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Biomedical subjects

A Vatrella

Publications and source records attributed to A Vatrella.

At least 19 recordsLinked to original sources
PubMed2006

ISSQoL: a new questionnaire for evaluating the quality of life of people living with HIV in the HAART era.

OBJECTIVE: To design a Health-related Quality of Life (HRQoL) instrument for HIV-infected people in the era of highly active antiretroviral therapy (HAART). METHODS: The self-administered questionnaire was developed by an Italian network including researchers, physicians, people living with HIV, national institutions and community-based organizations (CBO) through several steps: (1) review of existing HRQoL literature and questionnaires for HIV-infected people; (2) selection of relevant domains measuring HRQoL in HIV-infected people, and identification of new domains related to new aspects of HRQoL concerning HAART-treated individuals; (3) conduction of two pre-test analyses in independent groups of Italian HIV-positive people (n approximately =100) distributed throughout the country. The objectives of the first pre-test were to verify the usefulness of the questionnaire, to construct a form easily understandable by everyone, to define the domains and their significance; the second pre-test aimed at evaluating and reshaping the questionnaire based on a statistical analysis of the outcomes of first pre-test; (4) validation analysis. A large cohort of people with HIV infection was recruited for the last step. RESULTS: The internal consistence reliability (Cronbach's alpha) was >or=0.70 for all domains. Most domains had Cronbach's coefficient >0.80. All domains demonstrated convergent and discriminant validity. The final version of ISSQoL includes two sections: HRQoL Core Evaluation Form (9 domains) and Additional Important Areas for HRQoL (6 domains). The ISSQoL was administered together with two additional forms: a Daily Impact of Symptoms Form and a Demographic Information Form. The Additional Important Areas for HRQoL include social support, interaction with medical staff, treatment impact, body changes, life planning, and motherhood/fatherhood. CONCLUSION: The data reported in the present paper provide preliminary evidence of the reliability and validity of the ISSQoL questionnaire for the measurement of HRQoL in HIV-infected people. The direct involvement of HIV-positive people in all the phases of the project was a key aspect of our work.

Adult↗
PubMed2003

Molecular mechanisms of corticosteroid actions in chronic inflammatory airway diseases.

Although corticosteroids have been used for a long time as a very effective therapy of airway inflammatory diseases such as asthma, only recently the molecular basis of their mechanism of action has begun to be elucidated. These hormones exert their biological and pharmacological actions by binding to cytoplasmic receptors that, upon activation, translocate to the nucleus where they interact with specific genomic sequences thus modulating gene expression. However, many glucocorticoid effects responsible for their anti-inflammatory and anti-asthmatic activity take place irrespectively of receptor binding to DNA. In particular, ligand-bound glucocorticoid receptors can repress several different pro-inflammatory genes by physically associating, via protein-protein interactions, with various transcription factors and with the macromolecular complexes implicated in regulation of chromatin structure and function. In this regard, an important role is played by the influences of corticosteroids on the intrinsic histone acetyltransferase and deacetylase functions of coactivators and corepressors, respectively. Furthermore, the signal transduction pathways mediated by mitogen-activated protein kinases are newly recognized, key targets of glucocorticoids. Indeed, these enzymatic cascades are crucially involved in the regulation of gene expression in that they are essential for the activity of a high number of transcription factors. Therefore, the recent advances made in such a rapidly growing research field are providing new insights into the mode of action of corticosteroids, thereby also unveiling novel promising therapeutic strategies directly targeted to the molecular events underlying the inflammatory, immune, and apoptotic processes implicated in the pathogenesis of asthma and other airway diseases.

Asthma↗
PubMed2002

Potential role of potassium channel openers in the treatment of asthma and chronic obstructive pulmonary disease.

