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Overlap of functional heartburn and gastroesophageal reflux disease with irritable bowel syndrome

World Journal of Gastroenterology 2013年第35期19卷 5787-5797页

作者： Nicola de Bortoli irene martinucci Massimo Bellini Edoardo Savarino Vincenzo Savarino Corrado Blandizzi Santino Marchi Division of Gastroenterology University of Pisa Division of Gastroenterology University of Padua Division of Gastroenterology University of Genoa Division of Pharmacology and Chemotherapy University of Pisa

Several studies indicate a significant degree of overlap between irritable bowel syndrome(IBS)and gastroesophageal reflux disease(GERD).Likewise,both functional heartburn(FH)and IBS are functional digestive disorders that may occur in the same ***,data establishing a solid link between FH and IBS are lacking,mainly because the clinical definition of FH has undergone substantial changes over the *** available literature on the overlap between GERD or FH and IBS highlights considerable heterogeneity in terms of the criteria and diagnostic procedures used to assess heartburn and *** particular,several epidemiological studies included patients with concomitant IBS and GERD without any attempt to distinguish FH(as defined by the RomeⅢcriteria)from GERD via pathophysiological *** of these critical issues,there is preliminary evidence supporting a significantdegree of FH-IBS *** underscores the need for studies based on updated diagnostic criteria and accurate pathophysiological classifications,particularly to distinguish FH from *** distinction would represent an essential starting point to achieving a better understanding of pathophysiology in the subclasses of patients with GERD and FH and properly assessing the different degrees of overlap between IBS and the subcategories of *** present review article intends to appraise and critically discuss current evidence supporting a possible concomitance of GERD or FH with IBS in the same patients and to highlight the pathophysiological relationships between these disorders.

关键词： Functional gastrointestinal disorders Gastroesophageal reflux disease/Gastro-oesophageal reflux disease Irritable bowel syndrome Acidity(esophageal) Hypersensitivity

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Alginate controls heartburn in patients with erosive and nonerosive reflux disease

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World Journal of Gastroenterology 2012年第32期18卷 4371-4378页

作者： Edoardo Savarino Nicola de Bortoli Patrizia Zentilin irene martinucci Luca Bruzzone Manuele Furnari Santino Marchi Vincenzo Savarino Division of Gastroenterology Department of Internal MedicineUniversity of Genoa16126 GenoaItaly Division of Gastroenterology Department of SurgicalOncological and Gastroenterological SciencesUniversity of Padua35128 PaduaItaly Division of Gastroenterology Department of Internal MedicineUniversity of Pisa56100 PisaItaly

AIM:To evaluate the effect of a novel alginate-based compound,Faringel,in modifying reflux characteristics and controlling ***:In this prospective,open-label study,40 patients reporting heartburn and regurgitation with proven reflux disease(i.e.,positive impedance-pH test/evidence of erosive esophagitis at upper endoscopy) underwent 2 h impedance-pH testing after eating a refluxogenic *** were studied for 1 h under basal conditions and 1 h after taking 10 mL *** both sessions,measurements were obtained in right lateral and supine decubitus *** also completed a validated questionnaire consisting of a 2-item 5-point(0-4) Likert scale and a 10-cm visual analogue scale(VAS) in order to evaluate the efficacy of Faringel in symptom *** of the treatment was assessed using a 6-point Likert scale ranging from very good(1) to very poor(6).RESULTS:Faringel decreased significantly(P < 0.001),in both the right lateral and supine decubitus positions,esophageal acid exposure time [median 10(25th75th percentil 6-16) vs 5.8(4-10) and 16(11-19) vs 7.5(5-11),respectively] and acid refluxes [5(3-8) vs 1(1-1) and 6(4-8) vs 2(1-2),respectively],but increased significantly(P < 0.01) the number of nonacid reflux events compared with baseline [2(1-3)vs 3(2-5) and 3(2-4) vs 6(3-8),respectively].Percentage of proximal migration decreased in both decubitus positions(60% vs 32% and 64% vs 35%,respectively;P < 0.001).Faringel was significantly effective in controlling heartburn,based on both the Likert scale [3.1(range 1-4) vs 0.9(0-2);P < 0.001] and VAS score [7.1(3-9.8) vs 2(0.1-4.8);P < 0.001],but it had less success against regurgitation,based on both the Likert scale [2.6(1-4) vs 2.2(1-4);P = not significant(NS)] and VAS score [5.6(2-9.6) vs 3.9(1-8.8);P = NS].Overall,the tolerability of Faringel was very good 5(2-6),with only two patients reporting modest adverse events(i.e.,nausea and bloating).CONCLUSION:Our findings demonstrate t

