Nicola Murgia

Effects of sub-toxic Cadmium concentrations on bone gene expression program: Results of an in vitro study

Since occupational and environmental exposure to the heavy metal Cadmium (Cd) affects human health this study investigated the effects of exposure to a single, or multiple, sub-toxic Cd concentrations on sub-confluent and confluent human osteoblast growth and expression of specific bone differentiation markers. RT-PCR quantified gene expression of type I collagen, metalloprotease (MMP13), runt-related transcription factor-2 (RUNX2), osterix, osteocalcin, osteonectin, alkaline phosphatase, integrins and bone sialoprotein (BSP). Expression of fibroblast growth factors 1 and 2 (FGF1, FGF2), transforming growth factor-beta(3) (TGFbeta(3)) and bone morphogenetic protein-2 (BMP2) were also evaluated to determine whether Cd-related effects were mediated by an imbalance in expression. Depending on osteoblast concentration and maturation stages, Cd inhibited or stimulated cell growth, decreased type I collagen, increased MMP13, FGF1 and BMP2 gene expression and stimulated the mineralization process only in continuously exposed cultures. These results suggest that in vivo, acute or chronic exposure to sub-toxic Cd concentrations may affect bone formation differently and support the hypothesis that Cd-induced bone disorders may involve downstream changes in growth factor expression. The results are of interest in forensic and occupational medicine in establishing preventive measures to reduce professional exposure risks.

Airborne pollutants and lacunar stroke: a case cross-over analysis on stroke unit admissions.

Particulate air pollution is known to be associated with cardiovascular disease. The relation of particulate air pollution with cerebrovascular disease (CVD) has not been extensively studied, particularly in relation to different subtypes of stroke. A time-series study was conducted to evaluate the association between daily air pollution and acute stroke unit hospitalizations in Mantua, Italy. We analyzed 781 CVD consecutive patients living in Mantua county admitted between 2006–08. Data on stroke types, demographic variables, risk factors were available from the Lombardia Stroke Registry. Daily mean value of particulate matter with a diameter <10 µm (PM10), carbon monoxide, nitric oxide, nitrogen dioxide, sulphur dioxide, benzene and ozone were used in the analysis. The association between CVD, ischemic strokes subtypes and pollutants was investigated with a case-crossover design, using conditional logistic regression analysis, adjusting for temperature, humidity, barometric pressure and holidays. Among the 781 subjects admitted 75.7% had ischemic stroke, 11.7% haemorrhagic stroke 12.6% transient ischemic attack. In men admission for stroke was associated with PM10 [odds ratio (OR) 1.01, 95%; confidence interval (CI) 1.00–1.02; P<0.05]. According to the clinical classification, lacunar anterior circulation syndrome stroke type was related to PM10 level registered on the day of admission for both genders (OR: 1.01, 95%; CI: 1.00–1.02; P<0.05) while for total anterior circulation syndrome stroke only in men (OR: 1.04, 95%; CI 1.01–1.07; P<0.05). In conclusion, our study confirms that air pollution peaks may contribute to increase the risk of hospitalization for stroke and particulate matter seems to be a significant risk factor, especially for lacunar stroke.

Co-occurring psychiatric and substance use disorders among male detainees in Italy

This paper presents data on the prevalence of co-occurring substance use and psychiatric disorders among newly imprisoned males in Italy. Interviewers conducted semi-structured clinical interviews with n=302 male detainees seven days after their admission to the prison of Perugia from August 2005 through July 2006. Over half of male detainees (54.3%) had either a substance use disorder or another psychiatric disorder. One of every five detainees (20.9%) had comorbid substance use and psychiatric disorders. Compared to detainees with psychiatric disorder only, substance use disorder only, or no disorder, detainees with comorbid substance use and psychiatric disorders were significantly more likely to have severe impairment in the areas of employment, substance abuse, family and social functioning, and psychiatric symptoms. Findings underscore the need for careful diagnostic screening at intake, access to treatment during detention, and an effective transition to services at the time of release.

Clinical data and inflammation parameters in patients with cypress allergy treated with sublingual swallow therapy and subcutaneous immunotherapy.

The clinical efficacy of immunotherapy, either by high dose sublingual-swallow therapy (SLIT) or subcutaneous immunotherapy (SCIT), has been demonstrated in patients with pollinosis but few studies have been carried out analysing differences in these treatments in terms of an improvement of clinical and allergic phlogosis parameters. The aim of this double-blind placebo-controlled study is to investigate the efficacy of high dose SLIT and SCIT using a purified standardized Juniperus ashei extract in a population of allergic patients monosensitized to cypress. Forty patients with cypress-allergic rhino conjunctivitis were administered therapeutic or placebo SLIT or SCIT for 12 months. Laboratory parameters were studied, namely the eosinophil cationic protein (ECP) level in nasal lavage and in serum, as well as the number of eosinophils (EOS) in peripheral blood and in nasal lavage and the level of eosinophil chemotactic activity (ECA). These parameters were correlated with clinical symptoms, evaluated by means of the clinical symptoms score (CSS). After SCIT and SLIT the levels of ECP and ECA were reduced in nasal lavage. We also observed a significant reduction in the values of ECP in serum in the patients treated with SLIT. EOS were unchanged in peripheral blood, but significantly reduced in nasal lavage. These data were in accordance with the improvement of clinical symptoms, supported by the close correlation between CSS and laboratory parameters. Our data confirm a clinical improvement correlated with a decline in inflammation parameters after one year of immunotherapy, supporting the hypothesis that treatment with a major allergen of cypress is able to change the course of allergic rhinitis.

