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)

Platelet-activating factor (PAF) is a potent lipid mediator that has been implicated in asthma, sepsis, acute lung injury and ischemia/reperfusion injury. Its actions in the lungs include vasoconstriction, bronchoconstriction, and edema formation. Despite the fact that PAF exerts these actions within minutes, they are mediated by other lipid mediators, in particular eicosanoids generated by cyclooxygenase and lipoxygenase enzymes and sphingolipids generated by acid sphingomyelinase.We will discuss the mechanisms of the PAF-induced pressor responses that are triggered by thromboxane A(2) and leukotrienes, as well the PAF-induced increase in vascular permeability that is mediated by prostaglandin E(2) (PGE(2)) and ceramide.
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PMID:Mechanisms of platelet-activating factor (PAF)-mediated responses in the lung. 1641 1

When evaluating a dyspneic patient in the office, a quick initial assessment of the airway, breathing, and circulation, while gathering a brief history and focused physical examination are necessary. Most often, an acute cardiopulmonary disorder, such as CHF, cardiac ischemia, pneumonia, asthma, or COPD exacerbation, can be identified and treated. Stable patients who improve can be sent home, but those in acute distress with unstable or impending unstable conditions need to be transferred emergently to definitive care. Because of the difficult logistics involved in attempting to work up an outpatient for new onset of SOB, some patients will need to be transferred to the nearest ED for a definitive diagnosis.
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PMID:Dyspnea. 1647

We report a 22 years old male with chronic allergic rhinitis, who presented with asthma, prolonged fever, eosinophilia, cutaneous vasculitis, subcutaneous nodules, polyarthritis, ulcers in the nasal mucosa and external auditory canal, hematuria, proteinuria, renal failure, severe hypertension, pulmonary infiltrates and mesenteric ischemia with a perforation of the sigmoid colon. Arteriography showed multiple aneurysmae of intrarenal arteries and a skin biopsy showed a leukocytoclastic vasculitis. A diagnosis of Churg-Strauss syndrome was made. He was initially treated with steroids and cyclophosphamide but abandoned therapy. Eighteen years after the onset of the disease, he required hemodialysis. Eight months after being on dialysis, he suffered a reactivation of the disease with lung hemorrhage and finally died, due to an upper gastrointestinal bleeding caused by a duodenal ulcer.
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PMID:[Late reactivation of Churg-Strauss syndrome]. 1653 66

Cardiovascular disease is common in asthmatic patients but often is attributed to respiratory drug therapy. With mounting evidence for an inflammatory role in the development of cardiovascular disease, we hypothesized that the inflammation associated with asthma adversely affects the cardiovascular system independent of therapeutic interventions. The hypothesis was tested in a murine model of myocardial ischemia-reperfusion injury. BALB/C mice were sensitized by intraperitoneal injection of ragweed (RW) or normal saline (NS) and challenged by intratracheal instillation of RW or NS. Effective allergic sensitization and challenge were confirmed by hyperresponsiveness to aerosolized methacholine and bronchoalveolar lavage. In vivo myocardial ischemia-reperfusion injury was induced by ligation of the left anterior descending artery for 20 min, followed by reperfusion for 2 h. The infarct size (% risk area) and neutrophil density in the myocardial area at risk were significantly higher in the RW/RW group than in the control groups. The tissue neutrophil count correlated with the infarct size but did not correlate with blood neutrophil counts. Furthermore, in the RW/RW group, circulating granulocytes showed an enhanced expression of CD11b and P-selectin glycoprotein ligand-1, enhanced stimulated release of myeloperoxidase, and enhanced expression of P-selectin in the coronary vasculature. These results indicate that allergic responses in the airways enhance expression of attachment molecules in coronary vasculature and activate circulating neutrophils, resulting in recruitment of highly activated neutrophils to the infarct zone during an acute ischemia-reperfusion event, thereby enhancing tissue destruction.
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PMID:Severity of myocardial injury following ischemia-reperfusion is increased in a mouse model of allergic asthma. 1690 95

