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1.
Int Arch Allergy Immunol ; 152(3): 255-63, 2010.
Article in English | MEDLINE | ID: mdl-20150743

ABSTRACT

The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions.


Subject(s)
Environment , Epidemiologic Research Design , Respiratory Tract Diseases/epidemiology , Respiratory Tract Diseases/genetics , Asthma/epidemiology , Asthma/genetics , Bias , Case-Control Studies , Data Collection , Data Interpretation, Statistical , Databases, Factual , Environmental Pollution , Female , Housing , Humans , Italy/epidemiology , Longitudinal Studies , Male , Nutrition Surveys , Phenotype , Public Sector , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/genetics , Rhinitis, Allergic, Perennial/epidemiology , Rhinitis, Allergic, Perennial/genetics , Rhinitis, Allergic, Seasonal/epidemiology , Rhinitis, Allergic, Seasonal/genetics , Surveys and Questionnaires
2.
J Endocrinol Invest ; 33(4): 244-9, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19915386

ABSTRACT

BACKGROUND: Zoledronic acid (Zol) is used successfully to inhibit bone resorption in tumor bone disease of various human cancer. Zol inhibits the mevalonate pathway and other potential targets include the inhibition of tyrosine phosphatase activity, disruption of metalloproteinase, secretion and down-regulation of the catalytic subunit of telomerase (hTERT). The six-transmembrane epithelial antigen of prostate protein (STEAP) is a new marker highly expressed at all phases of prostate cancer. AIM: Here, we analyzed for the first time the effect of Zol on STEAP gene expression in prostate cancer cells. MATERIAL AND METHODS: We evaluated the effects of Zol in STEAP gene expression by RT real time PCR in androgen-sensitive (LNCaP) and androgen-non-sensitive (PC3 and DU145) cell lines. To confirm the pro-apoptotic effect of Zol, we also analyzed the caspase-3 gene expression, that resulted up-regulated in cancer cell apoptosis. RESULTS: Zol strongly decreased cell viability and lowered STEAP gene expression in a dose-dependent manner. In addition, this effect was accompanied by an increase of apoptotic index and an up-regulation of caspase-3 gene expression. CONCLUSION: Zol may affect cancer cells also by targeting the gene expression of STEAP.


Subject(s)
Antigens, Neoplasm/metabolism , Bone Density Conservation Agents/pharmacology , Cell Line, Tumor/drug effects , Diphosphonates/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Imidazoles/pharmacology , Oxidoreductases/metabolism , Prostatic Neoplasms/physiopathology , RNA, Messenger/metabolism , Antigens, Neoplasm/genetics , Apoptosis/drug effects , Caspase 3/genetics , Caspase 3/metabolism , Dose-Response Relationship, Drug , Humans , Male , Oxidoreductases/genetics , RNA, Messenger/genetics , Zoledronic Acid
3.
Reumatismo ; 61(1): 54-64, 2009.
Article in Italian | MEDLINE | ID: mdl-19370189

ABSTRACT

Bisphosphonates are the most commonly prescribed medications for the treatment of osteoporosis. Despite evidence supporting the anti-fracture efficacy of aminobisphosphonates approximately 50% of patients do not follow their prescribed treatment regimen and/or discontinue treatment within the first year. Poor compliance is associated with negative outcomes, including increased fracture risk. Tolerability and safety are among the causes of poor compliance. Intravenous bisphosphonates avoids the gastrointestial intolerance and the complex dosing instruction of the oral route ensuring full compliance which may provide improved efficacy. However, there are some concerns regarding potent intravenous bisphosphonates as zoledronic acid with respect to tolerability, mainly the acute phase response and to safety, mainly a theoretical risk of over suppression of bone turnover, renal toxicity and osteonecrosis of the jaw. In the HORIZON study, 152 patients on active treatment (82) or placebo (70) underwent to a bone biopsy after double tetracycline labeling. Bone biopsies (iliac crest) were obtained at the final visit at month 36, 1 year after the last infusion. The biopsies were analyzed by histomorphometry on bone sections and by micro-CT (microCT) analysis. One hundred forthy-three biopsies (76 zoledronic acid, 67 placebo) had at least one microCT parameter measured and 111 were available for quantitative histomorphometry (59 zoledronic acid, 52 placebo). Micro-CT analysis of bone structure revealed higher trabecular bone volume (BV/TV), decreased trabecular separation (Tb.Sp), and a strong trend towards improvement in connectivity density in biopsies obtained from patients treated with zoledronic acid, indicating preservation of trabecular bone structure with respect to placebo. Histomorphometric analysis obtained from patients treated with zoledronic acid exhibited reduction of bone turnover, as suggested by decreased activation frequency (Ac.F) by 63%, mineralizing surface (MS/BS), bone formation rate (BFR/BV). In addition, mineral appositional rate (MAR), reflecting the bone-forming capacity of osteoblastic teams at the bone multicellular unit (BMU) level, was significantly higher in patients on active treatment. No sign of excessive suppression of bone turnover or mineralization impairment was detected, confirming the safety of the treatment with intravenous zoledronic acid once a year. These interesting findings are discussed in the article, particularly in terms of new histomorphometric results and clinical findings supporting the tolerability and safety of zoledronic acid.


