Kyriaki Anastasiadou

Helicobacter pylori infection in patients with nonalcoholic fatty liver disease

OBJECTIVE Clinical data regarding Helicobacter pylori (Hp) infection in nonalcoholic fatty liver disease (NAFLD) are limited. The aim was the evaluation of Hp infection in patients with NAFLD and its association with disease severity. METHODS 28 patients with biopsy-proven NAFLD (15 with simple nonalcoholic fatty liver [NAFL], 13 with nonalcoholic steatohepatitis [NASH]) and 25 matched healthy controls were recruited. Blood samples for anti-Hp Immunoglobulin G (IgG) and standard biochemical tests were obtained after overnight fasting, and (13)C urea breath test was performed before liver biopsy in NAFLD group. RESULTS Higher rates of anti-Hp IgG (P=.038) were observed in NAFLD compared to control group. Only two NAFLD patients neither were Hp IgG seropositive nor did they have a history of eradication treatment compared to 11 control subjects (P=.002). Both Hp infection (assessed by history of Hp eradication treatment and/or Hp IgG seropositivity) (P=.034) and log(HOMA-IR) (P=.007) could independently predict NAFLD in logistic regression analysis. There were similar rates of Hp IgG seropositivity or positivity in (13)C urea breath test or their combination between NAFL and NASH patients. There were no significant differences in steatosis grade, fibrosis stage, lobular or portal inflammation, or ballooning, when NAFLD patients were divided according to Hp IgG seropositivity or (13)C urea breath test positivity. CONCLUSIONS Hp infection may represent one more hit contributing to the pathogenesis of NAFL, though not to the progression from NAFL to NASH. These results warrant further validation. If confirmed, eradicating Hp infection may have certain therapeutic perspectives in NAFLD treatment.

Impact of reactive oxygen species generation on Helicobacter pylori-related extragastric diseases: a hypothesis.

Abstract Helicobacter pylori (H. pylori) induces reactive oxygen species (ROS) production that contribute to pathogenesis of a variety of H. pylori-related gastric diseases, as shown in animal and human studies. Helicobacter pylori infection is also associated with variety of systemic extragastric diseases in which H. pylori-related ROS production might also be involved in the pathogenesis of these systemic conditions. We proposed that Hp-related ROS may play a crucial role in the pathophysiology of Hp-related systemic diseases including Alzheimer’s disease, multiple sclerosis, glaucoma and other relative neurodegenerative diseases, thereby suggesting introduction of relative ROS scavengers as therapeutic strategies against these diseases which are among the leading causes of disability and are associated with a large public health global burden. Moreover, we postulated that H. pylori-related ROS might also be involved in the pathogenesis of extragastric common malignancies, thereby suggesting that H. pylori eradication might inhibit the development or delay the progression of aforementioned diseases. However, large-scale future studies are warranted to elucidate the proposed pathophysiological mechanisms, including H. pylori-related ROS, involved in H. pylori-associated systemic and malignant conditions.

Haematoma caused by bone marrow aspiration and trephine biopsy

We report a case of a bone marrow aspiration and trephine biopsy (BMATB) associated haematoma in an 85-years old male without any predisposing risk factors. Six days after BMATB, he suffered from a massive thigh and buttock haematoma and a fall in haematocrit. It is important to know that BMATB can have complications aiding early recognition and therapy.

Autologous haematopoietic stem cell transplantation in a patient with refractory Crohn's disease

Dear Sir, Recent series reported successful autologous bone marrow-derived mesenchymal stromal cells transplantation in 10 patients with fistulising Crohns disease (CD).1 We wish to provide a relative experience on the long-term successful autologous haematopoietic stem cell transplantation (HSCT) in a patient with refractory CD who has completed a 31-month follow up. A 39-year-old male with moderate–severe CD, first diagnosed in 1994 involving the jejunum, ileum and colon was treated for eight years with conventional treatment schedules including corticosteroids mainly in disease relapses, mesalazine and one immunosuppressor (azathioprine). Because of a severe relapse in 2002, the patient was successfully treated by surgery (right colectomy/sigmoidectomy). He remains disease free for two years while on treatment …

