Diabetes and work: The need of a close collaboration between diabetologist and occupational physician.

AIM: The Italian Society of Occupational Medicine (SIML), the Italian Diabetes Society (SID) and the Association of Diabetologists (AMD) joined a working group that produced a consensus paper aimed to assess the available evidence regarding the interplay between specific working conditions, including shift- and night-time work, working activities at high risk of accidents and work at heights, working tasks requiring high-energy expenditure, working activities at extreme temperatures and diabetes. DATA SYNTHESIS: Diabetes is a group of metabolic disorders caused by defects in insulin secretion and/or action affecting millions of people worldwide, many of whom are or wish to be active members of the workforce. Although diabetes, generally, does not prevent a person from properly performing his/her working tasks, disease complications can significantly compromise a person's ability to work. Therefore, it appears evident the need to understand the relationship between occupational risk factors and diabetes. The working group included in the document some practical recommendations useful to ensure diabetic workers the possibility to safely and effectively undertake their jobs and to adequately manage and treat their disease, also in the workplace. In this perspective concerted action of all the workplace preventive figures, occupational physicians and diabetologists should be strongly encouraged. CONCLUSIONS: Further studies are necessary to define workplace-based interventions, which should be minimally invasive towards the work organization, allowing diabetic workers to fully realize their work skills while improving their wellbeing at work.

Changes in Lipid Composition During Manganese-Induced Apoptosis in PC12 Cells.

Lipid composition of membranes is fundamental to modulate signaling pathways relying on lipid metabolites and/or membrane proteins, thus resulting in the regulation of important cell processes such as apoptosis. In this case, membrane remodeling is an early event important for the activation of signaling leading to cell death and removal of apoptotic cells. In the present study, we analyzed phospholipid, cholesterol and fatty acid content during apoptosis induced by manganese in PC12 cells. Lipid analysis of whole cells and detergent-resistant membranes was carried out by HPLC/GC. Results showed that apoptosis is associated with changes in lipid composition detectable in whole cell extracts, namely cholesterol, phosphatidylserine and phosphatidylethanolamine decreases. Noteworthy, phosphatidylserine level reduction was detectable before to the detection of apoptosis, in correlation with our previous study carried out by radioactive labelling. By contrast, phosphatidylserine and phosphatidylethanolamine changes were not detected in detergent resistant membranes, which instead showed an altered composition in phosphatidylinositol, phosphatidylcholine and sphingomyelin in apoptotic cells.

Phosphatidylserine metabolism modification precedes manganese-induced apoptosis and phosphatidylserine exposure in PC12 cells.

Long-term exposure to high manganese (Mn) levels can lead to Parkinson-like neurological disorders. Molecular mechanisms underlying Mn cytotoxicity have been not defined. It is known that Mn induces apoptosis in PC12 cells and that this involves the activation of some signal transduction pathways. Although the role of phospholipids in apoptosis and signal transduction is well-known, the membrane phospholipid component in Mn-related damage has not yet been investigated. Phosphatidylserine (PS) facilitates protein translocation from cytosol to plasma membrane and PS exposure on the cell surface allows macrophage recognition of apoptotic cells. This study investigates the effects of MnCl2 on PS metabolism in PC12 cells, relating them to those on cell apoptosis. Apoptosis induction decreased PS radioactivity of PC12 cells incubated with radioactive serine. MnCl2 reduced PS radioactivity even under conditions that did not affect cell viability or PS exposure, suggesting that the effects on PS metabolism may represent an early event in cell apoptosis. Thus the latter conditions that also induced a greater PS decarboxylation were utilized for further investigating on the effects on PS synthesis, by measuring the activity and expression of PS-synthesizing enzymes, in cell lysates and in total cellular membranes (TM). Compared with corresponding controls, enzyme activity of MnCl2-treated cells was lower in cell lysates and greater in TM. Evaluating the expression of two isoforms of PS-synthesizing enzyme (PSS), PSSII was increased both in cell lysate and TM, while PSSI was unchanged. MnCl2 addition to control cell lysate reduced enzyme activity. These results suggest Mn plays a dual role on PS synthesis. Once inside the cell, Mn inhibits the enzyme/s, thus accounting for reduced PS synthesis in lysates and intact cells. On the other hand, it increases PSSII expression in cell membranes. The possibility that this occurs to counteract the direct effects of Mn ions on enzyme activity cannot be excluded. The effects on membrane enzyme activity and expression may also participate to PS exposure, observed at longer periods of treatment, by increasing membrane PS content.

