Search PubMed⌕ Search

Biomedical subjects

G Mazzocchi

Publications and source records attributed to G Mazzocchi.

At least 127 records · Page 7Linked to original sources

Effect of mevinolin on rat hepatocytes: a morphometric study.

A short-term (12 h) infusion with mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, significantly lowered plasma cholesterol concentration in rats. After 7 days of continuous treatment hypocholesterolaemia disappeared, and this was coupled with a notable increase in the average volume of hepatocytes. Liver-cell hypertrophy was associated with a striking proliferation of the membranes of both rough and smooth endoplasmic reticulum, as well as with a tremendous increase in the number of peroxisomes. These structural changes are interpreted as the morphologic counterpart of the compensatory response of rat liver to the prolonged inhibitory effect of mevinolin on cholesterol synthesis.

Animals↗

Long-term trophic effect of sodium restriction on the rat adrenal zona glomerulosa. I. Its partial independence of the renin-angiotensin system.

The mechanism of the trophic effect of chronic sodium restriction on the zona glomerulosa of the rat adrenals was investigated by combined morphometric and biochemical techniques. In the normal rats, prolonged sodium deprivation caused a significant hypertrophy of the zona glomerulosa and its parenchymal cells, coupled with a conspicuous rise in the plasma concentration of aldosterone. Analogous results were observed in animals simultaneously administered captopril and maintenance doses of angiotensin II. However, in this last case, the changes were significantly lower than those observed in the normal rats. These findings are compatible with the view that the activation of the renin-angiotensin system is not the sole mechanism involved in the stimulation of the growth and steroidogenic capacity of rat adrenal zona glomerulosa induced by chronic sodium restriction.

Adrenal Glands↗

Long-term trophic effect of sodium restriction on the rat adrenal zona glomerulosa. II. The possible involvement of the inhibition of the dopaminergic system.

The effects of chronic administration of metoclopramide or bromocriptine (two drugs which act as antagonist and agonist of dopamine receptors) on the zona glomerulosa of captopril-treated rats administered maintenance doses of angiotensin II, were investigated by combined morphometric and biochemical techniques. It was found that metoclopramide provoked a significant hypertrophy of the zona glomerulosa and its parenchymal cells, coupled with a persistent rise in the plasma concentration of aldosterone, only in rats fed a normal diet. Conversely, bromocriptine exerted an evident inhibitory effect on the zona glomerulosa growth and steroidogenic capacity only in chronically sodium-deprived animals. These findings strongly suggest that sodium balance modulates the activity of the dopaminergic system, whose chronic suppression may be involved in the mechanism underlying the extra-angiotensin adrenoglomerulotrophic effect of prolonged sodium restriction.

Adrenal Glands↗

A morphometric study of the effects of melatonin on the rat adrenal zona glomerulosa.

The effects of a long-term administration of melatonin on the zona glomerulosa were investigated both in "normal" rats and in animals in which the hypothalamo-hypophyseal-adrenal axis and the renin-angiotensin system had been pharmacologically interrupted. Melatonin caused a notable hypertrophy of zona glomerulosa cells and a significant rise in the plasma concentration of aldosterone in both groups of rats. These findings indicate that melatonin exerts in vivo a strong direct stimulatory action on the growth and steroidogenic capacity of the rat zona glomerulosa.

Adrenal Glands↗

Zona glomerulosa morphology and function in streptozotocin-induced diabetic rats.

