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Biomedical subjects

E Ferretti

Publications and source records attributed to E Ferretti.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cardiac effects of slow-release lanreotide, a slow-release somatostatin analog, in acromegalic patients.

Cardiac involvement, mostly characterized by left ventricular hypertrophy associated with various degrees of cardiac dysfunction, greatly contributes to the increased mortality and morbidity observed in acromegaly. Lanreotide is a new SRIF analog characterized by a slow-release (SR) formulation with the peculiarity of a 30-mg im administration every 10-14 days. In this study, 13 patients with postoperative active acromegaly (9 females, 4 males, 45.9 +/- 16.3 yr old) underwent an echo-Doppler and hormonal study before and during a 12-month period of treatment with SR-lanreotide. GH and insulin-like growth factor I plasma levels (mean +/- SD) decreased significantly throughout the study period (from 10.1 +/- 2.2 to 3.9 +/- 0.9 ng/mL for GH, P < 0.005; and from 511.0 +/- 33.0 to 305.0 +/- 34.2 ng/mL for insulin-like growth factor I, P < 0.0001). Left ventricular mass index (mean +/- SD, 137.1 +/- 7.5 g/m2 at baseline) decreased after 3 months (120.0 +/- 5.4 g/m2), 6 months (111.7 +/- 5.7 g/m2), and 12 months (110.3 +/- 5.2 g/m2) of treatment (P < 0.005 at each time-point). This reduction in left ventricular mass index was accompanied by an improvement in some indexes of left ventricular diastolic function, especially the isovolumetric relaxation time (mean +/- SD, 109.1 +/- 4.6 m/sec at baseline), which decreased after 3 months (91.9 +/- 2.8 m/sec), 6 months (92.3 +/- 3.2 m/sec), and 12 months (92.2 +/- 3.0 m/sec) of treatment (P < 0.005 at each time-point). We conclude that SR-lanreotide is able to improve cardiac morphology and functional abnormalities in acromegaly; whether such beneficial effects on cardiac parameters will contribute to improve life expectancy in these patients should be further investigated.

Acromegaly↗
PubMed1999

Evaluation of the adequacy of levothyroxine replacement therapy in patients with central hypothyroidism.

As there are few data on the evaluation of the adequacy of levothyroxine (L-T4) therapy in patients with central hypothyroidism (CH), a prospective study was performed to assess the accuracy of various parameters in the follow-up of 37 CH patients. Total and free thyroid hormones, TSH, and a series of clinical and biochemical indexes of peripheral thyroid hormone action have been evaluated off and on L-T4 therapy. Samples were taken before the daily administration of L-T4. In all patients off therapy, clinical hypothyroidism and low levels of free T4 (FT4) were observed, whereas values of FT3, total T4, and total T3 were below the normal range in 73%, 57%, and 19% of cases, respectively. Most of the indexes of thyroid hormone action were significantly modified after L-T4 withdrawal and exhibited significant correlation with free thyroid hormone levels. During L-T4 replacement therapy, 32 patients had circulating levels of FT4 and FT3 and indexes within the normal range with a mean L-T4 daily dose of 1.5 +/- 0.3 microg/kg BW. Despite normal serum FT4, 3 patients had borderline high values of FT3 and a clear elevation of serum-soluble interleukin-2 receptor concentrations, suggesting overtreatment. Low or borderline low FT4/FT3 levels indicated undertreatment in 2 patients. The clinical parameters lack the required specificity for the diagnosis or follow-up of CH patients. The L-T4 daily dose should be established, taking into account the weight, the age, and the presence of other hormone deficiencies or pharmacological treatment of CH patients. In conclusion, our results indicate that the diagnosis of CH is reached at best by measuring TSH and FT4 concentrations. In the evaluation of the adequacy of L-T4 replacement therapy, both FT4 and FT3 serum levels together with some biochemical indexes of thyroid hormone action are all necessary to a more accurate disclosure of over- or undertreated patients.

Adult↗
PubMed1998

Evaluation of musk contamination of freshwater fish in Italy by accelerated solvent extraction and gas chromatography with mass spectrometric detection.

Musk compounds play an important role as perfuming agents for household chemicals, detergents and cosmetics. It has been demonstrated that the oral absorption of these compounds in humans is significant in the case of contaminated fish. In this study we developed a new extraction procedure, using an accelerated solvent extraction system and a gas chromatography-mass spectrometry detection method, for the determination of 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta [g]-2-benzopyran, 7-acetyl-1,1,3,4,4,6-hexamethyltetralin, 4-acetyl-1,1-dimethyl-6-tert.-butylindan, 6-acetyl 1,2,3,3,5-hexamethylindan and 5-acetyl-1,1,2,6-tetramethyl-3-isopropylindan in freshwater fish samples, collected from several Italian rivers and one lake. 6,7-Dihydro-1,1,2,3,3-pentamethyl-4-(5H)-indanon was used as internal standard. The method provides a rapid and highly extraction procedure, and is sensitive in determining these musk compounds in freshwater fish samples. This is the first report on the contamination from musk compounds in freshwater fish collected in Italy.

