Publications by authors named "Concettina Fenga"

63 Publications

Perceived Stress in a Gender Perspective: A Survey in a Population of Unemployed Subjects of Southern Italy.

Front Public Health 2021 1;9:640454. Epub 2021 Apr 1.

Occupational Medicine Section, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.

Stressful life events, are differently handled by women and men. This study evaluates gender differences in perceived stress and health status among a sample of subjects going through a transition period from unemployment to work. This cross-sectional study enrolled 395 participants, 245 men (62%) and 150 (38%) women, between 19 and 67 years, that were going to be hired for a 6-month contract. Before being employed, all participants underwent a mandatory protocol consisting in a general medical check. Stress assessment was performed by using the Perceived Stress Scale (PSS). Most of the participants (68%) showed normal to low perceived stress level. But dividing the sample by gender, out of the remaining 32% with medium to high stress level, 11% male subjects and 22.7% females reported high perceived stress values. We found mean PSS values that are overlapping with those in the general population of developed countries. This study does not suggest an association between perceived stress and health or social parameters. However, our results highlight that the female gender is associated with higher stress level, pointing out the relevance of specific and designed interventions in the context of health promotion programs, especially in order to mitigate stress in more susceptible subjects.
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http://dx.doi.org/10.3389/fpubh.2021.640454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046934PMC
April 2021

Salivary Biomarkers and Work-Related Stress in Night Shift Workers.

Int J Environ Res Public Health 2021 03 19;18(6). Epub 2021 Mar 19.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Occupational Medicine Section, University of Messina, 98125 Messina, Italy.

Work organization, such as shifts and night work, can interfere with the perception of work-related stress and therefore on the development of pathological conditions. Night shift work, particularly, can have a negative impact on workers' wellbeing by interfering with the biological sphere. The aim of this study is to evaluate the associations between work activities, shift work effects and stress-related responses in 106 dock workers enrolled in southeast Italy. Dock workers' tasks consist of complex activities that seemed to affect more sleep quality than work-related stress. An analysis of salivary biomarkers such as cortisol, α-amylase, melatonin and lysozyme was performed along with validated psycho-diagnostic questionnaires. Alpha-amylase showed a significant negative correlation with the effort/reward imbalance score; thus, the measurement of salivary α-amylase is proposed as a sensitive and non-invasive biomarker of work-related stress. This study may provide new insights into developing strategies for the management of night shift work. Salivary biomarkers should be further investigated in the future in order to develop simple and effective tools for the early diagnosis of work-related stress or its outcomes.
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http://dx.doi.org/10.3390/ijerph18063184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003447PMC
March 2021

MicroRNAs alteration as early biomarkers for cancer and neurodegenerative diseases: New challenges in pesticides exposure.

Toxicol Rep 2020 21;7:759-767. Epub 2020 May 21.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Occupational Medicine Section, University of Messina, 98125, Messina, Italy.

This review summarizes the current knowledge linking cancer and neuro-degenerative diseases to dysregulation of microRNA network following pesticide exposure. Most findings revealed differential miRNA expression targeting biomolecules and pathways involved in various neoplastic localizations and neurodegenerative diseases. A growing body of evidence in recent literature indicates that alteration of specific miRNAs can represent an early biomarker of disease following exposure to chemical agents, including pesticides. Different miRNAs seem to regulate cell proliferation, apoptosis, migration, invasion, and metastasis many biological pathways through modulation of the expression of target mRNAs. The evaluation of miRNA expression levels may be used to develop new non-invasive strategies for the prediction and prognosis of many diseases, including cancer. However, the application of miRNAs as diagnostic and therapeutic biomarkers in the clinical field is extremely challenging.
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http://dx.doi.org/10.1016/j.toxrep.2020.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322123PMC
May 2020

Night shift work in resident physicians: does it affect mood states and cognitive levels?

J Affect Disord 2020 07 30;272:289-294. Epub 2020 Apr 30.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Occupational Medicine Section, University of Messina, Messina 98125, Italy.

Background: The effects of night shift work on health status have been widely studied. Night workers seem to smoke more, eat badly and show a low propensity to physical activity. Night work can be associated with an increase in cardiovascular and gastrointestinal disorders, alterations in immune response, diabetes, aging, hormonal imbalance, and premature death; alteration of circadian rhythm is also regarded as a risk factor for breast cancer and neuropsychiatric disorders. Moreover, several studies have highlighted the effects of sleep deprivation on clinical performance, quality of care and personal safety of healthcare personnel. No studies have investigated the effects of night work on Italian resident physicians and compared its effect across specialties. This study aims to assess the prevalence of sleep disorders, possible cognitive impairment and mood states, in relation to night shift work among resident physicians.

Methods: 80 resident physicians, attending the postgraduate training into an Hospital located in the South of Italy, were divided into 4 areas (medical, surgical, services and anaesthesia). They were recruited from July 2017 to June 2018 and participated to a survey consisting of 4 questionnaires to investigate the presence of sleep deprivation and sleep quality (Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index), their cognitive status (Mini Mental State examination) and mood profiles (Profile of Mood States, POMS). Analysis of variance was used for comparison of questionnaires scores across specialties.

