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)

The balance between prostaglandin (PG)I2, a potent vasodilator and inhibitor of platelet aggregation mainly produced by endothelial cells, and thromboxane (TX)A2, a vasoconstrictor and inducer of platelet aggregation and adhesion synthesized predominantly by platelets, seems to be relevant for the regulation of vessel tone and platelet aggregation. PGE2 has vasodilating properties, too. Thus, substances affecting the biosynthesis of PG and TX may have prophylactic and therapeutic, but also detrimental effects with regard to hypertension and atherosclerosis. A mechanism of action which is related to the PG system is discussed for a number of antihypertensive agents, e.g. propranolol, angiotensin converting enzyme inhibitors, furosemide and cicletanine. The vasoprotective effect of inhibition of platelet cyclooxygenase by acetylsalicylic acid is well known. Calcium antagonists, dipyridamole, estradiol, aprotinin and interferon have also been reported to possibly exert beneficial effects on PG/TX levels, while cyclosporin A and streptokinase have shown undesirable interactions with the PG system.
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PMID:[Vasoactive drugs with an effect on the prostaglandin system]. 141 11

Serum angiotensin converting enzyme activity is elevated in certain human granulomatous diseases. Angiotensin II modestly suppresses thymidine incorporation and augments gamma interferon production from human blood mononuclear cells. This suggests that angiotensin II may play an immunoregulatory role in human granulomatous inflammation. For this reason, the binding of angiotensin II to human peripheral blood mixed mononuclear cells, and to the human monocyte-like cell line, U-937, was studied. Angiotensin II binding to U-937 cells reveals a low level of saturable specific binding (Kd = 3 x 10(-10) M). However, binding to human cells is not easily reversible and is poorly inhibited in a competitive manner. In addition, the molecular integrity of the radioligand is not maintained following binding. Therefore, the definition of classical receptor binding cannot be fulfilled. Since binding is decreased by low temperatures and various metabolic inhibitors, it appears likely that endocytosis occurs, perhaps along with receptor binding. Angiotensin II or its breakdown products modulate the production of monocyte cAMP in spite of the inability to demonstrate classical cell surface receptors.
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PMID:Angiotensin II binding to human mononuclear cells. 254 64

Human peripheral blood monocytes synthesize a low level of angiotensin converting enzyme (ACE) when cultured in vitro for six days. If cell-free bronchoalveolar lavage fluid from sarcoidosis patients was included with the monocytes during culture, the monocyte ACE level increased significantly in a dose dependent manner. In contrast, the cell-free bronchoalveolar lavage fluid from control subjects and patients with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis raised basal monocyte levels little, if at all. These results suggested that sarcoid lavage fluid contains a soluble ACE-inducing factor (AIF) that was absent or present in much lower concentrations in the bronchoalveolar lavage fluid of the other patients studied. Initial attempts to characterize this AIF indicated an apparent molecular weight of greater than 5000 daltons as determined by Amicon ultrafiltration. The AIF was stable to heating at 56 degrees for 1 hour. This finding demonstrated that lavage ACE was not responsible for the AIF activity since lavage ACE is inactivated under these conditions. Gamma-interferon (macrophage-activating factor) was also eliminated as the agent responsible for AIF activity since gamma-interferon decreased rather than increased monocyte ACE. In summary, bronchoalveolar lavage fluid from sarcoid patients contains a soluble factor (AIF) that induces ACE in cultured monocytes. Action of this factor in vivo may be responsible for the increased ACE levels seen in the monocyte-derived epithelioid granuloma cells of sarcoidosis.
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PMID:Induction of angiotensin converting enzyme in cultured human monocytes by a factor present in the bronchoalveolar lavage fluid of sarcoidosis patients. 283 20

