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Biomedical subjects

A Fasoli

Publications and source records attributed to A Fasoli.

At least 55 records · Page 3Linked to original sources
PubMed1991

The protective effect of frusemide on the generation of superoxide anions by human bronchial epithelial cells and pulmonary macrophages in vitro.

Inhaled frusemide has been shown to inhibit bronchoconstriction induced by immunological and nonimmunological stimuli in asthmatic patients. The mechanisms by which this compound exerts its effect in asthmatic airways are unknown, but an inhibitory action on the activation of inflammatory cells or on the responsiveness of sensory epithelial nerves may be involved. In this study, we give evidence that frusemide prevents in part the activation of bronchial epithelial cells and pulmonary macrophages, as it reduces the rate of superoxide anion generation induced by IgE receptor cross-linking and by phorbol myristate acetate by 40-60%. The effect was not specific since we used stimuli which activate different signal transduction pathways for NADPH oxidase stimulation and frusemide was equally effective.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1991

A bronchial epithelial cell-derived factor in asthma that promotes eosinophil activation and survival as GM-CSF.

We have examined the in vitro interaction between bronchial epithelial cells and eosinophils derived from five asthmatics by determining the effect of epithelial cell-conditioned medium on the survival and activation of peripheral blood eosinophils. The supernatants of epithelial cells from six normal donors were used as control. The asthmatic epithelial cell-conditioned medium significantly increased the survival of eosinophils cultured for 3 (P less than 0.025) and 6 (P less than 0.05) days. The incubation of eosinophils with the supernatants of asthmatic epithelial cells for 1 h also increased the generation of superoxide anion and the release of leukotriene C4, triggered by phorbol myristate acetate and calcium ionophore, by more than twofold. The preincubation of asthmatic epithelial cell-conditioned media with saturating concentrations of a mono-specific antiserum against granulocyte-macrophage colony-stimulating factor (GM-CSF) completely abolished their activity, whereas the addition of recombinant human GM-CSF restored it. The supernatants of asthmatic epithelial cells contained 0.88 +/- 0.09 (SD) ng/5 X 10(5) cells immunoreactive GM-CSF, and this amount was significantly greater than that measured in the supernatants of normal epithelial cells (0.21 +/- 0.105, P less than 0.025). Bronchial epithelial cells from asthmatics also expressed increased levels of GM-CSF mRNA when compared with normal epithelial cells. Thus both the synthesis and release of GM-CSF by bronchial epithelial cells are upregulated in asthma, and this may contribute to the persistence of eosinophil infiltration and activation in asthmatic airways.

Adult↗
PubMed1991

Interleukin-1 binds to specific receptors on human bronchial epithelial cells and upregulates granulocyte/macrophage colony-stimulating factor synthesis and release.

Cultured human bronchial epithelial cells constitutively produce granulocyte/macrophage colony-stimulating factor (GM-CSF). An upregulation of the synthesis and release of GM-CSF from those cells might contribute to the persistence of infiltration and local activation of inflammatory cells in some inflammatory diseases of the airways, such as asthma. Increased levels of immunoreactive and biologically active interleukin-1 (IL-1) have been identified in the airway secretions of asthmatic patients, together with an increase in GM-CSF contents. As IL-1 is known to upregulate GM-CSF production in many cell populations, in this study we investigated the ability of IL-1 to bind to specific receptors on bronchial epithelial cells and promote GM-CSF synthesis and release. Bronchial epithelial cells possessed specific single-class surface receptors for recombinant IL-1. The addition of exogenous IL-1 led to a dose-dependent increase in the accumulation of GM-CSF mRNA and release of immunoreactive GM-CSF to the culture medium. Release of IL-1 in the bronchial mucosa during allergic and nonallergic responses may lead to enhanced GM-CSF synthesis and release by epithelial cells, thus promoting airway inflammation.

