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

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both heparin and the angiotensin converting enzyme inhibitor cilazapril inhibit intimal thickening in rat carotid arteries injured by the passage of a balloon catheter. The purpose of this study was to determine if combinations of the two drugs were more effective than either drug alone and whether the effect could be accounted for by inhibition of smooth muscle cell proliferation. Heparin (0.1-0.3 mg/kg/hr) administered by continuous intravenous infusion with or without cilazapril (0-25 mg/kg/day p.o.) produced a dose-dependent inhibition of smooth muscle accumulation at 14 days after rat carotid ballooning. At the lower doses, the inhibitory effects of heparin and cilazapril were additive when the drugs were used together. This overall effect on growth was reflected in decreased smooth muscle cell proliferation at 2 and 7 days. A 7-day course of heparin combined with cilazapril, a regimen that might be applicable in the clinical setting, produced an 80% inhibition of intimal thickening at 28 days. These results provide evidence that heparin and cilazapril together might prove to be more effective than either drug alone in the control of intimal hyperplasia after arterial injury.
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PMID:Heparin and cilazapril together inhibit injury-induced intimal hyperplasia. 183 26

Protamine given to neutralize heparin after extracorporeal circulation can trigger a catastrophic reaction in some patients. While searching for a biochemical basis for this reaction, protamine was tested as an inhibitor of human plasma carboxypeptidase N (CPN) or kininase I, the inactivator of anaphylatoxins and kinins. Human plasma and CPN purified from human plasma, (Mr = 280 K) or its isolated active subunit (Mr = 48 K) were the sources of enzyme. The hydrolysis of furylacryloyl (FA)-Ala-Lys was measured in a UV spectrophotometer and that of bradykinin and the synthetic C-terminal octapeptide of anaphylatoxin C3a (C3a8) by high performance liquid chromatography. Protamine inhibited the hydrolysis of FA-Ala-Lys by CPN, (IC50 = 3.2 X 10(-7) M); added human serum albumin (30 mg/ml) increased the IC50 to 7 X 10(-6) M. When plasma was the source of CPN, the IC50 was 2 X 10(-6) M. Protamine more effectively inhibited the hydrolysis of bradykinin and C3a8. The IC50 for protamine was 5 X 10(-8) M with CPN and bradykinin, 7 X 10(-8) M with CPN and C3a8 and with the 48 K subunit and bradykinin it was 7 X 10(-8) M of protamine. Heparin competes with CPN for protamine, because in high concentration (18 U/ml) it reverses the inhibition by protamine. Protamine did not inhibit angiotensin I converting enzyme (kininase II) or the endopeptidase 24.11 (enkephalinase). Kinetic studies showed the mechanism of protamine inhibition to be partially competitive; about 10-20% of the hydrolysis of bradykinin by CPN was not inhibited by protamine. Thus, by blocking the inactivation of mediators released in shock, protamine inhibition of CPN may be partially responsible for the catastrophic reaction observed to occur in some patients.
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PMID:Protamine inhibits plasma carboxypeptidase N, the inactivator of anaphylatoxins and kinins. 291 61

Treatment strategies in acute myocardial infarction are directed toward limitation of infarct size and reduction of frequency of complications. This goal is best achieved by early reperfusion of ischemic myocardium. All trials comparing thrombolytic treatment in acute myocardial infarction indicate that either streptokinase, APSAC, or rtPA reduce mortality significantly. Particularly patients at high risk (old patients, women) benefit most from thrombolytic treatment. Although, conservation of left ventricular function and risk reduction is best achieved by very early treatment, a reduction of mortality has even been shown if thrombolytic agents are if given before 12 hours after onset of symptoms. Primary PTCA is an attractive alternative to thrombolytic therapy particularly in patients with anterior wall myocardial infarction or cardiogenic shock. Routine PTCA early or late after thrombolytic treatment however does not alter the outcome of the patients. The value of rescue PTCA remains to be settled. Heparin as an adjunctive treatment of rtPA improves patency of the coronary arteries and reduces mortality. Newer anti-thrombotic agents like hirudin, argotraban, or monoclonal antibody 7E3 are even more promising for prevention of reocclusion after thrombolytic treatment. Of the conservative medical treatment aspirin, beta-blockade, nitrates, and magnesium all have been shown reduce mortality. Similar effects could not be proven for calcium antagonists or routine antiarrhythmic drugs. ACE-inhibitors are of value if given 3 days after onset of symptoms.
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PMID:[Myocardial infarct: acute intervention]. 815 63

