Papers by Elisabeth Vardaka

Helicobacter, 2007
Some studies suggest that Helicobacter pylori (H. pylori) infection would be a protective factor ... more Some studies suggest that Helicobacter pylori (H. pylori) infection would be a protective factor for the gastroesophageal reflux. The aim of this study was to explore this fact. A group of 72 children, admitted in a pediatric gastroenterology regional center in Northeast Romania, diagnosed with gastroesophageal reflux by 24-hour continuous esophageal pH monitoring (results were interpreted using the Boix-Ochoa score), underwent upper endoscopy with gastric biopsy to detect the presence of H. pylori by the rapid urease testing and for bacteriological and histologic examination. 19 children (26.39%) had H. pylori infection, while 53 (73.61%) did not. The grade of esophagitis was classified according to the Los Angeles classification system. Out of 47 children with esophagitis A, 16 (34.04%) had H. pylori infection, while out of the 25 children with esophagitis B, only 3 (12%) had H. pylori infection, with statistic significance (χ 2 = 54.69, P << 0.05, 95% confidence interval [CI]). Regarding the value of the Boix-Ochoa score, it appears that the presence of the H. pylori determines lower pH-metry scores (F = 8.13, P = 0.0015, 95% CI). The presence of the H. pylori was not an important factor in the gastroesophageal reflux. On the other hand its relationship with esophagitis appears to be inverse ratio. The fact that the H. pylori presence is statistically greater in the grade A esophagitis could confirm the hypothesis that the bacteria would slow down the development of the esophagitis.

Microorganisms, Apr 30, 2023
Cyanobacterial biomass such as spirulina (Arthrospira spp.) is widely available as a food supplem... more Cyanobacterial biomass such as spirulina (Arthrospira spp.) is widely available as a food supplement and can also be added to foods as a nutritionally beneficial ingredient. Spirulina is often produced in open ponds, which are vulnerable to contamination by various microorganisms, including some toxin-producing cyanobacteria. This study examined the microbial population of commercially available spirulina products including for the presence of cyanobacterial toxins. Five products (two supplements, three foods) were examined. The microbial populations were determined by culture methods, followed by identification of isolates using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF), and by 16S rRNA amplicon sequencing of the products themselves and of the total growth on the enumeration plates. Toxin analysis was carried out by enzyme-linked immunosorbent assay (ELISA). Several potentially pathogenic bacteria were detected in the products, including Bacillus cereus and Klebsiella pneumoniae. Microcystin toxins were detected in all the products at levels that could lead to consumers exceeding their recommended daily limits. Substantial differences were observed in the identifications obtained using amplicon sequencing and MALDI-TOF, particularly between closely related Bacillus spp. The study showed that there are microbiological safety issues associated with commercial spirulina products that should be addressed, and these are most likely associated with the normal means of production in open ponds.

