Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A radioimmunoassay for the binding protein for vitamin D and its metabolites (DBP) has been developed. Suitable rabbit anti-DBP antiserum was elicited after primary and one booster injection. Anti-DBP antisera, as well as antigroup-specific component antisera, produced a single, monospecific line of percipitation when reacted against purified DBP and human serum. DBP was iodinated with 125I and 125I-DBP was purified by gel filtration on Sephadex G-200. Binding of 125I-DBP by 20 nl of rabbit anti-DBP antisera was approximately 50% and was sharply competed for by 0.4-4.0 ng of DBP standard. Displacement of 125I-DBP by human serum dilutions or standard DBP gave identical curves, and only weak competition was observed with old and new world primate sera. Apo- and holo-DBP possessed indistinguishable immunoreactivity. The assay detects DBP in 1-10 nl of human serum with reasonable accuracy and with reasonable intra- and interassay precision. The mean serum concentration (+/- SEM) for a group of 40 normal adults was 525 +/- 24 mug/ml and no sex difference was observed. Higher levels were found in sera from pregnant women and women receiving oral contraceptives, and decreased concentrations were observed in premature cord and hypoproteinemic sera. No significant correlation between serum DBP levels and serum 25-hydroxycalciferol levels was found, and the DBP content of sera from vitamin D-deprived and vitamin D-treated subjects was indistinguishable from that of normal adults. DBP accounts for 6- of the alpha globulin in normal human serum. Considering the normal serum content of the parent vitamin and its metabolites to be approximately 0.1-0.2 mum, these immunoassay data confirm previous saturation analyses of human serum antiricketic sterol-binding capacity and suggest that greater than 95% of DBP circulates as the apoprotein under normal conditions.
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PMID:Radioimmunoassay of the binding protein for vitamin D and its metabolites in human serum: concentrations in normal subjects and patients with disorders of mineral homeostasis. 108 57

A double-blind, parallel group multicentre study was carried out to compare the effects of adding once daily treatment with lisinopril 10 or 20 mg and placebo to the treatment of 100 patients whose blood pressure was inadequately controlled with once daily atenolol 50 mg. Following a two-week run-in period, patients with a lying DBP between 95 mmHg and 115 mmHg were randomised to either lisinopril 10 mg or placebo once daily for four weeks. Blood pressure measurements were made approximately 24 h after the previous dose of study medication. After four weeks' treatment the dose of study medication was doubled for those patients whose lying DBP was greater than or equal to 90 mmHg and a final assessment was made after a further two weeks of treatment. Overall, six weeks' treatment with lisinopril produced a greater fall in lying blood pressures than placebo when added to atenolol therapy. The difference in favour of the additional ACE inhibitor therapy was 7.1 +/- 2.6/5.4 +/- 1.5 mmHg (mean +/- SEM) (P less than 0.01). Standing blood pressures showed similar behaviour in favour of the additional ACE inhibitor treatment (7.6 +/- 2.4/4.7 +/- 1.6 mmHg) (P less than 0.005). Heart rate was not altered significantly by either lisinopril or placebo treatment. The addition of lisinopril to treatment with atenolol produced a slight increase in the reported number of adverse events compared with placebo. The results of this study indicate that the addition of lisinopril 10-20 mg once daily to treatment with a beta-adrenoceptor blocking drug produces a worthwhile decrease in blood pressure in patients not responsive to beta-blocker therapy alone.
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PMID:A study of the effects of lisinopril when used in addition to atenolol. 133 43

In elderly hypertensive patients effect of antihypertensive treatment with Ca antagonist or ACE inhibitor on the heart were examined. Twenty-four elderly hypertensive patients with cardiac hypertrophy, aged 65-79 years old (mean +/- SEM, 71 +/- 1) were treated with Ca antagonist (nifedipine or nicardipine) or ACE inhibitor (captopril or enalapril) for 3 months. Thirteen patients had essential hypertension (EH: SBP greater than or equal to 160 mmHg and DBP greater than or equal to 95 mmHg, 70 +/- 1 years) and 11 had isolated systolic hypertension (ISH: SBP greater than or equal to 160 mmHg and DBP less than 95 mmHg, 74 +/- 2 years). Blood pressure (BP) and heart rate were measured every two weeks. In all patients, M-mode echocardiography was performed to measure left ventricular mass index (LVMI) and ejection fraction (EF), and the sympathetic nervous (plasma norepinephrine and epinephrine) and the renin-angiotensin system (plasma renin activity and aldosterone concentration), were assessed before and after 3 months of treatment. BP significantly decreased from 174 +/- 3/97 +/- 1 to 149 +/- 4/84 +/- 2 mmHg in EH and from 167 +/- 3/82 +/- 2 to 144 +/- 4/74 +/- 2 mmHg in ISH. LVMI was significantly reduced from 204 +/- 14 to 174 +/- 16 g/m2 in EH and from 179 +/- 14 to 156 +/- 12 g/m2 in ISH. EF showed no significant changes in either group. In ISH, the change in LVMI was significantly correlated with the change in systolic BP (r = 0.74, p less than 0.05). In EH, there was no significant relation between BP and LVMI changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of antihypertensive treatment in elderly hypertensive patients with cardiac hypertrophy]. 138 12

