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 de...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.展开更多
Cholesterol gallstone disease is a common clinical condition influenced by genetic factors,increasing age,female gender,and metabolic factors.Although laparoscopic cholecystectomy is currently considered the gold stan...Cholesterol gallstone disease is a common clinical condition influenced by genetic factors,increasing age,female gender,and metabolic factors.Although laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones,new perspectives regarding medical therapy of cholelithiasis are currently under discussion,also taking into account the pathogenesis of gallstones,the natural history of the disease and the analysis of the overall costs of therapy.A careful selection of patients may lead to successful nonsurgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent stones.The classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations,suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe),or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis,might be proposed as additional approaches for treating cholesterol gallstones.In this review we discuss old,recent and future perspectives on medical treatment of cholesterol cholelithiasis.展开更多
This article discusses a practical, evidence-based approach to the diagnosis and management of liver cirrhosis by focusing on etiology, severity, presence of complications, and potential home-managed treatments. Relev...This article discusses a practical, evidence-based approach to the diagnosis and management of liver cirrhosis by focusing on etiology, severity, presence of complications, and potential home-managed treatments. Relevant literature from 1985 to 2010 (PubMed) was reviewed. The search criteria were peer-reviewed full papers published in English using the following MESH headings alone or in combination: "ascites", "liver fibrosis", "cirrhosis", "chronic hepatitis", "chronic liver disease", "decompensated cirrhosis", "hepatic encephalopathy", "hypertransaminasemia", "liver transplantation" and "portal hypertension". Forty-nine papers were selected based on the highest quality of evidence for each section and type (original, randomized controlled trial, guideline, and review article), with respect to specialist setting (Gastroenterology, Hepatology, and Internal Medicine) and primary care. Liver cirrhosis from any cause represents an emerging health issue due to the increasing prevalence of the disease and its complications worldwide. Primary care physicians play a key role in early identification of risk factors, in the management of patients for improving quality and length of life, and for preventing complications. Specialists, by contrast, should guide specific treatments, especially in the case of complications and for selecting patient candidates for liver transplantation. An integrated approach between specialists and primary care physicians is essential for providing better outcomes and appropriate home care for patients with liver cirrhosis.展开更多
In gastroenterological practice,breath tests(BTs)are diagnostic tools used for indirect,non-invasive assessment of several pathophysiological metabolic processes,by monitoring the appearance in breath of a metabolite ...In gastroenterological practice,breath tests(BTs)are diagnostic tools used for indirect,non-invasive assessment of several pathophysiological metabolic processes,by monitoring the appearance in breath of a metabolite of a specific substrate.Labelled substrates originally employed radioactive carbon 14(^(14)C)and,more recently,the stable carbon 13 isotope(^(13)C)has been introduced to label specific substrates.The ingested^(13)C-substrate is metabolized,and exhaled^(13)CO_(2)is measured by mass spectrometry or infrared spectroscopy.Some^(13)C-BTs evaluate specific(microsomal,cytosolic,and mitochondrial)hepatic metabolic pathways and can be employed in liver diseases(i.e.simple liver steatosis,non-alcoholic steato-hepatitis,liver fibrosis,cirrhosis,hepatocellular carcinoma,drug and alcohol effects).Another field of clinical application for^(13)C-BTs is the assessment of gastric emptying kinetics in response to liquids(^(13)C-acetate)or solids(^(13)C-octanoic acid in egg yolk or in a pre-packed muffin or the^(13)C-Spirulina platensis given with a meal or a biscuit).Studies have shown that^(13)C-BTs,used for gastric emptying studies,yield results that are comparable to scintigraphy and can be useful in detecting either delayed-(gastroparesis)or accelerated gastric emptying or changes of gastric kinetics due to pharmacological effects.Thus,^(13)C-BTs represent an indirect,cost-effective and easy method of evaluating dynamic liver function and gastric kinetics in health and disease,and several other potential applications are being studied.展开更多
Consumption of natural products such as herbs,spices,plant-derived compounds,and foods is on the rise globally.The use of these substances is widely recognized as an integral part of culture and tradition,with the phi...Consumption of natural products such as herbs,spices,plant-derived compounds,and foods is on the rise globally.The use of these substances is widely recognized as an integral part of culture and tradition,with the philosophy being“no benefit is no harm”.The utility of medicinal plants and extracts is under scrutiny,and the scientific community needs to clarify many conceptual gaps.Medicinal plants are rich in bioactive phytochemicals that produce chemopreventive effects at different levels,including cellular,animal,and clinical.The ultimate translational value is often missing,and some studies suggest that botanicals may contain toxic compounds that cause acute or chronic toxicity.In this regard,the liver is the center,and herbal products can show protective effects or induce hepatotoxicity,thereby promoting liver cancer.In this review article,we examine a range of herbal products implicated in hepatocarcinogenesis and extend the discussion to herbal products that may be potentially involved in the prevention and treatment of liver carcinoma.展开更多
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.