Heart, Feb 9, 2022
To the Editor, In their review and metaanalysis, Rizos et al reported that omega3 supplementation... more To the Editor, In their review and metaanalysis, Rizos et al reported that omega3 supplementation at low and higher dosages showed no or weak associations with cardiovascular disease (CVD) outcomes, respectively. More recent reviews also showed protective activity of omega3 against CVD outcomes. For instance, omega3 (2–4 g/day) in patients with high or very high triglyceride (TG) levels decreases significantly highsensitivity C reactive protein (hsCRP), lipoproteinassociated phospholipase A2 (LpPLA2), and oxidised low density lipoprotein (LDL)cholesterol (oxLDL) levels, and the reduction of hsCRP is enhanced when coadministered with a statin; hsCRP, LpPLA2 and oxLDL levels are associated with the risk of the major CVD events; and longterm omega3 administration (over a median of 4.9 years) significantly decreases acute myocardial infraction (AMI), coronary revascularisation, unstable angina, cardiovascular death or stroke. Omega3 fatty acids exhibit a beneficial effect on CVD via reprogramming of TGrich lipoproteins metabolism, decreasing inflammatory mediators (cytokines and leukotrienes), and modulating cell adhesion molecules. Beyond CVD, metabolic syndrome (MetS) and Helicobacter pylori infection (Hp-I) are also significant healthcare burdens globally. Both disorders increase the risk of cardiocerebrovascular events, the end point of MetS, and omega3 fatty acids are beneficial against these disorders; omega3 supplements have favourable effects on MetSrelated parameters and inhibitory effects on Hp growth. In this regard, there is an association between HpI and MetSrelated morbidity, including cardiocerebrovascular events; MetS prevalence is higher in Hppositive patients; AMI is closely linked with MetS and Hp-I; HpI is an independent risk factor for atrial fibrillation (AF), which remains frequent arrhythmia in AMI and is closely linked with augmented subsequent cardiocerebrovascular mortality; Hprelated metabolic dysfunctionassociated fatty liver disease, the hepatic component of MetS, is a risk of AF; Hprelated galectin3 and MetS are implicated, as mediators, in the failure of heart and brain; and HpIrelated MetS might contribute to CVD pathophysiology by several mechanisms. Likewise, omega3 and, based on recent data, even omega6 supplements may reduce both atherosclerotic CVD and cancer mortality including HpIrelated MetS gastrointestinal malignancies. Therefore, eradication therapy and improvement of Hprelated MetS parameters mainly by omega3 supplements might benefit cardiocerebrovascular events and even prevention of certain cancers and thus further studies are warranted.

Journal of Gastroenterology and Hepatology, Dec 10, 2021
c 2021 The Korean Society of Neurogastroenterology and Motility J Neurogastroenterol Motil, Vol. ... more c 2021 The Korean Society of Neurogastroenterology and Motility J Neurogastroenterol Motil, Vol. 27 No. 1 January, 2021 www.jnmjournal.org TO THE EDITOR: In their recent study, Eisa et al concluded that gastroesophageal reflux disease (GERD) with concomitant metabolic syndrome (MetS) parameters is a risk factor of acute myocardial infarction (AMI) though this risk may be clinically insignificant. In this regard, there is increasing evidence for association between Helicobacter pylori infection (Hp-I) and insulin resistance (IR) or MetS and related morbidity, including GERD and cardiovascular disease (CVD); the prevalence of MetS is higher in Hppositive people; Hp-linked MetS is a risk factor of GERD and its eradication exhibits a positive effect against GERD in certain populations; AMI, a potentially fatal CVD complication, is closely linked with MetS; and Hp is a risk for acute coronary syndrome (ACS) including AMI, thus further investigation is warranted to estimate whether Hp eradication affects AMI occurrence. Specifically, both Hp-I and MetS are highly prevalent worldwide and epidemiological studies as well as meta-analyses have shown that obesity induces inflammation (especially abdominal, visceral obesity) and drives to MetS, thereby being an indirect risk factor for GERD. In this respect, the conventional claim that declining Hp prevalence has led to a rise in GERD requires to be better studied since, for instance, the current global prevalence of Hp-I varies from 39.9% to 84.2% whereas the comparable picture for GERD is quite less varying from 2.5% to 51.2%. Moreover, several data indicate that Hp may contribute to GERD pathogenesis by several mechanisms and its eradication results in adequate control of GERD symptoms and improves esophagitis. A recent meta-analysis also indicated that Hp-I increases the risk of CVD adverse events, particularly AMI; there is a link between Hp-related CagA cytotoxin and ACS and the odds ratio of AMI is twice as greater in Hp-positive patients. Likewise, MetS is a major risk factor for AMI, increases the risk of CVD adverse events more than 2-fold, whereas its recovery significantly decreases the risk for major adverse cardiovascular events including AMI. Moreover, Hp-I is an independent risk factor for atrial fibrillation (AF), which remains a frequent arrhythmia in AMI and is closely linked with augmented subsequent cardiovascular mortality; coronary artery disease is a risk factor for AF and coronary embolism due to AF is a cause of AMI; and Hp-related non-alcoholic fatty liver disease, the hepatic component of MetS, is a risk of AF. Finally, Hp-I–related MetS may contribute to the pathophysiology of CVD including AMI by several mechanisms, thereby signifying eradication therapy as AMI prevention strategy.
Journal of Viral Hepatitis, May 3, 2023
Alimentary Pharmacology & Therapeutics, Apr 1, 2014

