Evangelia Giartza-Taxidou

Five-year survival after Helicobacter pylori eradication in Alzheimer disease patients.

BackgroundAlzheimer disease (AD) is a progressive, fatal neurodegenerative condition. ObjectiveWe tested the hypothesis that eradication of Helicobacter pylori infection (Hp-I) could improve survival in a Greek cohort of AD patients, in a 5-year follow-up. MethodForty-six patients diagnosed with probable AD were enrolled in the analysis. Study population was classified into 3 groups: patients for whom Hp eradication treatment was successful; those for whom eradication of Hp had failed, they refused, and/or were noncompliant with eradication therapy; and those who were Hp negative at baseline. Cox proportional hazards model was built with all-cause mortality as the dichotomous outcome. ResultsDuring the 5-year follow-up [47.19±15.11 mo (range 12 to 60)], overall 21 patients died and 25 patients remained alive. Patients who died were older and exhibited lower mean MMSE score compared with the patients still alive. Successful eradication of Hp-I was associated with a significantly lower mortality risk [HR (95% CI)=0.287 (0.114-0.725), P=0.008]. The results were similar in adjusted and unadjusted models, for age and MMSE at baseline. ConclusionHp eradication regimen in AD patients is associated with a higher 5-year survival rate.

Gastrointestinal Immune System and Brain Dialogue Implicated in Neuroinflammatory and Neurodegenerative Diseases

A common characteristic of the central nervous system (CNS) neurodegenerative disorders is neuroinflammation, marked by augmented numbers of activated and primed microglia, increased inflammatory cytokines and decreased anti-inflammatory molecules. CNS neuroinflammation is a critical component in the progression of several neurodegenerative diseases which sensitize the brain to produce an exaggerated response to immune stimuli in the periphery. Neuroinflammation might initiate from the periphery and peripheral conditions through disrupted blood-brain barrier powerfully influence various brain pathologies. Gastrointestinal tract (GIT) represents a vulnerable area through which pathogens influence the brain and induce CNS neuroinflammation. The pathogens may access the CNS through blood, the nasal olfactory pathways and the GIT. Potential GI pathogens, such as Helicobacter pylori, induce humoral and cellular immune responses that, owing to the sharing of homologous epitopes (molecular mimicry), cross-react with CNS components thereby contributing and possibly perpetuating neural tissue damage. GIT is strictly connected to the CNS and a bi-directional communication exists between them. The brain is involved in regulating the immune and gut system. Conversely, limited attention has been paid on the GIT role in the development and regulation of the CNS autoimmune diseases. The GIT is the primary immune organ with specialized immunoregulatory and anti-inflammatory functions, represented by the gastrointestinal immune system (GIS). This review focuses on the potential GIS and brain dialogue implicated in neurodegenerative diseases. Gaining a better understanding of the relationship between GIS and CNS could provide an insight on the pathogenesis and therapeutic strategies of these disorders.

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].

Helicobacter pylori might contribute to nonalcoholic fatty liver disease–related cardiovascular events by releasing prothrombotic and proinflammatory factors

ur Tropenmedizin, Infektionskrankheiten und Sektion Nephrologie, Universit€atsmedizin Rostock, Rostock, Germany; Gastroenterologische Schwerpunktpraxis, Cottbus, Germany; Hepatologische Schwerpunktpraxis, Magdeburg, Germany; Klinik f€ ur Gastroenterologie und Infektiologie, E.-v.-Bergmann Klinikum, Potsdam, Germany, III. Medizinische Klinik, Krankenhaus DresdenFriedrichstadt, Dresden, Germany; Klinik f€ur Gastroenterologie und Hepatologie, Klinikum St. Georg GmbH, Leipzig, Germany, Klinik und Poliklinik f€ ur Innere Medizin I, Martin-Luther-Universit€at Halle-Wittenberg, Halle, Germany for the East German HCV Study Group.

