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)

Chest pain because of a disorder of the coronary circulation is assumed to be ischemic in nature. Irrespective of the underlying pathophysiological mechanism, it is accepted that all routes lead to myocardial ischemia in the pathway to anginal pain. The authors describe a patient with a history of vasoactive disorders including migraine, asthma, documented variant angina with prolonged episodes of chest pain, and scintigraphic evidence of inferior and posterior wall ischemia during exercise and ergonovine testing in the absence of significant underlying stenoses. Remarkably, severe retrosternal chest pain, ST segment depression in multiple leads, and relative increased uptake in the inferior and posterior walls on Tc-99m sestamibi tomographic images developed during pharmacologic coronary vasodilatation with dipyridamole, leading the authors to speculate as to the possible existence of a nonischemic chest pain syndrome caused by coronary vasodilatation either in association with variant angina or as a separate entity.
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PMID:Is cardiac migraine a clinical entity? 762 41

The lung is particularly exposed to various inhaled toxic products whose toxicity can be at least partly mediated by the generation of free radicals. Oxidants burden can also result from lung metabolism of xenobiotics or from activation of phagocytes. Free radicals are mainly derived from an univalent sequential reduction of molecular oxygen. Mitochondria is the main location of intracellular production which may also result from auto-oxidation of small molecules or function of some enzymes. To prevent the deleterious effects of free radicals produced by normal metabolism, cells are equipped with an antioxidant system composed of enzymes (superoxide dismutase, catalase, glutathione peroxidase) and non enzymatic substances such as glutathione, iron chelators, vitamin E and C, ceruleoplsamin). Targets of free radicals toxicity are phospholipids by initiation of lipid peroxidation, proteins which may be activated or inactivated via oxidation of sulfhydryl residues. Another target is DNA with possible strand breaks or mutation. Transcription activities can be also altered and it has been recently reported that some transcription factors such as NF-kB can be activated by oxidants. Under these circumstances free radicals may be considered as second messengers. Lung oxygen toxicity has been largely studied. Oxygen-induced lung lesions are non specific. It is possible to induce a resistance to 100% O2 by the pre-exposure of animals to 85% O2. This tolerance phenomenon is associated with an increased lung content in antioxidant substances. The mechanisms of gene regulation of antioxidant enzymes are still poorly understood in eukaryotes. Overproduction of free radicals in the lung is also involved in various clinical settings such as ischemia-reperfusion, exposure to ozone or NO2, acute respiratory distress syndrome, drug induced lung toxicity, pathogenesis of COPD, asthma, cancer and ageing. The precise role of free radicals among other mechanisms of lung injury is still unclear. A better knowledge of free radicals mechanisms of toxicity and of antioxidant regulation is needed to develop antioxidant therapeutic strategies.
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PMID:[Free radicals and respiratory pathology]. 773 56

Polymorphonuclear leukocytes are armed with an impressive arsenal of bactericidal agents that allow these cells to play a vital role in host defense against invading pathogens. However, these same agents can produce extensive cellular damage in host tissues when leukocytes are activated during inflammatory conditions. Recognition of this fact, when coupled with the observation that leukocyte adhesion to post-capillary venules is a critical first step in the inflammatory process, has led to the development of the concept that inhibition of neutrophil-endothelial cell adhesion (NECA) may represent a novel therapeutic strategy for the prevention of leukocyte-dependent injury in inflammatory conditions. Indeed, pharmacological or immunologic inhibition of NECA reduces cellular injury, dysfunction, and necrosis induced by ischemia/reperfusion, circulatory shock and resuscitation, organ transplantation, cardiopulmonary bypass, frostbite, and thermal trauma. NECA also appears to play an important role in the pathobiology of airway inflammation and asthma, pulmonary oxygen toxicity, arthritis, bacterial meningitis, and cerebral malaria. The aim of this review is to summarize the evidence implicating NECA in the pathogenesis of these inflammatory conditions.
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PMID:Role of neutrophil-endothelial cell adhesion in inflammatory disorders. 819 53

Potassium channel opener's (KCOs) were originally thought of as nonselective smooth muscle relaxants. However, recent investigations in animal models of both peripheral vascular disease (PVD) and asthma have revealed interesting effects of these drugs as unexpectedly low doses. Hemodynamically, KCOs are interesting in PVD since they have little effect on blood supply to normally perfused skeletal muscle, but enhance perfusion to chronically ligated ischemic tissue. In animal PVD models, SDZ PCO-400 and cromakalim have been shown to improve recovery of muscle energy stores from ischemia or to preserve performance under conditions of ischemic contracture. Beneficial effects in rat PVD models were manifest at doses below those affecting systemic blood pressure and may be attributable to a selective dilatation of collateral vessels. With regard to the airways, the apparent efficacy of KCOs as antiasthmatic drugs seems not to be attributable solely to their bronchodilator activity. Although KCOs elicit no antiinflammatory effect in animal models, studies with SDZ PCO-400 in guinea pigs sensitized to antigen or treated with immune complexes have revealed that expression of airway hyperreactivity is significantly inhibited at drug doses exhibiting only modest bronchodilator activity. At least part of this action can be attributed to inhibition at the level of neural innervation of the airways, possibly through attenuation of nonadrenergic noncholinergic (NANC) transmission.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapeutic potential of potassium channel openers in peripheral vascular disease and asthma. 825 25

