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

---

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

It is generally accepted that cardiac surgery is frequently associated with the development of systemic inflammatory response. This phenomenon is very variable clinically, and can be detected by measuring plasma concentrations of certain inflammatory markers. Complement component, cytokines and adhesion molecules are examples of these markers. Systemic inflammation can be potentially damaging to major organs. Several anti-inflammatory strategies have been used in recent years, aiming to attenuate the development of systemic inflammatory response. This article summarizes recently published literature concerning the use of anti-inflammatory techniques and pharmacological agents in cardiac surgery. In particular, the anti-inflammatory effects of off-pump surgery, leukocyte filtration, corticosteroids, aprotinin, phosphodiesterase inhibitors, dpoexamine, H2 antagonists and ACE inhibitors are reviewed. The overall conclusion is that although certain strategies reduce plasma levels of inflammatory mediators, convincing evidence of significant clinical benefits is yet to come.
...
PMID:A review of anti-inflammatory strategies in cardiac surgery. 1270 60

The prevalence of congestive heart failure (CHF) is increasing in the US and worldwide, partly because patients are living longer. Treatment of CHF is mostly on an outpatient basis, but inpatient care is required for decompensated CHF, acute CHF or poor response to outpatient treatment. Control of symptoms is usually achieved by diuresis. Intravenous (IV) vasodilators are an important adjunct to the inpatient treatment of CHF. They work mainly by reducing the afterload on the myocardium although preload reduction also occurs. After clinical stabilisation, the goal is to switch to a maintenance oral regimen to be continued as outpatient therapy. The range of IV vasodilators available for inpatient treatment of CHF includes nitrates, phosphodiesterase inhibitors, dobutamine, morphine, ACE inhibitors, B-type natriuretic peptides and endothelin receptor antagonists. As each agent may have a different mechanism or site of action, each agent may affect preload, contractility or afterload to a different extent and it may be desirable to choose one over the other in a particular clinical setting. Examples of standard therapy include dobutamine, milrinone and nitroglycerin. Nesiritide, a B-type natriuretic peptide, is a newer vasodilator and US FDA approved for use in acute CHF. However, most studies with this agent have been in small numbers of patients with anecdotal findings. Larger studies are warranted to pinpoint the efficacy and adverse effects of this agent. It is primarily used to reduce the acuity of decompensated CHF on admission to hospital.Endothelin receptor antagonists show promise in the management of acute CHF, but continue to be investigational. Long-term data on their efficacy and safety are limited. None of the endothelin receptor antagonists are FDA approved for use in patients with CHF.
...
PMID:Intravenous vasodilator therapy in congestive heart failure. 1274 47

Cardiovascular diseases including heart failure represent a common disease in patients referred for anesthesia. In most cases, heart failure is caused by left ventricular dysfunction due to coronary heart disease. The aims of the treatment of chronic heart failure are the relief of symptoms, the improvement of prognosis and the prevention of the progression of heart failure. The first-line treatment involves the underlying heart disease such as myocardial revascularisation procedures in coronary heart disease or the correction of valve diseases. The pharmacological therapy depends on the stage of heart failure and symptoms of the patient. Heart failure therapy includes ACE-inhibitors, betablockers, diuretics und digitalis. Nitrates can be prescribed in patients with symptomatic heart failure despite adequate therapy but calcium antagonists are not recommended. Repeated or prolonged treatment with positive inotropic agents like phosphodiesterase inhibitors or beta-adrenergic drugs increases mortality but this is commonly used in acute stages of heart failure refractory to treatment. Interactions of ACE-inhibitors or AT1- antagonists with anesthetic agents can lead to severe hypotension especially in hypovolemic patients. Whether those drugs should be continued perioperatively or not has been controversially discussed. The use of betablockers has a positive impact on cardiac morbidity and mortality during and early after surgery. Chronic treatment with diuretics can be associated with hypovolemia and an imbalance of electrolytes leading to hypotension and arrhythmia during anesthesia but careful evaluation prior to anesthesia can avoid such complications. The continuation of digitalis during anesthesia has been controversially discussed due to the various interactions with anesthetics.
...
PMID:[Current treatment of chronic heart failure]. 1289 47