Subject(s)
Diphosphonates/therapeutic use , Imidazoles/therapeutic use , Osteoporosis, Postmenopausal/drug therapy , Atrial Fibrillation/chemically induced , Biopsy , Bone Density , Bone Density Conservation Agents/administration & dosage , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/therapeutic use , Bone and Bones/metabolism , Bone and Bones/pathology , Diphosphonates/administration & dosage , Diphosphonates/adverse effects , Female , Femoral Fractures/etiology , Femoral Fractures/prevention & control , Follow-Up Studies , Humans , Imidazoles/administration & dosage , Imidazoles/adverse effects , Infusions, Intravenous , Multicenter Studies as Topic , Osteoporosis, Postmenopausal/complications , Randomized Controlled Trials as Topic , Renal Insufficiency/chemically induced , Retrospective Studies , Risk Factors , Safety , Spinal Fractures/etiology , Spinal Fractures/prevention & control , Time Factors , Zoledronic Acid
4.
Cancer Lett ; 273(1): 122-6, 2009 Jan 08.
Article in English | MEDLINE | ID: mdl-18793824

ABSTRACT

STEAP was identified by the strategy of suppression subtractive hybridizations in Los Angeles prostate cancer xenografts. It is expressed in prostate and other cancers, and not in most normal tissue; it can be used as a marker to evaluate biological samples from individuals suspected of having a disease associated with STEAP dysregulation, such as cancers, and may provide prognostic information useful in defining appropriate therapeutic options. The aim of this study was to test the STEAP mRNA detection in the serum of patients with different malignant tumours by using Real-Time reverse transcription PCR. The results were compared with biological samples obtained by age-matched non-malignant donors. Our data demonstrated that STEAP mRNA is detectable in serum of patients with different solid tumours whereas it is not amplifiable in non-malignant donors. This marker revealed with the molecular method of quantitative PCR in serum, may be useful to discriminate normal and cancer patients.


Subject(s)
Antigens, Neoplasm/blood , Biomarkers, Tumor , Neoplasms/diagnosis , Oxidoreductases/blood , Aged , Aged, 80 and over , Antigens, Neoplasm/genetics , Female , Humans , Male , Middle Aged , Oxidoreductases/genetics , RNA, Messenger/blood , Reference Standards , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity
5.
J Endocrinol Invest ; 31(6): 525-30, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18591885

ABSTRACT

Primary hyperparathyroidism (PHPT) is a common endocrine disease. High levels of PTH cause demineralization of bone and increased risk of fracture. On the other hand, the effect of PHPT on bone structure is more ambiguous. The aim of this study was to evaluate the effect of PHPT on cancellous bone volume, structure, and microarchitecture. Thirteen transiliac biopsy specimens taken in untreated post-menopausal women aged 65+/-5 yr with primary hyperparathyroidism were compared with 13 biopsies taken in normal women aged 66+/-6 yr. None of the patients presented any other disorder affecting bone metabolism. In these samples we evaluated the direct and indirect histomorphometric parameters of bone microarchitecture using an image analysis system consisting of an epifluorescent microscope (Leica DMR) connected to an analogic 3 CCD camera (Sony DXC 390P) and a computer equipped with specific software for histomorphometric analyses. No significant differences between PHPT patients and controls in cancellous bone volume, trabecular thickness, and number were found. Two-dimensional parameters showed a preserved microarchitecture in PHPT patients. On the other hand, indirect parameters of microarchitecture [Marrow Star Volume (MSV) and Trabecular Bone Pattern Factor (TBPf)] showed a significant compromising of microarchitecture in these patients. PHPT patients have similar structural parameters to normal subjects. Concerning microarchitecture, indirect approach by MSV and TBPf shows a significant compromising of connectivity. These results can explain trabecular fragility observed in clinical studies on PHPT.


