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| 1 | Biochemical mechanisms in drug-induced liver injury:Certainties and doubts显示文摘Drug-induced liver injury is a significant and still unresolved clinical problem.Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical development.Several xenobiotics are lipophilic substances and their transformation into hydrophilic compounds by the cytochrome P-450 system results in production of toxic metabolites.Aging,preexisting liver disease,enzyme induction or inhibition,genetic variances,local O2 supply and,above all,the intrinsic molecular properties of the drug may affect this process.Necrotic death follows antioxidant consumption and oxidation of intracellular proteins,which determine increased permeability of mitochondrial membranes,loss of potential,decreased ATP synthesis,inhibition of Ca2+-dependent ATPase,reduced capability to sequester Ca2+ within mitochondria,and membrane bleb formation.Conversely,activation of nucleases and energetic participation of mitochondria are the main intracellular mechanisms that lead to apoptosis.Non-parenchymal hepatic cells are inducers of hepatocellular injury and targets for damage.Activation of the immune system promotes idiosyncratic reactions that result in hepatic necrosis or cholestasis,in which different HLA genotypes might play a major role.This review focuses on current knowledge of the mechanisms of drug-induced liver injury and recent advances on newly discovered mechanisms of liver damage.Future perspectives including new frontiers for research are discussed. | Ignazio Grattagliano Leonilde Bonfrate Catia V Diogo Helen H Wang David QH Wang Piero Portincasa | 2009 | World Journal of Gastroenterology2009，15，39： | 30 |
| 2 | A silybin-phospholipids complex counteracts rat fatty liver degeneration and mitochondrial oxidative changes显示文摘AIM:To investigate the effectiveness of antioxidant compounds in modulating mitochondrial oxidative alterations and lipids accumulation in fatty hepatocytes.METHODS:Silybin-phospholipid complex containing vitamin E(Realsil) was daily administered by gavage(one pouch diluted in 3 mL of water and containing 15 mg vitamin E and 47 mg silybin complexed with phospholipids) to rats fed a choline-deprived(CD) or a high fat diet [20% fat,containing 71% total calories as fat,11% as carbohydrate,and 18% as protein,high fat diet(HFD)] for 30 d and 60 d,respectively.The control group was fed a normal semi-purified diet containing adequate levels of choline(35% total calories as fat,47% as carbohydrate,and 18% as protein).Circulating and hepatic redox active and nitrogen regulating molecules(thioredoxin,glutathione,glutathione peroxidase),NO metabolites(nitrosothiols,nitrotyrosine),lipid peroxides [malondialdehyde-thiobarbituric(MDA-TBA)],and pro-inflammatory keratins(K-18) were measured on days 0,7,14,30,and 60.Mitochondrial respiratory chain proteins and the extent of hepatic fatty infiltration were evaluated.RESULTS:Both diet regimens produced liver steatosis(50% and 25% of liver slices with CD and HFD,respectively) with no signs of necro-inflammation:fat infiltration ranged from large droplets at day 14 to disseminated and confluent vacuoles resulting in microvesicular steatosis at day 30(CD) and day 60(HFD).In plasma,thioredoxin and nitrosothiols were not significantly changed,while MDA-TBA,nitrotyrosine(from 6 ± 1 nmol/L to 14 ± 3 nmol/L day 30 CD,P < 0.001,and 12 ± 2 nmol/L day 60 HFD,P < 0.001),and K-18(from 198 ± 20 to 289 ± 21 U/L day 30 CD,P < 0.001,and 242 ± 23 U/L day 60 HFD,P < 0.001) levels increased significantly with ongoing steatosis.In the liver,glutathione was decreased(from 34.0 ± 1.3 to 25.3 ± 1.2 nmol/mg prot day 30 CD,P < 0.001,and 22.4 ± 2.4 nmol/mg prot day 60 HFD,P < 0.001),while thioredoxin and glutathione peroxidase were initially increased and then decreased.Nitrosothiols were constantly increased.MDA-TBA levels were five-fold increased from 9.1 ± 1.2 nmol/g to 75.6 ± 5.4 nmol/g on day 30,P < 0.001(CD) and doubled with HFD on day 60.Realsil administration significantly lowered the extent of fat infiltration,maintained liver glutathione levels during the first half period,and halved its decrease during the second half.Also,Realsil modulated thioredoxin changes and the production of NO derivatives and significantly lowered MDA-TBA levels both in liver(from 73.6 ± 5.4 to 57.2 ± 6.3 nmol/g day 30 CD,P < 0.01 and from 27.3 ± 2.1 nmol/g to 20.5 ± 2.2 nmol/g day 60 HFD,P < 0.01) and in plasma.Changes in mitochondrial respiratory complexes were also attenuated by Realsil in HFD rats with a major protective effect on Complex Ⅱ subunit CII-30.CONCLUSION:Realsil administration effectively contrasts hepatocyte fat deposition,NO derivatives formation,and mitochondrial alterations,allowing the liver to maintain a better glutathione and thioredoxin antioxidant activity. | Ignazio Grattagliano Catia V Diogo Maria Mastrodonato Ornella de Bari Michele Persichella David QH Wang Adriana Liquori Domenico Ferri Maria Rosaria Carratù Paulo J Oliveira Piero Portincasa | 2013 | World Journal of Gastroenterology2013，19，20： | 6 |
