Antineoplastic drugs contamination of workplace surfaces in two Portuguese hospitals

Despite the classification as known or suspected human carcinogens, by the International Agency for Research on Cancer, the antineoplastic drugs are extensively used in cancer treatment due to their specificity and efficacy. As human carcinogens, these drugs represent a serious threat to the healthcare workers involved in their preparation and administration. This work aims to contribute to better characterize the occupational exposure of healthcare professionals to antineoplastic drugs, by assessing workplace surfaces contamination of pharmacy and administration units of two Portuguese hospitals. Surface contamination was assessed by the determination of cyclophosphamide, 5-fluorouracil, and paclitaxel. These three drugs were used as surrogate markers for surfaces contamination by cytotoxic drugs. Wipe samples were taken and analyzed by HPLCDAD. From the total of 327 analyzed samples, in 121 (37%) was possible to detect and quantify at least one drug. Additionally, 28 samples (8.6 %) indicate contamination by more than one antineoplastic drug, mainly in the administration unit, in both hospitals. Considering the findings in both hospitals, specific measures should be taken, particularly those related with the promotion of good practices and safety procedures and also routine monitoring of surfaces contamination in order to guarantee the appliance of safety measures

Surfaces contamination with 5-Fluorouracil in two Portuguese hospitals

Background - The use of antineoplastic drugs in cancer therapy is increasing due to their action in cancer cells. Carcinogenic, mutagenic and teratogenic effects. Some studies demonstrated that nurses and pharmacy personnel involved in preparation or administration are exposed to antineoplastic drugs. Aim: assess 5-Fluorouracil (5-FU) contamination on the surfaces of two Portuguese Hospitals (preparation and administration units). 5-FU is one of the most frequently antineoplastic agent used in Portuguese Hospitals and can be easily absorbed through the skin. This drug can be used as an marker of surfaces contamination and exposure and have been extensively discussed in other studies

Green tea epigallocatechin-3-gallate (EGCG) oxidative stress and DNA damage

Epigallocatechin-3-gallate (EGCG) antioxidant properties have been demonstrated however, increasing evidence indicates that EGCG produces reactive oxygen species. The aim of this study was to evaluate the effect of EGCG intake during 90 days in hematological cardiovascular risk factors, vitamins A and E, DNA damage, and oxidative damage in human blood. Peripheral blood from 30 healthy individuals (10 males and 20 females; 18 – 45 years), was collected at time 0 (T0) and time 90 (T90). During 90 days, participants ingested capsules of green tea extract (225mg EGCG) daily. Hematological cardiovascular risk factors including lipid profile and liver function parameters were assessed using colorimetric methods. Vitamins A and E in serum were quantified by HPLC and analysis of DNA damage and oxidative damage was performed by comet assay. Our results showed that lipid profile and liver function parameters are not affected by EGCG and serum levels of vitamin E increased, but not vitamin A. An increase in DNA damage and DNA oxidative damage after 90 days of EGCG consumption was also reported. The results suggest that EGCG can induce DNA damage, possibly due to ROS induction, with an associated increase of the antioxidant vitamin E, however without alteration of hematological cardiovascular risk factors.info:eu-repo/semantics/publishedVersio

Profesionalna izloženost citotoksičnim lijekovima: koliko je važno čišćenje površina za njezino sprječavanje odnosno smanjenje

