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Intestinal epithelial barrier and neuromuscular compartment in health and disease

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World Journal of Gastroenterology 2020年第14期26卷 1564-1579页

作者： Vanessa D’Antongiovanni Carolina Pellegrini matteo fornai Rocchina Colucci Corrado Blandizzi Luca Antonioli Nunzia Bernardini Department of Clinical and Experimental Medicine University of PisaPisa 56126Italy Department of Pharmacy University of PisaPisa 56126Italy Department of Pharmaceutical and Pharmacological Sciences University of PadovaPadova 35131Italy

A number of digestive and extra-digestive disorders,including inflammatory bowel diseases,irritable bowel syndrome,intestinal infections,metabolic syndrome and neuropsychiatric disorders,share a set of clinical features at gastrointestinal level,such as infrequent bowel movements,abdominal distension,constipation and secretory *** lines of evidence indicate that morphological and molecular changes in intestinal epithelial barrier and enteric neuromuscular compartment contribute to alterations of both bowel motor and secretory functions in digestive and extra-digestive *** present review has been conceived to provide a comprehensive and critical overview of the available knowledge on the morphological and molecular changes occurring in intestinal epithelial barrier and enteric neuromuscular compartment in both digestive and extra-digestive *** addition,our intent was to highlight whether these morphological and molecular alterations could represent a common path(or share some common features)driving the pathophysiology of bowel motor dysfunctions and related symptoms associated with digestive and extra-digestive *** assessment might help to identify novel targets of potential usefulness to develop original pharmacological approaches for the therapeutic management of such disturbances.

关键词： Digestive disease Enteric nervous system Intestinal epithelial barrier Intestinal motility Metabolic disorders Neuropsychiatric disorders

Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage

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World Journal of Gastroenterology 2005年第26期11卷 4052-4060页

作者： Corrado Blandizzi matteo fornai Rocchina Colucci Gianfranco Natale Valter Lubrano Cristina Vassalle Luca Antonioli Gloria Lazzeri Mario Del Tacca Division of Pharmacology and Chemotherapy Department of Oncology Transplants and Advanced Technologies in Medicine University of PisaPisaItaly Department of Human Morphology and Applied Biology University of Pisa Pisa Italy Institute of Clinical Physiology National Research Council Pisa Italy Division of Pharmacology and Chemotherapy Department of Oncology Transplants and Advanced Technologies in Medicine University of Pisa Pisa Italy

AIM:This study investigated the mechanisms of protection afforded by the proton pump inhibitor lansoprazole against gastric injury induced by different non-steroidal anti-inflammatory drugs (NSAIDs) in rats. METHODS: Male Sprague-Dawley rats were orally treated with indomethacin (100 μmol/kg), diclofenac (60 μmol/kg), piroxicam (150 μmol/kg) or ketoprofen (150 μmol/kg). Thirty minutes before NSAIDs, animals were orally treated with lansoprazole 18 or 90 umol/kg. Four hours after the end of treatments, the following parameters were assessed: gastric mucosal PGE2, malondialdehyde (MDA), myeloperoxidase (MPO) or non-proteic sulfhydryl compounds (GSH) levels; reverse transcription-polymerase chain reaction (RT-PCR) of mucosal COX-2 mRNA; gastric acid secretion in pylorus-ligated animals; in vitro effects of lansoprazole (1-300 μmol/L) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate. RESULTS: All NSAIDs elicited mucosal necrotic lesions which were associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels were detected in the gastric mucosa of indomethacin- or piroxicam-treated animals. Indomethacin enhanced mucosal cyclooxygenase-2 expression, while not affecting cyclooxygenase-1. At the oral dose of 18 μmol/kg lansoprazole partly counteracted diclofenac-induced mucosal damage, whereas at 90 μmol/kg it markedly prevented injuries evoked by all test NSAIDs. Lansoprazole at 90 μmol/kg reversed also the effects of NSAIDs on MPO, MDA and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced cyclooxygenase-2 expression. However, both lansoprazole doses markedly inhibited acid secretion in pylorus-ligated rats. Lansoprazole concentration-dependently reduced the oxidation of LDLs in vitro. CONCLUSION: These results suggest that, besides the inhibition of acid secretion, lansoprazole protection against NSAID-induced gastr

关键词： Lansoprazole Gastric injury Non-steroidal anti-inflammatory drugs

Constipation,deficit in colon contractions and alpha-synuclein inclusions within the colon precede motor abnormalities and neurodegeneration in the central nervous system in a mouse model of alphasynucleinopathy

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Translational Neurodegeneration 2019年第1期8卷 48-62页

作者： Lucia Rota Carolina Pellegrini Laura Benvenuti Luca Antonioli matteo fornai Corrado Blandizzi Antonino Cattaneo Emanuela Colla Bio@SNS Laboratory Scuola Normale SuperiorePiazza dei Cavalieri 756126 PisaItaly Department of Pharmacy University of PisaVia Roma 5556126 PisaItaly Department of Clinical and Experimental Medicine University of PisaVia Roma 5556126 PisaItaly Neurotrophins and Neurodegenerative Diseases Laboratory Rita Levi-Montalcini European Brain Research InstituteViale Regina Elena 295Rome 00161Italy.

