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Biomedical subjects

P Colombo

Publications and source records attributed to P Colombo.

At least 19 recordsLinked to original sources
PubMed2006

A hybrid expressing genetically engineered major allergens of the Parietaria pollen as a tool for specific allergy vaccination.

BACKGROUND: Allergy is an immunological disorder affecting about 25% of the population living in the industrialized countries. Specific immunotherapy is the only treatment with a long-lasting relief of allergic symptoms and able to reduce the risk of developing new allergic sensitizations and inhibiting the development of clinical asthma in children treated for allergic rhinitis. METHODS: By means of DNA recombinant technology, we were able to design a head to tail dimer expressing disulphide bond variants of the major allergen of the Parietaria pollen. IgE binding activity was studied by Western blot, ELISA inhibition assays and the skin prick test. T cell recognition was studied by peripheral blood mononuclear cell proliferation. The immunogenicity of the hybrid was studied in a mouse model of sensitization. RESULTS: In vitro and in vivo analysis showed that the disruption of specific cysteine residues in both allergens caused a strong reduction in IgE binding activity of the PjEDcys hybrid. In addition,we were able to show that a reduction in the IgE epitope content profoundly reduced the anaphylactic activity of the hybrid (from 100 to 1,000 times less than wild-type allergens) without interfering with the T cell recognition. Sera from BALB/c mice immunized with the hybrid were able to bind the natural Parietaria allergens and to inhibit the binding of human IgE to wild-type Par j 1 and Par j 2 allergens up to 90%. CONCLUSION: Our results demonstrate that hybrid-expressing disulphide bond variants of the major allergens of the Parietaria pollen displayed reduced allergenicity and maintained T cell reactivity for induction of protective antibodies.

Allergens↗
PubMed2006

Formation of self-organized nanoparticles by lecithin/chitosan ionic interaction.

In this work the production of auto-assembled nanoparticles obtained by the mixing of chitosan and lecithin is presented. The size and surface charge of the nanoparticles were studied as function of the weight ratio between components, the viscosity of the polysaccharide and the pH of the colloidal suspension. In order to elucidate the structure of nanoparticles, micro-FT-IR and elastic neutron scattering experiments have been performed. Results evidenced a strong electrostatic interaction between components and a structure that is neither that of homogeneous spheres nor of coated unilamellar vesicles. Preliminary encapsulation experiments with progesterone, as model lipophilic drug, showed good encapsulation efficiencies.

Algorithms↗
PubMed2006

New transdermal bioadhesive film containing oxybutynin: In vitro permeation across rabbit ear skin.

Oxybutynin is used extensively in the treatment of patients with overactive bladder. The aim of this work was to realize and test in vitro a new transdermal bioadhesive film containing oxybutynin. Transdermal films were prepared by dissolving in water an adhesive (Plastoid), a film-forming polymer (polyvinyl alcohol), a plasticizer (sorbitol) and the drug. The mixture was then spread on siliconized paper and oven-dried. Permeation experiments were conducted in Franz-type diffusion cells using rabbit ear skin as barrier. The donor compartment contained a water solution, the prepared film (with or without backing) or the commercial patch (Oxytrol). The experiments were performed for 24h. Oxybutynin showed good permeation characteristics across the skin. When the film was applied in occlusive conditions the release profiles were much higher than in non-occlusive conditions, reaching 50% of drug permeated after 24h. Compared to the commercial patch Oxytrol, the film was more efficient suggesting that a smaller area or a lower drug loading could be employed. The results obtained show that the bioadhesive film can be a promising and innovative therapeutic system for the transdermal administration of oxybutynin.

Administration, Cutaneous↗
PubMed2006

Overweight and obesity in Italian adults 2004, and an overview of trends since 1983.

