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Biomedical subjects

A Fasoli

Publications and source records attributed to A Fasoli.

At least 19 recordsLinked to original sources
PubMed1992

Effects of slow release bezafibrate on the lipid pattern and on blood glucose of type 2 diabetic patients with hyperlipidaemia.

Ninety-eight type 2 diabetic patients with hyperlipidaemia in stable metabolic control with diet alone (41) or diet plus hypoglycaemic agents (57) were divided into two groups: group 1 was put on treatment with slow release bezafibrate 400 mg a day, while group 2 was considered as control. In group 1, after 1 month of bezafibrate, serum triglycerides fell by 47% and cholesterol by 13%. HDL cholesterol showed a non-significant trend toward an increase. Fasting blood glucose significantly decreased by 6%, fructosamine and glycated haemoglobin by 5%. During OGTT, the area under the curve of both serum C-peptide and blood glucose showed a trend toward a decrease after bezafibrate. However, the difference did not reach statistical significance. Thirty-six patients continued the treatment with the drug for 4 months and 23 for 8 months, without further changes of the lipid pattern and glycaemic control. In the control group no significant variation of the lipid levels occurred and diabetic control slightly worsened during the study. Bezafibrate has been proved to be effective in the treatment of hyperlipidaemia in type 2 diabetic patients. The drug seems moreover to improve glycaemic control. The mechanism by which bezafibrate produces this latter effect remains to be elucidated, though an increase of peripheral insulin sensitivity might be suggested.

Aged↗
PubMed1992

Increased expression of endothelin in bronchial epithelial cells of asthmatic patients and effect of corticosteroids.

We have previously demonstrated that human bronchial smooth muscle cells possess specific binding sites for the potent bronchoconstrictive peptide endothelin 1 and that primary cultures of human bronchial epithelial cells constitutively produce an endothelin-like material that binds to smooth muscle cell receptors with a kinetic ability analogous to that shown by the authentic peptide. To evaluate the potential role of airway epithelium-derived endothelin in the pathogenesis of asthma, we have examined here the expression of endothelin in the bronchial epithelial cells of 6 patients with symptomatic asthma and reversible airflow obstruction. The epithelial cells of 5 normal volunteers and 5 patients with chronic bronchitis and airflow obstruction unaffected by bronchodilators were tested as controls. The bronchial epithelial cells of all the asthmatic patients expressed preproendothelin 1 mRNA, as assessed by in situ hybridization, and released high amounts of mature and biologically active endothelin during a 48-h period of incubation (radioimmunoassay). By contrast, the epithelial cells from normal donors did not contain preproendothelin 1 transcripts, and the endothelin-like material in their supernatants was invariably below the detection limit of the assay. Only a few cells from 2 patients with chronic bronchitis expressed preproendothelin mRNA and endothelin immunoreactivity. When hydrocortisone (10(-6)M) was added to the culture medium of asthmatic bronchial epithelial cells for 48 h, the release of immunoreactive endothelin significantly decreased (p < 0.025), but the numbers of cells expressing preproendothelin 1 mRNA did not change to the same extent.

Adrenal Cortex Hormones↗
PubMed1992

Effects of bezafibrate on biosynthesis of cholesterol and on degradation of native and acetylated low-density lipoproteins in incubated human monocytes.

The effects of bezafibrate on 14C-acetate incorporation into non-saponifiable lipids and on degradation of native and acetylated [125I] low-density lipoproteins (LDL) in cultured human monocytes has been evaluated. The presence of bezafibrate in the incubation medium resulted in a decrease of labelled acetate incorporation into non-saponifiable lipids. In parallel with the decrease in sterol synthesis, bezafibrate produced an increase in total and specific degradation of native low-density lipoproteins, whereas the degradation of acetylated low-density lipoproteins was not affected by the drug. These data, though obtained with concentrations of bezafibrate in the incubation medium greater than those encountered in ordinary therapeutic conditions, support the hypothesis that bezafibrate inhibits cholesterol biosynthesis and increases removal of low-density lipoproteins by activating the specific receptor pathway.