Enzymatically inactive renin (IR) is the predominant circulating form of renin. Sympathetic activity may influence plasma renin activity (PRA) by regulation of the conversion of IR to active renin (AR, PRA). It has been demonstrated previously that beta blockade lowers PRA at least partly through inhibition of this conversion process. The authors hypothesized that beta blockade and intrinsic sympathomimetic activity (ISA) would have opposing effects on production of AR from its inactive precursor. Eighteen primary hypertensives (12 male, 6 female, mean age 57.7 +/- 2.7) were entered in a placebo-controlled, double-blind crossover study of the effects of equipotent doses of pindolol and propranolol on mean +/- SEM systolic BP, diastolic BP, heart rate, active renin (AR), total renin (TR), inactive renin (IR), and % AR/TR. Drug dose was titrated to achieve a goal DBP of 90 mmHg or less. Active renin was defined as the rate of generation of angiotensin I in 37 degrees C plasma at pH 5.7. Total renin was determined by preincubation of plasma aliquots with 1.5 mg/mL trypsin in the presence of 5 mM benzamadine for one hour at -4 degrees C prior to assay of renin activity. Inactive renin was calculated as TR minus AR. The BP responses achieve by dose titration of propranolol and pindolol were virtually identical at rest, indicating equivalent depressor effects of the two beta blockers. Heart rate and active renin were, however, lowered to a much greater extent with propranolol as compared with pindolol. The lack of significant pindolol-induced fall in % AR/TR suggests that this drug has little net effect on the formation of AR from IR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intrinsic sympathomimetic activity counteracts beta-blocker inhibition of renin activation. 256 12

Ambulatory blood pressures (systolic, SBP, diastolic, DBP) and heart rate were determined over 24 h every 15 min in the day and every 15 min in the night in 72 normal subjects aged 21 +/- 1 SEM with normal casual office pressures (WHO's criteria: office DBP less than or equal to 90 mmHg, office SBP less than or equal to 140 mmHg) and in 86 essential hypertensive subjects aged 21 +/- 1, with borderline office pressure (WHO's criteria: office DBP less than or equal to 95 mmHg, office SBP less than or equal to 160 mmHg). Complete 24-hour profiles (mean +/- SD) were reported. In the average, mean ambulatory DBP in the normal group was about 72.5 mmHg in "day time" (9 a.m.-9 p.m.) and 63.5 mmHg in "night time" (midnight-7 a.m.). Ambulatory SBP in the normal group were about 126 mmHg and 110 mmHg for the same time periods. In the borderline hypertensive group, the figures were 74 mmHg (day-time) and 67 mmHg (night time) for diastolic pressure and 140 mmHg (day time) and 118 mmHg (night time) for systolic pressure. However, when the normal and borderline groups were defined as above on the basis of office pressure, ambulatory blood pressure profiles in the two groups showed a large overlap. A method was proposed to reduce this overlap by partially reallocating the subjects on the basis of ambulatory blood pressure. First, a typical profile was defined for each group and a distance was defined between two arbitrary profiles. Then a subject in the normal (resp. hypertensive) group was reallocated to the hypertensive (normal) group if his profile was closer to the typical profile of the hypertensive (normal) group than the typical profile of his own group. Applied to ambulatory DBP profiles, this method reallocated 49 subjects (over the total of 158), significantly reduced the initial overlap of BP profiles between the two groups, and defined reference profiles for "normal" and "borderline" ambulatory blood pressures.
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PMID:A method to define reference profiles for ambulatory blood pressure, with application to blood pressure profiles in 158 young subjects. 322 39