Subject(s)
Hyperparathyroidism, Primary/pathology , Ilium/anatomy & histology , Aged , Bone Density/physiology , Bone Remodeling/physiology , Female , Humans , Hyperparathyroidism, Primary/physiopathology , Ilium/physiology , Middle Aged , Postmenopause/physiology
6.
Br J Sports Med ; 42(10): 845-9; discussion 849-50, 2008 Oct.
Article in English | MEDLINE | ID: mdl-17545276

ABSTRACT

OBJECTIVES: A few studies on small patient series have investigated the relationship between gastroesophageal reflux and bronchial responsiveness as expressed by exercise-induced bronchoconstriction (EIB), with non-conclusive results. The aim of this study was to evaluate whether the presence of acid in the oesophagus may influence EIB. METHODS: 45 patients with bronchial asthma underwent spirometry, exercise challenge on bicycle ergometer and 24 h oesophageal pH monitoring. Subjects with EIB (Forced expiratory volume in the first second (FEV1)) percentage decrease after exercise (DeltaFEV1) > or =15%, n = 28) were retested after a 2 week treatment course with omeprazole 40 mg/daily. Exercise at baseline was performed at the same time as oesophageal pH monitoring. RESULTS: In basal condition, there was no difference in FEV1, acid exposure time or number of refluxes measured during 24 h pH monitoring between patients with and without EIB. There was no relationship between spirometry results and DeltaFEV1 on one hand, and parameters of gastroesophageal reflux on the other. Nine patients with EIB (31.0%) and six patients without EIB (37.5%) had one or more episodes of GER during exercise challenge, without significant differences between the two groups. After gastric acid inhibition by omeprazole, DeltaFEV1 did not change significantly. CONCLUSIONS: The results indicate that acid in the oesophagus, or its short-term inhibition by proton pump inhibitors, has no influence on exercise-induced bronchoconstriction.


Subject(s)
Asthma, Exercise-Induced/etiology , Exercise/physiology , Gastroesophageal Reflux/complications , Adult , Bronchoconstriction/physiology , Esophageal pH Monitoring , Exercise Test , Female , Humans , Male , Respiratory Function Tests , Spirometry
7.
J Endocrinol Invest ; 30(9): 739-46, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17993765

ABSTRACT

UNLABELLED: Osteoporosis is a severe complication of glucocorticoid treatment. Bisphosphonates are a powerful therapeutic option to prevent osteoporotic fractures. The aims of this study were: a) to determine bone alterations induced by therapy with glucocorticoids (GC); b) to establish the efficacy of risedronate (Ris) in the prevention of these effects. We studied 40 female Sprague-Dawley rats randomly divided into 4 groups of treatment, administered 3 times a week sc: 1. CONTROL: vehicle of methylprednisolone (GC) + vehicle of Ris; 2. Ris: Ris 5 mug/kg body weight vehicle of GC; 3. GC: GC 7 mg/kg + vehicle of Ris; 4. GC+Ris: GC 7 mg/kg, Ris 5 microg/kg. Animals were treated for 30 days and then were sacrificed. Densitometry was performed at baseline and at the end of the treatment. Right tibiae were removed for histomorphometric analyses. The GC group showed a 7% decrease in bone density vs controls (p<0.05), while the GC+Ris group was associated with a 3.5% increase in bone density vs controls (p<0.05). In the GC group, histomorphometric evaluations showed reduced bone volume (BV/TV) and thinning of trabeculae (Tb.Th) vs controls (BV/TV: 31+/-1 vs 35+/-1%, p<0.05; Tb.Th: 43+/-2 vs 50+/-3 microm, p<0.01; Ac.f: 1.8+/-0.2 vs 1.6+/-0.3 N/yr). The GC+Ris group had increased BV/TV and Tb.Th, and reduced Ac.f vs the GC group. Ris also maintained trabecular microarchitecture. At the histological level, glucocorticoid-induced osteoporosis was characterized by decreased bone volume, reduced osteoblastic activity, and deterioration of microarchitecture. Ris counteracted these effects both by prolonging osteoblast activity, and by maintaining bone microarchitecture.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone and Bones/pathology , Etidronic Acid/analogs & derivatives , Glucocorticoids/adverse effects , Osteoporosis/chemically induced , Osteoporosis/prevention & control , Animals , Bone Density/drug effects , Bone Density/physiology , Bone Density Conservation Agents/pharmacology , Bone Resorption/drug therapy , Bone and Bones/drug effects , Disease Models, Animal , Etidronic Acid/pharmacology , Etidronic Acid/therapeutic use , Female , Osteoblasts/drug effects , Osteogenesis/drug effects , Osteogenesis/physiology , Osteoporosis/physiopathology , Random Allocation , Rats , Rats, Sprague-Dawley , Risedronic Acid
8.
J Clin Microbiol ; 45(10): 3470-3, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17652486

ABSTRACT

We report a case of fungemia caused by Candida magnoliae, a yeast never associated with human disease. The infection occurred in a 42-year-old Chinese patient with gastric cancer complicated by peritoneal carcinosis. Multiple blood cultures were positive for yeast; the species was well identified with biochemical and molecular methods. The phylogenetic analysis showed a close relationship of C. magnoliae to Candida krusei.