Healthcare workers who prepare or administer cytotoxic agents run the risk of exposure, and the risks for health are real even at doses lower than those applied in cancer patients, because, in theory, no dose is safe. The most common and problematic route of exposure is through the skin, especially as work surfaces can remain contaminated even after cleaning. This pilot study aimed to demonstrate the importance of having an effective surface decontamination protocol by determining surface contamination with cyclophosphamide, 5-fluorouracil, and paclitaxel as the most common cytotoxic drugs in an oncology day service. Samples were collected before and after drug handling and analysed with high performance liquid chromatography with diode array detection (HPLC-DAD). Of the 29 samples collected before drug handling 23 were contaminated, five of which with more than one drug. Of the 30 samples collected after drug handling 25 were contaminated, eight of which with more than one drug. The two time points did not significantly differ, which evidences a widespread contamination and ineffective cleaning. This calls for revising the cleaning protocol and handling procedure to place contamination under control as much as possible.U zdravstvenih radnika koji pripremaju ili primjenjuju citotoksične lijekove zdravstveni rizici zbog izloženosti su realni, čak i pri dozama nižima od onih koje se primjenjuju u bolesnika jer, načelno, nijedna doza nije neškodljiva za zdravlje. Najčešći i najproblematičniji put izlaganja jest koža, napose zato što radne površine gdjekad ostanu kontaminirane i nakon njihova čišćenja. Cilj ovoga preliminarnog istraživanja bio je pokazati koliko je važno osmisliti djelotvoran protokol za dekontaminaciju na temelju pokazatelja kontaminacije radnih površina jedinice za pripremu lijekova, jedinice za njihovu primjenu te bolesničkoga zahoda onkološke ambulante trima najčešćim citotoksičnim onkološkim lijekovima: ciklofosfamidom, 5-fluoroacilom i paklitakselom. Uzorke smo prikupljali prije rada s lijekovima te tri sata od početka rada s njima te ih analizirali tekućinskom kromatografijom s detektorom s nizom dioda (engl. high performance liquid chromatography with diode array detection, krat. HPLC-DAD). Od 29 uzoraka prikupljenih prije rada s lijekovima, 23 su bila kontaminirana, od kojih pet s više lijekova. Od 30 uzoraka prikupljenih tri sata nakon početka rada s lijekovima, njih 25 bilo je kontaminirano, od kojih osam s više lijekova. Kontaminacija površina prije i nakon početka rada s lijekovima nije bila značajno različita, što upozorava na raširenu kontaminaciju i nedjelotvorno čišćenje. Stoga bi trebalo revidirati postojeći protokol čišćenja i rukovanja lijekovima te svesti kontaminaciju na najmanju moguću mjeru

AVALIAÇÃO DO CUSTO HUMANO DO TRABALHO E DAS ESTRATÉGIAS DE MEDIAÇÃO DOS MÉDICOS DE UMA UNIDADE DE PRONTO ATENDIMENTO

This research sought to identify the human costs related to the medical activity in a Care Unit and to describe the strategies launched by these professionals to deal with costs. The study was conducted using the Ergonomics of Activity perspective. We conducted 13 semi-structured interviews and the data submitted to the lexical analysis using IraMuTeQ software. A negative predominance (84.2% of the analyzed discourses) was observed in the discourses related to human labor costs, with a description of the physiological repercussions of the work in the form of symptoms and diseases; besides physical, cognitive and affective repercussions, represented in the form of exhaustion, overload, exhaustion, fatigue, anxiety, sadness, emotional lability. The strategies identified in the speeches were classified into two axes: one related to the need for support, either by co-workers, other professionals, management, family members or friends; the second axis describes strategies in and out of work to deal with the costs identified, represented by physical activity, doing what they like, "detaching" from work, seeking religiosity and the resignification of work. The study promotes the demands of the researched unit and other research in the context of medical emergencies, with a view to changing the work context.Esta investigación buscó identificar los costos humanos relacionados con la actividad médica en una Unidad de Pronto Atención y describir las estrategias lanzadas por estos profesionales para hacer frente a los costos. El estudio fue conducido por la perspectiva de la Ergonomía de la Actividad. Se realizaron 13 entrevistas semiestructuradas y los datos sometidos al análisis léxico con el uso del software IraMuTeQ. En los discursos relativos a los costes se observó un predominio negativo (84,2%), con la descripción de las repercusiones fisiológicas del trabajo en forma de enfermedades; además de repercusiones físicas, cognitivas y afectivas, en la forma de agotamiento, sobrecarga, agotamiento, cansancio, ansiedad, tristeza, labilidad emocional. Las estrategias identificadas forman en dos ejes: uno relativo a la necesidad de apoyo, por los compañeros de trabajo, de otros profesionales, de la gestión, de familiares o de amigos; el segundo describe estrategias dentro y fuera del trabajo para lidiar con los costos identificados, representados por actividad física, hacer lo que le gusta, "desligarse" del trabajo, búsqueda de la religiosidad y de la resignificación del trabajo. El estudio fomenta demandas de la unidad y de otras investigaciones en el contexto de emergencias, con miras a los cambios del contexto de trabajo.Cette recherche visait à identifier les coûts humains liés à l'activité médicale dans une unité de soins et à décrire les stratégies lancées par ces professionnels pour faire face aux coûts. L'étude a été menée en utilisant la perspective de l'ergonomie de l'activité. Au total, 13 entretiens semi-structurés et les données soumises à l'analyse lexicale ont été réalisés à l'aide du logiciel IraMuTeQ. Une prédominance négative (84,2% des discours) a été observée dans les discours sur les coûts humains, avec une description des répercussions physiologiques du travail sous forme de maladies; Outre les répercussions physiques, cognitives et affectives, sous forme d'épuisement, de surcharge, d'épuisement, de fatigue, d'anxiété, de tristesse, de labilité émotionnelle. Les stratégies identifiées forment deux axes: l'un concernant le besoin de soutien de collègues, d'autres professionnels, de membres de la direction, de membres de la famille ou d'amis; la seconde décrit des stratégies dans et hors du travail pour faire face aux coûts identifiés, représentés par l'activité physique, faire ce qu'ils veulent, "éteindre" le travail, rechercher la religiosité et la resignification du travail. L'étude encourage les demandes d'unité et autres recherches dans le contexte des urgences, en vue de changer le contexte de travail.Esta pesquisa buscou identificar os custos humanos relacionados à atividade médica em uma Unidade de Pronto Atendimento e descrever as estratégias lançadas por estes profissionais para lidar com os custos. O estudo foi conduzido balizado pela perspectiva da Ergonomia da Atividade. Foram realizadas 13 entrevistas semiestruturadas e os dados submetidos à análise lexical com o uso do software IRaMuTeQ. Foram observados nos discursos relativos aos custos humanos do trabalho uma predominância negativa (84,2% dos discursos analisados), com a descrição de repercussões fisiológicas do trabalho na forma de sintomas e doenças; além de repercussões físicas, cognitivas e afetivas, representadas sob a forma de exaustão, sobrecarga, esgotamento, cansaço, ansiedade, tristeza, labilidade emocional. As estratégias identificadas nos discursos foram classificadas em dois eixos: um relativo à necessidade de apoio, seja pelos colegas de trabalho, de outros profissionais, da gestão, de familiares ou de amigos; o segundo eixo descreve estratégias dentro e fora do trabalho para lidar com os custos identificados, representados por atividade física, fazer o que gosta, “desligar-se” do trabalho, busca da religiosidade e da ressignificação do trabalho. O estudo fomenta demandas da unidade pesquisada e de outras pesquisas no contexto de emergências médicas, com vistas à mudanças do contexto de trabalho

