UMLS:C0018801 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Case 1 was a 79-year-old male suspected of tuberculous constrictive pericarditis. He was admitted to our hospital because of surgical treatment. His heart failure was NYHA IV. Culture of pleural effusion and pericardial effusion was negative. But ADA level in pericardial effusion was found to be increased. So tuberculosis was suspected. Cardiac catheterization date was compatible with constrictive pericarditis. Case 2 was a 73-year-old female. She was admitted because of heart failure (NYHA IV). As RVP wave indicated dip & platou at cardiac catheterization, she was diagnosed as constrictive pericarditis. ADA level in pleural effusion increased. So tuberculosis was suspected as etiology of constrictive pericarditis. In both cases, after pericardiectomy, heart failure improved to NYHA I. Results of pathological examination were tuberculous inflammation.
...
PMID:[Two cases of tuberculous constrictive pericarditis]. 942 37

Nitroglycerin (glyceryl trinitrate, GTN), originally manufactured by Alfred Nobel, has been used to treat angina and heart failure for over 130 years. However, the molecular mechanism of GTN biotransformation has remained a mystery and it is not well understood why "tolerance" (i.e., loss of clinical efficacy) manifests over time. Here we purify a nitrate reductase that specifically catalyzes the formation of 1,2-glyceryl dinitrate and nitrite from GTN, leading to production of cGMP and relaxation of vascular smooth muscle both in vitro and in vivo, and we identify it as mitochondrial aldehyde dehydrogenase (mtALDH). We also show that mtALDH is inhibited in blood vessels made tolerant by GTN. These results demonstrate that the biotransformation of GTN occurs predominantly in mitochondria through a novel reductase action of mtALDH and suggest that nitrite is an obligate intermediate in generation of NO bioactivity. The data also indicate that attenuated biotransformation of GTN by mtALDH underlies the induction of nitrate tolerance. More generally, our studies provide new insights into subcellular processing of NO metabolites and suggest new approaches to generating NO bioactivity and overcoming nitrate tolerance.
...
PMID:Identification of the enzymatic mechanism of nitroglycerin bioactivation. 1206 Jul 25

Glyceryl trinitrate (GTN) is used in the treatment of angina pectoris and cardiac failure, but the rapid onset of GTN tolerance limits its clinical utility. Research suggests that a principal cause of tolerance is inhibition of an enzyme responsible for the production of physiologically active concentrations of NO from GTN. This enzyme has not conclusively been identified. However, the mitochondrial aldehyde dehydrogenase (ALDH2) is inhibited in GTN-tolerant tissues and produces NO2- from GTN, which is proposed to be converted to NO within mitochondria. To investigate the role of this enzyme in GTN tolerance, cumulative GTN concentration-response curves were obtained for both GTN-tolerant and -nontolerant rat aortic rings treated with the ALDH inhibitor cyanamide or the ALDH substrate propionaldehyde. Tolerance to GTN was induced using both in vivo and in vitro protocols. The in vivo protocol resulted in almost complete inhibition of ALDH2 activity and GTN biotransformation in hepatic mitochondria, indicating that long-term GTN exposure results in inactivation of the enzyme. Treatment with cyanamide or propionaldehyde caused a dose-dependent increase in the EC50 value for GTN-induced relaxation of similar magnitude in both tolerant and nontolerant aorta, suggesting that although cyanamide and propionaldehyde inhibit GTN-induced vasodilation, these inhibitors do not affect the enzyme or system involved in tolerance development to GTN. Treatment with cyanamide or propionaldehyde did not significantly inhibit 1,1-diethyl-2-hydroxy-2-nitrosohydrazine-mediated vasodilation in tolerant or nontolerant aorta, indicating that these ALDH inhibitors do not affect the downstream effectors of NO-induced vasodilation. Immunoblot analysis indicated that the majority of vascular ALDH2 is present in the cytoplasm, suggesting that mitochondrial biotransformation of GTN by ALDH2 plays a minor role in the overall vascular biotransformation of GTN by this enzyme.
...
PMID:Role of mitochondrial aldehyde dehydrogenase in nitrate tolerance. 1457 60

