PubMed Health⌕ Search

Biomedical subjects

F Granata

Publications and source records attributed to F Granata.

At least 19 recordsLinked to original sources
PubMed2006

PRES: posterior or potentially reversible encephalopathy syndrome?

Posterior reversible encephalopathy syndrome (PRES) is an acronym that identifies a new clinico-neuroradiologic entity occurring in association with different conditions. We report a patient with eclamptic encephalopathy whose clinico-radiological picture normalised after prompt treatment. We suggest defining this condition as potentially RES, to emphasise that reversibility is not spontaneous but is usually related to an adequate treatment, and that the posterior localisation of the lesions, even if constant, may not represent the most relevant finding in some patients.

Adult↗
PubMed2004

Differential modulation of mediator release from human basophils and mast cells by mizolastine.

BACKGROUND: Basophils and mast cells play a major role in the pathogenesis of allergic disorders by releasing several proinflammatory mediators. Some histamine H1 receptor antagonists exert anti-inflammatory activities by modulating mediator release from basophils and mast cells. OBJECTIVE: To study the in vitro effects of mizolastine, an H1 receptor antagonist, on the release of eicosanoids, histamine and IL-4 from human basophils and lung mast cells. METHODS AND RESULTS: Mizolastine (10(-7)-10(-5) M) concentration-dependently inhibited the release of cysteinyl leukotriene C4 from anti-IgE-stimulated basophils (IC(50): 3.85+/-0.28 microM) and mast cells (IC(50): 3.92+/-0.41 microM). The same concentrations of mizolastine did not affect anti-IgE-induced prostaglandin D2 release from lung mast cells. In contrast, mizolastine enhanced up to 80% IgE-mediated histamine release (EC(50): 4.63+/-0.14 microM) from basophils, but not from mast cells and it significantly potentiated IL-4 release from basophils induced by anti-IgE. Mizolastine did not affect histamine release from basophils induced by formyl peptide, whereas it inhibited cysteinyl leukotriene C4 release (IC(50): 1.86+/-0.24 microM). Blockade of cytosolic phospholipase A2 and arachidonic acid mobilization by pyrrolidine-1 did not alter the effect of mizolastine on histamine release from basophils, thereby excluding accumulation of arachidonic acid metabolic intermediates as the cause of this effect. Mizolastine did not influence anti-IgE-induced activation of extracellular signal-regulated kinase-1 and -2 (ERK-1 and -2) in human basophils. CONCLUSIONS: Mizolastine efficiently inhibits LTC4 synthesis in human basophils and mast cells presumably by interfering with 5-lipoxygenase. In contrast, it enhances histamine and IL-4 release only from anti-IgE-stimulated basophils. Therefore, mizolastine differentially regulates the production of mediators from basophils and mast cells in a cell- and stimulus-specific fashion.

Antibodies, Anti-Idiotypic↗
PubMed2002

Cerebral angiography in the rat with mammographic equipment: a simple, cost-effective method for assessing vasospasm in experimental subarachnoid haemorrhage.

We report quantification of vasospasm following subarachnoid haemorrhage (SAH) and the effect of a new antivasospastic free radical scavenger (AVS) in rats, using an angiographic technique developed in our laboratory. We acquired single-exposure angiograms with mammographic equipment, using a 0.1 mm diameter focal spot and single-emulsion mammographic films. Contrast medium was injected through a PE50 catheter in the common carotid artery, after the external carotid artery had been ligated to divert flow towards the internal carotid artery territory. Measurements of the M1 and A1 segments and of the middle third of the basilar artery were made by projecting the angiograms directly as slides and using the endovascular catheter as an internal reference. We tested the technique on 40 male albino Sprague-Dawley rats divided into four groups: sham-operated+saline, SAH+saline, sham-operated+AVS and SAH+AVS. We were able to measure the diameter of the principal intracranial arteries in all the animals. With our technique, which is cost-effective when compared to many of those reported recently, we could detect intracranial vasospasm in all untreated rats with SAH, and confirm antivasospastic effects of AVS.

Animals↗
PubMed2002

Contrast-enhanced MR imaging with fat suppression in adult-onset septic spondylodiscitis.