PubMed, May 5, 2023
Nonalcoholic fatty liver disease (NAFLD), recently renamed as metabolic (dysfunction)-associated ... more Nonalcoholic fatty liver disease (NAFLD), recently renamed as metabolic (dysfunction)-associated fatty liver disease (MAFLD), is a complex, multifactorial disease that progresses via nonalcoholic steatohepatitis (NASH) towards severe liver complications. MAFLD/NAFLD affects up to a third of the global population. It is connected with metabolic syndrome parameters and has been increasing in parallel with the rates of metabolic syndrome parameters worldwide. This disease entity exhibits a strong immune-inflammatory dimension. In MAFLD/NAFLD/NASH, a vast network of innate immune cells is mobilized that can provoke liver damage, leading to advanced fibrosis, cirrhosis and its complications, including hepatocellular carcinoma. However, our understanding of the inflammatory signals that drive the onset and progression of MAFLD/NAFLD/NASH is fragmented. Thus, further investigation is required to better understand the role of specific innate immune cell subsets in the disease, and to aid the design of innovative therapeutic agents to target MAFLD/NAFLD/NASH. In this review, we discuss current concepts regarding the role of innate immune system involvement in MAFLD/NAFLD/NASH onset and progression, along with presenting potential stress signals affecting immune tolerance that may trigger aberrant immune responses. A comprehensive understanding of the innate immune mechanisms involved in MAFLD/NAFLD/NASH pathophysiology will help the discovery of early interventions to prevent the disease, and lead to potential innovative therapeutic strategies that may limit its worldwide burden.

PubMed, Dec 1, 2012
To the Editor, Fleming et al. (1), by reviewing the pathologic aspects of colorectal neoplasms, s... more To the Editor, Fleming et al. (1), by reviewing the pathologic aspects of colorectal neoplasms, summarized the pathogenesis and molecular classification of colorectal carcinoma (CRC) including mainly molecular pathways and environmental factors. However, they did not mention the potential pathologic aspects of environmental factors involved in colorectal oncogenesis, particularly in sporadic CRC. More than 95% of colorectal cancers are sporadic, also mentioned by the authors (1), without a significant hereditary risk. Geographic variation in the incidence of CRC is substantial with a higher incidence observed in the West. Environmental factors contribute considerably to this variation (2); the majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Dietary factors may influence the oncogenic process by modifying intestinal transit time, altering the flow and recycling of bile, or changing the intestinal bacterial flora composition. Numerous studies support a role for the gut microbiota in colorectal oncogenesis and the colonic microbiota drives the progression towards colorectal malignancy including generation of reactive metabolites and carcinogens, alterations in host carbohydrate expression and induction of chronic mucosal inflammation (3); long-term colonization of the colon by rogue commensal bacteria capable of inducing chronic DNA damage could contribute to sporadic CRC developement, thereby suggesting sporadic CRC as an infectious disease (4). In this regard, Helicobacter pylori (Hp), a curved spiral gram-negative bacterium found in the gastric mucosa of a large proportion of humans worldwide (>50%), has been evaluated as a possible etiologic agent for CRC and recent data indicate that there is a serological association between Hp infection (Hp-I) and the risk of CRC, especially for left-sided and early-stage cancers (5). Moreover, Hp seropositive subjects are associated with a modest increase in the risk for colorectal adenoma, and since Hp-I can increase the risk especially of advanced adenomas, the medical community should take into account that a preventive strategy is needed, and, furthermore, elucidating the pathophysiological role of Hp in the development of CRC is highly warranted (6). However, as mentioned by the authors (5,6), the serologic measurement of infection status is less than perfect, thereby representing a specific limitation of their studies. Indeed, the serological test does not discriminate between current and past infections and, apart from past infection that may even be more relevant for oncogenesis, such a distinction is essential because only current Hp-I induces humoral and cellular immune responses that produce or perpetuate chronic inflammatory processes in gastrointestinal tract with potential oncogenic sequelae; many neoplasms including colorectal adenomas and cancers arise at the sites of chronic inflammation and infection (7-10). Based on histology, the practical gold standard for Hp-I diagnosis, our own preliminary studies indicated Hp presence in malignant tissue in 34 of 41 (82.9%) patients with CRC (23 men, mean age 73.6±7.9 years) (11). Extending these preliminary data we currently included 50 patients (28 men, mean age 71.3±9.7 years) with CRC and 25 patients (13 men, mean age 72.8±10.1 years) with colonic polyps with the following results: Hp presence in malignant and polyp tissues of patients were observed in 84% and 64%, respectively, confirming our preliminary data (12). It is important to note that, apart from Cresyl fast violet staining mainly used to detect Hp, its presence was also documented by immunohistochemical method (using polyclonal rabbit anti-Hp antibody (dilution 1:50, DAKO, Athens, Greece) in adenoma and malignant colonic tissues. Specifically, in accordance with Hong et al. (6), Hp progressive increased presence was observed in our patients with adenomas associated with mild (50%) and moderate/high-grade (80%) dysplasia; the latter lesions are frequently described as advanced adenomas. However, contrary to the authors’ considerations (6), our series showed an increased Hp presence in left-sided (79%) than in the proximal colon (21%) adenomas; left-sided cancers were also observed in 70.7% of our patients, a finding also noticed by Zhang et al. (5), thereby suggesting that Hp-I might be associated with a rather relevant risk increase in the left CRC. The multistep model of gastric cancer postulates that there is initially an inflammation, caused mainly by Hp-I, which can lead to the development of chronic active gastritis. In a subset of these patients, this inflammatory process leads to the development of atrophic gastritis, followed by intestinal metaplasia, dysplasia, and, ultimately, early and advanced gastric cancer (13). It is considered that all stages prior to the development of high-grade dysplasia are potentially reversible, although this is still…