The nonviral gene delivery systems are usually not very effective in transferring gene into target cells, and the intensity and duration of the gene expression is very poor. The EBNA1/oriP maintain EBNA1/oriP-based plasmids as episome, contribute to nuclear transport of the plasmid and transcriptional up-regulation of target gene. The EBNA1/oriP based plasmid enhances the transfection rate as well as magnitude and longevity of gene expression. This article reviews recent preclinical gene therapy studies with the EBV plasmid vectors conducted against various diseases. For gene therapy against malignancies, the EBNA1/ oriP based plasmid encoding the HSV1-TK suicide gene was combined with a cationic polymer to transfer into HCC cell line. The expression level of TK gene was 100- to 1000-fold higher than the conventional plasmid. The sensitivity of HCC to ganciclovir (GCV) elevated several hundred-fold. The EBNA1/oriP based plasmid equipped with tumor specific promoter, such as CEA promoter, enabled targeted killing of CEA-positive tumor cell. Transfection of EBNA1/oriP based plasmid carrying IL-12 and IL-18 gene either locally, or systemically, induced therapeufic antitumor immune responses including augmentation of the cytotoxic T lymphocyte and natural killer activities and growth retardation of tumors. For gene therapy of congenital diseases and chronic diseases, the EBNA1/oriP based plasmid encoding the adenosine deaminase gene was transfered into human hematopoietic progenitor cells. The ADA activity was elevated 1.5-to 2-fold. Intracardiomuscrlar transfer of the EBNA1/oriP based plasmid encoding the beta-AR gene may be useful for the treatment of severe heart failure. Human tumor necrosis factoralpha (hTNFalpha) is one of the most important inflammatory cytokines. It has been implicated in many autoimmune and inflammatory diseases. sTNFR can efficiently neutralize the bioactivities of hTNFalpha. In primary study we cloned the chimeric protein sTNFR II-IgG Fc and expect to use it in the gene therapy of the inflammatory disease relative to TNF. In summary, The EBNA1/oriP based plasmid shows advantage in gene therapy of cancer, congenital and inflammatory diseases. Moreover, the EBNA1/oriP element may greatly contribute to the engineering of a human artificial chromosome, the ultimate device for controllable gene therapy.
...
PMID:[Progress of EBNA1/oriP-based plasmid applied in gene therapy]. 1610 85

Glyceryl trinitrate (GTN), also known as nitroglycerin, has been used to treat angina and heart failure for more than 130 years. Recently, it was shown that mitochondrial aldehyde dehydrogenase-2 (ALDH2) is responsible for formation of NO, the metabolite needed for GTN efficacy. In the present study, we show that the common G-to-A polymorphism in exon 12 of ALDH2--resulting in a Glu504Lys replacement that virtually eliminates ALDH2 activity in both heterozygotes and homozygotes--is associated with a lack of efficacy of sublingual GTN in Chinese subjects. We also show that the catalytic efficiency (Vmax/Km) of GTN metabolism of the Glu504 protein is approximately 10-fold higher than that of the Lys504 enzyme. We conclude that the presence of the Lys504 allele contributes in large part to the lack of an efficacious clinical response to nitroglycerin; we recommend that this genetic factor be considered when administering nitroglycerin to patients, especially Asians, 30-50% of whom possess the inactive ALDH2*2 mutant allele.
...
PMID:Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin. 1644 63

Besides other organic nitrates, nitroglycerin (glyceryl trinitrate; GTN) has been used to treat acute heart failure particularly due to ischemic heart disease. However, one of serious clinical problems of the GTN therapy, particularly a long-standing medication, is hemodynamic tolerance to GTN, manifested by the decreased therapeutic efficacy of the drug. The most recent studies have suggested that mitochondrial lipoate/dihydrolipoate system-dependent aldehyde dehydrogenase-2 plays a key role in nitric oxide release from GTN. The aldehyde dehydrogenase-2 performs three enzymatic activities of dehydrogenase, esterase and reductase. The reductase activity is responsible for bioactivation of organic nitrates, such as GTN yielding nitrite and dinitrate (1,2-GDN/1,3-GDN, approximately 8:1). In view of a large contribution of dihydrolipoic acid to stabilization and regeneration of thiol groups, necessary for the reductase activity of aldehyde dehydrogenase-2, we conducted studies aimed to determine whether lipoic acid administration to rats is able to prevent GTN tolerance. The studies were conducted on 4 groups of animals: control saline-treated, model GTN-tolerant, GTN + lipoic acid-treated, lipoic acid alone-administered groups. On the 9th day of experiment animals were given i.v. therapeutic dose of GTN. We measured in all animals systolic and diastolic blood pressure before injection of therapeutic dose of GTN into the cadual vein and during 20 min thereafter. Levels of nitric oxide and reactive oxygen species and activities of glutathione peroxidase and superoxide dismutase were assayed in the aorta, plasma and heart of all animals. In addition, levels of malondialdehyde, and non-protein thiols, and activities of glutathione S-transferase and gamma-glutamyl transpeptidase were evaluated in the heart and plasma. The obtained results indicate that treatment of rats with a combination of lipoic acid and GTN can efficiently counteract GTN tolerance.
...
PMID:The role of lipoic acid in prevention of nitroglycerin tolerance. 1861 39

Organic nitrates still are one of the most important drug classes used in the treatment of an acute coronary syndrome and stable coronary artery disease as well as acute and chronic congestive heart failure. The mechanism of vasodilatation comprises the release of nitric oxide, which in turn activates soluble guanylate cyclase and lowers the intracellular calcium content leading to relaxation of vascular smooth muscle. Recent research has demonstrated that highly reactive nitrates, such as nitroglycerin (or glyceryl trinitrate) and pentaerthrityl tetranitrate (PETN) are bioactivated by aldehyde dehydrogenase 2 (ALDH-2), an enzyme located in mitochondria. The enzyme, which bioactivates mono- and dinitrates is not yet identified. Despite being effective in the acute treatment of patients, its long-term efficacy is limited by the development of tolerance to nitrates and of endothelial dysfunction. Both of these side effects of nitrate therapy are due to increased production of reactive oxygen species. This review focuses on new aspects of the process of bioactivation of organic nitrates, the conception of oxidative stress of endothelial dysfunction and of the development of tolerance and their therapeutic consequences. Also discussed are more recent findings on nitric oxide donors such as molsidomine, PETN and the combination treatment of isosorbide dinitrate and hydralazine of patients with coronary artery disease and chronic heart failure.
...
PMID:[Recent findings on nitrates: their action, bioactivation and development of tolerance]. 1894 54

