Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Propionyl-L-carnitine (PLC) is under development as a therapeutic for the treatment of peripheral artery disease, coronary heart disease and chronic heart failure. Three methods were examined for labelling PLC in its propionyl group with positron-emitting carbon-11 (t12 = 20.3 min), one chemical and two chemoenzymatic. The former was based on the preparation of [11C]propionyl chloride as labelling agent via 11C-carboxylation of ethylmagnesium bromide with cyclotron-produced [11C]carbon dioxide and subsequent chlorination. Reaction of carrier-added [11C]propionyl chloride with L-carnitine in trifluoroacetic acid gave [11C]PLC in 12% radiochemical yield (decay-corrected) from cyclotron-produced [11C]carbon dioxide. However, the radiosynthesis was unsuccessful at the no-carrier-added (NCA) level of specific radioactivity. [11C]Propionate, as a radioactive precursor for chemoenzymatic routes, was prepared via carboxylation of ethylmagnesium bromide with [11C]carbon dioxide and hydrolysis. NCA [11C]PLC was prepared in 68 min in 14% radiochemical yield (decay-corrected) from [11C]propionate via sequential conversions catalysed by acetate kinase, phosphotransacetylase and carnitine acetyltransferase. A superior chemoenzymatic synthesis of NCA [11C]PLC was developed, based on the use of a novel supported Grignard reagent for the synthesis of [11C]propionate and conversions by S-acetyl-CoA synthetase and carnitine acetyltransferase. This gave an overall radiochemical yield of 30-48% (decay-corrected). This synthesis was automated for radiation safety and provides pure NCA [11C]PLC in high radioactivities ready for intravenous administration within 25 min from radionuclide production. The [11C]PLC is suitable for pharmacokinetic studies in human subjects with PET and the elucidation of the fate of the propionyl group of PLC in vivo.
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PMID:Automated chemoenzymatic synthesis of no-carrier-added [carbonyl-11C]propionyl L-carnitine for pharmacokinetic studies. 937 26

Fibrin D-dimer are the consequence of an excess of fibrinolysis. The raise of their level in coronary heart disease seems to be helpful to enhance the diagnosis of coronary ischemia. Prospective study over 4 months, including 22 patients (16 male, 6 female) divided in 2 subgroups: Group I: 10 patients investigated for stable angina Group II: 12 patients investigated for ACS without ST elevation. All patients underwent fibrin D-dimer dosage and coronarography. Fibrin D-dimer levels were higher in group II (924.5 ng/ml vs 703.9 ng/ml; p < 0.0001). In group II, 6 patients had ST depression with a level of fibrin D-dimer 879.5 ng/ml vs 969.6 ng/ml in the other 6 patients. We found a positive correlation between level of fibrin D-dimer and complexity of coronary lesions (1007 ng/ml in type C vs 675 ng/ml in type A lesions; p < 0.0001). Fibrin D-dimer seems highly implicated in coronary disease and if these results are confirmed by larger studies their routine dosage will be helpful in ACS.
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PMID:[Role of fibrin D-dimer in acute coronary syndrome. Prospective study of 22 cases]. 1512 4

Coronary disease accounts for the majority of deaths among patients with diabetes and the thrombotic milieu accelerated by diabetes results in unstable angina (UA), non-ST segment elevation myocardial infarction (NSTEMI) or ST-segment elevation myocardial infarction (STEMI) or death. Upstream use of a glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor with percutaneous coronary intervention (PCI) as part of an early invasive approach is preferred. However substantial numbers of patients present to rural or non-teaching hospitals without immediate access to a catheterization laboratory. Enhanced GP IIb/IIIa receptor mobilization, TXA2 production and platelet activation together present an extensive thrombotic challenge that may not be overcome with current doses of GP IIb/IIIa inhibitors when used without PCI. Heterogeneity of platelet aggregometric analysis may have identified GP IIb/IIIa doses used in clinical trials that may not fully overcome the thrombotic challenge in patients with diabetes. GUSTO-IV ACS failed to demonstrate a difference in mortality when used without PCI. The PURSUIT trial provided evidence that eptifibatide decreases death or non-fatal myocardial infarction (MI) in the main group and in the diabetic subgroup. Reductions in this primary endpoint were driven by the reduction in non-fatal MI. The PRISM and PRISM-PLUS trials demonstrated a reduction in death, MI or refractory ischaemia at 48 h or 7 days in the main cohort but not specifically in patients with diabetes. Data supporting use of GP IIb/IIIa inhibitors are inconsistent, raising the question of whether these agents should be used at all without PCI. Variability in experimental methodology of platelet aggregometry and selection of anticoagulant used during dose finding studies may have generated doses that are insufficient to overcome the thrombotic burden. A new marker of active inflammation, sCD40L is found to be upregulated at subtherapeutic doses of GP IIb/IIIa inhibitors, suggesting that rebound inflammatory processes may partially account for absence of clear evidence of benefit with some GP IIb/IIIa inhibitors in patients with diabetes experiencing UA/NSTEMI.
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PMID:Selection of glycoprotein IIb/IIIa inhibitors for upstream use in patients with diabetes experiencing unstable angina or non-ST segment elevation myocardial infarction. What have we learned in the last 10 years? 1558 37