Silica particle size and shape: in vitro effects on extracellular matrix metabolism and viability of human bronchial epithelial cells.

Crystal micro-morphology and dimension of silica particles could be responsible for the high prevalence of silicosis as recently found among goldsmiths. In the present study we investigated two samples of silica particles with different surface sizes and shapes for their capacity to induce changes in ECM component production. In addition we investigated if their different effects could be related to cytotoxicity and apoptotic effects. Human bronchial epithelial cells were cultured with or without a sample of Silica used for casting gold jewellery, named in our experiments Silica P or a commercial sample of Silica with different physical and chemical properties, named in our experiments Silica F. After 48 h of exposure PCR analysis determined levels of several matrix components. As induction of the apoptosis cascade, annexin assay, caspase 3 activity and cellular cytoxicity by MTT assay were assayed. Silica F promoted fibronectin, MMP12, tenascin C and Integrins b5 gene expressions more than Silica P. Silica P stimulated more TGFß1 and its TGFßR1 receptor than Silica F. Cytotoxic effects were induced by the two samples of Silica. On the contrary, no alteration in classic apoptotic marker protein expression was observed in presence of either Silica F or Silica P, suggesting silica particles affect ECM production and metalloproteases through a mechanism that does not involve apoptotic activation. Different Silica micromorphology and TGFß signal pathway are linked to lung fibrotic effects but the potential role Silica in apoptotic and toxic reaction remains to be ascertained.

[Epidemiological evidence of possible musculoskeletal, cardiovascular and neoplastic effects in professional drivers]. / Le evidenze epidemiologiche sui possibili danni muscoloscheletrici, cardiovascolari e neoplastici nei lavoratori del settore dei trasporti terrestri.

The road and rail transport sector, since the several work tipology and risk factors for workers safety and health, is an area where assessing exposure effects is very difficult. Muscoskeletal cardiovascular and neoplastic diseases are the disorders more frequently associated to professional drivers. The role of professional driving is rather well-defined in low back pain occurence, correlated to whole body vibration exposure. Professional drivers are at higher risk of ischemic cardiovascular diseases, but it is not clear whether the risk is attributable just to the occupational exposures or also to their life-style risk factors. Evidence of an excess of risk for lung, genito-urinary and hemolymphopoietic cancer is clear in the scientific literature for professional drivers. Anyway the lack in the control of confounding factors, in exposure assessment force to be very cautious in results interpretation.

[Reduction of tobacco smoking among physicians of a hospital in central Italy]. / Riduzione dell'abitudine al fumo di tabacco tra i medici di un'Azienda Ospedaliera dell'Italia centrale.

This study assessed the variations in smoking habit in physicians in a General Hospital in Central Italy in 12 years. Data were collected from medical records of workers who underwent health surveillance in 1998-99 and in 2010-11. The prevalence of smokers was 26.3% (male 25.6%, female 27.6%) in 1998-99 and 19.2% (male 19.8%, female 18.5%) in 2010-11. As compared to 1998-99, the prevalence of smokers in 2010-11 was reduced in both sex and in all age classes. Despite the relevant reduction, the prevalence of smokers among physicians remains still high. Occupational physicians could play an important role against tobacco smoking, as they can provide a brief counseling to all smoking physicians during medical health surveillance at workplace and take part in worksite health promotion programmes.

[Prolonged exposure to crystalline silica Min-U-Sil-5 influences apoptosis or extracellular matrix genes expression in human bronchial epithelial cells]. / L'esposizione prolungata alla silice cristallina Min-U-Sil-5 influenza l'espressione di geni della matrice extracellulare o coinvolti nell'apoptosi in cellule epiteliali bronchiali umane BEAS-2B.

