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Biomedical subjects

A Spada

Publications and source records attributed to A Spada.

At least 37 records · Page 2Linked to original sources
PubMed2004

Griseofulvin micronization and dissolution rate improvement by supercritical assisted atomization.

Supercritical assisted atomization (SAA) was used to micronize griseofulvin (GF), selected as a model compound, to verify the performance of this innovative process. SAA is based on the solubilization of supercritical carbon dioxide in a liquid solution containing the drug. The ternary mixture is then sprayed through a nozzle and microparticles are formed as a consequence of the enhanced atomization. Precipitation temperature and drug concentration in the liquid solution were studied to evaluate their influence on morphology and size of precipitated particles. A good particle size control was obtained and GF spherical particles with mean diameters ranging from 0.5 to 2.5 microm were produced with a narrow particle size distribution. Processed GF was characterized by high-performance liquid chromatography-UV/vis, headspace-gas chromatography-flame ionization detection, differential scanning calorimetry, BET and X-ray analyses. No drug degradation was observed and a solvent residue (acetone) less than 800 ppm was measured. GF microparticles showed good stability and surface areas ranging from about 4 to 6 m(2) g(-1); moreover, the micronized drug retained the crystalline habit. GF capsules were formulated with starch and used to compare the dissolution rate of SAA-processed and conventional jet-milled drug. A faster dissolution and a better reproducibility of the dissolution profile were observed for SAA-processed GF.

Antifungal Agents↗
PubMed2004

Circulating adiponectin levels and cardiovascular risk factors in acromegalic patients.

OBJECTIVE: Adiponectin (ApN) is an adipocytokine expressed in human adipose cells with anti-atherogenic and anti-inflammatory properties that plays a role in the pathophysiology of insulin resistance, metabolic syndrome and coronary artery disease. The aim of the study was to evaluate ApN secretion in patients with acromegaly, a chronic disease associated with insulin resistance and increased cardiovascular mortality, and to correlate ApN levels with hormonal, metabolic and cardiovascular parameters. DESIGN AND METHODS: The study included 32 patients with active acromegaly (11 male and 21 female, aged 48+/-11 years, duration of disease: 8+/-6 years, GH: 9.2+/-9.8 microg/l, IGF-I: 80+/-33 nmol/l (means+/-s.d.)) and 38 control subjects sex- and body mass index (BMI)-matched. In all subjects, serum ApN, leptin and ghrelin levels, BMI, waist circumference, insulin resistance (assessed by homeostasis model assessment and the quantitative insulin check index), lipid profile and blood pressure values were evaluated. RESULTS: Acromegalic patients and control subjects had similar ApN levels (9.4+/-3.5 vs 9.5+/-4.0 mg/l, NS), while when considering obese subjects acromegalic patients had ApN levels significantly higher than controls (10.2+/-4 vs 7.5+/-3 mg/l, P<0.05). No significant correlation between ApN and GH/IGF-I levels or duration of disease was found. ApN concentrations negatively correlated with BMI, waist circumference, glucose and diastolic blood pressure and positively with high-density lipoprotein cholesterol and ghrelin in controls, while all these correlations were lost in acromegalic patients. CONCLUSIONS: We provide evidence that, although metabolic and cardiovascular abnormalities are present in most acromegalic patients, in these subjects ApN levels are not reduced and, contrary to what is found in BMI-matched controls, do not correlate with cardiovascular risk factors. These data support the view that atherosclerosis is not the main determinant of cardiovascular mortality in acromegaly and suggest a permissive action of GH and/or IGF-I excess on ApN secretion.

Acromegaly↗
PubMed2003

Evidence of a secondary grapevine domestication centre detected by SSR analysis.