Airway smooth muscle (ASM) cells express various types of potassium (K+) channels which play a key role in determining the resting membrane potential, a relative electrical stability and the responsiveness to both contractile and relaxant agents. In addition, K+ channels are also involved in modulation of neurotransmitter release from airway nerves. The most important K+ channels identified in airways include large and small Ca2+-activated, delayed-rectifier, and ATP-sensitive channels. These K+ channels are structurally and functionally different, thus playing distinct roles in airway electrophysiology and pharmacology. Many in vitro and in vivo studies, performed in both animals and humans, have shown that K+ channel openers are able to induce hyperpolarization of ASM cells, bronchodilation, suppression of airway hyperresponsiveness (AHR), and inhibition of neural reflexes. Therefore, airway K+ channels represent a suitable pharmacological target for the development of new effective therapeutic options in the treatment of asthma and chronic obstructive pulmonary disease (COPD).

Animals↗
PubMed2002

Inhaled ultrasonically nebulized distilled water decreases exhaled nitric oxide in asthma.

Exhaled nitric oxide (eNO) is increasingly used as a marker of disease activity in asthma. Inhaled hypertonic saline has been shown to induce bronchoconstriction and to decrease eNO in asthmatic subjects, whereas the effects of hypotonic solutions on eNO in these patients have not been studied. To evaluate the effect of ultrasonically nebulized distilled water (UNDW), an indirect hypotonic stimulus, on eNO, 17 asthmatic patients were enrolled and eNO from lower airways was measured by chemiluminescence. UNDW significantly reduced FEV(1) >or= 20% in 9 subjects (UNDW+), but had no effect in eight patients (UNDW-). Baseline eNO concentration were found to be 51.3 +/- 11.1 ppb in UNDW+ and 32.9 +/- 7.5 ppb in UNDW- patients, respectively ( p = 0.199, NS). UNDW inhalation significantly decreased eNO (from 51.3 +/- 11.1 ppb to 31.0 +/- 7.1 ppb in UNDW+ ( p < 0.020, n = 9) and from 32.9 +/- 7.5 ppb to 26.2 +/- 7.3 ppb in UNDW- subjects ( p < 0.024, n = 8), respectively). eNO percentage reduction in UNDW+ patients was significantly higher compared with UNDW- subjects (-37 +/- 4% vs -23 +/- 3%, p = 0.021). There was no correlation between FEV(1) changes and eNO percentage decreases in both UNDW+ and UNDW- subjects. In UNDW+ patients, acute bronchodilation induced by salbutamol caused a recovery in both FEV(1) and eNO, though eNO levels remained lower than baseline values. We concluded that UNDW inhalation can significantly decrease eNO in asthmatic patients, either responders or nonresponders to this indirect osmotic challenge; the reduction in eNO levels was only partly dependent on acute changes in airway caliber.

Administration, Inhalation↗
PubMed2001

Effects of glucocorticoids on activation of c-jun N-terminal, extracellular signal-regulated, and p38 MAP kinases in human pulmonary endothelial cells.

Mitogen-activated protein kinases (MAPK) play a central role in signal transduction by regulating many nuclear transcription factors involved in inflammatory, immune, and proliferative responses. The aim of this study was to investigate, in human pulmonary endothelial cells, the effects of synthetic glucocorticosteroids on activation of c-jun N-terminal kinases, extracellular signal-regulated kinases, and p38 subgroups of the MAPK family. Human microvascular endothelial cells from lung were stimulated for 2 h with either H(2)O(2) (2 mM), IL-1beta (10 ng/mL), or tumour necrosis factor-alpha (10 ng/mL). Under these conditions, a remarkable increase in the phosphorylation pattern of c-jun N-terminal kinases, extracellular signal-regulated kinases 1/2, and p38 was detected. Pretreatment for 12 h with dexamethasone (100 nM) was able to prevent phosphorylation-dependent MAPK activation in stimulated cells, without substantially affecting the expression levels of these enzymes. Our results suggest that inhibition of MAPK signaling pathways in human pulmonary endothelial cells may significantly contribute, by interfering with activation of several different transcription factors, to the antiinflammatory and immunosuppressive effects of glucocorticosteroids.

Cells, Cultured↗
PubMed2001

Effect of inhaled heparin on water-induced bronchoconstriction in allergic asthmatics.

