Biomedical subjects

C Robba

Publications and source records attributed to C Robba.

At least 19 recordsLinked to original sources

PubMed2006

Clinical outcome of adjuvant endocrine treatment according to PR and HER-2 status in early breast cancer.

Patients with estrogen receptor (ER)+/progesterone receptor (PR)- and/or HER-2 overexpressing breast carcinomas may derive lower benefit from endocrine treatment. We examined retrospectively data from 972 breast cancer patients who received tamoxifen (725), tamoxifen + Gn-RH analogs (127) and aromatase inhibitors (120) as adjuvant treatments. ER+/PR- versus ER+/PR+ tumours were characterised by larger size (P = 0.001), higher tumour grade (P = 0.001), higher Ki-67 expression (P = 0.001) and lower mean ER (P = 0.000) and HER-2 expression (P = 0.000). At univariate analysis, tumour grading [hazard ratio (HR) = 4.0; 95% confidence interval (CI) = 1.4-11.1; P = 0.007], nodal status (HR = 3.4; 95% CI 1.2-5.7; P = 0.000), tumour diameter (HR = 2.9; 95% CI 1.7-4.7; P = 0.000) lack of PR expression (HR = 2.1; 95% CI 1.3-3.4; P = 0.002) and HER-2 overexpression (HR = 1.9; 95% CI 1.0-3.5; P = 0.03), as well as Ki 67 expression (HR = 1.7; 95% CI 1.0-2.7; P = 0.04) were associated with shorter disease-free survival (DFS). At the multivariate analysis, nodal status (HR = 3.6; 95% CI 1.9-6.8; P = 0.0001), lack of PR expression (HR = 2.3; 95% CI 1.3-4.0; P = 0.003) and tumour diameter (HR = 2.1; 95% CI 1.1-3.8; P = 0.018) retained their prognostic significance, whereas HER-2 overexpression was associated with a trend towards shorter DFS that was of borderline statistical significance (HR = 2.0; 95 % CI 1.0-3.9; P = 0.05). Our data suggest that lack of PR expression and HER-2 overexpression are both associated with aggressive tumour features, but the prognostic information of PR status on the risk of recurrence in endocrine-treated breast cancer patients is stronger.

Adult↗

PubMed1993

Genetics of renal damage in primary hypertension.

Little is known of the genetics of glomerular damage in essential hypertension in humans. The prevalence of end-stage renal disease due to primary hypertension varies from 20% to 30% of all cases of renal failure to as low as 0.002%. This depends not only on differences in diagnostic criteria but also on different racial susceptibility to the disease as well as on different genetic backgrounds in different subsets of individuals of the same race. A review of the literature is provided, together with an example of how a point mutation that causes hypertension in Milan hypertensive rats can provide a model to analyze this issue correctly.

Animals↗

PubMed1993

Erythrocyte Na+,K+,Cl- cotransport and kidney function in essential hypertension.

OBJECTIVE: To determine whether essential hypertensive patients with high Na+,K+,Cl- cotransport (COT) display alterations of some indices of kidney tubular reabsorption similar to those observed in Milan hypertensive (MHS) rats, which have high COT in both erythrocytes and kidney tubular cells, and hypertension caused by a primary increase of tubular reabsorption. DESIGN: Two sets of experiments were performed. First, renal function in two subgroups of hypertensive patients (one with 'high' and one with 'normal' COT was compared with that in normotensive controls. Secondly, the natriuretic and diuretic effects of a single oral dose of frusemide (25 mg) were analysed in six high- and in six normal- COT hypertensive patients. RESULTS: Compared with normotensives and with normal-COT hypertensives, high-COT hypertensives had lower fractional uric acid excretion and plasma renin activity with similar glomerular filtration rate and urinary sodium and potassium excretion. COT was negatively correlated with fractional uric acid excretion in the essential hypertensive patients but not in the normotensives. The diuretic natriuretic response to frusemide was much higher in high- than in normal-COT hypertensives. CONCLUSION: These results are consistent with the hypothesis that patients with high COT have abnormal renal handling of sodium similar to that observed in MHS rats.