Ascites often appears as a complication of several illnesses. The therapy is essentially based on the use of low-sodium diet, plasma or albumin infusion, diuretics and low-dosed ACE-inhibitors. To use the simple paracentesis or special techniques as Rhodiascit or Lee Veen Shunt means not to resolve definitively the problem and sometimes to cause undesirable complications. The authors present a new therapeutic tactics that joins the use of technique of double filtration of ascitic fluid and reinfusion of concentrated proteins (DFAF) with the injection in the peritoneal cavity of beta-interferon and the venous infusion of ATIII. Twenty patients affected by hepatic cirrhosis with the presence of ascitic fluid not treatable with the usual therapy have been subjected to this treatment. All the patients showed an immediate improvement of the clinical situation. After one year of observation, we describe our results. Twelve patients needed a further treatment with the DFAF technique, two patients died for the original pathology and six patients just needed an adjustment of pharmacologic therapy.
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PMID:[Reinfusion ascites therapy: considerations after a year's experience]. 748 Sep 64

Among the various anticancer drugs, used alone or in combination during courses of chemotherapy, anthracyclines (leader: doxorubicin) are responsible for direct myocardial toxicity, which can exceptionally be acute, but more often chronic with a delayed onset. This cardiotoxicity is directly proportional to the cumulative dose administered and the recommended total dose for doxorubicin is 550 mg/m2. The risk factors able to potentiate cardiotoxicity must be analysed before starting chemotherapy and follow-up by ultrasonography and/or isotope ejection fraction must be repeated before each course. The treatment of anthracycline-induced heart failure consists of digitalis alkaloids combined with angiotensin converting enzyme inhibitors. The cardiac toxicity of 5FU is currently explained by the theory of coronary spasm, based on clinical findings such as chest pain associated with ischaemic electrical modifications. The incidence of this toxicity is low, but it can be fatal. Exceptional examples include the cardiotoxicity induced by high-dose cyclophosphamide responsible for acute haemorrhagic myocarditis, potentiation of the cardiotoxic effect of anthracyclines by dacarbazine and plicamycin, and serious ventricular and supraventricular arrhythmias induced by amsacrine. Among the various cytokines used in oncology, interferon is responsible for heart failure, reversible after stopping treatment, but also for ventricular arrhythmias, or even sudden death, the pathophysiology of which still remains unclear.
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PMID:[Chemotherapy and cardiotoxicity]. 866 96

Diagnosis of inflammatory dilated cardiomyopathy relies on the histological and immunohistological examination of endomyocardial biopsies. Only with the demonstration of the etiological agents in the myocardium specific therapy can be attempted. Whereas the spontaneous course of endemic myocarditis with little hemodynamic impairment is fair, the prognosis of symptomatic myocarditis and dilated cardiomyopathy is poor, with complete restitution in 35% and a 10-year survival rate of 30%. Restriction of physical activity is a validated form of therapy with normalization of the heart size in 40 to 60%. Symptomatic medical therapy consists of digitalis, diuretics, ACE-inhibitors and vasodilators and betablocker therapy, where a reduction of mortality was demonstrated in clinical (sub)studies up to 60%. Specific forms of therapy in inflammatory cardiomyopathy rely on the demonstration or lack of viral persistence or signs of autoreactivity in the myocardial tissue. Immunosuppressive therapy in autoimmune forms improved cardiac function in up to 60% of the patients in controlled trials, when compared to controls (40%). The double-blind randomized myocarditis treatment trial, which unfortunately did not distinguish viral from autoimmune myocarditis could not demonstrate such a benefit, however. Depending on the etiology of the disease, immunomodulation with immunoglobulins or interferon or antiviral therapy with hyperimmunoglobulins are presently tested in clinical treatment trials (ESETCID) in patients with enterovirus-positive or cytomegalovirus-positive and adenovirus-positive chronic myocarditis. Specific therapies are aimed to avoid the progression of the disease which may ultimately lead to heart failure with a cardiac assist device or heart transplantation as ultimate therapeutic option.
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PMID:[Therapy of dilated cardiomyopathies with and without inflammation]. 959 34

A 78-year-old woman with renal cell carcinoma and pulmonary metastasis presented with reversible cardiomyopathy induced by gamma(gamma)-interferon. She was treated with gamma-interferon twice a week since November 1996. She presented with severe acute congestive heart failure and gamma-interferon was immediately discontinued in December 1997. Left ventricular fractional shortening was 38% before admission, 12% on admission, and improved to 31% by 40 days after discontinuation of interferon together with administration of diuretics and angiotensin converting enzyme inhibitor. We restarted the same gamma-interferon regimen because it was effective against renal cell carcinoma after 47 days. She has remained well with no significant changes of cardiac function or renal cell carcinoma for almost one year.
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PMID:[Gamma-interferon-induced cardiomyopathy during treatment of renal cell carcinoma: a case report]. 1092 66