关键词： Impedance pH-metry Nonerosive reflux disease Erosive esophagitis Nonacid reflux Proximal reflux

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Esophageal motility abnormalities in gastroesophageal reflux disease

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2014年第2期5卷 86-96页

作者： irene martinucci Nicola de Bortoli Maria Giacchino Giorgia Bodini Elisa Marabotto Santino Marchi Vincenzo Savarino Edoardo Savarino Division of Gastroenterology University of Pisa56124 PisaItaly Division of Gastroenterology Department of Internal MedicineUniversity of Genoa16132GenoaItaly Division of Gastroenterology Department of SurgeryOncology and GastroenterologyUniversity of Padua35128 PaduaItaly

Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophagealmotility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from nonerosive reflux disease to erosive reflux disease and Barrett's esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted.

关键词： Gastroesophageal reflux disease High-resolution manometry Ineffective esophageal motility Esophagogastric junction Transient lower esophageal sphincter relaxations

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Barrett's esophagus in 2016: From pathophysiology to treatment

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2016年第2期7卷 190-206页

作者： irene martinucci Nicola de Bortoli Salvatore Russo Lorenzo Bertani Manuele Furnari Anna Mokrowiecka Ewa Malecka-Panas Vincenzo Savarino Edoardo Savarino Santino Marchi Division of Gastroenterology University of Pisa Division of Gastroen terology University of Genoa Department of Digestive Tract Diseases Medical University of Lodz Division of Gastroenterology University of Padua

Esophageal complications caused by gastroesophageal reflux disease(GERD)include reflux esophagitis and Barrett’s esophagus(BE).BE is a premalignant condition with an increased risk of developing esophageal adeno-carcinoma(EAC).The carcinogenic sequence may progress through several steps,from normal esophageal mucosa through BE to EAC.A recent advent of functional esophageal testing(particularly multichannel intraluminal impedance and pH monitoring)has helped to improve our knowledge about GERD pathophysiology,including its *** findings(when properly confirmed)might help to predict BE neoplastic *** the last few decades,the incidence of EAC has continued to rise in Western ***,only a minority of BE patients develop EAC,opening the debate regarding the cost-effectiveness of current screening/surveillance ***,major efforts in clinical and research practice are focused on new methods for optimal risk assessment that can stratify BE patients at low or high risk of developing EAC,which should improve the cost effectiveness of screening/surveillance programs and consequently significantly affect health-care ***,the area of BE therapeutic management is rapidly *** eradication therapies have been shown to be effective,and new therapeutic options for BE and EAC have *** aim of the present review article is to highlight the status of screening/surveillance programs and the current progress of BE ***,we discuss the recent introduction of novel esophageal pathophysiological exams that have improved the knowledge of the mechanisms linking GERD to BE.

关键词： Gastroesophageal reflux disease Barrett’s esophagus Esophageal adenocarcinoma Impedance and pH monitoring Endoscopy

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How many cases of laryngopharyngeal reflux suspected by laryngoscopy are gastroesophageal reflux disease-related?

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World Journal of Gastroenterology 2012年第32期18卷 4363-4370页

作者： Nicola de Bortoli Andrea Nacci Edoardo Savarino irene martinucci Massimo Bellini Bruno Fattori Linda Ceccarelli Francesco Costa Maria Gloria Mumolo Angelo Ricchiuti Vincenzo Savarino Stefano Berrettini Santino Marchi Division of Gastroenterology University of Pisa56124 PisaItaly Ear Nose and Throat Audiology Phoniatrics UnitUniversity of Pisa56124 PisaItaly Division of Gastroenterology University of Padua35100 PaduaItaly Division of Gastroenterology University of Genoa16100 GenoaItaly

