Cosmetic Talcum Powder as a Causative Factor in the Development of Diseases of the Pleura

This chapter describes some of what is known about the effects of talc as cosmetic or pharmaceutical talcum powder on the pleura and other organs of the human body. It further describes some of the already known mechanisms of how it interacts with human cells and tissue to cause diseases, specifically in the pleura. The effects of talcum powder are well established that the range of diseases include clinical or subclinical inflammation, granulomatous disease and tumors, in the pleura mainly mesotheliomas. Also included are some preliminary evidence indicating what happens in vitro with macrophages in response to talc morphologically and the consequences following the treatment with the release of factors such as chemokines, cytokines and oxidants

Comments on the 2014 Helsinki Consensus Report on Asbestos

Background: The Finnish Institute of Occupational Health (FIOH) convened an Expert Committee in 2014 to update the 1997 and 2000 Helsinki criteria on asbestos, asbestosis, and cancer. Methods: The Collegium Ramazzini reviewed the criteria for pathological diagnosis of the diseases caused by asbestos presented in the 2014 Helsinki Consensus Report and compared them with the widely used diagnostic criteria developed in 1982 by the College of American Pathologists and the National Institutes of Occupational Safety and Health (CAP-NIOSH). Findings: The sections of the Helsinki Consensus Report dealing with pathological diagnosis are based on a biased and selective reading of the scientific literature. They are heavily influenced by the outdated and incorrect concept that analysis of lung tissue for asbestos bodies and asbestos fibers can provide accurate information on past exposure to asbestos. Five specific problems are :1.Over-reliance on the detection of “asbestos bodies” as indicators of past exposure to asbestos.2.Over-reliance on asbestos fiber counts in lung tissue as an indicator of past exposure to asbestos.3.Use of the scanning electron microscope (SEM) at low magnification as a tool for evaluation of asbestos-related disease.4.Failure to recognize that chrysotile is the predominant type of asbestos fiber found in pleural mesothelioma tissue.5.Postulating the existence of a threshold for development of an asbestos-related lung cancer.. Conclusion: Accurate diagnosis of the diseases caused by asbestos must be based on a carefully obtained history of occupational exposure. An accurate exposure history is a far more sensitive and specific indicator of asbestos exposure than asbestos body counting or lung fiber burden analysis. Ethical note: The sections of the 2014 Helsinki Consensus Report on asbestos, asbestosis, and cancer dealing with pathologic diagnosis of the diseases caused by asbestos appear to have been influenced by members of the Expert Committee with undisclosed financial conflicts of interest

ASBESTOS LUNG BURDEN DETERMINATION IN AN URBAN POPULATION FROM MILAN, ITALY. ANALYSIS OF A NECROSCOPIC SERIES FROM 2009 TO 2011.