Crystalline silica (Min-U-Sil-5) induces oxidative stress in human bronchial epithelial cells (BEAS-2B), through the intracellular accumulation of ROS that cause oxidative damage leading to the degradation of extracellular matrix (ECM) proteins and to the loss of cell adhesion molecules inducing apoptosis and genotoxic damage. This paper briefly summarizes some of the recent findings from our laboratories with emphasis on the molecular events by which the cronic and cumulative exposure to crystalline silica can induce cellular damage that promotes changes in extracellular matrix and in apoptosis gene expression.

Acute pneumonia in a fire-eater.

Fire-eater's lung, an acute exogenous lipoid pneumonia, is caused when street performers accidentally inhale pyrofluids. We report the case of a young fire-eater who, 12 hours after inhaling an iso-alkanebased pyrofluid, developed fever, dyspnoea, dry cough and intense right chest pain. Radiographic signs of pneumonia emerged two days later. Computed tomography (CT) scans visualized an irregular area of parenchymal consolidation with an air bronchiologram and peripheral ground-glass opacities in the right middle lobe. The diagnostic work-up included microbiological and lung function tests, optic fibre bronchoscopy and an in-depth cyto-immunological analysis of bronchoalveolar lavage fluid. Symptoms gradually improved over a few days. A CT scan one month later showed the thickened parenchymal area in the right middle lobe had almost completely disappeared.

[Smoking ban observance in a general hospital]. / Il rispetto del divieto di fumare in un'Azienda Ospedaliera.

Passive smoking is one of the main risk factors for severe chronic diseases. Hospitals are appropriate settings for promoting tobacco smoking cessation and preventing passive smoking. Moreover, since 2003 Italian Law (no 3/2003) forbids smoking in enclosed workplaces. The smoking ban should be strictly observed in hospitals. This study assessed smoking ban observance and exposure to ETS in a group of paramedical personnel working in a General Hospital (n=1037). Each subject answered a self-administered questionnaire. The prevalence of smokers was 31.2% in females and 31.5% in males. 83% of non-smokers and 66.6% of smokers approved the smoking ban in the hospital but 39.6% of non-smokers and 17.4% of smokers stated it was not observed. Percentages of, respectively, 57.0% and 31.1% in 2004 had dropped in 2005 and in 2006, after Law no 3/2003 was implemented. More than 90% of paramedical personnel declared that workers usually smoked in the workplace. 11.1% of non-smokers reported they were often exposed to ETS and 50% sometimes. These result show the smoking ban was not fully observed in the Hospital, where many workers reported they were exposed to ETS. Occupational Physicians should encourage health workers to stop smoking by offering appropriate counselling.

Comparative in vitro studies on the fibrogenic effects of two samples of silica on epithelial bronchial cells.

The small dimension and particle shape of silica in gypsum used to prepare moulds for lost wax casting might be responsible for the high prevalence of silicosis in gold jewellery. To test this hypothesis, human pulmonary epithelial cell (BEAS-2B) cultures were exposed to two samples of silica with different crystal micro-morphologies: Silica Powder (Silica P) which is used in casting gold jewellery, and no powder Silica (Silica F). Extracellular matrix (ECM) production was evaluated using radio-labelled precursors and quantified by RT-PCR analysis. Expression of basic fibroblast growth factor (FGF2) and its receptor (FGFR2) was also evaluated. The results demonstrated Silica P particles had a very fine lamellar crystalline structure while Silica F was characterized by larger rounded crystals. Silica P stimulated collagen production significantly more than Silica F and downregulated laminin and metalloprotease expression. Both silica samples down-regulated FGF2 but only Silica F enhanced FGF2 receptor expression. In conclusion each Silica sample promoted a profibrotic lung microenvironment in a different manner and also elicited different FGF2 signalling pathways. The data confirm that different micromorphology of Silica particles affects the fibrogenic potential and the molecular mechanisms of dust pathogenicity.

[Crystalline silica can induce oxidative stress by inhibiting glyoxalase system in bronchial epithelial cells]. / La silice cristallina (Min-U-Sil 5) induce stress ossidativo inibendo l'espressione del sistema delle gliossalasi in cellule bronchiali umane (BEAS-2B).