The concepts of chronobiology and chronopharmacology have become more and more important in medical practice nowadays. Today, the circadian variation in blood pressure and heart rate as well as in the occurrence of acute cardiovascular disease is quite obvious (ischemia, infarction, stroke and sudden death). However, biological rhythms are also present in episodes of dyspnoea in nocturnal asthma, in hormonal pulses, in the organization of the immunological system and in the processes of cellular proliferation. These acknowledgments have been leading to changes in our therapeutical approaches implying the definition of correct anti-hypertensive and anti-ischemic strategy was well as in the use of xanthins, corticosteroids, immunomodulators and cytostatics.
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PMID:[Biological rhythms in man. Particular aspects in medicine]. 848 69

Many patients undergoing investigation for coronary artery disease are unable to exercise adequately due to physical or psychological reasons. Thallium-201 imaging using dipyridamole or adenosine may then be a suitable method of assessing myocardial perfusion. In patients with asthma, these drugs are contraindicated because of the risk of provoking bronchospasm. This study assesses the safety of dobutamine for thallium-201 myocardial perfusion imaging in patients with asthma who were unable to perform adequate exercise. Dobutamine was infused at rates < or = 40 micrograms/kg/min in 30 asthmatic patients for thallium-201 emission tomography. The severity of the airway reactivity ranged from mild to severe (bronchodilator treatment ranging from inhaled beta 2 agonists alone to maximal therapy including oral steroids). Coronary angiography was performed in 20 patients. Minor side effects of dobutamine were frequent, but did not limit the infusion rate. There were no episodes of bronchospasm, but tolerable dyspnea occurred in 8 patients who had reversible ischemia; this rapidly resolved with termination of the infusion. There were no serious cardiac complications, but chest pain occurred in 67% of patients. Thallium-201 images were abnormal in 10 of 11 patients with coronary artery disease (sensitivity 91%) and normal in 7 of 9 with normal coronary arteries (specificity 79%). Dobutamine thallium-201 myocardial perfusion tomography is a safe procedure in patients with asthma.
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PMID:Safety of dobutamine stress for thallium-201 myocardial perfusion tomography in patients with asthma. 849 79

The normal functional state of the vasculature and the events leading to the development of significant arterial disease involve the interaction of important vasoactive substances, which play important modulating or initiating roles in the development of hypertension and arteriosclerosis. Three endothelins have now been identified, of which ET-1 is the best characterized. ET-1 is produced by epithelial, mesangial, neuronal and glial, and liver cells, and is the most potent vasoconstrictor yet found. Each endothelin is derived from a different gene on separate chromosomes, and each binds to at least 2 types of receptor. The plasma half-life of ET-1 is about 7 min, and this provides a rapid mechanism for adjusting vascular resistance or blood pressure. The actions of endothelin are mediated through several pathways of postreceptor signaling, including activation of the mitogen-activated protein kinase cascade, which give rise to its growth-stimulating properties. Secretion of ET-1 from cultured endothelial cells is stimulated by a wide range of substances, and is inhibited by some prostaglandins. Endothelin in turn stimulates secretion of nitric oxide, arginine vasopressin and atrial natriuretic peptide, and participates in the hormonal control of salt and water balance. Hypoxia and ischemia augment ET-1 secretion, as does insulin, and this could play a role in the accelerated vascular disease of diabetes. ET-1 also causes bronchoconstriction and has been implicated in the development of acute asthma, primary pulmonary hypertension and pulmonary fibrosis. Its role in hypertension is still debatable, though most of the manifestations of congestive heart failure can theoretically be explained by the actions of ET-1. Endothelin also has extensive renovascular and parenchymal effects in the kidney. It is hoped that a fuller understanding of the role of endothelins in normal or pathologic vasculature will lead to effective therapy based on antagonism or augmentation of specific functions.
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PMID:Endothelins as cardiovascular peptides. 873 84