Helicobacter pylori might be a potential therapeutic target in epilepsy

predict AIS development. Cartilage oligomeric matrix protein (COMP) is essential for the normal development of cartilage and for its conversion to bone during growth. It is expressed at high levels during skeletal development and long bone growth. Mutations in COMP produce clinical phenotypes of pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) [2,3]. These disorders are characterized by disproportionate short stature, brachydactyly, joint hypermobility, earlyonset osteoarthritis, and scoliosis [4]. Interestingly, the phenotypes in PSACH/MED cartilage disorders is not caused by the reduced amount of COMP but rather due to dysfunctional mutated COMP. Abnormal COMP protein cannot be transported out of the cell but rather builds up inside the chondrocyte and it ultimately leads to early chondrocytes death preventing normal bone growth [5]. Recently, in a microarray approach evaluating primary human osteoblasts, we found that COMP is one of the most differentially regulated genes in AIS compared to unaffected individuals [6]. COMP was found to be significantly down-regulated by 4-fold in AIS [6]. Consistent with the microarray analysis, relatively low levels of COMP mRNA transcripts in AIS were detected by RT-qPCR analysis. Altogether, these data suggest that low expression of COMP is associated with AIS. This is the first down-regulated gene described in AIS. Thus, we hypothesized COMP down-regulation would result to a low COMP serum level in AIS patients and this could be an important and novel biomarker in predicting scoliosis development. Supported by The Yves Cotrel Foundation, Institut de France.

Potential oncogenic properties of mobilized stem cells in a subpopulation of inflammatory bowel disease patients infected with Helicobacter pylori.

To the Editor: Marlicz et al concluded that Crohn’s disease (CD) triggers the mobilization of various types of stem cells, such as hematopoietic stem progenitor cells, into peripheral blood in patients suffering from this disease, while the significance and precise role of these mobilized cells in repair of damaged intestine requires further study. However, the authors did not discuss the possibility of potential oncogenic properties of the mobilized stem cells, at least in the subgroup of patients possibly infected with Helicobacter pylori (H. pylori). In this regard, although relative data indicate an absence or inverse association between H. pylori and inflammatory bowel disease (IBD), the prevalence of H. pylori infection in the IBD patients appears to be 38.2%– 47% in Europe. Moreover, enterohepatic and gastric Helicobacter species have been documented in fecal specimens from children with CD using polymerase chain reaction (PCR), and H. pylori, for example, was recently found in the intestinal mucosa of a patient affected by CD. Experimental data indicate that H. pylori infection leads to development of chronic inflammation, hyperplasia, metaplasia, dysplasia, and recruitment and accumulation of bone marrow-derived cells (BMDCs) in the mouse gastric epithelial mucosa. Nearly 25% of dysplastic lesions include cells originating from BMDCs, thereby indicating that BMDCs can participate in preneoplastic lesions preceding gastric carcinoma development; there is a role for engraftment of circulating BMDCs, which may contribute to tumor formation in animal models with H. pylori-induced chronic gastric inflammatory processes, thus further suggesting the possibility of the potential contribution of BMDCs in human gastrointestinal carcinoma. In this regard, we recently conducted a pilot study using tissue sections of biopsies of human gastric cancer in which H. pylori was detected by Cresyl violet staining. Moreover, stem cells and neovessels were detected by immunohistochemical method using a monoclonal antibody, anti-CD34; CD34, also mentioned by the authors, is a surface glycoprotein expressed on hematopoietic stem cells and is used as an important marker of these cells and neovessels. In addition, cyclin D1, involved in the regulation of cell proliferation, was also detected by immunohistochemical method. Other relative data indicate that H. pyloriinduced cytotoxin VacA exhibits chemotactic activities to the BMDCs and induces BMDCs to produce proinflammatory cytokines, leading to chronic inflammation with potential oncogenic consequences. Therefore, it would be reasonable to speculate that chronic H. pylori infection in both mice and humans induces repopulation of the stomach with BMDCs that may facilitate gastric cancer progression. These findings present a new way of thinking about the pathogenesis of upper gastrointestinal malignancy. The observation that BMDCs are the origin of H. pylori-induced gastric cancer can also be combined with supporting observations of BMDCs in other tumors such as Barrett’s esophageal adenocarcinoma, Kaposi sarcoma, cancer-associated fibroblasts, or benign and malignant tumors of the skin. Other relative data, using the stem cell marker CD44 (the integral membrane molecule CD44 is a marker of human hematopoietic stem and progenitor cells), indicate that the CD44þ gastric cancer stem cells show the stem cell properties of selfrenewal, the ability to form differentiated progeny, and, moreover, increased resistance for chemotherapy or radiation-induced cell death; H. pylori either directly or through a local inflammatory response is responsible for increased expression of CD44 and its variant CD44 v9, thereby suggesting a possible H. pylori induction of CD44þ BMDCs/gastric cancer stem cells involved in gastric cancer development and progression. Because H. pylori also induces inflammatory changes in colonic mucosa, it would be reasonable to further speculate that chronic H. pylori infection in humans induces repopulation of the colon with BMDCs that might facilitate colon cancer development and progression. In this respect, our own preliminary studies indicated the presence of H. pylori in malignant colonic tissue in 34 of 41 (82.9%) patients with colorectal cancer (23 men, mean age 73.6 6 7.9 years). Moreover, increased expression of CD44 in malignant tissue but not in the adjacent normal colonic mucosa was noticed in 31 of 41 (75.6%) patients with colorectal cancer. Extending these preliminary data we currently included 50 patients (28 men, mean age 71.3 6 9.7 years) with colorectal cancer and 25 patients (13 men, mean age 72.8 6 10.1 years) with colonic polyps with the following results: H. pylori presence and increased expression of CD44 in malignant tissue of patients were observed in 84% and 78%, respectively, confirming our preliminary data. Comparable data in adenomatous tissue of patients with colonic polyps were also observed in 64% and 16% of patients, respectively Copyright VC 2012 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.22911 Published online inWiley Online Library (wileyonlinelibrary.com).