Deficiência em micronutrientes em crianças de idade pré-escolar: método de quantificação laboratorial

IDI&CA2016_IPL/2016/MicroNut_ESTeSLA má nutrição conduz geralmente à deficiência em micronutrientes, contribuindo para o aumento dos riscos de morbilidade, mortalidade, estatura reduzida e perturbações cognitivas. As técnicas laboratoriais que permitem determinar os micronutrientes em estudos epidemiológicos de campo são em geral dispendiosas e com recurso a metodologias complexas, dai a necessidade de desenvolver metodologias mais rápidas e económicas. Assim, este estudo tem por objectivo: 1. Desenvolvimento de uma metodologia laboratorial para a quantificação simultânea das vitaminas A e E; 2. Avaliação dos níveis de deficiência de micronutrientes e de desnutrição nos primeiros 5 anos de vida, numa zona semi-rural de Angola.info:eu-repo/semantics/draf

Comet assay as a human biomonitoring tool: application in occupational exposure to antineoplastic drugs

Antineoplastic drugs are a heterogeneous group of chemicals used in the treatment of cancer, and have been proved by IARC to be mutagens, carcinogens and teratogens agents. In general, chemicals that interact directly with DNA by biding covalently or by intercalating, or indirectly by interfering with DNA synthesis, were among the first chemotherapeutics developed. Also, these drugs can induce reactive oxygen species that can lead to DNA damage and, consequently, mutations. These drugs are often used in combination to achieve synergistic effects on tumour cells resulting from their differing modes of action. However, most if not all of these chemical agents are generally nonselective and, along with tumour cells, normal cells may undergo cytotoxic/genotoxic damage. The in vivo exposure to antineoplastic drugs has been shown to induce different types of lesions in DNA, depending on the particular stage of cell cycle at the time of treatment. Besides the patients that use these drugs as a treatment, workers that handle and/or administer these drugs can be exposed to these substances; namely pharmacy, and nursing personnel in hospital context

Hospital surfaces contamination with antineoplastic drugs: influence of cleaning procedures