Streptozotocin-induced diabetic rats showed a significant lowering in both PRA (-31%) and basal plasma aldosterone concentration (-59%), coupled with a notable atrophy of the zona glomerulosa (-30%) and its parenchymal cells (-36%). Kalaemia and the blood level of ACTH were not affected. Insulin infusion reversed all the streptozotocin-evoked effects. Analogous, though less conspicuous, changes were induced by experimental diabetes also in rats whose hypothalamo-hypophyseal-adrenal axis and renin-angiotensin system had been pharmacologically interrupted by the simultaneous administration of dexamethasone-captopril and maintenance doses of ACTH-angiotensin II: the drops in the basal plasma aldosterone concentration and in the volume of zona glomerulosa and its cells ranged from -20% to -22%. In these animals, experimental diabetes significantly depressed the aldosterone response to the acute stimulation with angiotensin II (-55%), potassium (-50%), and ACTH (-43%). These findings indicate that the well known impairment of renin release may only partially account for the antiadrenoglomerulotrophic effect of experimental diabetes in rats. The hypothesis is advanced that the chronic lack of insulin may directly depress both the growth of the zona glomerulosa and the newly synthesis of some enzymes of aldosterone synthesis.

Adrenal Glands↗

An ultrastructural stereologic study of aldosterone secreting adrenal adenomas and of adjacent zona glomerulosa.

The ultrastructure of four aldosterone secreting adenomas and of the adjacent zona glomerulosa has been described by the use of stereological techniques. Adenomatous cells (about 2800 microns 3 in volume) invariably displayed a striking abundance of lipid droplets, which occupied about 30% of the cytoplasm. Mitochondria prevalently contained tubulo-lamellar or lamellar cristae, but some cells exhibited organelles with vesicular cristae. Smooth endoplasmic reticulum (SER) was not very abundant. Small lipofuscin-pigment granules were frequently seen and in a few cells they were exceedingly numerous. Zona glomerulosa cells were smaller (about 950 microns 3 in volume) and possessed mitochondria with typical tubulo-lamellar cristae, a plentiful SER and few lipid droplets. They showed the ultrastructural features of elements actively engaged in steroid synthesis. The possible origin of aldosteronoma cells from the zona glomerulosa is discussed.

Adenoma↗

A morphometric study of the effects of short-term starvation on rat hepatocytes.

Short-term (24 h) starvation induced a significant decrease in the liver weight and in the average volume of hepatocytes, together with a notable decrease in the hepatic concentration of proteins, glycogen, cholesterol and triglycerides. Hepatocyte atrophy was due for about 95% to the decrease in the membrane space, in which glycogen and endoplasmic reticulum membranes are contained, and for about 5% to the depletion of lipid droplets, in which cholesterol and triglycerides are stored. Nuclei, mitochondria and rough endoplasmic reticulum did not display appreciable modifications. The smooth endoplasmic reticulum underwent a net decrease, comparable with the decrease in the liver protein content, and the volume of dense-body compartment was increased, mainly through the rise in the number of microautophagic vacuoles and secondary lysosomes. These last findings were interpreted as the morphological counterpart of the fasting-induced enhancement of protein degradation in rat liver.

Animals↗

Effects of a prolonged treatment with aminoglutethimide on the zona fasciculata of rat adrenal cortex: a morphometric investigation.

The effects of a 7-day administration of aminoglutethimide (AG) on the adrenal zona fasciculata were examined in "normal" and dexamethasone/ACTH-treated rats. There was a 70-74% decrease in the concentration of corticosterone in blood, but no conspicuous qualitative changes suggesting cell degeneration occurred. Morphometry showed that AG induced a significant hypertrophy of the zona fasciculata and its parenchymal cells only in "normal" animals, which was due to an increase in the volume of the mitochondrial compartment and to proliferation of the smooth endoplasmic reticulum. This response to AG was considered to be non-specific and mediated by the enhanced secretion of ACTH following the decrease in the blood level of corticosterone. AG administration significantly increased the volume of the lipid-droplet compartment and the number of intramitochondrial lipid-like inclusions in both groups of animals. These changes were interpreted as the morphological counterpart of the AG-induced block of cholesterol utilization in steroid synthesis.

Adrenal Cortex↗

Effects of prolonged treatment with cyanoketone on the zona fasciculata of rat adrenal cortex. A combined morphometric and biochemical study.

