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Biomedical subjects

A Sacerdote

Publications and source records attributed to A Sacerdote.

At least 19 recordsLinked to original sources

Lacidipine prevents the hypertension and renal and cardiac changes induced by high-fructose diet in WKY rats.

Normotensive rats fed a high-fructose diet (HFD) develop hypertriglyceridemia, hyperinsulinemia, and hypertension. The glomerular changes observed in the kidneys of these animals are similar to those observed in diabetic rats. The aim of this study was to evaluate whether lacidipine, a calcium antagonist, could have a protective effect with this animal model. Forty male Wistar-Kyoto (WKY) rats were divided into four groups treated with HFD + placebo; HFD + lacidipine, 0.3 mg/kg/day; HFD + lacidipine, 3 mg/kg/day; or standard diet + placebo for 4 weeks. Urinary excretion of the stable metabolic products of nitric oxide (NO) was determined, because this vasoactive agent has been found to cause hemodynamic changes in the diabetic kidney. Glomerular size was determined by means of morphometric analysis. The results of this study show that lacidipine prevents (a) the HFD-induced increase in blood pressure in a dose-dependent manner; (b) the HFD-induced increase in glomerular size and fibronectin synthesis; and (c) the increase of collagen III synthesis in the heart. The drug had no effect on the increased urinary excretion of the stable metabolic products of NO. These data suggest that lacidipine might be useful in preventing the renal and cardiac damage caused by hypertension and non-insulin-dependent diabetes mellitus.

Animals↗

Antihypertensive drugs and the nervous system: ACE-inhibitors restore oscillatory potentials in hypertensives.

The authors have previously reported that oscillatory potentials (O.P.) of the electroretinogram are impaired in essential hypertensive patients before the appearance of funduscopic changes. They can therefore be considered an early marker of the nervous damage induced by hypertension. Aim of this study was to evaluate whether an antihypertensive regimen could influence the progression of this damage. O.P. were recorded in 35 essential hypertensives before antihypertensive treatment and after one-year treatment. The patients were randomly allocated into 4 treatment groups: 1) beta-blockers 2) ACE-Inhibitors 3) calcium antagonists 4) no pharmacological treatment. At the end of the study, blood pressure was significantly decreased in all but group 4. O.P., similar in the 4 groups at the beginning, were significantly higher at the end of the study only in patients treated with ACE-inhibitors. The results of this study suggest that although all hypotensive agents reduced blood pressure only ACE-I showed a protective effect on the retinal electric electrophysiology in hypertensive patients.

Adrenergic beta-Antagonists↗

Treatment of homozygous sickle cell disease with pentoxifylline.

This case report describes the sustained symptomatic and hematologic improvement in a 21-year-old woman with homozygous sickle cell (ss) disease during treatment with pentoxifylline, 400 mg three times daily after meals. Pain crises decreased from six to zero per year, hemoglobin level rose from 8.4 g/dL to 11.4 g/dL, hematocrit rose from 24.8% to 34.8%, lactate dehydrogenase level decreased from 375 IU/L to 322 IU/L, and total bilirubin level decreased from 1.8 mg/dL to 1.6 mg/dL. Mean corpuscular hemoglobin increased from 21.6 pg to 30 pg and mean corpuscular hemoglobin concentration increased from 24.1 g/dL to 34.5 g/dL. These changes were sustained for seven years except for a brief self-imposed hiatus in therapy during which period a pain crisis occurred. Further increase in pentoxifylline dosage to 400 mg four times daily did not result in any further improvement in these hematologic parameters. These results suggest that pentoxifylline reduces hemolysis in SS patients with a resulting improvement in anemia and a reduction in or elimination of pain crises.

Adult↗

Neither physical exercise nor alpha 1- and beta-adrenergic blockade affect plasma endothelin concentrations.