ACE (angiotensin-converting enzyme) inhibitors and PDE5 (phosphodiesterase type 5) inhibitors have each been reported to improve endothelial function in cardiovascular disease patients, but the comparative and combined effects of these two classes have not been studied previously. We sought to characterize the acute effects of ramipril alone, sildenafil alone, or their combination on endothelial function in patients with CHF (chronic heart failure). CHF subjects (n=64) were randomized to receive placebo, 10 mg of ramipril alone, 50 mg of sildenafil alone or a combination of ramipril and sildenafil in a double-blind manner. FMD (flow-mediated dilation) of the brachial artery was determined by high-resolution ultrasound imaging before and at 1, 2 and 4 h after administration of the study drug. Ramipril alone increased FMD at 4 h compared with placebo (+2.3+/-1.3%, P=0.02). Sildenafil alone increased FMD at 1, 2 and 4 h compared with placebo (+3.9+/-1.4, +4.6+/-1.8 and +3.7+/-1.3% respectively, all P<0.02). Sildenafil in combination with ramipril increased FMD at 1, 2 and 4 h when compared with placebo (+3.5+/-1.5, +4.5+/-1.8 and +4.8+/-1.3% respectively, all P<0.03). Ramipril and sildenafil both acutely improved FMD in patients with CHF, with additive effects evident at 4 h during combination therapy. Therefore further work to characterize chronic effects of combined ACE and PDE5 inhibition on endothelial function are warranted.
...
PMID:Inhibition of angiotensin-converting enzyme and phosphodiesterase type 5 improves endothelial function in heart failure. 1557 27

Peripheral arterial disease (PAD) may be asymptomatic, may be associated with intermittent claudication or may be associated with critical limb ischaemia. Coronary artery disease (CAD) and other atherosclerotic vascular disorders may coexist with PAD. Persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality and mortality from CAD. Smoking should be stopped and hypertension, diabetes mellitus, dyslipidaemia and hypothyroidism treated. HMG-CoA reductase inhibitors (statins) reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolaemia. Antiplatelet drugs such as aspirin or clopidogrel (especially the latter), ACE inhibitors and statins should be given to all persons with PAD. beta-Adrenoceptor antagonists should be given if CAD is present. The phosphodiesterase type 3 inhibitor cilostazol improves exercise time until intermittent claudication. Chelation therapy should be avoided. Correct implementation of medical therapy significantly reduces the excess mortality associated with PAD. In addition, medical therapy may result in significant improvements in walking ability that may obviate the need for lower extremity angioplasty with stenting and bypass surgery.
...
PMID:Drug treatment of peripheral arterial disease in the elderly. 1649 65

Systemic sclerosis (scleroderma) is considered as the most severe connective tissue disease. It is characterized by an abnormal immune activation, a vasculopathy and a fibrosis of the skin and of multiple internal organs. Numerous progress in the understanding of the pathogenesis with identification of key molecules have permit to introduce novel treatments that improve the management of some aspects of the disease. ACE inhibitors are effective in resolving renal crisis. Cyclophosphamide is useful for treatment of fibrosing alveolitis. Prostaglandins, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors permit to improve the treatment of the vascular complications (digital ulcerations, pulmonary arterial hypertension) of scleroderma.
...
PMID:[Pathogenic mechanisms in systemic sclerosis and their therapeutical consequences. Part 2: treatment]. 1671 Nov 51

Immunopharmacological studies show that medicines used in cardiovascular diseases (atherosclerosis, ischaemic heart disease, heart failure) can exert immunomodulatory effects on proinflammatory cytokines. In the paper the influence of statins, fibrates, angiotensin converting enzyme inhibitors (ACEI), beta-blockers, calcium channel blockers and phosphodiesterase inhibitors on the activity of cytokines was introduced.
...
PMID:[Drugs used in cardiovascular diseases and cytokines]. 1681 70

(1) Scleroderma and secondary Raynaud's phenomenon are frequently associated with increased morbidity for which no specific standardised treatment guidelines exist. (2) Current therapies for scleroderma target the immune system, with the goal of reducing inflammation and secondary tissue injury and fibrosis. Therapy targeting underlying vascular disease is designed to improve the symptoms of Raynaud's phenomenon and to reduce ischemic injury to involved organs. (3) Few controlled trials of therapy used for scleroderma are completed, and current treatments are largely based on organ-specific therapy and uncontrolled case series suggesting disease modification. (4) Recent randomised, controlled trials in scleroderma demonstrate promising results in the treatment of interstitial lung disease with cyclophosphamide, and vascular disease of the lungs and digits with endothelin receptor antagonists, the phosphodiesterase inhibitor sildenafil and prostacyclins, while trials with methotrexate show only modest benefit in controlling scleroderma-associated skin disease. (5) Prostacyclins are a therapeutic option in patients with secondary Raynaud's phenomenon. Modest benefits have also been shown with alpha1-antagonists and calcium channel blockers, while the effect of ACE inhibitors has been variable. Some data suggest some benefits to the use of the phosphodiesterase inhibitor sildenafil, the serotonin uptake inhibitor fluoxetine and the angiotensin receptor inhibitor losartan.
...
PMID:Current drug therapy for scleroderma and secondary Raynaud's phenomenon: evidence-based review. 1791 43

