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1.
J Transl Med ; 21(1): 875, 2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38041166

RESUMO

BACKGROUND: Asbestos lung content is regarded as the most reliable tool for causal attribution of malignant mesothelioma (MM) to previous asbestos exposures. However, there is a lack of studies on asbestos burden in lungs of MM patients in comparison with healthy individuals. This study aims to provide such a comparison, investigating, as well, differences in asbestos lung burden with sex and time trends. METHODS: Asbestos lung content has been assessed on formalin-fixed lung fragments using scanning electron microscopy coupled with energy dispersion spectroscopy (SEM-EDS) on individuals deceased from MM (cases) and healthy subjects without any lung disease who died from violent causes (controls) between 2005 and 2023. RESULTS: Asbestos and asbestos bodies (ABs) were found, respectively, in 73.7% and 43.2% of cases and in 28 and 22% of controls; in MM cases the most represented asbestos types were crocidolite and amosite, whereas in controls it was tremolite-actinolite asbestos. The concentration of both asbestos fibers and ABs was statistically significantly higher in MM cases compared to controls. The mean asbestos fibers width was also significantly higher in cases than controls. Males and females with MM showed similar asbestos and ABs concentrations, but females had higher concentrations of chrysotile, and significantly lower fibers width compared to males. Time trends show that MM lung asbestos concentrations decreased starting in 2011. DISCUSSION: The results suggest a correlation between asbestos burden in lungs and MM risk. The different concentration of chrysotile, as well as the different width of asbestos fibers in MM males and females might reflect a sex difference in response of the lung microenvironment to inhaled asbestos. Finally, this study provides the first pathological evidence of the effect of the ban of asbestos use, demonstrating a significant decrease of asbestos lung content after 2011.


Assuntos
Amianto , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Humanos , Feminino , Masculino , Mesotelioma Maligno/complicações , Asbestos Serpentinas , Estudos de Casos e Controles , Mesotelioma/patologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Pulmão/patologia , Microambiente Tumoral
2.
Carcinogenesis ; 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38069464

RESUMO

The causal attribution of asbestos related diseases to past asbestos exposures is of crucial importance in clinical and legal contexts. Often this evaluation is made based on the history of exposure, but this method presents important limitations. To assess past asbestos exposure, pleural plaques (PP), lung fibrosis and histological evidence of ferruginous bodies (FB) can be used in combination with anamnestic data. However, such markers have never been associated with a threshold value of inhaled asbestos. With this study we attempted to shed light on the dose-response relationship of PP, lung fibrosis and FBs, investigating if their prevalence in exposed individuals who died from malignant mesothelioma (MM) is related to the concentration of asbestos in lungs assessed using scanning electron microscopy equipped with energy dispersive spectroscopy. Moreover, we estimated the values of asbestos concentration in lungs associated with PP, lung fibrosis and FB. Lung fibrosis showed a significant positive relationship with asbestos lung content, whereas PP and FB did not. We identified, for the first time, critical lung concentrations of asbestos related to the presence of PP, lung fibrosis and FB at histology (respectively, 19 800, 26 400 and 27 400 fibers per gram of dry weight), that were all well-below the background levels of asbestos identified in our laboratory. Such data suggest that PP, lung fibrosis and FB at histology should be used with caution in the causal attribution of MM to past asbestos exposures, while evaluation of amphibole lung content using analytical electron microscopy should be preferred.