Animals↗
PubMed1998

The novel homeoprotein Prep1 modulates Pbx-Hox protein cooperativity.

The products of the mammalian Pbx and Drosophila exd genes are able to interact with Hox proteins specifically and to increase their DNA binding affinity and selectivity. In the accompanying paper we show that Pbx proteins exist as stable heterodimers with a novel homeodomain protein, Prep1. Here we show that Prep1-Pbx interaction presents novel structural features: it is independent of DNA binding and of the integrity of their respective homeodomains, and requires sequences in the N-terminal portions of both proteins. The Prep1-Pbx protein-protein interaction is essential for DNA-binding activity. Prep1-Pbx complexes are present in early mouse embryos at a time when Pbx is also interacting with Hox proteins. The use of different interaction surfaces could allow Pbx to interact with Prep1 and Hox proteins simultaneously. Indeed, we observe the formation of a ternary Prep1-Pbx1-HOXB1 complex on a HOXB1-responsive target in vitro. Interaction with Prep1 enhances the ability of the HOXB1-Pbx1 complex to activate transcription in a cooperative fashion from the same target. Our data suggest that Prep1 is an additional component in the transcriptional regulation by Hox proteins.

Animals↗
PubMed1998

Quantification of 17 beta-estradiol residues in bovine serum by liquid chromatography-tandem mass spectrometry with atmospheric pressure chemical ionization.

A method for the quantification of the natural hormone 17 beta-estradiol (17 beta-E2) in bovine serum by liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS-MS) was developed. Ethinylestradiol (EE2) was used as internal standard. Analytes were extracted from serum using acetate buffer, purified by C18 solid-phase extraction (SPE) and chromatographed on a polymeric reversed-phase (PLRP-S) LC column. They were ionized in a heated nebulizer (HN) interface operating in the negative ion mode, where only the intact deprotonated molecules, [M - H]-, were generated at m/z 271 and 295 for 17 beta-E2 and EE2, respectively. These served as precursor ions for collision-induced dissociation (CID) and diagnostic product ions were identified for the unambiguous hormone confirmation by selected reaction monitoring (SRM) LC-APCI-MS-MS. The method was validated on bovine serum and the limit of quantification (LOQ) was 30 pg ml-1 for 17 beta-E2. The inter-day precision (relative standard deviation, RSD) and accuracy (relative error, RE) derived from the analyses of validation samples at three concentrations ranged from 1.76 to 3.76 and from -4.18 to -2.01%, respectively. This method is currently being successfully applied to measure the bovine serum concentration of 17 beta-E2 in order to discriminate between the physiological concentrations of 17 beta/E2 and the hormone levels resulting from illegal administration.

Anabolic Agents↗
PubMed1998

Echocardiographic evidence for a direct effect of GH/IGF-I hypersecretion on cardiac mass and function in young acromegalics.

OBJECTIVE: The interpretation of echocardiographic abnormalities in acromegalic patients is complicated by non-specific age-related diseases, many of which are commoner in acromegaly. We have therefore investigated the cause-effect relationship between GH/IGF-I hypersecretion and precocious cardiovascular abnormalities in a series of young acromegalic patients. DESIGN: An open prospective study. PATIENTS: 20 acromegalic patients aged under 30 years, with normal blood pressure and glucose tolerance, and 20 age-matched control subjects. MEASUREMENTS: Cardiac morphological parameters and indices of systolic and diastolic function at rest were studied by Doppler echocardiography. RESULTS: Left ventricular mass (LVM) and LVM index (LVMi) were higher in acromegalics than in control subjects (215.0 +/- 15.4 g vs 140.8 +/- 8.5 g, P = 0.0002 and 109.8 +/- 5.9 g/m2 vs 82.1 +/- 3.7 g/m2, P = 0.0008, respectively), reaching values of left ventricular hypertrophy in 4 patients (20%). Both ejection fraction and fractional shortening were normal (66.4 +/- 2.1% vs 62.2 +/- 1.9% and 37.5 +/- 1.5% vs 35.8 +/- 1.3%, respectively), indicating normal left ventricular systolic function. Abnormalities of left and right diastolic ventricular filling were found, which consisted of an increased isovolumic relaxation time (99.2 +/- 2.7 ms vs 89.0 +/- 2.7 ms, P = 0.01) and impaired mitral and tricuspidal flow velocity curves. CONCLUSIONS: An increase in cardiac mass and subclinical biventricular diastolic dysfunction were observed in young acromegalic patients. These findings argue for a direct cause-effect relationship between GH/IGF-I hypersecretion and myocardial abnormalities, and indicate that careful cardiological evaluation is mandatory in all acromegalics, whatever their age.

