Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidized low-density lipoprotein (LDL) is implicated in atherogenesis, but the mechanisms that oxidize LDL in the human artery wall have proven difficult to identify. A powerful investigative approach is mass spectrometric quantification of the oxidized amino acids that are left in proteins by specific oxidation reactions. Comparison of these molecular fingerprints in biological samples with those produced in proteins by various in vitro oxidation systems can indicate which biochemical pathway has created damage in vivo. For example, the pattern of oxidized amino acids in proteins isolated from atherosclerotic lesions implicates reactive intermediates generated by myeloperoxidase, a major phagocyte enzyme. These intermediates include hypochlorous acid, tyrosyl radical, and reactive nitrogen species, each of which generates a different pattern of stable end products. Despite this strong evidence that myeloperoxidase promotes LDL oxidation in vivo, the antioxidant that has been tested most extensively in clinical trials, vitamin E, fails to inhibit myeloperoxidase pathways in vitro. Because the utility of an antioxidant depends critically on the nature of the pathway that inflicts tissue damage, interventions that specifically inhibit myeloperoxidase or other physiologically relevant pathways would be more logical candidates for the prevention of cardiovascular disease. Moreover, levels of oxidized amino acids in urine and plasma might reflect those in tissues and therefore identify individuals with high levels of oxidative stress. Trials with such subjects would seem more likely to uncover effective antioxidant therapies than trials involving the general population.
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PMID:Oxidized amino acids: culprits in human atherosclerosis and indicators of oxidative stress. 1203 94

The nitroxyl (HNO) donor Angeli's salt (Na(2)N(2)O(3); AS) is cytotoxic in vitro, inducing double strand DNA breaks and base oxidation, yet may have pharmacological application in the treatment of cardiovascular disease. The chemical profiles of AS and synthetic peroxynitrite (ONOO(-)) in aerobic solution were recently compared, and AS was found to form a distinct reactive intermediate. However, similarities in the chemical behavior of the reactive nitrogen oxide species (RNOS) were apparent under certain conditions. Buffer composition was found to have a significant and unexpected impact on the observed chemistry of RNOS, and varied buffer conditions were utilized to further distinguish the chemical profiles elicited by the RNOS donors AS and synthetic ONOO(-). Addition of HEPES to the assay buffer significantly quenched oxidation of dihydrorhodamine (DHR), hydroxylation of benzoic acid (BA), and DNA damage by both AS and ONOO(-), and oxidation and nitration of hydroxyphenylacetic acid by ONOO(-). Additionally, H(2)O(2) was produced in a concentration-dependent manner from the interaction of HEPES with both the donor intermediates. Interestingly, clonogenic survival was not affected by HEPES, indicating that H(2)O(2) is not a contributing factor to in vitro cytotoxicity of AS. Variation in RNOS reactivity was dramatic with significantly higher relative affinity for the AS intermediate toward DHR, BA, DNA, and HEPES and increased production of H(2)O(2). Further, AS reacted to a significantly greater extent with the unprotonated amine form of HEPES while the interaction of ONOO(-) with HEPES was pH-independent. Addition of bicarbonate only altered ONOO(-) chemistry. This study emphasizes the importance of buffer composition on chemical outcome and thus on interpretation and provides further evidence that ONOO(-) is not an intermediate formed between the reaction of O(2) and HNO produced by AS.
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PMID:Further evidence for distinct reactive intermediates from nitroxyl and peroxynitrite: effects of buffer composition on the chemistry of Angeli's salt and synthetic peroxynitrite. 1205 63

In vitro studies and experiments in animal models provide a large and compelling body of evidence that oxidation of low-density lipoprotein (LDL) and/or related oxidative mechanisms play a critical role in the initiation and progression of atherogenesis. A corollary to the theory that reactive oxygen and nitrogen species ("free radicals") are the key molecules in this process is that antioxidants that can protect LDL from peroxidation should decrease the risk of developing atherosclerosis, attenuate its progression, or even reverse established disease. However, recently, clinical trials employing the principal lipid-soluble dietary antioxidant, vitamin E, have provided mixed results indicating either benefit, no effect, or an adverse impact on patients with cardiovascular disease (CVD). Consideration of the design and outcome of these studies together with new reports about the action of antioxidants suggests approaches for new studies as well as a basis for current advice to patients.
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PMID:An update: vitamin E supplementation and heart disease. 1213 9