Helicobacter pylori might contribute to cancer and/or bone marrow-derived stem cell-related gastrointestinal oncogenesis

Helicobacter pylori might contribute to cancer and/or bone marrow-derived stem cell-related gastrointestinal oncogenesis

Helicobacter pylori and Colorectal Cancer Risk—Letter

Epplein and colleagues ([1][1]) reported that the overall Helicobacter pylori ( H. pylori ) seropositivity was not associated with colorectal cancer risk, and seropositivity to specific H. pylori proteins, particularly the toxin VacA antibodies, may be associated with a higher risk of colorectal

Impact of nitroglycerin and glucagon administration on selective common bile duct cannulation and prevention of post-ERCP pancreatitis.

Abstract Objective: Easy common bile duct (CBD) cannulation is associated with low complication rate. This study aimed to investigate the potential impact of nitroglycerin and glucagon administration on selective CBD cannulation and prevention of post-ERCP pancreatitis. Methods: A prospective single center, double–blind randomized study in which a total of 455 patients were randomly assigned to CBD cannulation by receiving 6 puffs (2.4 mg) sublingual nitroglycerin and glucagon 1 mg intravenously (n = 227, group A) or 6 puffs sterile water and 20 mg hyoscine-n-butyl bromide intravenously (n = 228, group B). After ERCP, patients were followed for the development of drugs’ side-effects and post-ERCP complications. Results: There were no statistically significant differences between the two groups regarding demographic data and ERCP findings. Success rate of selective CΒD cannulation was 95.15% in group A versus 82.29% in group B (p < .001). Time required for CBD cannulation was 2.82 ± 2.31 min in group A versus 4.27 ± 3.84 min in group B (p = .021). Needle-knife papillotomy was used in 11 (4.85%) patients of group A and 39 (17.11%) patients of group B (p = .001). The frequency of post-ERCP pancreatitis was significantly lower in group A than in group B (3.08% versus 7.46%, p = .037). No difference was observed between the two groups with regard to the occurrence of post-procedure hemorrhage. There was no procedure-related mortality; no adverse event related to the combination regimen was observed. Conclusions: Combined nitroglycerin and glucagon administration achieves a high selective CBC cannulation rates with concomitant reduction of post-ERCP pancreatitis incidence. However, further relative large-scale studies are needed to confirm our findings before definite conclusions can be drawn (Clinical trial registration number: NT: 4321).

P499 Folate regimen may reduce high homocysteine levels in a Greek cohort of patients with inflammatory bowel disease

Background: The degree of association between homocysteine metabolism and inflammatory bowel diseases (IBD) remains unknown and the association between hyperhomocysteinemia and thrombosis and oncogenesis remains controversial in IBD. The aim of this study was to investigate the serum homocysteine levels in patients with Crohn’s disease (CD) and ulcerative colitis (UC) and the potential folate therapeutic regimen against hyperhomocysteinemia. Methods: Serum levels of homocysteine were measured in 55 patients with (IBD) (28/55 CD and 31/55 UC patients). Patients with hyperhomocysteinemia received 15mg folate/day for 2 12 months. Levels of serum homocysteine were measured during folate treatment. Results: Hyperomocysteinemia was prevalent in 28/55 (50.90%) of patients studied (13 CD and 15 UC patients). Mean homocysteine levels among the patients with hyperhomocysteinemia were 17.72mmol/L with range 14.23 29.88mmol/L (normal values 3.7 13.9mmol/L) (Table 1). Folate was administered in 24/28 patients and serum levels of homocysteine were re-measured in 17 patients. In 14/17 patients lower levels of homocysteine were observed with a mean reduction of 5.25mmol/L by folate treatment. The baseline levels of homocysteine in these patients were 17.01 mmol/L and posttreatment 11.75mmol/L.