3.
Occup Med (Lond) ; 72(8): 534-540, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-35943161

RESUMO

BACKGROUND: In both the epidemiological and legal context, the causal attribution of asbestos-related lung diseases requires retrospective exposure assessment (REA). AIMS: To assess the correlation between the retrospective assessment of occupational and anthropogenic environmental exposure to asbestos and its content in the lung tissue. METHODS: Based on the available exposure information, a team of occupational physicians retrospectively assessed cumulative exposure to asbestos in 24 subjects who died of asbestos-related diseases. The asbestos lung content was analysed using analytical scanning electron microscope (SEM-EDS). The Log10 asbestos fibre count in the autoptic samples was predicted as a function of the Log10 estimated cumulative exposure using univariate regression analysis. RESULTS: The median count of asbestos fibres by grams of dry weight (ff/gdw) in the lung tissue was 81 339 (range 0-2 135 849.06); it was 287 144 (range 0-2 135 849.06) among the occupationally exposed, and 29 671 (range 0-116 891) among the subjects who only had anthropogenic environmental and/or household exposure. Amphiboles, and particularly amosite (52%) and crocidolite (43%), were detected in all the study subjects. Chrysotile was not detected in any of the samples. Overall, the retrospective estimate of lifetime cumulative exposure to asbestos showed a moderate correlation with the total asbestos fibre count in the autoptic lung, with the regression model explaining 38-55% of the total variance. CONCLUSIONS: Detailed information on occupational, environmental and household exposure circumstances would be indispensable for experienced industrial hygienists and/or occupational physicians to reliably assess past exposure to amphiboles or mixed types of asbestos.


Assuntos
Amianto , Humanos , Estudos Retrospectivos , Amianto/toxicidade
4.
Occup Med (Lond) ; 70(9): 672-679, 2020 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-33269398

RESUMO

BACKGROUND: Healthcare workers (HCWs) are commonly infected by SARS-CoV-2 and represent one of the most vulnerable groups. Adequate prevention strategies are necessary to guarantee HCWs' safety, as well as to prevent dissemination of the infection among patients. AIMS: To describe a case series of SARS-CoV-2-positive HCWs in a large public healthcare organization in Milan (Italy) during the most devastating weeks of the epidemic and analyse the sources, symptoms and duration of SARS-CoV-2 infection. METHODS: This study included 172 SARS-CoV-2-positive HCWs who were infected between the 25th of February and the 7th of April 2020. A nasopharyngeal swab (NPS) and RT-PCR were used to indicate. RESULTS: Initially, the most common sources of infection were other positive HCWs (49%). Medical doctors and nursing assistants were most frequently infected, with infection rates of 53/1000 and 50/1000, respectively. COVID-19 departments were less affected than internal medicine, surgery, intensive care, or emergency room. The most commonly reported symptom was mild cough, while loss of smell (anosmia) and loss of taste (ageusia) were reported as moderate and severe by 30-40% of HCWs. The time necessary for 50% of workers to recover from the infection was 23 days, while it took 41 days for 95% of HCWs to become virus-free. CONCLUSIONS: HCWs are commonly infected due to close contacts with other positive HCWs, and non-COVID departments were most affected. Most HCWs were asymptomatic or subclinical but contact tracing and testing of asymptomatic HCWs help identify and isolate infected workers.


Assuntos
Teste para COVID-19/estatística & dados numéricos , COVID-19/diagnóstico , Pessoal de Saúde/estatística & dados numéricos , Mão de Obra em Saúde/estatística & dados numéricos , Exposição Ocupacional/estatística & dados numéricos , SARS-CoV-2/isolamento & purificação , Adulto , COVID-19/epidemiologia , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Fatores de Risco
5.
Appl Ergon ; 83: 102796, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30611466

RESUMO

Biomechanical overload in the wrist flexor and extensor muscles, together with awkward hand positions during work activities, can result in occupational wrist and hand disorders. Dairy workers, specifically those that work in the milking parlor, are exposed to highly repetitive and forceful exertions of the upper limb throughout their work shift. There are very few studies that have investigated the determinants that contribute to the risk of distal upper limb musculoskeletal disorders among dairy workers. The purpose of the present study was to identify the variables affecting the biomechanical overload of the distal upper limb among milking parlor workers, define risk profiles, and propose possible interventions to reduce the high physical loads to the distal upper limb during milking activities. Forty male workers from the three most common milking parlor systems in Lombardy Italy were recruited to participate in this study. Multiple correspondence analysis of personal characteristics and occupational risk factors, followed by cluster analysis, led to the identification of three distinct groups of workers. Low, medium and high risk profiles were assigned to each group based on the risk assessments performed using the Strain Index and electromyography of the distal upper limb. The main risk determinants were workstation characteristics, work organization and milking routine. A well-organized milking routine, milking cluster weight below 2.4 kg or the use of supporting arms for the milking cluster may reduce the risk of biomechanical overload.