基金Supported by (in part) research grants from the Italian Ministry of University and Research (No. FIRB 2003 RBAU01RANB002)the Italian National Research Council (short-term mobility grant 2005)+2 种基金the University of Bari (grants No. ORBA09XZZT and No. ORBA08YHKX) (to Portincasa P)University of Bari (No. DR11598-2009)the National Institutes of Health (US Public Health Service) (research grants No. DK54012 and No. DK73917) (to Wang DQH)
文摘Cholesterol gallstone disease is a common clinical condition influenced by genetic factors,increasing age,female gender,and metabolic factors.Although laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones,new perspectives regarding medical therapy of cholelithiasis are currently under discussion,also taking into account the pathogenesis of gallstones,the natural history of the disease and the analysis of the overall costs of therapy.A careful selection of patients may lead to successful nonsurgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent stones.The classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations,suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe),or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis,might be proposed as additional approaches for treating cholesterol gallstones.In this review we discuss old,recent and future perspectives on medical treatment of cholesterol cholelithiasis.
文摘This article discusses a practical, evidence-based approach to the diagnosis and management of liver cirrhosis by focusing on etiology, severity, presence of complications, and potential home-managed treatments. Relevant literature from 1985 to 2010 (PubMed) was reviewed. The search criteria were peer-reviewed full papers published in English using the following MESH headings alone or in combination: "ascites", "liver fibrosis", "cirrhosis", "chronic hepatitis", "chronic liver disease", "decompensated cirrhosis", "hepatic encephalopathy", "hypertransaminasemia", "liver transplantation" and "portal hypertension". Forty-nine papers were selected based on the highest quality of evidence for each section and type (original, randomized controlled trial, guideline, and review article), with respect to specialist setting (Gastroenterology, Hepatology, and Internal Medicine) and primary care. Liver cirrhosis from any cause represents an emerging health issue due to the increasing prevalence of the disease and its complications worldwide. Primary care physicians play a key role in early identification of risk factors, in the management of patients for improving quality and length of life, and for preventing complications. Specialists, by contrast, should guide specific treatments, especially in the case of complications and for selecting patient candidates for liver transplantation. An integrated approach between specialists and primary care physicians is essential for providing better outcomes and appropriate home care for patients with liver cirrhosis.
文摘In gastroenterological practice,breath tests(BTs)are diagnostic tools used for indirect,non-invasive assessment of several pathophysiological metabolic processes,by monitoring the appearance in breath of a metabolite of a specific substrate.Labelled substrates originally employed radioactive carbon 14(^(14)C)and,more recently,the stable carbon 13 isotope(^(13)C)has been introduced to label specific substrates.The ingested^(13)C-substrate is metabolized,and exhaled^(13)CO_(2)is measured by mass spectrometry or infrared spectroscopy.Some^(13)C-BTs evaluate specific(microsomal,cytosolic,and mitochondrial)hepatic metabolic pathways and can be employed in liver diseases(i.e.simple liver steatosis,non-alcoholic steato-hepatitis,liver fibrosis,cirrhosis,hepatocellular carcinoma,drug and alcohol effects).Another field of clinical application for^(13)C-BTs is the assessment of gastric emptying kinetics in response to liquids(^(13)C-acetate)or solids(^(13)C-octanoic acid in egg yolk or in a pre-packed muffin or the^(13)C-Spirulina platensis given with a meal or a biscuit).Studies have shown that^(13)C-BTs,used for gastric emptying studies,yield results that are comparable to scintigraphy and can be useful in detecting either delayed-(gastroparesis)or accelerated gastric emptying or changes of gastric kinetics due to pharmacological effects.Thus,^(13)C-BTs represent an indirect,cost-effective and easy method of evaluating dynamic liver function and gastric kinetics in health and disease,and several other potential applications are being studied.
基金supported by funding from the European Union’s Horizon 2020 Research and Innovation program under the Marie Skłodowska-Curie Grant Agreement No.722619(FOIE GRAS)Grant Agreement No.734719(mtFOIE GRAS).
文摘Consumption of natural products such as herbs,spices,plant-derived compounds,and foods is on the rise globally.The use of these substances is widely recognized as an integral part of culture and tradition,with the philosophy being“no benefit is no harm”.The utility of medicinal plants and extracts is under scrutiny,and the scientific community needs to clarify many conceptual gaps.Medicinal plants are rich in bioactive phytochemicals that produce chemopreventive effects at different levels,including cellular,animal,and clinical.The ultimate translational value is often missing,and some studies suggest that botanicals may contain toxic compounds that cause acute or chronic toxicity.In this regard,the liver is the center,and herbal products can show protective effects or induce hepatotoxicity,thereby promoting liver cancer.In this review article,we examine a range of herbal products implicated in hepatocarcinogenesis and extend the discussion to herbal products that may be potentially involved in the prevention and treatment of liver carcinoma.