György Rumi

Protective effect of lactulose on dextran sulfate sodium-induced colonic inflammation in rats

Promising results have recently been obtained with pre- and probiotic therapy in ulcerative colitis (UC). The prebiotic potential of lactulose is well established, but it has not yet been investigated in experimental colitis models. The purpose of the study was to examine the effect of lactulose on an UC model induced by 3% dextran sulfate sodium (DSS) solution added to drinking water for 7 days in male Wistar rats. Lactulose (300–1000 mg/kg) or 5-aminosalicylic acid (5-ASA; 150 mg/kg) was administered orally twice daily for 6 days. Colonic ulceration area, colon length, body weight changes, diarrhea/bloody feces, colonic mucosal myeloperoxidase activity (MPO), thiobarbituric acid reactive substances (TBARS), and histology were examined. Treatment of animals with DSS for 7 days resulted in severe colonic lesions accompanied by diarrhea, bloody feces, a decrese in body weight, shortening of the colon length, and an increase in MPO activity as well as TBARS, compared to normal rats. Lactulose treatment ameliorated DSS-induced colitis in a dose-dependent manner, and at 1000 mg/kg all of the parameters examined, except TBARS, were shown to improve significantly as compared to controls. Daily administration of 5-ASA also significantly reduced the severity of colonic lesions following DSS treatment. These results demonstrated the protectiv effect of lactulose in this rat colitis model and suggested that the background of this lactulose effect may be due to alterations of colonic microflora.

Efficacy and safety of infliximab induction therapy in Crohn's Disease in Central Europe - A Hungarian nationwide observational study

BackgroundInfliximab (IFX) has proven to be an effective addition to the therapeutic arsenal for refractory, fistulizing, and steroid dependent Crohns disease (CD), with efficacy in the induction and maintenance of clinical remission of CD. Our objective in this study is to report the nationwide, multicenter experience with IFX induction therapy for CD in Hungary.MethodsDuring a 6-year-period, beginning in 2000, a total of 363 CD patients were treated with IFX as induction therapy (5 mg/kg IFX infusions given at week 0, 2 and 6) at eleven centers in Hungary in this observational study. Data analysis included patient demographics, important disease parameters and the outcome of IFX induction therapy.ResultsThree hundred and sixty three patients (183 women and 180 men) were treated with IFX since 2000. Mean age was 33.5 ± 11.2 years and the mean duration of disease was 6.7 ± 6.1 years. The population included 114 patients (31.4%) with therapy-refractory CD, 195 patients (53.7%) with fistulas, 16 patients (4.4%) with both therapy-refractory CD and fistulas, and 26 patients (7.2%) with steroid dependent CD. Overall response rate was 86.2% (313/363). A higher response rate was observed in patients with shorter disease duration (p = 0.05, OR:0.54, 95%CI:0.29-0.99) and concomitant immunosuppressant therapy (p = 0.05, OR: 2.03, 95%CI:0.165-0.596). Concomitant steroid treatment did not enhance the efficacy of IFX induction therapy. Adverse events included 34 allergic reactions (9.4%), 17 delayed type hypersensitivity (4.7%), 16 infections (4.4%), and 3 malignancies (0.8%).ConclusionIFX was safe and effective treatment in this cohort of Hungarian CD patients. Based on our experience co-administration of immunosuppressant therapy is suggested in patients receiving IFX induction therapy. However, concomitant steroid treatment did not enhanced the efficacy of IFX induction therapy.

Crohn's Disease Is Associated with Polymorphism of CARD15/NOD2 Gene in a Hungarian Population

Abstract: Crohns disease (CD) is commonly classified as an immune‐mediated disorder, but genetic and environmental factors seem to be important in its pathogenesis. Mutations within the CARD15/NOD2 gene have been associated with CD in the Caucasian population. The aim of our work was to investigate the allele frequency and clinical impact of the three common mutations in Hungarian CD patients and healthy controls. Seventy‐four CD patients and 107 controls were examined. The genotyping of the three common CARD15/NOD2 mutations (Arg702Trp, Gly908Arg, and Leu1007fsinsC) was carried out by restriction fragment length polymorphism (RFLP) and amplification refractory mutation system (ARMS) techniques. The demographic and clinical parameters were correlated with χ2 analysis. The overall prevalence of CARD15/NOD2 mutations in the Hungarian CD patients (33.78%) was significantly higher than in healthy control individuals (16.23%) (P < 0.025). The allele frequency of the Gly908Arg mutation did not differ, but the Arg702Trp and Leu1007fsinsC mutation were more common in CD patients than in controls. The onset of CD occurs about three years earlier in CARD15/NOD2 carriers. Carriage of the Arg702Trp and Leu1007fsinsC allele within the CARD15/NOD2 gene is associated with CD. These data are in line with similar findings showing a role of the CARD15/NOD2 protein in the etiopathogenesis of CD. The genotyping of these mutations might be used to identify high‐risk patients.