Binding, Competitive↗
PubMed1991

Mechanisms of calcium mobilization and phosphoinositide hydrolysis in human bronchial smooth muscle cells by endothelin 1.

We have previously demonstrated that human bronchial smooth muscle cells possess a single class of high-affinity binding sites for endothelin 1. In this study, we further characterized the receptor for endothelin 1 and evaluated the signal transduction mechanisms of this peptide. Stimulation of cultured human bronchial smooth muscle cells with endothelin 1 induced mobilization of Ca2+ from both intracellular and extracellular pools with a biphasic increase in cytoplasmic free Ca2+ concentration. Endothelin 1 increased cellular levels of inositol phosphates and diacylglycerol, indicating activation of phospholipase C, but induced production of inositol phosphates in smooth muscle cell membranes only in the presence of guanosine 5'-O-(thiotriphosphate) (GTP gamma S). Treatment of smooth muscle cells with pertussis toxin failed to block the endothelin 1-induced increase in inositol phosphate production and Ca2+ mobilization. These results suggest that the receptor for endothelin 1 in bronchial smooth muscle is coupled to phospholipase C through a pertussis toxin-insensitive G protein. Affinity crosslinking experiments identified the endothelin 1 receptor as a single band with an apparent molecular weight of approximately 70,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis, further supporting the functional evidence that endothelin 1 receptor belongs to the G protein-linked rhodopsin type of receptor superfamily.

Bronchi↗
PubMed1991

[Effects of etozoline in patients with acute cardiac failure].

Fifteen patients (10 M, 5 F; mean age 68.3 years) with acute heart failure III-IV NYHA class, were treated with etozoline (mean daily dose 666 mg) for 7 days. Symptoms of cardiac decompensation disappeared; no changes of blood pressure and heart rate were recorded. Daily urine volume increased from 790.9 +/- 327.0 ml to 1622.7 +/- 220.6 ml and body weight decreased from 71.5 +/- 5.8 kg to 69.6 +/- 5.2 kg. No changes of serum Na+, urinary Na+ excretion, appeared, but K+ excretion increased and serum K+ fell from 4.1 +/- 0.4 mEq/l to 3.6 +/- 0.45 mEq/l. No subjective side effects were reported. Renal-liver function and glyco-lipid balance were not affected. In conclusion, etozoline is a safe and effective diuretic agent in the treatment of acute cardiac failure.

Acute Disease↗
PubMed1990

Bronchial epithelial cells exposed to isocyanates potentiate activation and proliferation of T-cells.

Bronchial epithelial cells release chemotactic factors for lymphocytes and express HLA-DR antigens. Thus they may contribute to the T-cell-mediated inflammatory responses involved in a number of pulmonary diseases such as asthma. In this study, the in vitro exposure of human bronchial epithelial cells to toluene 2,4-diisocyanate (TDI), an inflammatory and asthmogenic stimulus presumed to act at least in part through immunological mechanisms, provoked cell damage followed by proliferation of the cells that survived the injury. At the time of the proliferative response, epithelial cells released factors that upregulated the activation and proliferation of T lymphocytes presensitized by antigen receptor triggering. The T-cell activating factors were interleukin (IL) 1- and 6-like substances, as demonstrated by the ability of specific antisera to inhibit most of the biological effect, and by the ability of recombinant IL-1 and IL-6 to reproduce it. Appreciable amounts of immunoreactive IL-1 and IL-6 were indeed recovered in the supernatants of TDI-exposed epithelial cells. The release of these cytokines may represent an important mechanism by which epithelial cells respond to some environmental stimuli and contribute to the persistence of inflammatory responses in the airways.

Alkaline Phosphatase↗
PubMed1990

Nedocromil sodium prevents the release of 15-hydroxyeicosatetraenoic acid from human bronchial epithelial cells exposed to toluene diisocyanate in vitro.

