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)

The c-Jun N-terminal kinases (JNKs) have been the subject of intense interest since their discovery in the early 1990s. Major research programs have been directed to the screening and/or design of JNK-selective inhibitors and testing their potential as drugs. We begin this review by considering the first commercially-available JNK ATP-competitive inhibitor, SP600125. We focus on recent studies that have evaluated the actions of SP600125 in lung, brain, kidney and liver following exposure to a range of stress insults including ischemia/reperfusion. In many but not all cases, SP600125 administration has proved beneficial. JNK activation can also follow infection, and we next consider recent examples that demonstrate the benefits of SP600125 administration in viral infection. Additional ATP-competitive JNK inhibitors have now been described following high throughput screening of small molecule libraries, but information on their use in biological systems remains limited and thus these inhibitors will require further evaluation. Peptide substrate-competitive ATP-non-competitive inhibitors of JNK have also now been described, and we discuss the recent advances in the use of JNK inhibitory peptides in the treatment of neuronal death, diabetes and viral infection. We conclude by raising a number of questions that should be considered in the quest for JNK-specific inhibitors.
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PMID:Inhibitors of c-Jun N-terminal kinases: JuNK no more? 1796 1

Different pathologic patterns in multiple sclerosis (MS) are reflected by alterations of metabolites in (1)H MR spectroscopy of the brain. Elevated choline (Cho), lactate (Lac), lipids and macromolecules are reliable markers for acute demyelination regardless of the clinical entity (also in acute disseminated encephalomyelitis). N-acetyl-aspartate (NAA) is a suitable marker for neuronal integrity. It is reduced in acute MS lesions and in normal appearing white matter, even distant to acute and chronic-lesions. Recovery from reduced NAA levels to subnormal values during remyelination, and varying time courses of NAA in normal appearing white matter during relapsing remitting disease indicate the value of this spectroscopic marker for monitoring activity and recovery. Inositol (Ins) is increased in chronic MS lesions being a marker for astrocytic gliosis. In viral disease, Cho and Ins are always increased, whereas a reduction of NAA mostly reflects an advanced or a detoriated clinical state. In bacterial brain abscesses, numerous amino acids, lipids and Lac can be elevated. In ischemia, especially the Lac/NAA in comparison with perfusion and diffusion weighted imaging seems to be a new measure for areas of metabolic need, and may help to better characterise the penumbra of the stroke and the final infarct size.
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PMID:(1)H MR spectroscopy of inflammation, infection and ischemia of the brain. 1840 47

For the first time it is proved, that patients with an acute virus myocarditis have statistically confirmed authentic reduction in quantity of thrombocytes, extention of parameters of a activated partial thrombin time, reduction in concentration of a heparin-antithrombin III (AT-III) complex against suppressed enzyme of antiradical protection - superoxide dismutase and it has led to activization of a malonic dialdehyde in erythrocytes, thrombocytes and blood serum. In case of the development of an acute virus infection especially caused cardiotrophic strain Consaki, virus CVB 1-CVB 4, thrombocytes, according to P. Nemetchek-Gansler, acquire not pertaining to them ability for phagocytosis of viruses with following reduction in quantity of thrombocytes and increase in aggregation abilities of thrombocytes what influence the state of duration index of contact aggregation of thrombocytes with the tendency to shorten this duration, and also it may develop hypoxia, an ischemia and the subsequent necrosis of cardiomyocytes, that is to an acute virus myocarditis that demands corresponding correction with medications.
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PMID:[Total index of thrombocyte aggregation in patients with an acute viral myocarditis]. 1866 37

Cardiac allograft vasculopathy (CAV) remains a life-threatening complication after heart transplantation (HT). Recipients with severe intimal thickening are 10-fold more likely to suffer cardiac events than those without severe hyperplasia. From July 1987 to July 2007, we performed 323 HTs with 5-year actuarial freedom from CAV of 69%, similar to the data reported by the International Society for Heart and Lung Transplantation, namely, 68% at 5 years. Therefore, CAV is not uncommon in Asia. The pathogenesis of CAV is initial endothelial injury followed by intimal hyperplasia and proliferation of vascular smooth muscle cells. It may be caused by both immunological events (involving T or B cells in response to donor major histocompatibility antigens, or natural killer [NK] cell-triggered recruitment of T cells not responsive to donor alloantigen) and nonimmunologic factors, such as older age, ischemia-reperfusion injury, viral infection (particularly cytomegalovirus [CMV] infection), immunosuppressive drugs, and classic risk factors, such as hyperlipidemia, insulin resistance, and hypertension. The therapy for CAV has been disappointing, despite prescriptions of statin lipid-lowering agents, calcium-channel blockers, angiotensin-converting enzyme inhibitors, and antiproliferative drugs. Patients with CAV are often not amenable to successful revascularization (medical or surgical) because of the diffuse obliterative process. Prophylaxis of CAV starts with modification of risk factors: hypertension, hyperlipemia, hyperglycemia, obesity, and smoking, as well as promotion of exercise programs. The HMG-CoA reductase inhibitors and antiproliferative drugs may slow the progression of CAV by various immunologic and nonimmunologic effects. Prevention of CMV infection reduces CAV. Mycophenolate mofetil and signal transduction inhibitors, such as everolimus, reduce intimal thickening and CAV.
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PMID:Treatment and prophylaxis of cardiac allograft vasculopathy. 1892 15

