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)

There have been no studies of the possibility of reversing the left ventricular hypertrophy (LVH) of chronically hemodialyzed hypertensive uremics (HDH) with long-term antihypertensive therapy. We have measured left ventricular sizes of eight (6 male, 2 female, aged 29 to 61 years) HDH with M-mode echocardiography, before and 12, 18 and 24 months after the start of a combined antihypertensive therapy which included ACE-inhibitors, beta-blockers and calcium-antagonists. Pre-treatment values for mean blood pressure (MBP), 116.6 +/- 2.9 mm Hg, end diastolic diameter (EDD), 62.6 +/- 6.6 mm, interventricular septum (IVS), 14.2 +/- 3.0 mm, and left ventricular mass index (LVMi), 239 +/- 61 g/m2, were all significantly higher than those for nine sex- and age-matched hemodialyzed normotensive subjects (HDN) with comparable hemoglobin (Hb) levels. During the antihypertensive treatment, both the systolic and diastolic BP decreased steadily (P = 0.0001; P = 0.0003; ANOVA) and significantly by the third month (P < 0.05; P < 0.01), reaching levels comparable to those of the HDN group after 12 months. At this time the LVMi (204 +/- 67) and the IVS (13.1 +/- 2.7), although both significantly lower than baseline, were still higher than in the HDN group, while the EDD was similar. After 24 months, however, both the IVS (12.3 +/- 3.1) and the LVMi (161 +/- 65) were no longer different from those of the HDN group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regression of left ventricular hypertrophy in hypertensive dialyzed uremic patients on long-term antihypertensive therapy. 825 65

Although hypertension and diabetes mellitus frequently appear as comorbidities, the pharmacotherapy of hypertension in patients with diabetes mellitus can aggravate underlying carbohydrate and lipid abnormalities. To evaluate the efficacy and safety of the long-acting angiotensin converting enzyme inhibitor ramipril in patients with insulin-dependent or non-insulin-dependent diabetes mellitus, the authors conducted a double-blind, placebo-controlled study. After a single-blind washout period, 58 patients were randomly assigned to receive 2.5 mg of ramipril or a 2.5-mg placebo, each once daily. Each patient underwent titration and maintenance phases for a total treatment period of 12 weeks. By the end of maintenance, 54% of patients maintained the target blood pressure 24 hours after receiving ramipril compared with 19% in the placebo group (P = 0.008). Between baseline and the end of maintenance, ramipril decreased mean supine systolic/diastolic blood pressure (SBP/DBP) measured 24 hours after the last dose by 9/8 mmHg (P < or = 0.001/P < or = 0.001); placebo decreased SBP/DBP by 2/4 mmHg (NS/P < or = 0.05). Between-group differences were significant (P < 0.05). During this time, blood glucose, hemoglobin Alc, lipoproteins, and biochemistry were unchanged in the ramipril group. There were no between-group differences in the number or types of adverse events. In our study of patients with diabetes mellitus, once-daily ramipril controlled blood pressure, was well tolerated, and had no effects on carbohydrate or lipid metabolism.
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PMID:Double-blind, placebo-controlled study of ramipril in diabetics with mild to moderate hypertension. 845 57

We report an unusual case in which complete remission of acute myeloid leukemia (AML) had lasted for almost 10 years in a patient who was 94 years and 7 months old as of September 1989. An 84 year-old man was admitted to our hospital with gingival bleeding on October 15, 1979. Hematological data were: RBC 327 x 10(4) microliters, hemoglobin concentration 10 g/dl, platelets 3.8 x 10(4) microliters and WBC 9000 microliters, including 34% blastic cells. Bone marrow aspiration showed nucleated cells 48.0 x 10(4)/microliters with 69.2% blastic cells. He was diagnosed as having AML (M2). Induction chemotherapy consisted of daunorubicin, cyclocytidine, an anhydride analogue of cytosine arabinoside, and prednisolone (DCP). Complete remission was achieved after 1 month of this therapy. After two cycles of consolidation therapy (DCP), intensification therapy (DCP) was performed twice. Thereafter, complete remission lasted without any further therapy, up to September 1989, when he died of pancreatic cancer. The prolonged disease-free survival in this extremely aged patient was attributed to the high sensitivity of leukemic cells to DCP therapy and his good performance status at the time of initial induction chemotherapy. This is the oldest patient with long-term remission, lasting for over 5 years, to be reported in Japan. If an elderly patient with typical acute leukemia has a good performance status, intensive chemotherapy should be tried at least once, while carefully controlling complications specific to the elderly.
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PMID:Ten-year complete remission in an 84 year-old patient with acute myeloid leukemia. 849 95