OBJECTIVE: The aim of this study was to investigate the effect of inhaled heparin on bronchoconstriction induced by ultrasonically nebulised distilled water (UNDW) in allergic asthmatics. METHODS: Eight atopic asthmatics, hyperresponsive to UNDW, were selected for this randomised, placebo-controlled, crossover double-blind study. On two consecutive days, these subjects underwent a UNDW challenge 45 min after inhaling aerosolised heparin (1000 U/kg) or placebo. RESULTS: Neither heparin nor placebo had a significant effect on base-line forced expiratory volume in 1 s (FEV1), but heparin significantly attenuated UNDW-induced bronchoconstriction, as shown by its efficacy in preventing the decreases in FEV1 produced by all doses of water (in comparison with placebo: P < 0.05 after 2 ml water; P < 0.01 after 4, 8 and 16 ml water). CONCLUSION: Inhaled heparin is able to exert a protective effect against the bronchoconstrictive response to UNDW in allergic asthmatics, and this action is likely due to inhibition of mast cell degranulation.

Administration, Inhalation↗
PubMed2001

Effects of non-bronchoconstrictive doses of inhaled propranolol on airway responsiveness to methacholine.

OBJECTIVES: The aim of this study was to evaluate the effects of non-bronchoconstrictive doses of propranolol on airway hyperresponsiveness to methacholine. METHODS: Double increasing concentrations (from 0.03 to 64 micrograms/ml) of inhaled propranolol were administered to a study population which included ten patients with mild asthma, ten rhinitics, and ten healthy control subjects. After the baseline bronchial responses to propranolol and methacholine, expressed as the cumulative provocative dose producing a 20% fall in forced expiratory volume in 1 s (PD20FEV1), were assessed, methacholine challenge was repeated after pretreatment with non-bronchoconstrictive doses of propranolol. RESULTS: The pharmacologically induced beta-blockade did not cause any effect in normal individuals, but it worsened airway responsiveness to methacholine in all asthmatics (geometric mean PD20 FEV1: 257 and 87 micrograms, respectively) and some rhinitics (geometric mean PD20 FEV1: 724 and 446 micrograms, respectively). CONCLUSION: Asthmatic patients were extremely sensitive to beta-blockers, whereas we observed a variable response to propranolol within the group of rhinitic subjects. This variability in the latter group is possibly because these individuals had different degrees of airway inflammation, increased parasympathetic activity, and beta-adrenoceptor dysfunction.

Administration, Inhalation↗
PubMed2001

Exhaled nitric oxide after inhalation of isotonic and hypotonic solutions in healthy subjects.

Airway nitric oxide (NO) homoeostasis is influenced by chemical and mechanical stimuli in humans; airway epithelium, which is an important site of NO production, is sensitive to osmotic challenge. The effect of inhaled hypotonic solutions on exhaled NO (eNO) is not known. In this study we evaluated the effect of ultrasonically nebulized distilled water (UNDW), a hypotonic indirect stimulus, on eNO levels. A total of 10 non-smoking healthy subjects were enrolled in the study. eNO was detected by chemiluminescence, and specific airway conductance (sGaw) was measured by plethysmography. Bronchial challenges with UNDW and with an isotonic solution were performed according to a double-blind experimental design. Baseline levels of eNO were 28.1+/-14.7 p.p.b. UNDW did not cause any significant change in sGaw (from 0.190+/-0.029 to 0.181+/-0.036 cm H(2)O x s(-1)). With respect to baseline values, the eNO concentration decreased significantly after inhalation of 8 or 16 ml of UNDW (from 26.0+/-13.1 to 17.2+/-8.5 and 16.6+/-7.7 p.p.b. respectively; P<0.001, n=10). After bronchial challenge with UNDW, eNO was significantly reduced in comparison with after inhalation of the isotonic solution. In five subjects, pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor NO synthesis, decreased NO levels from 21.7+/-8.5 to 10.0+/-3.3 p.p.b. Subsequent inhalation of 16 ml of UNDW did not cause any further decrease in NO levels (10.1+/-3.7 p.p.b.; not significant compared with L-NAME). We conclude that inhalation of aqueous solutions decreases eNO levels in healthy subjects, and that this effect is not associated with any significant change in airway calibre. The UNDW-induced decrease in eNO is not enhanced by pretreatment with the NO synthase inhibitor L-NAME, suggesting that inhaled solutions may interfere with the airway NO pathway in humans.

