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Biomedical subjects

A Ciaccia

Publications and source records attributed to A Ciaccia.

At least 37 records · Page 2Linked to original sources
PubMed1998

Detection of xanthine oxidase activity products by EPR and HPLC in bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease.

Xanthine oxidase (xanthine: oxygen oxidoreductase, EC 1.1.3.22), a molybdenum-containing hydroxylase that produces superoxide and uric acid from purine substrates and molecular oxygen, is involved in the oxidative stress underlying several human pathologies including lung diseases. An enzymatic activity similar to xanthine oxidase was previously reported in bronchoalveolar lavage fluid of patients with chronic obstructive pulmonary disease (COPD-BAL), by fluorometric analysis of DNA unwinding and cytochrome c reduction kinetics. Here we report the detection of xanthine oxidase activity products by electron paramagnetic resonance (EPR) in presence of the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and reversed-phase high-performance liquid chromatography (RP-HPLC) in COPD-BAL (n = 14, average age of patients 65 years, range 38-81) and BAL from healthy nonsmoker controls (n = 6, average age 64 years, range 44-73). Superoxide DMPO adducts were detected in COPD-BAL and in an in vitro system containing xanthine and xanthine oxidase (XA/XO), but not in BAL controls and when superoxide dismutase (SOD, 1000 I.U./ml) was added to COPD-BAL. The HPLC analyses after addition of xanthine showed production of uric acid in COPD-BAL and in the XA/XO system but not in BAL controls. These results support the involvement of xanthine oxidase in the mechanisms of superoxide production by BAL supernatant, which increases oxidative stress in chronic obstructive pulmonary disease.

Adult↗
PubMed1998

Hypo-osmolar aerosol induces hyperventilation in chronic non-asthmatic rhinitics.

The effect of a hypo-osmolar aerosol on transcutaneous O2 and CO2 time course (PtcO2, PtcCO2) was investigated in subjects affected by chronic non-atopic rhinitis, without any history of asthmatic symptoms and no airways hyper-responsiveness. Twelve normal subjects and 12 subjects affected by chronic idiopathic rhinitis, who had normal responsiveness to both hypo-osmolar aerosol and methacholine challenge as measured by the decrease in FEV1 (mean FEV1 decrease = 5% and PC20 > 16 mg, respectively) were studied. By means of a transcutaneous mono-electrode, it was possible to study the time course of PtcO2 and PtcCO2 during and after a 5-min inhalation of ultrasonically nebulized distilled water (output 2 ml/min-1). A significant decrease in PtcCO2 and increase in PtcO2 were observed during the challenge in rhinitics as compared with normal subjects [maximum decrease and maximum increase expressed as mean value (+/- SD) were -22% (+/- 6.9) and +12.6% (+/- 7.2), respectively]. No significant changes in either PtcCO2 and PtcO2 were observed after the test. The results of this study suggest that patients affected by idiopathic chronic rhinitis with absence of bronchial hyper-responsiveness may present a hyperventilatory response to the inhalation of hypo-osmolar aerosol; the mechanism of such a response might be due to an upregulation of the irritant receptors of the upper airways.

Adolescent↗
PubMed1998

Osteoprogenitor cells in cell populations derived from mouse and rat calvaria differ in their response to corticosterone, cortisol, and cortisone.

Osteoprogenitors present in cell populations derived from fetal or newborn rat and mouse calvaria differentiate in long term culture and form osteoblastic bone-forming colonies (bone nodules). Previous reports have indicated considerable differences between bone cell populations derived from these two species with regard to their proliferation in response to glucocorticoids. In the present investigation, we have focused on proliferation and differentiation of osteoprogenitor cells in these bone cell populations and evaluated the effect of corticosterone, the principal glucocorticoid of both mouse and rat. Cells were isolated by sequential collagenase digestion from calvaria of newborn (2-5 days) CD-1 mice [mouse calvariae (MC) cells] and term fetal Wistar rats [rat calvaria (RC) cells] and cultured for up to 25 days in alpha-minimal essential medium containing 10% fetal bovine serum (FBS), antibiotics, 50 microg/mL ascorbic acid, and 8-10 mmol/L beta-glycerophosphate. In agreement with previous observations by us and others, corticosterone increased cell growth in RC cell cultures, but inhibited cell growth in MC cultures. In RC cell cultures, corticosterone (1-1000 nmol/L) increased the nodule number in a dose-dependent manner (p < 0.001 for all concentrations above 3 nmol/L) with a maximal effect at 300 and 1000 nmol/L (threefold increase over control). In MC cells, on the other hand, corticosterone (0.3-1000 nmol/L) increased the nodule number only at 30 nmol/L (50%, p < 0.01) but inhibited nodule formation by 33% (p < 0.001) at 1000 nmol/L. In both RC and MC cultures a linear relationship was found between the number of cells plated and number of nodules formed. When cultures were treated with cortisol (30-300 nmol/L), similar effects were observed; the number of nodules dose dependently increased in RC cell cultures and dose dependently decreased in MC cell cultures. Significantly, however, the inactive glucocorticoid cortisone also increased bone nodule formation in RC cell cultures and decreased bone nodule formation in MC cell cultures. Carbenoxolone, which blocks 11 beta hydroxysteroid dehydrogenase and thus prevents conversion of cortisone to cortisol, partially inhibited the cortisone-induced effects on bone nodule formation in both RC and MC cell cultures, indicating that both RC and MC cells can convert inactive glucocorticoids to active metabolites. In conclusion, our results show that the glucocorticoids corticosterone and cortisol inhibit proliferation and differentiation of osteoprogenitors in MC cell cultures but stimulate these processes in rat-derived osteoprogenitors.

