Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly active atrial natriuretic peptide III (haANP III) was administered for the treatment of heart failure due to pregnancy induced hypertension (PIH) in 7 patients with success. The heart failure was rapidly controlled within 24-48 hours with lowering of the blood pressure, disappearance of edema and urinary protein and alleviation of subjective symptoms. The plasma level of renin, angiotensin, aldosterone (RAA) and SOD all decreased. The results suggested that haANP III had the ability to facilitate the excretion of sodium and water, dilate the blood vessels and inhibit the action of RAA, and it could effectively reduce heart load and improve the cardiac function. Therefore, haANP III seemed to be an ideal new drug in treating heart failure in PIH, and it would have a wide scope for future development.
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PMID:[The use of synthetic haANP III in the treatment of heart failure in pregnancy induced hypertension]. 824 44

In this study, total cytoplasmic (Cu,Zn-SOD) and mitochondrial (Mn-SOD) superoxide dismutase activities were measured in sera and pleural fluids from patients with squamous cell carcinoma of the lung. The results were compared with those of control subjects and those of patients with tuberculosis and chronic heart failure. Serum activities were found higher in all patient groups compared to control group. Highest values were however in tuberculosis group. In the correlation analysis, meaningful intra- and inter-correlations were established between enzyme activities in the samples. Results suggest that high serum and pleural fluid SOD activities are not specific biochemical parameters for carcinogenesis and, activities may also increase in some other degenerative diseases such as tuberculosis, chronic heart failure, etc. Therefore, we believe that it is not useful to use serum and pleural fluid SOD activities for diagnostic purposes in cancer. However, the activities of these enzymes in the biological samples might be used as nonspecific prognostic markers in assessing cellular and mitochondrial tissue destruction.
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PMID:Activities of total, cytoplasmic, and mitochondrial superoxide dismutase enzymes in sera and pleural fluids from patients with lung cancer. 892 62

The moose (Alces alces L.) in an acid rain affected region in south-west Sweden has developed a complex disease with numerous clinical signs, most of which are consistent with those of secondary copper (Cu) deficiency and/or molybdenosis in cattle and sheep. The clinical signs of the moose disease reported to date include diarrhoea, anorexia, emaciation, achromotrichia, alopecia, sudden heart failure and osteoporosis. Findings at necropsy included mucosal oedema, atrophied lymphoid tissues of the mucous membranes of the alimentary tract, neuropathy, neuronal degeneration and uni- or bilateral corneal opacity. In a study of clinically healthy animals from the affected region in Sweden over a 12-year period (1982-1994), the hepatic Cu concentration decreased by 50% and the liver and kidney cadmium (Cd) concentration decreased by 25-35%, while the molybdenum (Mo) concentration increased by 20-40%. These changes are probably related to an increase in the pH of the soil and water in the moose environment and a consequent change in the uptake of these elements by the plants consumed by the moose. It is noteworthy that the occurrence of the disease in the mid 1980s coincided with increased liming undertaken to counteract the noxious effects of acid rain in this region. Clinical signs and lesions of the moose disease resemble those reported for Cu deficiency and/or molybdenosis in cattle and sheep. To elucidate the complex, multi-faceted clinical signs of the moose disease, the clinical signs and necropsy findings are discussed in relation to the biochemical functions of certain well-known Cu-dependent enzymes, e.g. depigmentation of hair due to depressed tyrosinase activity, osteoporosis by depressed lysyl oxidase activity, sudden heart failure due to decreased activity of lysyl oxidase, cytochrome c oxidase and Cu/Zn-superoxide dismutase; in addition, mucosal lesions and ulcerations due to loss of activity of diamine oxidase as well as of lysyl oxidase and cytochrome c oxidase. It is concluded from the present findings that the moose disease is most probably a Cu deficiency and/or a molybdenosis-type syndrome.
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PMID:'Mysterious' moose disease in Sweden. Similarities to copper deficiency and/or molybdenosis in cattle and sheep. Biochemical background of clinical signs and organ lesions. 949 61