During the past 2 decades, randomized trials have proved the efficacy of several treatments for non-ST-elevation acute coronary syndromes (NSTE-ACSs), including aspirin, beta blockers, and coronary revascularization. However, the cumulative effectiveness of these evolving therapies in actual clinical practice remains unknown. The Atherosclerosis Risk In Communities (ARIC) surveillance study uses rigorous prospective community surveillance to monitor the epidemiology of coronary heart disease among subjects who are 35 to 74 years of age and reside in 4 United States communities, with a population totaling 370,000 subjects. We identified 6,379 ARIC surveillance patients who were hospitalized with NSTE-ACS (defined as cardiac chest pain and ST depression or T-wave inversion on the presenting electrocardiogram) between 1987 and 2000 and then analyzed 30-day and 1-year mortalities by calendar year of admission. Using logistic regression, 30-day mortality was modeled first using predictor variables of the calendar year, ARIC community, and indicators of severity and co-morbidity and then by adding variables for treatment with aspirin, beta blockers, and coronary revascularization to this model. Crude 30-day mortality decreased from 8.6% in 1988 to 3.6% in 2000 (p for trend <0.001), a trend that remained significant (p = 0.006) after adjustment for case severity and co-morbidity. The trend became nonsignificant after adjustment for treatment variables, suggesting that newer treatments may explain the improved survival. In conclusion, 30-day mortality from NSTE-ACS has decreased as treatment has improved.
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PMID:Fourteen-year (1987 to 2000) trends in the attack rates of, therapy for, and mortality from non-ST-elevation acute coronary syndromes in four United States communities. 1627 76

The authors describe a case of a 74-year-old man with advanced coronary heart disease in whom pulmonary hemorrhagic complications during therapy with ticlopidine and subsequently with clopidogrel and amiodarone were observed. Fever and massive hemoptysis following five days of ticlopidine treatment, before elective coronary angiography, were noticed. Transient interstitial X-ray changes of the right lung were visible. Three months later a new episode on the third day of clopidogrel administration was manifested. He was after PCI, performed because of ACS complicated with ventricular fibrillation. Two days following clopidogrel discontinuation hemoptysis remitted but after ten days occurred again (this time with bilateral X-ray changes). Amiodarone, given after VF, was stopped. Spectacular improvement with steroid treatment was observed. Indobufen (reversible COX- 1 inhibitor) as an antiplatelet therapy was availed. The authors discuss therapeutic dilemma concerning the patient with coexisting different diseases.
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PMID:[Recurrent hemoptysis following thienopyridines and amiodarone administration. therapeutic dilemma]. 1680 16

This paper provides a comprehensive up-to-date review of the medical and invasive management of patients with non- ST-segment elevation acute coronary syndromes (NSTE-ACS). The authors have summarized findings from key clinical trials published recent years that contribute to clinicians' understanding of how best to optimize therapy. The goals for the management of NSTE-ACS are rapid and accurate risk stratification, appropriate and institution-specific triage to interventional versus medical strategies and optimal pharmacologic therapy--all of which provide for a smooth and seamless transition of care between the emergency department and the cardiology service. High-risk features or absolute treatment trigger criteria that support more aggressive medical therapy (i.e., addition of small-molecule GP IIb/IIIa inhibitor to a core regimen of aspirin, enoxaparin, and in most cases, clopidogrel) and/or that would direct clinicians toward percutaneous, mechanical/interventional strategies as the preferred modality include, but are not limited to, the presence of one or more of the following: (1) elevated cardiac markers (troponin and/or CK-MB); (2) elevated levels of inflammatory markers (particularly CRP > 3 microg/dl); (3) age > 65 years; (4) presence of ST-T wave changes; (5) TIMI Risk Score greater than or equal to 4; (6) diabetes; and/or (7) clinical instability in the setting of suspected NSTE-ACS. Specific clinical, ECG and/or biochemical trigger points modulate the aggressiveness of both the medical therapy and the propensity to perform early angiography with or without subsequent revascularization in patients with NSTE-ACS. Although additional refinements and changes in ACS management are still to come, evidence-based strategies suggest that prompt mechanical revascularization is associated with the best possible clinical outcomes, particularly for patients with high-risk features and in whom benefits of adjunctive, pharmacoinvasive antithrombotic therapies can be consolidated. Patient transfer for cardiac catheterization/percutaneous coronary intervention (PCI) is strongly recommended in patients who manifest high-risk features and/or aggressive treatment trigger criteria, so that this high-risk subgroup may receive definitive, interventional and/or cardiology-directed specialty care at appropriate sites of care. When available, interventional management is preferred in these patients. The importance of safe and effective anticoagulation in the spectrum of management strategies has been confirmed, and the evidence in support of enoxaparin and other antithrombotic agents has been reviewed. Dosing recommendations for enoxaparin use in the setting of PCI have been issued by the CATH Panel and have been summarized in this consensus report. Similar recommendations have been presented for the use of oral antiplatelet agents and GP IIb/IIIa antagonists. The addition of statins, ACE-inhibitors and beta-blockers is also stressed as part of a comprehensive secondary cardioprotective strategy for patients with coronary heart disease.
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PMID:Strategies for optimizing outcomes in the NSTE-ACS patient The CATH (cardiac catheterization and antithrombotic therapy in the hospital) Clinical Consensus Panel Report. 1719 14

