Mária Figler

Capsaicin increases gastric emptying rate in healthy human subjects measured by 13C-labeled octanoic acid breath test

The role of capsaicin-sensitive primary afferent sensory nerves in the regulation of gastrointestinal motility in human is not clarified yet. In this study, we investigated the effect of 400 microg capsaicin given intragastrically on gastric emptying measured by 13C-octanoic acid breath test in ten healthy human subjects. Four parameters of gastric emptying curves were taken into consideration: 1) maximum value of the curve, 2) time belonging to this maximum, 3) slope of the rising part of the curve and 4) time belonging to the 50% of the area under the curve. Administration of 400 microg capsaicin significantly increased the slope of gastric emptying curve (from 0.1 +/- 0.01 to 0.139 +/- 0.014 U x min(-1), P < 0.05) and significantly decreased the time belonging to the maximum value of emptying curve (from 150 +/- 18 to 75 +/- 12 min, P < 0.05) and the time belonging to the 50% of the area under the curve (from 112 +/- 15 to 99 +/- 14 min, P < 0.05). According to our results 400 microg capsaicin enhances gastric emptying rate in healthy human subjects.

Plasma carnitine ester profiles in Crohn's disease patients characterized for SLC22A4 C1672T and SLC22A5 G-207C genotypes.

Crohns disease (CD) is a chronic inflammatory bowel disorder caused by environmental and genetic factors. The purpose of this study was to analyse the possible influence of functional variants of genes of OCTN cation transporters on the carnitine ester profile of patients with CD. Genotyping for SLC22A4 1672C --> T, SLC22A5-207G --> C mutations and three common NOD2 variants (R702W, G908R and 1007finsC) were performed in 100 adult CD patients and in ninety-four healthy controls by direct sequencing. The carnitine ester profile was determined using ESI triple quadrupole tandem MS. Contrary to the NOD2/CARD15 mutations, none of the SLC variants showed increased prevalence in the CD group, the prevalence of TC haplotype did not differ between the patients and the controls. In the mixed group of CD patients the fasting propionyl- (0.243 (sem 0.008) v. 0.283 (sem 0.014) micromol/l), butyryl- (0.274 (sem 0.009) v. 0.301 (sem 0.013)) and isovalerylcarnitine (0.147 (sem 0.006) v. 0.185 (sem 0.009)) levels were decreased; while the level of octenoyl- (0.086 (sem 0.006) v. 0.069 (sem 0.005)), myristoleyl- (0.048 (sem 0.003) v. 0.037 (sem 0.003)), palmitoyl- (0.140 (sem 0.005) v. 0.122 (sem 0.004)) and oleylcarnitine (0.172 (sem 0.006) v. 0.156 (sem 0.008); P < 0.05 in all comparisons) were increased. After sorting the patients into SLC22A genotype-specific subgroups, no significant differences could be observed between them. The carnitine ester profile data suggest selective involvement of the carnitine esters in CD patients, probably due to their altered metabolism.

Difference of interleukin-23 receptor gene haplotype variants in ulcerative colitis compared to Crohn’s disease and psoriasis

ObjectivePolymorphisms of the interleukin-23 receptor (IL23R) gene have been found to play a role in the development of several autoimmune diseases. Our aim was to examine the possible effect of not only simple individual variants, but of haplotypes composed of them.SubjectsWe analysed 263 patients with psoriasis, 199 patients with Crohn’s disease (CD), 282 patients with ulcerative colitis (UC), and 253 controls for rs1884444, rs11805303, rs7517847, rs2201841, rs10889677 and rs11209032 variants.MethodsThe genotypes were determined by using PCR/RFLP assay. Logistic regression analysis was used to compare the genotype distribution of the polymorphisms and haplotypes between the examined autoimmune diseases and healthy controls.ResultsRs1884444 was found to confer risk for UC and psoriasis, rs10889677 for CD and psoriasis, while rs2201841 and rs7517847 had effect only in CD. Using these SNPs we could study the susceptibility haplotype profiles in these diseases with special attention to UC. Eight different haplotypes could be differentiated. We found that the SNPs exert their susceptibility character in specific haplotype blocks, and the frequency of one haplotype differed significantly in UC compared with both other diseases and also with healthy controls. This haplotype conferred risk for UC, even while it had a somewhat lower frequency in the other diseases than in controls.ConclusionsThe data presented here serve as evidence for the need of haplotype analysis instead of just single standing SNP analysis when susceptibility is interpreted.

Association of n -3 and n -6 long-chain polyunsaturated fatty acids in plasma lipid classes with inflammatory bowel diseases

In order to establish the biochemical basis for dietary interventions, we investigated the fatty acid composition of plasma lipid classes in patients with inactive inflammatory bowel disease. In this cross-sectional study thirty patients with ulcerative colitis (UC), twenty-one with Crohn disease (CD) and twenty-four controls were investigated (mean age: UC, 40.8 (sd 12.1); CD, 37.6 (sd 11.0); control, 31.5 (sd 8.4) years). Fatty acid composition of plasma lipids was determined by high-resolution capillary GLC. In plasma phospholipids, significantly higher values of eicosapentaenoic (20 : 5n-3), docosapentaenoic (22 : 5n-3) and gamma-linolenic (18 : 3n-6) acids were found in control patients and patients with UC as compared to patients with CD [median % (weight by weight), control v. UC v. CD : 20 : 5n-3, 0.09 (interquartile range (IQR) 0.05) v. 0.14 (IQR 0.10) v. 0.16 (IQR 0.10), P < 0.05; 22 : 5n-3, 0.14 (IQR 0.10) v. 0.27 (IQR 0.16) v. 0.31 (IQR 0.10), P < 0.001; 18 : 3n-6, 0.02 (IQR 0.02) v. 0.03 (IQR 0.02) v. 0.05 (IQR 0.03), P < 0.05]. When compared to the control, values of the principal n-3 and n-6 long-chain PUFA, arachidonic acid (20 : 4n-6) and DHA (22 : 6n-3) were significantly higher in patients with UC but not in patients with CD [median % (w/w), UC v. control: 20 : 4n-6, 8.43 (IQR 3.23) v. 6.92 (IQR 2.96), P < 0.05; 22 : 6n-3, 1.22 (IQR 0.56) v. 0.73 (IQR 0.39), P < 0.05]. As seen there are considerable differences between the long-chain PUFA status of patients suffering from UC or CD. The data obtained in the present study do not support the concept of eicosapentaenoic acid or DHA deficiency in patients with either UC or CD.

Small doses of capsaicin given intragastrically inhibit gastric basal acid secretion in healthy human subjects.

Although the direct inhibitory effect of small dose of capsaicin on gastric secretory responses was proved in animal observations, the role of capsaicin-sensitive afferent nerves (CSAN) and the effect of capsaicin applied in small and high doses on gastric secretion in human has not been clarified yet. In this study we investigated the influence of different small doses (100-800 microg) of capsaicin given intragastrically through an orogastric tube on gastric basal secretory responses in 10 healthy human subjects. Gastric basal secretory responses (volume, H+-concentration, H+-output) were measured from the suctions of gastric juice for a 1-h period. It has been found that: a) capsaicin dose-dependently inhibited the volume and H+-output of gastric juice; b) ID50 was found to be about 400 microg for capsaicin on gastric acid secretion; c) the time interval for capsaicin-induced gastric inhibition existed for about 1 h indifferently from the higher dose (800 microg) of capsaicin given after. It has been concluded that the capsaicin (given in small doses) inhibits the gastric basal acid output via stimulation of the inhibition of capsaicin sensitive afferent nerves.

Marked diversity of IL23R gene haplotype variants in rheumatoid arthritis comparing with Crohn’s disease and ankylosing spondylitis

Haplotype tagging SNPs of interleukin-23 receptor gene rs1004819, rs7517847, rs7530511, rs2201841, rs1343151 and rs10889677 were determined in 396 patients with rheumatoid arthritis, 190 patients with Crohn’s disease, 206 patients with ankylosing spondylitis and 182 controls. Using regression analysis models the rs1004819, rs2201841, and rs10889677 SNPs were found to confer risk for Crohn’s disease and ankylosing spondylitis, while rs1343151 had a protective effect in both of these diseases, and the rs2201841 and rs10889677 SNPs showed susceptibility nature for rheumatoid arthritis. Using these SNPs we could study the susceptibility haplotype profiles in these diseases with special attention to the rheumatoid arthritis, first in the literature. Seven different haplotypes could be differentiated. We found that the SNPs exert their susceptibility character in specific haplotype blocks: thus, for rheumatoid arthritis the rs1343151 SNP was risk factor only in a specific haplotype surrounding; this can explain the controversial results published so far about this variant. More importantly, we observed, that while a specific haplotype can confer risk for rheumatoid arthritis, the same haplotype tended to protect against the development of the other two diseases. The data presented here serve evidence for the need of haplotype analysis instead of just single standing SNP analysis when susceptibility to or protection against a certain disease are interpreted.

The key-role of vagal nerve and adrenals in the cytoprotection and general gastric mucosal integrity.

