New competitive enzyme-linked immunosorbent assay for determination of metallothionein in tissue and sera.

Very little information is available concerning the relationship between metallothionein (MT) and diseases in humans. Several methods to measure MT levels exist but many of these assays are not sensitive to measure MT in human sera. A new sensitive competitive ELISA system has been developed using MT labeled with horseradish peroxidase as a conjugate and high-titre polyclonal antibodies obtained from rabbit immunoglobulin G for MT determination in human sera.

Cholinergic responses of ileal longitudinal muscle under short-lasting exposure to cupric ions.

1 The effect of short-term exposure to cupric ions (Cu2+) on electric field-stimulated (EFS) or agonist-induced contractions of guinea-pig isolated ileum was studied. 2 EFS elicited tetrodotoxin- and atropine-sensitive contractions that were concentration dependently inhibited by Cu2+ (IC50 = 14.7 +/- 4.

Time course and progression of pressure overload-induced cardiac hypertrophy in rats.

Aim: To study the time course and progression of pressure overload-induced left ventricular hypertrophy

Methods: Left ventricular hypertrophy was induced in rats by abdominal aorta constriction and assessed at different time points (10, 15, 20, 25, 35, and 45 days) after operation.

Results: The cardiac index (the ratio of heart weight to body weight) in aortic-banded animals was characterised by phasic changes when compared with the sham operated and the control animals. In aortic-banded rats the cardiac index rose sharply at days 10 and 15 after operation.

A reproducible model of cardiac hypertrophy in rats. Problems and obstacles we faced.

Aim: To develop a reproducible model of significant left ventricular hypertrophy in order to study the role played by the tumor suppressor protein 53 (P53) in the mechanisms of cardiac hypertrophy, the cross-talk with the other factors and the connection between expression and activity of P53, cardiac myocyte apoptosis and heart hypertrophy; to discuss the problems and obstacles we faced.

Methods: Male Wistar rats were used in the experiments. Left ventricular hypertrophy was induced by banding the abdominal aorta.

Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial.

Background: To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial by an open-label follow-up study lasting 4 years.

Methods: The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160-219 mmHg systolic and below 95 mmHg diastolic. The double-blind trial ended after a median follow-up of 2.

Results of the pilot study for the Hypertension in the Very Elderly Trial.

Background: The risks and benefits of treating hypertension in individuals older than 80 years are uncertain. A meta-analysis has suggested that a reduction in stroke events of 36% may have to be balanced against a 14% increase in total mortality.

Objectives: To report the results of the pilot study of the Hypertension in the Very Elderly Trial (HYVET), which is in progress to address these issues.

Systolic blood pressure variability as a risk factor for stroke and cardiovascular mortality in the elderly hypertensive population.

Objective: To investigate whether baseline systolic blood pressure variability was a risk factor for stroke, cardiovascular mortality or cardiac events during the Syst-Eur trial.

Design: The Syst-Eur study was a randomized, double-blind, placebo-controlled trial, powered to detect differences in stroke rate between participants on active antihypertensive treatment and placebo. Systolic blood pressure variability measurements were made on 744 participants at the start of the trial.

Time-related heart autonomic balance characteristics in healthy subjects.

Changes of the heart autonomic balance between morning (8-9 h) and afternoon (14-15 h) measurements were studied in 22 healthy subjects. The selection of these two daytime periods was substantiated by the established higher risk of cardiovascular incidents in the morning and the relative balance of the vegetative nervous system in the afternoon hours. The changes were analysed by RR-variability indices from ECG recordings in the resting state and with vegetative nervous system stimulation by the handgrip test and Valsalva manoeuvre.

Copper-homocysteine complexes and potential physiological actions.

During the last 2 decades it was proposed that atherogenesis was closely related to the homeostasis of homocysteine (hCys) and/or copper. We hypothesized that the physiological action of hCys may be connected with its ability to form complexes with Cu. Our results showed the presence of two different Cu-hCys complexes.