The present study analyzed the asbestos lung burden from a necroscopic series of the Milan general population. The study was performed on 55 cases free from asbestos-related disease undergone a judicial autopsy at the Forensic Institute of Forensic Medicine of Milan in the period running from 2009 to 2011. For each study case multiple lung samples were digested and vacuum-filtered on 0.2 \u3bcm pore size polycarbonate membranes and then were analyzed by both traditional Light Microscopy (for counting of morphologically typical Asbestos Bodies) and EDXA-Scanning Electron Microscopy (for counting of all asbestos fibers). The SEM-analysis also extended to the count of inorganic fibers other than asbestos. The Asbestos Bodies prevalence in the series was 14.5% with the positive cases having an AB count ranging from 10 to 110 AB/g dry. No Asbestos Bodies were found in the subjects younger than 30 years. Asbestos fibers were SEM-detected in 63.6% of the study cases, with a higher detection frequency for amphiboles than for chrysotile (58.2% versus 20%). An asbestos content lower than the SEM analytical sensibility was found in 80% of the subjects younger than 30 years. Commercial Amphiboles were detected as frequently as NonCommercial Amphiboles. NonCommercial amphiboles were mainly represented by tremolite fibers. The estimated median value was 110,000 ff/g dry (IQ range 62,250-275,000 ff/g dry) for all the asbestos fibers, 91,600 ff/g dry (IQ range 60,000-180,000 ff/g dry) for the amphibole fibers and 51,600 ff/g dry (IQ range 46,600-65,000 ff/g dry) for the chrysotile fibers. The maximum estimated burden for all asbestos fibers was 2,000,000 ff/g dry. Thirteen cases showed an amphibole burden higher than the Helsinki cut offs for occupational exposure: three cases showed a total amphibole burden higher than 1,000,000 ff/g, while other 10 cases showed an amphibole burden for fibers longer than 5 \u3bcm higher than the 100,000 ff/g dry. A comparison was performed between our results and the results coming from two distinct occupational-exposed populations examined by the same SEM laboratory. The maximum measured asbestos burden in our population was lower than the minimum measured asbestos burden among asbestos-textile workers, jute recycling workers and asbestos-cement workers. Just one asbestos-cement worker and 4 silk/cotton-textile workers showed asbestos lung concentrations overlapping our experimental results. A positive linear relationship was observed between asbestos lung burden and age at death. Sex, residential district, birthplace and smoking habit did not significantly influence the median asbestos lung burden. The mean dimension for the detected asbestos fibers was 4.19 x 0.19 \u3bcm with a 20.6 mean aspect ratio. Chrysotile fibers (mean dimension 2.74 x 0.09 \u3bcm) were significantly shorter and thinner than amphibole fibers, the NonCommercial Amphibole fibers (mean dimension 5.65 x 0.47 \u3bcm) being also significantly thicker than the Commercial Amphibole fibers (mean dimension 4.86 x 0.17 \u3bcm). Asbestos fibers traditionally supposed to be fibrogenic and carcinogenic in humans were very infrequently detected. The median talc burden was very similar to the median asbestos lung burden and the global non-asbestos fibers lung burden well outnumbered the asbestos fibers burden. Also for inorganic fibers other than asbestos a positive linear relationship with age at death was observed

Diagnostic limitations of lung fiber counts in asbestos-related diseases

# Background Lung dust fibre analyses have been used by some pathologists to estimate past asbestos exposure in the workplace and its related health risks. Asbestos, however, especially the predominately applied chrysotile asbestos type, undergoes translocation, clearance and degradation in the lungs. # Objectives We quantified the asbestos fibre and ferruginous (asbestos) body (FB) content in human tissue with respect to the German asbestos ban in 1993 and the interim period of more than 20 years in order to evaluate the diagnostic evidence of these analyses for asbestos-related diseases (ARD). # Methods Lung dust analyses have been used in empirical assessments of ARD since 1982. Tissue samples of about 2 cm^3^ were used and processed in standardized manner. FB was analysed by light microscopy and asbestos fibres by scanning transmission electron microscopy (STEM). # Results Chrysotile and amphibole fibre concentrations in the lung tissue depend roughly on the cumulative asbestos exposure levels in the workplace. However, the concentration of lung asbestos fibre and FB depends on the year of examination and especially on the interim period. As the interim period increases, the asbestos fibre burden decreases. There is no relationship between FB and chrysotile asbestos fibre concentrations and only a weak correlation between FB and crocidolite fibre concentrations. There was no significant difference in chrysotile and amphibole fibre concentrations as well as in FB counts between the different ARD. # Conclusions Due to the length of interim periods, a past exposure to chrysotile or amphibole asbestos can no longer be detected with FB or asbestos fibre measurement in lung tissue. This means that negative results of such measurements cannot disprove a qualified occupational case history of asbestos exposures and the related health risks due to the fibrogenic and carcinogenic potential of asbestos

Non-Neoplastic and Neoplastic Pleural Endpoints Following Fiber Exposure

Exposure to asbestos fibers is associated with non-neoplastic pleural diseases including plaques, fibrosis, and benign effusions, as well as with diffuse malignant pleural mesothelioma. Translocation and retention of fibers are fundamental processes in understanding the interactions between the dose and dimensions of fibers retained at this anatomic site and the subsequent pathological reactions. The initial interaction of fibers with target cells in the pleura has been studied in cellular models in vitro and in experimental studies in vivo. The proposed biological mechanisms responsible for non-neoplastic and neoplastic pleural diseases and the physical and chemical properties of asbestos fibers relevant to these mechanisms are critically reviewed. Understanding mechanisms of asbestos fiber toxicity may help us anticipate the problems from future exposures both to asbestos and to novel fibrous materials such as nanotubes. Gaps in our understanding have been outlined as guides for future research