Animals↗
PubMed1998

Chronic obstructive pulmonary disease international guidelines.

Although chronic obstructive pulmonary disease (COPD) has a public health importance similar to asthma, it has received less attention. The first guideline on the management of COPD was released in 1987 by the American Thoracic Society. In 1992 the Canadian Thoracic Society released its guidelines. In 1995 the European Respiratory Society and the Thoracic Society of Australia and New Zealand released their guidelines and the American Thoracic Society updated and expand its COPD guidelines. All these documents were followed in 1997 by the guidelines developed by the British Thoracic Society. These COPD guidelines show many similarities but also have some interesting differences. The aim of this paper is to review these similarities and discrepancies. Like all guidelines, COPD guidelines suffer from the limited amount of evidence-based medicine supporting them, a limitation that, however, provides a strong stimulus for further research.

Female↗
PubMed1998

CD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease.

To investigate whether the inflammatory process in peripheral airways is different in smokers who develop symptoms of chronic bronchitis and chronic airflow limitation and in asymptomatic smokers who do not develop chronic airflow limitation, we examined surgical specimens obtained from 16 smokers undergoing lung resection for localized pulmonary lesions. Nine had symptoms of chronic bronchitis and chronic airflow limitation and seven were asymptomatic with normal lung function. In peripheral airways, immunohistochemical methods were performed to identify neutrophils, macrophages, CD4+ and CD8+ T-lymphocytes infiltrating the airway wall, and morphometric methods were used to measure the internal perimeter, the airway wall area, and the smooth muscle area. The number of CD8+ T-lymphocytes and the smooth muscle area were increased in smokers with symptoms of chronic bronchitis and chronic airflow limitation as compared with asymptomatic smokers with normal lung function, while the number of neutrophils, macrophages, and CD4+ T-lymphocytes were similar in the two groups of subjects examined. We concluded that smokers who develop symptoms of chronic bronchitis and chronic airflow limitation have an increased number of CD8+ T-lymphocytes and an increased smooth muscle area in the peripheral airways as compared with asymptomatic smokers with normal lung function, supporting the important role of CD8+ T-lymphocytes and airway remodeling in the pathogenesis of chronic obstructive pulmonary disease.

Aged↗
PubMed1997

Inflammatory cells in the bronchial glands of smokers with chronic bronchitis.

To characterize the inflammatory process in the bronchial glands of smokers with chronic sputum production, we examined lobar bronchi from 18 subjects undergoing lung resection for localized pulmonary lesions, all with a history of cigarette smoking. Nine of the subjects had symptoms of chronic bronchitis and chronic airflow obstruction, and nine were asymptomatic, with normal lung function. The number of neutrophils, eosinophils, mast cells, macrophages, CD4+ and CD8+ T-lymphocytes, and the ratio of CD4+ to CD8+ cells were assessed in the bronchial glands, epithelium, and submucosa. Cells were identified through immunohistochemistry. Smokers with symptoms of chronic bronchitis had an increased number of neutrophils (p = 0.01) and macrophages (p = 0.03) and a decreased CD4+/CD8+ ratio (p = 0.01) in the bronchial glands as compared with asymptomatic smokers. Chronic bronchitic smokers also had an increased number of epithelial neutrophils (p = 0.04), whereas the numbers of macrophages and CD4+ and CD8+ T-lymphocytes in the epithelium and submucosa were similar in the two groups of smokers. No differences in numbers of eosinophils or mast cells were observed between bronchitic and asymptomatic smokers in any of the compartments examined. In conclusion, smokers with chronic sputum production have an increased infiltration of neutrophils and macrophages and an increased proportion of CD8+ T-lymphocytes in their bronchial glands, supporting the important role of bronchial-gland inflammation in the pathogenesis of chronic bronchitis.

Aged↗
PubMed1997

Increased VIP-positive nerve fibers in the mucous glands of subjects with chronic bronchitis.