Acromegaly↗
PubMed1997

Regulation of renal EGF receptor expression is normal in Denys-Drash syndrome.

In patients with Denys-Drash syndrome, mutations of the Wilms' tumor suppressor gene are associated with nephroblastomas and developmental abnormalities of the genital tract and renal glomerulus. Normally, the Wilms' tumor gene product (WT1) is expressed at high levels in visceral glomerular epithelial cells (VGEC) of the emerging fetal glomerulus. We demonstrate that WT1 could normally serve to suppress EGF receptor expression in VGEC, since immunoreactive EGF receptor is strikingly absent compared to epithelial cells of the emerging proximal and distal tubule, which lack WT1. When HEK293 cells were co-transfected with plasmids containing EGFR enhancer/promoter elements linked to a CAT reporter and plasmids containing WT1 cDNA, EGFR enhancer/promoter activity was suppressed by all wild-type WT1 isoforms, but not by deletion mutants of WT1 lacking normal zinc-finger or N-terminal domains. Surprisingly, plasmids expressing a Denys-Drash WT1 mutant (R394W) retained the ability to suppress EGFR promoter activity in this system. Furthermore, we found that immunoreactive EGFR was appropriately undetectable in glomeruli from a three-year-old girl with Denys-Drash syndrome and in sections of her Wilm's tumor. These data suggest that faulty suppression of EGFR cannot account for the abnormalities of glomerulogenesis seen in Denys-Drash patients.

Cell Line↗
PubMed1997

Insulin induces rapid changes of plasma leptin in lean but not in genetically obese (fa/fa) rats.

OBJECTIVES: To evaluate the plasma leptin concentration in lean and genetically obese fa/fa rats and to assess the response to 2 h hyperinsulinaemia. BACKGROUND: The recently discovered peptide leptin is a putative link between the size of the adipose mass and the hypothalamic centres controlling feeding behaviour. Several genetic models of animal obesity have been characterized as carriers of mutations of either the ob gene or leptin receptor. EXPERIMENTAL DESIGN: Lean (+/?) and obese (fa/fa) Zucker rats were studied under pentobarbital anaesthesia and underwent a 2 h euglycaemic hyperinsulinaemic clamp. Plasma leptin was measured in basal condition and at the end of the clamp study. Glucose rate of disappearance was evaluated by means of the isotope dilution technique using 3-3H-glucose as tracer. RESULTS: fa/fa rats showed a 40 fold higher leptin concentration compared to lean littermates (0.47 +/- 0.10 vs 19.55 +/- 1.50 ng/ml, P < 0.0001). Euglycaemic hyperinsulinaemia increased plasma leptin in lean but not in genetically obese rats. CONCLUSIONS: Our results suggest that insulin may be a regulator of in vivo leptin secretion by adipose tissue of lean rates whereas it is ineffective in increasing plasma leptin in obese Zucker rats.

Animals↗
PubMed1997

Role of guanine nucleotides as endogenous ligands of a kainic acid binding site population in the mammalian cerebellum.

An endogenous inhibitor of the membrane binding of kainic acid was extracted from pig brain tissue and purified. The substance was identified as GMP by structural analysis: Most likely it corresponds to an inhibitor previously extracted from the rat brain. The nucleotide is active as an inhibitor for kainate binding on goldfish brain synaptosomes, probably owing to direct displacement on receptor sites; it is also active on a low-affinity kainate site population in membranes from rat cerebellum. The interaction of GMP with the latter sites leads to a concentration-dependent kainate binding increase or inhibition, thus demonstrating that these sites can bind the nucleotide and cooperatively increase their affinity. Other guanine nucleotides show interaction with these sites, by either an increase (GTP) or inhibition (cyclic GMP or GDP) of kainate binding. These findings support the view that a guanine nucleotide is the endogenous ligand of a receptor in the mammalian cerebellum similar to the kainate binding protein present with high density in the cerebellum of lower vertebrates, whose function is probably connected to the role of the glial cells in this zone.