The present study investigates intracellular enzymatic pathways involved in the elimination of reactive oxygen species in the left ventricular myocardium of 10 individuals without heart failure and 12 patients with end-stage heart failure due to idiopathic dilated cardiomyopathy. Left ventricular enzyme activities, mRNA and protein levels of the hydrogen peroxide scavenging enzymes catalase (CAT) and glutathione peroxidase (GPX), and the superoxide anion scavenging enzymes mitochondrial (Mn-SOD) and cytosolic (Cu/Zn-SOD) superoxide dismutases were measured. In failing myocardium, there was a significant decrease in CAT activity (4.83+/-0.32 U/mg v 6.59+/-0.52, P<0.01) despite unchanged mRNA expression and protein levels. GPX, Mn-SOD and Cu/Zn-SOD were similar concerning activity, mRNA and protein levels. As indirect free radical markers, similar levels of the products of lipid peroxidation, malondialdehyde and 4-hydroxy-alkenals, and similar tissue nitrotyrosin content were measured. The decrease in CAT activity appears to be a post-transcriptional mechanism. A decreased myocardial capacity to scavenge hydrogen peroxide might lead to a shift in the intracellular redox balance which potentially results in activation of redox sensitive signalling pathways. Direct reactive oxygen species mediated damage was not detected by the methods applied.
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PMID:Antioxidative enzymes in human hearts with idiopathic dilated cardiomyopathy. 1065 96

Repeated bouts of ischemia in the heart lead to fibrosis and eventually to heart failure. Although certain genes, such as SOD or hemoxygenase and antisense to AT(1)R, ACE, and (beta(1)-AR can provide short-term protection of the heart from ischemia, there is no known mechanism for constantly responding to repeated incidences of ischemia. We hypothesized that a "vigilant vector," designed to be expressed specifically in the heart and switch on therapeutic genes only during hypoxia, would provide cardioprotection. To attain cardiac specificity, we inserted an MLC2v promoter into an adeno-associated virus (AAV) designed to deliver AS to AT(1)R and gfp. In in vitro experiments in cardiomyocytes (H9C2 cells), the MLC2v-AAV-gfp drove gene expression in all cells at levels comparable to a cytomegalovirus (CMV) promoter. In in vivo experiments, the rAAV-MLC2v-gfp was injected intravenously into mice or rats. Green fluorescence protein (GFP) DNA was located in kidney, heart (right and left ventricle), lung, adrenal and spleen. GFP mRNA, however, was expressed only in the heart and absent in other tissues. To switch on the rAAV transgene during ischemia, we inserted a hypoxia response element (HRE). This upregulates transcription when O(2) levels are low. Thus, there are 4 components to the vigilant vector; a gene switch (HRE), a heart-specific promoter (MLC2v), a therapeutic gene (AS-AT(1)R) and a reporter gene (gfp). To silence or lower basal level of expression while retaining specificity, we have reduced the length of the MLC2v promoter from 3 kb to 1775 bp or 281 bp. The truncated promoter is equally effective in heart specific expression. Preliminary studies with the rAAV-HRE-gfp in vitro show an increased expression in 1% O(2) in 4 to 6 hours. By adding additional hypoxia-inducible factor (HIFalpha) (5 microg), the MLC2v-gfp expression is increased by 4-fold in 1% O(2). Further amplification of the gene to 400-fold in 1% O(2) can be achieved with a double plasmid. The construct may serve as a prototype "vigilant vector" to switch on therapeutic genes in specific tissue with physiological signals.
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PMID:Vigilant vector: heart-specific promoter in an adeno-associated virus vector for cardioprotection. 1188 25