UNLABELLED: Chronic inflammation and reactive oxygen species (ROS) production induced by crystalline silica are involved in the development of silicosis and lung cancer pathogenesis. ROS can generate lipid peroxydation of cell membranes that can produce methylglyoxal (MG), a strong cell proliferation inhibitor and apoptosis inducer. MG is naturally removed by glyoxalase I (GI) and glyoxalase II (GII) through a glutathione (GSH) dependent mechanism. Therefore mRNA expression of glyoxalases is correlated to MG concentration and oxidative stress. OBJECTIVES: evaluate oxidative stress induced by crystalline silica by glyoxalases mRNA expression and methylglyoxal concentration MATERIAL AND METHODS: In bronchial epithelial cell culture (BEAS-2B), exposed to 50 microg/cm2 crystalline silica (Min-U-Sil 5), for 2, 6, 12, and 24 hours, GI and GII mRNA levels and MG intracellular concentration were measured respectively by Real-Time PCR and HPLC. RESULTS: Crystalline silica exposure induced a significant reduction in mRNA expression of glyoxalases and an increase of MG intracellular concentration. CONCLUSIONS: The results suggest a possible use of MG and mRNA expression of GI and GII as crystalline silica induced oxidative stress indicators.

[Smoke habit in a population of apprentices in middle of Italy]. / Abitudine al fumo in una popolazione di apprendisti dell'Italia centrale.

This study assessed the smoking habit in 7,159 apprentices (females: 53.3%) in central Italy. In the period 1996-2006, each apprentice underwent a compulsory health examination to assess fitness for work carried out by specialists in Occupational Medicine. Demographic data and information on schooling, smoking habit, alcohol and coffee intake were collected by a questionnaire. Overall, 51.9% of apprentices were smokers. Smokers were fewer among female apprentices than among the males (48.3% vs 55.9%; chi-square test, p < 0.001). No decrease in the prevalence of smokers was evident during the study period. Low educational level, and daily intake of alcohol and coffee significantly increased the risk of being a smoker. Finding a high percentage of smokers among Italian apprentices with a low educational level who are employed in jobs for which few qualifications are required indicates the need for work-place activities against tobacco smoking habit. Specialists in Occupational Medicine who perform regular health surveillance of workers could play a role in the anti-smoking campaign by integrating their routine work with brief counselling sessions aimed at preventing smoking in young workers and helping smokers to stop and by collaborating in work-place health promotion programmes.

[Urinary 1-naphthol in the general population of Umbria]. / 1-Naftolo urinario nella popolazione generale umbra. Risultati preliminari.

INTRODUCTION: Naphthalene, the most volatile polycyclic aromatic hydrocarbon (PAH), was recently classified as possible human carcinogen by International Agencies for Research on Cancer Humans may be exposed to naphthalene from a wide variety of sources, including occupation, environment, personal habits. We assessed urinary excretion of 1-naphthol (1-NAF), biomarker of naphthalene exposure, in non-occupationally exposed subjects. MATERIALS AND METHODS: Urinary 1-NAF, 1-hydroxypyrene (1-OHP), biomarker of exposure to pyrene and cotinine, biomarker of smoking habits, were measured in 104 adults (53 men, 51 women). RESULTS: 1-NAF concentrations overlapped in males and females (median: men 0.35 Microg/g creat; women: 0.46 microg/g creat). Median concentration of 1-NAF was 6-fold higher in smokers compared to nonsmokers (respectively, 7.7 microg/g creatinine vs 1.3 microg/g creatinine). Between smokers, urinary cotinine was positively correlated to 1-naphthol (rho: 0.69; p < 0.01) and 1-OHP (rho: 0.53; p < 0.01). Higher 1-OHP concentrations were found in smokers (median: smokers 0.16 microg/g creatinine, not-smokers 0.05 microg/g creatinine;). CONCLUSIONS: In our study population, we found that 1-NAF excretion is much higher as compared to 1-OHP excretion. This is due to the ubiquitous presence of naphthalene in the environment. Smoking considerably increase the exposure to naftalene.

