Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between March 1984 and February 1991, six orthotopic liver transplantations were performed at the Chang Gung Memorial Hospital in Taiwan. The indications for transplantation were Wilson's disease (5 patients) and biliary atresia (1 patient). Donors and recipients were matched only for size and ABO blood group compatibility, and the recipient operations were performed without the use of a venovenous bypass. Arterial reconstruction was carried out by end-to-end hepatic artery anastomosis (4), thoracic aortic conduit (1), or interposition of an iliac artery graft (1), whereas biliary reconstruction was accomplished by a choledochocholedochostomy using a T-tube stent (4) or a choledochocholedochostomy using an external cholecystostomy without stenting (2). Biliary complications occurred in three patients, and all required additional surgery. The average duration of donor-liver cold ischemia, operating time, and blood loss during surgery were 7 h and 50 min (range, 4.5-9 h), 13.5 h (range, 11.8-17 h), and 4,385 ml (range, 750-12,000 ml), respectively. The immunosuppressive regimens included a cyclosporin-steroid combination (n = 2) and a triple-drug combination (n = 4). All except one of the surviving patients experienced at least one rejection episode that was reversed by a methyl-prednisolone bolus and/or recycle. One patient developed a primary cytomegalovirus (CMV) infection that responded well to Ganciclovir treatment. Two of the patients died, one of injuries sustained in a traffic accident 3 years after transplantation, and the other of massive upper gastrointestinal bleeding. The overall survival value at 3 months was 83%, and the follow-up period ranged from 3 months to 7 years. All of the survivors have achieved complete rehabilitation and currently enjoy an excellent quality of life with normal liver function. Although the present study involved a small number of cases, our results indicate that liver transplantation can be successfully achieved in a high proportion of patients with acceptable morbidity, mortality, and cost in an Asian setting. The extreme shortage of donor organs is currently the most important obstacle limiting the application of liver transplantation in Taiwan.
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PMID:Liver transplantation in Taiwan: the Chang Gung experience. 145 66

Fulminant hepatic failure (FHF) is an acute and eventually fatal illness, caused by a severe hepatocyte damage with massive necrosis. Its hallmarks are hepatic encephalopathy and a prolonged prothrombin time (< 40%). FHF is currently defined as hyperacute (encephalopathy appearing within 7 days of the onset of jaundice), acute (encephalopathy appearing between 8 and 28 days) or subacute (encephalopathy appearing between 5 and 12 weeks). FHF can be caused by viruses, drugs, toxins, and miscellaneous conditions such as Wilson's disease, Budd-Chiari syndrome, ischemia and others. However, a single most common etiology is still not defined. Factors that are valuable in assessing the likelihood of spontaneous recovery are age, etiology, degree of encephalopathy, prothrombin time and serum bilirubin. The management is based in the early treatment of infections, hemodynamic abnormalities, cerebral edema, and other associated conditions. Liver transplant has emerged as the most important advance in the therapy of FHF, with a survival rate that ranges between 60 and 80%. The use of hepatic support systems, extracorporeal liver support and auxiliary liver transplantation are innovative therapies.
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PMID:[Fulminant hepatic failure]. 1219 94

The TNFalpha receptor super-family consists of several members sharing a sequence homology in a unique function domain, the death domain, which is located in the intracellular portion of the receptor. These so-called death receptors, including Fas, TNF-R1 and TRAIL-R1/TRAIL-R2, are expressed on hepatocytes. When stimulated by their ligands, FasL, TNFalpha or TRAIL, respectively, the death receptors can activate multiple death domain-initiated apoptosis programs, including both extrinsic and intrinsic pathways. A cascade of caspases is activated, which cleave proteins important for the cell structure and function. Activation of the intrinsic pathway also leads to mitochondrial release of several apoptotic proteins and mitochondrial dysfunction, which kill the cell through both caspase-dependent and caspase-independent mechanisms. Death receptor-induced hepatocyte apoptosis contributes to the development of a number of liver diseases, including viral hepatitis, inflammatory hepatitis, Wilson's disease, alcoholic liver disease, endotoxiemia-induced liver failure and ischemia/reperfusion-induced liver damage. This article comprehensively reviews the mechanisms of induction and regulation of death receptor-initiated apoptosis in hepatocytes, examines how these molecular events affect our understanding of the pathogenesis of these diseases and further discusses the potential therapeutic application of the knowledge. We hope we can provide a cohesive and integrated perspective on the many aspects of these complicated processes.
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PMID:Death receptor activation-induced hepatocyte apoptosis and liver injury. 1452 81