Bezafibrate↗
PubMed1991

Time course of IL1 and IL6 synthesis and release in human bronchial epithelial cell cultures exposed to toluene diisocyanate.

We have previously demonstrated that human bronchial epithelial cells release appreciable amounts of interleukin 1 (IL1) and interleukin 6 (IL6) when exposed to toluene diisocyanate (TDI) in vitro. TDI is an inflammatory and asthmogenic stimulus presumed to act at least in part through immunological mechanisms. The epithelial cell-derived IL1 and IL6 can promote T cell activation and proliferation in culture, and if this also happens in vivo they may contribute to the persistence of the inflammatory response of the bronchial mucosa observed in TDI-sensitive asthmatics. In this study, we confirmed the release of biologically active IL1 beta and IL6-like substances from bronchial epithelial cells exposed to isocyanates in vitro, and related the rate and the magnitude of the cytokine secretion with the pattern of IL1 beta and IL6 gene expression and the extent of epithelial cell injury. In the epithelial cell cultures exposed to TDI, there was a parallel, progressive increase in the expression of IL6 mRNA and in the secretion of IL6 protein between 48 hours and 6 days after exposure. By contrast, although increasing amounts of biologically active IL1 beta were detected in the supernatants of TDI-exposed epithelial cells throughout the 6-day period following exposure, augmented levels of IL1 beta mRNA were only evident 6 days after exposure, suggesting that TDI exposure might have initially affected the enzymatic cleavage of the intracellular IL1 beta precursor and the mechanisms which regulate the secretion of mature IL1 beta.

Blotting, Northern↗
PubMed1991

Levels of endothelin in the bronchoalveolar lavage fluid of patients with symptomatic asthma and reversible airflow obstruction.

We have previously demonstrated that human bronchial smooth muscle cells possess a single class of specific binding sites for the potent bronchoconstrictive peptide, endothelin 1, and that human bronchial epithelial cells constitutively release an endothelin-like material in culture, which binds to smooth muscle cell receptors with a kinetic analogous to that observed with the authentic peptide. To evaluate the potential role of endothelin in the pathogenesis of asthma, we examined in this study the release of endothelin in the airways of six patients with asthma, both at the time when they were symptomatic and had reversible airflow obstruction and during the remission phase of the disease induced by treatment. Five normal volunteers and five patients with chronic bronchitis and airflow obstruction unaffected by bronchodilators were tested as control subjects. The release of endothelin in airway mucosa was assessed by RIA with the bronchoalveolar lavage fluid recovered during bronchoscopy. Patients with asthma had increased amounts of immunoreactive endothelin in bronchoalveolar lavage fluid than normal control subjects or subjects with chronic bronchitis (p less than 0.05) in absence of any significant alteration in the levels of circulating peptide. Treatment of patients with asthma with oral corticosteroids and inhaled beta-agonists for 15 days resulted in improvement of airflow obstruction and in more than threefold reduction in the contents of endothelin in lavage fluid. Our findings indicate that the potent bronchoconstrictive substance, endothelin, may contribute to the pathogenesis of airflow obstruction in asthma.

Adult↗
PubMed1991

Cellular and biochemical characteristics of bronchoalveolar lavage fluid in symptomatic nonallergic asthma.