Results: Authors reported no sleep deprivation, no sleep disorders and their outcomes, no changes in intellectual efficiency and no cognitive impairment in this population, neither in the areas performing night shifts nor in those involving only day shifts. Mood states measured by POMS showed a borderline level of Anger-Hostility (A) value among the residents of the medical area and services, and an increase slightly beyond the physiological levels of the T-score 50 of Fatigue-Inertia (F) always in the same groups. An increase in the Vigour-Activity (V) value beyond T-score 50 levels was also observed among residents of all the areas considered.

Conclusions: Emotional involvement could be attributed to the gap between high professional demand and lack of experience and knowledge among trainees. Tutors should help their students in order to identify earlier changes in the mood. Improvement in the organization of the trainee's activity could reduce the emotional overload.
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http://dx.doi.org/10.1016/j.jad.2020.03.139DOI Listing
July 2020

Association between oxidative stress biomarkers and PON and GST polymorphisms as a predictor for susceptibility to the effects of pesticides.

Int J Mol Med 2020 Jun 16;45(6):1951-1959. Epub 2020 Mar 16.

Department of Biomedical and Dental Sciences and Morpho‑Functional Imaging, Occupational Medicine Section, University of Messina, I‑98125 Messina, Italy.

Low levels of pesticides persist in the environment and can affect the health of exposed subjects. Oxidative stress is considered as one of the mechanisms responsible for the adverse effects on human health and some molecules may represent useful biomarkers for the evaluation of this physiological balance. This study investigated the role of these biomarkers, such as advanced oxidation protein products (AOPP), advanced glycation end‑products (AGE) and reactive oxygen metabolites (ROMs) in relation to genetic polymorphisms of paraoxonase (PON)1, PON2, glutathione S‑transferase pi 1 (GSTP1), glutathione S‑transferase theta 1 (GSTT1) and glutathione S‑transferase mu 1 (GSTM1). An increase in the levels of these biomarkers is usually inversely associated with the depletion of the biological antioxidant potential (BAP). The results revealed a statistically significant difference in the sex‑dependent variation of AGE, BAP, AOPP and ROM protein levels. Furthermore, an association between the PON2 S331C gene polymorphism and the serum levels of AOPP, ROMs and BAP was found. Thus, compared with AGE, the levels of AOPP and ROMs provided a more sensitive biomarker, with an improved association with the PON2 genotype. Such an association strengthen the importance of PON in the occurrence of oxidative stress. According to these results, an individual's genetic background may be taken into account for the health surveillance of individuals occupationally exposed to pesticides, in order to define a cluster of highly susceptible workers so as to guarantee greater protection.
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http://dx.doi.org/10.3892/ijmm.2020.4541DOI Listing
June 2020

Genetic polymorphisms as determinants of pesticide toxicity: Recent advances.

Toxicol Rep 2019 7;6:564-570. Epub 2019 Jun 7.

Department of Clinical and Experimental Medicine - Occupational Medicine Section - University of Messina, Italy.

Occupational and environmental exposure to pesticides may induce harmful effects on human health by promoting the development of a wide range of disorders. Some of the most recently hypothesized mechanisms are oxidative stress and epigenetic modifications, however biological effects seem to be modulated mainly by the occurrence of genetic polymorphisms. The susceptibility to exposure can be evaluated by studying the most common polymorphisms of genes involved in the metabolism of organophosphorus compounds (cytochrome P450, glutathione transferase, acetyltransferases or paraoxonase 1). The aim of this article is to review recent literature data concerning the influence of genetic polymorphisms on pesticides-induced oxidative damage.
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http://dx.doi.org/10.1016/j.toxrep.2019.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595235PMC
June 2019

Biological risk for healthcare workers: current Italian law and guidelines on vaccination strategies.

Future Microbiol 2019 06 18;14:21-25. Epub 2019 Jun 18.

Department of Biomedical & Dental Sciences & Morphofunctional Imaging, Occupational Medicine Section, University of Messina, 98125 Messina, Italy.

The assessment and management of biological risk has always been a primary goal toward which occupational medicine has focused its efforts, in particular in healthcare workplaces. Healthcare professionals represent a category of workers at high risk for infections, many of which are vaccine-preventable diseases. There are various reasons for vaccinating healthcare workers, including to prevent illness among them so as to reduce absenteeism, to ensure an effective health service to users and to reduce social costs. Recently, the issue of vaccinations has been the subject of many debates. Vaccination is not always appreciated by health operators, and the reasons for low vaccination coverage are several and heterogeneous. This paper focuses on current Italian law and vaccination policies, along with the international background, evaluating the effectiveness of current policies and the consequences on public health. Overall, preventing infectious diseases means reducing costs, cases and outbreaks, shows responsibility toward third parties, and improves general welfare.
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http://dx.doi.org/10.2217/fmb-2018-0264DOI Listing
June 2019

Inflammation and Metabolism in Cancer Cell-Mitochondria Key Player.