Subject(s)
Candida/isolation & purification , Fungemia/microbiology , Stomach Neoplasms/complications , Adult , Base Sequence , Candida/classification , Candida/drug effects , Humans , Male , Microbial Sensitivity Tests , Molecular Sequence Data , Phylogeny
9.
J Endocrinol Invest ; 29(6): 563-7, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16840837

ABSTRACT

SS receptors are overexpressed in many tumors, mainly of neuroendocrine origin, thus enabling the treatment with SS analogs. The clinical experience of receptor radionuclide therapy with the new analog [90Y-DOTA0-Tyr3 ]-octreotide [90Y-DOTATOC] has been developed over the last decade and is gaining a pivotal role in the therapeutic workout of these tumors. It is well known that some procedures performed in diagnostic and therapeutic management of endocrine tumors, such as agobiopsy and hepatic chemoembolization, can be associated with the occurrence of symptoms related to the release of vasoactive amines and/or hormonal peptides from tumor cell lysis. This is the first report of a severe carcinoid crisis developed after receptor radionuclide therapy with 90Y-DOTATOC administered in a patient affected by liver metastases from bronchial neuroendocrine tumor (atypical carcinoid). Despite protection with H1 receptor antagonists, octreotide and corticosteroids, few days after the therapy the patient complained of persistent flushing of the face and upper trunk, severe labial and periocular oedema, diarrhoea and loss of appetite. These symptoms increased and required new hospitalisation. The patient received iv infusion of octreotide associated with H1 and H2 receptor antagonists and corticosteroid therapy, which induced symptom remission within few days. The case here reported confirms that radionuclide therapy is highly effective in determining early rupture of metastatic tissue and also suggests that pre-medication should be implemented before the radiopeptide administration associated with a close monitoring of the patient in the following days.


Subject(s)
Bronchial Neoplasms/pathology , Liver Neoplasms/secondary , Malignant Carcinoid Syndrome/chemically induced , Octreotide/analogs & derivatives , Aged , Bone Neoplasms/secondary , Bronchial Neoplasms/drug therapy , Bronchial Neoplasms/radiotherapy , Carcinoid Tumor/drug therapy , Carcinoid Tumor/radiotherapy , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/radiotherapy , Male , Octreotide/adverse effects , Octreotide/therapeutic use , Yttrium Radioisotopes/adverse effects
10.
J Endocrinol Invest ; 29(4): 358-62, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16699304

ABSTRACT

In 1990, a 55-yr-old woman was admitted to the Medical Department of our hospital for severe hypercortisolism complicated by secondary diabetes mellitus and serious hypokalemia. Although inferior petrosal sinus sampling did not show any significant difference between central and peripheral ACTH concentration, suggesting an ectopic source of ACTH secretion, diagnostic imaging was negative and Cushing's disease due to hyperplasia of the pituitary intermediate lobe was suspected. Medical treatment with bromocriptine and cyproheptadine led to a rapid and stabile normalization of adrenal function, so that after two months cyproheptadine was stopped and bromocriptine was tapered to a smaller dose. An attempt to discontinue medical treatment, carried out 3 yr later, was followed by a quick increase of ACTH and cortisol levels, which were normalized by the resumption of the bromocriptine. Adrenal function remained normal until 1994 when hypercortisolism relapsed despite the treatment. Chest radiography and computed tomography (CT) scan detected a 6 mm nodule in the middle lobe of the lung which proved to be a neuroendocrine tumor, with immunohistochemical positivity for ACTH. Nests of neuroendocrine cells (tumorlets) were also demonstrated in the surrounding lung tissue. After the lobectomy, the patient recovered completely from Cushing's syndrome and no symptoms and/or signs of recurrence have been observed over the subsequent follow-up period. Although cyclical spontaneous Cushing's syndrome could not be excluded, there was strong evidence that medical treatment with bromocriptine might have played a key role in long-lasting remission. To our knowledge, this is the second case described in literature of Cushing's syndrome caused by neuroendocrine lung tumor responsive to bromocriptine.