Effects of smoking, gender and occupational exposure on the risk of severe pulmonary fibrosis: a population-based case-control study

Objectives To estimate the effects of smoking, gender and occupational exposure on the risk of developing severe pulmonary fibrosis (PF), including dose-response and interaction effects. Methods National case–control study of 171 patients (cases) who had started a long-term oxygen therapy for PF in Sweden between February 1997 and April 2000, and 719 random control participants from the general population. Of these cases, 137 had probable idiopathic PF (IPF). The ORs for smoking, gender and occupational exposure were estimated using Mantel-Haenszel analysis and conditional logistic regression, controlling for age and year of diagnosis. Results The adverse effect of smoking was amplified by male gender and occupational exposure, OR 4.6 (95% CI 2.1 to 10.3) for PF, and OR 3.0 (1.3 to 6.5) for IPF, compared with in non-exposed women. Higher cumulative smoking exposure was linearly associated with increased risks. Compared with smoking less than 10 pack-years, smoking ≥20 pack-years was associated with increased risk of PF and IPF, OR 2.6 (1.4 to 4.9) and OR 2.5 (1.3 to 5.0), respectively. Conclusions Smoking has a dose-related association with increased risk of severe PF. Men with a history of smoking and occupational exposure is a particular risk group for developing severe PF.

COPD management according to old and new GOLD guidelines: an observational study with Italian general practitioners

Abstract Background: Guideline recommendations for COPD management are only partially applied within primary care clinical practice. Objective: To compare the COPD management by Italian general practitioners (GPs) according to either the old GOLD (oGOLD) or the new GOLD (nGOLD) guidelines. Research design and methods: Observational study in different Italian areas. A total of 176 GPs enrolled their patients with a COPD diagnosis. Questionnaires were used to collect data on: COPD symptoms, disease severity, exacerbations, prescribed pharmacological and non-pharmacological treatments. COPD severity was estimated according to oGOLD and nGOLD guidelines. Results: A total of 526 subjects had complete information to assess COPD severity level according to guidelines (symptoms level, spirometry, history of exacerbations). The investigated subjects were more frequently males (71.2%) with a mean age of 72.5 years, and ex-smokers (44.4%). GPs reported sufficient control of the disease in 47.2% of the subjects with over two exacerbations in the last 12 months. Most patients have moderate COPD (51.5%), according to oGOLD, and belong to D groups (high risk, more symptoms) (45.6%), according to nGOLD. Overall, a low use of post-bronchodilator spirometry (65.1%) and of pulmonary rehabilitation (13.4%) was shown. The results highlighted a low prescriptive appropriateness but with higher value according to nGOLD than oGOLD: 61.4% vs 35.6%. Study limitations: Prescription data only provide limited information to judge prescribing quality, thus the results have to be evaluated with caution; moreover, this study was not designed to assess the difference between oGOLD and nGOLD. Conclusions: Guideline recommendations are applied only partially within clinical practice. A higher prescriptive appropriateness is shown by GPs using nGOLD classification. This might be due to the fact that nGOLD, with respect to oGOLD, takes into account anamnestic usual features considered by GPs in their clinical practice.

Risk factors for respiratory work disability in a cohort of pulp mill workers exposed to irritant gases.

BackgroundThe association between chronic respiratory diseases and work disability has been demonstrated a number of times over the past 20 years, but still little is known about work disability in occupational cohorts of workers exposed to respiratory irritants. This study investigated job or task changes due to respiratory problems as an indicator of work disability in pulp mill workers occupationally exposed to irritants.MethodsData about respiratory symptoms and disease diagnoses, socio-demographic variables, occupational exposures, gassing episodes, and reported work changes due to respiratory problems were collected using a questionnaire answered by 3226 pulp mill workers. Information about work history and departments was obtained from personnel files. Incidence and hazard ratios for respiratory work disability were calculated with 95% confidence intervals (CI).ResultsThe incidence of respiratory work disability among these pulp mill workers was 1.6/1000 person-years. The hazard ratios for respiratory work disability were increased for workers reporting gassings (HR 5.3, 95% CI 2.7-10.5) and for those reporting physician-diagnosed asthma, chronic bronchitis, and chronic rhinitis, when analyzed in the same model.ConclusionsThis cohort study of pulp mill workers found that irritant peak exposure during gassing episodes was a strong predictor of changing work due to respiratory problems, even after adjustment for asthma, chronic bronchitis, and chronic rhinitis.