1. Myocardial injury caused by ischaemia and reperfusion comes from multiple pathogenic events, including endothelial damage, neutrophil extravasation into tissue, mast cell activation, and peroxidation of cell membrane lipids. These events are followed by myocardial cell alterations resulting eventually in cell necrosis. An enhanced formation of reactive oxygen species is widely accepted as a stimulus for tissue destruction and cardiac failure. 2. In this study, we have investigated the cardioprotective effects of M40403 in myocardial ischaemia-reperfusion injury. M40403 is a low molecular weight, synthetic manganese containing superoxide dismutase mimetic (SODm) that selectively removes superoxide anion. Ischaemia was induced in rat hearts in vivo by ligating the left anterior descending coronary artery. Thirty minutes after the induction of ischaemia, the ligature was removed and reperfusion allowed to occur for at least 60 min. M40403 (0.1-1 mg kg(-1)) was given intravenously 15 min before ischaemia. 3. The results obtained in this study showed that M40403 significantly reduced the extent of myocardial damage, mast cell degranulation and the incidence of ventricular arrhythmias. Furthermore, M40403 significantly attenuated, in a dose-dependent manner, neutrophil infiltration in the myocardium as well as the associated induction of lipid peroxidation. Calcium overload seen post-reperfusion of the ischaemic myocardium was also reduced by M40403. 4. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in cardiac tissue taken after reperfusion: this was attenuated by M40403. Moreover reperfused cardiac tissue sections showed positive staining for P-selectin and for anti-intercellular adhesion molecule (ICAM-1) in the vascular endothelial cells. M40403 treatment markedly reduced the intensity and degree of P-selectin and ICAM-1 in these tissues. No staining for nitrotyrosine, P-selectin or ICAM-1 was found in cardiac tissue taken at the end of the ischaemic period. 5. Overall, M40403 treatment reduced the morphological signs of myocardial cell injury and significantly improved survival. 6. Taken together, these results clearly indicate that M40403 treatment exerts a protective effect against ischaemia-reperfusion-induced myocardial injury, supporting a key role for superoxide anion in reperfusion injuries. This suggests that synthetic enzymes of SOD such as M40403, offer a novel therapeutic approach for the treatment of ischaemic heart disease where superoxide anion plays a dominant role.
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PMID:Protective effects of M40403, a selective superoxide dismutase mimetic, in myocardial ischaemia and reperfusion injury in vivo. 1211 Jun 15

Refracterin therapy of patients with chronic heart failure caused by coronary heart disease and postinfarction cardiosclerosis markedly promoted improvement in the pulmonary and systemic circulation in comparison with patients receiving traditional therapy. The mean functional class of chronic cardiac failure decreased by 43% under the effect of refracterin vs. 27% decrease in the group receiving traditional therapy. After 1-month refracterin course the end-systolic and end-diastolic sizes of the left ventricle decreased by 12 and 7%, respectively, ejection fraction increased by 7.2% in comparison with the initial level, total oxidant activity and MDA content in the plasma decreased significantly, while total antioxidant activity, catalase and SOD activities, cytochrome C, NADH, and NADPH levels increased. The prooxidant-antioxidant system was shifted towards antioxidants, which attests to activation of the defense and adaptive mechanisms after administration of refracterin, which is especially important in elderly patients with initially decreased reserve potentialities of the antioxidant defense system.
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PMID:Efficiency and mechanisms of the antioxidant effect of standard therapy and refracterin in the treatment of chronic heart failure in elderly patients with postinfarction cardiosclerosis. 1566 59

To circumvent the early lethality of manganese superoxide dismutase (SOD2)-deficient mice, we have used a skin-specific strategy with introduction of loxP sites flanking exon 3 of the SOD2 gene. To our surprise, when breeding a female keratin 14 Cre transgenic mouse to a SOD2 "floxed" male mouse, due to keratin 14 promoter-driven Cre expression in the oocytes, all offspring were heterozygous for SOD2. In sharp contrast to initial publications on SOD2(+/-) mice, the herein reported mice on a mixed genetic background (C57BL/6 x 129/Ola) in their heterozygous state (SOD(+/-)) revealed distinct ultrastructural damage of the myocard, with swelling and disruption of mitochondria and accumulation of lipid droplets, increased nitrotyrosine formation, and lipid peroxidation as well as activation of apoptosis signaling pathways in the heart in vivo. Strikingly, and so far unreported, we found a substantial decrease in the activity of the cytosolic copper, zinc superoxide dismutase (SOD1) in the heart tissue of SOD2(+/-) mice, suggesting that the breakdown of mitochondrial membranes in the heart of SOD2(+/-) mice results in the enhanced release of superoxide anion radicals or derivatives thereof with subsequent inactivation of cytosolic SOD1. This model may be particularly suited to long-term studies on age-related heart failure as well as other age-related diseases and the polygenic base of tissue-specific responses to oxidative injury.
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PMID:Heterozygous deficiency of manganese superoxide dismutase results in severe lipid peroxidation and spontaneous apoptosis in murine myocardium in vivo. 1589 Jun 20

Oxidative stress is associated with endothelial dysfunction in heart failure. The goals of this study were to determine whether 1) gene transfer of extracellular superoxide dismutase (ecSOD) reduces levels of superoxide and improves endothelial function in the aorta and mesenteric artery in rats with heart failure, and 2) the heparin-binding domain (HBD) of ecSOD, by which ecSOD binds to cells, is required for protective effects of ecSOD. Seven weeks after coronary ligation, in rats with heart failure and sham-operated rats, we injected adenoviral vectors intravenously that express ecSOD, ecSOD with deletion of the HBD (ecSODDeltaHBD), or a control vector. Four days after injection of viruses, responses to acetylcholine, ADP, and sodium nitroprusside were examined in rings of the aorta and mesenteric artery. ecSOD bound to endothelium and increased SOD activity in the aorta after gene transfer of ecSOD, not ecSODDeltaHBD. Gene transfer of ecSOD, but not ecSODDeltaHBD, reduced levels of superoxide and improved relaxation to acetylcholine and ADP in the aorta and mesenteric artery from rats with heart failure. Improvement of relaxation to acetylcholine in the mesenteric artery from rats with heart failure after gene transfer of ecSOD was mediated in part by hydrogen peroxide. The major finding of this study is that the HBD of ecSOD is necessary for protection against endothelial dysfunction in rats with heart failure. We speculate that a common gene variant in the HBD of ecSOD, which is a risk factor for ischemic heart disease, may be a risk factor for vascular maladaptation and endothelial dysfunction in heart failure.
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PMID:Gene transfer of extracellular superoxide dismutase improves endothelial function in rats with heart failure. 1601 12

Heart failure evokes diaphragm weakness, but the mechanism(s) by which this occurs are not known. We postulated that heart failure increases diaphragm free radical generation and that free radicals trigger diaphragm dysfunction in this condition. The purpose of the present study was to test this hypothesis. Experiments were performed using halothane-anesthetized sham-operated control rats and rats in which myocardial infarction was induced by ligation of the left anterior descending coronary artery. Animals were killed 6 wk after surgery, the diaphragms were removed, and the following were assessed: 1) mitochondrial hydrogen peroxide (H2O2) generation, 2) free radical generation in resting and contracting intact diaphragm using a fluorescent-indicator technique, 3) 8-isoprostane and protein carbonyls (indexes of free radical-induced lipid and protein oxidation), and 4) the diaphragm force-frequency relationship. In additional experiments, a group of coronary ligation animals were treated with polyethylene glycol-superoxide dismutase (PEG-SOD, 2,000 units x kg(-1) x day(-1)) for 4 wk. We found that coronary ligation evoked an increase in free radical formation by the intact diaphragm, increased diaphragm mitochondrial H2O2 generation, increased diaphragm protein carbonyl levels, and increased diaphragm 8-isoprostane levels compared with controls (P < 0.001 for the first 3 comparisons, P < 0.05 for 8-isoprostane levels). Force generated in response to 20-Hz stimulation was reduced by coronary ligation (P < 0.05); PEG-SOD administration restored force to control levels (P < 0.03). These findings indicate that cardiac dysfunction due to coronary ligation increases diaphragm free radical generation and that free radicals evoke reductions in diaphragm force generation.
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PMID:Diaphragmatic free radical generation increases in an animal model of heart failure. 1610 20


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