Front Oncol 2019 14;9:348. Epub 2019 May 14.

Department of Forensic Sciences and Toxicology, University of Crete, Heraklion, Greece.

Cancer metabolism is an essential aspect of tumorigenesis, as cancer cells have increased energy requirements in comparison to normal cells. Thus, an enhanced metabolism is needed in order to accommodate tumor cells' accelerated biological functions, including increased proliferation, vigorous migration during metastasis, and adaptation to different tissues from the primary invasion site. In this context, the assessment of tumor cell metabolic pathways generates crucial data pertaining to the mechanisms through which tumor cells survive and grow in a milieu of host defense mechanisms. Indeed, various studies have demonstrated that the metabolic signature of tumors is heterogeneous. Furthermore, these metabolic changes induce the exacerbated production of several molecules, which result in alterations that aid an inflammatory milieu. The therapeutic armentarium for oncology should thus include metabolic and inflammation regulators. Our expanding knowledge of the metabolic behavior of tumor cells, whether from solid tumors or hematologic malignancies, may provide the basis for the development of tailor-made cancer therapies.
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http://dx.doi.org/10.3389/fonc.2019.00348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527883PMC
May 2019

Immunohistochemical expression and localization of MMP-9, MMP-13, E-Cadherin and Ki-67 in road pavers' skin chronically exposed to bitumen products.

Histol Histopathol 2019 Oct 11;34(10):1141-1150. Epub 2019 Apr 11.

Department of Clinical and Experimental Medicine, Section of Occupational Medicine, University of Catania, Catania, Italy.

To investigate the matrix metalloproteinase (MMP)-9, (MMP)-13, E-Cadherin and Ki-67 expressions in road pavers' skin chronically exposed to bitumen products in order to contribute to a better understanding of the earlier tissue alteration. Skin punch biopsies from 16 daily exposed workers and a control group were studied by immunohistochemistry. Morphometric and densitometric analyses were also conducted. Morphological specimen evaluation of skin of road pavers showed epidermal thinning, flattening and loss of intercellular junction with a decreased expression of E-cadherin confined to the basal skin layer, together with MMP-9 and MMP-13 overexpressions in all epidermis layers, vascular structures and adnexa. No immunohistochemical alteration was reported for Ki-67 vs normal skin. Results from this study show that overexpression of MMP-9 and MMP-13 may represent an early response of the first human barrier to exposure to bitumen products. Regulation of MMPs could be one of the strategies to prevent primary skin disease.
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http://dx.doi.org/10.14670/HH-18-116DOI Listing
October 2019

Cadmium exposure and prostate cancer: insights, mechanisms and perspectives.

Front Biosci (Landmark Ed) 2018 03 1;23:1687-1700. Epub 2018 Mar 1.

Occupational Medicine, Department of Clinical and Experimental Medicine; University of Catania, I-95123 Catania, Italy,

Cadmium (Cd) is a metal found in group 12 (IIB) of the periodic table of elements together with zinc, a metal with which it is often conjugated in nature. Occupational exposure to Cd occurs in many industrial settings, by cigarette smoking, diet and due to environmental pollution. International Agency for Research on Cancer and other epidemiological studies suggested that Cd can lead to prostate cancer and likely to kidney and lung cancers. Although epidemiological studies seem to point towards such an association, the in vitro studies have not been compelling. The aim of this article is to summarize current knowledge about the association of Cd exposure and prostate cancer, that suggests that new studies to show the role of Cd in the pathogenesis of prostatate cancer.
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http://dx.doi.org/10.2741/4667DOI Listing
March 2018

Current evidence on the effect of dietary polyphenols intake on chronic diseases.

Food Chem Toxicol 2017 Dec 14;110:286-299. Epub 2017 Oct 14.

Biomedical, Odontoiatric, Morphological and Functional Images Department, Occupational Medicine Section, University of Messina, Messina 98125, Italy. Electronic address:

Polyphenols are secondary metabolites of plants. They comprise several antioxidant compounds and they are generally considered to be involved in the defense against human chronic diseases. During the last years, there has been growing scientific interest in their potential health benefits. In this comprehensive review, we focus on the current evidence defining the position of their dietary intake in the prevention/treatment of human chronic diseases, including prostate cancer and other types of cancer, cardiovascular diseases, diabetes mellitus and neurodegenerative diseases such as Alzheimer's and Parkinson's disease; we also discuss their ability to modulate multiple signalling transduction pathways involved in the pathophysiology of these diseases. Despite the fact that data regarding the biological functions of polyphenols can be considered exhaustive, evidence is still inadequate to support clear beneficial effects on human chronic diseases. Currently, most data suggest that a combination of phytochemicals rather than any single polyphenol is responsible for health benefit. More studies investigating the role of polyphenols in the prevention of chronic human diseases are needed, especially for evaluating factors such as gender, age, genotype, metabolism and bioavailability.
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http://dx.doi.org/10.1016/j.fct.2017.10.023DOI Listing
December 2017

CYP polymorphisms and pathological conditions related to chronic exposure to organochlorine pesticides.