The in vivo exposure to an asthmogenic stimulus, toluene diisocyanate (TDI), causes airway epithelial damage associated with inflammation and increased bronchial hyperresponsiveness. The latter mechanisms might partly be mediated by the release of eicosanoids from bronchial epithelial cells. We have previously demonstrated that the in vitro exposure of bronchial epithelial cells to TDI results in the release of immunoreactive 15-hydroxyeicosatetraenoic acid (15-HETE), a product of activation of the 15-lipoxygenase pathway with inflammatory properties. In the present study we show that TDI-induced release of 15-HETE from epithelial cells can be prevented by nedocromil sodium, an anti-asthmatic drug with anti-inflammatory properties. This mode of action of the compound may explain its clinical effectiveness in asthma.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Specific binding of endothelin on human bronchial smooth muscle cells in culture and secretion of endothelin-like material from bronchial epithelial cells.

Endothelin, synthesized by endothelial cells, is the most potent vasoconstrictor and bronchoconstrictor agent known. We investigated endothelin release from human bronchial epithelial cells and the binding of the peptide to autologous bronchial smooth muscle cells in culture. Epithelial and smooth muscle cells were isolated by enzymatic digestion of bronchial tissue obtained on surgery, and cultured to confluency by standard methods. Epithelial cells stained positively for cytokeratin filaments. Smooth muscle cells stained uniformly for alpha-smooth muscle actin. Immunoreactive endothelin contents in the supernatants of epithelial cells extracted on C8 Amprep columns were evaluated by radioimmunoassay. Epithelial cells released appreciable amounts of immunoreactive endothelin into the culture medium (from 0.65 to 2.1 pmol/ml). A single specific binding site for [125I]endothelin 1 was identified on bronchial smooth muscle cells with an apparent Kd of 113 pM and a maximal binding capacity of 22.1 fmol/10(6) cells. At room temperature the binding was saturable, reached equilibrium at 120 min (25 pM endothelin 1), and was slowly and incompletely reversed by unlabeled endothelin over a period of 8 h. Conditioned medium from epithelial cells inhibited the [125I]endothelin 1 binding, dose dependently, and the effect was antagonized by monospecific antiserum. Thus, human bronchial smooth muscle cells possess specific binding sites for endothelin 1 and human bronchial epithelial cells secrete an endothelin-like material. This may have a role in the pathogenesis of asthma.

Binding Sites↗
PubMed1989

Inhibition of cholesterol biosynthesis in freshly isolated blood mononuclear cells from normolipidemic subjects and hypercholesterolemic patients treated with bezafibrate.

Bezafibrate was given for 15 days at a dose of 200 mg t.i.d. to 4 normolipidemic subjects, to 5 patients with putative heterozygous familial hypercholesterolemia, and to 6 patients with primary hypercholesterolemia of the non-familial type. At the end of the treatment, the rate of incorporation of labelled acetate into non-saponifiable lipids in freshly isolated blood mononuclear cells decreased in all subjects. On the average, acetate incorporation decreased by 31% in cells from normolipidemic subjects, 41% in cells from familial, and 45% in cells from non-familial hypercholesterolemia patients. Results of the present study suggest that the lowering effect of bezafibrate on serum cholesterol is mainly due to the inhibition of cholesterol synthesis through the suppression of HMG-CoA reductase as was demonstrated in rat hepatocytes and in cultured human blood mononuclear cells.

Adult↗
PubMed1988

Changes in serum and lipoprotein lipids, and apolipoprotein B and A-I, in patients with different types of primary hyperlipoproteinaemia treated with gemfibrozil.