Adult↗
PubMed2000

New perspectives in asthma treatment.

The recent advances in the knowledge of the basic mechanisms underlying asthmatic inflammation have significantly contributed to the delineation of new therapeutic perspectives for asthma. There are currently three main approaches to the development of novel antiasthma treatments: 1) improvement in existing classes of drugs 2) identification of new compounds able to interfere with the complex network of proinflammatory mediators, cytokines, chemokines, and adhesion molecules involved in the pathogenesis of asthma 3) utilization of new forms of immunotherapy aimed at blocking the unbalanced Th2 response which characterizes the pathophysiology of asthma. Such a remarkable expansion in available therapeutic options will probably allow us, over the next decade, to treat asthma by more selectively targeting the pathogenetic events responsible for this widespread airway disease.

Anti-Asthmatic Agents↗
PubMed1997

Inhaled beclomethasone dipropionate (BDP) prevents seasonal changes in atopic asthmatics.

Inhaled corticosteroids are most effective drugs currently available for the treatment of bronchial asthma. They have been shown to reduce airway inflammation and hyperresponsiveness. The aim of this study was to assess the preventive effect of inhaled steroid therapy in seasonal asthma. In a double-blind study, two groups of 10 allergic asthmatics were randomly assigned to receive inhaled beclomethasone dipropionate (BDP), 500 micrograms b.i.d., or a matched placebo, two puffs b.i.d. The patients used inhaled salbutamol as needed. At the beginning of the study, and every month between February and June, the following parameters were assessed: lung function (forced expiratory volume in one second (FEV1); airway responsiveness (provocative dose of methacholine producing a 20% fall in forced expiratory volume in one second (PD20)), serum eosinophil cationic protein (ECP); and blood eosinophil count. All subjects recorded daily asthma symptoms, beta 2-agonist consumption and peak expiratory flow (PEF) values. In the placebo group, all parameters except FEV1 worsened significantly during the pollen season compared with preseasonal values (p < 0.001). BDP produced complete protection, although a slight change from baseline was found for symptom score (p < 0.01), beta 2-agonist consumption (p < 0.01), and eosinophil number (p < 0.05) in May, when the pollen load was highest. These data provide evidence that beclomethasone dipropionate treatment is able to inhibit the seasonal changes occurring during natural exposure in asthmatics. This preventive effect is probably due to the anti-inflammatory action of beclamethasone dipropionate, as documented by its effect on serum markers of airway inflammation.

Administration, Inhalation↗
PubMed1996

Serum eosinophil cationic protein (ECP) as a marker of disease activity and treatment efficacy in seasonal asthma.

This study was carried out to determine whether serum eosinophil cationic protein (ECP) represents a sensitive marker for disease activity in atopic asthmatic patients during the pollen season. The study, in double-blind fashion, was performed between February and June 1994. Two groups of 10 seasonal asthmatic patients randomly received two different treatments. The first group was treated with inhaled beclomethasone dipropionate (BDP) 500 micrograms bid; the second received a matched placebo (P). At the beginning and every month, blood samples for determination of ECP and eosinophil count were collected and lung function (FEV1) and methacholine responsiveness (PD20) were performed. Subjects recorded daily symptoms of asthma, salbutamol consumption, and peak expiratory flow (PEF) values. In the P group, all indices, except FEV1, showed significant changes during the pollen season (P < 0.001). In the BDP group, significant changes were detected for symptom score (P < 0.01), salbutamol consumption (P < 0.01), and eosinophil number (P < 0.05). Between the two groups, significant differences for symptom score (P < 0.001), salbutamol consumption (P < 0.001), ECP levels (P < 0.05), eosinophil count (P < 0.02), PD20 methacholine (P < 0.02), and PEF values (P < 0.01) were detected. Changes in serum ECP significantly correlated with changes in other parameters (P < 0.001), except FEV1. Our results provide evidence that serum ECP is a sensitive marker for monitoring of the disease activity in seasonal asthma. Furthermore, it may offer a useful tool for estimating treatment efficacy.