Atorvastatin has been extensively studied in the primary and secondary prevention of cardiovascular events, and may have some clinical advantages over various other statins in these respects. The principal primary prevention study of atorvastatin, ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm), revealed that atorvastatin reduced the relative risk of primary coronary heart disease (CHD) events by 36% (p = 0.0005) compared with placebo in patients with hypertension. Much published data confirm the secondary preventive benefits of atorvastatin in various clinical settings. The IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) and TNT (Treating to New Targets) trials demonstrate the preventive efficacy of atorvastatin in patients with stable CHD. Relative to simvastatin (in the IDEAL trial) and low-dosage atorvastatin (in the TNT trial), intensive atorvastatin therapy (80 mg/day) reduced the risk of nonfatal myocardial infarction (MI) by 17-22% (p < or = 0.02). Furthermore, the ALLIANCE (Aggressive Lipid-Lowering Initiation Abates New Cardiac Events) and GREACE (GREek Atorvastatin and Coronary-heart-disease Evaluation) trials highlight the benefits of atorvastatin in the 'real world' setting in patients with stable CHD. Compared with 'usual' care, atorvastatin reduced the risk of nonfatal MI by 47-59% (p < or = 0.0002).Moreover, the MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering), PROVE-IT (PRavastatin Or atorVastatin Evaluation and Infection Therapy) and IDEAL-ACS (Acute Coronary Syndromes) studies outline the benefits of high-dosage atorvastatin therapy started within 24-96 hours, 10 days or 2 months, respectively, of an acute coronary syndrome. Relative to placebo, pravastatin and simvastatin, atorvastatin reduced the risk of death or major cardiovascular events by 16-18% (p < or = 0.048). In patients undergoing revascularisation procedures, the AVERT (Atorvastatin VErsus Revascularisation Treatment) study revealed that 18 months' administration of atorvastatin 80 mg/day was at least as effective as angioplasty plus usual care in reducing the risk of ischaemic events in low-risk patients with stable coronary artery disease. Furthermore, the ARMYDA (Atorvastatin for Reduction in MYocardial DAmage during angioplasty) and ARMYDA-3 trials showed that 7 days' administration of atorvastatin 40 mg/day before coronary intervention significantly reduced the risks of periprocedural myocardial damage (ARMYDA), postprocedural MI (p = 0.025; ARMYDA) and atrial fibrillation (p = 0.003; ARMYDA-3) versus placebo. In addition, it has been reported that C-reactive protein levels and the combined incidence of cardiovascular events (death, MI and target segment revascularisation during the 6-month follow-up) were significantly higher in coronaropathic patients undergoing non-surgical revascularisation procedures (stent implantation) not receiving statin therapy compared with those treated with atorvastatin (80mg). Overall, therefore, the marked efficacy of atorvastatin in the primary and secondary prevention of cardiovascular events underscores the pivotal place that this statin has in general cardiovascular disease management, and suggests even greater potential clinical utility for the drug in some clinical settings.
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PMID:Atorvastatin efficacy in the primary and secondary prevention of cardiovascular events. 1791 May 19