Predictive value of clinic and ambulatory heart rate for mortality in elderly subjects with systolic hypertension.

Objective: To examine the association of clinic and ambulatory heart rate with total, cardiovascular, and noncardiovascular death in a cohort of elderly subjects with isolated systolic hypertension from the Systolic Hypertension in Europe Trial.

Methods: A total of 4682 patients participated, whose untreated blood pressure on conventional measurement at baseline was 160 to 219 mm Hg systolic and lower than 95 mm Hg diastolic. Clinic heart rate was the mean of 6 readings during 3 visits.

Ambulatory pulse pressure as predictor of outcome in older patients with systolic hypertension.

We enrolled 808 older patients with isolated systolic hypertension (160 to 219/71 <95 mm Hg) to investigate whether ambulatory measurement of pulse pressure and mean pressure can refine risk stratification. The patients (> or =60 years) were randomized to nitrendipine (10 to 40 mg/day) with the possible addition of enalapril (5 to 20 mg/day) or hydrochlorothiazide (12.5 to 25 mg/day) or to matching placebos.

Quality control of the blood pressure phenotype in the European Project on Genes in Hypertension.

Objectives: In the European Project on Genes in Hypertension (EPOGH) standardized epidemiological methods were used to determine complex phenotypes consisting of blood pressure (BP) in combination with other traits. In this report, we present the quality control of one of the BP phenotypes.

Methods: In seven European countries eight different research groups recruited random samples of nuclear families.

Prognostic significance of renal function in elderly patients with isolated systolic hypertension: results from the Syst-Eur trial.

Several reports suggest that markers of renal function such as serum creatinine, serum uric acid, and urinary excretion of protein may be related to cardiovascular complications and mortality. This study analyzed the data from the Syst-Eur trial, which was a randomized, placebo-controlled, double-blind intervention trial in elderly patients with isolated systolic hypertension. The purpose was to evaluate whether serum levels of creatinine and uric acid and urinary protein excretion at entry are related to subsequent morbidity and mortality.

[Studies on restraint ulcers in rats in conditions of acute copper deficiency].

In the present experiment, we have investigated the impact of the acute copper deficiency on the pathogenesis of stress ulcers' formation in rats during cold-restraint stress. A powdered milk diet, lasting for 5 days, causes a significantly decrease of stomach copper content in rat, comparing to content in rats receiving standard laboratory diet. The severity of mucosal disturbances, expressed as total number and area of stress ulcers, is most prominent in animals receiving hypocupric diet.

Withdrawal from treatment in the Syst-Eur Trial.

Objective: To investigate the reasons for withdrawal from double-blind randomized trials, and the reasons for changing treatment within a randomized therapeutic group.

Design: The Syst-Eur trial, in which 4695 older patients with systolic hypertension were randomized to active or placebo treatment.

Methods: The reasons for withdrawal from the trial were examined, both for patient-initiated and investigator-initiated withdrawals.

How well can blood pressure be controlled? Progress report on the Systolic Hypertension in Europe Follow-Up Study (Syst-Eur 2).

BACKGROUND: The randomised, double-blind, placebo-controlled Systolic Hypertension in Europe trial (Syst-Eur 1) proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in elderly patients with isolated systolic hypertension. In an attempt to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine, the Syst-Eur patients remained in open follow-up after the end of Syst-Eur 1. This paper presents the second progress report of this follow-up study (Syst-Eur 2).

Influence of acute copper deficiency, cold-restraint stress and the H2 blocker ranitidine on the severity of acute gastric mucosal lesions and lipid peroxidation in rats.

Acute copper deficiency produces disturbances in the microcirculation and structure of extracellular matrix proteins, causes an increase in mast cell population, which is followed by an increased content of their degranulation products, produces disturbances in histamine metabolism and decreases the activity of some antioxidant enzymes. These pathogenic mechanisms are similar to the processes underlying stress ulcer formation. The histamine H2-receptor antagonist ranitidine, a drug with the highest application for stress ulcer prophylaxis, has the ability to helate the copper ion and to influence its tissue distribution and the processes of generation and neutralization of reactive oxygen species (ROS).

