Krystyna Stec-Michalska

Helicobacter pylori Infection and Family History of Gastric Cancer Decrease Expression of FHIT Tumor Suppressor Gene in Gastric Mucosa of Dyspeptic Patients

Background:  The expression of a fragile histidine triad (FHIT) protein is lost in stomach tumors. The study aimed at determining whether FHIT expression is affected by Helicobacter pylori infection, strain virulence (vacA and cagA genes) and histopathological changes in the gastric mucosa of patients with functional dyspepsia having first‐degree relatives with gastric cancer.

Expression of somatostatin receptor subtype 3 in the gastric mucosa of dyspeptic patients in relation to Helicobacter pylori infection and a family history of gastric cancer

Background and Aim:  The cytotoxic activity of Helicobacter pylori contributes significantly to the pathogenesis of gastric carcinoma. A preliminary study suggested that somatostatin receptor subtype 3 (SSTR3) might play a role in cell apoptosis and the growth of gastric cancer. The aim of the present study was to determine the influence of H. pylori infection and a family history of gastric cancer on the expression of SSTR3 in the gastric mucosa of non‐cancer patients with dyspepsia.

Circadian rhythm abnormalities – Association with the course of inflammatory bowel disease

Crohns disease (CD) and ulcerative colitis (UC) are the main representatives of inflammatory bowel diseases (IBD), a group of chronic, immune system-mediated inflammatory diseases of the gastrointestinal (GI) tract. The pathogenesis of the intestinal lesions in IBD is not entirely identified and understood: excessive activation of the immune system may come as a result of the interaction of various environmental and infectious factors, genetic predisposition, and the mediation of abnormal intestinal flora. The main objective of the current study is to further identify the risk factors for the development of IBD. Currently, there is very little knowledge about circadian rhythm and IBD and there are only a few studies on the relationship between sleep disturbances and the course of the disease, as well as pro- and anti-inflammatory cytokine profile and general immune system functioning. Furthermore, the relationship between the expression of circadian rhythm genes and severe course of IBD is still unknown. The aim of this review is to show the current state of knowledge about the relationship between circadian rhythm disorders, sleep disturbance and inflammation in the GI tract and to analyze the possibility of employing this knowledge in diagnosis and treatment of IBD.

SATB1 expression in gastric mucosa in relation to Helicobacter pylori infection and family history of gastric cancer.

PURPOSE SATB1 protein, the altered levels of which are observed in tumour tissues, acts as a global regulator of gene expression. The aim of the study was to investigate the expression level of the SATB1 gene in gastric mucosa of dyspeptic patients in relation to the H. pylori infection, the family history of gastric cancer (FHGC), and histopathological changes. MATERIAL AND METHODS The study comprised 64 patients with dyspeptic symptoms. Group I - 28 control patients (10 H.pylori positive) without the FHGC. Group II - 36 patients (16 H. pylori positive) with the FHGC. The samples with normal mucosa (NM) or chronic superficial gastritis (CSG) were used for further analysis. qRT-PCR was used to determine the level of mRNA of SATB1. RESULTS The dominant histopathological changes in group I were NM and CSG. Specimens from group II have demonstrated an increasing frequency of atrophy (A) and intestinal metaplasia (IM). The A and IM specimens have shown increase of expression of the SATB1 and were excluded from further evaluation. In corpus samples of group II patients, the amount of SATB1 mRNA was higher than in antrum samples, regardless of H. pylori infection. The presence of bacterium resulted in the elevated SATB1 expression in corpus samples of group II patients only, while the genetic factor down-regulated SATB1 gene in the antrum samples of the H. pylori negative individuals. CONCLUSIONS The expression of SATB1 gene correlates with histological changes and is altered by the selected environmental and hereditary factors, and the observed changes may have an impact on the development of gastric cancer.