The origin of the grapevine was investigated with archaeobotanical, cultural and historical data. A primary domestication centre was located in the Near East region but there is no agreement on the existence or role of secondary domestication centres. In this work, PCR-based microsatellite analysis has been applied to study the origin of some Italian cultivated grapevines from in situ direct domestication of the wild autoctonous grapevine. Three different Italian locations in Grosseto, Cosenza and Nuoro were identified for this study, and domesticated grapevine as well as wild local accessions growing in these location, were analysed by SSR markers. Cluster analysis performed on Cosenza and Grosseto samples showed a high value of genetic distance between domesticated and wild accessions. On the contrary two cultivars (Bovale Murru and Bovale Muristellu) recovered in Nuoro (in the Sardinia island) were very close to some wild varieties. This suggests that the latter two cultivars may have originated from wild grapevines and consequently that in this location a secondary grapevine domestication event occurred. Six Lambrusco varieties were also included in this analysis as ancient putative ancestors of the cultivated grapevines. The molecular analysis excluded this hypothesis and suggest Lambrusco as an independent Vitis taxon.

DNA, Plant↗
PubMed2003

Brown jaw tumors: today's unusual presentation of primary hyperparathyroidism.

Primary hyperparathyroidism (pHPT) has changed its clinical features in the last decade becoming a mild biochemical disease, in which the classical fibrous cystic osteitis is a rare complication. The more frequent bone involvement in primary hyperparathyroidism is observed at the distal 1/3 of the radius, where the cortical bone is primarily represented. However, lumbar and femoral osteopenia or osteoporosis prevalently affect hyperparathyroid post-menopausal women. We report two, otherwise healthy, young male patients, who presented a painful jaw swelling. In both patients standard radiographic imaging revealed a low-density well-defined lesion, which caused jaw bone destruction. High levels of serum calcium (14.1-16.6 mg/dl, n.v. 8.1-10.4) and PTH (1172-1928 pg/ml, n.v. 10-65) indicated the presence of pHPT associated with hypertension, asymptomatic renal involvement and osteoporosis with normal serum 25-hydroxyvitamin D levels in both patients. A single huge parathyroid adenoma was successfully removed and within 2 months jaw lesions were almost completely re-mineralized without any other therapeutic intervention in both patients. In conclusion, although brown jaw tumors are a rare complication of the hyperparathyroidism, they should be considered and identified in young patients with severe pHPT. Moreover, such a complication seems to be independent from vitamin D deficiency, suggesting the involvement of other pathogenetic factors.

Adult↗
PubMed2003

Ghrelin secretion in severely obese subjects before and after a 3-week integrated body mass reduction program.

Ghrelin, the endogenous ligand of GH-secretagogue receptors, has been implicated in the regulation of feeding behavior and energy balance. Aim of the study was to investigate ghrelin levels in fasting conditions and after a standard meal test in obese subjects before and after a 3-week integrated body weight reduction (BWR) program (consisting of energy-restricted diet, exercise training, psychological counselling and nutritional education). Weight, height, fat mass, fat free mass (by impedentiometry), circulating ghrelin, insulin and leptin levels were evaluated in 10 obese subjects (3 male, 7 female; mean age: 35 +/- 9.3 yr; body mass index BMI: 45.2 +/- 10.6 kg/m2) before and after weight reduction. At baseline, obese subjects showed significantly lower ghrelin levels than controls, which were negatively correlated with BMI, weight, insulin and leptin levels. Fasting ghrelin levels were not modified by standard meal test in obese subjects (from 110.8 +/- 69.7 to 91.8 +/- 70.2 pmol/l p=ns), while a significant reduction was observed in controls (from 352.4 +/- 176.7 to 199.0 +/- 105.2 pmol/l; p<0.01). After a 3-week integrated BWR program obese subjects significantly reduced weight, BMI and leptin levels, while no significant changes were found both in fasting ghrelin and in ghrelin response after the meal. In conclusion, 5% weight loss obtained after a short-term period of integrated BWR program is not sufficient to normalize fasting ghrelin levels nor to restore the normal ghrelin suppression after a meal in severely obese subjects.

Adult↗
PubMed2003

Effects of hypothalamic neuropeptides on extracellular signal-regulated kinase (ERK1 and ERK2) cascade in human tumoral pituitary cells.