Annals of the New York Academy of Sciences, Jul 16, 2019
Gastroesophageal reflux disease (GERD) and the increasing rate of its associated complications, i... more Gastroesophageal reflux disease (GERD) and the increasing rate of its associated complications, including esophageal adenocarcinoma (EAC), has stimulated a plethora of studies attempting to evaluate provocative and protective factors. Helicobacter pylori (Hp) infection (Hp-I) was initially considered as a beneficial condition in GERD management based on rather limited data. Large-scale regional studies revealed an alternative approach, by suggesting a positive relationship between Hp-I and EAC development. Regarding pathophysiology, Hp-I induces gastric microbiota disturbances through hypochlorhydria and chronic inflammation, with a subsequent possible effect on the GERD−Barrett's esophagus (BE)−EAC cascade. Additionally, both direct effects on esophageal mucosa and indirect effects on known mechanisms of GERD, such as acid pocket and transient lower esophageal sphincter relaxation, remain to be elucidated. Hp contribution to carcinogenesis is related to oncogenic gastrin, cyclooxygenase-2, and prostaglandins; Ki-67 is also expressed and represents an index of BE-related malignancy. Moreover, Hp-I is vigorously suggested as a risk factor for metabolic syndrome, which may be the link between Hp-I and EAC. Although further studies are necessary to establish a pathophysiologic risk between Hp-I and the GERD−BE−EAC sequence, the theory of Hp protection against GERD seems outdated.
European Journal of Gastroenterology & Hepatology, Jul 1, 2016

Gastrointestinal Endoscopy, Dec 1, 2022
Neurodegeneration represents a component of the central nervous system (CNS) diseases pathogenesi... more Neurodegeneration represents a component of the central nervous system (CNS) diseases pathogenesis, either as a disability primary source in the frame of prototype neurodegenerative disorders, or as a secondary effect, following inflammation, hypoxia or neurotoxicity. Galectins are members of the lectin superfamily, a group of endogenous glycan-binding proteins, able to interact with glycosylated receptors expressed by several immune cell types. Glycan-lectin interactions play critical roles in the living systems by involving and mediating a variety of biologically important normal and pathological processes, including cell-cell signaling shaping cell communication, proliferation and migration, immune responses and fertilization, host-pathogen interactions and diseases such as neurodegenerative disorders and tumors. This review focuses in the role of Galectin-3 in shaping responses of the immune system against microbial agents, and concretely, Helicobacter pylori (Hp), thereby potentiating effect of the microbe in areas distant from the ordinary site of colonization, like the CNS. We hereby postulate that gastrointestinal Hp alterations in terms of immune cell functional phenotype, cytokine and chemokine secretion, may trigger systemic responses, thereby conferring implications for remote processes susceptible in immunity disequilibrium, namely, the CNS inflammation and/or neurodegeneration.
The American Journal of Gastroenterology, Nov 1, 2018

