA 3'UTR (untranslated region) AA genotype was associated with Crohn's disease (CD), while the NFKB1-94ins/delATTG mutation increased the risk for ulcerative colitis (UC). The aim of our study was to investigate these two polymorphisms and patients' response to medical therapy and/or disease phenotype in Hungarian inflammatory bowel disease (IBD) patients. METHODS: NFKBIA 3'UTR- and NFKB1-94ins/delATTG polymorphisms were investigated in 415 unrelated IBD patients (CD: 266 patients, mean age 35.2 +/- 12.1 years, duration 8.7 +/- 7.5 years; UC patients: 149, mean age 44.4 +/- 15.4 years, duration 10.7 +/- 8.9 years) and 149 controls by PCR-restriction fragment length polymorphism (RFLP) analysis. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: The NFKBIA 3'UTR and NFKB1-94ins/delATTG genotypes and allele frequencies were not significantly different among IBD and controls. In patients with UC, the 3'UTR GG genotype was associated with extensive colitis (55.3 vs. 29.4%, odds ratio 2.97, 95% confidence interval 1.45-6.08). The presence of variant alleles did not predict response to steroids, infliximab, or need for surgery. CONCLUSIONS: The NFKBIA 3'UTR GG genotype was associated with an increased risk for extensive colitis in Hungarian patients. In contrast, variant alleles did not predict response to medical therapy or need for surgery.

Lakatos PL, Szamosi T, Szilvasi A, Molnar E, Lakatos L, Kovacs A, Molnar T, Altorjay I, Papp M, Tulassay Z, Miheller P, Papp J, Tordai A, Andrikovics H, Anonymous00044. · 1st Department of Medicine, Semmelweis University, Budapest, Hungary. · Dig Liver Dis. · Pubmed #18499543 No free full text.

Abstract: BACKGROUND: North American and European genome-wide association scans have identified ATG16L1 and IL23R as novel inflammatory bowel disease (IBD) susceptibility genes and subsequent reports confirmed these findings in large independent populations. The aims of this study were to investigate the association and examine genotype-phenotype relationships in a Hungarian IBD cohort. METHODS: 415 unrelated IBD patients (CD: 266, age: 35.2+/-12.1 years, duration: 8.7+/-7.5 years and UC: 149, age: 44.4+/-15.4 years, duration: 10.7+/-8.9 years) and 149 healthy subjects were investigated. IL23R Arg381Gln (R381Q, rs11209026) and ATG16L1 Thr300Ala (T300A, rs2241880) polymorphisms were tested using LightCycler allele discrimination method. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: The association between IL23R rs11209026, ATG16L1 rs2241880 and CD was confirmed (OR(IL23R381Q): 0.38, 95% CI: 0.16-0.87; OR(ATG16L1300AA): 1.86, 95% CI: 1.04-3.40). No difference was found between patients with UC and either controls or CD. In CD, IL23R 381Gln heterozygosity was associated with inflammatory disease (70% vs. 34%, p=0.037), while disease restricted to the colon was more prevalent in patients with the ATG16L1 300Ala/Ala homozygosity (33.3% vs. 21.1%, p=0.036). In addition, carriage of the variant alleles did not predict response to steroids, infliximab or need for surgery. CONCLUSIONS: We confirmed that ATG16L1 and IL23R are susceptibility loci for CD in Hungarian CD patients. Further studies are needed to confirm the reported phenotype-genotype associations found in this study.

Papp M, Altorjay I, Dotan N, Palatka K, Foldi I, Tumpek J, Sipka S, Udvardy M, Dinya T, Lakatos L, Kovacs A, Molnar T, Tulassay Z, Miheller P, Norman GL, Szamosi T, Papp J, Anonymous00071, Lakatos PL. · 2nd Department of Medicine, University of Debrecen, Debrecen, Hungary. · Am J Gastroenterol. · Pubmed #18047543 No free full text.