Gemfibrozil was given at the dose of 600 mg twice daily to 16 type IIa, 13 type IIb and 11 type IV hyperlipoproteinaemic patients for four months. At the end of the fourth month of therapy low-density lipoprotein (LDL) cholesterol decreased on the average by 18% in type IIa, by 11% in type IIb and increased by 37% in type IV patients. Very-low-density lipoprotein (VLDL) cholesterol and triglycerides fell by 57% in type IIb and by 58% and 76% respectively in type IV subjects. High-density lipoprotein (HDL) cholesterol rose in all groups of patients owing to the increase of the HDL2 subfraction. However, in type IIa the change did not reach the level of statistical significance. Apoprotein B decreased in type IIa and in type IIb patients and apoprotein A-I significantly increased in type IIb and IV patients. The individual changes in total VLDL and LDL lipids and in apoprotein B could be related to their pretreatment level. The cholesterol triglyceride ratio significantly increased in LDL and HDL fractions and the effect was greater in the subgroup of patients with the greatest abnormality in lipoprotein lipid composition. On the whole the differential effects of gemfibrozil on serum lipoprotein concentration and composition in the various types of hyperlipoproteinaemia can be regarded as a trend toward a normalization and may be explained by the multiple effects of the drug on lipid metabolism.

Adolescent↗
PubMed1985

Changes in the serum lipoprotein pattern induced by two low-fat diets with a different vegetable content in hypercholesterolemic patients.

Thirty-two hypercholesterolemic outpatients were treated by a conventional low-fat diet (carbohydrate 56%; fat 25%; vegetable proteins 7%; animal proteins 12% of energy; P/S ratio 1.0). After 1 month T-C decreased by 11%, VLDL-C by 32%, LDL-C by 8%, HDLt-C by 10% and HDL2-C by 11%. Thirty-two comparable patients were treated by a different low-fat diet which provided 69% of energy as carbohydrate, 19% as fat, 7% as vegetable proteins and 5% as animal proteins; P/S ratio was 1.3. After 1 month T-C decreased by 9% and LDL-C by 12%. VLDL-C, HDL2-C and HDL3-C did not change significantly. A cross-over study on 24 patients confirmed that both diets have lowering effects on T-C and LDL-C levels, but only the conventional low-fat diet decreases VLDL-C and HDL2-C.

Adult↗
PubMed1984

[Significance of certain neoplastic markers in a series of patients with lung cancer].

Perchloric acid soluble proteins (PPS) and their content of N-acetylneuraminic acid (NANA) may serve as valuable tumor markers for a variety of malignant neoplasms. To evaluate their clinical significance, PPS, NANA and carcino-embryonic antigen (CEA) were measured in 32 patients with lung cancer. High PPS (greater than or equal to 0,73 mg/ml) and NANA (greater than or equal to 96 micrograms/ml) levels occurred in 8 of 50 (16%) healthy volunteers and respectively in 22% and 54% of patients. CEA levels were high (greater than or equal to 3 ng/ml) in 1 out of 21 (5%) healthy volunteers and in 83% of the patients; 84% of the patients showed an elevation of NANA and of CEA. The highest values of the three markers seem to be associated with extensive disease but no statistically significant difference has emerged from the comparison of patients with limited disease with the ones with extensive involvement. Changes of the tumor mass correlate with changes of serum levels of PPS, NANA and CEA. It is concluded that CEA determination is clinically valuable in lung cancer, while PPS and NANA do not provide greater information.

Adult↗
PubMed1984

Fenofibrate therapy of hypertriglyceridaemia. Differential effects on LDL cholesterol level in type IV and in type IIb primary hyperlipoproteinaemia.

Twenty five hypertriglyceridaemic patients (16 Type IV and 9 Type IIb) were treated with fenofibrate 300 mg/d. In Type IV patients serum triglycerides and VLDL cholesterol decreased, while LDL and HDL cholesterol rose significantly. In Type IIb patients, triglycerides and total, VLDL, IDL and LDL cholesterol were significantly reduced by the treatment. The correction of hypertriglyceridaemia by fenofibrate seems, therefore, to induce different changes in lipoproteins in Type IIb and in Type IV hyperlipoproteinaemic patients. The practical implications of these results are discussed.

Adult↗