Climate and stroke: a controversial association.

The study recently published by Wang et al. (2009), which is based on one of the largest population-based surveys, shows a trend in the occurrence of intracerebral hemorrhages (ICH) with temperature variations in Brisbane. His work showed a statistically significant increase (15%) of ICH for every 1°C increase in daily T° max. In the literature, the topic is considered controversial, and the study raised many observations that we would like to discuss in this paper. Our group in collaboration with the Department of Neurology at Sohag University (Fawi et al. 2009) in southern Egypt, under the patronage of the Egyptian Ministry for Higher Education, reported a similar trend of higher prevalence of hemorrhagic events in patients admitted to the local hospital during a 2-year survey. In southern Egypt, we observed a peculiar spring–summer trend: our researches demonstrated an astonishing increase in hemorrhagic events. Stroke unit admissions for hemorrhagic stroke reached the surprising prevalence of 47.7% while the local spring– summer temperature range was an average of 33°C (Tmax 40°C, Tmin 26°C). The hemorrhagic events in the autumn– winter time frame reached 31%. We then conducted another similar population-based study in 2006–2008 (Corea et al. 2009). The study included several patients living in the county of Mantua in northern Italy, where the local spring–summer temperature range reaches a maximum of 39.3°C and a minimum of 16°C (mean 29.3°C). We again observed that there was a correlation between increasing temperature and hemorrhagic stroke (Figs. 1 and 2). A report from Brazil (Rufca et al. 2009) found a similar relationship between stroke hospitalization and variation in temperature. A Scottish group recently showed how, in Glasgow (United Kingdom), the risk of ischemic stroke increased by 2.1% with each 1°C increase in T°(Dawson et al. 2009). Others have found similar results; for instance, a study in the province of Van in Turkey (Anlar at al. 2002) demonstrated that significantly greater incidences of ischemic stroke (IS) occurred during the summer, more than in any other season. European studies have reported that different seasonal patterns in the event of brain hemorrhages occurred, with a A. Giua (*) Clinica Neurologica, Università di Sassari, Sassari, Italy e-mail: alexgiua@alice.it

Crystalline silica Min-U-Sil 5 induces oxidative stress in human bronchial epithelial cells BEAS-2B by reducing the efficiency of antiglycation and antioxidant enzymatic defenses

Reactive oxygen species (ROS) play an important role as mediators of pulmonary damage in mineral dust-induced diseases. Studies carried out to date have largely focused on silica-induced production of ROS by lung phagocytes. In this study we investigated the hypothesis that crystalline silica Min-U-Sil 5 can induce elevations in intracellular ROS in human bronchial epithelial cells BEAS-2B, via an indirect mechanism that involves ROS-inducing intracellular factors, through a reduction of antiglycation (glyoxalase enzymes) and antioxidant (paraoxonase 1 and glutathione-S-transferases) enzymatic defenses. The results show that crystalline silica Min-U-Sil 5 causes a significant reduction in the efficiency of antiglycation and antioxidant enzymatic defenses, paralleled by an early and extensive ROS generation, thus preventing the cells from an efficient scavenging action, and eliciting oxidative damage. These results confirm the importance of ROS in development of crystalline silica-induced oxidative stress and emphasize the pivotal role of antiglycation/antioxidant and detoxifying systems in determining the level of protection from free radicals-induced injury for cells exposed to crystalline silica Min-U-Sil 5.

Hymenoptera venom allergy: work disability and occupational impact of venom immunotherapy

Objectives Little is known about the Hymenoptera venom allergy impact on work ability and the effect of venom immunotherapy (VIT) on work. The objective of this study was to evaluate the prevalence and predictors of work disability in patients treated with VIT and the effects of VIT on occupational functioning. Methods 181 patients, aged 18–71 years, treated with VIT while working, were investigated by questionnaire. Participants were classified into employed and self-employed and, based on work exposure to Hymenoptera, into three risk categories: high risk, occasionally high risk and low risk. Work disability was defined as having to have changed jobs/tasks and/or suffered economic loss because of Hymenoptera venom allergy. Predictors of work disability were assessed in logistic regression models. Results 31 (17%) patients reported work disability. Being self-employed and having the severe reaction at work were associated with work disability (p<0.01). Having a high-risk job for exposure to Hymenoptera was a significant predictor of work disability (OR 2.66, 95% CI 1.04 to 6.75). 24% of patients referred a positive effect of VIT on work. Determinants of the positive effect of VIT on work were having a high-risk job for exposure to hymenoptera (OR 3.60, 95% CI 1.52 to 8.51) and having already concluded VIT (OR 2.82, 95% CI 1.30 to 6.14). Conclusions Hymenoptera venom allergy could determine work disability. Patients with Hymenoptera venom allergy having a high-risk job for exposure to Hymenoptera seem to have higher risk of work disability and refer more frequently a positive effect of VIT on work.