Adult↗
PubMed1995

Effect of ipratropium bromide and/or sodium cromoglycate pretreatment on water-induced bronchoconstriction in asthma.

The mechanisms underlying water-induced bronchoconstriction are still not fully understood. Cholinergic reflexes and mast cell mediator release are currently believed to play an important pathogenetic role. In order to evaluate the relative contribution of each of these mechanisms, we studied the effect of ipratropium bromide (80 micrograms), a muscarinic antagonist, and sodium cromoglycate (20 mg), an inhibitor of mast cell mediator release, administered alone and in combination, in the prevention of bronchospasm induced by ultrasonic mist of distilled water (UMDW). Fifteen patients with documented atopic asthma and hyperresponsiveness to distilled water were selected for this randomized, placebo-controlled, double-blind study. Airway responses to pharmachological agents and bronchial challenge were measured by change in specific airways conductance (sGaw). Sodium cromoglycate had no effect on bronchial calibre, whilst ipratropium bromide and the combination of the two drugs produced a significant bronchodilation 30, 60 and 90 min after treatments. The maximal increase in sGaw (mean % +/- SD) was observed at 90 min: 63 +/- 28% and 58 +/- 22% after ipratropium bromide and the combined drugs respectively. UMDW (2, 4, 8, 16 ml water) caused a -36 +/- 19%, -42 +/- 19%, -49 +/- 18%, -56 +/- 15% mean % +/- SD fall in sGaw after placebo. Pretreatment with sodium cromoglycate abolished the bronchoconstriction to 2 ml (fall sGaw -5 +/- 23% NS) and significantly reduced the effect of 4 (-15 +/- 22%), 8 (-21 +/- 20%) and 16 ml (-24 +/- 18%) water.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

Protective effect of levodropropizine against cough induced by inhalation of nebulized distilled water in patients with obstructive lung disease.

Levodropropizine is a recently developed, peripherally active antitussive agent which is widely used in clinical practice. In order to obtain further information on the spectrum of activity of this compound in experimental clinical models, a double-blind controlled study was carried out to evaluate the potential effect of the drug against cough and bronchoconstriction induced by inhalation of an ultrasonically nebulized solution of distilled water in patients with obstructive lung disease. Twenty patients were randomly divided into two groups, which received levodropropizine (60 mg t.i.d.) or placebo respectively for 7 consecutive days. Parameters evaluated at baseline and on the last day of treatment included (i) results of respiratory function tests (FEV1, IVC, FVC, TIFF, PEF, MEF75, MEF50, MEF25) performed before the stimulation test with nebulized water; (ii) total number of coughs during a 2-hour period after the stimulation test; (iii) bronchial responsiveness, quantified by calculating the volume of nebulized water required to induce a 20% reduction of FEV1 below the basal level. At pretreatment, the tussive response was very similar in the two groups. A significant decrease in number of coughs (from 34.4 +/- 8.4 at baseline to 15.6 +/- 4.9 post-treatment, p less than 0.01) was observed after administration of levodropropizine, whereas placebo treatment produced no significant effect (number of coughs: 29.6 +/- 4.9 at baseline vs 24.8 +/- 9.6 post-treatment, N.S.). Bronchial responsiveness decreased significantly (compared to baseline) in both treatment groups, without any significant difference between drug and placebo. Respiratory function tests were not significantly affected by either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Efficacy and safety of teicoplanin in gram-positive pulmonary infections.