The G protein-coupled receptor (GPCR) activation has been demonstrated to affect the ERK1/2 cascade in different cell lines. We investigated the effects of hypothalamic neuropeptides acting via GPCR on this pathway in GH-secreting (GH-oma) and nonsecreting (NFPA) pituitary adenomas. GHRH increased ERK1/2 activity (236 +/- 80%) in both gsp- and gsp+ GH-omas, this effect being almost completely abolished by protein kinase C (PKC) blockade. Both GnRH and pituitary adenylate-activating peptide caused a similar PKC-dependent activation of ERK1/2 in most NFPA. Increasing cAMP by forskolin caused a protein kinase A-dependent increase of ERK activity (287 +/- 37%) in GH-omas and had no effect in NFPA. ERK cascade blockade in GH-omas did not affect basal and GHRH-stimulated GH release, whereas it totally prevented the 3-fold increase in cyclin D1 protein expression induced by GHRH. In conclusion, this study demonstrated that in pituitary adenomas the activation of GPCR by neurohormones caused a PKC-dependent activation of ERK1/2 cascade that, at least in GH-omas, resulted to be involved in cyclin D1 induction by GHRH. Moreover, a stimulatory effect of the protein kinase A-dependent pathway on ERK1/2 cascade occurred selectively in GH-omas, probably contributing to the mitogenic potential of the cAMP pathway in this cell type.

Adenoma↗
PubMed2003

Circulating ghrelin levels in patients with pancreatic and gastrointestinal neuroendocrine tumors: identification of one pancreatic ghrelinoma.

Ghrelin is a novel gastrointestinal hormone involved in several metabolic functions. Although the expression of ghrelin has been demonstrated in most gastrointestinal carcinoids and pancreatic tumors, the circulating levels of this peptide have been marginally assessed in patients with these disorders. We measured plasma ghrelin levels in 16 patients with gastrointestinal carcinoid (10 with midgut and 6 with gastric carcinoid), 24 patients with pancreatic tumor (8 with gastrinoma, 2 with insulinoma, 2 with vipoma, 1 with glucagonoma, and 11 with nonfunctioning tumor), and 35 healthy controls. Plasma ghrelin levels recorded in patients with gastroenteropancreatic tumors were similar to controls (mean +/- SE, 182.7 +/- 66.5 pM in patients vs. 329 +/- 32 pM in controls, P = not significant), and no significant difference between gastrointestinal and pancreatic, functioning and nonfunctioning, and metastatic and nonmetastatic tumors was observed. One patient with metastatic nonfunctioning pancreatic tumor had circulating ghrelin levels of 12,000 pM that were slightly reduced during chemotherapy and interferon therapy. Immunohistochemistry performed on peritoneal lesions showed an intense, focal cytoplasmic positivity for ghrelin. Despite the 50-fold increase in ghrelin concentrations, the patient had normal serum GH and IGF-I levels. In conclusion, the study showed that carcinoids and pancreatic tumors rarely cause ghrelin hypersecretion. However, in this series, 1 pancreatic ghrelinoma not associated with clinical features of acromegaly was identified.

Adolescent↗
PubMed2003

Ampicillin micronization by supercritical assisted atomization.

The micronization technique called supercritical assisted atomization (SAA) was used to produce ampicillin microparticles with controlled particle size and particle size distribution suitable for aerosol drug delivery. The process is based on the solubilization of supercritical CO2 in a liquid solution. The ternary mixture is then sprayed through a nozzle and, as a consequence of enhanced atomization, solid microparticles are formed. Water and organic solvents were tested with ampicillin to determine the influence of the solvent on the process mechanism. SAA process parameters were studied by testing different supercritical/liquid solvent flow ratios, ampicillin concentrations in the liquid solution and nozzle diameters. The effect of these parameters on morphology, particle size and particle size distribution of microparticles was analysed. Ampicillin particles suitable for aerosol delivery in the size range 1-5 microm were obtained using buffered water. Moreover, by varying the solute concentration, ampicillin particles in a narrower range (1-3 microm) than that usually suggested for aerosol deliverable drugs were obtained. This is an example of particle size tailoring by SAA.

Aerosols↗
PubMed2003

Plasma chromogranin A in patients with sporadic gastro-entero-pancreatic neuroendocrine tumors or multiple endocrine neoplasia type 1.