Subject(s)
ACTH Syndrome, Ectopic/complications , ACTH Syndrome, Ectopic/drug therapy , Bromocriptine/therapeutic use , Carcinoid Tumor/complications , Carcinoid Tumor/drug therapy , Cushing Syndrome/etiology , Lung Neoplasms/complications , Neoplasm Regression, Spontaneous , Carcinoid Tumor/pathology , Female , Humans , Lung Neoplasms/pathology , Middle Aged
11.
Micron ; 36(7-8): 609-16, 2005.
Article in English | MEDLINE | ID: mdl-16242341

ABSTRACT

The increasing use of densitometric devices for assessing bone fragility has progressively strengthened the assumption that mass is the most important property determining bone mechanical competence. Nevertheless, structure and microarchitecture are relevant aspects of bone strength. The study of microarchitecture is based on the measure of width, number, and separation of trabeculae as well as on their spatial organization. There are several methods to assess bone architecture, particularly at the trabecular level. In particular, histomorphometry, based on the use of optical microscopy and on the principles of quantitative histology and stereology, evaluates microarchitecture two-dimensionally, even if these measures appear well correlated to the three-dimensional structure and properties of bone. In addition, new computerized methods allow the acquisition of more sophisticated measurements by means of a digitizer have been introduced to integrate the use of the microscope. These methods supply information on trabecular width as well as on its distribution and on the organization of the trabeculae in the marrow space. Microarchitecture seems to be a determinant of bone fragility independent of bone density and it is important for understanding the mechanisms of bone fragility as well as the action of the drugs used to prevent osteoporotic fractures. Several in vivo studies (on animals and humans) can provide an additional interpretation for the anti-fracture effect of such drugs. For instance, bisphosphonates and parathyroid hormone seem to preserve or even improve microarchitecture. The challenge for the future will be to evaluate bone quality in vivo with the same or better resolution and accuracy than the invasive methods used today.


Subject(s)
Bone Density , Bone and Bones/cytology , Bone and Bones/physiology , Animals , Biomechanical Phenomena , Bone Density/drug effects , Bone Diseases/pathology , Bone Diseases/physiopathology , Bone and Bones/drug effects , Connective Tissue/pathology , Connective Tissue/ultrastructure , Diphosphonates/pharmacology , Fractures, Bone/pathology , Fractures, Bone/physiopathology , Haversian System/cytology , Haversian System/pathology , Histocytochemistry , Humans , Image Processing, Computer-Assisted , Osteoporosis/pathology , Osteoporosis/physiopathology , Parathyroid Hormone/pharmacology , Rats
12.
Biochem Biophys Res Commun ; 302(4): 679-84, 2003 Mar 21.
Article in English | MEDLINE | ID: mdl-12646222

ABSTRACT

Lacidipine, a dihydropyridine-based calcium antagonist (DHP), has already been demonstrated to possess antioxidant activity and to reduce the intracellular production of reactive oxygen species (ROS). To verify if this effect is a peculiarity of this molecule, or belongs to other DHPs, the activity of lacidipine was compared with those of amlodipine, lercanidipine, nimodipine, and nifedipine. The DHPs were incorporated in bovine aortic endothelial cells (BAECs). Cu(2+)-oxidized LDL (ox-LDL, 5 microM) was incubated with BAECs for 5 min. 2',7'-Dichlorofluorescein (DCF) as expression of intracellular ROS production was measured by flow cytometry. Ox-LDL induced a strong increase in intracellular ROS formation (p<0.001) that was significantly reduced only with lacidipine and lercanidipine (p from <0.05 to <0.01); the effect of lacidipine, however, resulted in being much more evident than lercanidipine (p<0.01); amlodipine, nimodopine, and nifedipine had no effect on ROS formation. The lowest IC50s, i.e. the concentrations determining the 50% reduction of ROS, were obtained with lacidipine (p<0.01). The inhibitory effect of lacidipine on ox-LDL-induced ROS production in endothelial cells is a peculiarity of this molecule through its antioxidant activity.


Subject(s)
Antioxidants/pharmacology , Dihydropyridines/pharmacology , Endothelium, Vascular/metabolism , Amlodipine/chemistry , Amlodipine/metabolism , Amlodipine/pharmacology , Animals , Antioxidants/chemistry , Antioxidants/metabolism , Cattle , Cells, Cultured , Dihydropyridines/chemistry , Dihydropyridines/metabolism , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Fluoresceins/metabolism , Humans , Lipoproteins, LDL/metabolism , Molecular Structure , Nifedipine/chemistry , Nifedipine/metabolism , Nifedipine/pharmacology , Nimodipine/chemistry , Nimodipine/metabolism , Nimodipine/pharmacology , Reactive Oxygen Species/metabolism
13.
Allergy ; 57(7): 600-6, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12100300