The effects of a 7-day administration of cyanoketone (CKT) on the adrenal zona fasciculata were examined in "normal" and dexamethasone/ACTH-infused rats. The drug caused a 48-56% decrease in the blood concentration of corticosterone, coupled with a 53-58% lowering in the activity of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), in both groups of animals. In the "normal" rats, CKT induced a significant hypertrophy of the zona fasciculata and its parenchymal cells, due to an increase in volume of the mitochondrial compartment and to proliferation of the smooth endoplasmic reticulum (SER), as well as a notable rise in both the volume of the lipid-droplet compartment and the intracellular concentration of total cholesterol. The activity of 11 beta-hydroxylase was conspicuously enhanced. All these responses of zona fasciculata cells to CKT did not occur in dexamethasone/ACTH-treated animals, and therefore they were considered to be non-specific and mediated by the augmented secretion of ACTH following lowering of the corticosterone level in the blood. In the dexamethasone/ACTH-infused rats, the only morphological change induced by CKT was a significant decrease in the surface area per cell and surface density of the SER, which was interpreted as the morphological counterpart (not masked by the increased level of circulating ACTH) of the drug-induced inhibition of the microsomal 3 beta HSD.

3-Hydroxysteroid Dehydrogenases↗

Investigations on the possible involvement of the dopaminergic system in the modulation of the growth and steroidogenic capacity of the rat adrenal zona glomerulosa: a coupled morphometric and biochemical study.

The effects of metoclopramide (MTC) and bromocriptine (BRC) (two drugs which act as antagonist and agonist of DOPA-receptors, respectively) on the zona glomerulosa of dexamethasone/ACTH-treated rats were investigated by coupled biochemical and morphometric techniques. Short-term (1-h) MTC administration significantly increased the plasma concentration of aldosterone, while long-term (7-day) MTC administration, as well as short- and long-term treatment with BRC did not cause any apparent change. Long-term MTC administration was found to significantly potentiate both the rise in the plasma level of aldosterone and the hypertrophy of the zona glomerulosa and its parenchymal cells induced by a prolonged treatment with angiotensin II (AII), but not those evoked by a chronic sodium deprivation alone or combined with AII infusion. Long-term BRC administration notably counteracted the effects of sodium restriction (coupled or not with AII infusion), but not those induced by the administration of AII alone. Long-term MTC administration partially reversed both the lowering of the plasma concentration of aldosterone and the atrophy of the zona glomerulosa and its parenchymal cells caused by a prolonged sodium-loading (combined or not with captopril infusion), but not those produced by the administration of captopril alone. On the other hand, long-term BRC treatment induced a further significant reduction in the blood level of aldosterone and the volume of zona glomerulosa and its cells only in captopril-treated animals. These findings are consistent with the view that the dopaminergic system exerts a maximal tonic inhibitory effect not only on the secretory activity, but also on the growth and steroidogenic capacity of the rat zona glomerulosa. Furthermore, they suggest that the activity of the dopaminergic system is in turn controlled by the sodium balance, being almost completely suppressed by a prolonged sodium deprivation.

Adrenal Cortex↗

Effect of long-term inhibition of hydroxy-methylglutaryl coenzyme A reductase by mevinolin on the zona fasciculata of rat adrenal cortex. A combined morphometric and biochemical study.

The effects of a 7-day infusion with mevinolin, a potent competitive inhibitor of hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase, on the adrenal zona fasciculata were examined in normal and dexamethasone/ACTH-treated rats. In both groups of animals, the drug caused a lowering in plasma and intra-adrenal cholesterol concentrations, as well as a slight decrease in the blood level of corticosterone. Morphometry of zona fasciculata cells showed that specific mevinolin-induced changes (i.e. those occurring in both groups of rats and therefore not due to enhanced release of ACTH following decrease in circulating corticosterone) are severe lipid-droplet depletion and a conspicuous increase in smooth endoplasmic reticulum (SER) and peroxisomes. The hypothesis is discussed that these morphological changes express a compensatory response of zona fasciculata cells to counteract the mevinolin-induced inhibition of cholesterol synthesis in both liver and adrenal cortex.