Microalbuminuria predicts early mortality and renal disease in non-insulin-dependent diabetic patients. In insulin-dependent diabetic patients, angiotensin converting enzyme inhibition decreases microalbuminuria and retards the progression of renal disease. The aim of this study was to evaluate the effect of low dose ramipril on albumin excretion rate (AER) and blood pressure in non-insulin-dependent diabetic patients with persistent microalbuminuria (AER > 20 < 200 micrograms/min) and normal blood pressure or mild hypertension. The study was a randomized, double-blind, placebo-controlled clinical trial of 6 months duration at 14 hospital-based diabetes centers in northeastern Italy. Blood pressure, plasma glucose, and body weight were determined every month; AER, serum creatinine, glycosylated hemoglobin, and plasma lipids at baseline, after 1 month, and at the end of the study. Of 122 non-insulin-dependent diabetic patients randomly allocated in blocks of four to receive either ramipril (1.25 mg/day) or placebo, 108 (54 in the ramipril group and 54 in the placebo group) completed the study. At baseline, age, duration of diabetes, body mass index, and glycosylated hemoglobin were similar in the two groups and remained unchanged throughout the study. In the placebo group, AER rose from a baseline median of 65 micrograms/min (range 53 to 76, 95% confidence Interval) to 72 micrograms/min (57 to 87) and to 83 micrograms/min (62 to 104) after 1 and 6 months, respectively, but fell from 62 micrograms/min (48 to 76) to 45 micrograms/min (33 to 57) and to 53 micrograms/min (38 to 69), respectively, in the ramipril group, a significant difference between the groups (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of low-dose ramipril on microalbuminuria in normotensive or mild hypertensive non-insulin-dependent diabetic patients. North-East Italy Microalbuminuria Study Group. 854 Oct 2

We performed a case-control study to determine whether molecular variants of genes of the renin-angiotensin system were associated with the presence of albuminuria in non-insulin dependent diabetes mellitus (NIDDM). A total of 180 diabetic patients with persistent microalbuminuria [median urinary albumin (interquartile range) of 74 (54 to 126 mg/liter)] were matched with two control groups of diabetic patients without microalbuminuria [median urinary albumin 7 (5 to 10) mg/liter] for variables known to be associated with raised urinary albumin concentration including hemoglobin A1c and triglyceride. One control group was also matched for blood pressure and the other group was not, to allow assessment of interactions with hypertension. Association with the I/D polymorphism of the ACE gene and M235T variant of the angiotensinogen gene (AGT) with microalbuminuria and retinopathy was examined. There were no significant differences in genotype frequency between cases and controls for ACE or AGT irrespective of blood pressure matching. However, among subjects with microalbuminuria, those with the ACE DD genotype had a significantly greater urinary albumin excretion than individuals with a non-DD genotype [median 88 (68 to 170) mg/liter vs. 67 (53 to 113) mg/liter, P < 0.001]. More subjects with the DD than non-DD genotype had persistent albuminuria > 100 mg/liter, twice the upper normal range (60% vs. 38%, P = 0.006). When increased albumin excretion occurs, the presence of the ACE DD genotype appears to be associated with higher urinary albumin levels. No association with retinopathy was observed.
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PMID:U.K. Prospective Diabetes Study. XV: Relationship of renin-angiotensin system gene polymorphisms with microalbuminuria in NIDDM. 858 51