We studied 18 patients (age range, 53-90 yr) with at least one cardiovascular risk factor who were treated with electroconvulsive therapy (ECT) and compared effects of five pretreatments: no drug; esmolol, 1.3 or 4.4 mg/kg; or labetalol, 0.13 or 0.44 mg/kg. Each patient received all five treatments, during a series of five ECT sessions. Pretreatment was administered as a bolus within 10 s of induction or anesthesia. Doses of methohexital and succinylcholine were constant for the series of treatments and the assignment to no drug or to drug and dose was determined by randomized block design. Measurements of systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR) were recorded during the awake state and 1, 3, 5, and 10 min after the seizure. The deviation of ST segments from baseline was measured by an electrocardiogram (ECG) monitor equipped with ST-segment analysis software. The results (mean +/- SEM) show that without pretreatment, there were significant (P < 0.05) peak increases in SBP and HR (55 +/- 5 mm Hg and 37 +/- 6 bpm, respectively), recorded 1 min after the seizure. Comparable reductions (by approximately 50%) in these peak values were achieved after esmolol (1.3 mg/kg) or labetalol (0.13 mg/kg), and cardiovascular responses were nearly eliminated after the same drugs in doses of 4.4 and 0.44 mg/kg, respectively. The deviation of ST-segment values from baseline in any lead was not measurably influenced by either antihypertensive drug. SBP values were lower after labetalol 10 min after the seizure, but not after esmolol. Asystolic time after the seizure was not significantly longer with either drug.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative effects of esmolol and labetalol to attenuate hyperdynamic states after electroconvulsive therapy. 786 25

The hypotensive effect, kinetics, and concentration-response relationship of labetalol, alpha beta- and alpha 1-adrenoceptor blocking drug, were studied in seven women with a moderate-to-severe hypertension (averaged diastolic blood pressure [DBP] of 100 to 120 mm Hg measured during a 1- to 2-day hospitalization period) during the third trimester of pregnancy who received the oral twice-daily doses of 150 to 450 mg. These dosages were individually selected by attaining a therapeutic goal of DBP < or = 100 mm Hg or systolic blood pressure (SBP)/DBP reduction of > 30/15 mm Hg, as compared with the pretreatment value, at any time during the 12-hour dosing interval for a 3- to 5-day dosage escalation period. Labetalol concentrations in plasma were measured by a high-performance liquid chromatography with fluorescence detection, and the plasma drug concentration-response relationship was analyzed by a sigmoidal Emax model. Labetalol decreased significantly (P < 0.05 to 0.01) the pretreatment SBP/DBP (166.3 +/- 5.2/110.3 +/- 3.0 mm Hg, mean +/- SEM) without any recognizable side-effects during the twice-daily dosing period in the mothers. Peaked concentrations occurred at 1 hour postdose in all patients. The elimination half-lives ranged from 4.3 to 6.9 hours, and the apparent oral clearance from 31.9 to 73.3 mL/min/kg. The pharmacodynamic parameters (Emax and EC50) analyzed by the Emax model revealed a 3- to 5-fold interindividual variability. The gestational ages at delivery ranged from 34 to 37 weeks, and the birth weights were < 2000 g in 6 of the 7 neonates. Four neonates developed respiratory distress syndrome after delivery, and one infant died of pulmonary hypoplasia 3 months later. The results indicate that 1) labetalol orally administered in a twice-daily regimen as done in this study is an effective antihypertensive drug in women with hypertension during late pregnancy, and 2) interindividual variability in the kinetic factor (e.g., oral clearance) as well as that in the pharmacodynamic factor (e.g., EC50) appear to be related to the overall variability in the hypotensive responsiveness to the drug. However, whether labetalol and/or hypertension per se would have been related to the fetal outcome remains unanswered from the present study.
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PMID:Labetalol in hypertension during the third trimester of pregnancy: its antihypertensive effect and pharmacokinetic-dynamic analysis. 822 70

The present study was undertaken to compare the effects of first-line antihypertensive drugs in Japanese patients. Four antihypertensive drugs were studied: trichlormethiazide (TCT), nifedipine retard (NIF), atenolol (ATN), and enalapril malate (ENP). Thirty-eight patients (16 men and 22 women; age, 53.3 +/- 8.8 years, mean +/- SD) were enrolled in the study. After a control period of 2 to 4 weeks, the four drugs were administered according to a randomized, cross-over design, the duration of each treatment period being 8 to 12 weeks. The initial dose of each drug was increased until blood pressure (BP) fell to less than 150/90 mmHg. The maximum doses of TCT, NIF, ATN, and ENP were 4, 40, 50, and 20 mg/day, respectively. The protocol was completed in 25 of the 38 patients. The BPs (SBP/DBP) at the end of each period were 168 +/- 3 (mean +/- SEM)/105 +/- 1 (control), 149 +/- 4/ 98 +/- 2 (TCT), 138 +/- 3/89 +/- 2 (NIF), 151 +/- 4/94 +/- 2 (ATN), and 152 +/- 4/97 +/- 2 mmHg (ENP). The BP during NIF treatment was significantly lower than during the other treatments. This finding suggests that the calcium antagonist had a greater hypotensive effect than the other first-line antihypertensive drugs studied. The subjects seem to more closely resemble black rather than white populations with respect to their response to antihypertensive treatment.
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PMID:Comparison of first-line antihypertensive drugs by a randomized cross-over method--a preliminary report. 874 8