OBJECTIVE: As circulating chromogranin A (CgA) has been claimed to be the best general neuroendocrine marker so far available, we evaluated the usefulness of CgA determination in the clinical assessment of patients with sporadic gastro-entero-pancreatic neuroendocrine tumors (GEP NETs) or multiple endocrine neoplasia type 1 (MEN 1). DESIGN AND METHODS: Plasma CgA levels were measured using a commercial enzyme-linked immunosorbent assay in 61 patients with sporadic GEP NET and in 25 with MEN 1 including 16 with GEP NET. Controls were 50 healthy volunteers, 46 patients with pituitary adenoma and 35 patients with primary hyperparathyroidism. RESULTS: The cutoff value for CgA established in our healthy subjects (as mean+2 s.d.) was 20 U/l. CgA levels were above the normal range in 71/77 patients with sporadic or MEN 1-related GEP NETs (92%), in four out of nine MEN 1 patients without GEP NETs (44%), and only in 22/81 control patients with pituitary or parathyroid disease (27%). Furthermore, CgA levels of over 100 U/l occurred in 36/77 patients with GEP NETs (47%) and only in one patient with a non-functioning pituitary adenoma. In the patients with GEP NETs, both tumor burden and secretory activity affected CgA levels, and successful surgical resection was associated with markedly decreased CgA values. CONCLUSIONS: Plasma CgA was confirmed to be a reliable marker for GEP NETs. Moreover, in MEN 1 patients the finding of very high CgA levels strongly suggests the presence of a GEP NET, as both primary hyperparathyroidism and pituitary adenomas rarely cause marked CgA increases.

Adenoma↗
PubMed2003

[Genetic changes in human pituitary adenomas].

In the last few years molecular biology technologies have provided important insights into mechanisms possibly involved in pituitary tumor formation. Several evidences indicate that the majority of pituitary adenomas is monoclonal, thus implying that they derive from the replication of a single mutant cell. In about 30-40% of GH-secreting adenomas mutations at codon 201 and 227 of GNAS1 gene that codes for the Gs alpha subunit have been identified. These mutations, named gsp for Gs protein, cause the constitutive, hormone-independent, activation of adenylyl cyclase and consequent overproduction of cAMP, that is mitogenic in somatotropes. Screening studies carried out on large series of acromegalic patients carrying tumors with or without gsp oncogene failed to detect clinical differences between the two groups. The existence of mechanisms induced by gsp mutations and able to counteract the mitogenic potential of this oncogene has been hypothesized. In particular, several events including the low expression of mutant Gs, the induction of phosphodiesterases, that are involved in cAMP degradation, and of the inducible cAMP early repressor (ICER) that represses cAMP induced gene expression, together with a high sensitivity to somatostatin have been characterized in gsp positive tumors. As far as the loss of oncosuppressors is concerned, no mutations of these genes have been so far reported, while they are frequently expressed at low levels in pituitary tumors. However, the nature of initiating and promoting events involved in tumor formation remains to be clarified in the majority of pituitary tumors.

Adenoma↗
PubMed2002

Impaired estrogen-induced negative feedback on gonadotropin secretion in patients with gonadotropin-secreting and nonfunctioning pituitary adenomas.

BACKGROUND: Several in vitro studies suggest that gonadotropin-secreting pituitary adenomas (Gn-omas) and non functioning pituitary adenomas (NFPA) originate from gonadotroph cells. Patients with Gn-oma and NFPA frequently show abnormal gonadotropin response to TRH. The aim of the study was to investigate whether the estrogen-induced negative feedback is operating in either patients with Gn-oma or NFPA. MATERIALS AND METHODS: Serum gonadotropin levels were evaluated at 24 h after ethinylestradiol administration (1 mg per os; EE2 test) in seven patients with a diagnosis of Gn-oma, based on the presence of high follicle-stimulating hormone (FSH) and/or lutenising hormone (LH) levels with normal or high levels of sex steroids, in 22 patients with NFPA with normal or low levels of gonadotropin and sex steroids, and 30 sex- and age-matched healthy subjects. A normal response to EE2 test was arbitrarily defined as a serum LH and FSH decrease of at least 40 and 30% below basal levels. RESULTS: Among patients with Gn-oma, only one had a normal FSH inhibition and another, a normal LH inhibition. Among the 22 patients with NFPA, the EE2 test caused a normal FSH or LH reduction in 10 and 15, respectively, while a normal reduction of both FSH and LH was observed in nine. CONCLUSIONS: The study demonstrates that estrogen-induced negative feedback of gonadotropin secretion is disrupted in almost all patients with Gn-oma and in half of those with NFPA. This defective feedback is reminiscent of the resistance to thyroid hormones and glucocorticoids observed in patients with thyroid-stimulating hormone- (TSH-) and adrenocorticotropic hormone- (ACTH-)secreting adenomas, respectively.