Decrease in serum levels of vitamin A and zeaxanthin in patients with colorectal polyp

OBJECTIVE Several retrospective and prospective epidemiological investigations have demonstrated that a diet rich in carotenoids could prevent the development of pre-cancerous and neoplastic lesions of the digestive tract. The aim of this examination was to analyse the correlation between colorectal polyps with different histological classifications and serum carotenoid levels. DESIGN AND METHODS A 10 ml blood sample was taken from all of the patients after the colonoscopic diagnosis. The serum levels of vitamin A, lutein, zeaxanthin, alpha- and beta-cryptoxanthin, alpha- and beta-carotene were measured in patients with adenomatous colorectal polyp (n = 59, 35 males, 24 females) by high-pressure liquid chromatography (HPLC) and compared with those in healthy subjects (n = 20, 10 males, 10 females). The patients were separated into four groups depending on their histological findings. RESULTS The serum levels of vitamin A and zeaxanthin were significantly lower in all patients with polyps (vitamin A: 0.913 +/- 0.112 micromol/l, zeaxanthin: 0.071 +/- 0.012 micromol/l) than in the control healthy group (vitamin A: 2.036 +/- 0.354 micromol/l, zeaxanthin: 0.138 +/- 0.048 micromol/l). The lowest levels were found in patients with focal adenocarcinoma in the polyp. There were no significant differences in the serum levels of other carotenoids. The serum levels of cholesterol, haemoglobin, total protein and albumin were normal in these patients. CONCLUSIONS There are close and inverse correlations between the serum level of carotenoids and colorectal polyps with different histological grades. The low mean carotenoid levels in patients with adenocarcinoma in the polyp indicate that deficiency of carotenoids may be an important factor in the development of colorectal cancer.

Hemochromatosis (HFE) gene mutations and hepatitis C virus infection as risk factors for porphyria cutanea tarda in Hungarian patients

Aim: It is not clear whether the mutations in hemochromatosis (HFE) gene and hepatitis C virus (HCV) infection act independently in the pathogenesis of porphyria cutanea tarda (PCT). The prevalence of both risk factors varies greatly in different parts of the world. PCT patients from Hungary were evaluated to assess both factors.

Gastrin and pentagastrin enhance the tumour proliferation of human stable cultured gastric adenocarcinoma cells.

The effect of gastrin on stimulating tumour proliferation has been evaluated on human pancreas cancer cells in culture and in tumours transplanted to nude mice. The presence of CCK-B/gastrin-like receptor responsible for that effect of gastrin has been proved in colonic (WiDr, HT-29, YAMC) and pancreatic (PANC-1, BON) cell lines. The aim of our study was to examine the stimulating effect of gastrin and pentagastrin on the growth of human gastric adenocarcinoma cell line. The human gastric adenocarcinoma cell line (AGS, CRL-1739) was purchased from ATCC (Rockville, MA, USA). Gastrin-17 was purchased from Sigma-Aldrich (Budapest, Hungary), pentagastrin was from Zeneca Limited (Macclasfield, UK). The cells were incubated in DMEM containing 10% FCS on 96-well culturing plate with 10(4) cells/well starting cell number at 37 degrees C with 5% CO2. The proliferation rates were detected: by the measurements of the metabolically active cells with Owens reagent and the determination of protein content, and by cell counting in a haemocytometer at several incubation times. As a result, we detected similar proliferation rates using gastrin-17 or pentagastrin in the incubation medium. The stimulating effect of gastrin/pentagastrin on cell line proliferation was in correlation with its concentration. Our results proved that pentagastrin is a 10 times less effective stimulator of proliferation of gastric cancer than gastrin-17, and that AGS human adenocarcinoma cell line might be CCK receptor positive.

Prevalence of the factor V Leiden mutation in human inflammatory bowel disease with different activity

BACKGROUND the developmental mechanism of inflammatory bowel disease (IBD) in patients is unknown, but it may be influenced by different environmental and genetical factors. AIMS of this study were: (1) to classify the IBD patients according the disease activity; and (2) to determine the presence of factor V Leiden mutation in IBD patients. PATIENTS AND METHODS the observation was carried out in 49 patients with Crohns disease (CD) and 29 patients with ulcerative colitis (UC). None of them had a history of thrombotic episodes. IBD was diagnosed by conventional clinical, endoscopic, radiological and histological criteria. The factor V Leiden mutation was detected by the polymerase chain reaction (PCR) method. Crohns disease activity index (CDAI) was evaluated using the method of the National Cooperative Crohns Disease Study. We determined the UC disease activity according to Truelove-Witts classification. RESULTS The prevalence of factor V Leiden mutation was increased in both populations of the patients to compare it with healthy persons (14.28 and 27.58% vs. 5.26%, n=7/49 and 8/29 vs. 3/57). The statistical analysis did not show a significant relationship between the CDAI or the Truelove-Witts grade in UC and the presence of Leiden mutation. CONCLUSION the presence of factor V Leiden mutation probably has a role in the development of IBD. Our results suggest a higher prevalence of this mutation in Central European patients than in Southern, Northern Europe or America, may be due to the genetical differences of these populations.

Changes of serum carotenoids in patients with esophageal, gastric, hepatocellular, pancreatic and colorectal cancer.

