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Biomedical subjects

A Rappelli

Publications and source records attributed to A Rappelli.

123 records · Page 7Linked to original sources
PubMedDate not supplied

Natriuretic peptides receptors in human aldosterone-secreting adenomas.

Atrial natriuretic peptide (ANP) and B-type or brain natriuretic peptide (BNP) inhibit aldosterone secretion in humans both in vitro and in vivo. Unresponsiveness of aldosterone-secreting adenomas (aldosteronomas) to ANP in vitro and in vivo, might be due to reduced expression of the biologically-active natriuretic peptide receptor type A (NPr-A) and/or increased expression of the clearance receptor for natriuretic peptides (NPr-C). Therefore, we have analyzed NPr gene expression and ANP binding sites in human adrenals and aldosteronomas. Using reverse transcription and polymerase chain reaction, we cloned and characterized cDNAs for NPr-A, NPr-C, and the receptor (NPr-B) for the C-type natriuretic peptide (CNP). Total RNA from three normal human adrenals (obtained at surgery from patients with renal cancer) and five aldosteronomas were used for Northern analysis. NPr-A mRNA (approximately 4 kb) and NPr-B mRNA (approximately 4 kb) were expressed without significant differences in adrenals and in aldosteronomas except in an aldosteronomas that contained only very low amounts of NPr mRNAs. The gene expression of NPr-C was barely detectable both in adrenals and in aldosteronomas. ANP binding sites were analyzed by autoradiography with 125I-labeled ligand in other six aldosteronomas. Only one of the adenomas analyzed showed ANP binding sites with density of granules similar to nonadenomatous glomerulosa, whereas the others had significantly reduced densities. In summary, aldosteronomas express the genes encoding for NPr but mainly NPr-A, similarly to control adrenals. On the contrary, the binding sites for ANP are greatly reduced in most aldosteronomas. A somatic mutation or a post-transcriptional defect that reduces ANP binding sites might be present in some aldosteronomas.

Adenoma↗
PubMedDate not supplied

Expression of type 1 angiotensin II receptors in human aldosteronomas.

Type 1 angiotensin II (AII) receptors (AT1 receptors), besides stimulation of aldosterone secretion, seem to transduce the growth factor-like activity of AII on glomerulosa cells. Although a local renin-angiotensin system and AII synthesis have been found in human adrenals and aldosteronomas, it is unclear whether aldosteronomas express AT1 receptors. Utilizing polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) with primers complementary to both genomic and cDNA sequences of human AT1 receptor, we have amplified and cloned a 734 bp fragment of the AT1 coding region. This DNA, after cloning and sequencing, was used for Northern analysis. Total RNA was extracted from 5 non-tumorous adrenals and 5 aldosteronomas. AT1 mRNA (approximately 2.4 kb) was expressed in all the aldosteronomas tested. Densitometric analysis of AT1 signals, corrected by beta actin expression, when compared to non-tumorous adrenals, did not show significant differences. AT1 receptor density and affinity in cell membrane obtained from 9 non-tumorous adrenal cortex and 8 aldosteronomas were also studied. 125I-AII was used as ligand and Dup 753 as AT1 antagonist: AT1 receptor density and affinity were not significantly different in aldosteronomas vs non-tumorous adrenal cortex. In conclusion, the expression of AT1 gene and the formation of an apparently normal receptor suggest that AT1 receptor should have a role in aldosteronoma cell biology.

Adrenal Cortex Neoplasms↗
PubMedDate not supplied

The natriuretic peptide system in obesity-related hypertension: new pathophysiological aspects.

The association between obesity and hypertension is well known but the pathophysiology of weight-related changes on blood pressure is still a matter of debate. Although obesity-related hypertension is considered to be sodium-sensitive, little attention has been given to a possible pathophysiological role of Atrial Natriuretic Peptides (ANP) and their receptors (NPr) system. Since the early phase of weight loss induced by very-low-calorie diet or fasting is followed by a significant increase in diuresis and natriuresis together with an increase in circulating ANP, we focused our attention on the possible role of adipose tissue in mediating these changes. We first demonstrated that human and rat adipose tissue contain high levels of mRNA specific for both type A (NPr-A), which is biologically active, and type C (NPr-C) which is biologically inactive, receptors. We then demonstrated in the rat that fasting exerts a tissue-specific and gene-specific suppression of NPr-C gene expression in adipose tissue that appears to be accompanied by an increased biological activity of ANP. These experimental observations were confirmed in man studying gene expression of NPr-A and NPr-C in adipose tissue obtained through subcutaneous peri-umbilical needle aspiration in obese and non-obese hypertensive patients. We found that NPr-A: NPr-C mRNA ratio was significantly lower in obese hypertensive patients as compared with non-obese hypertensives. These findings suggest that overxpression of the clearance receptor in the obese may trap more molecules of circulating ANP so reducing their biological activity at renal level. More recent results were obtained in obese hypertensive patients in whom the intravenous bolus injection of ANP (0.6 mg/kg body weight) was performed before and after four days of very-low-calorie diet which induced a weight loss accompanied by a significant reduction of BP and an increase in the urinary excretion of cGMP. The infusion of ANP after low-calorie diet was followed by an increase of ANP levels similar to that observed before diet, but plasma cGMP, diuresis and natriuresis significantly increased only after caloric restriction and the effects of ANP infusion on BP were more pronounced. Taken together our studies suggest that the abundance of NPr-C in adipose tissue may play a significant role in explaining at least part of the sodium retention characteristic of obesity associated hypertension.