Abstract: BACKGROUND: Antibodies to Saccharomyces cerevisiae (S. cerevisiae) (ASCA) and porin protein-C of Escherichia coli (anti-OmpC) are associated with disease phenotype and may be of diagnostic importance in inflammatory bowel diseases (IBD). Our aim was to determine whether a panel of new antibodies against bacterial proteins and carbohydrates could help differentiate among the various forms of IBD, and whether they were associated with particular clinical manifestations in a Hungarian cohort of IBD patients. METHODS: Six hundred fifty-two well-characterized, unrelated, consecutive IBD patients (CD [Crohn's disease] 557, men/women 262/295, duration 8.1 +/- 11.3 yr; ulcerative colitis [UC] 95, men/women 44/51, duration 8.9 +/- 9.8 yr) and 100 healthy and 48 non-IBD gastrointestinal (GI) controls were investigated. Sera were assayed for anti-OmpC and antibodies against a mannan epitope of S. cerevisiae (gASCA), laminaribioside (ALCA), chitobioside (ACCA), and mannobioside (AMCA). TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined by reviewing the patients' medical charts. RESULTS: Sixty-six percent of the CD patients had at least one of the investigated antibodies. Among glycan antibodies, gASCA or the combination of gASCA and atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) was most accurate for differentiating between CD and UC. ASCA and gASCA assays performed similarly. Increasing amount and level of antibody responses toward gASCA, ALCA, ACCA, AMCA, and OmpC were associated with more complicated disease behavior (P < 0.0001) and need for surgery in CD (P= 0.023). A serological dosage effect was also observed. gASCA and AMCA antibodies were associated with NOD2/CARD15, in addition to a gene-dosage effect. No serotype-phenotype associations were found in UC. CONCLUSIONS: Antibody response to this new panel of serological markers was associated with complicated disease phenotype, NOD2/CARD15 genotype, and a need for surgery in this eastern European IBD cohort.

Fischer S, Lakatos PL, Anonymous00281, Lakatos L, Kovacs A, Molnar T, Altorjay I, Papp M, Szilvasi A, Tulassay Z, Osztovits J, Papp J, Demeter P, Schwab R, Tordai A, Andrikovics H. · 1st Department of Medicine, Semmelweis University, Budapest, Hungary. · Scand J Gastroenterol. · Pubmed #17505995 No free full text.

Abstract: OBJECTIVE: MDR1 (ABCB1), a member of the ATP-binding cassette (ABC) transporters, is an attractive candidate gene for the pathogenesis of inflammatory bowel diseases (IBD) and perhaps for response to therapy. Since limited data are available on MDR1 and ABCG2 polymorphisms in East European IBD patients, the aim of this study was to investigate ABCG2 and MDR1 variants and responses to medical therapy and/or disease phenotype in Hungarian patients. MATERIAL AND METHODS: A total of 414 unrelated IBD patients (Crohn's disease (CD): 265, age: 35.2+/-12.1 years, duration: 8.7+/-7.6 years and ulcerative colitis (UC): 149, age: 44.4+/-15.4 years, duration: 10.7+/-8.9 years) and 149 healthy subjects were investigated. ABCG2 G34A, C421A and MDR1 C3435T, G2677T/A single nucleotide polymorphisms (SNPs) were detected using real-time polymerase chain reaction (PCR). Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: The frequency of the ABCG2 and MDR1 SNPs was not significantly different among IBD, CD, UC patients and controls. There was no difference in risk for steroid resistance in CD patients carrying variant ABCG2 (19.6% versus non-carriers 18.4%, p=NS) or MDR1 3435T (CC: 22.2% versus CT/TT: 17.6%) alleles. In addition, carriage of the variant allele was not associated with disease phenotype, presence of extra-intestinal manifestations, smoking, response to infliximab therapy or the need for surgery. In UC, the carriage of variant ABCG2 alleles seemed to be preventive for arthritis (15.5% versus 31.7%, OR: 0.39, 95% CI: 0.16-0.98). CONCLUSIONS: MDR1 and ABCG2 SNPs were not associated with disease susceptibility or disease phenotype in Hungarian patients, and variant alleles did not predict the response to medical therapy or the need for surgery. Further studies are needed to clarify the association between the presence of ABCG2 variants and arthritis in UC.

