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)

Programmed cell death or apoptosis is a physiologically important process in neurogenesis wherein approximately 50% of the neurons apoptose during maturation of the nervous system. However, premature apoptosis and/or aberrations in apoptosis control contribute to the pathogenesis of a variety of neurological disorders including acute brain injury such as trauma, spinal cord injury, ischemic stroke and ischemia/reperfusion as well as chronic disease states such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, spinal muscular atrophy, and diabetic neuropathy. The current review will focus on two major topics, namely, the general concepts of our current understanding of the apoptosis death machinery, its mediators and regulation, and the relationship between aberrant apoptosis and genesis of neurodegenerative disorders. This knowledge of apoptosis mechanisms will underpin the basis for development of novel therapeutic strategies and treatment modalities that are directed at control of the neuronal apoptotic death program.
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PMID:Apoptosis in acute and chronic neurological disorders. 1497 68

Epilepsy is a chronic disease, often with an onset during childhood and characterized by spontaneous and recurrent seizures. It concerns 0.5-1% of children under 16 years of age. A classification proposed by the International League Against Epilepsy (ILEA) in 2001 takes into account recent genetic factors involved in epilepsy and attenuates the sharp demarcation between generalized and partial seizures. This classification tends to define whether imaging is indicated or not. Imaging is useless in simple cases of fits associated with hyperthermia and in benign idiopathic epilepsy. It is debated if it is a first episode of epilepsy without a particular context and no neurological signs. In all other cases of epilepsy in children, imaging is indicated. In descending order of frequency the possible causes include malformations (as abnormal gyral development and phakomatoses), hypoxic-ischemic lesions, non-accidental injuries, infections, metabolic diseases and tumors. Being much more sensitive than computed tomography (CT), magnetic resonance imaging (MRI) is the technique of choice to identify an underlying cause in symptomatic epilepsy. Clinical data are mandatory in order to direct a proper MRI investigation. The recently developed diffusion-weighted sequence is particularly useful in the acute phase of certain events such as hypoxia-ischemia, trauma and metabolic disease. CT scan is used in emergency situations and also as a complement to MRI for example to identify calcified lesions. In this way, imaging contributes to establish the nature and define the extension of epileptogenic lesions, thereby guiding therapeutic management. MRI also allows follow-up of the consequences of repeated seizures (such as mesial temporal sclerosis and selective neuronal necrosis) on the cerebral parenchyma and plays a role in the establishment of a prognosis.
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PMID:[Imaging in paediatric epilepsy]. 1573 36

Atherosclerosis is a chronic disease potentially involving the whole arterial system that causes a spectrum of clinical manifestations ranging from acute myocardial infarction to stable angina or stroke. The continuous accumulation of lipids, and fibrous and inflammatory elements in the arterial wall of the coronary tree leads to progressive lumen narrowing with subsequent ischemia and symptom-limited exercise. Acute coronary syndromes (unstable angina, acute myocardial infarction) have a more complex and dynamic pathogenesis of which coronary plaque rupture and thrombosis represent only the final common pathway that suddenly compromises resting coronary flow. As only some plaques lead to clinical manifestations whereas many others remain asymptomatic, the aim of this review was to analyze the complex mechanisms leading to plaque complication and rupture with respect to systemic and local features.
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PMID:[Pathogenesis of acute coronary syndromes: the activated plaque]. 1594 13