Adipose Tissue↗
PubMedDate not supplied

[Study on the medium normalized velocity of circumferential lengthening of the fiber using ultrasound. I. Evaluation of left-ventricular compliance].

The following parameters obtained by echocardiography have been measured in a group of normal subjects and in a group suffering from hypertrophic subaortic stenosis (IHSS): 1) speed of mitral valve protodiastolic closing (MVV); 2) circumferential lengthening speed of the fibre (MVCL) both standardized and otherwise. There is a good correlation between MVCL and MVV (P = 0.01 and 0.05). Since a low mitral valve closing rate is an indirect index for measuring ventricular compliance, the use of the MVCL can be considered valid for the same purposes. Using this it has in fact been possible to distinguish subjects with IHSS in which lower MVV is an index of reduced compliance, from normal subjects.

Cardiomyopathy, Hypertrophic↗
PubMedDate not supplied

[Study on the medium normalized velocity of circumferential lengthening of the fiber using ultrasound. II. Use of the construction of left-ventricle performance curves].

Telediastolic pressure and volume can readily be employed as expressions of sarcomere length when constructing ventricular performance curves for the normal heart. In pathological hearts, however, these parameters are rendered inadequate as a result of altered compliance, which means that diastolic lengthening of the muscle fibre cell must be determined from telediastolic stress and linear compliance, corrected for wall thickness (muscle fibre stretch, strain index). Ventricular performance curves were constructed for normal subjects and patients with hypertrophic subaortic stenosis, using the normalised mean rate of circumferential lengthening of the fibre as the expression of fiber strength. Comparison was made with the mean circumferential shortening rate and the ejection fraction as the expression of ventricular effort. It was found that both normal subjects and stenosis patients lay on the same curve, the latter acting low down through having short sarcomeres.

Cardiomyopathy, Hypertrophic↗
PubMedDate not supplied

[Evaluation of the safety and efficacy of the lisinopril + hydrochlorothiazide and captopril + hydrochlorothiazide combinations in the treatment of essential arterial hypertension].

The aim of this study was to assess the efficacy and tolerability of the combinations of lisinopril (LIS) 20 mg + hydrochlorothiazide (HCTZ) 12.5 mg and captopril (CAP) 50 mg + HCTZ 25 mg in moderately hypertensive patients not adequately controlled by LIS or CAP alone. The study was multicentre (11 centres), open, random and carried out in parallel groups. After two weeks' placebo run in patients were randomly assigned to LIS 10-20 mg/o.d. or CAP 25-50 mg/b.i.d. treatment for 6 weeks. After this, patients with supine diastolic blood pressure (SDBP) greater than 90 mmHg were treated with the combinations LIS 20 mg + HCTZ 12.5 mg/o.d. or CAP 50 mg + HCTZ 25 mg/o.d. for 4 weeks; this dose was doubled if DBP was found to be greater than 90 mmHg after 2 weeks' combined therapy. A total of 175 patients were enrolled (92 females and 83 males) of which 153 completed the study. The LIS + HCTZ association caused a significant reduction of DBP in comparison to the other combined treatment (88.1 +/- 0.7 vs 90.3 +/- 0.7; p = 0.026). The statistical analysis of mean SBP values showed no significant difference between the two groups (144.0 +/- 1.3 vs 146.8 +/- 1.3; p = 0.15). At the end of the study 79.5% of patients treated with LIS + HCTZ presented normal results (DBP less than or equal to 90 mmHg), whereas the percentage of similar results in the comparison group was 72%. The percentage of "responder" patients to therapy (DBP reduced by 10 mmHg or more in relation to basal values) was 96.3% in the LIS + HCTZ group and 86.7% in the CAP + HCTZ group. In the CAP + HCTZ group 0.6% of patients reported adverse reactions, while only 0.3% were observed in the LIS + HCTZ group.

Adolescent↗
PubMedDate not supplied

[Nonischemic changes of the ST segment in dynamic electrocardiography].