| 3 | Over-the-scope-clip closure of long lasting gastrocutaneous fistula after percutaneous endoscopic gastrostomy tube removal in immunocompromised patients:A single center case series显示文摘Over-the-scope-clips(OTSC~?) have been shown to be an effective and safe endoscopic treatment option for the closure of gastrointestinal perforations, leakages and fistulae. Indications for endoscopic OTSC~? treatment have grown in number and also include gastro cutaneous fistula(GCF) after percutaneous endoscopic gastrostomy(PEG) tube removal. Non-healing GCF is a rare complication after removal of PEG tubes and may especially develop in immunosuppressed patients with multiple comorbidities. There is growing evidence in the literature that OTSC~? closure of GCF after PEG tube removal is emerging as an effective, simple and safe endoscopic treatment option. However current evidence is limited to the geriatric population and short standing GCF, while information on closure of long standing GCF after PEG tube removal in a younger population with significant comorbidities is lacking. In this retrospective single-center case-series we report on five patients undergoing OTSC~? closure of chronic GCF after PEG tube removal. Four out of five patients were afflicted with long lasting, symptomatic fistulae. All five patients suffered from chronic disease associated with a catabolic metabolism(cystic fibrosis, chemotherapy for neoplasia, liver cirrhosis). The mean patient age was 43 years. The mean dwell time of PEG tubes in all five patients was 808 d. PEG tube dwell time was shortest in patient 5(21 d). The mean duration from PEG tube removal to fistula closure in patients 1-4 was 360 d(range 144-850 d). The intervention was welltolerated by all patients and no adverse events occured. Successful immediate and long-term fistula closure was accomplished in all five patients. This single center case series is the first to show successful endoscopic OTSC~? closure of long lasting GCF in five consecutive middleaged patients with significant comorbidities. Endoscopic closure of chronic persistent GCF after PEG tube removal using an OTSC~? was achieved in all patients with no immediate or long-term complications. OTSC~? is a promising endoscopic treatment option for this condition with a potentially high immediate and long term success rate in patients with multiple comorbidities. | Henriette Heinrich Christoph Gubler Piero V Valli | 2017 | World Journal of Gastrointestinal Endoscopy2017，9，2： | 2 |
| 4 | CT angiography in acute ischemic stroke:preliminary results显示文摘 | Piero V Lawrence N T Neil M B | 2002 | Stroke2002，33，： | 1 |
| 5 | Relationship between changes of soil microbial biomass content and imazamox and benfluralin degradation显示文摘 | Costantino V Cristiano C Piero P | 2002 | Biol Fertile Soils2002，，35： | 1 |
| 6 | Influence of nimodipine on cerebral blood flow in cerebral ischemia显示文摘 | POZZILLIC C PIERO V PANTANO P | 1989 | J Neurology1989，236，4： | 1 |
| 7 | C-reacive Protein and interleukin-6 leveld are related to renal function in predialytic chronic renal failure显示文摘 | Panichi V Migliori M De Piero S | 2002 | Nephron2002，91，4： | 1 |
| 8 | Dysphagia-pathophysiology,diagnosis and treatment显示文摘 | Cecconi E Di Piero V | | 0，，： | 1 |
| 9 | Aminergic tone correlates of migraine and tension-type headache: a study using the tridimensional personality questionaire显示文摘 | Di Piero V Bruti G Venturi P | 2002 | Headache2002，41，1： | 1 |
| 10 | Dynamics of maturation,seasonality of reproduction and spawning grounds of the Jumbo squid Dosidicus gigas(Cephalopoda:Ommastrephidae)in Peruvian waters显示文摘 | Ricardo T Piero V Miguel R | 2001 | Fisheries research2001，54，1： | 1 |
| 11 | Dysphagia pathophysiology, diagnosis and treatment显示文摘 | Ceeconi E Di Piero V | 2012 | Front Neurol Neurosci2012，30，： | 1 |
| 12 | Bromocriptine and speech therapy in non-fluent chronic aphasia after stroke 显示文摘 | BRAGONI M ALTIERI M DI PIERO V | 2000 | Neurol Sci2000，21，1： | 1 |
| 13 | Analysis of energy comparison for crops in European agricultural systems 显示文摘 | PIERO V GIANPIETRO V | 2003 | Biomass and Bioenergy2003，25，1： | 1 |
| 14 | Dysphagia- pathophysiology, diagnosis and treatment 显示文摘 | Cecconi E Di Piero V | 2012 | Front Neural Neurosci2012，30，： | 1 |
| 15 | Dysphagia-pathophysiology,diagnosis and treatment显示文摘 | Cecconi E Di Piero V | 2012 | Front Neurol Neurosci2012，30，： | 1 |
| 16 | CT angiography in acute ischemic stroke: preliminary results 显示文摘 | Piero V Lawrence NT Nell MB | 2002 | Stroke2002，18，3： | 1 |
| 17 | Sjogren's syndrome presenting as ischemic stroke显示文摘 | Bragoni M Di Piero V Priori R | 1994 | Stroke1994，25，： | 1 |
| 18 | Dynamics of maturation, seasonality of reproduction and spawning grounds of the jumbo squid Dosidicus gigas (Cephalopoda: Ommastrephidae ) in Peruvian waters 显示文摘 | RICARDO T PIERO V MIGUEL R | 2001 | Fisheries Research2001，54，： | 1 |
| 19 | How do crop plants tolerate acid soils? Mechanisms of alumi- num tolerance and phosphorous efficiency显示文摘 | Kochian L V Hoekenga O A Pieros M A | 2004 | Annu Rev Plant Biol2004，，55： | 1 |
| 20 | Bromocriptine and speech therapy in non-fluent aphasia after stroke显示文摘 | Bragoni M Altieri M Di Piero V | | 0，，01： | 1 |
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