UNLABELLED The serum levels of carotenoids (vitamin A, lutein, zeaxanthin, alfa- and beta cryptoxanthin, alfa- and beta-carotene) were measured in healthy persons (n=40) and in 98 patients with different malignant gastrointestinal diseases (44 patients with colon adenocarcinoma, 21 with gastric cancer, 15 with hepatocellular adenocarcinoma, 10 patients with pancreas adenocarcinoma and eight patients with esophagus cancer). The serum levels of carotenoids were measured with high-pressure liquid chromatography. The sera of the patients were taken at the time of the diagnosis. RESULTS the measurements indicated that (1) the serum level of vitamin A and zeaxanthin were significantly lower in all of these groups (except of pancreas adenocarcinoma), but the extent of the A decrease was different in the patients with different types of gastrointestinal malignancy. The serum level of vitamin A was in the healthy subjects 2.072+/-0.332 mmol/l and in the case of gastrointestinal malignancies was 0.77+/-0.14 mmol/l (P<0.001) The serum level of zeaxanthin was in the healthy subjects 0.143+/-0.057 mmol/l and at the malignancies was 0.042+/-0.014 mmol/l (P<0.01). (2) There were no significant differences in the serum levels of other carotenoids in the checked groups. (3) The serum level of cholesterol, total protein, albumin and haemoglobin were in the normal range in these patients. These results indicate that the carotenoids may be responsible nutritional factors (as nutritional scavengers) in the development of different malignant diseases. This supposed role in the carcinogenesis does not depend fully on the vitamin A activity.

Gastrointestinal cytoprotection: from basic science to clinical perspectives.

Abstract.An essential point of cytoprotection is that the prostaglandins are able to prevent chemical-induced gastric mucosal damage without affecting gastric acid secretion, this being originally suggested as a property specific to prostaglandins. Since then gastrointestinal cytoprotection has been shown with various agents (anticholinergic agents, H2RA, growth factors) and retinoids the latter differing from the actions of vitamin A. In examining the various components of gastrointestinal cytoprotection we have performed studies in isolated cells, stable cell lines, animal experiments, healthy human subjects, and in patients with gastrointestinal diseases. Our attention has focused on the effects of cytoprotective agents on cellular viability, mitochondrial and DNA damage, oxygen free radicals, natural antioxidant systems, mucosal biochemistry, vascular events, gastrointestinal mucosal protection as well as in their prevention of different human diseases. This paper gives a short overview on the different approaches for the exploring gastrointestinal cytoprotection.

Leiden mutation (as genetic) and environmental (retinoids) sequences in the acute and chronic inflammatory and premalignant colon disease in human gastrointestinal tract.

BACKGROUND Tumor, calor, dolor, pallor and functio laesa are together involved in the different acute and chronic inflammatory processes. The processes involved in the inflammation are determined by differently acquired and hereditary factors. Recently the presence of a new genetic marker (Leiden point mutation) was found in Crohns disease and ulcerative colitis. On the other hand, the GI mucosal integrity was proven on gastrointestinal mucosal damage to be produced by different chemicals, xenobiotics, drugs. In human observations, the serum level of retinoids (vitamin A, lutein, zeaxanthin, alpha-, beta-carotene) was proven in patients with chronic gastrointestinal inflammatory bowel disease. The aims of this study were (1) to measure the prevalence of Leiden mutation; (2) to identify the changes in the serum retinoid level in patients with Helicobacter pylori infection of the stomach (n=24), hepatitis C infection (n=75), ileitis terminalis (Crohns disease; n=49), ulcerative colitis (n=35), colon polyposis (n=59) and adenocarcinoma in colon polyps (n=9), and 57 healthy persons were used in the control group; (3) to compare the directions of the changes in the measured parameters in the acute (H. pylori and hepatitis C infections), chronic (ileitis terminalis, ulcerative colitis) GI inflammatory diseases and in colon polyposis without and with malignisation. METHODS The Leiden mutation was measured by the method of polymerase chain reaction, the retinoid level in the patients serum was measured by high liquid cromathografic method (HPCL). RESULTS (1) It has been found that the prevalence of Leiden mutation increased significantly in patients with ileitis terminalis (P<0.001), ulcerative colitis (P<0.001), colon polyposis (P<0.001) and with colon polyps with malignisation (P<0.01). (2) Serum level of vitamin A and zeaxantin were decreased significantly in all group of patients except for the group with H. pylori infections. (3) alpha- and beta-carotenes were found to be practically at the same level as those in the control groups, except in patients of colon polyps with malignisation. (4) The vitamin A, lutein, zeaxantin, alpha- and beta-carotenes were decreased in patients with ileitis terminalis. CONCLUSIONS (1) The essential role of retinoids (carotenoids) as environmental factors are suggested for keeping GI mucosal integrity in human healthy subjects and patients. (2) Leiden mutation, as a genetic marker, can be used in the screening of patients with ileitis terminalis, ulcerative colitis and colon polyposis (without and with malignisation). (3) An opposite direction can be found between the increased prevalence of Leiden mutation and decrease of serum levels of retinoids in group of patients with ileitis terminalis, ulcerative colitis and colon polyposis (without and with malignisation).