Papp M, Altorjay I, Norman GL, Shums Z, Palatka K, Vitalis Z, Foldi I, Lakos G, Tumpek J, Udvardy ML, Harsfalvi J, Fischer S, Lakatos L, Kovacs A, Bene L, Molnar T, Tulassay Z, Miheller P, Veres G, Papp J, Anonymous00415, Lakatos PL. · 2nd Department of Medicine, University of Debrecen, Debrecen, Hungary. · Inflamm Bowel Dis. · Pubmed #17417801 links to  free full text

Abstract: BACKGROUND: Antibodies directed against Saccharomyces cerevisiae (ASCA), perinuclear components of neutrophils (pANCA), and porin protein C of Escherichia coli (anti-OmpC) are reported to be associated with disease phenotype and may be of diagnostic importance in inflammatory bowel disease (IBD). Since limited data are available from Eastern Europe, we assessed the above antibodies in Hungarian IBD patients. METHODS: In all, 653 well-characterized, unrelated consecutive IBD patients (Crohn's disease [CD]: 558, m/f: 263/295, duration: 8.1 +/- 10.7 years; ulcerative colitis [UC]: 95, m/f: 44/51, duration: 8.9 +/- 9.8 years) and 100 healthy subjects were investigated. Sera were assayed for anti-Omp and ASCA by enzyme-linked immunosorbent assay (ELISA) and ANCA by indirect immunofluorescence assay (IIF). TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: Anti-Omp, ASCA, and atypical pANCA antibodies were present in 31.2%, 59.3%, and 13.8% of CD, 24.2%, 13.7%, and 48.5% of UC patients, and in 20%, 16%, and 5.6% of controls, respectively. ASCA and anti-Omp positivity were associated with increased risk for CD (odds ratio [OR](ASCA) = 7.65, 95% confidence interval [CI]: 4.37-13.4; OR(Omp) = 1.81, 95% CI: 1.08-3.05). In a logistic regression analysis, anti-Omp and ASCA were independently associated with ileal and noninflammatory disease, but not with a risk for surgery or response to steroids or infliximab. A serology dosage effect was also observed. ASCA and anti-Omp antibodies were associated with NOD2/CARD15, in addition to a gene dosage effect. No associations were found in UC. CONCLUSIONS: Serological markers were useful in the differentiation between CD and UC in an Eastern European IBD cohort. Reactivity to microbial components was associated with disease phenotype and NOD2/CARD15 genotype, further supporting the role of altered microbial sensing in the pathogenesis of CD.

Papp M, Lakatos PL, Anonymous00217, Palatka K, Földi I, Udvardy M, Hársfalvi J, Tornai I, Vitális Z, Dinya T, Kovács A, Molnár T, Demeter P, Papp J, Lakatos L, Altorjay I. · Debreceni Egyetem, Orvos- es Egészségtudományi Centrum, Belgyógyászati Intézet, Gasztroenterológiai Tanszék, Debrecen. · Orv Hetil. · Pubmed #17087019 No free full text.

