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)

More than a century ago, Jonathan Hutchingson, a surgeon-dermatologist, identified the first case of sarcoidosis at King's College, London. The disease is now known as a commonplace multisystem disorder characterized by the formation of noncaseating granulomata. The diagnosis of sarcoidosis is established by recognizing clinicoradiologic findings and providing histologic evidence of non-caseating granuloma. Serum angiotensin converting enzyme levels are high in about two thirds of the patients and hypercalcemia is a feature in one of every ten victims of sarcoidosis. Immunologic abnormalities include depression of cutaneous delayed-type hypersensitivity, accumulation of T-cells at the site of activity, hyperactive B-cells, and the presence of circulating immune complexes. The course and prognosis of the disease usually correlate with the mode of onset. An acute onset with erythema nodosum indicates a good prognosis and spontaneous resolution; whereas, an insidious onset may be followed by relentless, progressive fibrosis. Mortality and morbidity are caused by pulmonary fibrosis, cardiac arrhythmias, renal failure, neurologic involvement, and blindness. Corticosteroids and chloroquine relieve symptoms and suppress inflammation and granuloma formation.
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PMID:Sarcoidosis. 220 9

We suggest that polymyalgia rheumatica with giant cell arteritis (PR-GCA) is an arachidonic acid metabolites mediated disease which can be diagnosed more accurately and monitored more precisely for therapeutic benefits by the serial determinations of the major urinary prostaglandin F, serum urinary lysozymes, serum acid phosphatase, and serum angiotensin converting enzyme rather than by the erythrocyte sedimentation rate, and, when necessary by temporal artery biopsy. The pathogenetic role proposed for prostaglandins (PG) and, even more precisely perhaps, the leukotrienes in this disease is consistent with the several published clinical observations that non-steroidal anti-inflammatory drug treatment produces in some cases a therapeutic paradox of symptomatic relief with concurrent, if clinically silent, progression of the arteritis, even to blindness. Furthermore, the impressive response of PR-GCA to low maintenance dose steroid therapy, a clinical conundrum for decades, is rationally explained on the basis of depressed or obstructed PG metabolism early on in the metabolic cascade. These views warrant clinical evaluation, confirmation or correction in whole or in part, and may increase our understanding of PR-GCA.
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PMID:Polymyalgia rheumatica and giant cell arteritis--rational diagnosis and treatment predicated and disordered prostaglandin metabolism. 627 May 20

Twenty-four cats with spontaneous systemic hypertension were retrospectively studied. Blood pressure (BP) was measured indirectly by the Doppler technique in 17 cats (mean systolic 219.4 +/- 43.2 mm Hg) and directly by femoral arterial puncture in 15 cats (mean systolic/diastolic 233.2 +/- 40.9/148.1 +/- 28.7 mm Hg). All cats had bilateral retinal hemorrhages and/or detachments. Twenty cats presented because of blindness. Other presenting signs included polyuria/polydipsia, weight loss, neurological signs, and/or epistaxis. Diagnostic tests were performed to determine the presence and the cause of any secondary organ damage. Common findings included retinal hemorrhages/detachments, low-grade systolic murmurs, cardiomegaly with left ventricular hypertrophy (LVH), small kidneys, mild azotemia, and urine specific gravity < or = 1.020. Only 3 cats had hyperthyroidism. One cat was transiently diabetic. Necropsies on 2 cats with neurological signs showed nephrosclerosis, arteriosclerosis, and multifocal cerebral hemorrhages. Twenty cats were treated with diuretics, beta-adrenergic antagonists, and/or an angiotensin converting enzyme (ACE) inhibitor. One cat was treated with methimazole only, and 1 was treated with insulin transiently. The median survival of the 24 cats was 18 months. Response to therapy did not appear to have an impact on survival time.
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PMID:Spontaneous systemic hypertension in 24 cats. 804 80

Hyperglycemia plays a decisive role in development of diabetic retinopathy, nephropathy and neuropathy. Unfortunately, even modern antidiabetic means often fail to install normoglycemia or near normoglycemia. They also bear an important risk for hypoglycemia. What glucose levels (as measured by Hb-A1c) may be tolerated without consequences for the patient is unknown so far; therefore, we should presently still aim at lowering the blood glucose as often and as close to normal as possible and try to avoid severe hypoglycemias. Those who care for diabetics carry a high responsibility. The care diabetics should be improved as follows: Regular ophthalmologic controls could reduce occurrence of visual losses or blindness. Efficient lowering of hypertension prevents occurrence and progression of nephropathy. ACE-inhibitors turned out to be also useful in normotonic diabetics, because they prevent progression of nephropathy. Diabetics bearing a risk for lesions on the feet should be identified, instructed and treated adequately. This is the only way to reduce the rate of amputations. Risk factors for general arteriosclerosis should be efficiently treated or avoided, particularly in diabetics. In consideration of these factors, morbidity and mortality of diabetic patients could be influenced more efficiently. There is no justification for any defeatist attitude.
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PMID:[Can late sequelae of diabetes be avoided? Various critical observations]. 829 33