Magnesocene adducts of alkylamines were prepared and characterized. Treatment of 3-amino-2,4-dimethylpentane, isopropylamine, tert-butylamine, benzylamine, or N-isopropylbenzylamine with magnesocene at ambient temperature in toluene afforded the amine adducts Cp2Mg(NH2CH(CH(CH3)2)2) (91%), Cp2Mg(NH2iPr) (80%), Cp2Mg(NH2tBu) (67%), Cp2Mg(NH2CH2Ph) (80%), and Cp2Mg(NH(CH(CH3)2)(CH2C6H5)) (91%). These adducts are stable at ambient temperature, and Cp2Mg(NH2CH(CH(CH3)2)2) can be sublimed at 60 degrees C/0.05 Torr without any evidence for reversion to magnesocene. The solid-state structure of Cp2Mg(NH2CH(CH(CH3)2)2) contains eta5- and eta2-cyclopentadienyl ligands, and the hydrogen atoms on the coordinated amine nitrogen atom participate in intramolecular and intermolecular hydrogen bonding to the eta2-cyclopentadienyl ligand. The observed hydrogen bonding is relevant to the path by which cyclopentadiene is eliminated from metal cyclopentadienyl CVD source compounds during film growth employing acidic element hydrides as co-reactants.
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PMID:Intramolecular and intermolecular N-H...C(5)H(5)(-) hydrogen bonding in magnesocene adducts of alkylamines. Implications for chemical vapor deposition using cyclopentadienyl source compounds. 1223 29

The composition and structure of boron carbonitride (BCN) films were studied. The films were continuously deposited on fibres by atmospheric pressure CVD. The precursors were ammonia, trimethyl borate and toluene. The composition was determined by photoelectron spectra of boron 1s, nitrogen 1s, carbon 1s and oxygen 1s. By fixing the C 1s peak at 285 eV, the position of the B 1s peak and the N 1s peak in the BCN films was equal to BN films. The C content of the films increases from about 6 at% to 60 at%, leaving the stoichiometric boron/nitrogen ratio as well as the oxygen content below 10 at% unchanged. Generally, the carbon content in the films is lower than predicted by the precursor ratios. Obviously, the insertion of carbon into the film is decreased in the presence of ammonia, which is known to etch carbon. With a decreasing ammonia/toluene ratio, the undesired effect in the reaction is suppressed and the carbon deposition becomes considerable. Transmission electron microscopic studies were performed on cross-sections of the coated fibres. High-resolution images generally show a hexagonal turbostratic structure with different orientation preferences of the atomic lamellae similar to hexagonal turbostratic boron nitride and pyrolytic carbon. When a noticeable carbon concentration (20 at%) is reached, the atomic sheets become uniformly distributed in all directions in space.
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PMID:Structure and composition studies of chemical vapour-deposited BCN fibre coatings. 1239 99

The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure, bicycle exercise test, electrocardiogram and echocardiography were studied [ P(coronary artery disease) <5%]. Whole-body insulin sensitivity and insulin-stimulated myocardial glucose uptake were measured during hyperinsulinaemic euglycaemic glucose clamp with fluorine-18 fluorodeoxyglucose, and myocardial rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion = (standard deviation/mean)] was 13% and 29% respectively. Although inter-individual variability of glucose uptake and blood flow at rest was of the same magnitude, no correlation was found between these measures. Regional and global insulin-stimulated myocardial glucose uptake correlated linearly with whole-body insulin sensitivity ( r=0.51, P<0.05 and r=0.56, P<0.01). The strongest independent association by multivariate linear regression analysis was found between myocardial glucose uptake and hyperaemic blood flow ( r=0.63, P<0.005). We conclude that in healthy elderly subjects, insulin-stimulated myocardial glucose uptake is homogeneous throughout the left ventricle, but has moderate inter-individual variability. Inter-individual variability of insulin-stimulated myocardial glucose uptake is primarily explained by variability in coronary vascular reactivity and tissue insulin sensitivity.
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PMID:Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects. 1245 94

Cardiovascular disease is commonly observed in patients with chronic renal failure and this is a leading cause of death in patients with end-stage renal disease undergoing maintenance dialysis. Myocardial energy production is a very crucial aspect of cardiac function. Therefore, to evaluate energy metabolism of myocardial muscle in peritoneal dialysis (PD) patients, we carried out the following study using Magnetic resonance spectroscopy (MRS). Fourteen chronic renal failure patients and eight healthy volunteers were enrolled. The ratio of the phosphocreatine peak to the beta-phosphate to ATP peak (PCr/beta-ATP) was calculated from their MR spectra obtained by 31P-MR spectroscopy (Gyroscan S15, Philips). To determine the correlation between cardiac function and energy status, the left atrial diameter, the left ventricular (LV) end-diastolic diameter, the ejection fraction, the fraction of shortening and the LV mass index were measured by echocardiography. Peripheral blood sampling was also performed for creatinine, blood urea nitrogen, hematocrit, hemoglobin, beta2-microglobuline, intact parathyroid hormone. PCr/beta-ATP was significantly lower in PD (1.03 +/- 0.15 vs. 1.40 +/- 0.18: p = 0.0002), although all patients showed normal systolic function. No correlation was found between PCr/beta-ATP and cardiac function or hematological or biochemical markers. A negative correlation was present between PCr/beta-ATP and dialysis duration (r = 0.57, p < 0.05). Altered energy status of the myocardium in PD should be considered even if the patients did not show any systolic dysfunction. 31P-MRS is a useful tool to evaluate the energy status of the myocardium.
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PMID:Alteration of energy production by the heart in CRF patients undergoing peritoneal dialysis. 1270 22