Adenoma↗
PubMed2002

Mitogen-activated protein kinase cascade in human normal and tumoral parathyroid cells.

The calcium-sensing receptor (CaR) activation has recently been shown to modulate the ERK1 and ERK2 cascade in different cell lines. The present study investigated this pathway in human normal and tumoral parathyroid cells. In cells from normal parathyroids and almost all hyperplasia increasing extracellular calcium concentrations (Ca(o)(2+)) induced a significant activation of ERK1 and -2, the percent stimulation over basal activity (at 0.5 mM Ca(o)(2+)) being 545 +/- 140 and 800 +/- 205 in normal cells and 290 +/- 71 and 350 +/- 73 in hyperplasia at 1 and 2 mM Ca(o)(2+), respectively. This effect was mediated by CaR because it was mimicked by the receptor agonist gadolinium and neomycin. Basal and Ca(o)(2+)-stimulated ERK1 and -2 activity was nearly abolished by the PKC inhibitor calphostin C, and PKA changes did not affect ERK1 and -2 activity. PI3K blockade by wortmannin, known to prevent G protein betagamma subunit effect on ERK1 and -2, induced a 30% reduction of the Ca(o)(2+)-stimulated ERK1 and -2 activity. Adenomatous cells showed high PKC-dependent ERK1 and -2 activity in resting conditions that was unresponsive to high Ca(o)(2+). A role of MAPK on PTH secretion was suggested by the finding that PD98059, a specific MEK inhibitor, abolished the inhibitory effect of 1.5 mM Ca(o)(2+) on PTH release from normal parathyroid cells. In conclusion, these data first demonstrate that CaR activation, through the PKC pathway and, to a lesser extent, PI3K, increases ERK1 and -2 activity in normal parathyroid cells and this cascade seems to be involved in the modulation of PTH secretion by Ca(o)(2+). Interestingly, this signaling pathway is disrupted in parathyroid tumors.

Adenoma↗
PubMed2001

Absence of thyroid transcription factor-1 expression in human parathyroid and pituitary glands.

Thyroid transcription factor-1 (TTF-1), a tissue-specific nuclear transcription factor involved in the embryogenesis and differentiation of human thyroid, lung and brain, has been recently identified in other rat tissues, including parafollicular C cells and parathyroid chief cells. Based on this distribution, a possible role for this factor in calcium homeostasis has been suggested. This study investigated the presence of TTF-1 transcripts and protein in human tissues expressing the calcium sensing receptor (CaSR). Using a RT-PCR technique, complemented by Southern blot analysis, TTF-1 expression was detected in human C cells (two medullary thyroid carcinomas), but not in normal and adenomatous (four adenomas and three hyperplasia) parathyroid, and normal and adenomatous (six adenomas) pituitary tissues. CaSR was expressed in all samples. The absence of expression was confirmed by Western blot. In contrast to previous studies in the rat, this study demonstrates the absence of TTF-1 transcripts in the human adult parathyroid and pituitary glands, although a role for this factor during the ontogeny of these organs cannot be excluded.

Blotting, Western↗
PubMed2001

In vitro release of activin A from human normal and pathological thyroid tissues.

Activin A is a dimeric glycoprotein belonging to the transforming growth factor beta (TGF-beta) superfamily characterized by the ability to affect FSH secretion. Activin A was originally indicated as a gonadal product but the expression of activin A has been successively identified in several different tissues, including the thyroid gland. The aim of this study was to evaluate the release of activin A from human normal and pathological thyroid tissues in culture. Activin A concentration was evaluated in media obtained from primary culture of perinodular normal tissues (no.=2), hyperplastic hyperfunctioning thyroid tissues due to Graves' disease (no.=3) and autonomous thyroid adenomas (no.=3). Detectable levels of activin A were found in the incubation media from all tissues, without significant differences between normal and pathological samples. We conclude that activin A is secreted by follicle thyroid cells in normal and pathological conditions.