Malignant pleural mesothelioma retrospective analysis of the demographics, asbestos lung fibre burden and pathology

Abstract: Background: Asbestos mining operations have left South Africa with a legacy of asbestos contamination. Hence asbestos-related diseases continue to be a problem. Currently there are no South African studies that have determined the relationship between asbestos type, fibre sizes or asbestos burden and the development of histological subtypes of mesothelioma. Objectives: The aim of this study was to describe the demographics and asbestos fibre burden of individuals with mesothelioma. The associations between the asbestos type, fibre sizes and asbestos burden and the histological subtype of mesothelioma were also determined. Methods: The records of all deceased miners, ex-miners, Asbestos Relief Trust and Kgalagadi Relief Trust compensation Trust claimants in the PATHAUT database who were histologically diagnosed with mesothelioma for the period Jan 2006 – Dec 2016 (11 years) were reviewed...M.Tech. (Biomedical Technology

Asbestos-Related Pleural Diseases: The Role of Gene-Environment Interactions

Several pleural diseases have been associated with asbestos exposure. Asbestos exposure may lead to the development of benign pleural diseases, such as pleural plaques, diffuse pleural thickening, and pleural effusion, as well as to the development of malignant mesothelioma, a highly aggressive tumour of the pleura. Asbestos exposure related to pleural diseases may be occupational or environmental. Although the causal relationship between asbestos-related pleural diseases and asbestos exposure has been well confirmed, the role of genetic factors in the development of these diseases needs to be further investigated and elucidated. The results of the studies performed so far indicate that in addition to asbestos exposure, genetic factors as well as the interactions between genetic factors and asbestos exposure may have an important impact on the risk of asbestos-related pleural diseases, especially malignant mesothelioma. This chapter aims to present how the risk of developing asbestos-related pleural diseases may be influenced by asbestos exposure, genetic factors, interactions between different genetic factors, as well as interactions between different genetic factors and asbestos exposure