The heart is capable of utilizing a variety of substrates to produce the necessary ATP for cardiac function. AMP-activated protein kinase (AMPK) has emerged as a key regulator of cellular energy homeostasis and coordinates multiple catabolic and anabolic pathways in the heart. During times of acute metabolic stresses, cardiac AMPK activation seems to be primarily involved in increasing energy-generating pathways to maintain or restore intracellular ATP levels. In acute situations such as mild ischemia or short durations of severe ischemia, activation of cardiac AMPK appears to be necessary for cardiac myocyte function and survival by stimulating ATP generation via increased glycolysis and accelerated fatty acid oxidation. Whereas AMPK activation may be essential for adaptation of cardiac energy metabolism to acute and/or minor metabolic stresses, it is unknown whether AMPK activation becomes maladaptive in certain chronic disease states and/or extreme energetic stresses. However, alterations in cardiac AMPK activity are associated with a number of cardiovascular-related diseases such as pathological cardiac hypertrophy, myocardial ischemia, glycogen storage cardiomyopathy, and Wolff-Parkinson-White syndrome, suggesting the possibility of a maladaptive role. Although the precise role AMPK plays in the diseased heart is still in question, it is clear that AMPK is a major regulator of cardiac energy metabolism. The consequences of alterations in AMPK activity and subsequent cardiac energy metabolism in the healthy and the diseased heart will be discussed.
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PMID:Role of AMP-activated protein kinase in healthy and diseased hearts. 1684 22

The immune response to foreign or self antigens mediates liver damage during viral or autoimmune hepatitis. However, it now appears that also specific antigen-independent liver diseases, where liver damage has been attributed to occur from oxygen radical formation, seem to be mediated by cells of the innate and adaptive immune response. These liver disorders include alcoholic liver disease, non-alcoholic fatty liver disease or non-alcoholic steatohepatitis, and ischemia/reperfusion injury that impairs the function of liver grafts. Here it seems that breakdown of the gastrointestinal barrier might increase the concentration of bacterial toxins in the portal blood, which then activate cells of the innate immune system, e. g., Kupffer cells, but, depending on the nature of the toxin, probably also conventional T cells. Invariant NKT cells which specifically recognize glycolipid antigens were supposed to become activated during metabolic disorders related to obesity. However, both steatohepatitis as well as ischemia/reperfusion injury are associated with a Th1 cytokine response characterized by IFNgamma and TNFalpha elevation, that might reflect an NKT cell response on the one hand, but also conventional T lymphocytes, in particular CD4 (+) T cells, are critical for the pathophysiology of these disorders. In 1992 we described a model of T cell-dependent liver injury inducible by the T cell-mitogenic lectin concanavalin A. This model of immune-mediated liver injury was intensively used to study pathophysiological immune effector mechanisms as well as cytokine signaling important for hepatocellular apoptosis, inhibition of apoptosis and regeneration. Recently it became evident that the inflammatory response in this model is regulated by specific cytokine signals as well as by immune regulator cells. The immune-regulatory functions of the liver are of particular interest with respect to the scavenger function of this organ, being continuously exposed to foreign antigenic material from the gut which should be eliminated without causing chronic disease.
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PMID:Cellular and cytokine-mediated mechanisms of inflammation and its modulation in immune-mediated liver injury. 1723 22

Pilonidal disease is a common chronic disorder of the sacrococcygeal area affecting young people. Recent reports have advocated different surgical approaches, such as open or closed technique, but recurrence complicates all forms of treatment. We conducted this case review to evaluate the validity of Limberg flap reconstruction method in the treatment of chronic recurrent pilonidal disease. In the period between September 2003 and December 2004, 32 male patients with complicated/recurrent pilonidal disease were operated on using the Limberg flap reconstruction method. The patients' mean age was 26.4 + 1.6 years (range 19-47 years). All patients fared well, had a satisfactory wound healing, had minimal pain and were mobilized immediately after surgery. They stayed at hospital for 6 to 32 hours. No patient had serious wound infection or flap ischemia. They all returned to normal activity within 4 to 12 days. Follow-up ranged between 14 and 28 months. No patient had recurrence during the above period. Limberg flap reconstruction has several advantages compared to the classical surgical methods for the treatment of pilonidal disease. The patients have a short hospital stay, are mobilized soon after surgery and have a minimal morbidity and recurrence rate.
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PMID:Limberg flap reconstruction for the treatment of pilonidal sinus disease. 1727 44