This paper provides a comprehensive up-to-date review of the medical and invasive management of patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), and ST-elevation myocardial infarction (STEMI), as supported by recent updates to the ACC/AHA Guidelines. The authors have summarized findings from key clinical trials published in recent years that contribute to clinician's understanding of how best to optimize therapy. The goals for the management of NSTE-ACS and STEMI are rapid and accurate risk stratification, appropriate and institution-specific triage to interventional versus medical strategies and optimal pharmacologic therapy - all of which provide for a smooth and seamless transition of care between the emergency department and the cardiology service. High-risk features or absolute treatment trigger criteria that support more aggressive medical therapy (i.e., addition of a small molecule gylcoprotein [GP] IIb/IIIa inhibitor to a core regimen of aspirin, enoxaparin or other anticoagulants, and in most cases, clopidogrel) and/or that would direct clinicians toward percutaneous interventional strategies as the preferred modality include, but are not limited to the presence of one or more of the following: 1) elevatedcardiac markers (troponin and/or CK-MB); 2) age older than 65 years; 3) presence of ST-T-wave changes; 4) TIMI Risk Score >/= 5; 5) clinical instability in the setting of suspected NSTE-ACS. Although additional refinements and changes in ACS management are still to come, evidence-based strategies suggest that prompt mechanical revascularization is associated with the best possible clinical outcomes, particularly for patients with high-risk features and in whom benefits of adjunctive, pharmacoinvasive antithrombotic therapies can be consolidated. Transfer for cardiac catheterization/percutaneous coronary intervention (PCI) is strongly recommended in patients who manifest high-risk features and/or aggressive treatment trigger criteria, so that this high-risk subgroup may receive definitive, interventional and/or cardiology-directed specialty care at appropriate sites of care. When available, interventional management is preferred in these patients. The importance of safe and effective anticoagulation in the spectrum of management strategies has been confirmed, and the evidence in support of enoxaparin and other antithrombotic agents has been reviewed. Dosing recommendations for enoxaparin use in the setting of PCI have been issued by the CATH Panel and have been summarized in this consensus report. Similar recommendations have been presented for the use of oral antiplatelet agents and GP IIb/IIIa antagonists. The addition of statins, angiotensin-converting enzyme (ACE) inhibitors and beta-blockers is also stressed as part of a comprehensive secondary cardioprotective strategy for patients with coronary heart disease.
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PMID:Pharmacoinvasive management of acute coronary syndrome: incorporating the 2007 ACC/AHA guidelines: the CATH (cardiac catheterization and antithrombotic therapy in the hospital) Clinical Consensus Panel Report--III. 1818 May 24

Atherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. Recently, CD4+CD25+Foxp3+ regulatory T (Treg) cells and Th17 cells have been described as two distinct subsets from Th1 and Th2 cells and have the opposite effects on autoimmunity. Th17/Treg balance controls inflammation and may be important in the pathogenesis of plaque destabilization and the onset of acute coronary syndrome [ACS, including unstable angina (UA) and acute myocardial infarction (AMI)]. To assess whether this balance was broken in patients with coronary heart disease, we detected Th17/Treg functions on different levels including cell frequencies, related cytokine secretion and key transcription factors in patients with AMI, UA, stable angina (SA) and controls. The results demonstrated that patients with ACS revealed significant increase in peripheral Th17 number, Th17 related cytokines (IL-17, IL-6 and IL-23) and transcription factor (RORgammat) levels and obvious decrease in Treg number, Treg related cytokines (IL-10 and TGF-beta1) and transcription factor (Foxp3) levels as compared with patients with SA and controls. Results indicate that Th17/Treg functional imbalance exists in patients with ACS, suggesting a potential role for Th17/Treg imbalance in plaque destabilization and the onset of ACS.
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PMID:The Th17/Treg imbalance in patients with acute coronary syndrome. 1829 18

During 2000 to 2002, 700 men (59 +/- 10 years) and 148 women (65 +/- 9 years) patients with first event of an ACS were randomly selected from cardiology clinics of Greek regions. Afterwards, 1078 population-based, age-matched and sex-matched controls were randomly selected from the same hospitals. The frequency ratio between men and women in the case series of patients was about 4:1, in both south and north Greek areas. Hierarchical classification analysis showed that for north Greek areas family history of coronary heart disease, hypercholesterolemia, hypertension, diabetes (explained variability 35%), and less significantly, dietary habits, smoking, body mass index, and physical activity status (explained variability 4%) were associated with the development of ACS, whereas for south Greek areas hypercholesterolemia, family history of coronary heart disease, diabetes, smoking, hypertension, dietary habits, physical activity (explained variability 34%), and less significantly body mass index (explained variability <1%), were associated with the development of the disease.
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PMID:Hierarchical analysis of cardiovascular risk factors in relation to the development of acute coronary syndromes, in different parts of Greece: the CARDIO2000 study. 1838 34


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