Molecular Alterations in Asbestos-Related Lung Cancer

Background: Asbestos is a well known cancer-causing mineral fibre, which has a synergistic effect on lung cancer risk in combination with tobacco smoking. Several in vitro and in vivo experiments have demonstrated that asbestos can evoke chromosomal damage and cause alterations as well as gene expression changes. Lung tumours, in general, have very complex karyotypes with several recurrently gained and lost chromosomal regions and this has made it difficult to identify specific molecular changes related primarily to asbestos exposure. The main aim of these studies has been to characterize asbestos-related lung cancer at a molecular level. Methods: Samples from asbestos-exposed and non-exposed lung cancer patients were studied using array comparative genomic hybridization (aCGH) and fluorescent in situ hybridization (FISH) to detect copy number alterations (CNA) as well as microsatellite analysis to detect allelic imbalance (AI). In addition, asbestos-exposed cell lines were studied using gene expression microarrays. Results: Eighteen chromosomal regions showing differential copy number in the lung tumours of asbestos-exposed patients compared to those of non-exposed patients were identified. The most significant differences were detected at 2p21-p16.3, 5q35.3, 9q33.3-q34.11, 9q34.13-q34.3, 11p15.5, 14q11.2 and 19p13.1-p13.3 (p<0.005). The alterations at 2p and 9q were validated and characterized in detail using AI and FISH analysis in a larger study population. Furthermore, in vitro studies were performed to examine the early gene expression changes induced by asbestos in three different lung cell lines. The results revealed specific asbestos-associated gene expression profiles and biological processes as well as chromosomal regions enriched with genes believed to contribute to the common asbestos-related responses in the cell lines. Interestingly, the most significant region enriched with asbestos-response genes was identified at 2p22, close to the previously identified region showing asbestos-related CNA in lung tumours. Additionally, in this thesis, the dysregulated biological processes (Gene Ontology terms) detected in the cell line experiment were compared to dysregulated processes identified in patient samples in a later study (Ruosaari et al., 2008a). Commonly affected processes such as those related to protein ubiquitination, ion transport and surprisingly sensory perception of smell were identified. Conclusions: The identification of specific CNA and dysregulated biological processes shed some light on the underlying genes acting as mediators in asbestos-related lung carcinogenesis. It is postulated that the combination of several asbestos-specific molecular alterations could be used to develop a diagnostic method for the identification of asbestos-related lung cancer.Bakgrund: Asbest är en välkänd cancerframkallande mineralfiber, som i kombination med tobaksrökning ökar risken för lungcancer flerfalt. Flera in vitro och in vivo studier har visat att asbest kan framkalla kromosomskador och förändringar i genexpression. Lungtumörer har i allmänhet mycket komplicerade karyotyper med flera återkommande duplicerade och deleterade kromosomregioner, vilket har gjort det svårt att identifiera specifika molekylära avvikelser som kan associeras med asbestexponering. Det främsta syftet med dessa studier har varit att karaktärisera asbestrelaterad lungcancer på molekylär nivå. Metoder: Prover från asbestexponerade och icke exponerade patienter med lungcancer undersöktes med hjälp av jämförande genomisk hybridisering på mikroarray (aCGH) och fluorescerande in situ hybridisering (FISH) för att identifiera kromosomavvikelser, samt med mikrosatellitanalys för att identifiera allel-obalans (AI). Dessutom utfördes in vitro studier på asbestexponerade cellinjer med hjälp av mikroarrays som mäter enskilda geners expression. Resultat: Aderton kromosomregioner med asbestrelaterade avvikelser identifierades. De mest markanta skillnaderna upptäcktes i 2p21-p16.3, 5q35.3, 9q33.3-q34.11, 9q34.13-q34.3, 11p15.5, 14q11.2 och 19p13.1-p13.3 (p<0,005). Avvikelserna på kromosomarmarna 2p och 9q karakteriserades i detalj och verifierades med hjälp av AI- och FISH-analys på prover från ett ökat antal patienter. In vitro studier genomfördes för att undersöka tidiga förändringar i genexpression som orsakats av asbestexponering i tre olika lungcellinjer. Resultaten avslöjade särskilda asbestrelaterade genexpressionsprofiler och biologiska processer, samt kromosomregioner berikade med gener som antas bidra till de gemensamma asbestrelaterade responserna i cellinjerna. Den mest signifikanta regionen, överrepresenterad med asbestresponsgener, var 2p22 som ligger nära det tidigare identifierade området på 2p med asbestrelaterade kromosomavvikelser i lungtumörer. I denna avhandling jämfördes också de förändrade biologiska processerna (genontologiska termerna) som upptäcktes i cellinjeexperimentet med förändrade processer som identifierats i asbestexponerade och icke exponerade patienters prover, i en senare studie (Ruosaari et al., 2008a). Gemensamt förändrade processer var bl.a. kopplade till protein ubiquitinering, jontransport och överraskande nog, luktförnimmelse. Slutsatser: Kartläggningen av specifika kromosomavvikelser och förändrade biologiska processer kastar ljus över de bakomliggande generna som fungerar som medlare i asbestrelaterad lungkarcinogenes. Det kan antas att en kombination av flera asbestspecifika molekylära förändringar kunde användas för att utveckla en diagnostisk metod, som följaktligen kunde särskilja mellan asbestrelaterad och icke asbestrelaterad lungcancer.TAUSTA: Asbesti on tunnettu syöpää aiheuttava mineraalikuitu, jolla on tupakoinnin yhteydessä synergistinen vaikutus keuhkosyövän riskiin. Useat in vitro- ja in vivo-tutkimukset ovat osoittaneet, että asbesti voi aiheuttaa kromosomivaurioita ja muutoksia geenien ilmentymisessä. Keuhkosyövän karyotyyppi on yleensä hyvin monimutkainen ja toistuvat kromosomialueiden monistumat sekä häviämät ovat yleisiä. Tästä syystä on ollut vaikeaa tunnistaa spesifisiä molekyylitason muutoksia, jotka liittyvät pääasiassa asbestialtistumiseen. Päätavoite näissä tutkimuksissa on ollut asbestiin liittyvän keuhkosyövän tunnistaminen molekyylitasolla. MENETELMÄT: Asbestialtistuneiden ja altistumattomien keuhkosyöpäpotilaiden näytteet tutkittiin käyttäen vertailevaa genomista hybridisaatiota mikrosiruilla (aCGH) ja fluoresenssi in situ hybridisaatiota (FISH), joilla havaitaan kromosomialueiden kopiolukumuutokset, sekä mikrosatelliittianalyysia, jolla havaitaan alleeliepätasapaino (AI). Lisäksi asbestialtistuneita solulinjoja tutkittiin käyttäen geeniekspressiomikrosiruja. TULOKSET: Kahdeksallatoista kromosomialueella osoitettiin kopiolukueroja asbestialtistuneiden ja altistumattomien potilaiden näytteiden välillä. Merkittävimmät erot havaittiin kromosomialueilla 2p21-p16.3, 5q35.3, 9q33.3-q34.11, 9q34.13-q34.3, 11p15.5, 14q11.2 ja 19p13.1-p13.3 (p <0,005). Muutokset 2p ja 9q alueilla karakterisoitiin tarkemmin ja varmennettiin käyttäen AI- ja FISH-analyysejä laajemmassa tutkimusaineistossa. Lisäksi mikrosiruilla tutkittiin muutokset geenien ilmentymisessä asbestialtistuksen jälkeen kolmessa eri keuhkosolulinjassa. Tutkimuksessa tunnistettiin asbestialtistukseen liittyviä geenien ilmentymisprofiileja sekä muuttuneita biologisia prosesseja. Lisäksi havaittiin solulinjoille yhteisten asbestiin liittyvien vastegeenien rikastuttamia kromosomaalisia alueita. Merkittävin asbestivastegeenejä sisältävä alue oli 2p22, joka sijaitsee lähellä aiemmin keuhkosyövissä tunnistettua asbestiin liittyviä kopiolukumuutoksia sisältävää aluetta 2p:ssa. Tässä väitöskirjassa vertailtiin myös asbestialtistuneiden solulinjojen muuttuneita biologisia prosesseja (geeniontologiatermejä) niihin muuttuneisiin prosesseihin, joita myöhemmin havaittiin asbestialtistuneiden potilaiden näytteissä (RUOSAARI et al., 2008a). Yhteiset muuttuneet prosessit liittyivät proteiinien ubikitinaatioon, ionikuljetukseen ja yllättävästi hajuaistimukseen. JOHTOPÄÄTÖKSET: Spesifisten kopiolukumuutosten ja muuttuneiden biologisten prosessien tunnistaminen asbestiin liittyvässä keuhkosyövässä valottaa taustalla olevia geenejä, jotka toimivat välittäjinä asbestin aiheuttamassa keuhkokarsinogeneesissä. Useita asbestiin liittyviä molekyylitason muutoksia voitaisiin käyttää asbestiin liittyvän ja liittymättömän keuhkosyövän erottavien diagnostisten menetelmien kehittämisessä