Assuntos
Doenças dos Trabalhadores Agrícolas/etiologia , Indústria de Laticínios/estatística & dados numéricos , Doenças Musculoesqueléticas/etiologia , Análise e Desempenho de Tarefas , Adulto , Eletromiografia , Humanos , Masculino , Doenças Profissionais , Extremidade Superior , Local de Trabalho
6.
Toxicol Lett ; 316: 20-26, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31465813

RESUMO

Health-care personnel handling antineoplastic drugs could be at risk for adverse health effects. We aimed to evaluate genotoxic and cytotoxic effects of antineoplastic drug exposure of personnel preparing and administering such drugs in three Oncology Hospitals in Italy enrolling 42 exposed subjects and 53 controls. Furthermore, we aimed to study the possible influence of XRCC1 and hOGG1 DNA repair genes polymorphisms on genotoxicity induced on buccal cells. We performed workplace and personal monitoring of some drugs and used exposure diary informations to characterize the exposure. Urinary 5-FU metabolite (α-fluoro-ß-alanine) was measured. Buccal Micronucleus Cytome (BMCyt) assay was used to evaluate DNA damage and other cellular anomalies. GEM and 5-FU contamination was found in 68% and 42% of wipe/swab samples respectively. GEM deposition was found on workers' pads while no α-fluoro-ß-alanine was found. BMCyt-assay showed higher genotoxicity and cytotoxicity on nurses administering antineoplastics than on preparators and controls. Among micronucleus (MN) positive (with MN frequency higher than 1.5‰) exposed subjects, the percentage of those carrying XRCC1 mut/het genotype was higher than in MN positive-controls. Using the sensitive BMCyt assay, we demonstrated that handling antineoplastics still represents a potential occupational health risk for workers that should be better trained/informed regarding such risks.


Assuntos
Antineoplásicos/efeitos adversos , Desoxicitidina/análogos & derivados , Monitoramento Ambiental/métodos , Fluoruracila/efeitos adversos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos , Mucosa Bucal/efeitos dos fármacos , Recursos Humanos de Enfermagem no Hospital , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Enfermagem Oncológica , Adulto , Antineoplásicos/urina , Biomarcadores/urina , Estudos de Casos e Controles , DNA Glicosilases/genética , Desoxicitidina/efeitos adversos , Desoxicitidina/urina , Feminino , Fluoruracila/urina , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/metabolismo , Exposição Ocupacional/prevenção & controle , Polimorfismo Genético , Medição de Risco , Fatores de Risco , Urinálise , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Gencitabina
7.
J Prev Med Hyg ; 60(1): E12-E17, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31041405

RESUMO

INTRODUCTION: In recent years, a phenomenon known as "vaccine hesitancy" has spread throughout the world, even among health workers, determining a reduction in vaccination coverage (VC).A study aimed at evaluating VC among healthcare workers (HCWs) in 10 Italian cities (L'Aquila, Genoa, Milan, Palermo, Sassari, Catanzaro, Ferrara, Catania, Naples, Messina) was performed. MATERIALS AND METHODS: Annex 3 of the Presidential Decree n. 445 of 28 December 2000 was used to collect information on the vaccination status of HCWs. The mean and standard deviation (SD) were calculated with regard to the quantitative variable (age), while absolute and relative frequencies were obtained for categorical data (sex, professional profile, working sector, vaccination status). The connection between VC and the categorical variables was evaluated by chi-square method (statistical significance at p < 0.05). The statistical analyses were performed by SPSS and Stata software. RESULTS: A total of 3,454 HCWs participated in the project: 1,236 males and 2,218 females.The sample comprised: physicians (26.9%), trainee physicians (16.1%), nurses (17.2%) and other professional categories (9.8%). Low VC was generally recorded. Higher VC was found with regard to polio, hepatitis B, tetanus and diphtheria, while coverage was very low for measles, mumps, rubella, pertussis, chickenpox and influenza (20-30%). CONCLUSIONS: This study revealed low VC rates among HCWs for all the vaccinations. Measures to increase VC are therefore necessary in order to prevent HCWs from becoming a source of transmission of infections with high morbidity and/or mortality both within hospitals and outside.


Assuntos
Enfermeiras e Enfermeiros/estatística & dados numéricos , Médicos/estatística & dados numéricos , Cobertura Vacinal/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Transmissão de Doença Infecciosa do Profissional para o Paciente , Itália , Masculino , Pessoa de Meia-Idade
8.
Occup Med (Lond) ; 67(7): 574-578, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29016828

RESUMO

BACKGROUND: European Union (EU) Directive 89/391 addressed occupational health surveillance, which recommends to provide workers with 'access to health surveillance at regular intervals', aiming to prevent work-related and occupational diseases. AIMS: To investigate how EU countries adopted this Directive. METHODS: We invited one selected representative per member state to complete a questionnaire. RESULTS: All 28 EU countries implemented the Directive in some form. Workers' health surveillance (WHS) is available to all workers in 15 countries, while in 12, only specific subgroups have access. In 21 countries, workers' participation is mandatory, and in 22, the employer covers the cost. In 13 countries, access to WHS is not available to all workers but depends on exposure to specific risk factors, size of the enterprise or belonging to vulnerable groups. In 26 countries, the employer appoints and revokes the physician in charge of WHS. Twelve countries have no recent figures, reports or cost-benefit analyses of their WHS programmes. In 15 countries where reports exist, they are often in the native language. CONCLUSIONS: Coverage and quality of occupational health surveillance should be evaluated to facilitate learning from good practice and from scientific studies. We propose a serious debate in the EU with the aim of protecting workers more effectively, including the use of evidence-based WHS programmes.


Assuntos
Emprego/legislação & jurisprudência , Saúde Ocupacional/normas , Vigilância da População/métodos , Análise Custo-Benefício , Emprego/estatística & dados numéricos , Europa (Continente)/epidemiologia , Humanos , Doenças Profissionais/epidemiologia , Saúde Ocupacional/estatística & dados numéricos , Inquéritos e Questionários , Recursos Humanos
9.
Am J Transplant ; 17(5): 1370-1379, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27862923

RESUMO

The aim of this study (ClinicalTrials.gov, NCT01744470) was to determine the efficacy and safety of two different doses of extended-release tacrolimus (TacER) in kidney transplant recipients (KTRs) between 4 and 12 mo after transplantation. Stable steroid-free KTRs were randomized (1:1) after 4 mo: Group A had a 50% reduction in TacER dose with a targeted TacER trough level (C0 ) >3 µg/L; group B had no change in TacER dose (TacER C0 7-12 µg/L). The primary outcome was estimated GFR at 1 year. Of 300 patients, the intent-to-treat analysis included 186 patients (group A, n = 87; group B, n = 99). TacER C0 was lower in group A than in group B at 6 mo (4.1 ± 2.7 vs. 6.7 ± 3.9 µg/L, p < 0.0001) and 12 mo (5.6 ± 2.0 vs. 7.4 ± 2.1 µg/L, p < 0.0001). Estimated GFR was similar in both groups at 12 mo (group A, 56.0 ± 17.5 mL/min per 1.73 m²; group B, 56.0 ± 22.1 mL/min per 1.73 m²). More rejection episodes occurred in group A than group B (11 vs. 3; p = 0.016). At 1 year, subclinical inflammation occurred more frequently in group A than group B (inflammation score [i] >0: 21.4% vs. 8.8%, p = 0.047; tubulitis score [t] >0: 19.6% vs. 8.7%, p = 0.076; i + t: 1.14 ± 1.21 vs. 0.72 ± 1.01, p = 0.038). Anti-HLA donor-specific antibodies appeared only in group A (6 vs. 0 patients, p = 0.008). TacER C0 should be maintained >7 µg/L during the first year after transplantation in low-immunological-risk, steroid-free KTRs receiving a moderate dose of mycophenolic acid.


Assuntos
Rejeição de Enxerto/etiologia , Isoanticorpos/sangue , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Tacrolimo/farmacologia , Doadores de Tecidos , Transplantados , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/sangue , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/farmacologia , Isoanticorpos/imunologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
11.
Am J Transplant ; 16(9): 2670-5, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26990694

RESUMO

Pretransplantation adaptation of the daily dose of tacrolimus to CYP3A5 genotype is associated with improved achievement of target trough concentration (C0 ), but whether this improvement affects clinical outcomes is unknown. In the present study, we have evaluated the long-term clinical impact of the adaptation of initial tacrolimus dosing according to CYP3A5 genotype: The transplantation outcomes of the 236 kidney transplant recipients included in the Tactique study were retrospectively investigated over a period of more than 5 years. In the Tactique study, patients were randomly assigned to receive tacrolimus at either a fixed dosage or a dosage determined by their genotype, and the primary efficacy end point was the proportion of patients for whom tacrolimus C0 was within target range (10-15 ng/mL) at day 10. Our results indicate that the incidence of biopsy-proven acute rejection and graft survival were similar between the control and the adapted tacrolimus dose groups, as well as between the patients who achieve the tacrolimus C0 target ranges earlier. Patients' death, cancer, cardiovascular events, and infections were also similar, and renal function did not change. We conclude that optimization of initial tacrolimus dose using pharmacogenetic testing does not improve clinical outcomes.


Assuntos
Citocromo P-450 CYP3A/genética , Rejeição de Enxerto/tratamento farmacológico , Falência Renal Crônica/genética , Transplante de Rim/efeitos adversos , Farmacogenética , Tacrolimo/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Genótipo , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Tacrolimo/farmacocinética , Distribuição Tecidual
12.
Work ; 55(4): 747-756, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28059827

RESUMO

BACKGROUND: Dairy milking is a demanding work task that has been associated with hand and wrist musculoskeletal disorders. Clinical approaches to identify the early effects of musculoskeletal disorders among dairy parlor workers' wrist have not been well defined. OBJECTIVES: The purpose of this pilot study was to develop a study protocol that would assist in the identification and quantification of hand and wrist disorders among dairy workers that perform tasks in the dairy parlor. Additionally, such a study protocol was needed to perform relatively rapid assessments of the wrist/hand on large samples of dairy workers. METHODS: Fourteen dairy parlor workers were assessed for i) upper limb symptoms and work history through questionnaire, ii) a physical examination of the upper limb and in particular wrists and iii) wrist ultrasonography. An additional 21 unexposed paired participants (the control group) also participated in the data collection. RESULTS: The study results identified two ultrasound acoustic windows characterized by the highest predictive value for alteration of the wrist's structure. Study results indicated an impairment of the distal median nerve in structure and mobility and impairment of the distal tendon of the muscle extensor carpi ulnaris that included dislocation and frank damage. CONCLUSIONS: This study identified at least two acoustic windows that should be assessed with ultrasound studies on larger groups and in prospective periodical health surveillance of dairy workers. The study confirmed the wrist was at risk for biomechanical stress among workers conducting milking tasks in the dairy parlors.


Assuntos
Transtornos Traumáticos Cumulativos/diagnóstico , Indústria de Laticínios/métodos , Traumatismos do Punho/diagnóstico , Adulto , Doenças dos Trabalhadores Agrícolas/epidemiologia , Doenças dos Trabalhadores Agrícolas/patologia , Estudos Transversais , Transtornos Traumáticos Cumulativos/epidemiologia , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Ultrassonografia/métodos
13.
Occup Med (Lond) ; 65(8): 667-72, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26452392

RESUMO

BACKGROUND: Hepatitis E virus (HEV) infection is endemic in many developing countries, causing substantial morbidity. Transmission is primarily faeco-oral and is associated with both sporadic infections and epidemics in areas where poor sanitation and weak public health infrastructures exist. Recently, it has become clear that HEV is also an endemic disease in industrialized countries. Moreover, a porcine reservoir and growing evidence of zoonotic transmission have been reported in these countries, suggesting the possibility of occupational transmission to man. AIMS: To summarize the current knowledge on the epidemiology and prevention of transmission of HEV infection in occupational settings. METHODS: The following key words were used to explore PubMed: hepatitis E, disease, epidemiology, profession(al), occupation(al). RESULTS: After screening of the results, 107 publications were retained. In non-endemic regions, seroprevalence varied from a few per cent (2-7.8%) in Europe, Japan and South America to 18.2-20.6% in the USA, Russia, UK, southern France and Asia. A meta-analysis of 12 cross-sectional studies evaluating HEV immunoglobulin G (IgG) seroprevalence in individuals occupationally exposed to swine showed greater odds of seropositivity in the exposed group but also a high degree of heterogeneity. A funnel plot suggested publication bias. CONCLUSIONS: There was a significant association between occupational exposure to swine and HEV IgG seroprevalence, but the level of prevalence detected depended also on the type of HEV IgG kits used. Further research, including on mechanisms and risk factors for infection, as well as the development of better serological tests for identification of infection, is required.


Assuntos
Criação de Animais Domésticos , Doenças Transmissíveis Emergentes/virologia , Vírus da Hepatite E/patogenicidade , Hepatite E/transmissão , Doenças Profissionais/virologia , Exposição Ocupacional/prevenção & controle , Doenças dos Suínos/virologia , Animais , Ásia/epidemiologia , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/transmissão , Reservatórios de Doenças , Europa (Continente)/epidemiologia , Feminino , Hepatite E/prevenção & controle , Humanos , Masculino , Doenças Profissionais/prevenção & controle , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/transmissão
14.
Am J Transplant ; 15(3): 800-5, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25588704

RESUMO

CYP3A4*22 is an allelic variant of the cytochrome P450 3A4 associated with a decreased activity. Carriers of this polymorphism may require reduced tacrolimus (Tac) doses to reach the target residual concentrations (Co). We tested this hypothesis in a population of kidney transplant recipients extracted from a multicenter, prospective and randomized study. Among the 186 kidney transplant recipients included, 9.3% (18 patients) were heterozygous for the CYP3A4*22 genotype and none were homozygous (allele frequency of 4.8%). Ten days after transplantation (3 days after starting treatment with Tac), 11% of the CYP3A4*22 carriers were within the target range of Tac Co (10-15 ng/mL), whereas among the CYP3A4*1/*1 carriers, 40% were within the target range (p = 0.02, OR = 0.19 [0.03; 0.69]). The mean Tac Co at day 10 in the CYP3A4*1/*22 group was 23.5 ng/mL (16.6-30.9) compared with 15.1 ng/mL (14-16.3) in the CYP3A4*1/*1 group, p < 0.001. The Tac Co/dose significantly depended on the CYP3A4 genotype during the follow-up (random effects model, p < 0.001) with the corresponding equivalent dose for patients heterozygous for CYP3A4*22 being 0.67 [0.54; 0.84] times the dose for CYP3A4*1/*1 carriers. In conclusion, the CYP3A4*22 allelic variant is associated with a significantly altered Tac metabolism and carriers of this polymorphism often reach supratherapeutic concentrations.


Assuntos
Alelos , Citocromo P-450 CYP3A/genética , Imunossupressores/farmacocinética , Transplante de Rim , Tacrolimo/farmacocinética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Hum Exp Toxicol ; 33(2): 170-84, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23857031

RESUMO

Concentrations of 36 polychlorinated biphenyl (PCB) congeners were measured in serum of 372 Italian residents of general population living in Novafeltria, Pavia, and Milan. Total PCB level differed significantly between these sites (p < 0.0001) with median concentrations of 836.50, 1354.57, and 2062.08 pmol/g lipid, respectively. However, there is no evidence for the difference in distribution of total PCB levels by genders. Total dioxin-like PCBs differed significantly (p < 0.0001) between the sites (median 109.78, 50.88, and 166.99 pmol/g lipid, respectively) and genders of Novafeltria and Pavia (p = 0.011 and 0.009, respectively). PCB 138, 153, 170, and 180 differed significantly between the places of residence (p < 0.0001) with higher values in Milan population. In the overall population, total PCB and PCB 138, 153, 156, 170, and 180 correlated positively with age (correlations range between 0.320 and 0.569, p < 0.0001). In Novafeltria, the correlations ranged between 0.545 and 0.670, and in Pavia, the correlations ranged between 0.516 and 0.666. In Milan, correlations with age range between 0.327 and 0.417 for total PCB and congeners 138, 153, and 180. With an exception of PCB 170, there was no evidence of significant difference in the distribution of most abundant PCB congeners and total PCB across the body mass index categories.


Assuntos
Poluentes Ambientais/sangue , Bifenilos Policlorados/sangue , Adulto , Idoso , Envelhecimento , Índice de Massa Corporal , Exposição Ambiental , Poluentes Ambientais/química , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Bifenilos Policlorados/química , Fatores Sexuais , Adulto Jovem
16.
Hum Exp Toxicol ; 32(12): 1323-39, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23857032

RESUMO

Despite extensive use of organochlorinated pesticides (OCPs) such as dichlorodiphenyltrichloroethane (DDT) in Italy in the 1940s to 1970s, especially for public health control of malaria mosquitoes, information on their exposure levels among the general population is limited. These OCPs can be a source of health risk to human. A total of 137 blood samples were collected from residents of the general population of three Italian towns, Novafeltria, Pavia and Milan, to determine the levels of eight OCPs in blood serum. The concentrations of beta-hexachlorocyclohexane, hexachlorobenzene (HCB), 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethylene, 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE), 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane, 1,1-dichloro-2,2-bis (4-chlorophenyl)ethane, 1,1,1-trichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)-ethane and 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane were measured by gas chromatography-mass spectrometry. Variations in serum concentrations of OCPs with respect to place of residence, gender, age and body mass index (BMI) were evaluated by non-parametric tests. p,p'-DDE and HCB were the most abundant and major contributors of total OCP concentration. Their levels differed significantly between the three towns with a trend Milan > Novafeltria > Pavia (p < 0.0001). Females had significantly higher concentrations of HCB and p,p'-DDE than males in the overall population sample. HCB concentrations were significantly higher in females than in males of Milan (p = 0.029). We observed positive correlations of p,p'-DDE and HCB with age in Novafeltria subjects (r = 0.468, p = 0.004). Total OCP concentrations differed significantly across BMI categories (p = 0.018) in overall population. We have demonstrated a clear pattern of the main OCPs in a fairly large population. Generally, our study provides information on OCPs exposure among the Italian general population and provides indications for further investigations.


Assuntos
Poluentes Ambientais/sangue , Hidrocarbonetos Clorados/sangue , Praguicidas/sangue , Adulto , Idoso , Índice de Massa Corporal , Colesterol/sangue , Monitoramento Ambiental , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Adulto Jovem
17.
Toxicology ; 307: 123-35, 2013 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-23116691

RESUMO

The immune system can be the target of many chemicals, with potentially severe adverse effects on the host's health. In Western countries pesticides, together with new and modified patterns of exposure to chemicals, have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, certain autoimmune diseases and cancers. Xenobiotics may initiate, facilitate or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors, modifying immune tolerance and activation pathways. The purpose of this article is to update the evidence of pesticide immunotoxicity. Even if experimental data as well as sporadic human studies indicate that some pesticides can affect the immune system, overall, existing epidemiological studies are inadequate to raise conclusions on the immunotoxic risk associated to pesticide exposure. The available studies on the effects of pesticides on human immune system have several limitations including poor indication on exposure levels, multiple chemical exposures, heterogeneity of the approach, and difficulty in giving a prognostic significance to the slight changes often observed. Further studies are necessary, and they should be preferably carried out through comparison of pre and post-exposure findings in the same group of subjects with a matched control group. Attempt should be made to define the prognostic significance of slight changes often observed. Animal and in vitro studies are also important and necessary to scientifically support epidemiological evidences on pesticide-induced immunotoxicity.


Assuntos
Doenças do Sistema Imunitário/induzido quimicamente , Praguicidas/toxicidade , Carbamatos/toxicidade , Fungicidas Industriais/toxicidade , Humanos , Hidrocarbonetos Clorados/toxicidade , Sistema Imunitário/efeitos dos fármacos , Fatores Imunológicos/toxicidade , Intoxicação por Organofosfatos/etiologia
18.
G Ital Med Lav Ergon ; 34(3 Suppl): 393-7, 2012.
Artigo em Italiano | MEDLINE | ID: mdl-23405671

RESUMO

Our experience in assessment and management of chemical risk in agriculture consists of three lines: i) definition and modeling of the relationships between different exposure determinants to create the possibility of doing risk assessment without measurements ii) identification, from the Acceptable Operator Exposure Levels (AOEL), of provisional biological exposure indices for pesticides; iii) identification of analytical approaches adequate for the production of the measures needed to support the above mentioned activities starting from the use of multi-residue methods, allowing the determination in one run of several active ingredients and metabolites.


Assuntos
Agricultura , Exposição Ocupacional , Praguicidas , Humanos , Exposição Ocupacional/efeitos adversos , Praguicidas/efeitos adversos , Praguicidas/urina , Medição de Risco
19.
G Ital Med Lav Ergon ; 34(3 Suppl): 406-8, 2012.
Artigo em Italiano | MEDLINE | ID: mdl-23405674

RESUMO

Agricultural activities expose workers to biological risk, due to the close contact that could occur with pathogens' reservoirs, such as soil, animals, manure and animal products. The paper describes factors that have contributed on the reduction or eradication of zoonoses, such as brucellosis, salmonellosis and bovine tuberculosis (monitoring and prevention of animal infectious diseases, industrialization and mechanization of agricultural activities), and on the other hand the emergence of new risks and new diseases (adaptability of microorganisms, generation of new strains, antibiotic resistance, dissemination of vectors). The role of Occupational Medicine in the prevention of zoonoses is discussed.


Assuntos
Cruzamento , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/prevenção & controle , Zoonoses/etiologia , Animais , Humanos , Fatores de Risco
20.
G Ital Med Lav Ergon ; 34(3 Suppl): 423-4, 2012.
Artigo em Italiano | MEDLINE | ID: mdl-23405679

RESUMO

Tebuconazole (TEB) is a fungicide widely used in vineyards. This work aimed at the identification of urinary metabolites of TEB for the biological monitoring of exposure, and to study their kinetics of excretion. Major urinary metabolites of TEB in rats are t-butyl-hydroxy-and-carboxy-tebuconazole (TEB-OH and TEB-COOH). TEB and these metabolites were determined in urine samples of 5 wine growers who collected each void before (24 hours), during and after (48 hours) TEB application. These chemicals were found in 95%, 100% and 100% of the samples with levels of < 1.5-13.4 microg/L for TEB, 5.2-749 microg/L for TEB-OH e 2.8-234 microg/l for TEB-COOH. TEB-OH is the major metabolite of TEB, its concentration increases at the end of exposure and peaks after 16-24 hours. TEB-COOH has similar pattern. TEB-OH and TEB -COOH are promising candidates for biological monitoring of TEB exposure; preliminary results suggest the day after the application as the best sampling time.


Assuntos
Agricultura , Fungicidas Industriais/urina , Exposição Ocupacional/análise , Triazóis/urina , Humanos , Fatores de Tempo , Vitis
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