Influence of cigarette smoking on the level of mRNA of somatostatin receptor 3 (SSTR3) in the gastric mucosa of patients with functional dyspepsia

PURPOSE Helicobacter pylori (H. pylori) infection and smoking of cigarettes increase individual risk to gastric carcinoma. In stomach tumors, an expression of somatostatin receptor 3 (SSTR3) is diminished or completely lost. The purpose of these studies was to determine the influence of smoking cigarettes and H. pylori infection on the expression of SSTR3 in patients with functional dyspepsia. MATERIALS AND METHODS The study comprised 109 patients with functional dyspepsia in the age range 28-61 years. The total 218 biopsies used for analysis were divided into two groups: group I - 176 biopsies from non-smokers (72 from H. pylori positive ones), and group II - 42 biopsies from cigarette smokers (28 from H. pylori positive patients). The SSTR3 mRNA amount in the gastric mucosa (1 biopsy from the antrum and 1 biopsy from the corpus) was determined by real time RT-PCR. The presence of H. pylori colonization in the stomach tissue was evaluated by multiplex PCR. RESULTS In the H. pylori negative samples the amount of the SSTR3 mRNA was significantly lower for smokers than for non-smokers (by 40%, p < 0.010). Infection with H. pylori caused reduction of the level of SSTR3 mRNA in non-smoking patients by ca. 30% (p < 0.01), while in samples from smokers the SSTR3 mRNA level was similar regardless of H. pylori infection. CONCLUSIONS The cigarettes smoking and H. pylori infection are independent factors leading to decreasing of the SSTR3 mRNA level in gastric mucosa of patients with functional dyspepsia.

Serum Cyclophilin A Correlates with Increased Tissue MMP-9 in Patients with Ulcerative Colitis, but Not with Crohn’s Disease

BackgroundCyclophilin A (CyPA) is an immunomodulatory protein, high expression of which correlates with poor outcome of patients with inflammatory diseases. However, its role in inflammatory bowel disease (IBD) has not been studied.AimThis study analyzes the correlation between cyclophilin A, matrix metalloproteinase (MMP)-9, and tissue inhibitor of MMP (TIMP)/MMP-9 complexes in the inflamed and non-inflamed colon mucosa of UC and CD patients.MethodsSerum and biopsy specimens from inflamed and non-inflamed colonic mucosa of 38 patients with IBD (19 with UC and 19 with CD) and 16 controls were included in our study. We measured serum and tissue level of CyPA, and tissue level of TNF-α, MMP-9, TIMP-1/MMP-9, and TIMP-2/MMP-9 using ELISA method.ResultsOur results indicated that serum, but not tissue CyPA is increased in UC, rather than in CD patients, compared to the control. The increase correlated with higher tissue concentration of MMP-9 and TNF-α, especially in the UC group. Moreover, we observed significantly higher level of TIMP-1/MMP-9 in UC and CD group, which overlapped with the change in MMP-9. There was no change in TIMP-2/MMP-9 in the analyzed groups.ConclusionThe current study suggests that serum CyPA may be an independent additional marker of IBD, especially of UC. Higher CyPA level may be followed by increased MMP-9 in those patients. However, further studies are necessary to verify the role of CyPA in IBD development.

G protein-coupled receptor 30 (GPR30) expression pattern in inflammatory bowel disease patients suggests its key role in the inflammatory process : a preliminary study

BACKGROUND AND AIMS G protein-coupled receptor 30 (GPR30) is a recently de-orphanized estrogen receptor that mediates the effects of estrogens on different cells. It has been postulated that in inflammatory bowel diseases (IBD) activation of GPR30 blocks the pathways dependent on pro-inflammatory cytokines. The aim of our study was to investigate GPR30 expression in patients with IBD and its potential implication in future therapies. METHODS Fifty-seven patients were enrolled in our study: 20 subjects with Crohns disease (CD), 22 with ulcerative colitis (UC) and 15 controls. In each subject, biopsies were taken from various left-colonic locations. Gene and protein expression of GPR30 was quantified using real time RT-PCR or Western blot. RESULTS GPR30 mRNA and protein expression were detected in all tested colonic tissues. No significant differences in GPR30 gene expression were observed. In non-inflamed areas, GPR30 protein was strongly increased in CD patients, but moderately in UC patients (p= 0.014 and p=0.143, respectively, vs. controls). In CD patients, a significantly lower GPR30 protein content in inflamed than in non-inflamed tissue was observed (p=0.039). The change was independent of patient gender. CONCLUSION Our observations indicate that GPR30 may play a role in the development and progression of inflammatory lesions in IBD, thus affecting disease severity, and consequently IBD treatment. Therefore, GPR30 may become an attractive target for novel anti-IBD drugs, particularly in CD.

G protein-coupled receptor 55 (GPR55) expresses differently in patients with Crohn’s disease and ulcerative colitis

Abstract Aim: To investigate the levels of G protein-coupled receptor 55 (GPR55) expression in colonic tissue of inflammatory bowel disease (IBD) patients and healthy controls, and its potential implication in IBD treatment. Methods: Fifty patients were enrolled in our prospective study: n = 21 with Crohn’s disease (CD) and n = 16 with ulcerative colitis (UC); 19 women and 18 men. Control consisted of 13 non-IBD patients. In each subject, two biopsies were taken from different colonic locations. In IBD patients, biopsies both from endoscopically inflamed and non-inflamed areas were drawn and the development of inflammation confirmed in histopathological examination. GPR55 mRNA and protein expression were measured using real-time PCR and Western blot, respectively. Results: GPR55 expression at mRNA and protein level was detected in all samples tested. The level of GPR55 mRNA expression in non-inflamed colonic areas was comparable in all analyzed groups (p = .2438). However, in the inflamed tissues GPR55 mRNA expression was statistically significantly (p < .0001) higher (6.9 fold) in CD patients compared to UC. Moreover, CD patients manifested higher (12.5 fold) GPR55 mRNA expression in inflamed compared with non-inflamed colonic tissues (p < .0001). Although no significant differences were stated, GPR55 protein level tends to decrease in IBD as compared to control. Conclusions: Different patterns of GPR55 expression at mRNA level were observed in IBD patients. We speculate that GPR55 is crucial for the mucosal inflammatory processes in IBD, particularly in CD and its expression may affect disease severity, and response to treatment. The GPR55 receptors may become an attractive target for novel therapeutic strategies in IBD.

The influence of Helicobacter pylori eradication on the expression and methylation status of the FHIT gene in non-cancerous gastric mucosa of dyspeptic patients

To investigate the effect of Helicobacter pylori (H. pylori) eradication on the expression level of the FHIT gene and its methylation status in the gastric mucosa of dyspeptic patients with or without a family history of gastric cancer (FHGC).

Diagnostic value of measuring serum serotonin and urinary 5-hydroxyindoleacetic acid concentration in the diagnosis of functional dyspepsia

Wstęp: Patogeneza dyspepsji czynnościowej jest niedostatecznie poznana. Rozpoznanie ustalane jest na podstawie objawów subiektywnych, niemniej ciągle poszukuje się przyczyn i obiektywnych wykładników, które ułatwiłyby diagnostykę i wyjaśniły różnorodność objawów klinicznych tej choroby. Cel: Ocena wydzielania i metabolizmu serotoniny w różnych postaciach klinicznych dyspepsji czynnościowej. Materiał i metody: Badania wykonano w grupie 25 osób klinicznie zdrowych (K) oraz u 25 osób z zespołem bólów w nadbrzuszu (epigastric pain syndrome – EPS) i 25 pacjentów z zespołem dolegliwości poposiłkowych (postprandial distress syndrome – PDS), w wieku od 19 do 49 lat (średnio 34,6 ±13,4 roku). Rozpoznanie dyspepsji czynnościowej opierano na III Kryteriach Rzymskich. Wykluczono także zakaże nie H. pylori. Na 7 dni przed i w dniu badania pacjenci otrzymywali jednakową dietę. Krew do badania pobierano na czczo, a następnie prowadzono 24-godzinną zbiórkę moczu. Stężenie serotoniny w surowicy i kwasu 5-hydroksyindolo octowego (5-HIAA) w moczu oznaczano metodą ELISA z użyciem przeciwciał firmy IBL (nr katalogowy – RE 59121, RE 59131). Wyniki: Stężenie serotoniny w surowicy wynosiło w grupie osób zdrowych 162,9 ±49,1 ng/ml, z zespołem EPS – 225,8 ±113,3 ng/ml (p < 0,05), a z zespołem dolegliwości poposiłkowych – 152,7 ±83,2 ng/ml (p > 0,05). Wydalanie 5-HIAA z moczem wynosiło odpowiednio w grupach: K – 5,65 ±2,31 mg/dobę, EPS – 4,12 ±1,85 mg/dobę (p < 0,01) i PDS – 3,06 ±1,61 mg/dobę (p < 0,01). Abstract