Endothelins (ET) are recently discovered vasoconstrictor agents released from endothelial cells and have been the object of intense investigation by researchers. Many of the factors that seem to influence the release of ET are modified by prolonged exercise. The purpose of this study was to investigate the effect of physical exercise on ET plasma concentrations and the effect of alpha- and beta-blockade on ET concentrations at rest and during exercise. Fifteen young volunteers (age 20-35 years) performed an exercise test on a bicycle ergometer. The starting workload of 50 W was increased by 30 W every 3 min until maximal heart rate was achieved; after a 2 min recovery period at 50 W the test continued for 15 min at 60% maximal work load. Blood samples were taken for ET determination before and after the test. After 1 week, the test was repeated. In the 2 days before either the first or the second test, each volunteer randomly received carvedilol (C) (25 mg), an alpha 1-adrenoceptor and beta-adrenoceptor blocker. There was no significant difference in ET concentrations after exercise with or without C administration (1.24 +/- 0.66, 1.42 +/- 0.83, 1.66 +/- 1.15, 1.61 +/- 0.87 pg/mL), showing that prolonged aerobic exercise does not affect plasma ET levels. Moreover, in our healthy young volunteers, blockade of alpha- and beta-adrenoceptors had no effect on ET levels at rest and after exercise.

Adrenergic alpha-1 Receptor Antagonists↗

Follow up of young people with high casual blood pressure.

High blood pressure (BP), often borderline hypertension, can be also found in adolescents. In these subjects the haemodynamic pattern, high cardiac output and normal vascular resistance, differs from that of older hypertensives. Although the risk for hypertension is higher in this group than in the general population, only a minority of them will develop sustained hypertension later in life. They can therefore be viewed as an enriched pool of future hypertensives but not as true prehypertensives. The aim of this longitudinal study was to analyse the relation between casual BP measured in high school students and in the same subjects 3 years later. In 1990, an extensive study on BP was carried out in 1062 high school students aged 18 years. Sitting BP, heart rate, weight, and body mass index (BMI) were measured in each subject. After 3 years, the 50 subjects with the highest BP level recorded in 1990 were recalled. Forty-five subjects (90%, 30 males and 15 females) agreed to undergo a second examination. They were seen as outpatients in the Hypertension Centre of our institute. BP was measured with a mercury sphygmomanometer after a 10 min rest three times in 5 min. Systolic and diastolic BP were significantly reduced after 3 years (137 +/- 13 vs 132 +/- 10 P = 0.002; 92 +/- 4 vs 85 +/- 6 P = 0.0001, mm Hg). By means of a multiple regression test, including parameters recorded in 1990, systolic blood pressure (SBP) (R = 0.53 Slg F = 0.0002) and diastolic blood pressure (DBP) (R = 0.60 Slg F = 0.0001) were shown as the main determinants of SBP, while DBP was related only to previous BMI (R = 0.37 Slg F = 0.01). The reduction of both SBP and DBP after 3 years could be explained either by a true, spontaneous decrease of BP or as a consequence of different environmental conditions during the second examination (more prolonged resting time, repeated measurements). However, data of this study demonstrate that casual SBP and DBP are the main determinants of future SBP, thus confirming the prognostic value of casual BP measurement in young people. Moreover, our data emphasises the role of BMI as the main determinant of future high DBP.

Adolescent↗

Metabolic effects of atenolol and doxazosin in healthy volunteers during prolonged physical exercise.

Nonselective beta-blockers may reduce exercise performance, not only through hemodynamic but also through metabolic effects. During prolonged physical exertion, lipolysis induced by plasma epinephrine occurs through beta-adrenoceptors of adipocytes. Therefore, beta-blockade may reduce release of free fatty acids (FFA) from adipocytes and consequently the energy supply for muscle cells. In this single-blind study, we compared the metabolic effects of atenolol with those of doxazosin, an alpha 1-blocker, during exercise in 26 young volunteers (age 20-35 years). All subjects performed an exercise test on a bicycle ergometer 5 h after consuming a standard breakfast. The starting workload of 50 W was increased by 30 W every 3 min until maximal heart rate (HR) was achieved; after a 2-min recovery period at 50 W the test was continued for 15 min at 60% maximal workload. Before and at the end of the test, blood samples were taken for glucose, lactate, and FFA determination. After 1 week, the test was repeated; the volunteers randomly received atenolol or doxazosin for 2 days before the second test. Exercise performance, plasma glucose, and lactate were not affected by either drug. The concentration of FFA was unchanged in subjects treated with doxazosin but was significantly reduced after the test in subjects treated with atenolol. Our data demonstrate that neither doxazosin nor atenolol impairs exercise performance in young volunteers. Atenolol reduces plasma FFA concentration possibly by inhibiting lipolysis. Doxazosin, in contrast, does not alter this parameter. Therefore, doxazosin may be a antihypertensive drug of potential benefit in treatment of hypertensive patients engaging in sports or undergoing a program of physical training.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Oscillatory potentials in subjects with treated hypertension.