We have undertaken cellular and biochemical examination of bronchoalveolar lavage fluid from nonallergic patients with asthma to determine the nature and degree of inflammatory process in symptomatic asthma. Six patients with asthma (mean methacholine provocative concentration causing a 20% fall in FEV1 was 0.26 mg/ml) and six control subjects underwent fiberoptic bronchoscopy with bronchoalveolar wash. The patients with asthma shed a higher number of epithelial cells into lavage fluid than normal control subjects (p less than 0.05). Their lavage fluid also contained increased numbers of neutrophils (p less than 0.025), eosinophils (p less than 0.025), and basophilic cells (p less than 0.025), and increased proportion of activated T cells (p less than 0.05). The basophilic cells were mast cells, as indicated by positive labeling with the monoclonal antibody MCG35. Biochemical analysis of lavage fluid demonstrated exudation of protein molecules in airways of patients with asthma with increased contents of albumin (p less than 0.05) and fibronectin (p less than 0.05). In the lavage fluid of patients with asthma, there were also increased amounts of interleukin-1-beta (IL-1-beta) (p less than 0.025), interleukin-6 (IL-6) (p less than 0.025), and granulocyte-macrophage, colony-stimulating factor (GM-CSF) (p less than 0.05), as compared with lavage fluid of normal control subjects. Immunocytochemical evaluation of lavage cells demonstrated that IL-1-beta, IL-6, and GM-CSF were mostly produced by nonciliated epithelial cells and/or monocytes. IL-1, IL-6, and GM-CSF can prime granulocytes to respond to other stimuli and can promote T cell activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Human bronchial epithelial cells modulate CD3 and mitogen-induced DNA synthesis in T cells but function poorly as antigen-presenting cells compared to pulmonary macrophages.

This study was undertaken to investigate the ability of bronchial epithelial cells (ECs) to function as accessory cells. Pulmonary monocytes were our reference cells. ECs and pulmonary monocytes were isolated from the bronchial mucosa and pulmonary parenchyma of subjects undergoing lobectomy for standard clinical reasons. Circulating autologous T cells were rigorously depleted of accessory cells to the extent that they lost the capacity to respond to mitogenic lectins alone. ECs restored mitogen-induced DNA synthesis and DNA synthesis triggered by CD3 cross-linking in T cells, as did pulmonary macrophages, and this was unrelated to HLA-DR expression. The ability of promoting T cell proliferation after CD3 cross-linking was, in part, due to the secretory products of ECs, since their supernatants were also effective. Interferon-gamma-treated ECs were capable of presenting antigens to autologous T cells. This was an HLA-DR-restricted phenomenon, but EC efficiency in this system was less than 40% of efficiency demonstrated by pulmonary monocytes. However, ECs greatly upregulated antigen-specific responses supported by pulmonary monocytes.

Antigen-Presenting Cells↗
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↗
PubMed1978

An evaluation of quantitative agarose-gel electrophoresis of serum lipoproteins.

The method of Hatch et al. (Hatch, F.T., Lindgren, F.T., Adamson, G.L., Jensen, L.C. and Wong, A.W. (1973) J. Lab. Clin. Med. 81, 946-960) of quantitative determination of serum lipoproteins has been compared with preparative ultracentrifugation and chemical analysis of the lipoprotein fractions and a good concordance was demonstrated. The replacement of the coefficients proposed by Hatch et al. by the ones derived from the present study does not bring about relevant changes of the results when the harmonic mean of two calibration factors, derived from serum cholesterol and triglycerides, is used, thus indicating that this method of calculation minimizes the effect of variation of the chemical composition of lipoproteins. The method is sufficiently reliable and reproducible for practical pruposes and is recommended as the standard method for the clinical laboratory.

Cholesterol↗
PubMed1978

Low-fat diet versus low-carbohydrate diet in the treatment of type IV hyperlipoproteinaemia.

The response to dietary management was studied in 24 hypertriglyceridaemic out-patients. Fourteen patients were kept on a diet low in fat and cholesterol and high in polyunsaturated fatty acids; 10 of these patients subsequently followed a period of low-carbohydrate diet. At the end of the first period a significant decrease of serum triglyceride, cholesterol and beta-lipoproteins was observed; after the second feeding period no substantial change of serum lipoprotein pattern occurred. Ten patients were given a low-carbohydrate diet that produced a significant fall of the levels of triglycerides and pre-beta-lipoproteins. Six of these subjects continued the experiment with the low-fat diet; during this period a further trend toward reduction of serum triglyceride, cholesterol and beta-lipoproteins was observed which, however, was not statistically significant. We conclude that serum triglyceride levels can be lowered both by a low-carbohydrate diet and by a low-fat diet, but the latter has the advantage of also producing a significant fall of serum cholesterol and beta-lipoproteins.

Adult↗