ABSTRACT

BACKGROUND: Italian data on the prevalence of allergic rhinitis are sparse and with wide variations, maybe because of different diagnostic criteria and methods of investigation. This study analyzes the information on rhinitis collected in northern Italy through standardized methods within the European Community Respiratory Health Survey. METHODS: A screening questionnaire was sent by mail to a random sample of the general population aged 20-44 years, and nonresponders were contacted again by phone, achieving a final response rate of 86% (6031/7000). Among the responders, 914 randomly selected underwent a standardized clinical interview, skin prick test (SPT) and total and specific immunoglobulin (Ig)E determination. RESULTS: The overall prevalence of self-reported allergic rhinitis was 15.9% (95% CI 15.0-16.8%). Allergic rhinitis was more common in men below 35 years and in women older than that (P = 0.006), in urban areas (P < 0.001) and in early responders (P < 0.001). A larger percentage of subjects (37.7%) reported nasal symptoms when exposed to indoor or outdoor allergens. Atopy was present in 79% of the subjects reporting allergic rhinitis. CONCLUSIONS: This study demonstrates that the prevalence of allergic rhinitis in northern Italy is similar to the prevalence observed in other European countries and that this disease is more common in urban areas.


Subject(s)
Hypersensitivity, Immediate/epidemiology , Rhinitis, Allergic, Perennial/epidemiology , Adult , Female , Health Surveys , Humans , Hypersensitivity, Immediate/diagnosis , Immunoglobulin E/blood , Italy/epidemiology , Male , Prevalence , Rhinitis, Allergic, Perennial/diagnosis , Skin Tests , Surveys and Questionnaires
14.
J Biol Chem ; 276(17): 13750-5, 2001 Apr 27.
Article in English | MEDLINE | ID: mdl-11278710

ABSTRACT

Oxidized low density lipoprotein (ox-LDL) has been suggested to affect endothelium-dependent vascular tone through a decreased biological activity of endothelium-derived nitric oxide (NO). Oxidative inactivation of NO is regarded as an important cause of its decreased biological activity, and in this context superoxide (O(2)) is known to inactivate NO in a chemical reaction during which peroxynitrite is formed. In this study we examined the effect of ox-LDL on the intracellular NO concentration in bovine aortic endothelial cells and whether this effect is influenced by ox-LDL binding to the endothelial receptor lectin-like ox-LDL receptor-1 (LOX-1) through the formation of reactive oxygen species and in particular of O(2). ox-LDL induced a significant dose-dependent decrease in intracellular NO concentration both in basal and stimulated conditions after less than 1 min of incubation with bovine aortic endothelial cells (p < 0.01). In the same experimental conditions ox-LDL also induced O(2) generation (p < 0.001). In the presence of radical scavengers and anti-LOX-1 monoclonal antibody, O(2) formation induced by ox-LDL was reduced (p < 0.001) with a contemporary rise in intracellular NO concentration (p < 0.001). ox-LDL did not significantly modify the ability of endothelial nitric oxide synthase to metabolize l-arginine to l-citrulline. The results of this study show that one of the pathophysiological consequences of ox-LDL binding to LOX-1 may be the inactivation of NO through an increased cellular production of O(2).


Subject(s)
Imidazolines , Lipoproteins, LDL/metabolism , Nitric Oxide/metabolism , Oxygen/metabolism , Receptors, LDL/metabolism , Superoxides/metabolism , Allopurinol/pharmacology , Animals , Antibodies, Monoclonal/pharmacology , Antioxidants/pharmacology , Aorta/metabolism , Ascorbic Acid/pharmacology , Aspirin/pharmacology , Bradykinin/pharmacology , CHO Cells , Catecholamines/pharmacology , Cattle , Cells, Cultured , Chromans/pharmacology , Cricetinae , Dose-Response Relationship, Drug , Endothelium, Vascular/metabolism , Enzyme Inhibitors/pharmacology , Flow Cytometry , Free Radical Scavengers/pharmacology , Hemostatics/pharmacology , Humans , Mice , Probucol/pharmacology , Protein Binding , Reactive Oxygen Species/metabolism , Receptors, Oxidized LDL , Scavenger Receptors, Class E , Thrombin/pharmacology , Time Factors , omega-N-Methylarginine/pharmacology
16.
Article in English | MEDLINE | ID: mdl-11108443