The complement system not only plays an important role in the defense system, but also contributes to the amplification of inflammation if activated in excess or inappropriately controlled. Complement activation through one of three pathways is tightly controlled by various regulators of complement activation (RCA) which are constitutively expressed on various cells in order to restrict excessive activation. Complement activation may generate polypeptides, so-called anaphylatoxins, and membrane attack complex (MAC) with large molecular mass. Anaphylatoxins (C3a, C4a, and C5a) produced by activation of the complement is considered to bridge innate and acquired immunity. Considering that C5a is more potent than C3a, but the serum concentration of C3 is 10 times higher than that of C5, the overall effects of C3a may be comparative with those of C5a. Since both anaphylatoxins are considered to exert their actions through rhodopsin-typed receptors, their receptor antagonists are targets for the discovery of anti-inflammatory and immune-modulating drugs. Complement activation may be related to the pathophysiology of various refractory disorders including ARDS, asthma, septic syndrome, SLE, rheumatoid arthritis, ischemia-reperfusion injury, and psoriasis etc. Pharmacological manipulation of the complement system may consist of various strategies including (1) inhibitors of complement activation at various levels, (2) receptor antagonists of anaphylatoxins, C3a and C5a, and (3) inhibitors of C5a including monoclonal antibody. Candidate agents concerning the above-mentioned manipulations have being produced and some are now in progress toward clinical trials in patients with certain diseases.
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PMID:[Complement activation and inflammation]. 1691 66

Activated protein C (APC), a plasma serine protease, is best known for its ability to inhibit blood clot formation. APC acts as an anticoagulant by degrading coagulation cofactors Va and VIIIa, thereby attenuating the coagulation cascade. Over the past 15 years, impressive research advances have provided novel insights into the diverse biological activities of this molecule. APC is now viewed not only as an anticoagulant but also as a signaling molecule that provides a pivotal link between the pathways of coagulation, inflammation, apoptosis, and vascular permeability. The protective effect of APC supplementation in patients with severe sepsis likely reflects the ability of APC to modulate multiple pathways implicated in sepsis pathophysiology. This review attempts to summarize key studies that support the therapeutic potential of APC in conditions beyond sepsis such as stroke, ischemia-reperfusion injury, lung injury, asthma, pancreatitis, wound healing, and angiogenesis. A comprehensive PUBMED literature review up to May 2006 was conducted.
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PMID:Activated protein C in sepsis and beyond: update 2006. 1712 35

The selectin family of cellular adhesion molecules plays an important role in the cellular infiltration and molecular signaling associated with ischemia/reperfusion (I/R). Selectins are essential in the recruitment and infiltration of leukocytes to sites of inflammation, and consequently, selectin blockade represents an important area of current research in the potential alleviation of the cell-mediated injury associated with I/R. Previously, treatments targeted at only a single selectin have proven ineffective, due to compensation by uninhibited cell-adhesion molecules. However, pan-selectin antagonists - those inhibitors capable of blocking the actions of all three selectins - have demonstrated great potential in blocking the initial events in the leukocyte-endothelium adhesion cascade. A number of therapeutics have been developed, with the most promising results demonstrated by a class of non-oligosaccharide, small-molecule selectin antagonists. TB-1269 and OC-229 are two of the most promising of inhibitors in this class - they are capable of binding all three selectins, they have been demonstrated to reduce neutrophil infiltration following ischemia/reperfusion, and they have been associated with reduced tissue damage in experimental animal models of ischemia/reperfusion involving the liver, the heart, the kidneys, and the whole body. Furthermore, TBC-1269 has recently undergone successful phase I and phase IIa clinical trials for asthma and psoriasis. Though the timing of selectin inhibition is essential in attenuating leukocyte infiltration and cell-mediated injury, the transient blockade of selectin function, in a well-controlled setting, could be an extremely beneficial intervention in ischemia/reperfusion injury.
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PMID:Selectin inhibitors and their proposed role in ischemia and reperfusion. 1745 92