We experienced a 24-year-old Japanese man, who was a hepatitis B virus carrier with nephrotic syndrome. Liver biopsy showed that he was suffering from chronic hepatitis (activity 2, fibrosis 2). Renal biopsy revealed membranous nephropathy(MN) with focal segmental glomerulosclerosis(FGS). Immunofluorescentic findings revealed the presence of HBe antigen along the glomerular capillaries as well as HBe antigenemia in circulation. Therefore, we diagnosed this case as HB virus-related membranous nephropathy associated with FGS lesions. He was treated with interferon(IFN) alpha-2b for over a month and angiotensin converting enzyme inhibitor. These therapies reduced urinary protein excretion from 4-6 g/day to 1-2 g/day, in accordance with a decrease in the titer of HBV DNA polymerase. The second renal biopsy revealed that the histological change from MN to membranoproliferative glomerulonephritis Type III after IFN therapy. These results suggest that IFN therapy might be effective for HB virus-related MN associated with FGS.
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PMID:[Effect of interferon therapy on hepatitis B virus related membranous nephropathy associated with focal segmental glomerulosclerosis]. 1128 Feb 14

Two patients with chronic hepatitis C were treated with alpha 2 beta (alpha2beta) interferon and ribavirin for 6 months. Neither patient responded to therapy. Both patients developed painless skin nodules, the histology of which was compatible with sarcoidosis. During therapy, both patients also had an elevation of angiotensin converting enzyme (ACE) levels. ACE levels reverted to normal and the skin lesions resolved a few months after cessation of interferon/ribavirin therapy. A repeat liver biopsy in one patient at the end of therapy revealed multiple hepatic granulomas (which were not evident on biopsy before therapy). In conclusion, interferon/ribavirin therapy can evoke a sarcoid-like response, with skin lesions, hepatic granuloma, and elevation of ACE levels. These appear to have been reversible in the above cases.
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PMID:Manifestation of sarcoidosis during interferon and ribavirin therapy for chronic hepatitis C: a report of two cases. 1217 11

NSAIDs, including aspirin (acetylsalicylic acid), are frequently used and effective in a broad variety of inflammatory diseases, i.e. rheumatic carditis and pericarditis. Myocarditis may constitute another suitable indication for NSAIDs in order to relieve the symptoms of the presumed viral infection or because pericardial effusion is often associated with this condition. However, concerns have been raised about their indiscriminate use in myocarditis. To clarify this issue, we conducted a systematic review of the literature concerning myocarditis, aspirin and NSAIDs. We examined five animal studies of NSAIDs (indomethacin and ibuprofen) and aspirin in coxsackievirus B3- and B4-induced myocarditis. These studies indicated a deleterious effect of NSAIDs and aspirin in this setting, demonstrating a 2- to 3-fold increase in inflammation, myocytes necrosis and even mortality when compared with placebo. This possible deleterious effect was more predominant when NSAIDs or aspirin were administered during the acute and subacute phases of myocarditis; however, it was still noted when NSAIDs were administered during the late phase of the disease (the effect of aspirin was not evaluated in late phase studies). According to these animal studies, such effect might be attributed to decreased viral clearance (possibly via interferon inhibition) and/or exaggerated cytotoxic response (via interleukin-2 or inhibition of suppressor cells factors) and/or coronary artery spasm. We found one animal study looking at autoimmune myocarditis and it did not demonstrate any beneficial or detrimental effect of aspirin. Moreover, recent data suggest that aspirin and NSAIDs may counteract part of the efficacy of ACE inhibitors and be deleterious in chronic heart failure. Taken together, these studies point to a possible deleterious effect of aspirin and NSAIDs in human myocarditis. In view of these animal studies and in the absence of controlled studies of aspirin or NSAIDs in human myocarditis, we do not recommend indiscriminate treatment with NSAIDs or high-dose aspirin in patients with myocarditis where there is no or minimal associated pericarditis.
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PMID:Risks versus benefits of NSAIDs including aspirin in myocarditis: a review of the evidence from animal studies. 1458 71


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