Toxicol Rep 2017 26;4:335-341. Epub 2017 May 26.

Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Greece.

The association between genetic variations in the cytochrome P450 (CYP) family genes and pathological conditions related to long-term exposure to organochlorine compounds (OCs) deserves further elucidation. OCs are persistent organic pollutants with bioaccumulative and lipophilic characteristics. They can act as endocrine disruptors and perturb cellular mechanisms. Prolonged exposure to OCs has been associated with different pathological manifestations. CYP genes are responsible for transcribing enzymes essential in xenobiotic metabolism. Therefore, polymorphisms in these genetic sequences a. alter the metabolic pathways, b. induce false cellular responses, and c. may provoke pathological conditions. The main aim of this review is to define the interaction between parameters a, b and c at a mechanistic/molecular level, with references in clinical cases.
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http://dx.doi.org/10.1016/j.toxrep.2017.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615117PMC
May 2017

8-Hydroxydeoxyguanosine as a biomarker of oxidative DNA damage in workers exposed to low-dose benzene.

Toxicol Rep 2017 31;4:291-295. Epub 2017 May 31.

Department of Clinical and Experimental Medicine - University of Messina, Messina 98125, Italy.

The present study aims to investigate the relation between exposure to low-dose benzene and the occurrence of oxidative DNA damage in gasoline station workers, as well as the possible role of interfering or confounding factors. Urine levels of 8-OHdG were evaluated by a competitive immunoassay in a group of 80 men, employed in gasoline stations located in East Sicily and compared with a control group (n = 63) of male office employees not occupationally exposed to benzene. Information regarding socio-demographic characteristics, lifestyle and job-related records were provided through a questionnaire. Significantly higher (p < 0.05) urinary t,t,-MA and 8-OHdG levels were observed in gasoline station attendants compared to subjects not exposed to benzene. Pearson's test demonstrated a strong correlation (r = 0.377, p < 0.001) between 8-OHdG and benzene exposure level. 8-OHdG significantly correlated also with job seniority, (r = 0.312, p < 0.01), whereas the relation with age resulted weaker (r = 0.242, p < 0.05). Multiple linear regression analysis, performed to exclude a role for confounding factors, showed that variables like gender, smoking habit, alcohol consumption and BMI did not have a significant influence on the measured biomarkers. No subject enrolled in the study presented signs or symptoms of work-related disease or other illness linked to oxidative stress. These results suggest that low-level chronic exposure to benzene among gasoline station attendants can determine oxidative damage on DNA, as indicated by alteration of 8-OHdG which may represent a non-invasive biomarker of early genotoxic damage in exposed subjects.
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http://dx.doi.org/10.1016/j.toxrep.2017.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615153PMC
May 2017

Worldwide legislative challenges related to psychoactive drugs.

Daru 2017 Jun 2;25(1):14. Epub 2017 Jun 2.

University of Crete, Medical School, Department of Toxicology and Forensic Sciences, Heraklion, Greece.

The discovery of a "new" psychoactive substance is a relatively exceptional event, while the regulatory response usually involved the assessment of risks to public health and inclusion of the novel substance in the national list of controlled substances. However, in recent years we have witnessed the rapid emergence of new chemical substances, which elude international control and pose a challenge to existing processes and a threat to the credibility of control systems. We currently review and present characteristics of these legal and illegal new substances and issues regarding their global monitoring and regulatory measures already taken, or in the process of being taken, for their control. The concept of prohibition applied in active substance-related legislation is rather hazard ridden as balance is required between the ban on substances of potential therapeutic use and the access on the market of high-risk substances. Current and future laws regarding psychoactive compounds.
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http://dx.doi.org/10.1186/s40199-017-0180-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455135PMC
June 2017

The risk of HCV infection among health-care workers and its association with extrahepatic manifestations (Review).

Mol Med Rep 2017 May 24;15(5):3336-3339. Epub 2017 Mar 24.

Section of General, Clinical and Oncological Pathology, Department of Biomedical and Biotechnological Sciences, University of Catania, I‑95123 Catania, Italy.

Health care workers (HCWs) are frequently exposed to different biological agents during their activities and are frequently monitored. Among these infectious agents, human hepatitis C (HCV) can infect HCWs. In this review article, the risk of HCV infection among HCWs is discussed along with extrahepatic HCV-related malignancies, such as non‑Hodgkin lymphoma. Accidental contamination, represented by percutaneous and mucocutaneous infections is the main risk factor for such infection. The compliance of the protection procedures, included in the current regulation for HCWs, is the most important issue to reduce the risk of pathogen infections that in turn may produce reduction of infection‑associated malignancies.
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http://dx.doi.org/10.3892/mmr.2017.6378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428681PMC
May 2017

New insights on 'old' toxicants in occupational toxicology (Review).

Mol Med Rep 2017 May 24;15(5):3317-3322. Epub 2017 Mar 24.