Adult↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1987

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↗

PubMed1987

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↗

PubMed1987

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↗

PubMed1987

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↗

PubMed1986

Sex differences in adrenocortical structure and function. XXII. Light- and electron-microscopic morphometric studies on the effects of gonadectomy and gonadal hormone replacement on the rat adrenal cortex.

The cytological aspects of sexual dimorphism in the rat adrenal cortex and its relationship to the gonads have been investigated. The adrenal glands of mature female rats were heavier than those of males, and morphometry showed that this was almost exclusively due to conspicuous differences in the volume of cells of the zona fasciculata (ZF) and zona reticularis (ZR). Stereology demonstrated that the volume of the mitochondrial and lipid droplet compartments, as well as the surface area per cell of mitochondrial cristae and smooth endoplasmic reticulum tubules, were markedly higher in the ZF and ZR cells of female animals. Orchiectomy increased and ovariectomy decreased the adrenal weight, by eliciting hypertrophy and atrophy, respectively, of ZF and ZR cells; these effects of gonadectomy were reversed by the appropriate gonadal hormone replacement. It is suggested that the sexual dimorphism of the rat adrenal cortex may depend upon the inhibitory action of testosterone and the stimulatory effect of estradiol on the hypothalamo-hypophyseal-adrenal axis.

Adrenal Cortex↗

PubMed1986

Short- and long-term effects of ACTH on the adrenal zona glomerulosa of the rat. A coupled stereological and enzymological study.

Short-term ACTH treatment provoked a decrease in volume of the lipid-droplet compartment in rat zona glomerulosa cells, and a rise in plasma and intracellular concentrations of corticosterone and aldosterone. It enhanced activities of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), 11 beta-hydroxylase (11 beta OH) and 18-hydroxylase (18OH). Long-term ACTH administration produced a hypertrophy of the zona glomerulosa and its parenchymal cells, a result of the increase in volume of the smooth endoplasmic reticulum and the mitochondrial compartment. The surface area per cell of mitochondrial inner membranes increased; the tubular cristae were transformed into a homogeneous population of vesicles. The plasma and intracellular concentrations of corticosterone further increased, whereas those of aldosterone fell below basal levels (the "aldosterone-escape" phenomenon). The activities of 3 beta HSD and 11 beta OH were enhanced, that of 180H decreased. Therefore, ACTH stimulates zona glomerulosa growth and transforms parenchymal elements into zona fasciculata cell-types. Cyanoketone nullified acute ACTH effects on plasma and intracellular concentrations of corticosterone and aldosterone, but did not affect the activities of 11 beta OH and 18OH. Chronic ACTH treatment produced similar results, although 18OH activity was not suppressed. The mechanism underlying the "aldosterone-escape" phenomenon may thus involve a rise in the intracellular concentration of corticosterone, caused by the enhanced synthesis and activation of 3 beta HSD and 11 beta OH.

3-Hydroxysteroid Dehydrogenases↗

PubMed1986

Effects of chronic administration of a methionine-enkephalin analogue on the zona glomerulosa of the rat adrenal cortex.

The effects of D-ala2-met-enkephalinamide (DALA) on the zona glomerulosa of dexamethasone-ACTH-treated rats were investigated by coupled radioimmunologic and morphometric techniques. Short-term DALA administration provoked a significant increase in the aldosterone plasma level along with a notable lipid droplet depletion in zona glomerulosa cells. Long-term DALA treatment induced a striking hypertrophy of zona glomerulosa cells and a further rise in the blood concentration of aldosterone. These findings seem to indicate that DALA is involved not only in the acute enhancement of aldosterone output but also in the stimulation of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

Adrenal Cortex↗

PubMed1986

Further studies on the effects of prolonged prolactin administration on the zona glomerulosa of the rat adrenal cortex.