Daily measures of maximum temperature, particulate matter less than or equal to 10 micro m in aerodynamic diameter (PM10), and gaseous pollution (ozone, nitrogen dioxide, sulfur dioxide, and carbon monoxide) were collected in Denver, Colorado, in July and August between 1993 and 1997. We then compared these exposures with concurrent data on the number of daily hospital admissions for cardiovascular diseases in men and women > 65 years of age. Generalized linear models, assuming a Poisson error structure for the selected cardiovascular disease hospital admissions, were constructed to evaluate the associations with air pollution and temperature. After adjusting the admission data for yearly trends, day-of-week effects, ambient maximum temperature, and dew point temperature, we studied the associations of the pollutants in single-pollutant models with lag times of 0-4 days. The results suggest that O3 is associated with an increase in the risk of hospitalization for acute myocardial infarction, coronary atherosclerosis, and pulmonary heart disease. SO2 appears to be related to increased hospital stays for cardiac dysrhythmias, and CO is significantly associated with congestive heart failure. No association was found between particulate matter or NO2 and any of the health outcomes. Males tend to have higher numbers of hospital admissions than do females for all of the selected cardiovascular diseases, except for congestive heart failure. Higher temperatures appear to be an important factor in increasing the frequency of hospitalization for acute myocardial infarction and congestive heart failure, and are associated with a decrease in the frequency of visits for coronary atherosclerosis and pulmonary heart disease.
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PMID:Temperature, air pollution, and hospitalization for cardiovascular diseases among elderly people in Denver. 1289 52

Healthy endothelium plays a central role in cardiovascular control. Therefore endothelial dysfunction (ED), which is characterized by an imbalance between relaxing and contracting factors, procoagulant and anticoagulant substances, and between proinflammatory and antiinflammatory mediators, may play a particularly significant role in the pathogenesis of atherosclerosis and cardiovascular disease. ED is thought to be an early physiologic event in the development of atherosclerosis, occurring before morphologic changes in the vessel wall can be detected. It is closely related to different risk factors of atherosclerosis, to their intensity and their duration. The involvement of risk factors in ED is also supported by results of intervention studies that showed regression of ED with treatment of risk factors. Further, it was shown that ED is significantly and directly correlated with the occurrence of cardiac events. The common denominator whereby different risk factors cause ED is most probably increased oxidative stress and consequently decreased bioavailability of nitrogen oxide. Endothelial dysfunction promotes atherosclerosis and probably plays an important role in the development of thrombotic complications in late stages of the disease. As ED is a key underlying factor in the atherosclerotic process, markers of endothelial abnormalities have been proposed, but loss of endothelium-dependent vasodilation has became a broadly accepted indicator of endothelial dysfunction. Using these non-invasive tests it is possible to follow the dose-response of harmful effects or risk factors, and the effects of preventive procedures on vessel wall function.
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PMID:Endothelial dysfunction and cardiovascular disease. 1367 56

Serum albumin, transferrin, and prealbumin levels decrease as glomerular filtration rate (GFR) declines, even prior to the start of dialysis. The levels of these serum proteins are also associated with creatinine levels and lean body mass. Lean body mass also decreases with advancing renal failure. While all of these measures are regarded as reflections of nutritional status, each are strongly associated with any of several indicators of inflammation: positive acute-phase proteins or the cytokines that regulate their synthesis rate, in both longitudinal and cross-sectional studies. Inflammation in turn is associated with comorbid conditions, cardiovascular disease, chronic infections, age, and vascular access type. Additionally, dialysis patients are subjected to oxidative stress and exposure of blood to foreign antigens in the dialysis process that also potentially contribute to inflammation. In otherwise healthy individuals reduced protein and calorie intake does not cause hypoalbuminemia since albumin fractional catabolic rate (FCR) and resting energy expenditure (REE) normally decrease in response. The simultaneous occurrence of decreased protein intake and inflammation prevent these homeostatic compensations to reduced nitrogen and energy intake from occurring, resulting in decreasing albumin, transferrin, and prealbumin levels and loss of muscle mass. Nutritional intake may also be challenged as a result of renal failure associated with anorexia, gastroparesis, and socioeconomic factors, which may all cause nutritional intake to be sufficiently marginal so that the combined effects of inflammation and decrease protein intake are expressed as decreased visceral and somatic protein stores.
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PMID:Serum albumin concentration in dialysis patients: why does it remain resistant to therapy? 1453 80


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