Adrenal Cortex↗

The GH-releasing hormone (GHRH) test in acromegaly before and after adenomectomy.

The GHRH test may represent a new tool in the study of GH dynamics in acromegaly. GH responsiveness to GHRH 1-40 (50 micrograms iv) has been studied in 21 acromegalic patients. Nineteen out of 21 had active disease. Five patients were also studied 1-12 months after neurosurgery. Two apparently cured acromegalics were studied 1-2 yr after surgery. GH secretion has been evaluated in all patients by means of TRH, bromocriptine and insulin hypoglycemia tests, too. GH response to GHRH has also been performed in 14 normal subjects. In acromegaly, GH responses after GHRH (p less than 0.01 vs placebo) were variable. The GH peak ranged from 8 to 445 ng/ml in patients with active disease. Maximum GH increase after GHRH (calculated as peak/basal value ratio) was significantly reduced in acromegaly (2.9 +/- 0.5 ng/ml; mean +/- SE) in comparison to controls (34.1 +/- 10.9 ng/ml; p less than 0.01). No significant differences in GH pattern after GHRH were found between untreated and previously treated patients with active disease. A significant correlation was found between GH basal levels and GH incremental area (p less than 0.05) and between GH basal and peak levels (p less than 0.01) after GHRH. A significant increase in PRL secretion was observed in acromegalic patients after GHRH (p less than 0.01 vs placebo). No discernable variation was found in the other pituitary hormones pattern after the peptide administration. A positive correlation was observed between GH increase after GHRH and insulin hypoglycemia (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

Vasoactive intestinal peptide (VIP) stimulates aldosterone secretion by rat adrenal glands in vivo.

VIP acutely enhanced the plasma concentration of aldosterone (but not that of corticosterone) both in normal rats, and in rats chronically treated with dexamethasone and ACTH or captopril and angiotensin II. VIP increased aldosterone blood concentration in chronically captopril-treated animals, but not in rats in which ACTH secretion was inhibited by dexamethasone. These findings suggest that VIP is specifically involved in the stimulation of the secretory activity of rat zona glomerulosa, and that this action of VIP requires a normal level of circulating ACTH.

Adrenal Glands↗

Atrial natriuretic factor (ANF) inhibits the growth and the secretory activity of rat adrenal zona glomerulosa in vivo.

A prolonged infusion with ANF induced atrophy of zona glomerulosa cells of rat adrenals and lowering of plasma concentration of aldosterone, without provoking significant changes in PRA. It also notably reduced the rise in the aldosterone plasma level caused by the acute stimulation with angiotensin II. Zona fasciculata cells and the blood concentration of corticosterone did not display any significant change. These findings are interpreted to indicate that ANF exerts an inhibitory effect on the growth and secretory activity of rat zona glomerulosa.

Adrenal Glands↗

Neuropeptide-Y acutely stimulates rat zona glomerulosa in vivo.

Neuropeptide-Y (NPY) acutely enhanced the plasma concentration of aldosterone (but not that of corticosterone) in both normal animals and in rats whose hypothalamo-hypophyseal axis and renin-angiotensin system were pharmacologically interrupted. The maximal response was obtained with a dose of 150 micrograms/kg. This dose of NPY raised the activity of 11 beta-hydroxylase and 18-hydroxylase in the capsular adrenal (zona glomerulosa), but not that of 11 beta-hydroxylase in the inner adrenocortical layers (zonae fasciculata and reticularis). These findings seem to indicate that NPY is specifically and directly involved in the acute stimulation of the late steps of the secretory activity of the rat zona glomerulosa.

Adrenal Cortex↗

Growth hormone response to growth hormone-releasing hormone in normal and uraemic children. Comparison with hypoglycaemia following insulin administration.