Oxidative stress is a common feature in most hepatopathies. In recent years, evidence has accumulated that reactive oxygen species (ROS) induce a number of functional changes either deleterious or adaptive in the capability of the hepatocytes to produce bile and to secrete exogenous and endogenous compounds. This review is aimed to describe the mechanisms involved in these alterations. For this purpose, we will summarize: 1) The current evidence that acutely-induced oxidative stress is cholestatic, by describing the mechanisms underlying the hepatocyte secretory failure, including the disorganization of the actin cytoskeleton and its most noticeable consequences, the impairment of tight-junctional structures and the endocytic internalization of canalicular transporters relevant to bile formation. 2) The role for oxidative-stress-activated signalling pathways in the pathomechanisms described above, particularly those involving Ca2+ elevation and its consequent activation of Ca2+ -dependent PKC isoforms. 3) The mechanisms involved in the adaptive response against oxidative stress mediated by ROS-responsive transcription factors, involving up-regulation of GSH-synthesizing enzymes, GSH-detoxifying enzymes and the hepatocellular efflux pumps; this response enhances the co-coordinated inactivation by GSH conjugation of lipid peroxides and their further cellular extrusion. 4) The manner this adaptive response can be surpassed by the sustained production of ROS, thus inducing transcriptional and posttranscriptional changes in transporters relevant to bile formation, as has been shown to occur, for example, after long-term administration of aluminum to rats, in the Long-Evans Cinnamon rat (a model of chronic hepatic copper accumulation mimicking Wilson's disease), and in ischemia-reperfusion injury.
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PMID:Oxidative stress: a radical way to stop making bile. 1837 63

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are created in normal hepatocytes and are critical for normal physiologic processes, including oxidative respiration, growth, regeneration, apoptosis, and microsomal defense. When the levels of oxidation products exceed the capacity of normal antioxidant systems, oxidative stress occurs. This type of stress, in the form of ROS and RNS, can be damaging to all liver cells, including hepatocytes, Kupffer cells, stellate cells, and endothelial cells, through induction of inflammation, ischemia, fibrosis, necrosis, apoptosis, or through malignant transformation by damaging lipids, proteins, and/or DNA. In Part I of this review, we will discuss basic redox biology in the liver, including a review of ROS, RNS, and antioxidants, with a focus on nitric oxide as a common source of RNS. We will then review the evidence for oxidative stress as a mechanism of liver injury in hepatitis (alcoholic, viral, nonalcoholic). In Part II of this review, we will review oxidative stress in common pathophysiologic conditions, including ischemia/reperfusion injury, fibrosis, hepatocellular carcinoma, iron overload, Wilson's disease, sepsis, and acetaminophen overdose. Finally, biomarkers, proteomic, and antioxidant therapies will be discussed as areas for future therapeutic interventions.
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PMID:Nitric oxide and redox regulation in the liver: part II. Redox biology in pathologic hepatocytes and implications for intervention. 2040 Jan 12

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are created in normal hepatocytes and are critical for normal physiologic processes, including oxidative respiration, growth, regeneration, apoptosis, and microsomal defense. When the levels of oxidation products exceed the capacity of normal antioxidant systems, oxidative stress occurs. This type of stress, in the form of ROS and RNS, can be damaging to all liver cells, including hepatocytes, Kupffer cells, stellate cells, and endothelial cells, through induction of inflammation, ischemia, fibrosis, necrosis, apoptosis, or through malignant transformation by damaging lipids, proteins, and/or DNA. In Part I of this review, we will discuss basic redox biology in the liver, including a review of ROS, RNS, and antioxidants, with a focus on nitric oxide as a common source of RNS. We will then review the evidence for oxidative stress as a mechanism of liver injury in hepatitis (alcoholic, viral, nonalcoholic). In Part II of this review, we will review oxidative stress in common pathophysiologic conditions, including ischemia/reperfusion injury, fibrosis, hepatocellular carcinoma, iron overload, Wilson's disease, sepsis, and acetaminophen overdose. Finally, biomarkers, proteomic, and antioxidant therapies will be discussed as areas for future therapeutic interventions.
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PMID:Nitric oxide and redox regulation in the liver: Part I. General considerations and redox biology in hepatitis. 2044 70