OBJECTIVE: Overweight has been increasing in several developed countries over the last few decades. No update information on the issue is available for Italy. DESIGN AND SETTING: We conducted a computer assisted personal in-house interview survey in March-April 2004, on a sample of 2932 Italian individuals (1407 men and 1525 women) aged 18 years or over, representative of the general adult Italian population. Information on weight and height was self-reported. RESULTS: Overall, 3.4% of the Italian adult population were underweight (< 18.5 kg/m2, 0.9% of men and 5.8% of women), 31.3% were overweight (25.0-29.9 kg/m2, 38.4% of men, 24.7% of women), and 8.2% were obese (> or = 30.0 kg/m2, 7.4% of men and 8.9% of women). Overweight or obesity was reported by 14.2% of subjects aged 18-24 years (20.6% of men and 7.6% of women). The highest proportions of overweight and obese subjects were in the 45-64 year age group for men (51.4% overweight, 10.0% obese) and in the > or = 65 year age group for women (38.8% overweight, 13.8% obese). Age- and sex-standardised prevalence of overweight or obesity was 36.0% for more educated subjects, and 54.0% for less educated ones. It was 32.3% in northern, 44.3% in central and 47.0% in southern Italy. Overweight increased from 1983 to the early 1990s, and levelled off thereafter. Prevalence of obesity remained around 8-9% across the last 20 years. CONCLUSIONS: Trends of overweight and obesity in Italy are more favourable than in several developed countries. Still, approximately 15 million of Italian adults are overweight and 4 million obese.

Adolescent↗
PubMed2006

Factors responsible for differences between asymptomatic subjects and patients presenting an IgE sensitization to allergens. A GA2LEN project.

The synthesis of allergen-specific IgE is required for the development of allergic diseases including allergic rhinitis and allergic asthma (patients), but many individuals with allergen-specific IgE do not develop symptoms (asymptomatic subjects). Differences may exist between asymptomatic subjects and patients. Whether the presence of allergen-specific IgE translates into clinical allergy most likely depends on a complex interplay of multiple factors. These include a family history of atopy, the levels of total serum IgE and, allergen-specific IgE or IgG, epitope-specificity of IgE and their degree of polyclonality (mono- vs polysensitized), as yet unidentified serum factors, the balance of T regulatory cells (Treg) and Th1/Th2 cells, the polymorphisms of the high affinity receptor for IgE (FcepsilonRI) and other factors regulating the activation of FcepsilonRI-bearing cells. Asymptomatic subjects may be more often monosensitized than patients who may be more often polysensitized. There are many unanswered important questions that need to be addressed in order to better understand how IgE sensitization translates into clinical allergy. The assessment of differences between the asymptomatic and symptomatic groups of subjects represent one of the scientific programs of Global Allergy and Asthma European Network funded by the European Union and the hypotheses underlying these differences are presented in this paper.

Allergens↗
PubMed2005

Effects of new smoking regulations in Italy.

BACKGROUND: From 10 January 2005 the Italian government banned smoking in all indoor public places. We conducted a population-based survey to provide information on attitudes towards smoking regulation and to disentangle the impact of the smoking ban on tobacco consumption. PATIENTS AND METHODS: We considered data from a survey on smoking, based on 3114 subjects aged 15 or over, representative of the general adult Italian population in terms of age, sex, geographic area and socioeconomic status. RESULTS: Once smoke-free policies were introduced, support for them in the public opinion tended to increase. In Italy, smoke-free policies accounted for around 8% decrease in cigarette consumption in the short run. Moreover, tobacco bans were almost universally accepted, and the smoke-free legislation did not seem to unfavourably affect the business of restaurants or cafes. CONCLUSIONS: The results of our study on the first extensive smoking ban in a large country show the advantages of smoke-free legislations, which may have major public health implications.

Female↗
PubMed2005

Tobacco dependence in the general population in Italy.