Endothelial progenitor cells (EPCs) participate in vascular healing during both acute injury and chronic disease. The quantity and quality of circulating EPCs correlate inversely with the severity of vascular disease, such that reduced number and/or function of EPCs are significant independent risk factors for impaired healing capacity, dysfunctional endothelium, and progression of atherosclerosis and vascular disease. EPC therapy assists healing of cardiac and limb ischemia and has great potential for improving the quality of life and longevity of patients with severe cardiovascular and peripheral vascular disease who are not candidates for conventional revascularization procedures. In addition, EPCs can be used to promote vascular graft patency. This review focuses on the characterization of EPCs, positive and negative regulators of EPCs, the role of EPCs in vascular disease, and the potential for EPC therapy to ameliorate the sequelae of severe peripheral vascular disease.
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PMID:Endothelial progenitor cells: a primer for vascular surgeons. 1805 25

Cardiovascular disease remains the most common cause of death in the developed world and is predicted by the World Health Organization to kill approximately 20 million people worldwide each year until at least 2015. In light of these figures, work on producing superior tools for clinical use in the cardiovascular field is intensive. As proteins are the primary effectors of cellular function, a significant majority of this work focuses on the role of proteins in the cardiovascular system in physiological and pathological states in order to outline both mechanisms and markers of disease. One of the most effective ways to investigate these on a global basis is through proteomic analysis, which allows for broad spectrum screening of cellular protein or peptide complements during cardiovascular pathogenesis. Furthermore, specific technologies are now available to screen animal model or human blood samples for novel, improved markers of chronic disease states, such as atherosclerosis or for earlier indicators of acute myocardial stress, including ischemia/reperfusion injury and heart failure. This review summarizes current literature on the key aspects of proteomics and peptidomics related to clinical cardiovascular science.
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PMID:The role of proteomics in clinical cardiovascular biomarker discovery. 1866 14

Bile ducts are supplied with blood exclusively via hepatic arteries. Obstruction of large arteries is rapidly compensated for by the opening of preexisting intrahepatic or transcapsular collateral arteries, which prevents ischemic damage. Ischemic bile duct injury may occur when small hepatic arteries or the peribiliary vascular plexus are injured, or when all possible arterial blood supplies are interrupted, as is the case in transplanted liver with hepatic artery thrombosis. Most causes of bile duct ischemia are iatrogenic. Systemic diseases involving small hepatic arteries may also be implicated. Depending on the extent and velocity of the arterial obstructive process, ischemic cholangiopathy may present as acute formation of biliary casts, bile duct necrosis, or chronic disease resembling primary sclerosing cholangitis. In many patients, correction of arterial obstruction is not possible. When biliary drainage or reconstruction is not possible or has failed, liver transplantation is the only means of providing potential cure.
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PMID:Ischemic cholangiopathy. 1881 77

Episodes of acute renal failure (ARF) are not always fully reversible and may lead to chronic disease, due in part to an inadequate regenerative response. The Notch signaling pathway is involved in determining cell fate during development, and tissue maintenance and repair in adult organs. The purpose of this study was to examine the role of the Notch pathway in renal regeneration following ARF. Kidney injury, induced by ischemia-reperfusion, resulted in early activation of the Notch pathway, as evidenced by increased expression of Notch1 and Notch2 intracellular domain (cleaved Notch). The effect of exogenous administration of the Notch ligand Delta-like-4 (DLL4) on recovery from ARF was then studied. Rats were pretreated by intraperitoneal injection of DLL4 or vehicle control. Two days following the last DLL4 dose, ARF was induced by bilateral renal artery clamping for 45 min followed by reperfusion. The severity of renal injury was similar in DLL4 and control rats. Renal recovery was facilitated by DLL4 treatment, as evidenced by faster return of serum creatinine to baseline by 48 h in DLL4-treated rats as against 5 days in vehicle-treated control rats. Cell proliferation was higher in the DLL4-treated group. In conclusion, activation of the Notch pathway occurs following ARF. Pretreatment with the Notch ligand DLL4 enhanced recovery from ARF and represents a potential novel therapeutic option for regenerating the injured kidney.
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PMID:Effect of Notch activation on the regenerative response to acute renal failure. 1982 77


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