Background:Gastrointestinal dysfunction can affect Parkinson’s disease(PD)patients long before the onset of motor ***,little is known about the relationship between gastrointestinal abnormalities and the development of *** to other animal models,the human A53T alpha-synuclein(αS)transgenic mice,Line G2–3,developsαS-driven neurological and motor impairments after 9 months of age,displaying a long presymptomatic phase free of central nervous system(CNS)***:To determine whether this line can be suitable to study constipation as it occurs in prodromal PD,gastrointestinal functionality was assessed in young mice through a multidisciplinary approach,based on behavioral and biochemical analysis combined with electrophysiological recordings of mouse intestinal ***:We found that the A53TαS mice display remarkable signs of gastrointestinal dysfunction that precede motor abnormalities andαS pathology in the CNS by at least 6 ***αS mice show a drastic delay in food transit along the gastrointestinal tract,of almost 2 h in 3 months old mice that increased to more than 3 h at 6 *** impairment was associated with abnormal formation of stools that resulted in less abundant but longer pellets excreted,suggesting a deficit in the intestinal *** agreement with this,electrically evoked contractions of the colon,but not of the ileum,showed a reduced motor response in both longitudinal and circular muscle layers inαS mice already at 3 months of age,that was mainly due to an impaired cholinergic transmission of the underlying enteric nervous ***,the presence of insoluble and aggregatedαS was found in enteric neurons in both myenteric and submucosal plexi only in the colon of 3 months oldαS mice,but not in the small intestine,and exacerbated with age,mimicking the increase in transit delay and the contraction deficit showed by behavioral and electrical recordings ***:Gastrointest

关键词： Alpha-synuclein Constipation Gastrointestinal dysfunction Bowel dysmotility Non-motor symptoms Parkinson’s disease Enteric nervous system Alpha-synucleinopathy

Detailing the ultrastructure’s increase of prion protein in pancreatic adenocarcinoma

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World Journal of Gastroenterology 2021年第42期27卷 7324-7339页

作者： matteo Bianchini Maria Anita Giambelluca Maria Concetta Scavuzzo Gregorio Di Franco Simone Guadagni matteo Palmeri NiccolòFurbetta Desirée Gianardi Niccola Funel Claudio Ricci Raffaele Gaeta Luca Emanuele Pollina Alfredo Falcone Caterina Vivaldi Giulio Di Candio Francesca Biagioni Carla Letizia Busceti Luca Morelli Francesco fornai General Surgery Unit Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisa 56124Italy Human Anatomy Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisa 56124Italy Division of Surgical Pathology Department of SurgicalMedicalMolecular Pathology and Critical AreaUniversity of PisaPisa 56124Italy Division of Medical Oncology Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisa 56124Italy IRCCS Neuromed Istituto Neurologico MediterraneoPozzilli 86077Italy EndoCAS(Center for Computer Assisted Surgery) University of PisaPisa 56124Italy

BACKGROUND Recent evidences have shown a relationship between prion protein(PrPc)expression and pancreatic ductal adenocarcinoma(PDAC).Indeed,PrPc could be one of the markers explaining the aggressiveness of this ***,studies investigating the specific compartmentalization of increased PrPc expression within PDAC cells are lacking,as well as a correlation between ultrastructural evidence,ultrastructural morphometry of PrPc protein and clinical *** data,as well as the quantitative stoichiometry of this protein detected by immuno-gold,provide a significant advancement in understanding the biology of disease and the outcome of surgical *** To analyze quantitative stoichiometry and compartmentalization of PrPc in PDAC cells and to correlate its presence with prognostic data METHODS Between June 2018 and December 2020,samples from pancreatic tissues of 45 patients treated with pancreatic resection for a preoperative suspicion of PDAC at our Institution were *** the frozen section excluded a PDAC diagnosis,or the nodules were too small for adequate sampling,patients were ruled out from the present *** blotting was used to detect,quantify and compare the expression of PrPc in PDAC and control tissues,such as those of non-affected neighboring pancreatic tissue of the same *** quantify the increase of PrPc and to detect the subcellular compartmentalization of PrPc within PDAC cells,immuno-gold stoichiometry within specific cell compartments was analyzed with electron ***,an analysis of quantitative PrPc expression according to prognostic data,such as cancer stage,recurrence of the disease at 12 mo after surgery and recurrence during adjuvant chemotherapy was *** The amount of PrPc within specimen from 38 out of 45 patients was determined by semi-quantitative analysis by using Western blotting,which indicates that PrPc increases almost three-fold in tumor pancreatic tissue compared with healthy panc

关键词： Pancreatic ductal adenocarcinoma Prion protein Western blotting Electron microscopy Cellular compartmentalization Neuroinvasion