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Biomedical subjects

Mario Cazzola

Publications and source records attributed to Mario Cazzola.

At least 73 records · Page 4Linked to original sources
PubMed2004

Salmeterol/fluticasone propionate in a Single Inhaler Device versus theophylline+fluticasone propionate in patients with COPD.

STUDY OBJECTIVES: The aim of this study was to compare the relative efficacy in terms of improvement in symptoms and lung function of salmeterol/fluticasone propionate (SLM/FP) combination administered through the Diskus inhaler versus theophylline (THEO) added to FP Diskus in patients with stable chronic obstructive pulmonary disease (COPD). METHODS AND MEASUREMENTS: Eighty patients were randomized to receive 4 months of treatment in one of two treatment groups: (1) fixed combination of SLM 50 microg and FP 500 microg Diskus, 1 inhalation twice daily; or (2) FP Diskus 500 microg, 1 inhalation twice daily, plus oral titrated THEO twice daily. Patients attended the clinic before and after 4, 8, 12 and 16 weeks of treatment for evaluations of pulmonary function, and dyspnea, which was assessed using an analogic visual scale. Also the supplemental salbutamol use was measured. RESULTS: . Sixty-six patients completed the 4-month treatment period: 37 patients receiving SLM/FP and 29 patients receiving THEO+FP. Patients were withdrawn for various reasons, the most common of which were poor compliance with the protocol, exacerbation and GI events. A gradual increase in FEV(1) was observed with each treatment. Maximum significant increases in FEV(1) over baseline values that were observed after 4 months of treatment were as follows: SLM/FP 0.172 l (95% CI: 0.084-0.260) and THEO+FP 0.155 l (95% CI: 0.054-0.256). SLM/FP experienced significantly (p<0.05) greater improvements in dyspnea, and required significantly fewer supplemental salbutamol treatments than the THEO+FP group. CONCLUSIONS: Our results suggest that SLM/FP combination may provide substantial benefits in both physiologic and clinical outcomes in symptomatic patients with COPD. It also causes a more effective control than THEO+FP.

Aged↗
PubMed2004

Potential genetic influences on the response to asthma treatment.

Genetic factors play a key role in determining the widely heterogeneous response to pharmacological treatment detectable among asthmatics. In particular, polymorphisms of the genes encoding relevant anti-asthma drug targets contribute significantly to such a variability. Therefore, it is very important to characterize asthmatic patient's genotypes and the related phenotypic patterns, in order to predict the individual therapeutic outcome. This pharmacogenetic approach will eventually help clinicians to optimize and personalize anti-asthma treatment, and will also provide useful information with regard to pre- and post-marketing evaluation of both effectiveness and side effects of newly introduced drugs.

Anti-Asthmatic Agents↗
PubMed2004

Survivin expression in acute leukemias and myelodysplastic syndromes.

We analyzed by immunocytochemistry the expression of survivin in bone marrow cells from 36 acute myeloid leukemia (AML) cases, from 98 patients with myelodysplastic syndrome (MDS), and from 41 non hemopathic subjects. Our aim was to evaluate whether abnormalites in survivin expression were associated with peculiar laboratory and clinical findings, altered apoptosis levels or altered proliferative rate. In normal samples survivin was never detectable. It was detected in almost all AML and MDS cases. In AML and in MDS with more than 5% bone marrow blasts survivin levels higher than in RA and RARS were observed (P=0.04). In MDS a tendential inverse correlation between survivin and TUNEL positivity was identified (P=0.08), whereas survivin expression was independent of the proliferative rate. Survivin levels did not predict disease progression in MDS; among AML patients treated with intensive polichemotherapy, survivin expression was significantly higher in resistant cases (P=0.01). Our findings confirm the high incidence of survivin expression in AML. Its abnormal expression also in MDS may play a role in promoting aberrantly increased cell viability and contribute to the altered homeostatic balance between cell growth and cell death.

Apoptosis↗
PubMed2004

Macrolide and occult infection in asthma.