Oscillatory potentials of the ERG proved to be a sensitive indicator even in mild disturbances of retinal circulation, such as the first stage of hypertensive retinopathy (WHO classification). Oscillatory indexes (OIs) and blood pressure levels of 24 hypertensive patients in stage 1 of the WHO classification, who underwent an antihypertensive therapy for the first time, were considered. The patients were retested after a mean period 8 months. a strict inverse correlation was found between OIs and blood pressure levels.

Adult↗

Oscillatory potentials of the electroretinogram in hypertensive patients.

Because alteration of oscillatory potentials of the electroretinogram has been described in diabetic patients without signs of diabetic retinopathy as an early marker of changes in microcirculation, we studied the behavior of these potentials in patients with early-onset hypertension. Electroretinograms were recorded in 24 subjects with essential hypertension (blood pressure > 140/90 mm Hg) and in 9 age-matched normotensive control subjects (blood pressure < 140/90 mm Hg). Diabetes and ocular diseases were considered exclusion criteria. Sitting blood pressure was measured by a single investigator with a mercury sphygmomanometer after each subject had been at rest for 10 minutes. Funduscopic changes in all subjects did not exceed stage I World Health Organization classification. The oscillatory index was calculated by adding waves O1, O2, and O3 within the b wave of the electroretinogram. Statistical analysis was performed with Student's t test for paired and unpaired data and linear regression. The oscillatory index was significantly reduced in hypertensive patients compared with normotensive subjects. An inverse relationship was observed when systolic and diastolic blood pressures were plotted against the oscillatory index. In conclusion, our data demonstrate that the electrical activity of the retina is altered early in the course of hypertension and that the influence of systolic pressure on the oscillatory index is greater than that of diastolic pressure.

Adult↗

Effects of chronic treatment with losartan on blood pressure, endothelin-like immunoreactivity and nitric oxide in normotensive rats.

BACKGROUND: Losartan is a new angiotensin II type 1 (AT1) receptor antagonist and an antihypertensive drug. Nitric oxide is a vasodilating agent and endothelins are powerful vasoconstrictors, both synthesized by and released from endothelial cells. Angiotensin II promotes the release of endothelins in cultured cells and this effect is prevented by losartan. Nitric oxide is also synthesized in the macula densa; therefore this substance may affect the regulation of renin excretion. OBJECTIVE: The aim of the present study was to evaluate the effects of losartan on blood pressure, endothelin-like immunoreactivity and nitric oxide in normotensive rats. MATERIALS AND METHODS: Male Wistar-Kyoto rats were divided into two groups. One group (n = 10) was treated with losartan at 10 mg/kg once a day by gavage for 4 weeks and a placebo group (n = 10) was given the same volume of water once a day by gavage. Blood pressure was measured weekly with a tail cuff and 24-h urine was collected at the beginning and at the end of the study. After 4 weeks all rats were killed and blood samples taken. Endothelin-like immunoreactivity was determined in plasma and urine using a 125I endothelin radioimmunuoassy kit. The stable metabolic products of nitric oxide, NO2- and NO3-, were measured in urine by the brucine method. RESULTS: After 4 weeks blood pressure was significantly lower in the losartan group (131 +/- 4 versus 118 +/- 6 mmHg, P = 0.001). Plasma endothelin-like immunoreactivity was similar in both groups while 24-h urinary endothelin-like immunoreactivity was significantly increased in the losartan group (29 +/- 25, 32 +/- 21, 43 +/- 19, 72 +/- 30 pg/24 h; F = 0.0003). NO2- and NO3- were unchanged in both groups. CONCLUSIONS: Our data show that chronic AT1 receptor blockade does not modify plasma endothelin-like immunoreactivity but increases urinary endothelin-like immunoreactivity. The significance of this finding remains obscure. It may represent a compensatory mechanism against the sustained vasodilation caused by losartan. Nitric oxide does not seem to affect the antihypertensive effect of losartan, since the urinary excretion of nitric oxide metabolites was unchanged.

