Christos Stergiopoulos

Association between Helicobacter pylori infection and mild cognitive impairment

The association of Helicobacter pylori infection and Alzheimers disease (AD) has recently been addressed, but no relative data exist regarding mild cognitive impairment (MCI), a prodromal phase of AD. The aim of this prospective study was to evaluate H. pylori infection, by histology in a Greek MCI cohort. Sixty‐three consecutive patients with amnestic MCI and 35 normal controls underwent upper gastrointestinal endoscopy, histologic and serological examinations. The prevalence of H. pylori infection was 88.9% (56/63) in MCI patients and 48.6% (17/35) in anaemic controls, as confirmed by biopsy (P < 0.001, odds ratio: 8.47, 95% CI: 3.03–23.67). Mean serum anti‐H. pylori IgG concentration and plasma total homocysteine (Hcy) titre were higher in MCI patients than controls (74.86 ± 57.22 vs. 17.37 ± 9.30 U/ml; and 16.03 ± 4.28 vs. 13.5 ± 1.20 μmol/l; P < 0.001 and P = 0.015, respectively). When compared with the anaemic participants, MCI patients exhibited more often multifocal (body and antral) gastritis (92.1% vs. 68.6%; P = 0.03); in H. pylori positive MCI patients cognitive state correlated with serum anti‐H. pylori IgG concentration. In conclusion, H. pylori prevalence was significantly higher in MCI patients than controls. This infection might contribute, at least in part, to the pathophysiology of MCI, possibly through induction of chronic atrophic gastritis and elevated Hcy consequences.

Helicobacter pylori infection and Parkinson's disease: apoptosis as an underlying common contributor.

Nielsen et al. [1] state that Helicobacter pylori infection (Hp-I) may play an important role in the pathogenesis of Parkinson s disease (PD) by triggering microglia activation through the humeral or vagal afferent pathways. In this regard, apoptotic rather than necrotic microglia-associated nerve cell death appears to underlie a number of common neurological conditions including PD, Alzheimer s disease (AD), glaucoma or multiple sclerosis [2]. The latter diseases are also associated with Hp-I [2–4]; likewise, an association of glaucoma with neurodegenerative diseases (PD and AD) via apoptotic cell death has been reported. Hp, apart from Fas–FasL apoptotic pathway [2], is capable of inducing apoptotic effects through the mitochondrial apoptotic pathway involving the activation of the pro-apoptotic proteins Bax and Bak, activation of certain caspases, or through inducible nitric oxide (NO);NO is a rapidly diffusing gas and a potent neurotoxin that may contribute to apoptotic neuronal cell death in degenerative neuropathies [4], including PD. In particular, increased endothelin-1 (a potent constrictor of arterioles and venules), NO and inducible nitric oxide synthase (iNOS) levels are associated with Hp-I [2]. Relative data in AD indicate that endothelin-1-like immunoreactivity in the AD brains is significantly more increased in frontal and occipital cortex than that in the control brains, thereby explaining the decreased cerebral blood flow in patients with AD. Besides, the synthesis of NO, the peroxynitrite reactive production and the protein tyrosine nitration are activated over the entire chronic course of AD, and the presence of Abeta increases the presence of neuronal NOS and iNOS isoforms over the chronic course of AD in pyramidal-like neurons [2]; NO contributes to mitochondrial fragmentation via S-nitrosylation of dynamin-related protein 1, a protein involved in mitochondrial fission. These findings might provide a new target for drug development in AD.Moreover, redox reactions triggered by excessive levels of NO can contribute to protein misfolding, the hallmark of a number of neurodegenerative disorders, including PD andAD [5]. Finally, apart from humeral and vagal afferent pathways, mentioned by the authors [1], Hp might access brain via oral-nasal-olfactory pathway or by circulating monocytes (possibly infected with Hp owing to defective autophagy) through disrupted blood–brain barrier, leading to neurodegeneration [3].

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 …

Distant cutaneous metastasis preceding the diagnosis of ductal cholangiocarcinoma

© 2008 The Authors JEADV 2009, 23, 169–243 Journal compilation

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.

Obstructive Sleep Apnea and Environmental Contributors for Barrett's Esophagus

Dear Editor:Leggett et al1 concluded that obstructive sleep apnea (OSA) is associated with an increased risk for Barretts esophagus (BE) via body mass index (BMI) and gastroesophageal reflux disease (GERD)–independent mechanisms. The authors1 considered that increased levels of inflammatory cyt

Eradication of Helicobacter pylori infection might have a positive impact on subpopulations with endoscopic gastro-oesophageal reflux disease.