To define the clinical characteristics, prognosis and treatment of myocardial infarction (MI) in the elderly, we retrospectively compared the files of 101 patients aged > or = 75 years (mean: 82 +/- 4 years) and of 120 others aged < or = 65 years (mean: 55 +/- 4.7 years). The figures corresponding to younger patients are presented in brackets. The elderly group included 60.4% women (5%: p < 0.001), 58.9% hypertensive subjects (38.3%: p = 0.005); 30.4% diabetics (11.7%: p = 0.0013) and 12.6% smokers (66.1%: p < 0.001); 20.8% of the elderly had a history of MI (10%: p = 0.002), 15.8% of arteriopathy of the lower limbs (8.3%: p = 0.001) and 6.9% of cerebrovascular accident (1.7%: p = 0.02). Elderly patients were admitted after an average of 26.6 hours (10.4 hours: p < 0.001). Only 56.4% (79.2%) reported typical MI pain, 22.8% (7.5%) had a painless form, 31.8% (4.2%) an initial left ventricular failure, 21.8% (7.5%) a global cardiac dysfunction and 20.8% (4.2%) a cardiogenic shock (p < 0.001 for all comparisons). 63.4% had an anterior MI (40.8%: p < 0.001), 40.6% a Q-form (29.6%: p = NS) and 22.2% an atrial fibrillation (0.8%: p < 0.001). Serum myoglobin and total CK concentrations were significantly lower in elderly subjects. 20.8% of them received beta-blockers (86.7%), 43.6% aspirin (80%), 14.6% oral anticoagulant (56.7%), but 63.4% were given diuretics (25.2%) and 31.7% digitalis alkaloids and positive inotropic drugs (6.7%) (p < 0.001 for all these comparisons). Heparin, nitrates, calcium channel blockers, ACE inhibitors and antiarrhythmics were prescribed as often regardless of age. Only 10 elderly patients (9.9%) were treated with thrombolytics (77: 65%: p < 0.001); 6 (5.9%) underwent coronary angiography (43: 35.8%: p < 0.001), 2 (2%) angioplasty (11: 9.2%) and one (1%) coronary bypass surgery (12: 10%). 35 elderly patients (34.7%) died while in hospital (5: 4.2%), 22 suddenly, 10 in cardiogenic shock and 3 due to arrhythmias. 38 cases (37.8%) of heart failure (21: 17.5%), 21 (20.8%) recurrences of coronary insufficiency (8: 6.7%) and 11 (10.9%) mechanical complications of MI (4: 3.3%) were also observed (p < 0.001 for all these comparisons). Due to lack of sufficient data, we could not define the status of the surviving patients discharged from hospital. The wider use of thrombolytics, angiography and angioplasty (coronary bypass surgery still having a heavy mortality and morbidity) is probably the best way to improve the prognosis of MI in the elderly.
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PMID:[Myocardial infarction in the elderly. Comparison between 2 groups of patients over 75 and under 65 years of age]. 953 67

Inhibitors of angiotensin converting enzyme (ACE inhibitors) have been introduced more than fifteen years ago into the treatment of hypertension, congestive heart failure, myocardial infarction and diabetic nephropathy. The therapeutic success is related to their action in reduction of plasma and tissue angiotensin II concentrations and potentiation of endogenous kinins. They are able to improve myocardium metabolic status, prevent cardiac hypertrophy, limit myocardial infarct size, and thus prevent heart failure. Since 1987 ACE inhibitors are introduced in the clinical practice in our clinic. We introduced the therapy with lisinopril (Lopril), in 70% of patients among 2855 patients that were admitted in Coronary Care Unit in 1997 and 1998. Lisinopril was introduced as soon as the patient was admitted, together with fibrinolitic, Heparin and Aspirin therapy. Since that time we noticed decrease in postinfarction heart failure in comparison to previous years. We recommend permanent therapy with a small doses of ACE inhibitors in patients with heart infarction.
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PMID:[Converting enzyme inhibitors in acute myocardial infarct and heart failure]. 1035 28

The general pharmacotherapeutic issues surrounding AMI are complex and expanding, especially with regard to treatment aimed at the [table: see text] culprit, coronary atherosclerotic thrombus. Basic, well-established therapy includes the routine administration of oxygen, nitroglycerin, aspirin, and at times morphine, with selected cases invoking caution with respect to these agents (e.g., nitroglycerin and the risk of hypotension in right ventricular infarction; contraindication to nitrolycerin in patients on sildenafil). Cardioprotective agents, especially beta-adrenergic antagonists, should be considered early in light of their demonstrated benefit; others, such as ACE inhibitors, need not be administered in the ED. Heparin, both UFH and the newer LMWHs, have well-established roles in acute coronary syndromes. The GP IIb/IIIa inhibitors are the most recent addition to the pharmacologic armamentarium; their role is evolving rapidly as research on this frontier continues. Table 2 reviews recommended dosing of selected agents in acute coronary syndromes.
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PMID:General pharmacologic treatment of acute myocardial infarction. 1137 87