[Two cases of insulinoma treated as a psychiatric disease].

The insulin producing tumors are rare diseases and sometimes the diagnostics is very difficult. We present two cases of insulinoma treated as psychiatric diseases. We discuss the difficulties and particularities in the diagnostic process.

Interaction between nonsteroidal anti-inflammatory drug intake and calcium-channel blocker-based antihypertensive treatment in the Syst-Eur trial.

Objective: To assess the relationship between chronic intake of nonsteroidal anti-inflammatory drugs (NSAID) and outcome, in particular (gastrointestinal) bleeding and to investigate whether the effect of chronic NSAID intake was similar in untreated and treated elderly hypertensives.

Methods: Eligible patients (> or = 60 years, with systolic blood pressure 160-219 mm Hg and diastolic blood pressure < 95 mm Hg) were randomised to active treatment or placebo. Active treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both, titrated or combined to reduce the sitting systolic blood pressure by at least 20 mm Hg to below 150 mm Hg.

Reduced concentrations of soluble adhesion molecules after antioxidant supplementation in postmenopausal women with high cardiovascular risk profiles--a randomized double-blind study.

Background: One of the suggested mechanisms of increased cardiovascular risk in postmenopause is a loss of the antioxidant effects of estrogens. It has been shown that classical cardiovascular risk factors increase oxidative stress on the arterial wall, and that endothelial cells react to this insult by increased expression of cellular adhesion molecules (CAM), which in turn are markers of arterial wall inflammation.

Methods: A randomized, placebo-controlled, double-blind study was performed in 60 postmenopausal women with high cardiovascular risk profiles, but free from clinical atherosclerotic disease.

Hypertension in the Very Elderly Trial (HYVET): protocol for the main trial.

A number of trials and meta-analyses have demonstrated clear benefits of blood pressure (BP) reduction in patients aged <80 years with regard to the reduction in stroke and cardiovascular events. However, a variety of studies have suggested that the positive relationship between BP and cardiovascular mortality is weakened or indeed reversed in the very elderly. Most intervention trials to date have either excluded or not recruited sufficient patients aged > or =80 years to determine whether there is a significant benefit from treatment in this age group.

Follow-up of renal function in treated and untreated older patients with isolated systolic hypertension. Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.

Background: In the outcome trials that provided information on renal function in older hypertensive patients, diuretics and beta-blockers were mostly used as first-line drugs. The long-term renal effects of calcium-channel blockers remain unclear.

Objective: To compare the changes in renal function in 2,258 treated and 2,148 untreated patients with isolated systolic hypertension, of whom 455 had diabetes mellitus and 390 had proteinuria.

Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators.

Context: The clinical use of ambulatory blood pressure (BP) monitoring requires further validation in prospective outcome studies.

Objective: To compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension.

Design: Substudy to the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial, started in October 1988 with follow up to February 1999.

Serum level of IgG autoantibodies against oxidized low density lipoproteins and lag-phase of serum oxidation in coronary heart disease--inverse correlation.

High affinity IgG autoantibodies (ABs) against oxLDLs and lag-phase of serum oxidation were tested in patients with coronary heart disease (CHD). Fifty one (37 M/14 F) patients with CHD defined as Q-wave myocardial infarction and/or stenosis of more than 50% and 51 (34 M/17 F) healthy blood donors as controls participated in this study. LDLs were isolated by gradient ultracentrifugation and oxidized with CuSO4.

Systolic Hypertension in Europe (Syst-Eur) trial phase 2: objectives, protocol, and initial progress. Systolic Hypertension in Europe Investigators.

The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (> or = 60 years) patients with isolated systolic hypertension (systolic BP > or = 160 mm Hg and diastolic BP < 95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial.