Workplace health promotion: results of a combined multidisciplinary intervention over a long period - preliminary results.

OBJECTIVE: Obesity is a multifactorial disease that is one of the major public health problems. It is the result of the interaction between behavioral, social and endocrine-metabolic components. Already in the 80s, it was highlighted by the World Health Organization (WHO) that the workplace is an ideal setting for introducing health promotion programs. The aim of the present study was to implement a health promotion program among healthcare workers (HCWs) operating in an Emergency Hospital in Southern Italy, combining diet, sports activity and motivational support over a 24-month period. PATIENTS AND METHODS: Participants were HCWs operating in an Emergency Hospital in Southern Italy. The inclusion criteria were as follows: overweight or obesity, i.e., body mass index (BMI) >25 kg/m2, or waist circumference >102 cm (males), >88 cm (females); dyslipidemia without pharmacological treatment, i.e., total cholesterol >220 mg/dL, or high-density lipoprotein (HDL) cholesterol <35 mg/dL, or low-density lipoprotein cholesterol (LDL) >130 mg/dL, or triglycerides >200 mg/dL; fasting glucose levels >120 mg/dl and/or reduced tolerance to glucose or diabetes mellitus, without pharmacological treatment was determined through HbA1c. RESULTS: The analysis was conducted on 36 participants. Follow-up was performed after twelve (T12) and twenty-four months (T24). The average systolic blood pressure (SBP) and diastolic blood pressure (DBP) values decreased during the time period. The average BMI of both male and female HCWs was significantly reduced from T0 to T12 and from T0 to T24. The triglyceride levels gradually decreased, but not significantly, from T0 to T24. The average blood glucose values decreased from T0 to T12 and from T12 to T24. The number of subjects who started to perform physical activity increased significantly between T0 and T12 and between T0 and T24. CONCLUSIONS: The findings have led to a significant change in HCWs' lifestyles and body perceptions, as well as their ability to work.

Comfort rules for face masks among healthcare workers during COVID-19 spread.

BACKGROUND: The outbreak of Coronavirus disease 2019 (COVID-19) made imperative the use of protective devices as a source control tool. As there is no definite antiviral treatment and effective vaccine, the only efficient means of protecting and mitigating infectious contagion has been the use of personal protective equipment, especially by healthcare workers. However, masks affect the humidification process of inhaled air, possibly leading to a basal inflammatory state of the upper airways. STUDY DESIGN: This is a single-center observational study conducted at the University Hospital of Catania from April 1, 2020, to June 31, 2020. METHODS: We analyzed the role of protective masks on the elimination of upper airways complaints in healthcare workers of the University Hospital of Catania. We evaluated 277 subjects through a self-administered 17 item questionnaire based on respiratory, work performance and health-related quality of life domains. RESULTS: A higher prevalence of nasal and ocular symptoms, perceived reduced work performance, difficulty in concentrating, and sleep disorders were found. After two weeks adhering to a list of good practices that we recommended, significant reversibility of the symptoms investigated and work performance enhancement were observed. CONCLUSIONS: Despite clinical complaints related to personal protective equipment, effective amelioration through usage rules is easily obtained. Given the essential use of protective masks, healthcare workers have to adhere to appropriate work and safety prevention rules.

Pesticide exposure and gender discrepancy in breast cancer.

OBJECTIVE: It is biologically plausible that occupational and environmental pesticide exposure may contribute to breast cancer risk. Persistent chemical compounds, such as pesticides, tend to be lipophilic and are detected in human breast milk and adipose tissue. Therefore, the present systematic review aims to clarify the gender difference in breast cancer concerning pesticide exposure. MATERIALS AND METHODS: A total of 70 studies satisfied the inclusion criteria and were included in the systematic review. RESULTS: From the studies analyzed, it was observed that exposure to pesticides could be a risk factor for breast cancer in women, in particular in young women and in women who experienced menarche at a young age. In contrast, no association was found for breast cancer in men. Female breast cancer is correlated with estrogen receptor-negative tumor characteristics. Breast cancer in men was no correlated with pesticide exposure. CONCLUSIONS: Breast cancer in women has been linked to estrogen receptor positivity, but this positivity appears to be inversely related to fertility. The estrogen-like effects of organochlorine pesticides could be the cause of the observed gender differences.

Transmission mode associated with coronavirus disease 2019: a review.

OBJECTIVE: In late December 2019 in Wuhan (China), Health Commission reported a cluster of pneumonia cases of unknown etiology, subsequently isolated and named Severe Acute Respiratory Syndrome (SARS) Coronavirus 2 (CoV-2). In this review, the main transmission routes and causes of mortality associated with COVID-19 were investigated. MATERIAL AND METHODS: A review was carried out to recognize relevant research available until 10 April 2020. RESULTS: The main transmission routes of COVID-19 have been the following: animal to human and human-to-human pathways, namely: respiratory transmission; oro-fecal transmission; air, surface-human transmission. Transmission from asymptomatic persons, healthcare transmission, and interfamily transmission have been well documented. CONCLUSIONS: SARS-CoV-2 possesses powerful pathogenicity and transmissibility. It is presumed to spread primarily via respiratory droplets and close contact. The most probable transmission pathway is definitely the inter-human one. Asymptomatic patients seem to play a crucial role in spreading the infection. Because of COVID-19 infection pandemic potential, careful surveillance is essential to monitor its future host adaptation, viral evolution, infectivity, transmissibility, and pathogenicity in order to gain an effective vaccine and flock immunity and reduce mortality as soon and as much as it is possible.

The Efficacy and Safety of Lenalidomide plus Rituximab in an Orbital Relapse of Diffuse Large B-Cell Lymphoma.

A 74-year-old male with diffuse large B-cell lymphoma, with an Ann Arbor stage IV-A, was submitted to immune-chemotherapy in 2014, with complete remission of the disease. Two years later, he presented with a left eye swelling leading to exophthalmos and blurred vision. A core biopsy was performed and revealed a local relapse of the disease. He was considered unfit for intensive salvage chemotherapy and was treated with a combination of rituximab and lenalidomide. After six courses of rituximab plus lenalidomide, the patient showed complete remission and was submitted to maintenance therapy with lenalidomide. After 24 months since the start of lenalidomide monotherapy, we did not observe any progression. In this experience, rituximab plus lenalidomide, without radiotherapy, was a safe and effective therapeutic combination in an elderly patient with a localized relapse of DLBCL who was unfit to receive more aggressive therapies.

Detecting familial hypercholesterolemia by serum lipid profile screening in a hospital setting: Clinical, genetic and atherosclerotic burden profile.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is underdiagnosed and public cholesterol screening may be useful to find new subjects. In this study, we aim to investigate the prevalence of FH patients in a hospital screening program and evaluate their atherosclerotic burden using intima-media thickness (IMT). METHODS AND RESULTS: We screened 1575 lipid profiles and included for genetic analysis adults with a low-density lipoprotein (LDL) cholesterol >190 mg/dL and triglycerides <200 mg/dL and first-degree child relatives with LDL cholesterol >160 mg/dL and triglycerides <200 mg/dL. The diagnosis of FH was presumed by Dutch Lipid Clinic Network (DLCN) criteria and confirmed by the presence of the genetic variant. Mean common carotid intima-media thickness (IMT) was assessed using consensus criteria. After confirming LDL cholesterol value and excluding secondary hypercholesterolemia, 56 subjects with a DLCN ≥4 performed genetic analysis. Of these, 26 had an FH genetic variant. The proportion of patients with a mutation having a DLCN score of 6-8 was 75%; in individuals with a DLCN score >8 it was 100%. Mean IMT was higher in FH patients compared to non FH (0.73 [0.61-0.83] vs 0.71 [0.60-0.75] mm, p < 0.01). Moreover, we detected two mutations not previously described. Finally, simple regression analysis showed a correlation of IMT with LDL cholesterol >190 mg/dL and corneal arcus (p < 0.01 and p < 0.001, respectively). CONCLUSIONS: A hospital screening was useful to detect FH subjects with increased atherosclerosis. Also, next-generation sequencing was able to detect new FH mutations.

PhoB activation in non-limiting phosphate condition by the maintenance of high polyphosphate levels in the stationary phase inhibits biofilm formation in Escherichia coli.

Polyphosphate (polyP) degradation in Escherichia coli stationary phase triggers biofilm formation via the LuxS quorum sensing system. In media containing excess of phosphate (Pi), high polyP levels are maintained in the stationary phase with the consequent inhibition of biofilm formation. The transcriptional-response regulator PhoB, which is activated under Pi limitation, is involved in the inhibition of biofilm formation in several bacterial species. In the current study, we report, for the first time, we believe that E. coli PhoB can be activated in non-limiting Pi conditions, leading to inhibition of biofilm formation. In fact, PhoB was activated when high polyP levels were maintained in the stationary phase, whereas it remained inactive when the polymer was degraded or absent. PhoB activation was mediated by acetyl phosphate with the consequent repression of biofilm formation owing to the downregulation of c-di-GMP synthesis and the inhibition of autoinducer-2 production. These results allowed us to propose a model showing that PhoB is a component in the signal cascade regulating biofilm formation triggered by fluctuations of polyP levels in E. coli cells during stationary phase.

Short-term UV-B exposure induces metabolic and anatomical changes in peel of harvested lemons contributing in fruit protection against green mold.

UV-B radiation (UVBR) is a small fraction of the solar spectrum from 280 to 315nm. UVBR produces photomorphogenic acclimation responses in plants, modulating their cellular structure and physiology. Here, changes in the peel of harvested lemons after short time exposure to UVBR were analyzed and its potential effects against fungal infection were studied. In the flavedo, UVBR treatment induced variations in the respiratory profiles and increased the phenolic compound contents. Final products of the flavonoid pathway (flavones, flavonols and anthocyanins) increased more markedly than their precursors (flavanones and dihydroflavonols). The increased accumulation of soluble phenolics in the flavedo of treated lemons is associated with the high antioxidant activity found in the flavedo of these samples. Supporting the biochemical determinations, anatomical observations showed abundant intravacuolar deposits of phenolic compounds and an increase in the cell wall thickness in UVBR-treated samples. Metabolic and anatomical modifications associated to UVBR improved natural defenses against Penicillium digitatum, the causal agent of green mold disease. Our results suggest that mature postharvest lemons exposed to the artificial radiation showed phenotypic plasticity, allowing an acclimation response to UVBR which confers fruit resistance to pathogens. Thus, combination of UVBR with other treatments could represent an important improvement to control postharvest diseases on citrus.

Environmental phosphate differentially affects virulence phenotypes of uropathogenic Escherichia coli isolates causative of prostatitis.

K-12 Escherichia coli cells grown in static media containing a critical phosphate (Pi) concentration ≥25 mM maintained a high polyphosphate (polyP) level in stationary phase, impairing biofilm formation, a phenomenon that is triggered by polyP degradation. Pi concentration in human urine fluctuates according to health state. Here, the influence of environmental Pi concentration on the occurrence of virulence traits in uropathogenic E. coli (UPEC) isolated from acute prostatitis patients was evaluated. After a first screening, 3 isolates were selected according to differential biofilm formation profiles depending on media Pi concentration. For each isolate, biofilm positive and negative conditions were established. Regardless of the isolate, biofilm formation capacity was accompanied with curli and cellulose production and expression of some key virulence factors associated with adhesion. When the selected isolates were grown in their non-biofilm-forming condition, low concentrations of nalidixic acid and ciprofloxacin induced biofilm formation. Interestingly, similar to laboratory strains, polyP degradation induced biofilm formation in the selected isolates. Data demonstrated the complexity of UPEC responses to environmental Pi and the importance of polyP metabolism in the virulence of clinical isolates.

Pediatric autoimmune neuropsychiatric disorder associated with group a streptococcal infection: the role of surgical treatment.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive compulsive disorders (OCD) consistently exacerbate in temporal correlation to a Group A beta-haemolytic streptococcal infection. In children with PANDAS, there is speculation about whether tonsillectomy or adenotonsillectomy might improve the neuropsychiatric course. Our objective was to examine whether such surgery impacted remission or, in patients without remission, modified clinical course of the disease, streptococcal antibody titers, neuronal antibodies or clinical severity of Obsessive-Compulsive Disorder (OCD) and/or tics. Study participants (n = 120) with positive PANDAS criteria were recruited, examined, and divided into surgical or non-surgery groups. The surgical group consisted of children with tonsillectomy or adenotonsillectomy (n=56). The remaining children were categorized as non-surgery (n=64). Clinical follow-up was made every 2 months for more than 2 years. Surgery did not affect symptomatology progression, streptococcal and neuronal antibodies, or the clinical severity of neuropsychiatric symptoms in these children. In conclusion, in our series clinical progression, antibody production, and neuropsychiatric symptom severity did not differ on the basis of surgical status. We cannot uphold surgical management as likely to impact positive remission rates, course of OCD/tics, or antibody concentrations in children with PANDAS.

Tetanus immunity in construction workers in Italy.

BACKGROUND: Tetanus is a serious vaccine-preventable disease that remains a significant health risk in certain occupations. Since 2006, Italy has reported the highest number of cases in Europe. Some professions, such as construction workers, are more exposed to tetanus. AIMS: To evaluate tetanus immunity status and associated factors in construction workers in Italy. METHODS: A cross-sectional study of construction workers attending for periodic occupational health surveillance at one site in Italy between September 2011 and January 2013. Serum tetanus antitoxin levels were measured and analysed according to demographic and clinical variables. RESULTS: All 5275 workers attending for health surveillance between September 2011 and January 2013 agreed to participate. Protective tetanus antitoxin levels (>0.1 IU/ml) were found in 4116 workers (78%). Multivariate logistic regression analysis suggested that the following risk factors were significantly associated with inadequate immunization status: older age (age >58 years, odds ratio [OR] 1.78, 95% confidence intervals [CIs] 1.76-1.84), poor education (no formal education: OR 3.74, 95% CI: 3.69-3.78), unskilled work tasks (OR 2.71, 95% CI: 2.67-2.77) and country of origin (Egypt: OR 1.72, 95% CI: 1.67-1.77; Morocco: OR 1.69, 95% CI: 1.62-1.76). CONCLUSIONS: In this study, a significant proportion of construction workers in Italy were not adequately immunized against tetanus, as required by Italian law. Occupational health professionals should promote and implement vaccination campaigns, especially among migrant workers, for public health and legal reasons.

Formulation and characterization of silk fibroin films as a scaffold for adipose-derived stem cells in skin tissue engineering.

Skin substitutes are epidermal, dermal or complete bilayered constructs, composed by natural or synthetic scaffolds and by adherent cells such as fibroblasts, keratinocytes or mesenchymal stem cells. Silk fibroin is a promising polymer to realize scaffolds, since it is biocompatible, biodegradable, and exhibits excellent mechanical properties in terms of tensile strength. Moreover, fibroin can be added of others components in order to modify the biomaterial properties for the purpose. The aim of this work is to prepare silk fibroin films for adipose-derived stem cell (ADSCs) culture as a novel feeder layer for skin tissue engineering. Pectin has been added to promote the protein conformational transition and construct strength, while glycerol as plasticizer, providing biomaterial flexibility. Eighteen formulations were prepared by casting method using fibroin, pectin (range 1-10% w/w), and glycerol (range 0-20% w/w); films were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry assay, to select the optimal composition. A stable fibroin conformation was obtained using 6% w/w pectin, and the best mechanical properties were obtained using 12% w/w glycerol. Films were sterilized, and human ADSCs were seeded and cultured for 15 days. Cells adhere to the support assuming a fibroblastic-like shape and reaching confluence. The ultrastructural analysis evidences typical active-cell features and adhesion structures that promote cell anchorage to the film, thus developing a multilayered cell structure. This construct could be advantageously employed in cutaneous wound healing or where the use of ADSCs scaffold is indicated either in human or veterinary field.

Influence of night-shift and napping at work on urinary melatonin, 17-ß-estradiol and clock gene expression in pre-menopausal nurses.

Night-workers experience disruption of the sleep-wake cycle and light at night which may increase breast cancer risk by suppressing the nocturnal melatonin surge, resulting in higher levels of circulating estrogens. Night-work may also deregulate peripheral clock genes which have been found to be altered in breast cancer. This study investigated urinary 6-sulfatoxymelatonin (aMT6s), serum 17-beta-estradiol levels in premenopausal shift nurses at the end of the night-shift compared to a control group of daytime nurses. Peripheral clock gene expression in lymphocytes were also investigated. All participants were sampled in the follicular phase of the menstrual cycle. The effect of nurses’ ability to take a short nap during the night-shift was also explored. The shift-work group had significantly lower aMT6s levels than daytime nurses independently of a nap. Night-shift napping significantly influences 17-beta-estradiol levels resulting in higher outcomes in nurses who do not take a nap compared to napping group and daytime workers. Peripheral clock genes expression investigated was not significantly different among the groups. Our findings suggest that shift nurses experience changes in aMT6s levels after a night-shift. Napping habits influence 17-beta-estradiol levels at the end of a night-shift. These findings might be related to the increased cancer risk reported in night-shift workers and suggest that a short nap during night-shifts may exert a positive effect.

Use of Phosphite Salts in Laboratory and Semicommercial Tests to Control Citrus Postharvest Decay.

Potassium phosphite (KP) concentrations that inhibited the germination of 50% of Penicillium digitatum conidia were 229, 334, 360, 469, 498, or 580 mg/liter at pH 3, 4, 5, 6, 7, or 8, respectively. Increasing phosphate content in media reduced phosphite toxicity. To control green or blue mold, fruit were inoculated with P. digitatum or P. italicum, then immersed 24 h later in KP, calcium phosphite (CaP), sodium carbonate, sodium bicarbonate, or potassium sorbate for 1 min at 20 g/liter for each at 25 or 50°C. Mold incidence was lowest after potassium sorbate, CaP, or KP treatments at 50°C. CaP was often more effective than KP but left a white residue on fruit. KP was significantly more effective when fruit were stored at 10 or 15°C after treatment compared with 20°C. Acceptable levels of control were achieved only when KP was used in heated solutions or with fungicides. KP was compatible with imazalil (IMZ) and other fungicides and improved their effectiveness. KP increased thiabendazole or IMZ residues slightly. Phosphite residues did not change during storage for 3 weeks, except they declined when KP was applied with IMZ. KP caused no visible injuries or alteration in the rate of color change of citrus fruit in air or ethylene at 5 µl/liter.

A study of HLA class I and class II 4-digit allele level in Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are represented by rare but life-threatening cutaneous adverse reactions to different drugs. Previous studies have found that in a Han Chinese population from Taiwan and other Asian Countries, a strong genetic association between HLA-class I alleles (B*15:02, B*58:01) and SJS and TEN was induced by carbamazepine and allopurinol, respectively. To identify genetic markers that covered the MHC region, we carried out a case-control association enrolling 20 Caucasian patients with SJS/TEN. Our patient series included 10 cases related to paracetamol, 7 to allopurinol and 3 to different drugs (plaquenil, itraconazol, nabumetone). Healthy controls were represented by 115 Caucasian bone marrow or stem cell donors. The HLA-A*, B*, C*, DRB1*, DQB1*, DQA1* and DPB1* genotyping were determined. The frequencies of HLA-A*33:03 as well as C*03:02 and C*08:01 were significantly higher in SJS/TEN patient subgroup showing allopurinol drug-induced severe cutaneous adverse reactions (SCAR) as compared to controls (28.6% vs 0%, P=0.00002, Pc=0.0011; 28.6% vs 0%, P=0.00002, Pc=0.001; 28.6% vs 0%, P=0.00002, Pc=0.001, respectively). In the same subgroup the frequencies of B*58:01, DRB1*15:02 and DRB1*13:02 alleles, although considerably higher than in control group (42.8% vs 5.2%, P=0.003; 28.6% vs 1.7%, P=0.005; 28.6% vs 3.5%, P=0.037, respectively), appeared no more statistically different after P correction (Pc=0.248; Pc=0.29; Pc=1.00, respectively). In addition, in 10 of the 20 SJS/TEN patient subgroup with paracetamol-induced SCAR no statistically significant association with HLA alleles could be found. However, in the same SJS/TEN patient subgroup showing allopurinol drug-induced SCAR, haplotype analysis indicated that B*58:01, DRB1*13:02 and DRB1*15:02 alleles, that in a single allele analysis lost statistical significance after P correction, may still confer susceptibility, because the B*58:01-DRB1*13:02 and DRB1*15:02-DQB1*05:02 are positively associated with the disease (14.2% vs 0.43%, P= 0.00001, Pc=0.00028; 14.2% vs 0.43%, P=0.00001, Pc=0.00028, respectively). Our results show that in contrast to SCAR-related to paracetamol, where HLA alleles do not appear to be involved, HLA molecules behave as a strong risk factor for SCAR-related to allopurinol even when a limited number of patients are considered.

[Obstructive Sleep Apnea Syndrome (OSAS): The role model of the Occupational Health Physician in specific clinical cases.]. / Sindrome delle Apnee Ostruttive nel Sonno (OSAS): ruolo del Medico Competente di Medicina del Lavoro desunto da specifi ci casi clinici.

Nowadays Sleeping disorders are a very interesting topic in Occupational medicine, they are involved in reduction of working performances and increased risk of work accidents (in work environment or while driving). Medical surveillance made from the Occupational Health Physician can be very helpful in early diagnosis of this kind of disease; during 2008 we fi nd out Obstructive Sleeping Apnea Disease (OSAS) in some Healthcare workers. We reported some clinical cases that show the role model of the occupational health physician in this kind of sickness. Our Experience shows the duty of Occupational health physician it's not limited to medical surveillance, but also to Health Promotion (as wrote in D.Lgs 81/08). This can be obtained by clinical and occupational solutions, like correct work shift planning and lifestyle changes; so the interest of the occupational physician have to be focused on introducing in medical surveillance also measures of health promotion regarding sleep disorders with the aim of preserving health condition in workers.

Cellular damage induced by a sequential oxidative treatment on Penicillium digitatum.

AIM: To investigate the cellular damage on Penicillium digitatum produced by a sequential oxidative treatment (SOT), previously standardized in our laboratory, to prevent the conidia growth. Lethal SOT consists of 2-min preincubation with 10 ppm NaClO followed by 2-min incubation with 6 mmol l(-1) CuSO(4) and 100 mmol l(-1) H(2)O(2) at 25°C. METHODS AND RESULTS: After the application of lethal SOT or sublethal SOT (decreasing only the H(2)O(2) concentration), we analysed several conidia features such as germination, oxygen consumption, ultrastructure and integrity of the cellular wall and membrane. Also, we measured the production of reactive oxygen species (ROS) and the content of thiobarbituric acid-reactive species (TBARS). With the increase of H(2)O(2) concentration in the SOT, germination and oxygen consumption of conidia became inhibited, while the membrane permeability, ROS production and TBARS content of conidia increased. Several studies revealed ultrastructural disorganization in P. digitatum conidia after lethal SOT, showing severe cellular damage without apparent damage to the cell wall. In addition, mycelium of P. digitatum was more sensitive than conidia to the oxidative treatment, because growth ceased and permeability of the membranes increased after exposure of the mycelium to a SOT with only 50 mmol l(-1) H(2)O(2) compared to a SOT of 100 mmol l(-1) for these effects to occur on conidia. CONCLUSION: Our insights into cellular changes produced by the lethal SOT are consistent with the mode of action of the oxidant compounds, by producing both alteration of membrane integrity and intracellular damage. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results allow the understanding of SOT effects on P. digitatum, which will be useful to develop a reliable treatment to control postharvest diseases in view of its future application in packing houses.

[Guidelines for the safe outpatient practice of aesthetic surgery]. / Linee guida per un esercizio sicuro della Chirurgia Estetica in regime ambulatoriale.

This paper presents guidelines for the safe outpatient practice of aesthetic surgery. These guidelines have been prepared by the Lombard Association of Plastic Surgery for Outpatients (ALChiPlA), an association confined to board certified plastic surgeons and holders of official authorizations issued by the Lombard ASL to perform outpatient surgery. The cornerstone of these guidelines is the health and safety of patients, who are turning to this type of surgery in ever increasing numbers. This is the first and thus far the only attempt of its kind and its value is increased by the fact that it has been prepared by specialists who have been carrying out this type of surgery in outpatient situations for years.

Fluoro-edenite fibres induce lung cell apoptosis: an in vivo study.

We previously showed that apoptosis in the lungs of sheep exposed to fluoro-edenite fibres is induced via the receptor pathway. The present study was performed to gain further insights into the mechanisms of activation of programmed cell death induced by the fibres. Fluoro-edenite fibres are similar in size and morphology to some amphibolic asbestos fibres. They have been found in benmoreitic lavas, in the local stone quarry, in building materials and in road paving at Biancavilla, a town in eastern Sicily (Italy), where epidemiological surveys revealed a cluster of mortality from pleural mesothelioma. Inhalation of asbestos fibres can cause chronic inflammation and carcinogenesis. Since fluoro-edenite has been shown to activate the apoptotic process, we set out to characterise the expression of apoptosis-regulating proteins in fluoro-edenite-exposed lung disease and sought to determine if apoptosis results from fluoro-edenite exposure. Lung tissue from apparently healthy sheep habitually grazing near Biancavilla was processed for immunohistochemical localisation of bcl-2 and bax. Results showed epithelial and interstitial bax overexpression, especially in cells directly in contact with the fibres, and negative bcl-2 immunoexpression. TUNEL-positive cells were detected in alveoli and connective tissue. The integrity of alveolar epithelium and alveolar apoptosis are critical determinants in the pathways that initiate fibrogenesis in the lung and fibroblastic foci are usually found close to abnormal or denuded alveolar epithelium. Our results are consistent with the hypothesis that apoptosis is an important mechanism for removing cells with irreparable fluoro-edenite-induced genetic changes that predispose them to a neoplastic evolution.