Section of Occupational Medicine, Department of Biomedical, Odontoiatric, Morphological and Functional Images, University of Messina, Policlinico 'G. Martino', I‑98125 Messina, Italy.

In order to deliver the best possible working environment, it is essential to identify professional conditions that could be harmful for worker's health and prevent (or limit) the occurrence of such conditions. The appropriate use of personal protective equipment and the development of appropriate regulations allowed to reduce the prevalence of 'classic' occupational diseases, such as occupational hearing loss or asbestosis, just to name a few. Nowadays, environmental pollution seems to be one of the most relevant concerns for human and animal health, and toxicology is becoming one of the most prominent fields of interest in occupational settings. An increasing number of studies demonstrate that the presence of toxicants in the workplace could be responsible for the development of chronic diseases, even at doses that were considered 'safe'. The present review summarizes some of the most recent advancements in occupational toxicology, focusing on topics that have long been debated in the past and that have recently returned to the fore.
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http://dx.doi.org/10.3892/mmr.2017.6374DOI Listing
May 2017

Immunomodulatory effects in workers exposed to naturally occurring asbestos fibers.

Mol Med Rep 2017 May 24;15(5):3372-3378. Epub 2017 Mar 24.

Section of Human Anatomy and Histology, Department of Biomedical and Biotechnology Sciences, University of Catania, Catania, Italy.

Natural asbestiform fibers are defined 'naturally occurring asbestos' (NOA) and refer to the mineral as a natural component of soils or rocks. The release of NOA fibers into the air from rocks or soils by routine human activities or natural weathering processes represents a risk for human beings. Fluoro-edenite (FE) is a NOA fiber detected in the benmoreitic lava in the area of Biancavilla, South-west slope of Mt. Etna. The aim of the present study was to investigate FE immunotoxicity pathways in a group of 38 occupationally exposed construction workers, in order to find any biological markers of its effect. Subjects underwent respiratory function tests and HRCT total chest scanning. Serum IL-1β, IL-6, IL-8 and TNF-α were measured. The presence of PPs was significantly greater in subjects exposed than in the control (25 vs. 2). In subjects exposed to FE, IL-1β and TNF-α values were significantly higher than the controls. The previously observed increase of IL-1β and IL-18 showed a probable involvement of the proteic complex defined inflammosome by FE fibers.
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http://dx.doi.org/10.3892/mmr.2017.6384DOI Listing
May 2017

Immunological effects of occupational exposure to lead (Review).

Mol Med Rep 2017 May 24;15(5):3355-3360. Epub 2017 Mar 24.

Department of Biomedical and Biotechnological Sciences, Laboratory of Translational Oncology and Functional Genomics, Section of General and Clinical Pathology and Oncology, University of Catania, I-95124 Catania, Italy.

It is well-known that occupational and environmental exposure to several factors, including benzene, heavy metals, chemicals and mineral fibers, is associated with the risk of developing a great number of diseases. Numerous studies have been carried out in order to investigate the mechanisms of toxicity of these substances, with particular regard to the possible toxic effects on the immune system. However, little is known about the influence of heavy metals, such as lead, on the immune system in human populations. Lead is a heavy metal still used in many industrial activities. Human exposure to lead can induce various biological effects depending upon the level and duration of exposure, such as toxic effects on haematological, cardiovascular, nervous and reproductive systems. Several studies demonstrated that exposure to lead is associated to toxic effects also on the immune system, thus increasing the incidence of allergy, infectious disease, autoimmunity or cancer. However, the effects of lead exposure on the human immune system are not conclusive, mostly in occupationally exposed subjects; nevertheless some immunotoxic abnormalities induced by lead have been suggested. In particular, in vivo, in vitro and ex vivo lead is able to improve T helper 2 (Th2) cell development affecting Th1 cell proliferation. Further studies are required to better understand the mechanisms of lead immunotoxicity and the ability of lead to affect preferentially one type of immune response.
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http://dx.doi.org/10.3892/mmr.2017.6381DOI Listing
May 2017

Non‑infective occupational risk factors for hepatocellular carcinoma: A review (Review).

Mol Med Rep 2017 Feb 14;15(2):511-533. Epub 2016 Dec 14.

Occupational Medicine, Department of Clinical and Experimental Medicine, University of Catania, I-95123 Catania, Italy.

Liver cancer is the second leading worldwide cause of cancer‑associated mortalities. Hepatocellular carcinoma, which accounts for the majority of liver tumors, ranks fifth among types of human cancer. Well‑established risk factors for liver cancer include the hepatitis B and C viruses, aflatoxins, alcohol consumption, and oral contraceptives. Tobacco smoking, androgenic steroids, and diabetes mellitus are suspected risk factors. Current knowledge regarding non‑infective occupational risk factors for liver cancer is inconclusive. The relevance of liver disorders to occupational medicine lies in the fact that the majority of chemicals are metabolized in the liver, and toxic metabolites generated via metabolism are the predominant cause of liver damage. However, their non‑specific clinical manifestations that are similar in a number of liver diseases make diagnosis difficult. Furthermore, concomitant conditions, such as viral hepatitis and alcohol or drug abuse, may mask liver disorders that result from occupational hepatotoxic agents and block the demonstration of an occupational cause. The identification of environmental agents that result in human cancer is a long and often difficult process. The purpose of the present review is to summarize current knowledge regarding the association of non‑infective occupational risk exposure and HCC, to encourage further research and draw attention to this global occupational public health problem.
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http://dx.doi.org/10.3892/mmr.2016.6046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364850PMC
February 2017

Fluoro-edenite induces fibulin-3 overexpression in non-malignant human mesothelial cells.