The presence and distribution of neuropeptide-containing nerves within bronchial surgical specimens has been investigated in bronchitic (n = 12) and in nonbronchitic subjects (n = 7). Lung tissue, obtained from patients undergoing thoracotomy for limited lung lesions, was processed immediately and analyzed for nerves using the streptavidin-biotin complex peroxidase method with antisera to the neural marker protein gene product 9.5 (PGP 9.5) and the neuropeptides vasoactive intestinal peptide (VIP), substance P (SP), calcitonin-gene related peptide (CGRP). There were no significant differences between the two groups with respect to the density of PGP 9.5-, SP-, or CGRP-positive nerves in both the locations assessed (smooth muscle layer and glands). The density of VIP-positive nerves was significantly higher in the glands of bronchitic than in nonbronchitic subjects. A negative relationship was found between the presence of airway inflammation, as indexed by mononuclear cell tissue infiltration, and the density of PGP 9.5-positive nerves in both smooth muscle and glands. Likewise, a relationship was found between the smoking history (packs/yr and age of onset of smoking) and the density of VIP-positive nerves in glands. These findings support a role for VIP in the hallmark of chronic bronchitis, i.e., sputum production.

Adult↗
PubMed1997

Subcutaneous emphysema of the chest wall: a case with unusual presentation.

Subcutaneous emphysema (SE) is the presence of air or other gas in the subcutaneous tissue and is generally associated with pneumothorax and/or pneumomediastinum. We describe an unusual presentation of SE of the chest wall without radiological evidence of pneumothorax or pneumomediastinum, which aetiopathogenesis remains open to several hypotheses in spite of an accurate clinical study.

Adult↗
PubMed1996

Xanthine oxidase activity in bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a serious respiratory pathology characterized by irreversible limitation of expiratory flow and includes chronic obstructive bronchitis, chronic airflow limitation, and emphysema. To determine whether xanthine oxidase activity increased in the airspaces of COPD patients, we examined bronchoalveolar lavage fluid (BAL) from COPD patients recruited during a 2-year clinical study. Filtered BAL supernatant from COPD patients and healthy nonsmoking controls was examined by fluorometric analysis of DNA unwinding (FADU) and spectrophotometric assays (cytochrome c reduction kinetics and uric acid kinetics). Compared to controls, filtered BAL supernatant of subjects with COPD exhibited a detectable clastogenic activity probably related to superoxide production. The method of BAL preparation as an acellular system strongly suggests that superoxide production may be due to xanthine oxidase activity.

Adult↗
PubMed1996

Effect of subchronic in vivo exposure to nitrogen dioxide on lung tissue inflammation, airway microvascular leakage, and in vitro bronchial muscle responsiveness in rats.

OBJECTIVES: In a previous study on bronchoalveolar lavage fluid from rats exposed in vivo for seven days to 10 ppm nitrogen dioxide (NO2), it has been shown that there is an influx of macrophages into the airways. The present study investigated the effect of seven day exposure to 10 ppm NO2, on: (a) lung tissue inflammation and morphology; (b) airway microvascular leakage; (c) in vitro contractile response of main bronchi. METHODS: Lung tissue was studied by light microscopy, after fixing the lungs by inflation with 4% formalin at a pressure of 20 cm H2O. Microvascular leakage was measured by extravasation of Evans blue dye in the larynx, trachea, main bronchi, and intrapulmonary airways. Smooth muscle responsiveness was evaluated by concentration-responses curves to acetylcholine (10(-9)-10(-3) M), serotonin (10(-9)-10(-4) M), and voltage-response curves (12-28 V) to electrical field stimulation. RESULTS: Histology showed an increased total inflammation at the level of respiratory bronchioles and alveoli. No influx of inflammatory cells was found in the main bronchi. A loss of cilia in the epithelium of small airways and ectasia of alveolar capillaries was also found. By contrast, no alterations to microvascular permeability or modification of bronchial smooth muscle responsiveness was found. CONCLUSIONS: Subchronic exposure to 10 ppm NO2 causes airway inflammation and structural damage, but does not cause any persistent alteration to microvascular permeability or bronchial smooth muscle responsiveness in rats.

Acetylcholine↗
PubMed1996

Association between toluene diisocyanate-induced asthma and DQB1 markers: a possible role for aspartic acid at position 57.