Multiple sclerosis and seizures: possible role of Helicobacter pylori

We have read with interest the proposition by Anderson and Rodriguez [1] that an increase in interleukin (IL)-18, and its associated induction of indoleamine 2, 3-dioxygenase (IDO) and quinolinic acid, mediates seizure activity in multiple sclerosis (MS) at least partly via an increase in interferon-gamma (IFN-c), accompanied by blood–brain barrier (BBB) permeability. Recent studies showed an association between Helicobacter pylori infection (Hp-I) and epilepsy, especially with poor prognosis [2]. Moreover, using histology, the practical gold standard for current Hp-I diagnosis, we showed a strong association between Hp-I and MS in a Greek cohort [3]. In this respect, we proposed that Hp-I, by inducing pro-inflammatory cytokine production and BBB disruption [4], may lead to neuroinflammation and neuronal damage in epilepsy, thereby triggering seizures induction and epilepsy progression [5]. Specifically, a series of factors have been implicated in inducing BBB disruption, including inflammatory mediators (e.g. cytokines and chemokines induced by Hp-I) and oxidative stress [5,6]. Hp could indirectly affect the brain through the release of numerous pro-inflammatory cytokines, such as IL-1b, IL-18, IFN-c [7] mentioned by the authors, or tumor necrosis factor (TNF)-a acting at a distance. TNF-a may contribute to BBB disruption and pathogenesis of neuronal inflammatory damage in neurodegenerative diseases and epilepsy; IL-1b, IL-6, and TNF-a influence the pathogenesis of seizures and course of epilepsy, and the primary BBB lesion is involved in seizures induction/epileptogenesis [8]. Likewise, an influx of Hp-infected monocytes, owing to defective autophagy resulting in Hp replication in autophagic vesicles, through the disrupted BBB might lead to brain degeneration and epilepsy development partially by potential activation of natural killer cells and IFN-c production, detrimental for MS; Hp VacA cytotoxin promotes intracellular survival of the bacterium and modulates host immune responses. Of note, Hp is known to be associated with the increase in IDOdependent mechanisms. Viewing the aforementioned data and because half of the world s population is infected withHp, it would be interesting to know whether the authors have considered Hp-I as a potential confounder involved in the pathophysiology of MS-associated increased seizure activity and therefore its management.

Relationship between Helicobacter pylori infection and autoimmune disorders.

* Corresponding author: Jannis Kountouras , MD, PhD, Professor of Medicine, Department of Gastroenterology, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, 8 Fanariou St, Byzantio, 551 33 Thessaloniki, Greece, Phone: + 3

Multiple sclerosis, idiopathic dilated cardiomyopathy, and insulin-dependent diabetes mellitus: a common mechanism of irregular immune regulation.

BackgroundMultiple sclerosis (MS), idiopathic dilated cardiomyopathy (DCM), and diabetes mellitus-1 (DM-1) are polygenic autoimmune diseases with a pivotal autoimmune component affecting young adults. They share a number of characteristics, thereby suggesting common underlying pathways or mechanisms. Typically, the aforementioned diseases are organ-specific autoimmune disorders of unknown etiology, but with strong evidence of tissue-destructive activity of the humoral and/or cellular immune system in the end-organ tissues affected (ie, the myelin components in MS, the myocytes of myocardium in DCM, and the insulin-secreting &bgr; islets in DM-1). Case ReportWe herein describe a 35-year-old white Greek man who presented with coexisting MS, DCM, and DM-1 diagnosed over a period of 7 years. The patient was successfully treated and is asymptomatic until present time. ConclusionThe clustering of these 3 autoimmune diseases in our patient supports the concept of an immune-mediated damage in these diseases, an important aspect for an effective therapeutic choice by neurologists. However, the immunopathogenetic association between MS and other autoimmune remains speculative, thereby warranting further clarification.

The emerging role of helicobacter pylori-induced metabolic gastrointestinal dysmotility and neurodegeneration.

Helicobacter pylori infection (Hp-I) is a prevalent disorder identified in the majority of the population in many countries around the world and is responsible for substantial gastrointestinal morbidity. Likewise, neurodegenerative diseases such as Alzheimers disease, Parkinsons diseases, multiple sclerosis or glaucoma defined as ocular Alzheimers disease, are associated with a large public health burden and are among the leading causes of disability. Emerging evidences suggest that Hp-I may be associated with neurodegenerative conditions. Moreover, Hp-I could be a predictor of metabolic syndrome (MetS). Hp-I and its related MetS may induce gastrointestinal tract dys-motility disorders with systemic complications possibly including central nervous system neurodegenerative pathologies. We hereby explore the emerging role of Hprelated metabolic gastrointestinal dys-motilities on the molecular pathophysiology of Hprelated neurodegenerative and gastrointestinal disorders. Improving understanding of such Hp-I pathophysiology in brain pathologies may offer benefits by application of new relative therapeutic strategies including novel opportunities toward enhancing Hp eradication.