Animals↗
PubMed1997

Acute effects of octreotide, cabergoline and a combination of both drugs on GH secretion in acromegalic patients.

PURPOSE: The acute GH lowering effects of a single dose of either octreotide (OCT) or cabergoline (CAB), given alone and in combination, were studied in a series of 21 patients with acromegaly. PATIENTS AND METHODS: Plasma GH was measured for 8 hours after a single subcutaneous injection of OCT (100 micrograms) and for 48 hours after a single oral dose of CAB (0.5 mg) in all patients. Fourteen patients, who did not suppress GH levels below 5 micrograms/L after either OCT or CAB given alone, also received a combination of both drugs (OCT 100 micrograms s.c. + CAB 0.5 mg p.o. 24 h before OCT). RESULTS: GH levels were acutely suppressed by more than 50% in 15/21 cases after OCT alone and in 5/21 after CAB alone, respectively (P < 0.01). In the 14 patients who received the combined test, the magnitude of GH suppression was significantly higher than after OCT alone 4, 6 and 8 hours after OCT administration (P < 0.02). In patients with mixed GH/PRL-secreting tumors, the additive effect of OCT and CAB was observed at each time point. CONCLUSION: These results suggest that combined therapy with OCT and CAB may be more effective in suppressing GH secretion than either compound given alone, especially in patients with GH/PRL-secreting adenomas.

Acromegaly↗
PubMed1996

Mesenchymal regulation of differentiation of intestinal epithelial cells.

Intestinal epithelial differentiation requires the presence of mesenchyme, but the exact nature of this epithelial-mesenchymal interaction is unknown. The role of humoral and extracellular matrix factors in determining intestinal epithelial differentiation was examined by exposing a nontransformed, immature, rat small-intestinal cell line (IEC-6) to intestinal fibroblast-conditioned media or by growing the cells on matrix deposited by intestinal fibroblasts. Differentiation was assessed morphologically and by induction of the disaccharidase sucrase, which is a marker of intestinal epithelial maturation. When exposed to fetal intestinal fibroblast-conditioned medium or grown on extracellular matrix prepared from fetal intestinal fibroblasts, IEC-6 cells showed a significant increase in sucrase activity. The addition of cortisol to IEC-6 cells cultured on intestinal matrix also led to increased sucrase expression, as measured by enzyme activity and protein and messenger RNA levels. Ultrastructurally, cells cultured on intestinal fibroblast matrix in the presence of cortisol displayed a more differentiated phenotype. In contrast, there was no induction of sucrase activity in cells exposed to lung-conditioned media or grown on lung fibroblast matrix. These studies suggest that both humoral and matrix factors from intestinal mesenchyme are involved in intestinal epithelial differentiation and that these factors appear to be organ specific.

Animals↗
PubMed1996

Progesterone and estradiol inhibit CFTR-mediated ion transport by pancreatic epithelial cells.

The cystic fibrosis (CF), gene product, CF transmembrane conductance regulator (CFTR), is responsible for adenosine 3',5'-cyclic monophosphate (cAMP)-activated Cl- transport in epithelial cells, and mutant CFTR accounts for the pathology in the CF pancreas. We have previously shown that both isolated rabbit pancreatic acini and the human pancreatic duct cell line PANC-1 possess a cAMP-activated Cl- conductance identified as CFTR. We report here that preincubation in either of the female hormones progesterone or beta-estradiol inhibits activation by cAMP, but not by Ca2+ ionophore, of PANC-1 cell volume reduction under isotonic conditions. cAMP-activated cell volume reduction is sensitive to antisense, but not sense, CFTR oligodeoxynucleotide. Furthermore, progesterone inhibits cAMP-activated Cl- efflux from rabbit acinar cells. Moreover preincubation with progesterone, but not beta-estradiol, reduces CFTR mRNA and protein levels as measured using polymerase chain reaction amplification of reverse-transcribed acinar RNA and Western blots of protein from acinar membranes. We conclude that female hormones inhibit CFTR functional activity in pancreatic epithelial cells by different mechanisms.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Macroprolactinomas as cause of delayed puberty. A report of two cases and effects of medical therapy.

About 3-5% of pituitary tumors occur in pediatric patients, often showing a considerable severity during childhood and puberty and major difficulties in their therapeutic management. As far as macroprolactinomas are concerned, surgery is often not resolutive, so that the need for postoperative treatment, consisting of either radiotherapy or bromocriptine, is the rule for tumors with extrasellar extension. In the present manuscript we report two cases of macroprolactinomas in adolescent patients suffering from delayed puberty, short stature and ocular symptoms together with hormonal levels indicating the presence of hypopituitarism. In both patients bromocriptine therapy showed a particular efficacy both in controlling tumor size and growth and in reducing clinical signs and symptoms. We conclude proposing DA-therapy as a first line of management in adolescents affected by macroprolactinomas, even in the presence of neurological symptoms.