On the whole, diabetic microangiopathy can be understood as the clinical renal-retinal syndrome. About 10% of all diabetics die of end-stage renal failure, more frequent in IDDM. With an incidence of 14% diabetic retinopathy is one of the major causes of blindness in adulthood. In the non-proliferative state, the pathological changes are limited to the retina, whereas the alterations affect both retina and vitreous in the proliferative state. Photocoagulation is the treatment of choice. If photocoagulatory treatment is not possible because of cataract, vitreous surgery (pars-plana vitrectomy) could improve visual prognosis. The clinical features hypertension, proteinuria and finally renal failure define the term "diabetic nephropathy". The increased intraglomerular pressure is the main pathological alteration of incipient nephropathy. Microalbuminuria essentially determines the prognosis: in IDDM it concerns the incidence of a manifest nephropathy, in NIDDM the excessively increased incidence of cardiovascular mortality. Sonographically, the kidneys are large with bright and wide parenchyma. Along with the development of end-stage renal disease the kidney size diminishes. According to Mogensen, nephropathy is divided into five stages: Stage 1, the early stage, is defined by hypertrophy and hyperfiltration. Stage 2 shows incipient structural changes without any clinical findings. Stage 3 is characterised by persistent microalbuminuria. Stage 4 leads to increasing renal failure and stage 5 to end-stage renal disease and the necessity of dialysis treatment. Incipient nephropathy demands a strict treatment of both hypertension and diabetes. In the meantime, ACE inhibitors are the treatment of choice. In case of dialysis treatment continuous ambulant peritoneal dialysis (CAPD) is usually preferred.
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PMID:[Diabetic microangiopathy]. 847 38

Morbidity and mortality in diabetes are caused mainly by its vascular complications, both in the microcirculation and in the large vessels. Diabetic nephropathy and retinopathy are the clinical hallmarks of microangiopathy, which may lead to end-stage renal failure and blindness. The cardiovascular complications in diabetes consist mainly of an accelerated form of atherosclerosis. Systemic hypertension is an early and frequent phenomenon. Nocturnal hypertension is also more frequent in people with diabetes compared with the nondiabetic population. Capillary hypertension has been demonstrated in type 1 diabetic patients. Poor metabolic control may induce elevation in blood pressure, but data are conflicting. The prevalence of white-coat hypertension in the diabetic population is comparable with that in the nondiabetic population. Prospective observational studies in type 1 and type 2 patients have revealed that abnormally increased urinary albumin excretion and other potentially modifiable risk factors--such as hypertension, smoking, poor metabolic control, and social class--predict increased all-cause mortality and cardiovascular mortality. Arterial hypertension is a risk factor in the initiation and progression of diabetic micro- and macroangiopathy. Diabetes, hypertension, and smoking are the three most important risk factors for fatal and nonfatal stroke. A randomized, double-blind, parallel study has revealed that the 5-year major cardiovascular disease rate was lowered by 34% for antihypertensive treatment compared with placebo. Furthermore, the study found a trend for lower all-cause mortality for low-dose antihypertensive-treated diabetic patients. Effective blood pressure reduction with ACE inhibitors and/or non-ACE inhibitors, frequently in combination with diuretics, reduces albuminuria, delays the progression of nephropathy, postpones end-stage renal failure, and improves survival in diabetic nephropathy.
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PMID:Diabetic hypertensive patients. Is this a group in need of particular care and attention? 1009 4

Diabetic retinopathy is the most common systemic disease capable of leading to blindness. Laser treatment of diabetic retinopathy is standardized; in most cases it can prevent blindness, provided the diagnosis is made in good time. Since impairment of vision is a late complication, systemic screening examinations are of particular importance if we are to reliably determine the optimal time for treatment. Advances in vitreoretinal surgery make possible the treatment of such late manifestations as vitreous hemorrhage and tractive retinal detachment. Provided that stage-oriented and timely treatment is forthcoming, these formerly hopeless cases should become a rare exception. The currently sole confirmed medical treatment is optimal control of blood sugar--based on the HBA1c value--and of blood pressure. The clinical efficacy of inhibitors of angiotensin converting enzyme or protein kinase C is presently undergoing investigation.
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PMID:[Diabetic retinopathy--screening is a requirement. Don't wait until vision becomes impaired]. 1078 19