To evaluate the effects of marginal zinc (Zn) deficiency on Zn absorption and metabolism, three groups of infant rhesus monkeys (n = 4/group) were fed from birth to 5 months of age either a regular infant formula (5 mg Zn/L) or a low-Zn formula (1 mg Zn/L). Since iron (Fe) intake may affect Zn absorption, the low-Zn formula was given without (1 mg Fe/L) or with Fe fortification (12 mg/L). At monthly intervals, Zn absorption and retention were assessed by gavage feeding with 65Zn and whole-body counting immediately after and on days 4, 7, and 11 after intubation. Blood samples were drawn before dosing for analyses of various potential markers of Zn status. Infants fed low-Zn formula had lower weight gain than controls; however, length growth was similar in all groups. 65Zn retention was considerably higher in both groups fed low-Zn formula (40%) than in the control group (20%), whereas plasma Zn levels were normal in all infants. Plasma metallothionein levels were generally very low and detectable in only 5 samples of 48; however, 4 of these were found in control infants. Neutrophil chemotaxis assessed at the end of the study was impaired in low-Zn infants compared to controls. In addition, low-Zn infants had increased levels of interleukin-2 at the end of the study. No differences were seen between the groups in hemoglobin levels, total white blood cells/absolute neutrophil counts, or plasma activities of 5'-nucleotidase or angiotensin converting enzyme. In conclusion, marginal Zn intake in infant rhesus monkeys resulted in increased Zn retention, which was not enough to completely compensate for the lower Zn intake. The higher level of iron fortification studied did not affect Zn retention significantly.
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PMID:Effect of infant formula zinc and iron level on zinc absorption, zinc status, and immune function in infant rhesus monkeys. 864 84

There will always be birth defects and pregnancy complications due to factors beyond our control. However, we are rapidly discovering many interventions women can use to optimize their chances of having a healthy pregnancy and baby. Most of these, such as immunization and normalization of a diabetic woman's glycosylated hemoglobin level, are most effective when begun before conception. Since the discovery of the congenital rubella syndrome in 1941, there has been a steady accumulation of information on the prevention of birth defects through preconception health. In just the last few years, we have learned that folic acid can decrease neural tube defects, angiotensin converting enzyme inhibitors are teratogenic, and zidovudine can decrease the vertical transmission rate of human immunodeficiency virus. The Varivax vaccine released last year is expected to decrease the perinatal morbidity from varicella. By using the time before conception, we may be able to fully maximize the benefits of good nutrition, exercise, medical screening, and avoidance of environmental toxins.
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PMID:Preconception health care for the primary care practitioner. 877 69

From proteolytic digest of swine hemoglobin, we isolated four peptide, E-1 (Phe-Gln-Lys-Val-Val-Ala), E-2 (Phe-Gln-Lys-Val-Val-Ala-Gly), peptide 30-3 (Phe-Gln-Lys-Val-Val-Ala-Lys) and H-1 (Gly-Lys-Lys-Val-Leu-Gln). These peptides inhibited angiotensin I-converting enzyme activity with an IC50 of 5.8, 7.4, 2.1 and 1.9 microM, respectively. Oral administration of 50 mg/kg E-1 and 50 mg/kg H-1 decreased blood pressure in spontaneously hypertensive rats. In normotensive rats, oral administration of 500 mg/kg E-1 and 500 mg/kg H-1 inhibited the pressor effect of i.v. administrated 300 ng/kg angiotensin I, possibly by inhibiting its conversion to angiotensin II. These results suggest that these peptides are orally effective inhibitors of angiotensin I-converting enzyme that have a hypotensive effect.
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PMID:Antihypertensive effect of angiotensin I-converting enzyme inhibitory peptides derived from hemoglobin. 881 89