In studies and assessments of human beings done in natural settings, it is assumed that the period tau of circadian rhythms, including ones of systolic (SBP) and diastolic (DBP) blood pressure, is equal to 24 hours. To test this hypothesis, SBP and DBP rhythms were studied in 112 medication-free, non-hospitalized subjects (62 males, 47.1 + 2.0 years [x +/- SEM], and 50 females, 54.5 +/- 2.1 years) by 48 h ambulatory blood pressure monitoring (ABPM). Of these, 26 were hypertensive (diurnal SBP > 140 mmHg and diurnal DBP > 90 mmHg) and 86 normotensive. All subjects were synchronized by their habitual daytime activities from approximately 08:00 h to approximately 23:00 h +/- 1 h and by sleep at night. The BP was assessed at 15-minute intervals during a continuous 48h span using a Spacelabs model #90207 ABPM. The time series data of each subject were individually evaluated by power spectra analysis for the prominent tau of the SBP and DBP rhythms. The prominent tau differed from 24 hours in 22/112 subjects for SBP and in 16/112 subjects for DBP. Generally, in these individuals the tau was less than 24 hours. The occurrence of non-24 h tau's was more frequent in hypertensive than normotensive subjects; the difference between the groups in the distribution of the prominent tau's by class (tau = 24 h, tau = 12, 12 h > tau < 24 h, etc.) was statistically significant (chi 2 test = 19.1; p < 0.001). No difference in the distribution of tau's of blood pressure was detected according to the subject's age and gender. These findings suggest that ABPM done only for a duration of 24 h may be too short to characterize accurately the features of the day-night variation in human BP, including the precise period of its rhythm.
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PMID:Variability in the period of the blood pressure circadian rhythm in human beings. 916 91

The effect of angiotensin-converting enzyme (ACE) inhibitors on the diabetic retinal circulation has not been studied previously. The aim of this study was to evaluate the effect of ACE inhibition and beta-blockade on retinal blood flow (RBF) in a group of 45 hypertensive diabetic subjects using a randomized double-blind trial over a period of 12 months. Laser Doppler velocimetry and computed image analysis were used to measure RBF. The changes in blood pressure over 12 months were comparable (perindopril [PE]: systolic [SBP] 152.1 +/- 3.3 and diastolic [DBP] 97.2 +/- 1.7 mm Hg to SBP 136.8 +/- 3.4 and DBP 85.8 +/- 2.1; atenolol: SBP 158.9 +/- 5.1 and DBP 97.5 +/- 1.6 mm Hg to SBP 137.9 +/- 3.4 and DBP 85.1 +/- 1.6; P = .607, mean +/- SEM). RBF decreased from 17.19 +/- 2.21 microL x min(-1) to 14.18 +/- 1.50 microL x min(-1) in the PE group (n = 15, P = .208) while it increased with atenolol from 15.80 +/- 1.24 microL x min(-1) to 16.99 +/- 1.18 microL x min(-1) (n = 17, P = .399). The comparison of percentage changes in RBF (PE -7.16% +/- 11.49%; atenolol, +15.31% +/- 9.51%) reached statistical significance (P < .05). There was an increase in RBF in 33.3% of subjects receiving PE and in 70.6% of those receiving atenolol. Similar trends were found for retinal conductance. There were no significant changes in the parameters of retinal vascular permeability. Albuminuria decreased to a greater degree with PE, but did not reach significance (PE, 112.1 +/- 39.5 mg/24 h to 88.6 +/- 30.5 mg/24 h; atenolol, 87.3 +/- 51.7 mg/24 h to 82.1 +/- 47.7 mg/24 h). This suggests that ACE inhibition therapy may promote a hemodynamic milieu in the hypertensive diabetic retinal circulation that serves to protect against the progression of diabetic retinopathy, whereas beta-blockade has the opposite effect.
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PMID:Effect of angiotensin-converting enzyme inhibition with perindopril and beta-blockade with atenolol on retinal blood flow in hypertensive diabetic subjects. 986 68


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