Homeostasis of metal ions such as Zn(2+) is essential for proper brain function. Moreover, the list of psychiatric and neurodegenerative disorders involving a dysregulation of brain Zn(2+)-levels is long and steadily growing, including Parkinson's and Alzheimer's disease as well as schizophrenia, attention deficit and hyperactivity disorder, depression, amyotrophic lateral sclerosis, Down's syndrome, multiple sclerosis, Wilson's disease and Pick's disease. Furthermore, alterations in Zn(2+)-levels are seen in transient forebrain ischemia, seizures, traumatic brain injury and alcoholism. Thus, the possibility of altering Zn(2+)-levels within the brain is emerging as a new target for the prevention and treatment of psychiatric and neurological diseases. Although the role of Zn(2+) in the brain has been extensively studied over the past decades, methods for controlled regulation and manipulation of Zn(2+) concentrations within the brain are still in their infancy. Since the use of dietary Zn(2+) supplementation and restriction has major limitations, new methods and alternative approaches are currently under investigation, such as the use of intracranial infusion of Zn(2+) chelators or nanoparticle technologies to elevate or decrease intracellular Zn(2+) levels. Therefore, this review briefly summarizes the role of Zn(2+) in psychiatric and neurodegenerative diseases and highlights key findings and impediments of brain Zn(2+)-level manipulation. Furthermore, some methods and compounds, such as metal ion chelation, redistribution and supplementation that are used to control brain Zn(2+)-levels in order to treat brain disorders are evaluated.
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PMID:Brain-Delivery of Zinc-Ions as Potential Treatment for Neurological Diseases: Mini Review. 2210 82

Liver transplantation has been an accepted treatment for end-stage liver disease since the 1980s. The development of living donor liver transplantation (LDLT) was driven by limited deceased donor organ donation and a response to the growing demand for the option of liver replacement. LDLT is now performed with high rates of success due to judicious donor and recipient selection, careful preoperative planning, excellent anesthesia management, and prompt detection and treatment of complications. The first successful liver transplantation in Asia was performed in 1984, in Chang Gung Memorial Hospital in a Taiwanese adolescent with Wilson's disease, complicated by end-stage liver cirrhosis. The longest Asian liver transplant survivor has now been living for 26 years and that patient's transplant was also performed in Chang Gung Memorial Hospital. Through December 31, 2011, a total of 924 (783 living donor, 141 deceased donor) liver transplants have been performed at the Kaohsiung Chang Gung Memorial Hospital, where both graft and patient survivals are excellent. For biliary atresia, hepatitis B virus cirrhosis, and hepatocellular carcinoma recipients, our 5-year LDLT survival rates are 98%, 94%, and 90%, respectively. Our overall (deceased and living donor) actuarial 3-year survival rate is 91%. Innovative techniques in LDLT represent technical refinements in hepatic vein, portal vein, hepatic artery, and biliary reconstruction approaches. Hepatic vein reconstruction is highlighted by venoplasty reconstructions in both graft hepatic vein orifices and recipient hepatic veins, to ensure adequate outflow and decrease ischemia times during implantation. Vascular interposition to reconstruct middle hepatic vein tributaries with either fresh or cryopreserved vessels is used when the middle hepatic vein is not routinely harvested with the graft. We have extended the routine use of microsurgical techniques, initially for hepatic artery reconstruction, to biliary reconstruction where the possibility of duct-to-duct reconstruction is performed with accuracy and precision in pediatric non-biliary atresia and in multiple, small bile ducts. Long-term survival has always been related to the immunosuppression regimen, which influences outcome. Newer drugs do not equate to lesser complications. Rather, improvement in how we can find new uses for old drugs is now the norm. Less immunosuppression, as long as hepatic function is maintained at an acceptable level, decreases the chances of long-term complications related to immunosuppression use.
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PMID:More than a quarter of a century of liver transplantation in Kaohsiung Chang Gung Memorial Hospital. 2275 15

Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis). Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson's disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis.
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PMID:Metabolic pancreatitis: Etiopathogenesis and management. 2408 60