Marine and Freshwater Research, 2020
Cyanobacteria are an essential biological component of phytoplankton water quality assessment. Ho... more Cyanobacteria are an essential biological component of phytoplankton water quality assessment. However, there are some problems associated with the widely used everyday practices of sampling, estimation and use of cyanobacteria when calculating phytoplankton indices assessing water quality. Many indices were developed during the implementation of the Water Framework Directive, considered the most innovative European environmental legislation. Most indices include cyanobacteria as a composition or bloom metric. Problems with the indices concern the exclusion of most chroococcalean taxa from cyanobacterial biovolume estimations in lakes and reservoirs of the Mediterranean region, treatment of the mucilage of colonial chroococcalean taxa in biovolume estimations and overlooking of deep-water cyanobacterial blooms due to sampling depth. These problems may lead to a biased view of water quality. In this paper we argue in favour of including all cyanobacteria taxa and their mucilage in biovolume estimations and considering a sampling depth that covers deep-water maxima, such as those formed by Planktothrix rubescens or colonial chroococcalean taxa.

Current Molecular Medicine, Feb 7, 2018
Helicobacter pylori infection (Hp-I) is a prevalent disorder identified in the majority of the po... more 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 Alzheimer's disease, Parkinson's diseases, multiple sclerosis or glaucoma defined as ocular Alzheimer's 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.

Alzheimers & Dementia, Mar 11, 2019
Beydoun et al. [1], investigated in a large national retrospective cohort study the association o... more Beydoun et al. [1], investigated in a large national retrospective cohort study the association of Helicobacter pylori (Hp) seropositivity with an incidence of all-cause and Alzheimer’s disease (AD) dementia and with AD dementia mortality. Data were extracted from the National Health and Nutrition Surveys III, phase 1 (1988–1991), and 1999–2000 and were linked with Medicare and National Death Index registries. Surveys followed a stratified, multistage probability cluster sampling design and included in-home basic health as well as demographic interviews followed by in-depth health examinations in a mobile examination center. With respect to pooled sample population (N 5 5927 adults), 45 years of age was set as the baseline limit, men consisted of 45.8% of participants and race composed primarily of non-Hispanic whites (80.9%) as well as non-Hispanic blacks (8.6%) andMexican Americans (3.4%). There was a follow-up to 2013 and main exposure was Hp seropositivity. As covariates were regarded, wave of survey (1988–1991 vs. 1999–2000), age, gender, raceethnicity, educational level, poverty income ratio, current smoking status, and measured body mass index. The authors concluded that Hp seropositivity is directly associated with incidence of all-cause and AD dementia and with AD mortality. This main outcome was restricted, albeit, only to men. Sex along with socioeconomic status was considered to be the main effect modifiers. It is noteworthy to emphasize that the authors performed also multiple adjustments including components of metabolic syndrome (MetS) (smoking status, weight status, measured hypertension, hyperglycemia, dyslipidemia–high-density lipoprotein, and dyslipidemia-triacylglycerol). The association between Hp-I and incident AD in particular was independent of MetS among men and higher socioeconomic status [1]. Future intervention studies, by using histology, should examine the impact of Hp infection (Hp-I) and its eradication on various cognitive disorders [1].
Cellular and Molecular Life Sciences, Apr 20, 2019
Alimentary Pharmacology & Therapeutics, Mar 18, 2013
Digestive Diseases and Sciences, Aug 5, 2022
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Papers by Elisabeth Vardaka