The modality and duration of anticoagulation before, during, and after cardioversion of atrial fibrillation--either with or without guidance by transesophageal echocardiography (TEE)--is still an unresolved issue. Intravenous infusion of unfractionated heparin until effective anticoagulation with phenprocoumon or warfarin is used as the standard therapy. However, this approach may be associated with several days of hospitalization because of the necessity for intravenous heparin administration. Moreover, there may be an increased risk of bleeding complications or, conversely, episodes of undercoagulation. Low-molecular weight heparin is an attractive alternative as it not only provide a safe and predictable level of anticoagulation with fewer side effects but can also be administered safely on an outpatient basis. In addition, no anticoagulation monitoring is needed. The ACE study (Anticoagulation in Cardioversion using Enoxaparin) is a randomized, prospective, open-label multicenter trial comparing the safety and efficacy of subcutaneous enoxaparin with intravenous heparin/oral phenprocoumon before and after cardioversion (stratified to TEE guidance or no TEE guidance). This article presents the rationale, design and status of the ACE study.
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PMID:Low molecular weight heparin for prevention of thromboembolic complications in cardioversion--rationale and design of the ACE study (Anticoagulation in Cardioversion using Enoxaparin). 1200 41

Five types of drug therapy can be considered after stroke: antiplatelet therapy, anticoagulation with heparin or warfarin, blood-pressure-lowering therapy with ACE-inhibitors and diuretics, and finally cholesterol-lowering with statins. Aspirin therapy is the best-documented treatment to avoid another stroke, both in the acute and the long-term perspective. Warfarin treatment is fairly well documented for stroke patients with atrial fibrillation. Heparin therapy increases the risk for serious haemorrhage. Blood-pressure-lowering with a combined ACE-inhibitor and diuretic regimen has been shown to reduce the recurrence rate in younger patients with hemorrhagic as well as ischemic stroke. Statin therapy could be offered to younger stroke patients with a history of coronary heart disease. The increased occurrence of malignant diseases during statin therapy in elderly patients in one study deserves further investigations.
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PMID:[Drug therapy after stroke should be evidence-based. Organizational, economic and ethical decisions direct the choice of treatment]. 1471 39

The mode and duration of anticoagulation in the setting of cardioversion of atrial fibrillation-either with or without guidance by transesophageal echocardiography (TEE)-is still an unresolved issue. Oral anticoagulation with warfarin or phenprocoumon is frequently used but may be associated with an increased risk of bleeding complications or, conversely, episodes of undercoagulation. Moreover, it takes several days to reach full anticoagulation with oral compounds. This phase may be covered with intravenous heparin but this requires prolonged hospitalization. Low-molecular weight heparin is an attractive alternative as it not only provides a safe and predictable level of anticoagulation with few side effects but can also be administered safely on an outpatient basis. In addition, anticoagulation monitoring is usually unnecessary. The ACE study (Anticoagulation in Cardioversion using Enoxaparin) compared the safety and efficacy of subcutaneous enoxaparin with intravenous heparin/oral phenprocoumon before and after cardioversion (stratified to TEE guidance or no TEE guidance). This article summarizes the study rationale and design. The results will be published shortly.
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PMID:Use of subcutaneous enoxaparin compared to intravenous heparin and oral phenprocoumon in the setting of cardioversion--the ACE study (Anticoagulation in Cardioversion using Enoxaparin). 1507 Dec 60

We previously reported that a combined therapy with heparin/warfarin and renin-angiotensin system (RAS) inhibitors dramatically reduces proteinuria for prolonged periods in advanced IgA nephropathy (IgAN). In the present study, we prospectively analyzed whether the combined therapy can inhibit the progressive decline in renal function of patients with progressive IgAN. Patients who had a marked linearity of decline in loss of glomerular filtration rate (GFR), assessed by reciprocal serum creatinine plots vs. time for more than one year, were recruited in this study if they were histologically diagnosed as IgAN at this point of declining renal function. Twelve patients were eligible for trial entry; reciprocal serum creatinine plot suggested end-stage renal failure within 5 years. All patients were treated with continuous intravenous infusion of heparin for 8 weeks, followed by oral administration of warfarin, ACE inhibitors and/or angiotensin II receptor blockers and dypiridamole. Eight patients were further given corticosteroid for 2 years because of the presence of acute glomerular lesions such as cellular crescent or angionecrosis. All patients were followed-up for at least 12 months, and the mean follow-up period was 34 +/- 20 (range 12-79) months. After the combined therapy, urinary protein excretion was significantly reduced from 2.4 +/- 1.5 g/day at baseline to 0.7 +/- 0.5 g/day at final observation, while the mean serum creatinine was not significantly different. Of note, the mean slope of 1/serum creatinine significantly increased from -0.009 to +0.0002 dl/mg/week (p < 0.05). Moreover, histological analysis of a repeat kidney biopsy which was performed in 5 patients at 2 years after the institution of the combined therapy revealed that the percentage of cellular/fibrocellular crescent and the degree of mesangial matrix expansion were significantly attenuated (19-->0.1% and 1.6-->0.6 score, respectively) while the percentage of global sclerosis and tubulointerstitial lesion did not increase. These results indicate that our combined therapy with heparin/warfarin and RAS inhibitors can inhibit the progressive decline in renal function Combined Heparin/Warfarin and RAS Inhibitors in Progressive IgAN 115 of patients with progressive IgAN through its marked antiproteinuric and anti-inflammatory effects.
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PMID:Prospective trial of combined therapy with heparin/warfarin and renin-angiotensin system inhibitors in progressive IgA nephropathy. 1749 47


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