BACKGROUND: Measures of tobacco dependence are mainly used in the clinical setting, but limited information is available on tobacco dependence on a population level. MATERIALS AND METHODS: To obtain estimates of tobacco dependence on a population level, a six-item Fagerstrom questionnaire was used in two surveys, conducted in 2002-2003 on a sample of 6773 individuals aged 15 years or over, representative of the Italian adult population. RESULTS: Overall, 27.1% of Italian adults described themselves as current cigarette smokers (32.2% of men, 22.4% of women). Of all smokers, 42.8% were classified as very low dependent, 28.6% as low dependent, 11.0% as intermediate, 13.8% as high and only 3.8% as very high dependent. The proportions of very low/low dependent were 67.4% in men and 76.8% in women. Those of high/very high dependent smokers were 21.4% in men and 12.5% in women, but only 2.8% at age 15-17 years and 8.4% at age 18-24 years. Only 23% of smokers, moreover, found it difficult to avoid smoking in places where smoking was forbidden. CONCLUSIONS: The observation that over two-thirds of smokers on a population level in Italy report low or very low dependence has useful implication for intervention on stopping smoking, particularly in the young, who appear to be low dependent. However, in this age group cessation rates were comparatively low.

Adolescent↗
PubMed2004

Intradural spinal metastasis of renal clear cell carcinoma causing cauda equina syndrome.

Metastasis of renal clear cell carcinoma to the spinal cord are quite rare. Intradural localization causing a cauda equina syndrome has been previously reported only in two cases. The present report details the clinical, surgical and neuroradiological findings of a third case requiring emergency surgery, and presents data available from a brief review of cases reported in the literature. From the data available in the literature, we suggest that cerebral and spinal MRI and PET imaging should be widely performed in the staging of patients treated for renal clear cell carcinoma, in order to early detect CNS involvement.

Adenocarcinoma, Clear Cell↗
PubMed2004

Multicenter trial for the set-up of a MRI quality assurance programme.

Many international protocols related to RMI-QC program are focused on acquisition methods and analysis of several image quality parameters but rarely normality ranges or measurement frequencies are presented. To address this problem we investigated the variability of many magnetic resonance imaging (MRI) systems with the set-up of multicenter trial. The trial was set up to investigate short-and mid-term variability of two fundamental nongeometric image quality parameters: signal-to-noise (SNR) and integral percent uniformity (U%). Ten centers (12 devices) participated to data collection consisting of a three-step-protocol. First, 10 consecutive images of a phantom were collected with a spin echo sequence. As second step the series collection was repeated 24 h later. Finally a single image acquisition was performed twice a week for 5 weeks. The analysis of results allowed us to define a "physiological" variability of +/-3% of the reference level for both parameters and to conclude that a weekly measurement is adequate to detect relevant variations of device performance.

Analysis of Variance↗
PubMed2004

Assessing the presence of abnormal regulation of cortisol secretion by membrane hormone receptors: in vivo and in vitro studies in patients with functioning and non-functioning adrenal adenoma.

Regulation of cortisol secretion by aberrant hormone receptors may play a role in the pathogenesis of ACTH-independent Cushing's syndrome. In this study, the topic was evaluated by combining in vivo and in vitro approaches. Cortisol responses to various stimuli (standard meal, GnRH + TRH, cisapride, vasopressin, glucagon) were assessed in 6 patients with clinical or subclinical adrenal Cushing's syndrome, and non-functioning adrenal adenoma in two cases. Abnormal responses were observed in three patients with Cushing's syndrome; one patient showed a gastric inhibitory polypeptide (GIP)-dependent cortisol rise after meal, together with responses after GnRH and cisapride; the second patient showed an LH-dependent cortisol response to GnRH, and in the third cortisol rose after cisapride. The pattern of receptor expression performed by RT-PCR showed that while GIP-R was only expressed in tumor from the responsive patient, 5-hydroxytryptamine type 4 receptor and LH-R were also present in normal adrenal tissues and tissues from non-responsive patients. Interestingly, an activating mutation of Gsalpha gene was identified in one of these tumors. Therefore, cortisol responses to agents operating via Gs protein coupled receptors (in one case associated with Gsalpha mutation) were found in Cushing's patients, while these responses were absent in the others. The finding of receptor expression in normal and non-responsive tumors suggests that different mechanisms are probably involved in inducing in vivo cortisol responses.