Adolescent↗
PubMed1995

Rabbit pancreatic acini express CFTR as a cAMP-activated chloride efflux pathway.

Cystic fibrosis transmembrane conductance regulator (CFTR) is responsible for adenosine 3',5'-cyclic monophosphate (cAMP)-activated chloride transport in epithelial cells. Isolated rabbit pancreatic acini possess a cAMP-activated chloride efflux mechanism distinct from zymogen granule secretion. To determine whether CFTR is expressed in acini, we used polymerase chain reaction (PCR) to amplify a 480-base pair (bp) sequence from reverse-transcribed rabbit acinar RNA. The PCR product was consistent with a 480-bp band amplified in T84 cells, and its sequence was > 90% homologous to human CFTR. CFTR antibody M3A7 recognized a 180- and a 160-kDa protein from acinar membranes consistent with bands seen in Chinese hamster ovary (CHO) cells transfected with CFTR. To determine if CFTR was responsible for the cAMP-activated chloride efflux previously demonstrated in pancreatic acini, we incubated acinar cells for 20 h with 1.75 microM CFTR antisense or sense oligodeoxynucleotide. Chloride efflux, in response to 8-bromoadenosine 3',5'-cyclic monophosphate and phorbol ester but not to calcium ionophore, was selectively inhibited by CFTR antisense oligodeoxynucleotide. Antisense oligodeoxynucleotide did not inhibit acinar amylase secretion. These findings indicate that isolated pancreatic acini can be used for future studies of CFTR expression and function.

Amylases↗
PubMed1994

Homogeneous pyrimidine nucleotidase from human erythrocytes: enzymic and molecular properties.

A pyrimidine nucleotidase with unique specificity has been obtained for the first time as an homogeneous protein from the cytosolic fraction of human erythrocytes. Both conventional chromatography and f.p.l.c. techniques have been used in the purification procedure. The final enzyme preparation gave a single protein band of M(r) = 23,500 on SDS/PAGE under both reducing and non-reducing conditions. The native enzyme was eluted at M(r) = 45,000 in gel filtration chromatography on Superose 12, suggesting a dimeric structure. Amino acid analysis was consistent with an acidic isoelectric point and revealed the presence of six half-cystine and two methionine residues per subunit. The enzyme was active on a variety of pyrimidine nucleoside monophosphates, being most active on the 3'-monophosphates. Km values for 3'dUMP, 3'UMP, 5'dUMP, 5'UMP, 5-fluoro-2'dUMP, ranged from 192 microM to 1.15 mM. The enzyme activity was inhibited by both reaction products, orthophosphate, and the nucleoside formed. Product inhibition studies suggested an Ordered Uni-Bi mechanism for the reaction. The enzyme required Mg2+ for its activity, while heavy metals cations were strongly inhibitory. The enzyme activity was inhibited by metal chelating agents and it was sensitive to thioreactive reagents. The isoelectric point was 5.4 and the optimum activity pH was 6.5.

5'-Nucleotidase↗
PubMed1994

Histological study of pancreatic beta-cell loss in relation to the insulitis process in the non-obese diabetic mouse.

Non-obese diabetic (NOD) mice spontaneously develop an autoimmune diabetes with higher incidence in females than in males. In order to elucidate possible factors involved in the different incidence of diabetes between male and female mice, we studied the progression of pancreatic beta-cell loss in relation to mononuclear cell infiltration of the pancreas (insulitis). We examined the pancreas of 76 NOD mice (39 males and 37 females) of different ages. The beta-cell content was assessed by immunoperoxidase staining of sections with an anti-insulin serum and the severity of insulitis was determined by haematoxylin staining of the same sections. A semi-quantitative criterion was used to grade both parameters. The results showed that females have a faster loss of beta-cell mass, which progressively decreases with the increase of severity of insulitis. In males, a medium to severe degree of insulitis is required before initial loss of beta cells occurs. Under the age of 10 weeks there was a significantly lower content of beta cells in females than males (2.84 +/- 0.03 vs 2.67 +/- 0.07; P = 0.02). Since we never observed a significant difference in the degree of mononuclear cell infiltration in age-matched males and females, these data support the hypothesis of weaker beta-cell resistance to immunological attack in female mice. Thus beta-cell sensitivity, in addition to immunological activity, is an important factor in the pathogenesis of insulin dependent diabetes.

Aging↗