Spinal infections typically involve vertebrae as well as discs, and for this reason they are called septic spondylodiscitis. Magnetic resonance imaging is the most sensitive imaging method for the evaluation of this group of spinal diseases. The use of contrast-enhanced T1-weighted sequences with fat suppression, if correctly applied, may increase information provided by MRI. Firstly, this technique allows the primary vertebral focus, which often precedes disc involvement, to be identified at a very early stage. When the disease spreads, T1-weighted fat-suppressed gadolinium dimeglumine (Gd-DTPA) enhanced images provide macroscopic details of the primary vertebral focus, disc involvement patterns, and pathways of infection diffusion. All this information, when correlated with laboratory tests, may be useful in identifying the infectious agents (tuberculous vs piogenic forms), thus enabling a suitable therapy to be started. This technique is also useful in the assessment of the real extension of the disease, providing a clear depiction of paravertebral space involvement and of psoas muscle abscesses. Dangerous complications, such as meningitis, myelitis, and epidural abscesses, may be more promptly diagnosed and fully evaluated with fat-suppressed post-contrast T1-weighted images. Finally, this imaging technique may help to differentiate infectious processes from degenerative disorders, extradural neoplastic processes, and rheumatic diseases.

Adipose Tissue↗
PubMed2001

Histamine induces exocytosis and IL-6 production from human lung macrophages through interaction with H1 receptors.

Increasing evidence suggests that a continuous release of histamine from mast cells occurs in the airways of asthmatic patients and that histamine may modulate functions of other inflammatory cells such as macrophages. In the present study histamine (10(-9)-10(-6) M) increased in a concentration-dependent fashion the basal release of beta-glucuronidase (EC(50) = 8.2 +/- 3.5 x 10(-9) M) and IL-6 (EC(50) = 9.3 +/- 2.9 x 10(-8) M) from human lung macrophages. Enhancement of beta-glucuronidase release induced by histamine was evident after 30 min and peaked at 90 min, whereas that of IL-6 required 2-6 h of incubation. These effects were reproduced by the H(1) agonist (6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)heptane carboxamide but not by the H(2) agonist dimaprit. Furthermore, histamine induced a concentration-dependent increase of intracellular Ca(2+) concentrations ([Ca(2+)](i)) that followed three types of response, one characterized by a rapid increase, a second in which [Ca(2+)](i) displays a slow but progressive increase, and a third characterized by an oscillatory pattern. Histamine-induced beta-glucuronidase and IL-6 release and [Ca(2+)](i) elevation were inhibited by the selective H(1) antagonist fexofenadine (10(-7)-10(-4) M), but not by the H(2) antagonist ranitidine. Inhibition of histamine-induced beta-glucuronidase and IL-6 release by fexofenadine was concentration dependent and displayed the characteristics of a competitive antagonism (K(d) = 89 nM). These data demonstrate that histamine induces exocytosis and IL-6 production from human macrophages by activating H(1) receptor and by increasing [Ca(2+)](i) and they suggest that histamine may play a relevant role in the long-term sustainment of allergic inflammation in the airways.

Calcium↗
PubMed2001

Treatment of mastocytosis: pharmacologic basis and current concepts.

Mastocytosis is a rare, heterogeneous disorder characterized by a marked increase in mast cell density in various tissues. Mast cells from different human tissues are heterogeneous. So far, there is no cure for systemic mastocytosis. Conventional therapy is based on agents that antagonize mediators released from mast cells, drugs that inhibit the release of mediators and agents that modulate mast cell proliferation. This pharmacologic approach is satisfactory in the majority of patients with indolent mastocytosis. At the beginning of the new millennium, the therapy of severe forms of aggressive mastocytosis remains a challenge for students of this intriguing disorder.

Adenylyl Cyclases↗
PubMed2001

Inhibitory effect of somatostatin on neutral amino acid transport in isolated brain microvessels.

In the presence of somatostatin-14 or some of its receptorial agonists, the uptake of large neutral amino acids by isolated brain microvessels was found to be inhibited up to 50%, no other transport system being affected. Although the luminal and abluminal sides of brain endothelial cells are both capable of taking up large neutral amino acids, only uptake from the abluminal side appears to be inhibited by somatostatin. The involvement of a type-2 somatostatin receptor was suggested by assays with a series of receptor-specific somatostatin agonists, and was confirmed by the release of inhibition caused by a specific type-2 receptor antagonist. A type-2-specific mRNA was indeed shown to be present in both bovine brain microvessels ex vivo and primary cultures of endothelial cells from rat brain microvessels.