Panorama dos processos bioqu?micos e gen?ticos presentes no mesotelioma maligno.

O mesotelioma maligno (MM) ? um c?ncer extremamente agressivo, com elevado per?odo de lat?ncia e resistente aos protocolos de quimioterapia, al?m de ser extremamente fatal, com taxa de sobreviv?ncia m?dia inferior a um ano. O desenvolvimento do MM ? fortemente correlacionado com a exposi??o ao amianto e erionita, assim como ao v?rus s?mio 40. Apesar de v?rios pa?ses terem banido o uso de amianto, o MM tem se mostrado de dif?cil controle e sua incid?ncia tende a aumentar nos pr?ximos anos. No Brasil, o MM n?o ? amplamente estudado do ponto de vista gen?tico e bioqu?mico. Al?m disso, poucos estudos epidemiol?gicos foram realizados at? o momento, e o perfil de incid?ncia do MM n?o est? bem estabelecido na popula??o brasileira. O objetivo deste estudo foi revisar a literatura em rela??o ao processo de transforma??o maligna e seus respectivos mecanismos de tumorig?nese no MM.Malignant mesothelioma (MM) is a highly aggressive form of cancer, has a long latency period, and is resistant to chemotherapy. It is extremely fatal, with a mean survival of less than one year. The development of MM is strongly correlated with exposure to asbestos and with other factors, such as erionite and simian virus 40. Although various countries have banned the use of asbestos, MM has proven to be difficult to control and there appears to be a trend toward an increase in its incidence in the years to come. In Brazil, MM has not been widely studied from a genetic or biochemical standpoint. In addition, there have been few epidemiological studies of the disease, and the profile of its incidence has yet to be well established in the Brazilian population. The objective of this study was to review the literature regarding the processes of malignant transformation, as well as the respective mechanisms of tumorigenesis, in MM