Teicoplanin is a new antibiotic obtained from a culture filtrate of Actinoplanes teichomyceticus with potent activity against aerobic and anaerobic gram-positive bacteria and having a high affinity for healthy or inflamed bronchial mucosa and pulmonary parenchyma. To investigate the efficacy and safety of this drug, we selected 13 patients suffering from lower respiratory tract infections caused by gram-positive organisms. Pathogens isolated from sputum or bronchial aspirate were: 8 Staphylococcus aureus, 1 Staphylococcus epidermidis, 3 Streptococcus pneumoniae and 1 Streptococcus species. We began treatment as monotherapy at the dosage of 400 mg daily (200 mg x 2) I.M. only after microbiological evaluation. 11 patients (84.6%) were clinically and bacteriologically cured, 1 (7.7%) showed definite clinical improvement but persistence of causative agent and 1 (7.7%) failed to respond. The mean treatment period was 8.3 days. No major adverse effect was observed. We conclude that teicoplanin is a very efficacious and well-tolerated antibiotic for therapy of gram-positive pulmonary infections.

Adult↗
PubMedDate not supplied

An acute bronchodilator test with tiotropium or salmeterol does not allow a subdivision of patients according to responses.

BACKGROUND: The possibility that individual chronic obstructive pulmonary disease (COPD) patients respond better to either tiotropium or salmeterol has been suggested and an acute bronchodilator test might help to guide the choice of therapy. OBJECTIVES: We explored the responses to tiotropium and salmeterol within the first 3 h using the recommended dosages (18 microg for tiotropium and 50 microg for salmeterol) in order to verify whether there are differences in the short-term bronchodilator effects between these two long-acting bronchodilators in patients with stable COPD. Moreover, we investigated whether these differences could discriminate between the two agents. METHODS: Forty consecutive patients with COPD, but in a stable phase of the disease, participated in this double-blind, double-dummy, randomized crossover study. The study involved a screening visit and 2 study days separated by at least 1 week. For determination of the onset of action, we measured FEV1 at 10, 20, 30, 60 and 90 min, and again 2 and 3 h after inhalation of single study drug. RESULTS: At all time points, both tiotropium and salmeterol caused significant (p< 0.001) changes from baseline. A mean increase of 12% above baseline was reached 66 min (95% CI: 45-87) after tiotropium and 59 min (95% CI: 41-77) after salmeterol. Nine patients after tiotropium and 5 patients after salmeterol did not have this type of improvement. A mean increase of 200 ml above baseline was reached 76 min (95% CI: 52-101) after tiotropium and 76 min (95% CI: 52-100) after salmeterol. Eighteen patients after tiotropium and 15 patients after salmeterol did not have this improvement. Twenty-one patients after tiotropium and 24 patients after salmeterol reached an improvement that was at the same time 12% and 200 ml greater than baseline. CONCLUSIONS: These data clearly show that the bronchodilator effects of tiotropium and salmeterol within the first hours after their acute administration are similar in patients with stable COPD when they are evaluated as mean changes from baseline in FEV1. Therefore, they question the direct therapeutic relevance of a subdivision of patients according to bronchodilator responses to tiotropium or salmeterol.

Administration, Inhalation↗
PubMedDate not supplied

Exhaled nitric oxide as a marker of adverse respiratory health effect in environmental disease.

The presence of, and the possibility to assay, nitric oxide (NO) in exhaled breath of humans caused a great deal of interest in relation to understanding the physiological and pathophysiological role of this molecule. Most studies have measured exhaled NO by chemiluminescence and detection depends on the photochemical reaction between NO and ozone generated in the analyzer. Here we discuss the role of exhaled NO as a physiological method to evaluate the effect of environmental changes on lower and upper airways in healthy subjects; particularly, its potential application as non invasive marker of the effect of outdoor and indoor air pollution on the respiratory tract.

Air Pollutants↗
PubMedDate not supplied

[Effects of cigarette smoking on the caliber of the small airways in healthy young smokers].

Although many studies have demonstrated the deleterious effect of cigarette smoking on lung function, nevertheless, a relative minority of smokers develop significative functional impairment. In this study we examined the ventilatory function in a group (n = 18) of young healthy smokers and in a control group of non smokers (n = 8). The two groups didn't show significative differences in spirometric tests. However in smokers the indexes of small airways calibre (FEF50 and FEF25) were slightly lower than for non smokers.

Adolescent↗