Amino Acids, Neutral↗
PubMed2000

Secretory phospholipases A2 induce beta-glucuronidase release and IL-6 production from human lung macrophages.

Secretory phospholipases A2 (sPLA2s) are a group of extracellular enzymes that release fatty acids at the sn-2 position of phospholipids. Group IIA sPLA2 has been detected in inflammatory fluids, and its plasma level is increased in inflammatory diseases. To investigate a potential mechanism of sPLA2-induced inflammation we studied the effect of group IA (from cobra venom) and group IIA (human synovial) sPLA2s on human macrophages. Both sPLA2s induced a concentration- and Ca2+-dependent, noncytotoxic release of beta-glucuronidase (16.2 +/- 2.4% and 13.1 +/- 1.5% of the total content with groups IA and IIA, respectively). Both sPLA2s also increased the rate of secretion of IL-6 and enhanced the expression of IL-6 mRNA. Preincubation of macrophages with inhibitors of the hydrolytic activity of sPLA2 or cytosolic PLA2 did not influence the release of beta-glucuronidase. Incubation of macrophages with p-aminophenyl-mannopyranoside-BSA (mp-BSA), a ligand of the mannose receptor, also resulted in beta-glucuronidase release. However, while preincubation of macrophages with mp-BSA had no effect on beta-glucuronidase release induced by group IIA sPLA2, it enhanced that induced by group IA sPLA2. A blocking Ab anti-mannose receptor inhibited both mp-BSA- and group IIA-induced beta-glucuronidase release. Taken together, these data indicate that group IA and IIA sPLA2s activate macrophages with a mechanism independent from their enzymatic activities and probably related to the activation of the mannose receptor or sPLA2-specific receptors. The secretion of enzymes and cytokines induced by sPLA2s from human macrophages may play an important role in inflammation and tissue damage associated with the release of sPLA2s.

Aniline Compounds↗
PubMed2000

Phosphocholine and phosphoethanolamine during chick embryo myogenesis: a (31)P-NMR study.

Elevated contents of phosphoethanolamine (Etn-P) and/or phosphocholine (Cho-P), a common feature of most tumours with respect to normal counterparts, may also occur in non-cancerous proliferating tissues. The significance of these alterations in relation to cell proliferation, differentiation and maturation is scarcely understood. In this work, the Cho-P and Etn-P pools were measured by (31)P-NMR in extracts of chick embryo pectoral muscle at different days of development. The average concentration of these metabolites exhibited the highest values (respectively, 1.5 and 3.0 micromol/mg DNA) on days 9-11 and decreased at later stages of myogenesis. While, however, Cho-P maintained substantial levels (above 1.0 micromol/mg DNA) also during myotube formation (days 11-18) and stepwise decreased (to about 0.5 micromol/mg DNA) upon fibres' maturation, Etn-P gradually decreased between day 11 and hatching time (down to about 0.2 micromol/mg DNA). These results demonstrate that significant changes may occur in the steady-state pools of these metabolites during normal in vivo cellular development and differentiation, and are consistent with: (a) high rates of phospholipid biosynthesis reported in the literature for proliferating myoblasts; (b) sustained phosphatidylcholine synthesis maintained also during myoblast fusion; and (c) decreased requirement of phospholipid synthesis in the last phase of in ovo myofibre maturation.

Animals↗
PubMed1999

Immunological modulation of human cardiac mast cells.

Human mast cells, by elaborating various cytokines, chemokines and proinflammatory mediators play a complex role in several allergic and inflammatory disorders. Mast cells have been identified in human heart tissue in close proximity to the sarcolemma, in perivascular and adventitial locations and in the shoulder region of coronary atheroma. Human heart mast cells (HHMC) can be isolated from patients undergoing heart transplantation and can be immunologically activated in vitro to induce the release of tryptase, chymase, cysteinyl leukotriene C4 and prostaglandin D2. Several cytokines (e.g., stem cell factor and TNF-alpha) reside in secretory granules of HHMC. Mast cell density is increased in the hearts of patients with ischemic and idiopathic dilated cardiomyopathy. Cardiac mast cells might contribute to the evolution of atherosclerosis, dilated cardiomyopathy, cardiac and systemic anaphylaxis through the release of cytokines and vasoactive and proinflammatory mediators.

Arteriosclerosis↗
PubMed1993

Antiproliferative effects and DNA hypomethylation by 5-aza-2'-deoxycytidine in human neuroblastoma cell lines.