ABSTRACT

The clinical efficacy of local nasal immunotherapy (LNIT) in patients with allergic rhinitis is amply documented. The aim of the study was to determine the effect on bronchial hyperresponsiveness (BHR) assessed at baseline and after 3 years of LNIT or pharmacological treatment alone. Forty-three randomized patients with allergic oculorhinitis were enrolled (26 positive to Graminaceae and 17 to Parietaria judaica pollens). All patients were asked whether they were willing to follow a 3-year treatment course involving preseasonal LNIT with a powder extract of Graminaceae or Parietaria pollens. Twenty-four patients (16 allergic to Graminaceae and eight to Parietaria) selected LNIT and the other 19 opted for symptomatic pharmacological treatment only. The latter was considered the control group. On the basis of positive or negative bronchial hyperresponsiveness and the LNIT, four subgroups were established and followed in open conditions, during which a record was kept of symptom scores, drug use, spirometry and methacholine test findings. After 3 years, patients treated with LNIT had a significant reduction of symptoms and drug intake. In the controls, symptoms worsened, thus requiring more drugs to control them. Bronchial hyperresponsiveness significantly improved in hyperreactive patients receiving LN7IT 10 of whom were no longer hyperreactive and one at a higher threshold. Among controls, bronchial hyperresponsiveness did not change, with the exception of three nonreactive patients who became hyperreactive, one of them with asthma. These findings confirm the efficacy of LNIT in allergic rhinitis suggesting that it might have systemic activity interfering with bronchial hyperresponsiveness and hence the onset of bronchial asthma.


Subject(s)
Bronchial Hyperreactivity/therapy , Rhinitis, Allergic, Seasonal/therapy , Administration, Intranasal , Adolescent , Adult , Child , Female , Forced Expiratory Volume , Humans , Immunotherapy , Male , Middle Aged , Pilot Projects
17.
Respiration ; 67(5): 510-3, 2000.
Article in English | MEDLINE | ID: mdl-11070454

ABSTRACT

BACKGROUND: Although formoterol, a new long-acting beta(2)-adrenergic agonist, has a rapid bronchodilating action, no studies have previously examined whether it can provide equally rapid protection against exercise-induced bronchospasm (EIB). AIM: The aim of the study was to assess the effect of inhaled formoterol against EIB 15 min and 4 h after administration in asthmatic athletes. METHODS: The protective effect of a formoterol (12 microg) dry-powder inhalation was evaluated in 14 EIB-positive asthmatic athletes (13 males, mean age 16.8 years), in a double-blind, placebo-controlled, two-period cross-over study. On each treatment day, the subjects underwent two cycloergometric exercise tests 15 min and 4 h after receiving formoterol or placebo. RESULTS: Formoterol induced significant bronchodilation in comparison with placebo both 15 min and 4 h after administration (p = 0.007 and p = 0.004); placebo treatment had no effect on EIB, the maximum percent fall in FEV(1) after exercise being 29.3 +/- 14.3% and 22.9 +/- 13. 7% at 15 min and 4 h, respectively. Formoterol offered good protection against EIB in 12 athletes (86%) who experienced a decrease in FEV(1) after exercise <10% both 15 min and 4 h after administration. The mean maximum percent fall in FEV(1) after formoterol was 5.9+/-7.2% at 15 min (p < 0.0001), and 5.8 +/- 6.9% at 4 h (p < 0.0001). There was no statistically significant difference in resting heart rate before and after medication with placebo or formoterol, nor was the heart rate at the end of exercise significantly different on the 2 treatment days. No side effect was observed in either group. CONCLUSIONS: This study demonstrates that formoterol dry powder inhalation is effective in protecting asthmatic athletes as early as 15 min after dosing. Furthermore, the data confirm the long duration of its protective effect and the absence of any significant adverse effects after acute administration.


Subject(s)
Adrenergic beta-Agonists/therapeutic use , Asthma, Exercise-Induced/drug therapy , Ethanolamines/therapeutic use , Administration, Inhalation , Adolescent , Adrenergic beta-Agonists/administration & dosage , Adult , Child , Cross-Over Studies , Double-Blind Method , Ethanolamines/administration & dosage , Female , Forced Expiratory Volume , Formoterol Fumarate , Humans , Male , Sports , Time Factors
18.
J Biol Chem ; 275(17): 12633-8, 2000 Apr 28.
Article in English | MEDLINE | ID: mdl-10777555

ABSTRACT

In this study we examined the effect of oxidized low density lipoprotein (ox-LDL) on the intracellular production of reactive oxygen species (ROS) in bovine aortic endothelial cells (BAECs) and whether this increase occurs through its binding to the endothelial receptor lectin-like ox-LDL receptor-1 (LOX-1). Furthermore, this study also aimed to ascertain whether the binding of ox-LDL to LOX-1 is associated with NF-kappaB activation. ox-LDL induced a significant dose-dependent increase in ROS production after a 30-s incubation with BAECs (p < 0.01). ROS formation was markedly reduced in BAECs incubated with anti-LOX-1 monoclonal antibody (p < 0.001), while control nonimmune IgG produced no effect. ox-LDL induced a time- and dose-dependent significant increase in ROS formation only in CHO-K1 cells stably expressing bovine LOX-1 (p < 0.001), while no increase was present in CHO-K1 cells. The activation of the transcription factor NF-kappaB in BAECs was evident after a 5-min incubation with ox-LDL and was attenuated by anti-LOX-1 monoclonal antibody. The conclusion is that one of the pathophysiological consequences of ox-LDL binding to LOX-1 may be the activation of NF-kappaB through an increased ROS production.


