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| 1 | Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage显示文摘AIM: This study investigated the mechanisms of protection afforded by the proton pump inhibitor lansoprazole against gastric injury induced by different non-steroidal antiinflammatory 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 μmol/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 gastric damage depends on a reduction in mucosal oxidative injury, which is also responsible for an increment of sulfhydryl radical bioavailability. It is also suggested that lansoprazole does not influence the downregulation of gastric prostaglandin production associated with NSAID treatment. | Corrado Blandizzi Matteo Fornai Rocchina Colucci Gianfranco Natale Valter Lubrano Cristina Vassalle Luca Antonioli Gloria Lazzeri Mario Del Tacca | 2005 | World Journal of Gastroenterology2005，11，26： | 9 |
| 2 | Intestinal epithelial barrier and neuromuscular compartment in health and disease显示文摘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 dysfunctions.Several 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 diseases.The 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 diseases.In 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 disorders.This assessment might help to identify novel targets of potential usefulness to develop original pharmacological approaches for the therapeutic management of such disturbances. | Vanessa D’Antongiovanni Carolina Pellegrini Matteo Fornai Rocchina Colucci Corrado Blandizzi Luca Antonioli Nunzia Bernardini | 2020 | World Journal of Gastroenterology2020，26，14： | 6 |
| 3 | 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显示文摘Background:Gastrointestinal dysfunction can affect Parkinson’s disease(PD)patients long before the onset of motor symptoms.However,little is known about the relationship between gastrointestinal abnormalities and the development of PD.Contrary 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)dysfunction.Methods: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 preparations.Results: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 months.YoungαS 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 months.Such impairment was associated with abnormal formation of stools that resulted in less abundant but longer pellets excreted,suggesting a deficit in the intestinal peristalsis.In 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 system.Interestingly,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 data.Conclusions:Gastrointestinal dysfunction in A53TαS mice represents an early sign ofαS-driven pathology without concomitant CNS involvement.We believe that this model can be very useful to study disease-modifying strategies that could extend the prodromal phase of PD and haltαS pathology from reaching the brain. | Lucia Rota Carolina Pellegrini Laura Benvenuti Luca Antonioli Matteo Fornai Corrado Blandizzi Antonino Cattaneo Emanuela Colla | 2019 | Translational Neurodegeneration2019，8，1： | 5 |
| 4 | NKG2A and COVID-19: another brick in the wall显示文摘Coronavirus disease 2019(COVID-19)is a viral infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2;formerly designated as 2019-nCoV),a novel betacoronavirus firstly identified during a burst of respiratory illness cases in Wuhan City,Hubei Province,China.1 Unfortunately,within a few weeks,the SARS-COV2 virus started to spread globally,producing a pandemic of an extremely spreadable and potentially fatal disease,becoming a cause of great concern for global public health.1 Despite the current estimates of COVID-19 case fatality rate suggest that this coronavirus is less deadly than other pathogens driving other large-scale outbreaks,such as SARS,Middle East respiratory syndrome,or Ebola,the main concern is that this infection is able to spread more easily than other diseases,including seasonal influenza. | Luca Antonioli Matteo Fornai Carolina Pellegrini Corrado Blandizzi | 2020 | Cellular & Molecular Immunology2020，17，6： | 3 |
| 5 | Parkinson-like syndrome induced by continuous MPTP infusion:convergent roles of the ubiquitin-proteasome system and α-synuclein显示文摘 | Fornai F Schlüter OM Lenzi P | 2005 | Proc Natl Acad Sci USA2005，102，9： | 1 |
| 6 | Parkinson-like syndrome induced by continuous MPTP infusion:Convergent roles of the ubiquitin-proteasome system and α-synuclein显示文摘 | Fornai F Schluter O M Lenzi P | 2005 | PNAS2005，102，9： | 1 |
| 7 | Recent knowledge on molecular components of Lewy bodies discloses future therapeutic strategies in Parkinson' s disease 显示文摘 | Fornai F Lenzi P Gesi M | 2003 | Curr Drug Targets CNS Neurol Disord2003，2，3： | 1 |
| 8 | Parkinson-like syndrome induced by continuous MPTP infusion: convergent roles of the ubiquitin-proteasome system and alpha-synuelein 显示文摘 | Fornai F Schliiter O M Lenzi P | 2005 | Proc Nat1 Acad Sci U S A2005，102，9： | 1 |
| 9 | Characterization of mechanisms underlying the effects of esomeprazole on the impairment of gastric ulcer healing with addition of NSAID treatment显示文摘 | Colucci R Fornai M Antonioli L | 2009 | Dig Liver Dis2009，41，6： | 1 |
| 10 | Neurokinin 1 receptor expression and substance P physiological actions are developmentally regulated in the rabbit retina显示文摘 | Casini G Dal Monte M Fornai F Bosco L Willems D Yang Q | 2004 | Neuroscience2004，124，1： | 1 |
| 11 | The role of nitric oxide in focally-evoked limbic seizures 显示文摘 | Proctor MR Fornai F Afshar JK | 1997 | Neuroscience1997，76，4： | 1 |
| 12 | Noradrenergie modulation of methamphetamine-induced striatal dopamine depletion 显示文摘 | Fornai F Alessandri MG Torracca MT | 1998 | Ann N Y Aead Sei1998，844，： | 1 |
| 13 | Preliminary observations on the effect of hypoxic and hyperbaric stress on pulmonary gas exchange in breath-hold divers显示文摘 | Garbella E Piarulli A Fornai E | 2011 | Diving Hyperb Med2011，41，2： | 1 |
| 14 | Dose-dependent protective effects of apomorphine against methamphetamine-induced nigrostriatal damage显示文摘 | Fornai F Battaglia G Gesi M | 2001 | Brain Res2001，898，： | 1 |
| 15 | Fine structure and biochemical mechanisms underlying nigrostriatal inclusions and cell death after proteasome inhibition显示文摘 | Fornai F Lenzi P Gesi M | 2003 | J Neurosci2003，23，26： | 1 |
| 16 | Lithium delays progression of amyotrophic lateral sclerosis显示文摘 | Fornai F Longone P Cafaro L | 2008 | Proc Natl Acad Sci USA2008，105，： | 1 |
| 17 | Recent knowledge on molecular components of lewy bodies discloses future therapeutic strategies in Parkinson's disease显示文摘 | Fornai F Lenzi P C esi M | 2003 | Curt Drug Targets CNS Neurol Disord2003，2，3： | 1 |
| 18 | Role of coxibs in the strategies for gastrointestinal protection in patients requiring chronic non-steroidal anti-inflammatory therapy显示文摘 | Corrado Blandizzi Marco Tuccori Rocchina Colucci Matteo Fornai Luca Antonioli Narcisa Ghisu Mario Del Tacca | 2008 | Pharmacological Research2008，，2： | 1 |
| 19 | Effects of pretreatment with N-(2-chloroethyl) -N-ethyl-2-bromobenzylamine ( DSP-4 ) on methamphetamine pharmacokineties and striatal dopamine losses 显示文摘 | Fornai F Giorgi FS Alessandri MG | 1999 | J Neurochem1999，72，2： | 1 |
| 20 | Selective blockade of mGluS metabotropic glutamate receptors is protective against methamphetamine neurotoxicity显示文摘 | Battaglia G Fornai F Busceti CL | | 0，，06： | 1 |
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