PURPOSE OF REVIEW: A small percentage of asthma exacerbations are linked with infection by an atypical bacterium, such as Chlamydia pneumoniae or Mycoplasma pneumoniae. These bacteria also have been proposed to cause occult chronic lower airway inflammation and to initiate nonatopic asthma in adults. Consequently, the logical procedure would be to eliminate these pathogens as soon and as thoroughly as possible using antibiotics. Nonetheless, antibiotics are not recommended even for the treatment of acute asthma exacerbations except as needed for comorbid conditions. These discrepancies highlight the need to define the role, if any, of antimicrobials that are active against atypical pathogens, mainly macrolides, but also tetracyclines and fluoroquinolones, in the treatment of asthma. RECENT FINDINGS: Macrolides are antibiotics with both antimicrobial and antiinflammatory activities. Some studies have documented that these agents could be useful in the treatment of occult infection in asthma because of their antimicrobial activity against atypical pathogens. They could also lead to reduction of the airways inflammation by decreasing the transcription of mRNA for a variety of cytokines and inhibiting interleukin-8 release by eosinophils, and therefore improvement of symptoms and pulmonary function. These effects are not caused by bronchodilation, elevation of serum theophylline level, or steroid-sparing mechanism. SUMMARY: The available clinical evidence seems to support use of macrolides in the treatment of asthma because of their antimicrobial activity. However, studies that may confirm this hypothesis are scarce and with limited scientific value because of their open, uncontrolled design.

Asthma↗
PubMed2004

Alternative and/or integrative therapies for pneumonia under development.

PURPOSE OF REVIEW: Increasing antimicrobial resistance among common respiratory bacteria has created challenges in selecting appropriate therapy for pneumonia. Fortunately, the analysis of genome sequences has allowed us to find novel, nontraditional targets that are involved in disease pathogenesis or in adaptation and growth in infection sites. The advantage of the nonclassical targets is that targeting these sites could ablate infection without inducing resistance. Interfering with bacterial adhesion, inhibiting, neutralizing and clearing endotoxin, and administering cytokines as immunoadjuvants are the most promising alternative or integrative treatments for pneumonia that are under development. RECENT FINDINGS: Interference with bacterial adhesion is possible using inhibitors of sortase or inactivators of the srtA gene against gram-positive bacteria, inhibitors of the periplasmic chaperone or those of usher function against gram-negative bacteria, novel polysaccharides that are present on echinoderm surfaces, antiadhesin vaccines, or the passive administration of antiadhesin antibodies. Inhibition, neutralization, and clearance of endotoxin possibly interferes in the lipid A biosynthetic pathway or using lipid A analogues with reduced or lack of ability to activate the major endotoxin receptors or proteins such as recombinant Limulus antilipopolysaccharide factor, bactericidal/permeability increasing protein, or lipopolysaccharide binding protein. Tumor necrosis factor 70-80, an adenoviral vector that encodes murine tumor necrosis factor alpha, and recombinant interferon gamma seem to be the most promising cytokines for use as immunoadjuvants for the treatment of pneumonia. SUMMARY: Ideally, potential treatment of life-threatening bacterial pneumonia will combine immunoadjuvant and conventional antibiotic therapy. Compounds capable of stimulating early host defense and microbial clearance, but not the later phases of inflammatory tissue injury associated with sepsis, may be advantageous.

Anti-Bacterial Agents↗
PubMed2004

Clinical significance of neutrophil CD177 mRNA expression in Ph-negative chronic myeloproliferative disorders.