To delineate the pathogenesis of the reduction in hemoglobin occurring in renal transplant patients treated with angiotensin converting enzyme inhibitors (ACEI) and azathioprine (AZA) a controlled, prospective trial of ACEI withdrawal was conducted. The ACEI was replaced by nifedipine or clonidine in 15 kidney transplant patients immunosuppressed with AZA and prednisone (enalapril in 14 and captopril in 1). Before and during 10 to 12 weeks after withdrawal of the ACEI, AZA metabolites, renal function parameters and hematological parameters including erythropoietin and reticulocytes were evaluated. Enalaprilat levels were measured and compared with 15 similar patients matched for transplant function and enalapril dosage immunosuppressed with cyclosporine and prednisone. AZA metabolites did not differ significantly in the presence or absence of the ACEI. Enalaprilat levels also showed no significant difference between the two patient groups treated with AZA or cyclosporine. Hematocrit and hemoglobin increased significantly from 37.5 +/- 6.4 to 39.7 +/- 3.6% (mean +/- SD, P = 0.02) and 12.8 +/- 2.2 to 13.5 +/- 1.2 g/dl, P = 0.04, respectively, 10 to 12 weeks after ACEI treatment had been discontinued. Simultaneously numbers of reticulocytes and erythropoietin concentrations rose significantly after 2, 4 and 10 weeks, with a peak at two weeks (from 14.1 +/- 3.8 to 20.6 +/- 8.0/1000, P < 0.05 and from 14.3 +/- 12.4 to 29.3 +/- 54.5 mU/ml, P < 0.05, respectively). In conclusion, ACEI-related anemia in renal transplant recipients seems to be due to the erythropoietin-lowering effect of this group of drugs. A pharmacokinetic interaction between AZA and enalapril is not likely since plasma enalaprilat levels were independent of the immunosuppressive regimen and AZA metabolite levels were unchanged in the presence and absence of the ACEI. Several mechanisms by which angiotensin converting enzyme blockade may cause a decrease in circulating erythropoietin are discussed.
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PMID:Mechanism of angiotensin converting enzyme inhibitor-related anemia in renal transplant recipients. 887 73

An insertion/deletion (I/D) of the human angiotensin converting enzyme (ACE) gene is a major determinant of circulating ACE levels. Recent studies suggest that the ACE I/D polymorphism may influence the risk of developing nephropathy in patients with insulin dependent diabetes mellitus (IDDM), although the mechanism responsible for the effect is unknown. Since an early increase in glomerular filtration rate (GFR) may also be a risk factor for the development of diabetic nephropathy, we sought to determine if the ACE I/D polymorphism influenced renal hemodynamic function in patients with IDDM. Genomic DNA was obtained from 39 normotensive male and female patients with uncomplicated IDDM (mean duration 3.4 years; range 1 to 6 years), and from 20 non diabetic control subjects. The ACE I/D polymorphism was determined using the polymerase chain reaction. Subjects were divided into three groups based on their ACE genotype. Values for GFR, renal plasma flow (ERPF), filtration fraction, and renal vascular resistance were determined in both groups using classic inulin and paraaminohippurate clearance techniques. Blood glucose was maintained between 4 to 6 mmol/liter in the patients with IDDM using a modified euglycemic clamp technique. Mean values for GFR were significantly greater in patients homozygous for the I allele (143 +/- 7 ml/min/1.73 m2) compared to patients homozygous for the D allele (121 +/- 3 ml/min/1.73 m2, P < 0.01), while the mean GFR values for the heterozygous patients were intermediate. ERPF was also significantly greater in patients homozygous for the I allele (850 +/- 103 ml/min/1.73 m2) compared to patients homozygous for the D allele (672 +/- 31 ml/min/1.73 m2, P < 0.04), while there were no differences in the values for mean arterial pressure, glycosylated hemoglobin, or albumin excretion rates amongst the groups. There was no dominant effect of the ACE gene I/D polymorphism in the control group. These results suggest that: (1) the ACE gene I/D polymorphism influences glomerular filtration and renal plasma flow rates in patients with early uncomplicated IDDM; and (2) differences in renal hemodynamic function do not appear to explain the protection against the development of diabetic nephropathy offered by the I allele.
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PMID:Angiotensin converting enzyme gene polymorphism and renal hemodynamic function in early diabetes. 899 25


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