Oncol Lett 2016 Nov 26;12(5):3363-3367. Epub 2016 Aug 26.

Section of General and Clinical Pathology and Oncology, Department of Biomedical and Biotechnological Sciences, University of Catania, I-95124 Catania, Italy.

Exposure to asbestos is associated with the development of mesothelioma. In addition to asbestos, other fibers have been identified as risk factors for malignant and non-malignant diseases of the lungs. Among these, fluoro-edenite (FE) was found in patients from Biancavilla (Sicily, Italy) with pleural and lung disease, suggesting its role for tumor expansion. In this context, the identification of early biomarkers useful for the diagnosis of cancer is mandatory. Fibulin-3 represents an important marker for the diagnosis of mesothelioma. However, it remains to be determined whether it is directly associated with exposure to asbestos-like fibers. In the present study, peripheral blood levels of fibulin-3 from 40 asbestos-exposed workers were compared with those detected in 27 street cleaners from Biancavilla. Intriguingly, the results showed that fibulin-3 levels were higher in the group of street cleaners compared with those of the asbestos-exposed workers, suggesting that these workers used the personal protective equipment according to the current regulations. These data suggest that subjects exposed to FE should be monitored for the risk of mesothelioma. FE and volcanic particulates are probably contained within dust inhaled by street cleaners from Biancavilla during their work activities. Based on these criteria, in this study, such fibers were used to treat mesothelial cells (MeT5A) in order to verify whether fibulin-3 levels are affected by these treatments. The results showed that only treatment with FE was associated with fibulin-3 overexpression at both the transcript and protein levels. It was previously demonstrated that mesothelial cells exhibited low levels of p27 following treatment with FE. Notably, p27 downregulation is associated with stathmin upregulation in cancer, conferring an aggressive phenotype of tumor cells. This observation prompted us to perform a computational evaluation demonstrating the activation of stathmin in lung cancer in patients exposed to asbestos. Overall, it can be speculated that both fibulin-3 and stathmin overexpression may be associated with the malignant transformation of mesothelial cells following exposure to asbestos-like fibers.
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http://dx.doi.org/10.3892/ol.2016.5051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103952PMC
November 2016

Effects of mutations in Wnt/β-catenin, hedgehog, Notch and PI3K pathways on GSK-3 activity-Diverse effects on cell growth, metabolism and cancer.

Biochim Biophys Acta 2016 12 6;1863(12):2942-2976. Epub 2016 Sep 6.

Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that participates in an array of critical cellular processes. GSK-3 was first characterized as an enzyme that phosphorylated and inactivated glycogen synthase. However, subsequent studies have revealed that this moon-lighting protein is involved in numerous signaling pathways that regulate not only metabolism but also have roles in: apoptosis, cell cycle progression, cell renewal, differentiation, embryogenesis, migration, regulation of gene transcription, stem cell biology and survival. In this review, we will discuss the roles that GSK-3 plays in various diseases as well as how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTOR, Ras/Raf/MEK/ERK, Wnt/beta-catenin, hedgehog, Notch and TP53. Mutations that occur in these and other pathways can alter the effects that natural GSK-3 activity has on regulating these signaling circuits that can lead to cancer as well as other diseases. The novel roles that microRNAs play in regulation of the effects of GSK-3 will also be evaluated. Targeting GSK-3 and these other pathways may improve therapy and overcome therapeutic resistance.
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http://dx.doi.org/10.1016/j.bbamcr.2016.09.004DOI Listing
December 2016

Release of nickel and chromium in common foods during cooking in 18/10 (grade 316) stainless steel pots.

Contact Dermatitis 2017 Jan 1;76(1):40-48. Epub 2016 Nov 1.

Department of Biomedical Sciences and Morphological and Functional Images, University of Messina, 98125, Messina, Italy.

Background: Literature data on the release of nickel and chromium from stainless steel cookware during food preparation are contrasting, have often been obtained with uncommon foods and/or procedures, and are thus not widely applicable.

Objectives: To assess the release of nickel and chromium from 18/10 (grade 316) stainless steel pots in cooking conditions that are common in an urban lifestyle.

Methods: Tomato sauce and lemon marmalade were cooked for 1 h, alone or with added EDTA, in used or unused stainless steel pots from different manufacturers. Additionally, aqueous solutions at pH 2.3, 7.7 and 9 were boiled for 1 h in the same pots. Metal release was assessed with inductively coupled plasma mass spectrometry.