AIM:To investigate the prevalence of gastroesophageal reflux disease(GERD) in patients with a laryngoscopic diagnosis of laryngopharyngeal reflux(LPR).METHODS:Between May 2011 and October 2011,41 consecutive patients with laryngopharyngeal symptoms(LPS) and laryngoscopic diagnosis of LPR were empirically treated with proton pump inhibitors(PPIs) for at least 8 wk,and the therapeutic outcome was assessed through validated questionnaires(GERD impact scale,GIS;visual analogue scale,VAS).LPR diagnosis was performed by ear,nose and throat specialists using the reflux finding score(RFS) and reflux symptom index(RSI).After a 16-d wash-out from PPIs,all patients underwent an upper endoscopy,stationary esophageal manometry,24-h multichannel intraluminal impedance and pH(MII-pH) esophageal monitoring.A positive correlation between LPR diagnosis and GERD was supposed based on the presence of esophagitis(ERD),pathological acid exposure time(AET) in the absence of esophageal erosions(NERD),and a positive correlation between symptoms and refluxes(hypersensitive esophagus,HE).RESULTS:The male/female ratio was 0.52(14/27),the mean age ± SD was 51.5 ± 12.7 years,and the mean body mass index was 25.7 ± 3.4 kg/m *** subjects reported one or more ***-five out of 41 patients also had typical GERD symptoms(heartburn and/or regurgitation).The most frequent laryngoscopic findings were posterior laryngeal hyperemia(38/41),linear indentation in the medial edge of the vocal fold(31/41),vocal fold nodules(6/41) and diffuse infraglottic oedema(25/41).The GIS analysis showed that 10/41 patients reported symptom relief with PPI therapy(P < 0.05);conversely,23/41 did not report any clinical *** the same time,the VAS analysis showed a significant reduction in typical GERD symptoms after PPI therapy(P < 0.001).A significant reduction in LPS *** the other hand,such result was not recorded for *** was detected in 2/41 patients,and ineffective esophageal motility

关键词： Laryngopharyngeal reflux Gastroesophageal reflux Multichannel impedance and pH monitoring Extra-esophageal reflux syndromes Chronic laryngitis

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Esophageal testing: What we have so far

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World Journal of Gastrointestinal Pathophysiology 2016年第1期7卷 72-85页

作者： Nicola de Bortoli irene martinucci Lorenzo Bertani Salvatore Russo Riccardo Franchi Manuele Furnari Salvatore Tolone Giorgia Bodini Valeria Bolognesi Massimo Bellini Vincenzo Savarino Santino Marchi Edoardo Vincenzo Savarino Gastroenterology Unit Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of Pisa Gastroenterology Unit Department of Internal MedicineUniversity of Genoa Surgery Unit Department of SurgerySecond University of Naples Gastroenterology Unit Department SurgeryOncology and GastroenterologyUniversity of Padua

Gastroesophageal reflux disease(GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry(HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h p H-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and p H monitoring can detect acid and non-acid reflux events. Endo FLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal p H-metry. Future studies are required of these techniques to evaluate their diagnostic accuracy and usefulness, although the available data are promising.

关键词： Gastroesophageal reflux disease Highresolution manometry Multichannel impedance and pH BRAVO EndoFLIP PEP-test Restech

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Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system

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Neural Regeneration Research 2025年第11期20卷 3209-3210页

作者： Marta García-Juan Mario Villa irene Benito-Cuesta Lara Ordónez-Gutiérrez Francisco Wandosell Centro de Biología Molecular“Severo Ochoa”(CSIC-UAM) Nicolas Cabrera 1Universidad Autónoma de MadridMadridSpain Fisiología Animal Departamento de BiologíaFacultad de CienciasUniversidad Autónoma de MadridMadridSpain Department of Clinical Neuroscience CMM Karolinska Universitetssjukhuset SolnaStockholmSweden Departamento de Bioquímica y Biología Molecular Universidad Complutense de MadridMadridSpain Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED) MadridSpain

Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and *** cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino *** process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein *** of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).