Abstract: BACKGROUND: Since functional differences were found among three major haptoglobin phenotypes, haptoglobin polymorphism was reported to be associated with the risk and clinical course of different inflammatory diseases. The aim of the study was to investigate the Hp polymorphism distribution in Hungarian Crohn's disease patients. METHODS: 511 Hungarian IBD patients were investigated (Crohn's disease patients: 468, m/f ratio: 233/235, duration 8.2 +/- 6.7 ys, and ulcerative colitis patients: 43, m/f: 22/21, duration: 9.5 +/- 10.6 ys) and 384 healthy subjects served as controls. Hp phenotypes were determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis of sera followed by immunoblotting. Clinical data were come by the questionnaires prepared by the physicians. RESULTS: The frequency of haptoglobin-1 allele was significantly higher in Crohn's disease (0.395) compared to the controls (0.345; OR: 1.24, 95%CI: 1.02-1.52, p = 0.03), but the phenotype distribution showed no such differences. Haptoglobin phenotype was associated to disease behavior in Crohn's disease (B1 and B2, in haptoglobin 1-1 and 2-2: 36.6%-34.3% and 32.4%-32.5% vs. in 2-1: 44.9% and 20.3%; ORB1Hp2-1 vs. others: 2.06, 95%CI: 1.29-3.28). Furthermore, an increased frequency of primary sclerosing cholangitis was observed in haptoglobin 2-2, compared to the 1-1 (6.5% vs. 0.0%, p = 0.039). No associations were found in ulcerative colitis. CONCLUSIONS: haptoglobin-1 allele was associated with Crohn's disease, whereas the phenotypes with the disease behavior and frequency of primary sclerosing cholangitis, exhibiting a disease-modifying effect.

Lakatos PL, Fischer S, Claes K, Kovacs A, Molnar T, Altorjay I, Demeter P, Tulassay Z, Palatka K, Papp M, Rutgeerts P, Szalay F, Papp J, Vermeire S, Lakatos L, Anonymous00243. · First Department of Medicine, Semmelweis University, Budapest, Hungary. · Inflamm Bowel Dis. · Pubmed #16670524 links to  free full text

Abstract: BACKGROUND: Recent data suggest that haplotypic variants of the DLG5 gene on 10q23 are associated with susceptibility to inflammatory bowel disease (IBD) in Germany. In view of the geographical differences in frequency of genetic markers and the absence of data in Central European patients, our aim was to determine the DLG5 R30Q variant in Hungarian IBD patients. MATERIALS AND METHODS: We investigated 773 unrelated IBD patients (age 38.1 +/- 10.3 years; duration, 8.8 +/- 7.5 years; Crohn's disease [CD]: 639; male/female, 309/330; duration, 8.4 +/- 7.1 years; ulcerative colitis [UC]: 134; male/female, 63/71; duration, 10.6 +/- 8.9 years) and 150 healthy subjects. DLG5 R30Q and TLR4 D299G variants were tested by polymerase chain reaction/restriction fragment length polymorphism. DNA was screened for NOD2/CARD15 mutations by denaturing high-performance liquid chromatography. Detailed clinical phenotype was determined by reviewing the medical charts. RESULTS: The frequency of the R30Q variant allele was not significantly different in IBD (22.0%), CD (20.8%), and UC (27.6%) patients compared with healthy control subjects (28.0%). In CD, the 113A variant allele was associated with steroid resistance (16.3% vs noncarriers, 7.6%; odds ratio [OR], 2.4; 95% CI 1.3-4.5; P = 0.013). In a logistic regression model carriage of DLG5 R30Q, perianal involvement and frequent relapses were independently associated with steroid resistance. No phenotype-genotype associations were found in UC patients, although a trend toward more extensive disease was observed in carriers of the variant allele (OR = 2.1; 95% CI 0.95-4.4; P = 0.07). CONCLUSIONS: The present data strongly contrast previous data from Germany. DLG5 113A is not associated with disease susceptibility, but there was a tendency for this allele to confer resistance to steroids. Further studies are required to evaluate the significance of DLG5 in other populations from geographically diverse regions.