Results: The release of nickel and chromium increased with cooking/boiling time, was higher with unused pots, at low pH or with EDTA, and was sometimes remarkably different between manufacturers. In all experiments, the amounts released were below known allergy-triggering thresholds.

Conclusions: Under common conditions, the use of 18/10 stainless steel pots is considered to be safe for the majority of nickel-allergic and/or chromium-allergic subjects. However, the total amount of nickel contained in foods and released from pots may exceed the individual threshold for triggering allergy, potentially causing problems for highly sensitive patients, or, conversely, contribute to induction of immunotolerance by oral low-dose exposure.
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http://dx.doi.org/10.1111/cod.12692DOI Listing
January 2017

Early effects of fluoro-edenite: correlation between IL-18 serum levels and pleural and parenchymal abnormalities.

Future Oncol 2016 Dec 27;12(23s):59-62. Epub 2016 Sep 27.

Department of Clinical & Experimental Medicine, Occupational Medicine, University of Catania, Catania, Italy.

Fluoro-edenite (FE) is a natural mineral asbestos-like fibrous species first isolated in Biancavilla, Sicily. In order to clarify potential involvement of IL-18 in the pathogenesis of FE-induced chest abnormalities, we analyzed IL-18 serum levels in FE-exposed workers (FEEW) and correlated them with pleural and parenchymal abnormalities. A total of 21 FEEWs, residing in Biancavilla for >30 years, with a working seniority of 17 ± 6.1 years were examined. High-resolution computed tomography scans revealed low grade of fibrosis in 8 (38%) FEEWs, and pleural plaques (PPs) in 13 (62%) FEEWs. The mean IL-18 level was 203.13 ± 90.43 pg/ml. Pearson correlation showed a significant association (p < 0.0001) between IL-18 and PPs and parenchymal abnormality scores. Data suggest a potential role of IL-18 in the pathogenesis of these diseases.
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http://dx.doi.org/10.2217/fon-2016-0338DOI Listing
December 2016

Toxicological and efficacy assessment of post-transition metal (Indium) phthalocyanine for photodynamic therapy in neuroblastoma.

Oncotarget 2016 10;7(43):69718-69732

Department of Toxicology and Forensic Sciences, Faculty of Medicine, University of Crete, Heraklion, Greece.

Metallo-phthalocyanines due to their photophysical characteristics as high yield of triplet state and long lifetimes, appear to be good candidates for photodynamic therapy (PDT). Complexes with diamagnetic metals such as Zn2+, Al3+ Ga3+ and In3+meet such requirements and are recognized as potential PDT agents. Clinically, Photofrin® PDT in neuroblastoma therapy proved in pediatric subjects diagnosed with progressive/recurrent malignant brain tumors increased progression free survival and overall survival outcome. Our study focuses on the dark toxicity testing of a Chloro-Indium-phthalocyanine photosensitizer (In-Pc) upon SH-SY5Y neuroblastoma cell line and its experimental in vitro PDT. Upon testing, In-Pc has shown a relatively high singlet oxygen quantum yield within the cells subjected to PDT (0.553), and 50 μg/mL IC50. Classical toxicological and efficacy assessment were completed with dynamic cellular impedance measurement methodology. Using this technology we have shown that long time incubation of neuroblastoma cell lines in In-Pc (over 5 days) does not significantly hinder cell proliferation when concentration are ≤ 10 μg/mL. When irradiating neuroblastoma cells loaded with non-toxic concentration of In-Pc, 50% of cells entered apoptosis. Transmission electron microscopy has confirmed apoptotic characteristics of cells. Investigating the proliferative capacity of the in vitro treated cells we have shown that cells that "escape" the irradiation protocol, present a reduced proliferative capacity. In conclusion, In-Pc represents another photosensitizer that can display sound PDT properties enhancing neuroblastoma therapy armentarium.
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http://dx.doi.org/10.18632/oncotarget.11942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342510PMC
October 2016

Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases (Review).

Int J Mol Med 2016 Oct 2;38(4):1012-20. Epub 2016 Sep 2.

Department of Biomedical, Odontoiatric, Morphological and Functional Images, Occupational Medicine Section, 'Policlinico G. Martino' Hospital, University of Messina, I‑98125 Messina, Italy.

Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear. To date, studies have suggested that although exposure to pesticides can affect the immune system functionally, the development of immune disorders depends on the dose and duration of exposure to pesticides. However, many of the respective studies exhibit limitations, such as a lack of information on exposure levels, differences in the pesticide administration procedures, difficulty in characterizing a prognostic significance to the weak modifications often observed and the interpretation of obtained results. The main challenge is not just to understand the role of individual pesticides and their combinations, but also to determine the manner and the duration of exposure, as the toxic effects on the immune system cannot be separated from these considerations. There is a clear need for more well‑designed and standardized epidemiological and experimental studies to recognize the exact association between exposure levels and toxic effects and to identify useful biomarkers of exposure. This review focuses on and critically discusses the immunotoxicity of pesticides and the impact of cytokine levels on health, focusing on the development of several chronic diseases.
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http://dx.doi.org/10.3892/ijmm.2016.2728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029960PMC
October 2016

Influence of multi-walled carbon nanotubes on the cognitive abilities of Wistar rats.