Activins↗
PubMed2001

Prognostic value of the acute DMSA scan in children with first urinary tract infection.

We attempted to verify in a group of 101 children with first urinary tract infection whether it was possible to identify groups of patients with different risks of developing renal scarring by taking into account both the extent of kidney involvement documented in the acute phase of infection using a dimercaptosuccinic acid (DMSA) scan, and the presence or absence of vesicoureteral reflux (VUR). The frequency of persistent lesions in kidneys with mild-moderate lesions (less than 50% of kidney involvement) in the presence of VUR or in non-refluxing kidneys was similar (P=0.1447), while the frequency of persistent lesions in kidneys with severe lesions in the presence of VUR was significantly higher than the frequency of persistent lesions in non-refluxing kidneys (P=0.0089). The extent of kidney involvement and the presence of VUR make possible the identification of different categories of risk of scarring: in the "low risk group" (normal kidney with/without VUR) the risk of scarring is 0%; in the "intermediate risk group" (mild lesions with/without VUR; extensive lesions without VUR) the risk of scarring is between 14% and 38%, while in the "high risk group" (extensive lesions with VUR) the risk of scarring is 88%. Quantifying the risk of scarring could help in planning the treatment or in modifying the later strategy.

Adolescent↗
PubMed2001

Acute renal cortical scintigraphy in children with a first urinary tract infection.

This prospective study, performed in 101 children with a first symptomatic urinary tract infection (UTI), evaluates the diagnostic value of clinical, biological, and ultrasound parameters in detecting children with acute renal infection documented by dimercaptosuccinic acid (DMSA) scintigraphy. In children with a positive DMSA scan, mean C-reactive protein (CRP) was higher than in children with a normal DMSA scan (114+/-64 vs. 67+/-38 mg/dl, mean+/-SD, P=0.0002). The sensitivity and specificity of CRP was 64% and 68%, respectively. In children with severe kidney involvement, mean CRP and white blood count (WBC) were higher than in children with mild/moderate disease (151+/-83 vs. 92+/-55 mg/dl for CRP, P=0.0149; 20,100+/-6,854 vs. 15,023+/-6,145 WBC/ mm3 for WBC, P=0.0131). The sensitivity and specificity was 85% and 20% for CRP, and 77% and 18% for WBC, respectively. One or more areas of abnormal cortical echogenicity were documented in 3% of kidneys with positive DMSA scans. Dilatation of the collecting system was observed in 24% of kidneys. The sensitivity and specificity of ultrasonography was 27% and 89%, respectively. In conclusion, clinical, biological, and ultrasound parameters do not accurately distinguish cystitis from pyelonephritis in children with UTI and do not identify children with severe renal damage. Accordingly, we recommend that DMSA scan should be added to the initial work-up of children with UTI.

Adolescent↗
PubMed2001

Activin A serum levels and aging of the pituitary-gonadal axis: a cross-sectional study in middle-aged and elderly healthy subjects.

Aim of the study was to investigate activin A serum concentration in healthy adult males and post-menopausal females over a wide age-range and its correlation to gonadotropins, inhibin B and testosterone concentrations. The study included 73 males (aged 30-101 years) and 42 postmenopausal females (aged 50-104 years). Blood samples were collected after an overnight fast to measure serum activin A, inhibin B, LH, FSH, and gonadal steroid levels. A significant increase in serum activin A levels over age in both genders, especially in the oldest age-groups, was observed. Serum inhibin B and testosterone concentrations showed a sharp decrease in male subjects, reflecting the age-related decrease of testicular function and by consequence serum FSH and LH significantly increased. In female subjects LH and FSH levels were very high in subjects in their 50s and showed a continuous decline due to pituitary aging. Simple and multivariable regression analyses demonstrated the lack of correlation between activin A and FSH in both males and females. In conclusion, a steep increase in activin A levels is present during aging in both genders, especially in the last decades of life. The physiologic role and site of production of activin A in old subjects remain to be clarified.

Activins↗