The effects of a prolonged treatment with prolactin on the morphology and hormone secretion of adrenal zona glomerulosa of gonadectomized testosterone-replaced rats were investigated by coupled morphometric and radioimmunologic techniques. The dexamethasone/captopril-induced atrophy of zona glomerulosa cells (-42%) and fall in the blood level of aldosterone (-37%) were partially counteracted by chronic prolactin administration: the values had increased by about 15% and 17%, respectively, but remained lower than in the control animals. The prolonged treatment with prolactin of dexamethasone/captopril-administered ACTH/angiotensin II-replaced rats provoked a striking increase in the zona glomerulosa cell volume (24%) and in the blood level of aldosterone (33%) above the control values. The possibility is discussed whether prolactin may be directly involved in the stimulation of the growth and steroidogenic capacity of rat zona glomerulosa, without interacting with the gonads and interfering with the hypothalamo-hypophyseal axis and the renin-angiotensin system.

Adrenal Cortex↗

PubMed1986

Investigations on the effects of long-term administration of a methionine-enkephalin analogue on the adrenal zona fasciculata of rats treated with dexamethasone or dexamethasone and ACTH.

Prolonged (7 days) methionine-enkephalin (DALA) treatment provoked a dose-dependent increase in the volume of zona fasciculata cells of dexamethasone-administered rats, along with a notable rise in the plasma concentration of corticosterone and the activity of 11 beta-hydroxylase. Comparable dose-dependent effects were observed after chronic administration of ACTH to dexamethasone-suppressed rats. The chronic administration of the maximum dose of DALA (500 micrograms/kg/day) was found to significantly further the trophic action of ACTH on the zona fasciculata of dexamethasone-treated animals. It is suggested that enkephalins act independently of and synergistically with ACTH in stimulating the growth and steroidogenic capacity of the rat adrenal zona fasciculata.

Adrenal Cortex↗

PubMed1986

Evidence that long-term methionine-enkephalin administration stimulates rat adrenal zona fasciculata.

Short-term methionine-enkephalin (DALA) treatment did not induce evident changes in the adrenal zona fasciculata and in the basal corticosterone output of dexamethasone-treated rats administered with maintenance doses of ACTH. Conversely, prolonged (5 days) DALA treatment caused a notable hypertrophy of zona fasciculata cells, along with a significant increase in the plasma concentration of corticosterone. It is suggested that enkephalins exert a trophic action on the rat zona fasciculata.

Adrenal Cortex↗

PubMed1986

Further studies on the inhibitory effects of somatostatin on the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

Chronic somatostatin administration was found to partially reverse the ACTH-enhanced growth of the rat zona glomerulosa. The effect of somatostatin was completely superposable to that of captopril, a specific inhibitor of the angiotensin-converting enzyme, and the inhibitory actions of these two agents did not cumulate. Neither somatostatin nor captopril counteracted the ACTH-induced stimulation of the growth and steroidogenic capacity of the rat zona fasciculata. These findings support the view that somatostatin acts as an exclusive and specific modulator of the adrenoglomerulotrophic action of the renin-angiotensin system.

Adrenal Glands↗

PubMed1986

Short- and long-term effects of angiotensin II on the rat adrenal zona glomerulosa. A coupled stereological and enzymological study.

Long-term angiotensin II administration induced a time-dependent increase in the volume of rat zona glomerulosa cells and in the plasma concentration of aldosterone. Cell hypertrophy is coupled with comparable increases in the surface area per cell of mitochondrial cristae and in the activity per cell of 18-hydroxylase. 11 beta-hydroxylase activity was not affected. These findings allow to suggest that the angiotensin-II-enhanced growth of rat zona glomerulosa is associated with the de novo synthesis of 18-hydroxylase.

Adrenal Cortex↗

PubMed1986

Effects of prolactin administration on the zona glomerulosa of the rat adrenal cortex: stereology and plasma hormone concentrations.

The effects of short and prolonged treatments with prolactin on the morphology and hormone secretion of the rat adrenal zona glomerulosa were investigated by coupled morphometric and radioimmunological techniques. Short-term prolactin administration did not alter plasma aldosterone concentration or zona glomerulosa morphology. Conversely, chronic prolactin treatment caused both a notable hypertrophy of zona glomerulosa cells and a significant rise in the blood level of aldosterone. The possibility is discussed that prolactin may be involved in the control of the growth and steroidogenic capacity of the rat adrenal zona glomerulosa.

Adrenal Cortex↗