Subject(s)
Endothelium, Vascular/metabolism , Lipoproteins, LDL/metabolism , NF-kappa B/metabolism , Reactive Oxygen Species/metabolism , Receptors, LDL/metabolism , Animals , Anticholesteremic Agents/pharmacology , Antioxidants/pharmacology , Ascorbic Acid/pharmacology , CHO Cells , Cattle , Cells, Cultured , Chromans/pharmacology , Cricetinae , Fluoresceins/metabolism , Humans , Hydrogen Peroxide/metabolism , Probucol/pharmacology , Protein Binding , Receptors, Oxidized LDL , Scavenger Receptors, Class E , Time Factors
19.
Infection ; 28(1): 38-41, 2000.
Article in English | MEDLINE | ID: mdl-10697790

ABSTRACT

UNLABELLED: The aim of the study was to evaluate the prevalence of antibodies to Chlamydia pneumoniae in a random population sample of 369 young adults (aged 20-44 years), living in Verona, Italy. IgG and IgM titers were measured by micro-immunofluorescence. IgG antibodies, greater or equal to 16, were found in 104/177 (58.8%) men and 76/192 (39.6%) women (p < 0.001). No relationship was found between IgG seropositivity, age, social class, education and family size. Factors positively associated with IgG seropositivity included smoking (p < 0.001), occupational status (employed vs unemployed: p = 0.02; students vs unemployed: p < 0.01) and living area (suburban [65.0%] vs urban area [45.3%]: p = 0.03). The geometric mean of IgG titers was higher in students (GM: 26.05) than in both employed (GM: 11.02) and unemployed persons (GM: 4.80) (p < 0.01 and p < 0.001, respectively). IgG titres > or = 512 and/or IgM titers > or = 16 (suggestive of a recent C. pneumoniae infection) were found in 39 subjects (10.6%). Recent infection was more frequent in spring (14.9%), with no significant variation in the other seasons (mean prevalence 6.7%) (p < 0.01). Recent infection was also associated with cigarette smoking. On the other hand, no significant association was found between respiratory symptoms and serologic evidence of recent infection. IN CONCLUSION: 1) the prevalence of antibodies to C. pneumoniae in young adults from Verona is similar to that found in European countries, and therefore, in Europe, it seems not related to latitude or climate; 2) male sex, tobacco smoking, employment status and living in a suburban area are independent risk factors of infection; 3) the infection is subclinical in most cases.


Subject(s)
Antibodies, Bacterial/blood , Chlamydia Infections/epidemiology , Chlamydophila pneumoniae/immunology , Adult , Climate , Employment , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Italy/epidemiology , Male , Risk Factors , Seroepidemiologic Studies , Sex Factors , Smoking/adverse effects
20.
Eur Respir J ; 14(5): 1044-8, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10596688

ABSTRACT

In the early 1990s a multicentre survey on asthma was performed on the young adult population (European Community Respiratory Health Survey - ECRHS). This study is to be repeated in order to estimate changes in the prevalence of asthma-like symptoms during the last decade and to assess the social and economic costs of the disease and their variations among countries. The self-administered questionnaire devised for this purpose is a two-page questionnaire. The first page contains the same items as those used in the first survey with four additional questions related to: 1) the frequency and severity of asthma attacks; 2) the presence of chronic bronchitis; 3) smoking habits; and 4) a visual analogue scale assessing perception of outdoor pollution. The second page aims to collect information regarding the direct and indirect costs of asthma. The influence of the length of the questionnaire on the response rate was assessed in a pilot study in Italy. Two random samples of 150 subjects received either the one-page questionnaire (first page) or the two-page questionnaire. The response rate was compared with that obtained from the first postal wave in the 1991-1992 survey. Although the response rate was unchanged when using the one-page questionnaire (45% versus 45%), it decreased by 7% when the two-page questionnaire was used (38% versus 45%). On the basis of these results, no problem should arise if four more questions are added to the one-page questionnaire. The slight reduction in the response rate of the two-page questionnaire is worrying but could be corrected by the use of telephone interviews.


Subject(s)
Asthma/epidemiology , Surveys and Questionnaires , Adult , European Union , Female , Health Surveys , Humans , Male , Mass Screening/methods , Pilot Projects , Prevalence
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