Toluene diisocyanate (TDI) is the most common cause of occupational asthma in western countries. The aim of this study was to investigate whether genetic factors are involved in toluene diisocyanate-induced asthma. We studied the frequency of human leucocyte antigen (HLA) class II genetic markers in three groups of subjects: 1) subjects with TDI-induced asthma (n = 30); 2) exposed subjects with no history of TDI-induced asthma (n = 12); and 3) normal subjects not exposed to TDI (n = 126). Venous blood samples were collected from the three groups and the polymorphic second exon of DQA and DQB genes was amplified by the polymerase chain reaction (PCR) method. Evaluation of HLA class II gene products in TDI-induced asthma cases showed a positive association with HLA-DQB1 * 0503 and a negative association with HLA-DQB1 * 0501 alleles, which differed at residue 57 for a single amino acid, i.e. aspartic acid in DQB1 * 0503 and valine in DQB1 * 0501. No significant difference was found in the distribution of DQA1 alleles between asthmatics and controls. Our results confirm the hypothesis that HLA-DQB1 * 0503 has a role in conferring susceptibility to TDI-induced asthma and that residue 57 of HLA-DQB1 is a potentially critical location.

Adult↗
PubMed1996

Oral vs inhaled asthma therapy. Pros, cons and combinations.

A number of oral and inhaled drugs are available for the long term management of patients with persistent asthma, yet the disease continues to be associated with significant morbidity and mortality. Over the past years, inhaled glucocorticoids have become established as a cornerstone of maintenance therapy because of their demonstrated clinical efficacy, ability to reduce bronchial inflammation and good tolerability. Other inhaled drugs (e.g. sodium cromoglycate, nedocromil, long-acting beta 2 agonists) also play a role in the long term treatment of patients with asthma. However, many patients (especially children and the elderly) find inhalers difficult to use, and poor inhalation technique can affect the amount of drug reaching the lungs and response to therapy. Oral drug administration is simple, but, until recently, oral asthma therapy has primarily consisted of sustained-release theophylline and glucocorticoids. Theophylline has a narrow therapeutic index, necessitating regular monitoring of serum drug concentrations, and long term oral glucocorticoid therapy is associated with potentially serious adverse events including osteoporosis with bone fracture. The recent development of orally administered leukotriene receptor antagonists (e.g. zafirlukast) and 5-lipoxygenase inhibitors (e.g. zileuton) offers novel mechanisms of action and potential solutions to compliance issues associated with regular administration of inhaled asthma therapy. These drugs have demonstrated efficacy as maintenance therapy in patients with asthma and, importantly, lack the adverse effects associated with long term systemic glucocorticoid therapy. Further clinical trials and the increasing use of these new therapies will help to establish the precise role of orally administered leukotriene receptor antagonists and 5-lipoxygenase inhibitors in the long term management of patients with asthma.

Administration, Inhalation↗
PubMed1996

Methotrexate in the treatment of systemic glucocorticoid-dependent severe persistent asthma: a word of caution.

Methotrexate should not be prescribed to every systemic glucocorticoid-dependent asthmatic. In fact, while methotrexate may be advantageous in selected patients, every attempt to control asthma with regular anti-asthma agents should be made. Most studies on the effects of methotrexate in the treatment of systemic glucocorticoid-dependent asthmatics include small numbers of patients and are all of relatively short duration. Thus, large long-term multicentre trials are urgently needed. In these studies, a uniform accepted definition of systemic glucocorticoid-dependent asthmatics should be used. For the time being, we reinforce the recommendation of the NHLBI/ WHO panel that methotrexate and other systemic glucocorticoid sparing drugs should be considered experimental medications, and used only in selected patients under the supervision of an asthma specialist with previous experimental experience.

Asthma↗
PubMed1996

Efficacy of topical tuaminoheptane combined with N-acetyl-cysteine in reducing nasal resistance. A double-blind rhinomanometric study versus xylometazoline and placebo.

The aim of this study was to functionally evaluate the decongestant effect of a topical intranasal drug (Rhinofluimucil consisting of tuaminoheptane sulphate (CAS 6411-75-2, THS), a vasoconstrictor, combined with N-acetyl-cysteine (CAS 616-91-1, NAC). This was a double-blind randomized study, versus both xylometazoline and placebo. 18 subjects (8M and 10F, aged 20-47 years), unaffected by any rhinitic pathology, underwent anterior rhinomanometry. Following the basal evaluation (T0), subjects were randomly divided into three groups and subjected, in a double-blind manner, to nasal instillations (2 puffs per nostril) of THS/NAC (R), xylometazoline (O) and saline solution (P), respectively. Rhinomanometry was repeated after 5, 10 and 20 min (T5, T10, T20). Resistance and flow were measured in both nostrils at a pressure gradient of 150 Pa. After R and O nasal resistance significantly decreased from 0.30 Pa to 0.19 Pa and from 0.31 Pa to 0.17 Pa, respectively, and flow significantly increased; no effects were observed with placebo. In this study, THS/NAC showed rapid decongestant properties, with a significant decrease of resistance and increase of inspiratory flow. The same finding was observed with xylometazoline, but not with the placebo. The decongestant effect was rapid: it could already be observed at T5, and remained constant up to T20 without any rebound effect.

Acetylcysteine↗