Primary DNA damage in chrome-plating workers.

In order to evaluate the primary DNA damage due to occupational exposure to chromium (VI), DNA strand-breaks and apoptosis in peripheral lymphocytes were measured in a group of 19 chrome-plating workers. DNA strand-breaks was assessed by alkaline (pH>13) single-cell microgel electrophoresis ('comet') assay, while apoptosis was measured by flow-cytometry after propidium iodide staining of the cells. Concentrations of chromium in urine, erythrocytes and lymphocytes were investigated as biological indicators of exposure. A group of 18 hospital workers (control group I) and another 20 university personnel (control group II) without exposure to chromium were also studied as controls. The results of the study show that chrome-plating workers have higher levels of chromium in urine, erythrocytes and lymphocytes than unexposed workers. Comet tail moment values, assumed as index of DNA damage, are increased in chromium-exposed workers and results are significantly correlated to chromium lymphocyte concentrations. No difference emerged in the percentage of apoptotic nuclei in exposed and unexposed workers. The study confirms that measurements of chromium in erythrocytes and lymphocytes may provide useful information about recent and past exposure to hexavalent chromium at the workplace. The increase in DNA strand-breaks measured by comet assay suggests this test is valid for the biological monitoring of workers exposed to genotoxic compounds such as chromium (VI).

Laparoscopic cholecystectomy in adult patients with sickle cell disease.

Cholecystectomy is a common surgical procedure performed in patients with sickle cell disease (SCD). Postoperative complications, including acute painful vaso-occlusive crisis and acute chest syndrome, have been described frequently after either traditional or laparoscopic cholecystectomy (LC). It's still not clear if preoperative blood transfusion, hyperhydration, intraoperative body temperature conservation may reduce complications rate. The Authors reviewed the charts of seven patients with SCD operated on LC for symptomatic gallbladder lithiasis and describe their perioperative management. In 3 patients preoperative endoscopic removal of stones was achieved. Five patients with HB lower than 9 g/dl and/or HbS higher than 40% were transfused preoperatively and all the patients were hyperhydrated. Intraoperative monitoring was achieved for early recognition of ventilation to perfusion mismatch and acid-base balance or temperature modifications. The Authors reported only one case of postoperative lower extremities pain. This study suggests that LC is a safe procedure in SCD if appropriate monitoring and perioperative management are achieved.

Blood cadmium concentrations in the general population of Umbria, central Italy.

The aims of this study were (a) to assess blood cadmium (B-Cd) concentrations and to establish a tentative reference interval; (b) to identify significant determinants of B-Cd, in a population from Umbria, Central Italy, which was not occupationally exposed to cadmium (Cd). Four hundred and thirty-four healthy blood-donors volunteered to answer a questionnaire and provide a blood sample for B-Cd analysis, which was performed by graphite furnace atomic absorption spectrophotometry. Blood Cd concentrations ranged from non-detectable values, i.e. below 0.1 microgram/l up to 3.4 micrograms/l and were not normally distributed. The median values and the 95th percentiles were 0.7 and 2.0 micrograms/l, respectively. Concentrations of B-Cd were more than double in smokers than in non-smokers, median values being 1.1 micrograms/l and 0.5 microgram/l, respectively. In current smokers, B-Cd values correlated with the number of cigarettes smoked daily (rs = 0.40, P = 0.0001) and with the cumulative exposure to cigarette smoke (rs = 0.35, P = 0.0001). Concentrations of B-Cd correlated with age in the non-smokers, but not in the smokers and were significantly higher in women than in men only in the non-smokers. Both in smokers and non-smokers, B-Cd concentrations were similar in subjects living in urban or in rural areas. In the whole study population the lower and the upper tentative reference limit were < 0.1 and 2.2 micrograms/l, respectively, as computed by a non-parametric rank-based method. The upper limit was approximately double in smokers than in non-smokers (3.1 micrograms/l and 1.6 micrograms/l, respectively). Our results show that B-Cd concentrations in a general population from Umbria are in the range reported for general populations in Northern Italy and other European Countries. Smoking was the strongest determinant of B-Cd concentrations and age had a lesser effect.