Ambulatory ECG monitoring has become increasingly important in the diagnostic workup of patients investigated for chest pain and in the evaluation of patients with known ischemic heart disease. Following the demonstration of ischemic episodes not associated with anginal symptoms, the diagnosis of myocardial ischemia is based solely on the detection of ST segment shifts; however several conditions associated with non-ischemic ST segment changes during ambulatory ECG monitoring might potentially be misleading. These conditions include: 1) ST segment changes in the normal population: it is a rare finding in specifically designed studies that however are probably affected by a "pretest referral bias"; caution is therefore suggested in diagnosing ischemia when episodes of ST segment depression are mild (< 2 mm) and occur at high heart rates (> 120 beats/min); 2) postural changes, usually easily recognized by the typical "square" pattern of the ST segment trend; 3) ST segment changes related to respiratory manoeuvres, quite rare and usually mild; 4) ST segment changes due to drugs; 5) ST segment changes caused by rhythm and conduction disturbances. Lastly the significance of ST segment changes in patients with angina and normal coronary arteries is discussed, following recent observations of reduced coronary flow reserve and/or abnormal myocardial metabolism in a sizable proportion of these patients.

Arrhythmias, Cardiac↗
PubMedDate not supplied

[Use of normalized velocities in the echocardiographic evaluation of left ventricular performance].

The mean circumferential contraction rate of the myocardial fiber cell (Mvcf) and the ejection fraction (EF) are echocardiographic parameters commonly employed in the assessment of left ventricular performance. In cases where septal asynchonism due to fibrosis or bundle-branch block make their determination impossible, however, one is forced to use parameters obtained from movement of the posterior wall. Investigation of normal subjects and patients with idiopathic hypertrophic subaortic stenosis showed that the "normalized" systolic velocity of the posterior wall (Vpws) and the non-normalized mean velocity (PWV) closely fitted Mvcf and that Vpws offered a good fit with EF. It is suggested that a non-invasive way of obtaining sufficiently reliable data for the evaluation of cardiac performance is offered by these two parameters.

Cardiomyopathy, Hypertrophic↗
PubMedDate not supplied

[Standardized protodiastolic median velocity of the posterior wall (dpwV) used as an index of relaxation in the construction of left ventricular function curves].

The standardized mean protodiastolic speed of the posterior wall (Vpwd), non standardized speed (DEV) and maximum speed (DEVM) obtained with ultrasounds, are capable of distinguishing subjects with hypertrophic subaortic stenosis (IHSS), in whom there is a diminution in compliance, from normal subjects. As this compliance diminution is liable to limit fibrocell lengthening to the extent of its distension speed, the Vpwd has been used in the plotting of ventricular function curves in replacement of telediastolic volume (as an expression of fibre lengthening). An excellent correlation was found between Vpwd and mean speed of circumferential shortening of the fibre (Mvcf) and the ejection fraction (EF) used as indices of cardiac work. The comparison shows that the two groups lie on the same curve of ventricular function and that subjects with IHSS operate low down owing to the brevity of their sarcomeres. The Vpwd can thus be utilized as an indirect index of fibre length and in the plotting of left ventricular function curves.

Cardiomyopathy, Hypertrophic↗
PubMedDate not supplied

[Normalized median velocity of circumferential fiber lengthening studied with ultrasonics. III. Comparison with the normalized protodiastolic median "velocity" of the posterior wall].

Both mitral valve closing speed (MVV) and the mean standardized circumferential lengthening of the myocardial fibrocell (MVCL), between which a good correlation exists, may be used as indirect indices of ventricular compliance. These two indices have been compared with those obtained echocardiographically from the movement of the posterior wall of the ventricle in a group of normal subjects and in a group suffering from hypertrophic subaortic stenosis (IHSS). The comparison between MVCL and mean standardized speed of protodiastolic prolapse of the posterior wall (Wpwd) was fairly significant (P=0.01); that between MVCL and mean speed of protodiastolic prolapse of the posterior wall (DEV) was only slightly significant (P=0.05) or was not significant at all; that between MVCL and the maximum speed of protodiastolic release (DEVM) was slightly significant (P=0.05). Although the correlation between MVV and the various indices obtained from the movement of the posterior wall (DEV, DEVM, Vpwd) were quite significant (P=0.01), it is considered that Vpwd is preferable as an indirect index of ventricular compliance. As it is capable of distinguishing subjects with IHSS from normal subjects inthose cases in which the movement of valvular peaks, modified or impeded by inflammatory or fibrotic processes does not a-low MVV to be measured, we think Vpwd can be usefully employed as it can in all those circumstances in which it is impossible to measure MVCL owing to alterations to normal septal synchronism (infarction and fibrosis of the septum, branch blocks, etc.).

Aortic Stenosis, Subvalvular↗