Adenoma↗
PubMed2004

The recombinant major allergen of Parietaria judaica and its hypoallergenic variant: in vivo evaluation in a murine model of allergic sensitization.

BACKGROUND: Par j 1 represents the major allergenic component of Parietaria judaica pollen. Its three-dimensional structure is stabilized by four disulphide bridges. A family of three-dimensional mutants of the recombinant Par j 1 (rPar j 1) allergen, showing reduced allergenicity and retained T cell recognition has been recently developed by site-directed mutagenesis. OBJECTIVE: To develop and characterize a murine model of IgE sensitization to rPar j 1. To evaluate similarities between the murine model and the human IgE response. To investigate in this model the recognition of a hypoallergenic mutant of Par j 1, and to study the immune responses elicited in mice by the mutant itself. METHODS: BALB/c mice were sensitized by two intraperitoneal immunizations with rPar j 1 in alum on days 0 and 21. Allergen-specific serum IgE and IgG responses were studied by direct ELISA and immunoblotting, ELISA inhibition and competitive ELISA. Cell proliferation was evaluated in splenocyte cultures. RESULTS: Sensitization with rPar j 1 induced high levels of IgE and IgG1 vs. low levels of IgG2a. Mouse antibodies specific to rPar j 1 were able to compete with human IgE for recognition of rPar j 1. IgE from mice immunized with rPar j 1 showed a significantly reduced binding activity towards the hypoallergenic variant rPjC, which lacks three disulphide bridges. On the contrary, rPjC was recognized by IgG1 and IgG2a antibodies as well as rPar j 1. The proliferative response to rPjC by splenocytes from mice immunized with rPar j 1 was comparable to that stimulated by rPar j 1. Immunization with rPjC induced low levels of IgE antibodies to the rPjC itself, while IgG and proliferative responses were similar to those induced by rPar j 1. CONCLUSION: Conformational variants of allergens, displaying reduced allergenicity accompanied by retained IgG and T cell recognition, offer a safe, specific and flexible approach to immunotherapy of type I allergy. Our mouse model of IgE sensitization to a recombinant allergen, mimicking the human response to its native counterpart, could provide valuable information for pre-clinical testing of such hypoallergenic molecules.

Allergens↗
PubMed2004

Cytogeography and the evolutionary significance of B chromosomes in relation to inverted rearrangements in a grasshopper species.

The analysis of geographic distribution of polymorphic cytological markers, briefly termed as cytogeography, can be considered an important tool to be applied when studying the evolutionary significance of chromosome variability within a species, either to unravel the adaptive significance of chromosome polymorphisms or to investigate the parasitic nature of some genomic elements. In this article we review cytogeographical studies in Trimerotropis pallidipennis, a grasshopper species whose South American populations display geographical patterns of distribution of inversion and B chromosome polymorphisms. Several lines of evidence that issue from the analysis of the geographic distribution of polymorphic markers suggest that inverted chromosomes are special sequences that are maintained by deterministic forces. On the other hand, the pattern of distribution of B chromosome polymorphism clearly demonstrates its selfish nature, being more frequent in those populations in central environments. We also present the analysis of 272 individuals of T. pallidipennis from Uspallata, and demonstrate that Bs in this population have some influence on body size, enlarging many of the morphometric characters of individuals and we propose it could be the consequence of its genotypic disequilibrium with one inversion. These investigations are finally discussed with regard to the models proposed for the maintenance of B chromosomes in natural populations and in relation to the possible interactions with chromosome inversions.

Animals↗
PubMed2003

Buccal delivery of thiocolchicoside: in vitro and in vivo permeation studies.

