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| 1 | Role of matrix metalloproteinases in cholestasis and hepatic ischemia/reperfusion injury:A review显示文摘Matrix metalloproteinases(MMPs) are a family ofproteases using zinc-dependent catalysis to break down extracellular matrix(ECM) components, allowing cell movement and tissue reorganization. Like many other proteases, MMPs are produced as zymogens, an inactive form, which are activated after their release from cells. Hepatic ischemia/reperfusion(I/R) is associated with MMP activation and release, with profound effects on tissue integrity: their inappropriate, prolonged or excessive expression has harmful consequences for the liver. Kupffer cells and hepatic stellate cells can secrete MMPs though sinusoidal endothelial cells are a further source of MMPs. After liver transplantation, biliary complications are mainly attributable to cholangiocytes, which, compared with hepatocytes, are particularly susceptible to injury and ultimately a major cause of increased graft dysfunction and patient morbidity. This paper focuses on liver I/R injury and cholestasis and reviews factors and mechanisms involved in MMP activation together with synthetic compounds used in their regulation. In this respect, recent data have demonstrated that the role of MMPs during I/R may go beyond the mere destruction of the ECM and may be much more complex than previously thought. We thus discuss the role of MMPs as an important factor in cholestasis associated with I/R injury. | Giuseppina Palladini Andrea Ferrigno Plinio Richelmi Stefano Perlini Mariapia Vairetti | 2015 | World Journal of Gastroenterology2015，21，42： | 6 |
| 2 | Metabolic shift in liver: Correlation between perfusion temperature and hypoxia inducible factor-1α显示文摘AIM: To study at what temperature the oxygen carried by the perfusate meets liver requirements in a model of organ perfusion. METHODS: in this study, we correlated hypoxia induciblefactor(Hi F)-1α expression to the perfusion temperature and the hepatic oxygen uptake in a model of isolated perfused rat liver. Livers from Wistar rats were perfused for 6 h with an oxygenated medium at 10, 20, 30 and 37 ℃. Oxygen uptake was measured by an oxygen probe; lactate dehydrogenase activity, lactate release and glycogen were measured spectrophotometrically; bile flow was gravitationally determined; p H of the perfusate was also evaluated; Hi F-1α m RNA and protein expression were analyzed by real time-polymerase chain reaction and ELi SA, respectively. RESULTS: Livers perfused at 10 and 20 ℃ showed no difference in lactate dehydrogenase release after 6 h of perfusion(0.96 ± 0.23 vs 0.93 ± 0.09 m U/min per g) and had lower hepatic damage as compared to 30 and 37 ℃(5.63 ± 0.76 vs 527.69 ± 45.27 m U/min per g, respectively, P s < 0.01). After 6 h, tissue ATP was significantly higher in livers perfused at 10 and 20 ℃than in livers perfused at 30 and 37 ℃(0.89 ± 0.06 and 1.16 ± 0.05 vs 0.57 ± 0.09 and 0.33 ± 0.08 nmol/mg, respectively, P s < 0.01). No sign of hypoxia was observed at 10 and 20 ℃, as highlighted by low lactate release respect to livers perfused at 30 and 37 ℃(121.4 ± 12.6 and 146.3 ± 7.3 vs 281.8 ± 45.3 and 1094.5 ± 71.7 nmol/m L, respectively, P s < 0.02), and low relative Hi F-1α m RNA(0.40 ± 0.08 and 0.20 ± 0.03 vs 0.60 ± 0.20 and 1.47 ± 0.30, respectively, P s < 0.05) and protein(3.72 ± 0.16 and 3.65 ± 0.06 vs 4.43 ± 0.41 and 6.44 ± 0.82, respectively, P s < 0.05) expression.CONCLUSION: Livers perfused at 10 and 20 ℃ show no sign of liver injury or anaerobiosis, in contrast to livers perfused at 30 and 37 ℃. | Andrea Ferrigno Laura Giuseppina Di Pasqua Alberto Bianchi Plinio Richelmi Mariapia VairettiAndrea Ferrigno | 2015 | World Journal of Gastroenterology2015，21，4： | 5 |
| 3 | Localization and role of metabotropic glutamate receptors subtype 5 in the gastrointestinal tract显示文摘Metabotropic glutamate receptor subtype 5(mGluR5) is a Group I mGlu subfamily of receptors coupled to the inositol trisphosphate/diacylglycerol pathway. Like other m Glu R subtypes, mGluR5 s contain a phylogenetically conserved, extracellular orthosteric binding site and a more variable allosteric binding site, located on the heptahelical transmembrane domain. The mGluR5 receptor has proved to be a key pharmacological target in conditions affecting the central nervous system(CNS) but its presence outside the CNS underscores its potential role in pathologies affecting peripheral organs such as the gastrointestinal(GI) tract and accessory digestive organs such as the tongue, liver and pancreas. Following identification of mGluR5s in the mouth, various studies have subsequently demonstrated its involvement in mechanical allodynia, inflammation, pain and oral cancer. mGluR5 expression has also been identified in gastroesophageal vagal pathways. Indeed, experimental and human studies have demonstrated that mGluR5 blockade reduces transient lower sphincter relaxation and reflux episodes. In the intestine, mGluR5s have been shown to be involved in the control of intestinal inflammation, visceral pain and the epithelial