The PRV-1 gene has been proposed as a marker of polycythaemia vera (PV). PRV-1 and NB1 are alleles of the polymorphic gene CD177, which belongs to the Ly-6/uPAR superfamily, and their coding regions differ at only four nucleotides. We studied neutrophil CD177 mRNA levels in normal subjects and in 235 patients with Ph-negative chronic myeloproliferative disorders (CMD), including PV, essential thrombocythaemia and myelofibrosis with myeloid metaplasia. Additional disease states were investigated for comparison. Highly variable neutrophil CD177 mRNA levels were observed in normal individuals. Neutrophils isolated from the bone marrow, or from peripheral blood following granulocyte colony-stimulating factor administration showed markedly higher CD177 expression than circulating granulocytes on steady state. Increased neutrophil CD177 mRNA levels were detected in all CMD. Elevated values were also found in reactive conditions and in disorders such as chronic myeloid leukaemia and myelodysplastic syndromes. In the differential diagnosis between PV and secondary erythrocytosis, the assay sensitivity was 68% while its specificity was 60%. These findings indicate that an elevated neutrophil CD177 mRNA level is not a specific marker for the diagnosis of PV nor for that of CMD. From a clinical viewpoint, neutrophil CD177 mRNA overexpression is rather a marker of abnormal neutrophil production and/or release in patients with CMD.

Adult↗
PubMed2004

Somatic deletion of the normal beta-globin gene leading to thalassaemia intermedia in heterozygous beta-thalassaemic patients.

Two beta-thalassaemia patients, whose constitutive genotype was beta(39C)/beta(39C-->T), had the clinical phenotype beta-thalassaemia intermedia. Analysis of leucocyte DNA showed the presence of the mutated beta(39C-->T)-gene exclusively, while the normal beta(39C)-gene was also present in reticulocyte RNA. Deletional analysis of chromosome 11p15.5 on leucocyte DNA showed large deletions including the beta-globin gene. Two populations of erythroid progenitors, one heterozygous and the other hemizygous for the beta(39C-->T) mutation, were demonstrated in one case. This confirms that, in heterozygous individuals, beta-thalassaemia intermedia may be caused by inactivation of the beta-locus in trans as a result of chromosome 11p15.5 deletions in a subpopulation of haematopoietic cells.

Adult↗
PubMed2004

Ferroportin gene silencing induces iron retention and enhances ferritin synthesis in human macrophages.

Missense mutations in the ferroportin gene (SLC11A3) result in haemochromatosis type 4 [HFE4, Online Mendelian Inheritance in Man (OMIM) reference 606069] or ferroportin disease, an autosomal dominant disorder characterized by predominantly reticuloendothelial iron accumulation. To verify whether HFE4 is caused by defective iron recycling because of loss of functionality of ferroportin, we down-regulated SLC11A gene expression in human macrophages by using small interfering RNAs (siRNAs). Transfection experiments with ferroportin siRNAs resulted in a marked reduction (about two-thirds on average) in ferroportin mRNA levels as detected by quantitative real time polymerase chain reaction. When macrophages were grown in medium supplemented with iron, cells transfected with siRNAs displayed three- to eightfold increases in staining intensities following Perls reaction. These macrophages also showed significant increases in H-ferritin content. The observation that ferroportin mRNA down-regulation to levels compatible with haplo-insufficiency causes increased iron retention and H-ferritin synthesis in cultured macrophages has important implications. First, this indicates that ferroportin levels must be finely regulated in order to maintain cellular iron homeostasis, and that both copies of SLC11A3 must function efficiently to prevent iron accumulation. Second, this observation supports the hypothesis that reticuloendothelial iron overload in patients with ferroportin disease is caused by loss-of-function mutations in the SLC11A3 gene that mainly impair macrophage iron recycling.

Cation Transport Proteins↗
PubMed2004

Inhaled combination therapy with long-acting beta 2-agonists and corticosteroids in stable COPD.