Each of the 4 groups of medications considered preferred therapies for treatment of T2DM by the ADA/EASD panel--insulin, sulfonylureas, TZDs, and incretin-based therapies (GLP-1 receptor agonists)--possesses significant advantages and disadvantages to be considered when individualizing treatment. Insulin and the sulfonylureas are the most researched therapies available, as well as the most cost-effective and the most effective in achieving glycemic goals. The TZDs have been shown to improve various markers of pancreatic beta-cell function; however, there is a risk of edema and heart failure with the TZDs; rosiglitazone has been associated with an increase in cardiovascular events. GLP-1 receptor agonists and DPP-4 inhibitors address different pathophysiologic causes than do other diabetes medications and offer the benefit of a low incidence of hypoglycemia. Moreover, GLP-1 receptor agonists promote weight loss, whereas DPP-4 inhibitors are generally weight neutral.
...
PMID:Selecting among ADA/EASD tier 1 and tier 2 treatment options. 1974 22

Tumour necrosis factor alpha (TNF-alpha) is implicated in post-ischemic myocardial dysfunction. Two distinct TNF-alpha receptors are shed from cell membranes and circulate in plasma as soluble sTNFR1 and sTNFR2 proteins. The aim of the study was to establish factors associated with plasma concentrations of TNF-alpha and its receptors in patients with coronary artery disease (CAD). Since adenosine inhibits the expression of TNF-alpha, two functional polymorphisms in genes encoding enzymes participating in adenosine metabolism, i.e. AMP deaminase-1 (AMPD1, C34T) and adenosine deaminase (ADA, G22A), were analyzed. Plasma concentrations of TNF-alpha, sTNFR1, and sTNFR2 were measured using ELISA in 167 patients with CAD. Common factors significantly associated with higher TNF-alpha, sTNFR1, and sTNFR2 were lower glomerular filtration rate (GFR), older age, higher BNP, lower blood haemoglobin, and the presence of asthma or chronic obstructive pulmonary disease (COPD). Higher TNF-alpha and sTNFR1 concentrations were also associated with the presence of heart failure (HF), lower ejection and shortening fraction, the presence of diabetes or metabolic syndrome, lower serum HDL cholesterol, and higher uric acid. In multivariate analysis the common independent predictors of higher TNF-alpha, sTNFR1, and sTNFR2 were lower GFR, lower HDL cholesterol, higher BNP, and the presence of asthma or COPD. There were no associations between AMPD1 C34T or ADA G22A genotypes and TNF-alpha or its receptors. In conclusion, the concentrations of TNF-alpha, sTNFR1, and sTNFR2 reflect the impairment of cardiac and renal function in patients with CAD. Metabolic syndrome and diabetes are associated with higher plasma concentrations of TNF-alpha and its receptors.
...
PMID:Plasma concentrations of TNF-alpha and its soluble receptors sTNFR1 and sTNFR2 in patients with coronary artery disease. 1984 93

Alcohol has complex effects on the cardiovascular system. The purpose of this article is to review physio-pathological effects of alcohol on cardiovascular and related systems and to describe its role in hypertension and cardiovascular disease. The relationship between alcohol and hypertension is well known, and a reduction in the alcohol intake is widely recommended in the management of hypertension. Moreover, alcohol has both pressor and depressor actions. The latter actions are clear in Oriental subjects, especially in those who show alcohol flush because of the genetic variation in aldehyde dehydrogenase activity. Repeated alcohol intake in the evening causes an elevation in daytime and a reduction in nighttime blood pressure (BP), with little change in the average 24-h BP in Japanese men. Thus, the hypertensive effect of alcohol seems to be overestimated by the measurement of casual BP during the day. Heavy alcohol intake seems to increase the risk of several cardiovascular diseases, such as hemorrhagic stroke, arrhythmia and heart failure. On the other hand, alcohol may act to prevent atherosclerosis and to decrease the risk of ischemic heart disease, mainly by increasing HDL cholesterol and inhibiting thrombus formation. A J- or U-shaped relationship has been observed between the level of alcohol intake and risk of cardiovascular mortality and total mortality. It is reasonable to reduce the alcohol intake to less than 30 ml per day for men and 15 ml per day for women in the management of hypertension. As a small amount of alcohol seems to be beneficial, abstinence from alcohol is not recommended to prevent cardiovascular disease.
...
PMID:Physio-pathological effects of alcohol on the cardiovascular system: its role in hypertension and cardiovascular disease. 2007 36

1 2 3 Next >>