Modulators of potassium channels are of great interest for their potential scientific as well as clinical value. These agents may be used for a variety of illnesses including asthma, hypertension, myocardial ischemia, and arrhythmias. The development of KATP openers and blockers has opened a large area of research, particularly on their potential role in the pathogenesis of myocardial ischemia. While much work has shown protective effects for KATP openers, it is unknown whether currently existing agents are optimal. It is also possible that KATP openers may be useful for other types of ischemia such as peripheral vascular disease and cerebral ischemia. It would be exciting to develop agents which not only would protect ischemic myocardium, but also reduce the severity of peripheral and cerebral ischemia. The convergence of the KATP opener studies and the preconditioning area of study was a classical intersection of two seemingly independent lines of research. This convergence has been largely responsible for the heightened interest in KATP. Our quest for knowledge on the role of KATP openers in myocardial ischemia and their potential utility has only just begun.
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PMID:The role of ATP-sensitive potassium channels in myocardial ischemia: pharmacology and implications for the future. 880 3

The intercellular adhesion molecule (ICAM) 1 is an Ig-like cell adhesion molecule expressed by several cell types, including leukocytes and endothelial cells. It can be induced in a cell-specific manner by several cytokines, for example, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma, and inhibited by glucocorticoids. Its ligands are the membrane-bound integrin receptors LFA-1 and Mac-1 on leukocytes, CD43, the soluble molecule fibrinogen, the matrix factor hyaluronan, rhinoviruses, and Plasmodium falciparum malaria-infected erythrocytes. ICAM-1 expression is predominantly transcriptionally regulated. The ICAM-1 promoter contains several enhancer elements, among them a novel kappa B element which mediates effects of 12-O-tetradecanoylphorbol-13-acetate, interleukin-1, lipopolysaccharide, tumor necrosis factor-alpha, and glucocorticoids. Expression regulation is cell specific and depends on the availability of cytokine/hormone receptors, signal transduction pathways, transcription factors, and posttranscriptional modification. ICAM-1 plays a role in inflammatory processes and in the T-cell mediated host defense system. It functions as a costimulatory molecule on antigen-presenting cells to activate MHC class II restricted T-cells, and on other cell types in association with MHC class I to activate cytotoxic T-cells. ICAM-1 on endothelium plays an important role in migration of (activated) leukocytes to sites of inflammation. ICAM-1 is shed by the cell and detected in plasma as sICAM-1. Regulation and significance of sICAM-1 are as yet unclear, but sICAM-1 is increased in many pathological conditions. ICAM-1 may play a pathogenetic role in rhinovirus infections. Derangement of ICAM-1 expression probably contributes to the clinical manifestations of a variety of diseases, predominantly by interfering with normal immune function. Among these are malignancies (e.g., melanoma and lymphomas), many inflammatory disorders (e.g., asthma and autoimmune disorders), atherosclerosis, ischemia, certain neurological disorders, and allogeneic organ transplantation. Interference with ICAM-1 leukocyte interaction using mAbs, soluble ICAM-1, antisense ICAM-1 RNA, and in the case of melanoma mAb-coupled immunotoxin, may offer therapeutic possibilities in the future. Integration of knowledge concerning membrane-bound and soluble ICAM-1 into a single functional system is likely to contribute to elucidating the immunoregulatory function of ICAM-1 and its pathophysiological significance in various disease entities.
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PMID:Intercellular adhesion molecule-1. 883 67

In choosing a pharmacologic agent for stress testing, the clinician must keep a number of things in mind, such as the diagnostic utility of the agent or in what situations a vasodilator or catecholamine will be the better choice. Although all stress agents produce similar diagnostic accuracy for CAD, vasodilators have a higher cardiac uptake than catecholamines, and the addition of exercise improves the heart/background contrast ratios. With regard to physiologic comparisons, exercise or dobutamine will double coronary perfusion compared with baseline flow, but vasodilators produce a threefold or fourfold increase. The clinician should also keep in mind that adenosine will produce the shortest duration of hyperemia, whereas dobutamine and arbutamine produce a longer effect, and dipyridamole has the longest duration. If electrophysiologic considerations are important, exercise and catecholamines accelerate sinoatrial and atrioventricular conduction and are not typically associated with heart block. In contrast, adenosine can cause transient atrioventricular block, but this rarely occurs with dipyridamole. Clinical factors also must be considered. Although clinical utility of pharmacologic stress agents in the first 24 hours after infarction has not been demonstrated, the prognostic utility of vasodilators in the subsequent 2- to 4-day period has been shown. With patients with pulmonary disease (asthma) who do not have wheezing, dipyridamole can be used, but dobutamine or arbutamine should be used in patients with recent respiratory failure or bronchospasm before testing. In patients with left bundle branch block, vasodilators are the preferred stress agents rather than synthetic catecholamines or dynamic exercise. In the first crossover thallium imaging, there was good overall agreement in segmental perfusion comparing adenosine and dipyridamole, but there was a tendency for adenosine to detect more ischemia. The clinical significance (if any) for these findings has yet to be determined.
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PMID:Comparison of pharmacologic stress agents. 898 83


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