Introduction: The raising frequency of cancer diseases is leading to a widespread application of antineoplastic drugs, thus increasing the probability of workplace surfaces contamination. Most of these drugs are classified by the International Agency for Research on Cancer as known or suspected human carcinogens. Skin absorption is the main route for antineoplastic drugs exposure in occupational settings, therefore cleaning protocols have paramount influence in surfaces contamination and, consequently, in exposure. The aim of this study was to assess surfaces contamination in a Portuguese chemotherapy unit before and during drug administration, in both preparation and administration facilities. Methods: Samples were collected by wipe-sampling from potentially contaminated surfaces selected by previous protocol observation. Samples were analyzed by HPLCDAD. Cyclophosphamide (CP), 5-fluorouracil (5FU), and paclitaxel (PTX) were used as surrogate markers for surfaces contamination for all cytotoxic drugs. Results: From the 34 samples collected before any preparation and administration activities, 41.2% were contaminated with 5-FU (4.0-84.7 ng/cm2) and 23.5% of the samples were contaminated with CP (19.8-139.6 μg/cm2). Only 2 samples presented contamination by PTX (5.9%) with a maximum value of 3.7 ng/cm2. Of the 37 samples collected during preparation and administration of antineoplastic drugs, 48.7% were contaminated with 5-FU (1.9-88.7 ng/cm2) and 24.3% with CP (12.0-93.9 μg/cm2). None of the samples showed contamination with PTX. Discussion: Data showed differences in contamination levels before and after the handling of antineoplastic drugs in preparation and in administration settings. These results point out the importance of cleaning procedures. This is well in accordance to previous studies that showed how the type of cleaning procedures and products used can be determinant for surfaces decontamination

Relation between DNA damage measured by comet assay and OGG1 Ser326Cys polymorphism in antineoplastic drugs biomonitoring

Antineoplastic drugs are hazardous chemical agents used mostly in the treatment of patients with cancer, however health professionals that handle and administer these drugs can become exposed and develop DNA damage. Comet assay is a standard method for assessing DNA damage in human biomonitoring and, combined with formamidopyrimidine DNA glycosylase (FPG) enzyme, it specifically detects DNA oxidative damage. The aim of this study was to investigate genotoxic effects in workers occupationally exposed to cytostatics (n = 46), as compared to a control group with no exposure (n = 46) at two Portuguese hospitals, by means of the alkaline comet assay. The potential of the OGG1 Ser326Cys polymorphism as a susceptibility biomarker was also investigated. Exposure was evaluated by investigating the contamination of surfaces and genotoxic assessment was done by alkaline comet assay in peripheral blood lymphocytes. OGG1 Ser326Cys (rs1052133) polymorphism was studied by Real Time PCR. As for exposure assessment, there were 121 (37%) positive samples out of a total of 327 samples analysed from both hospitals. No statistically significant differences (Mann-Whitney test, p > 0.05) were found between subjects with and without exposure, regarding DNA damage and oxidative DNA damage, nevertheless the exposed group exhibited higher values. Moreover, there was no consistent trend regarding the variation of both biomarkers as assessed by comet assay with OGG1 polymorphism. Our study was not statistically significant regarding occupational exposure to antineoplastic drugs and genetic damage assessed by comet assay. However, health professionals should be monitored for risk behaviour, in order to ensure that safety measures are applied and protection devices are used correctly

From cilia to cancer: the two splicing variants of the human TBCCD1 gene

Funds are from Instituto Politécnico de Lisboa, IPL/2017/CILIOPAT/ESTeSL.Almost all human genes that contain multiple exons undergo alternative splicing. Therefore, a single gene can originate multiple mRNA isoforms which causes a dramatic increase in the variability of the expected proteome. Noteworthy, phenotypic variability and disease susceptibility in human populations are related to alternative splicing. Published work from our group identified a new human centrosomal protein, TBCC domain-containing 1 (TBCCD1). Our studies revealed that this gene undergoes alternative splicing producing at least two transcripts encoding proteins. Here we analyze the differential functions of the two splicing variants (TBCCD1v1 and TBCCD1v2). Both variants present distinct cellular localization being TBCCD1v1 essentially centrosomal, whereas TBCCD1v2 is cytoplasmatic. The screening for TBCCD1v2 proximity interactome using BioID identified 19 proteins that functionally group in kinetochore, MT/cilia, and DNA-binding proteins. Striking, the overexpression of TBCCD1v2 decreases the levels of the kinetochore protein CENP-M, a protein upregulated in tumors. On the other hand, the TBCCD1v1 is involved in MT organization and is required to maintain the distal structure of the mother centriole. Our BioID screening for TBCCD1v1 interactors revealed 82 distinct proteins including several well-known proteins encoded by ciliopathy genes. A wider analysis of how TBCCD1v1 levels impact cellular physiological proteome showed that the group of proteins presenting fold changes in their levels vs control cells is enriched in proteins involved in focal adhesions, namely HSPA5/GRP-78/BiP, PDIA3, RPS10, MSN, TGM2, and PPP1R12A. Together our results show that we are still far from having a complete picture of the functional importance of TBCCD1 and how its deregulation may be associated not only with the development of ciliopathies but also with more common diseases like cancer.info:eu-repo/semantics/publishedVersio