Inflammatory eicosanoids generated by the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism are now known to have at least 6 receptors: OXE, which recognizes 5-HETE and 5-oxo-ETE; a putative receptor recognizing a potent 5-oxo-ETE metabolite, FOG(7); the LTB(4) receptors, BLT1 and BLT2; the cysteinyl leukotriene receptors, CysLT(1) and CysLT(2), which recognize leukotrienes LTC(4), LTD(4), LTE(4) and LTF(4). The 5-LO pathway is activated in many diseases and invokes inflammatory responses not affected by glucocorticoids, but therapy with selective BLT1 or CysLT(1) antagonists in asthma has met with variable success. Studies show that 5-LO pathway eicosanoids are not primary mediators in all cases of asthma, but may be especially important in severe persistent asthma, aspirin- and exercise-induced asthma, allergic rhinitis, COPD, idiopathic pulmonary fibrosis, atherosclerosis, atopic dermatitis, acne and ischemia-related organ injury. These disorders appear to involve multiple 5-LO pathway eicosanoids and receptor subtypes, suggesting that inhibition of the pathway at the level of 5-LO may be necessary for maximal efficacy.
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PMID:Pharmacotherapy of diseases mediated by 5-lipoxygenase pathway eicosanoids. 1748 54

The purpose of the study was to assess the influence of structural and functional changes in the myocardium of the right and left ventricle (RVand LV) on the development of ischemia and arrhythmia in chronic obstructive pulmonary disease (COPD) and bronchial asthma (BA). The subjects of the study were 156 patients with either persistent BA (81 patients) or COPD (75 patients). Patients with decompensated cor pulmonale were excluded. ECG, 24-hour ECG monitoring, and echocardioscopy were performed. The study found that the occurrence of supraventricular and ventricular extrasystoles (SVES and VES) in patients with mild COPD or BA depended on the condition of RV diastolic function and on LV diastolic function and myocardial ischemia as well in COPD. In moderate BA the processes of myocardial remodeling correlate with myocardial ischemia, RV dysfunction and increased pulmonary arterial pressure (PAP), as well as with lipid dismetabolism. The appearance of SVES in patients with severe BA is connected with interventricular septal hypertrophy, LV dysfunction, and increased PAP, while VEC appear due to myocardial ischemia and hypercholesterolemia. In severe COPD the occurrence of SVES and VES does not depend on structural and functional changes in the myocardium, while myocardial ischemia is connected with LV hypertrophy. In BA ischemia depends on the development of RV and LV diastolic dysfunction, as well as hypercholesterolemia.
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PMID:[The myocardial condition in chronic obstructive pulmonary disease and bronchial asthma]. 1752 Aug 83

The respiratory system, including the lung and upper airways, succumbs to injury and disease through acute or chronic exposures to adverse environmental agents, in particular, those that promote increased oxidative or inflammatory processes. Cigarette smoke and other forms of particulate or gaseous air pollution, allergens, microorganisms infections, and changes in inspired oxygen may contribute to lung injury. Among the intrinsic defenses of the lung, the stress protein heme oxygenase-1 constitutes an inducible defense mechanism that can protect the lung and its constituent cells against such insults. Heme oxygenases degrade heme to biliverdin-IXalpha, carbon monoxide, and iron, each with candidate roles in cytoprotection. At low concentrations, carbon monoxide can confer similar cyto and tissue-protective effects as endogenous heme oxygenase-1 expression, involving antioxidative, antiinflammatory, antiproliferative, and antiapoptotic effects. Lung protection by heme oxygenase-1 or its enzymatic reaction products has been demonstrated in vitro and in vivo in a number of pulmonary disease models, including acute lung injury, cigarette smoke-induced lung injury/chronic obstructive pulmonary disease, interstitial lung diseases, ischemia/reperfusion injury, and asthma/airway inflammation. This review summarizes recent findings on the functions of heme oxygenase-1 in the respiratory system, with an emphasis on possible roles in disease progression and therapies.
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PMID:Protective functions of heme oxygenase-1 and carbon monoxide in the respiratory system. 1784 32


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