BACKGROUND Our laboratory group observed earlier that the gastric mucosal cytoprotective effect of prostacyclin (PGI(2)) disappeared after surgical vagotomy in rats. Similarly to this, the beta-carotene induced gastric cytoprotection disappeared in adrenalectomized rats too. AIMS In these studies we aimed to investigate the possible role of vagal nerve and adrenals in the development of gastric mucosal lesions induced by exogenously administered chemicals (ethanol, HCl, NaOH, NaCl and indomethacin), and on the effects of cytoprotective and antisecretory drugs (atropine, cimetidine), and scavengers (vitamin A and beta-carotene). METHODS The observations were carried out in fasted CFY strain rats. The gastric mucosal lesions were produced by intragastric (i.g.) administration of narcotising agents (96% ethanol; 0.6 M HCl; 0.2 M NaOH; 25% NaCl) or subcutaneously (s.c.) administered indomethacin (20 mg/kg) in intact, surgically bilaterally vagatomized, and adrenalectomized rats without or with glucocorticoid supplementation (Oradexon, 0.6 mg/kg given i.m. for 1 week). The gastric mucosal protective effect of antisecretory doses of atropine (0.1-0.5-1.0 mg/kg i.g.) and cimetidine (10-25-50 mg/kg i.g.), and vitamin A and beta-carotene (0.01-0.1-1.0-10 mg/kg i.g.) was studied. The number and severity of mucosal gastric lesions was numerically or semiquantitatively measured. In other series of observations the gastric acid secretion and mucosal damage were studied in 24 h pylorus-ligated rats without and with acute bilateral surgical vagotomy. RESULTS It was found that: (1) the chemical-induced gastric mucosal damage was enhanced in vagotomized and adrenalectomized rats, meanwhile the endogenous secretion of gastric acid, and the development of mucosal damage can be prevented by surgical vagotomy; (2) the gastric cyto- and general protection produced by the drugs and scavengers disappeared in vagotomized and adrenalectomized rats; (3) the gastric mucosal protective effects of drugs and of scavengers returned after sufficient glucocorticoid supplementation of the rats. CONCLUSION It has been concluded that the intact vagal nerve and adrenals have a key role in the gastric mucosal integrity, and in drugs- and scavengers-induced gastric cyto- and general mucosal protection.

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.

Plasma carnitine ester profiles in Crohn's disease and ulcerative colitis patients with different IGR2230a_1 genotypes.

An association has been repeatedly demonstrated between inflammatory bowel disease (IBD) and the IBD5 locus in the 5q31 chromosomal region. The aim of the present study was to examine the prevalence of the IGR2230a_1 intronic nucleotide polymorphism of the slc22a5 gene (coding for the OCTN2 carnitine transporter protein) lying within this region, and its possible relationship with the carnitine metabolism in Hungarian IBD patients and controls. We genotyped by restriction fragment length polymorphism 200 Crohns disease (CD) and 246 ulcerative colitis (UC) patients, as well as 187 healthy controls. From plasma samples we determined detailed carnitine ester profiles of 76 CD, 43 UC patients and 45 control persons using electrospray ionization triple quadruple tandem mass spectrometry. The distribution of the genotypes was not significantly different in the CD or the UC group compared with the controls. We found no significant alterations of the carnitine profile in the carrier/non‐carrier or the homozygote/non‐homozygote comparisons in both the CD and the UC groups, stratified by IGR2230a_1 genotype. Our data suggest that this polymorphism alone is not associated with CD and UC in the Hungarian population, and has no effect on the carnitine metabolism.

Fatty acid composition of plasma lipid classes in chronic alcoholic pancreatitis.

Background/Aims: Supplementation of n–3 long-chain polyunsaturated fatty acids (LCPUFA) is considered as adjuvant therapy in acute pancreatitis. We investigated plasma fatty acid status in chronic pancreatitis (CP). Methods: Patients with alcoholic CP (n = 56, gender: 33/23 male/female, age: 60.0 [14.0] years (median [IQR]), who reported giving up alcohol consumption several years ago and 51 control subjects were included into the study. The fatty acid composition of plasma phospholipids (PL), triacylglycerols (TG) and sterol esters (STE) was analyzed. Results: The sum of monounsaturated fatty acids was significantly higher in patients with CP than in controls (PL: 12.83 [3.35] vs. 12.20 [1.95], TG: 40.51 [6.02] vs. 37.52 [5.80], STE: 20.58 [7.22] vs. 17.54 [3.48], CP vs. control, % weight/weight, median [IQR], p < 0.05). Values of arachidonic acid were significantly lower in patients with CP than in controls (PL: 10.57 [3.56] vs. 11.66 [3.25], STE: 8.14 [2.63] vs. 9.24 [2.86], p < 0.05). Values of eicosapentaenoic acid and docosahexaenoic acid did not differ and there was no difference in the ratio of n–3 to n–6 LCPUFA. Conclusion: Our present data do not furnish evidence for the supplementation of n–3 LCPUFA to the diet of CP patients in relatively good clinical condition.