Prostanoids are cyclic lipid mediators which arise from enzymic cyclooxygenation of linear polyunsaturated fatty acids, e.g. arachidonic acid (20:4 n 6, AA). Biologically active prostanoids deriving from AA include stable prostaglandins (PGs), e.g. PGE(2), PGF(2alpha), PGD(2), PGJ(2) as well as labile prostanoids, i.e. PG endoperoxides (PGG(2), PGH(2)), thromboxane A(2) (TXA(2)) and prostacyclin (PGI(2)). A "Rabbit aorta Contracting Substance" (RCS) played important role in discovering of labile PGs. RCS was discovered in the Vane's Cascade as a labile product released along with PGs from the activated lung or spleen. RCS was identified as a mixture of PG endoperoxides and thromboxane A(2). Stable PGs regulate the cell cycle, smooth muscle tone and various secretory functions; they also modulate inflammatory and immune reactions. PG endoperoxides are intermediates in biosynthesis of all prostanoids. Thromboxane A(2) (TXA(2)) is the most labile prostanoid (with a half life of 30 s at 37 degrees C). It is generated mainly by blood platelets. TXA(2) is endowed with powerful vasoconstrictor, cytotoxic and thrombogenic properties. Again the Vane's Cascade was behind the discovery of prostacyclin (PGI(2)) with a half life of 4 min at 37 degrees C. It is produced by the vascular wall (predominantly by the endothelium) and it acts as a physiological antagonist of TXA(2). Moreover, prostacyclin per se is a powerful cytoprotective agent that exerts its action through activation of adenylate cyclase, followed by an intracellular accumulation of cyclic-AMP in various types of cells. In that respect PGI(2) collaborates with the system consisting of NO synthase (eNOS)/nitric oxide free radical (NO)/guanylate cyclase/cyclic-GMP. Both cyclic nucleotides (c-AMP and c-GMP) act in synergy as two energetic fists which defend the cellular machinery from being destroyed by endogenous or exogenous aggressors. Recently, a new partner has been recognized in this endogenous defensive squadron, i.e. a system consisting of heme oxygenase (HO-1)/carbon monoxide (CO)/biliverdin/biliverdin reductase/bilirubin. The expanding knowledge on the pharmacological steering of this enzymic triad (PGI(2)-S/eNOS/HO-1) is likely to contribute to the rational therapy of many systemic diseases such as atherosclerosis, diabetes mellitus, arterial hypertension or Alzheimer diseases. The discovery of prostacyclin broadened our pathophysiological horizon, and by itself opened new therapeutic possibilities. Prostacyclin sodium salt and its synthetic stable analogues (iloprost, beraprost, treprostinil, epoprostenol, cicaprost) are useful drugs for the treatment of the advanced critical limb ischemia, e.g. in the course of Buerger's disease, and also for the treatment of pulmonary artery hypertension (PAH). In this last case a synergism between prostacyclin analogues and sildenafil (a selective phosphodiesterase 5 inhibitor) or bosentan (an endothelin ET-1 receptor antagonist) points our to complex mechanisms controlling pulmonary circulation. At the Jagiellonian University we have demonstrated that several well recognised cardiovascular drugs, e.g. ACE inhibitors (ACE-I), statins, some of beta-adrenergic receptor antagonists, e.g. carvedilol or nebivolol, anti-platelet thienopyridines (ticlopidine, clopidogrel) and a metabolite of vitamin PP--N(1)-methyl-nicotinamide--all of them are endowed with the in vivo PGI(2)-releasing properties. In this way, the foundations for the Endothelial Pharmacology were laid.
...
PMID:Prostacyclin among prostanoids. 1827 80

Microvascular abnormalities and fibrosis are important targets of therapy in systemic sclerosis (scleroderma). Calcium channel blockers, ACE inhibitors, sartans, phosphodiesterase-5 inhibitors and serotonin re-uptake blockers are used for Raynaud's phenomenon. Intravenous prostanoids (alprostadil, iloprost, epoprostenol, treprostinil) and endothelin receptor antagonists (bosentan, sitaxsentan, ambrisentan) show efficacy in treatment of pulmonary hypertension and distal ischemia. Successful treatment of digital ulcers secondary to systemic sclerosis was possible with sildenafil and bosentan. A platelet gel is currently in clinical trials for scleroderma-related digital ulcers. Several drugs, which directly reduce excessive production of collagens and other connective tissue proteins have been applied in systemic sclerosis. These include interferon gamma, d-penicillamine, kolchichicine, calcitriol, and imanitib. However, so far, strategies to control fibrosis by directly reducing excessive connective tissue production have been disappointing in controlled studies.
...
PMID:[Current treatment of systemic sclerosis. Part II. Vascular and antifibrotic treatment]. 1894 47


<< Previous 1 2 3 4 5 6 Next >>

---