barrier function. In the liver, mGluR5s have a permissive role in the onset of ischemic injury in rat and mice hepatocytes. Conversely, livers from mice treated with selective negative allosteric modulators and mGluR5 knockout mice are protected against ischemic injury. Similar results have been observed in experimental models of free-radical injury and in vivo mouse models of acetaminophen intoxication. Finally, mGluR5s in the pancreas are associated with insulin secretion control. The picture is, however, far from complete as the review attempts to establish in particular as regards identifying specific targets and innovative therapeutic approaches for the treatment of GI disorders. | Andrea Ferrigno Clarissa Berardo Laura G Di Pasqua Veronica Siciliano Plinio Richelmi Mariapia Vairetti | 2017 | World Journal of Gastroenterology2017，23，25： | 3 |
| 4 | Lobe-Specific Heterogeneity and Matrix Metalloproteinase Activation after Ischemia/Reperfusion Injury in Rat Livers显示文摘 | Giuseppina Palladini Andrea Ferrigno Vittoria Rizzo Eleonora Boncompagni Plinio Richelmi Isabel Freitas Stefano Perlini Mariapia Vairetti | 2012 | Toxicologic Pathology2012，，5： | 2 |
| 5 | Liver plays a central role in asymmetric dimethylargininemediated organ injury显示文摘Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;inducible.ADMA is synthesized by protein methyltransferases followed by proteolytic degradation.ADMA is metabolized to citrulline and dimethylamine,by dimethylarginine dimethylaminohydrolase(DDAH) and enters cells through cationic amino-acid transporters extensively expressed in the liver.The liver plays a crucial role in ADMA metabolism by DDAH-1 and,as has been recently demonstrated,it is also responsible for ADMA biliary excretion.A correlation has been demonstrated between plasma ADMA levels and the degree of hepatic dysfunction in patients suffering from liver diseases with varying aetiologies:plasma ADMA levels are increased in patients with liver cirrhosis,alcoholic hepatitis and acute liver failure.The mechanism by which liver dysfunction results in raised ADMA concentrations is probably due to impaired activity of DDAH due to severe inflammation,oxidative stress,and direct damage to DDAH.High plasma ADMA levels are also relevant as they are associated with the onset of multiorgan failure(MOF).Increased plasma concentration of ADMA was identified as an independent risk factor for MOF in critically-ill patients causing enhanced Intensive Care Unit mortality:a significant reduction in nitric oxide synthesis,leading to malperfusion in various organs,eventually culminating in multi organs dysfunction. | Andrea Ferrigno Laura G Di Pasqua Clarissa Berardo Plinio Richelmi Mariapia Vairetti | 2015 | World Journal of Gastroenterology2015，21，17： | 2 |
| 6 | Pharmacological principles undely- ing oxygen - ozone therapy 显示文摘 | Richelmi P Valdenassi L Berte F | 2001 | Riv Neurotadiol2001，14，1： | 1 |
| 7 | Bone remodelling in osteoarthrosic subjects undergoing a physical exercise program显示文摘 | Simona Bellometti Francantonio Berte Plinio Richelmi | 2002 | Clinica Chimica Acta2002，325，12： | 1 |
| 8 | Pharmacological principles underlying oxygen-ozone therapy显示文摘 | Richelmi P Valdenassi L Berte F | 2001 | Riv Neuroradiol2001，14，： | 1 |
| 9 | Pharmacological principles underlying oxygen2Ozone therapy 显示文摘 | Richelmi P Valdenassi L Berte F | 2001 | Rivistadi Neuroradiologia2001，14，1： | 1 |
| 10 | Pharmacological principles underlying oxygen-ozone therapy 显示文摘 | Richelmi P Valdenassi L Berte F | 2001 | Rivista di Neuroradiologia2001，1，： | 1 |
| 11 | Pharmacological principles underlying oxygeno-zone therapy 显示文摘 | Richelmi P Valdenassi L Berte F | 2001 | Rivistadi Neuroradiologia2001，，： | 1 |
| 12 | Pharmacological principles underlying oxygen2Ozone therapy显示文摘 | Richelmi P Valdenassi L Berte F | 2001 | Rivista di Neuroradiologia2001，14，1： | 1 |
| 13 | Dopamine partial receptor agonists reduce ethanol intake in the rat 显示文摘 | Bono G Balducci C Richelmi P | 1996 | Eur J Pharmacol1996，296，3： | 1 |
| 14 | On the role of mi- tochondria in cell injury caused by vanadate - induced Ca2+ overload 显示文摘 | Richelmi P Mirabelli F Salis A | 1989 | Toxieology1989，57，： | 1 |
| 15 | Pharmacological principles underlying oxygeno-zone therapy显示文摘 | Richelmi P Valdenassi L Berte F | 2001 | Rivistadi Neuroradiologia2001，14，1： | 1 |
| 16 | Pharmacological principles un- derlying oxygen-ozone therapy 显示文摘 | Richelmi P Valdenassi L Berte F | 2001 | Riv Neuroradiol2001，14，： | 1 |
| 17 | Pharmacological principles underlying oxygen2Ozone therapy显示文摘 | Richelmi P Valdenassi L Berte F | | 0，，01： | 1 |
| 18 | Phamacological principles underlying oxygen-ozone therapy显示文摘 | Richelmi P Valdenassi L Berte F | 2001 | Riv Neuroradiol2001，14，1： | 1 |
| 19 | Pharmacological principles underlying oxygen-ozone therapy显示文摘 | Richelmi P Valdenassi L Berte F | 2001 | Rivistadi Neuroradiologin2001，，： | 1 |
| 20 | Pharmacological principles underlying oxygen-ozone therapy显示文摘 | Richelmi P Valdenassi L Berte F | 2001 | Riv Neuroradiol2001，14，： | 1 |
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