Angiotensin Receptor Antagonists↗

Involvement of the renin angiotensin system in the pathogenesis of postexercise proteinuria.

Proteinuria after strenuous exercise is common in healthy subjects. The pathophysiologic mechanism of postexercise proteinuria (PEP) is not clear, although the phenomenon has long been known and many explanatory theories have been proposed. It is widely recognized that angiotensin II may increase filtration of protein through the glomerular membrane, and that its concentration in plasma increases during exercise. The aim of this study was to evaluate possible involvement of angiotensin II in the pathogenesis of PEP. Of 25 young volunteers who performed maximal aerobic exercise, eight showed PEP. The exercise was repeated after an interval of at least one week, now 90 minutes after administration of captopril (25 mg). Captopril did not affect the achieved work load of the maximal blood pressure and heart rate during the exercise, but PEP was not found. As it was possible to prevent PEP by administering an angiotensin-converting enzyme inhibitor, the study supports the theory that the renin angiotensin system is involved in the pathogenesis of PEP.

Adult↗

Abnormalities of the cardiovascular response to cold pressor test in type 1 diabetes. Correlation with blood glucose control.

Left-ventricular (LV) function in type 1 diabetics without clinical heart disease was compared with that found in matched normal subjects. Although diabetics had a normal LV ejection fraction (66% +/- 6%), they showed a trend toward smaller left ventricles. Their cardiovascular response to a cold pressor test was abnormal and cardiac function after the cold pressor test correlated with hemoglobin A1c levels: Average hemoglobin A1c was inversely related to ejection fraction and early filling volume and directly related to the ratio of pre-ejection period to ejection time (PEP/LVET) after a cold pressor test. Hemoglobin A1c at the time of study correlated more closely with PEP/LVET after cold pressor test than did the six-month average hemoglobin A1c level, suggesting that cardiac function fluctuates with recent changes in blood glucose control. Thus, even when diabetics have a normal LV ejection fraction, an abnormal cardiovascular response to stress may still be present, and such abnormalities correlate with blood glucose control.

Adult↗

Pituitary-adrenocortical function in chronic renal failure: studies of episodic secretion of cortisol and dexamethasone suppressibility.

Pituitary-adrenocortical function was studied in patients with chronic renal failure (CRF) and compared with that in normal subjects. All CRF patients were on chronic hemodialysis. The mean morning plasma total and free (nonprotein bound) cortisol levels were higher in patients with CRF. Episodic secretion of cortisol was studied in plasma sampled every 20 min for 24 h. CRF patients demonstrated normal circadian rhythmicity, as evidence by times of peak secretory activity and number of peaks per 24 h. Mean 24-h plasma total cortixol levels were twice the normal levels in CRF patients. Nine of 10 patients with CRF did not suppress plasma total cortisol levels with 1 mg dexamethasone. Four of 10 patients with CRF suppressed with 2 mg dexamethasone orally for 2 days, 5 patients suppressed after 8 mg dexamethasone administration, and 1 patient with CRF resisted suppression. Hemodialysis did not alter mean 24-h cortisol levels or numbers of secretory episodes but produced a shift of secretory activity into the dialysis time period. These studies show alterations in cortisol dynamics in which increased plasma cortisol levels and dexamethasone resistance coexist with normal circadian rhythmicity.

Adrenal Cortex↗

[Wilms' tumor. Our clinical experience].

The survival of children with Wilms' tumour is evaluated in 11 males and 12 females treated between 1967 and 1975 in the light of the clinical stage, age at diagnosis, and sex. The subjects were aged from 4 months to 6 years. Six were in stage I, 4 in stage II, 4 in stage III, 7 in stage IV, and 2 in stage V. Survival in stage I was 100% at 36 months and gradually decreased with the stage. Patients aged less than 2 years presented a survival of 50% two years after diagnosis, compared to 24% in those over 2 years old. Sex appears to be irrelevant to prognosis.

Age Factors↗