Palatka K, Serfozo Z, Veréb Z, Bátori R, Lontay B, Hargitay Z, Nemes Z, Udvardy M, Erdodi F, Altorjay I. · 2nd Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, Nagyerdei körút 98, Debrecen H-4001, Hungary. · World J Gastroenterol. · Pubmed #16586542 links to  free full text

Abstract: AIM: To study the expression of endothelial and inducible nitric oxide synthases (eNOS and iNOS) and their role in inflammatory bowel disease (IBD). METHODS: We examined the effect of sera obtained from patients with active Crohn's disease (CD) and ulcerative colitis (UC) on the function and viability of human umbilical vein endothelial cells (HUVEC). HUVECs were cultured for 0-48 h in the presence of a medium containing pooled serum of healthy controls, or serum from patients with active CD or UC. Expression of eNOS and iNOS was visualized by immunofluorescence, and quantified by the densitometry of Western blots. Proliferation activity was assessed by computerized image analyses of Ki-67 immunoreactive cells, and also tested in the presence of the NOS inhibitor, 10(-4) mol/L L-NAME. Apoptosis and necrosis was examined by the annexin-V-biotin method and by propidium iodide staining, respectively. RESULTS: In HUVEC immediately after exposure to UC, serum eNOS was markedly induced, reaching a peak at 12 h. In contrast, a decrease in eNOS was observed after incubation with CD sera and the eNOS level was minimal at 20 h compared to control (18%+/-16% vs 23%+/-15% P<0.01). UC or CD serum caused a significant increase in iNOS compared to control (UC: 300%+/-21%; CD: 275%+/-27% vs 108%+/-14%, P<0.01). Apoptosis/necrosis characteristics did not differ significantly in either experiment. Increased proliferation activity was detected in the presence of CD serum or after treatment with L-NAME. Cultures showed tube-like formations after 24 h treatment with CD serum. CONCLUSION: IBD sera evoked changes in the ratio of eNOS/iNOS, whereas did not influence the viability of HUVEC. These involved down-regulation of eNOS and up-regulation of iNOS simultaneously, leading to increased proliferation activity and possibly a reduced anti-inflammatory protection of endothelial cells.

Palatka K, Serfozo Z, Veréb Z, Hargitay Z, Lontay B, Erdodi F, Bánfalvi G, Nemes Z, Udvardy M, Altorjay I. · 2nd Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, Hungary. · Scand J Gastroenterol. · Pubmed #16036527 No free full text.

Abstract: OBJECTIVE: The role of nitric oxide (NO) in the pathophysiology of inflammatory bowel disease (IBD) is controversial. The aim of this study was to investigate the expression and localization of nitric oxide synthase isoforms (iNOS, eNOS) in IBD colonic mucosa. MATERIAL AND METHODS: Forty-four patients with IBD (24 ulcerative colitis (UC), 20 Crohn's disease (CD) and 16 controls) were investigated by colonoscopy. iNOS and eNOS in tissue sections was demonstrated by histochemistry (NADPH-diaphorase reaction) and immunohistochemistry. Cell type analysis and quantitative assessment of the iNOS immunoreactive (IR) cells and densitometry of iNOS in immunoblots were also performed. RESULTS: iNOS-IR cells were significantly numerous in inflamed mucosa of UC (64+/-4 cells/mm2) than in CD (4+/-2 cells/mm2). iNOS-IR/CD15-IR cells showed significant elevation in inflamed (i) versus uninflamed (u) UC mucosa (UCu 8+/-3%, UCi 85+/-10%) In CD, the percentage of iNOS-IR/CD68-IR cells was lower in inflamed sites (CDu 23+/-8%, CDi 4+/-3%). Immunoblot of biopsies revealed significant elevation of iNOS in active UC compared with uninflamed sites, whereas in CD no significant changes were detected. Differences were observed in eNOS and endothelial marker CD31 immunoreactivity. In patients with UC and in controls the ratios of eNOS/CD31-IR vessels were 82.3% and 92.0% respectively, whereas in CD the ratio was 8.3% with a concomitantly significant increase of CD31-IR vessels. The distribution and morphological characteristics of the NOS-IR inflammatory cells and endothelia were similar to those showing NADPH-diaphorase reactivity. CONCLUSIONS: Differences observed in the expression and distribution of NOS isoforms in immune and endothelial cells may contribute to better understanding of the structural and physiological changes in UC and CD.