5-Aza-2'-deoxycytidine (5-AZA-CdR) is an inhibitor of DNA methylation, and its antileukemic activity has been shown in preclinical and clinical studies. This paper describes the ability of 5-AZA-CdR to inhibit DNA methylation, DNA synthesis and cell growth in several human neuroblastoma cell lines. The stability of cell growth inhibition was ascertained, as well as the ability of the metabolite thymidine to enhance the antiproliferative effect of 5-AZA-CdR. The activity of phosphorylating enzyme deoxycytidine kinase (dCK) was correlated to different levels of sensitivity in several cell lines. The results obtained indicate that 5-AZA-CdR may be an agent for the chemotherapy of neuroblastoma.

Antigens, Differentiation↗
PubMed1992

Expression in murine and human neuroblastoma cell lines of VGF, a tissue specific protein.

Screening by different means has demonstrated the presence, in human and murine neuroblastoma cell lines, of VGF, a gene product identified in a limited number of neuronal and endocrine cells. Indirect immunofluorescence and Western and Northern blot analyses have shown the presence of this protein in some of the tested lines, confirming that VGF is not an ubiquitous molecule. Further studies, using human SK-N-BE and murine N18TG2 lines, showed that VGF expression is upregulated during differentiation, suggesting that various species, including man, express VGF and regulate it in a similar manner. The subcellular localization of the protein, which is associated with vesicles, its electrophoretic molecular profile and its specific release under different conditions are all consistent with results reported in other cells. Neuroblastomas are thus added to the class of VGF-positive cells and provide a new in vitro model for investigation of the structural and functional properties of this protein.

Animals↗
PubMed1986

Safety profile of ofloxacin: the Italian data base.

In clinical trials performed in Italy, 2,003 patients, suffering from various infectious diseases, have so far been treated with ofloxacin. In most cases dosages of 200 mg, 300 mg or 400 mg b. i. d. have been used. In all, 130 adverse reactions have been recorded in 116 patients (5.8%): gastrointestinal events (mostly nausea, vomiting and gastric pain) in 4.8% of the patients, neurological events (mostly headache and insomnia) in 0.7%, cutaneous reactions in 0.4% and others in 0.5% cases. The drug-event causal relationship was assessed by the investigators as unlikely in 5.0% of the events, as possible in 47.1%, as probable in 31.4% and as almost certain in 16.5%. The severity of adverse reactions was judged as mild in 55% of the cases, as moderate in 38% and as severe in 7%. In 30 patients (1.5%), treatment was discontinued because of occurrence of side effects. Abnormal laboratory values probably related to treatment were reported in 25 patients (2.1%). Ofloxacin is well tolerated and shows a safety profile comparable with that of the best tolerated oral antibacterials.

Adolescent↗
PubMed1983

Ceftazidime in treatment of acute pulmonary exacerbations in patients with cystic fibrosis.

The pharmacokinetics and clinical efficacy of ceftazidime, a cephalosporin with activity against Pseudomonas aeruginosa, were studied in children with cystic fibrosis. Ceftazidime had high in vitro activity against P. aeruginosa strains isolated from our patients, with a mean MIC90 of 8 micrograms/ml. The first dose of 50 mg/kg IV of ceftazidime achieved serum concentrations of 40.8 +/- 19.7 micrograms/ml at one hour and 3.8 +/- 1 micrograms/ml at four hours after administration (mean values +/- SD). The MIC90 was exceeded by serum concentrations for up to three hours. The elimination of the drug from the blood followed a biexponential decay with an elimination half-life of 60.4 +/- 6.8 min and a total body clearance of 6.0 +/- 3.1 ml/min/kg. Renal clearance of the drug accounted for 75% of the total clearance; these are higher values than those reported for adults. Peak concentrations of ceftazidime in the sputum two hours after a single administration were 4.13 +/- 2.06 micrograms/ml; after seven and 14 days of treatment, sputum concentrations were significantly lower. Eleven children with acute pulmonary exacerbation were treated for 14 days with ceftazidime at a dose of 150 mg/kg/day (12 treatment courses). Significant clinical and radiologic improvements were obtained in nine of 12 patients. In six of 11 cases the P. aeruginosa count decreased by 10(4) CFU/ml. Ceftazidime was well tolerated, and no side effects appeared during treatment.

Acute Disease↗