According to transplant registries, grafts from elderly donors have lower survival rates. During 1999-2005, we evaluated the outcomes of 89 patients who received a liver from a donor aged > or = 60 years and managed with the low liver-damage strategy (LLDS), based on the preoperative donor liver biopsy and the shortest possible ischemia time (group D > or = 60-LLDS). Group D > or = 60-LLDS was compared with 198 matched recipients, whose grafts were not managed with this strategy (89 donors < 60 years, group D < 60-no-LLDS and 89 donors aged > or =60 years, group D > or = 60-no-LLDS). In the donors proposed from the age group of > or =60 years, the number of donors rejected decreased during the study period and the LLDS was found to be responsible for this in a significant manner (47% vs. 60%, respectively P < 0.01). Among the recipients transplanted, the clinical features (age, gender, viral infection, child and model for end-stage liver disease score) were comparable among groups, but group D > or = 60-LLDS had a lower mean ischemia time: 415 +/- 106 min vs. 465 +/- 111 (D < 60-no-LLDS), P < 0.05 and vs. 476 +/- 94 (D > or = 60-no-LLDS), P < 0.05. After a median follow-up of 3 years, the 1- and 3-year graft survival rates of group D > or = 60-LLDS (84% and 76%) were comparable with group D < 60-no-LLDS (89% and 76%) and were significantly higher than group D > or = 60-no-LLDS (71% and 54%), P < 0.005. In conclusion, the LLDS optimized the use of livers from elderly donors.
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PMID:Liver transplantations with donors aged 60 years and above: the low liver damage strategy. 1904 Apr 83

The unique immunologic environment of the liver, together with its anatomic location downstream of the gut, influences the maturation and function of its interstitial dendritic cell (DC) populations. These well-equipped, antigen-presenting cells play critical roles in regulation of innate and adaptive immunity. New information is emerging about the molecular regulation of liver DC maturation and function, and their tolerogenic potential, while new insight is being gained regarding interactions between liver DC and other immune effector cell populations (NK, NKT cells) in addition to T cells. During transplantation, factors that affect liver DC biology include ischemia-reperfusion injury, liver regeneration, viral infection and the actions of anti-inflammatory and immunosuppressive drugs. Herein, we review the molecular and cell biology of hepatic DC populations in relation to the regulation of alloimmune responses and liver transplant outcome.
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PMID:Dendritic cell immunobiology in relation to liver transplant outcome. 1948 29

Pandemic influenza A (H1N1) virus infection is rapidly spreading and has also become a common problem in Germany. Many cases with severe clinical presentation and death have been documented, especially in persons with underlying medical conditions. As of December 15, 2009, Germany has reported 119 H1N1-associated deaths. We report here the first H1N1-associated death in Germany, a 36-year-old woman with morbid obesity. The patient underwent a laparotomy with colon resection due to colon ischemia, a rare visceral complication in such cases. In this article an attempt has been made to reflect the state of requirements in terms of safety, occupational health, hygiene and working conditions with respect to activities involving logistics in the diagnostics, treatment (also surgical) and handling of such patients. Given the rapidly evolving nature the outbreak of human infection with the novel influenza A (H1N1) virus, influenza vaccination is recommended as the only way to prevent the infection of health care workers and patients with underlying medical conditions.
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PMID:[Hemicolectomy for ischemic colitis : A case report of a (H1N1) virus-associated death]. 2018 77

Perturbation of the endoplasmic reticulum (ER) results in a conserved stress response called the unfolded protein response (UPR). Macrophages undergoing a UPR respond to LPS with log-fold increased production of IFN-beta, a cytokine with diverse roles in innate and adaptive immunity. In this study, we found that thapsigargin-induced ER stress augmented recruitment of IFN regulatory factor-3, CREB binding protein/p300, and transcriptional machinery to the murine ifnb1 promoter during LPS stimulation. Although full synergistic IFN-beta production requires X-box binding protein 1 (XBP-1), this UPR-regulated transcription factor did not appreciably bind the ifnb1 promoter. However, XBP-1 bound a conserved site 6.1 kb downstream of ifnb1, along with IFN regulatory factor-3 and CREB binding protein only during concomitant UPR and LPS stimulation. XBP-1 physically associates with p300, suggesting a mechanism of multimolecular assembly at the +6.1 kb site. Luciferase reporter assays provide evidence this +6 kb region functions as an XBP-1-dependent enhancer of ifnb1 promoter activity. Thus, this study identifies a novel role for a UPR-dependent transcription factor in the regulation of an inflammatory cytokine. Our findings have broader mechanistic implications for the pathogenesis of diseases involving ER stress and type I IFN, including viral infection, ischemia-reperfusion injury, protein misfolding, and inflammatory diseases.
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PMID:XBP-1 couples endoplasmic reticulum stress to augmented IFN-beta induction via a cis-acting enhancer in macrophages. 2066 Mar 50

Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD), with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC). Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2-15%) versus cirrhosis (15-20%) is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular system and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.
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PMID:Acetaldehyde adducts in alcoholic liver disease. 2071 42

Demyelination is characterized by the loss of myelin with the preservation of axons. Demyelinating diseases can be classified into several categories: demyelination due to inflammation, viral infection, osmotic derangements and hypoxic ischemia. In particular, osmotic myelinolysis is representative, and is associated with hyperosmolality, hypokalemia or rapid correction of hyponatremia. Osmotic myelinolysis was reported to be associated with underlying conditions, such as alcoholism, diuretics and malnutrition. A 67-year-old woman with hypertension was scheduled to undergo both total knee replacements (TKR). She was observed to be lethargic with dysphagia and quadriplegia after the second TKR. She had been taking diuretics for a long time, and did not have an adequate amount of food intake due to patient controlled analgesia and a gastric ulcer after the first TKR. A laboratory examination revealed hypokalemia but normonatremia. T2 weighted-MRI revealed abnormal high signal intensity in the basal ganglia and periventricular area. This case was diagnosed with osmotic myelinolysis associated with hypokalemia without an apparent sodium imbalance.
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PMID:Extensive demyelinating change in cerebrum after a total knee replacement -A case report-. 2128 40


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