However, this conclusion might represent only one side of the coin; in a large retrospective cohort study of 20 918 Chinese individuals, Wu et al. [2] concluded that the Hp-I decline within a 7-year period coincides with the substantial drop in duodenal ulcer and the increase in GORD incidence; however, GORD is rarely triggered after Hp eradication. Moreover, although Hp eradication may lead to more resilient GORD in a subset of patients, the Hp eradication benefits outweigh the risks, especially in Asian populations with a high incidence of gastric cancer [3]. In this regard, our data show that Hp-I is frequent in Greek endoscopic GORD patients and its eradication leads to better control of GORD symptoms and improves oesophagitis [4,5]; consistent associations were shown by others [4], as also reported by the authors [1]. Remarkably, ex-supporters of the theory that Hp ‘protects’ against GORD relented their initial findings, claiming that Hp eradication does not cause or protect against GORD, thereby recommending Hp eradication in GORD [4]. In addition, although epidemiological studies do not suggest any causality with Hp, these studies support our and others’ findings; for instance, apart from the data of Wu et al. [2], contrary to expectation, patients hospitalized with duodenal ulcers (61 548 patients), obviously attributed to Hp-I, had a significant 70% excess risk of oesophageal adenocarcinoma [4]. Sufficient evidence further potentiates the concern that Hp is not ‘protective’ against GORD [4]. Hp could contribute to GORD pathogenesis through several mechanisms including release of several mediators (cytokines-prostaglandins-nitric oxide-gastrin-induced increased acidity) or direct damage of oesophageal mucosa by Hp products [5].

Ki-67 and Bax expression in esophageal mucosa might have implications in ablative therapies for Barrett’s esophagus, dysplasia, and adenocarcinoma

Dear Editor, We read with considerable interest the paper by Lewis et al. [1], who concluded that the buried glandular tissue of postablation patients with Barrett’s esophagus (BE), and mainly with esophageal high-grade dysplasia (HGD) and esophageal adenocarcinoma (EA), still exhibits a higher superficial or deep expression of the oncogene Ki-67 than normal esophageal epithelium, thereby having potential implications for the follow-up management of these patients, because it is unclear whether the true risk of neoplastic progression is adequately reduced. Although the authors measured preand postablation levels of cyclo-oxygenase (COX)-2 (indicating increased neoplastic potential in BE), Ki-67 (indicating cellular proliferation), and Bcl-2 protein (indicating resistance to apoptosis), they did not measure a simultaneous prEApoptotic oncoprotein, such as Bax, which opposes the effects of Bcl-2 and Ki-67 oncogenes, possibly associated more robustly with BE–HGD–EA sequence, and thus having a greater impact on the follow-up management of these patients. In this regard, BE-associated EA is now the most common esophageal malignancy in Western countries; in the United States and England, the incidence is increasing faster than any other cancer [2]. EA demonstrates extremely rapid progression [3], and the mortality rates from esophageal cancer per 100,000 person-years are approximately 8 in the United States, 13 in Japan, 17 in France, and 36 in rural China. On the other hand, mortality from esophageal cancer in Greece is among the lowest in the world (3.5 per 100,000 person-years; WHO 1995). It has been argued that populations with unusually low disease rates can provide valuable insights into the etiologic processes [4]. Previous studies have attempted to identify risk factors in dietary, lifestyle, and medical conditions of the Greek population. Although some inverse association was found between EA and vegetables and fruits consumed in large quantities, no clear-cut answer has emerged as to why the incidence of EA is so low in Greece [5]. Therefore, we tried to provide an explanation for the low incidence of EA in Greece through molecular-based ethnic differentiations. The role of oncogene Ki-67, promoting cell proliferation and oncogenesis, and the Bcl-2 and Bax proteins, important regulators of programmed cell death (apoptosis), was investigated in a Greek cohort of BE patients and gastroesophageal reflux disease (GERD) controls [6]. GERD is well-recognized, premalignant condition that has a pivotal role in BE–HGD–EA sequence [7, 8]. Specifically, of 270 patients who underwent upper gastrointestinal endoscopic and histologic evaluation due to GERD symptoms, 31 patients with BE (typical salmon-pink lesions) and 21 GERD controls were ultimately included in the study. Esophageal mucosa biopsy specimens also were evaluated immunohistochemically for Ki-67, Bax, and Bcl-2 expressions. Increased expression of Ki-67 was observed in BE patients compared with GERD controls (P = 0.01). Increased expression of Bax was noticed in the total BE patients compared with GERD controls (P \ 0.001). Bcl-2 expression did not differ between the two groups. J. Kountouras D. Chatzopoulos C. Zavos G. Deretzi S. A. Polyzos E. Gavalas P. Klonizakis E. Vardaka P. Katsinelos C. Stergiopoulos J. Moschos E. Giartza-Taxidou Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece

Comment on “Therapeutic Application of an Extract of Helicobacter pylori Ameliorates the Development of Allergic Airway Disease”

A recent study by van Wijck et al. ([1][1]) concluded that experimental application of Helicobacter pylori extract after sensitization effectively inhibits allergic airway disease, thereby extending the previously published prophylactic application to prophylactic and therapeutic applications in

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.