Thiocolchicoside, a muscle-relaxant agent, is administered by the oral, intra-muscular and topical route. After oral administration the extent of bioavailability compared with intra-muscular administration is low, due to a first pass effect. In this paper, the delivery of thiocolchicoside through oral mucosa is studied to improve the bioavailability. Thiocolchicoside in vitro permeation through porcine oral mucosa and in vivo buccal transport in humans were investigated. Two dosage forms, a bioadhesive disc and a fast dissolving disc for buccal and sublingual administration of thiocolchicoside, respectively, were designed. The in vitro permeation of thiocolchicoside through porcine buccal mucosa from these dosage forms was evaluated and compared with in vivo absorption. Results from in vitro studies demonstrated that thiocolchicoside is quite permeable across porcine buccal mucosa and that permeation enhancers, such as sodium taurocholate and sodium taurodeoxycholate, were not able to increase its flux. The in vivo thiocolchicoside absorption experiments, in which the drug loss from oral cavity was measured, indicated that both formulations could be useful for therapeutic application. The fast dissolving (sublingual) form resulted in a quick uptake of 0.5 mg of thiocolchicoside within 15 min whereas with the adhesive buccal form the same dose can be absorbed over an extended period of time.

Administration, Buccal↗
PubMed2003

Elevated E-cadherin and alpha/beta-catenin expression after androgen deprivation therapy in prostate adenocarcinoma.

The histological patterns of anti-androgen-treated prostate adenocarcinoma mimic high grade tumors classified according to the widely used Gleason scoring system. However, the biological characteristics of anti-androgen treated carcinoma are largely unknown. E-cadherin, alpha-catenin, and beta-catenin adhesion molecules are down-regulated in pharmacologically untreated high grade prostate carcinoma. In this study, we used immunohistochemical techniques to investigate their expression in twenty acinar adenocarcinomas after anti-androgen therapy in prostatectomy specimens. After adrogen ablation therapy, expression of all these adhesion molecules was higher than that of pretreatment biopsies of the same patient group and high grade matched untreated controls. These results emphasize the inaccuracy of the Gleason score for anti-androgen-treated prostate adenocarcinoma and the more differentiated phenotype of prostate adenocarcinoma after anti-hormonal therapy.

Adenocarcinoma↗
PubMed2003

Prognostic and clinical correlates of angiographically diffuse non-obstructive coronary lesions.

OBJECTIVE: To make a prospective assessment of the clinical and prognostic correlates of angiographically diffuse non-obstructive coronary lesions. DESIGN: Angiographic vessel and extent scores were calculated in 228 clinically stable patients (mean (SD) age, 60 (11) years; 43 women, 185 men) undergoing prospective follow up for the composite end point of death and myocardial infarction. The effect on outcome of clinical variables (age, sex, previous myocardial infarction, diabetes mellitus, smoking habit, systemic hypertension, hypercholesterolaemia, ejection fraction) and angiographic variables (vessel and extent score) was evaluated by Cox's proportion hazard model. RESULTS: The vessel score was 3 in 34 patients (15%), 2 in 78 (34%), 1 in 87 (38%), and 0 in 29 (13%). Median extent score was 60 (range 6-110; first quartile 40, third quartile 70). Forty one events (nine deaths and 32 myocardial infarcts) occurred over a median follow up period of 30 months. Age and extent score were the only multivariate predictors of outcome, but the latter provided 28% additional prognostic information after adjustment for the most predictive variables (gain in chi2 = 7, p < 0.01). A vessel score of 3 was associated with worse survival, while no significant discrimination was possible among the other groups. However, assignment of patients to two groups according to an ROC curve derived cut off value for the extent score made it possible to obtain significant discrimination of survival even in cases with vessel scores of 0 to 2. Age and diabetes were clinical markers of a higher extent score. CONCLUSIONS: The angiographic extent score is a powerful marker of adverse outcome independent of severity and the number of flow limiting coronary lesions, and may reflect the link between clinical risk profile and diffusion of coronary atherosclerosis. Thus it should be of clinical value for targeting aggressive preventive measures.

Aged↗