Long-acting beta(2)-agonists (LABAs) have been shown to be effective first-line bronchodilators in the treatment of COPD patients, and inhaled corticosteroids (ICSs) have been shown to reduce the frequency and/or severity of exacerbations in COPD patients. The concomitant use of a LABA and an ICS can influence both airway obstruction (ie, smooth muscle contraction, increased cholinergic tone, and loss of elastic recoil), and airway inflammation (ie, increased numbers of neutrophils, macrophages, and CD8+ lymphocytes, elevated interleukin-8 and tumor necrosis factor-alpha levels, and protease/antiprotease imbalance). They are also able to reduce the total number of bacteria adhering to the respiratory mucosa in a concentration-dependent manner without altering the bacterial tropism for mucosa, and to preserve ciliated cells. Several clinical trials support the concept of inhaled combination therapy with LABAs and corticosteroids in stable COPD patients. This type of therapy not only improves airflow obstruction but also provides clinical benefits, as manifested by sustained reduction in overall symptoms, improvements in health-related quality of life, and reductions in exacerbations. All of these effects are very important because, despite recent advances in our understanding of COPD and its treatment, therapy remains suboptimal for a considerable number of patients.

Administration, Inhalation↗
PubMed2004

Anti-IgE monoclonal antibody (omalizumab) in the treatment of atopic asthma and allergic respiratory diseases.

Since the discovery of immunoglobulin E (IgE) antibodies thirty-six years ago, our understanding of the mechanisms of allergy has improved to such an extent that we can now better differentiate allergy from non-allergic hypersensitivity, and allergic/atopic from intrinsic/non-atopic bronchial asthma. IgE antibodies are crucial immune mediators of airway inflammation in allergic atopic asthma and IgE-mediated hypersensitivity reactions are the likely mechanisms of allergen-induced airway obstruction. In addition, IgE may cause chronic airway inflammation in asthma through effector cells activated via high-affinity (Fcepsilon RI) or low-affinity (Fcepsilon RII) IgE receptors. Therapeutic anti-IgE antibodies able to reduce free IgE levels and to block the binding of IgE to Fcepsilon RI without cross-linking IgE and triggering degranulation of IgE-sensitised cells have been developed. This non-anaphylactogenic anti-IgE monoclonal antibody (rhuMAb-E25; omalizumab) binds IgE at the same site as these antibodies bind Fcepsilon RI and Fcepsilon RII. As a consequence, omalizumab inhibits IgE effector functions by blocking IgE binding to high-affinity receptors on IgE effector cells and does not cause mast cell or basophil activation because it cannot bind to IgE on cell surfaces where the Fcepsilon R1 receptor already masks the anti-IgE epitope. Studies in patients with atopic asthma demonstrated that omalizumab decreases serum IgE levels and allergen-induced bronchoconstriction during both the early and late-phase responses to inhaled allergen. In several clinical controlled trials omalizumab resulted to be able to reduce asthma-related symptoms, to decrease corticosteroid use and to improve quality of life of asthmatic patients. The anti-IgE approach to asthma treatment has several advantages, including concomitant treatment of other IgE-mediated diseases (allergic rhinitis, allergic conjunctivitis, atopic dermatitis and food allergies), a favourable side-effect profile and a twice-monthly dosing frequency.

Anti-Allergic Agents↗
PubMed2004

Hypereosinophilic syndrome and cyclic oscillations in blood cell counts. A clonal disorder of hematopoiesis originating in a pluripotent stem cell.

We studied a patient with hypereosinophilic syndrome (HES) who had myeloproliferative features, was unresponsive to imatinib mesylate, and showed cyclic oscillations in blood cell counts. No rearrangement in PDGFRA, PDGFRB and ETV6 genes was detected. Clonal analysis of hematopoiesis consistently showed skewed X-chromosome inactivation patterns in both granulocytes and T-lymphocytes, indicating a clonal myeloproliferative disorder originating in a pluripotent stem cell.

Adult↗
PubMed2004

TP53 codon 72 polymorphism in patients with chronic myeloid leukemia.

A single nucleotide polymorphism at TP53 codon 72 means that two alleles exist: A1 (proline residue, Pro72) and A2 (arginine residue, Arg72). The Pro72 variant of p53 has a lower apoptotic potential. We found that allele A1 was more frequent in patients with chronic myeloid leukemia (CML) than in controls, and among CML patients who had no cytogenetic response than among responders.

Adult↗