关键词： homeostasis system hereafter

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Embryo-to-lamella transition of grain boundary twins in magnesium

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Journal of Magnesium and Alloys 2023年第12期11卷 4485-4497页

作者： Mariyappan Arul Kumar irene J Beyerlein Materials Science and Technology Division Los Alamos National LaboratoryLos AlamosNM 87545USA Mechanical Engineering Department Materials DepartmentUniversity of CaliforniaSanta BarbaraCA 93106USA

A combined experimental and computational analysis is performed to investigate the less commonly studied embryo-to-lamella transition of deformation twins in magnesium. This work aims to understand the structural variables controlling the embryo-to-lamella transition from grain boundaries. Statistical analysis of hundreds of early-stage twins in the lightly deformed microstructure reveals a prevailing wedge shape,with a much thicker base along the grain boundary(GB) where they originate and a thinner tip terminating in the crystal. The analysis also shows that the GB base is super thick and identifies a minimum GB twin thickness among all early-stage twins that is about one micron. A crystal plasticity-based full-field model is employed to calculate the driving forces to migrate the boundary of a three-dimensional GB twin embryo. The stress analysis, considering a full range of embryo shapes and neighboring grain orientations, indicate that the twin embryo is most likely going to form a wedge shape when it first propagates. The calculations predict that the thickness of the embryo at the GB needs to be significantly larger than its length into the crystal in order to propagate into the crystal. The analysis finds that the more aligned the twin embryo variant is with basal slip in the neighboring grain, the thinner the twin embryo needed for propagation.

关键词： Magnesium Twin embryo Crystal plasticity Nucleation Grain neighbor

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Pollen Tube Growth: a Delicate Equilibrium Between Secretory and Endocytic Pathways

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Journal of Integrative Plant Biology 2009年第8期51卷 727-739页

作者： Alessandra Moscatelli Aurora irene Idilli Dipartimento di Biologia L. Gorini Università degli Studi di MilanoVia Celoria 26 20133 Milano Italy

Although pollen tube growth is a prerequisite for higher plant fertilization and seed production, the processes leading to pollen tube emission and elongation are crucial for understanding the basic mechanisms of tip growth. It was generally accepted that pollen tube elongation occurs by accumulation and fusion of Golgi-derived secretory vesicles （SVs） in the apical region, or clear zone, where they were thought to fuse with a restricted area of the apical plasma membrane （PM）, defining the apical growth domain. Fusion of SVs at the tip reverses outside cell wall material and provides new segments of PM. However, electron microscopy studies have clearly shown that the PM incorporated at the tip greatly exceeds elongation and a mechanism of PM retrieval was already postulated in the mid-nineteenth century. Recent studies on endocytosis during pollen tube growth showed that different endocytic pathways occurred in distinct zones of the tube, including the apex, and led to a new hypothesis to explain vesicle accumulation at the tip; namely, that endocytic vesicles contribute substantially to V-shaped vesicle accumulation in addition to SVs and that exocytosis does not involve the entire apical domain. New insights suggested the intriguing hypothesis that modulation between exo- and endocytosis in the apex contributes to maintain PM polarity in terms of lipid/protein composition and showed distinct degradation pathways that could have different functions in the physiology of the cell. Pollen tube growth in vivo is closely regulated by interaction with style molecules. The study of endocytosis and membrane recycling in pollen tubes opens new perspectives to studying pollen tube-style interactions in vivo.

关键词： endocytosis exocytosis membrane recycling polarized growth pollen tube

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Efficient Algorithms for Approximating Particular Solutions of Elliptic Equations Using Chebyshev Polynomials

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Communications in Computational Physics 2007年第3期2卷 501-521页

作者： Andreas Karageorghis irene Kyza Department of Mathematics and Statistics University of CyprusP.O.Box 205371678 NicosiaCyprus Department of Mathematics University of CreteP.O.Box 2208GR-71409 HeraklionGreece.

In this paper,we propose efficient algorithms for approximating particular solutions of second and fourth order elliptic *** approximation of the particular solution by a truncated series of Chebyshev polynomials and the satisfaction of the differential equation lead to upper triangular block systems,each block being an upper triangular *** systems can be solved efficiently by standard *** numerical examples are presented for each case.

关键词： Chebyshev polynomials Poisson equation biharmonic equation method of particular solutions.

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