Diabetes is a major risk factor for cardiovascular events. Indeed, people with diabetes are 2-4 times more likely to die from cardiovascular causes than individuals without diabetes. Despite evidence to suggest that the burden of cardiovascular disease may be decreasing in Western populations, this trend has not been repeated in diabetic populations. Diabetes is also the most common cause of new-onset end-stage renal disease, blindness and amputations. The growing incidence of diabetes throughout the world, particularly in developing nations, suggests that diabetes-related cardiovascular disease and other chronic cardiovascular diseases will constitute a serious global threat to health and well-being. The HOPE (Heart Outcomes Prevention Evaluation) study was designed to determine if the angiotensin converting enzyme (ACE) inhibitor, ramipril, prevents cardiovascular events in high risk patients. As people with diabetes have a high risk of such events, this group was specified for inclusion and analysis in the HOPE study. The HOPE study was designed to include up to 4,000 people with diabetes and was designed with high power to detect an 18% risk reduction in the diabetic sub group alone. A total of 3,577 individuals with diabetes were randomised to receive either 10 mg of ramipril or placebo. After a period of 4.5 years of follow-up, the group of patients receiving ramipril had a statistically and clinically significant risk reduction of 25% in the primary outcome of myocardial infarction (MI), stroke or cardiovascular (CV) death. This comprises a 37% risk reduction in CV death, a 22% risk reduction in MI, a 33% reduction in stroke and a 24% reduction in all-cause mortality. The MICRO-HOPE (Microalbuminuria, Cardiovascular, and Renal Outcomes) sub study assessed the effect of ramipril on diabetic nephropathy. This was detected by a centrally measured urine albumin:creatinine ratio and confirmed by timed urine collection. Ramipril significantly reduced the risk of overt nephropathy by 22% (P = 0.045), and overt nephropathy, laser therapy or dialysis by 15% (P = 0.05). ACE inhibition with ramipril represents a new macrovascular and microvascular preventive therapy for people with diabetes.
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PMID:Diabetes and the HOPE study: implications for macrovascular and microvascular disease. 1171 57

Retinopathy is the most common complication of diabetes, and a leading cause of blindness in people of working age. Optimal blood pressure and metabolic control can reduce the risk of diabetic retinopathy, but are difficult to achieve in clinical practice. In the EUCLID Study, the angiotensin converting enzyme (ACE) inhibitor lisinopril reduced the risk of progression of retinopathy by approximately 50%, and also significantly reduced the risk of progression to proliferative retinopathy. These findings are consistent with extensive evidence that the renin-angiotensin system is expressed in the eye, and that adverse effects of angiotensin II on retinal angiogenesis and function can be inhibited by ACE inhibitors or angiotensin II-receptor blockers. However, in the EUCLID Study retinopathy was not a primary end-point and the study was not sufficiently powered for the eye-related outcomes. Hence, the Diabetic Retinopathy Candesartan Trials (DIRECT) programme has been established to determine whether AT(1)-receptor blockade with candesartan can prevent the incidence and progression of diabetic retinopathy. This programme comprises three studies, involving a total of 4500 patients recruited from about 300 centres worldwide. The patients are normotensive or treated hypertensive individuals, and so the DIRECT programme should assess the potential of an AT(1)-receptor blocker to protect against the pathological changes in the eye following diabetes.
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PMID:The retinal renin-angiotensin system: implications for therapy in diabetic retinopathy. 1214 Jul 27

Age-related macular degeneration (AMD) is a major cause of blindness in the United States. AMD can be categorized into an atrophic (dry) form and a neovascular (wet, exudative) form. The atrophic form involves alterations of pigment distribution, loss of RPE cells and photoreceptors and diminished retinal function due to an overall atrophy of the cells. The neovascular AMD involves proliferation of abnormal choroidal vessels, which penetrate the Bruch's membrane and RPE layer into the subretinal space, thereby forming extensive clots and/or scars. Both environmental and genetic factors are suspected to play a role in AMD. Despite extensive genetic screening of candidate genes only two associations have been identified with AMD (Adenosine triphosphate (ATP)-binding cassette rim (ABCR) protein and apolipoprotein E gene-ApoE). The ABCR protein is retinal specific and accounts for only 3% of AMD cases. ApoE is not specific to the retina, and has been more intriguingly associated with Alzheimer's, another disease of age. The most consistent major risk factor in AMD is age. Our studies on the ACE gene show an association of protection with an Alu element insert, which might be affecting the level of the ACE gene. The ApoE 4 allele and the ACE Alu+/+ genotype have both been shown to be a risk for Alzheimer's and protective for AMD. Given these recent genetic associations, we should examine possible common pathways in diseases of age and their interaction with human genetic polymorphisms.
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PMID:Age-related macular degeneration: a new viewpoint. 1270 41


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