The uraemic syndrome is characterized by several endocrinological disturbances. This study was undertaken in order to evaluate the GH response to growth hormone-releasing hormone (GRH) in children with chronic renal failure (CRF) and to compare the results with those observed after insulin hypoglycaemia. Twenty-two children with CRF, 10 undergoing continuous ambulatory peritoneal dialysis (CAPD) and 12 on conservative treatment (CT), age ranges 2-15 years, were studied and the data were compared with those from 14 children with normal renal function and normal hormonal behaviour, affected by short stature (NC), and those form 13 healthy adult volunteers (NA). The GRH test (l micrograms/kg body weight, iv) was carried out in 8 CAPD, 8 CT, 9 NC and 10 NA subjects. The blood samples were taken every 30 min for 3 h in CAPD and CT and for 2 h in NC and NA starting at 09.00 h. The following hormones were measured: GH, LH, FSH, Prl, TSH and cortisol (F). The insulin test (0.1 U/kg body weight, iv) was carried out in 5 CAPD, 5 CT, 10 NC and 9 NA on blood samples taken every 30 min for 2 h, measuring GH and glycaemia. No adverse effects were observed after the infusion of GRH. GRH administration induced a prompt response in all subjects, but GH plasma levels were significantly higher in uraemic children than in adults (peak value of 43.5 +/- 8.2, 45.0 +/- 8.4, 27.8 +/- 6.0; 13.5 +/- 2.6 micrograms/ml in CAPD, CT, NC and NA, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of ACTH and aminoglutethimide administration on the morphological and functional responses of rat adrenal zona fasciculata to a prolonged treatment with 4-aminopyrazolo-pyrimidine.

The prolonged administration of the hypocholesterolaemic drug 4-APP induced morphological changes in rat zona fasciculata cells (AER hypertrophy, peroxisome proliferation and lipid droplet depletion), enabling them to synthesise their own cholesterol and to maintain an adequate level of corticosterone output. Chronic ACTH administration provoked, in zona fasciculata cells of 4-APP-treated rats, a further increase in the AER and the volume of peroxisome compartment, coupled with a significant rise in the volume of the mitochondrial compartment and in the surface area per cell of mitochondrial cristae; the volume of the lipid droplet compartment did not change, whereas the plasma level of corticosterone significantly increased. These findings indicate that the modified adrenocortical cells of 4-APP-treated rats possess a good functional reserve, being still able to enhance their growth and steroidogenic capacity in response to ACTH. Aminoglutethimide, a drug blocking cholesterol utilisation in steroid synthesis, lowered the blood level of corticosterone in 4-APP/ACTH-administered rats; it increased the intra-adrenal concentration of cholesterol, but did not provoke lipid droplet accumulation in zona fasciculata cells. This result may suggest that in adrenal lipid droplets is stored only exogenous cholesterol taken up from plasma lipoproteins.

Adenine↗

An ultrastructural morphometric study of the effects of chronic melatonin administration on the zona fasciculata of rat adrenal cortex.

The effects of a long-term administration of melatonin on the adrenal zona fasciculata were investigated both in 'normal' rats and in animals whose hypothalamo-hypophyseal-adrenal axis had been interrupted by a prolonged infusion with dexamethasone or dexamethasone plus maintenance doses of ACTH. In the 'normal' rats, melatonin caused a notable atrophy of zona fasciculata cells, coupled with a significant lowering in the plasma concentration of corticosterone. On the contrary, in dexamethasone- or dexamethasone plus ACTH-infused animals, melatonin induced an evident hypertrophy of zona fasciculata cells which, however, was not associated with a rise in the corticosterone blood level. The hypothesis is advanced that the direct stimulatory effect of melatonin on the growth of zona fasciculata in 'normal' rats can be masked by the concurrent inhibition of the hypophyseal release of ACTH. The possible mechanism of the direct effect of melatonin on the zona fasciculata is discussed in the light of evidence indicating that this hormone enhances the intracellular catabolism of corticosterone, which is well-known to exert a powerful direct depression of the growth and steroidogenic capacity of rat adrenocortical cells.

Adrenal Cortex↗