Exp Ther Med 2016 Sep 1;12(3):1311-1318. Epub 2016 Jul 1.

Scientific Educational Center of Nanotechnology, Far Eastern Federal University, 690950 Vladivostok, Russia.

Studies of the neurobehavioral effects of carbon nanomaterials, particularly those of multi-walled carbon nanotubes (MWCNTs), have concentrated on cognitive effects, but data are scarce. The aim of this study was to assess the influence of MWCNTs on a number of higher nervous system functions of Wistar rats. For a period of 10 days, two experimental groups were fed with MWCNTs of different diameters (MWCNT-1 group, 8-10 nm; MWCNT-2 group, 18-20 nm) once a day at a dosage of 500 mg/kg. In the open-field test, reductions of integral indications of researching activity were observed for the two MWCNT-treated groups, with a parallel significant (P<0.01) increase in stress levels for these groups compared with the untreated control group. In the elevated plus-maze test, integral indices of researching activity in the MWCNT-1 and MWCNT-2 groups reduced by day 10 by 51 and 62%, respectively, while rat stress levels remained relatively unchanged. In the universal problem solving box test, reductions in motivation and energy indices of researching activity were observed in the two experimental groups. Searching activity in the MWCNT-1 group by day 3 was reduced by 50% (P<0.01) and in the MWCNT-2 group the relevant reduction reached 11.2%. By day 10, the reduction compared with controls, was 64% (P<0.01) and 58% (P<0.01) for the MWCNT-1 and MWCNT-2 groups, respectively. In conclusion, a series of specific tests demonstrated that MWCNT-treated rats experienced a significant reduction of some of their cognitive abilities, a disturbing and worrying finding, taking into consideration the continuing and accelerating use of carbon nanotubes in medicine and science.
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http://dx.doi.org/10.3892/etm.2016.3495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997982PMC
September 2016

Colon Cancer Cells Gene Expression Signature As Response to 5- Fluorouracil, Oxaliplatin, and Folinic Acid Treatment.

Front Pharmacol 2016 23;7:172. Epub 2016 Jun 23.

Department of Toxicology and Forensic Sciences, Medical School, University of Crete Heraklion, Greece.

5-FU cytotoxicity mechanism has been assigned both to the miss-incorporation of fluoronucleotides into RNA and DNA and to the inhibition of thymidylate synthase. 5-FU is one of the most widely used chemotherapeutic drugs, although it has severe side effects that may vary between patients. Pharmacogenetic studies related to 5-FU have been traditionally focused on the rate-limiting catabolic enzyme, dihydropyrimidine dehydrogenase that breaks 80-85% of 5-FU into its inactive metabolite. Choosing the right dosing scheme and chemotherapy strategy for each individual patient remains challenging for personalized chemotherapy management. In the general effort toward reduction of colorectal cancer mortality, in vitro screening studies play a very important role. To accelerate translation research, increasing interest has been focused on using in vivo-like models such as three-dimensional spheroids. The development of higher throughput assays to quantify phenotypic changes in spheroids is an active research area. Consequently, in this study we used the microarray technology to reveal the HT-29 colorectal adenocarcinoma cells gene expression signature as response to 5-FU/OXP/FA treatment in a state of the art 3D culture system. We report here an increased reactive oxygen species production under treatment, correlated with a decrease in cell viability and proliferation potential. With respect to the HT-29 cells gene expression under the treatment with 5-FU/OXP/FA, we found 15.247 genes that were significantly differentially expressed (p < 0.05) with a fold change higher that two-fold. Among these, 7136 genes were upregulated and 8111 genes were downregulated under experimental conditions as compared to untreated cells. The most relevant and statistic significant (p < 0.01) pathways in the experiment are associated with the genes that displayed significant differential expression and are related to intracellular signaling, oxidative stress, apoptosis, and cancer.
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http://dx.doi.org/10.3389/fphar.2016.00172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917556PMC
July 2016

Natural carcinogenic fiber and pleural plaques assessment in a general population: A cross-sectional study.

Environ Res 2016 10 26;150:23-29. Epub 2016 May 26.

Occupational Medicine, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

Natural carcinogenic fibers are asbestos and asbestiform fibers present as a natural component of soils or rocks. These fibers are released into the environment resulting in exposure of the general population. Environmental contamination by fibers are those cases occurred in: rural regions of Turkey, in Mediterranean countries and in other sites of the world, including northern Europe, USA and China. Fluoro-edenite(FE) is a natural mineral species first isolated in Biancavilla, Sicily. The fibers are similar in size and morphology to some amphibolic asbestos fibers, whose inhalation can cause chronic inflammation and cancer. The aim of the current study is to assess the presence and features of pleural plaques (PPs) in Biancavilla's general population exposed to FE through a retrospective cross-sectional study. All High-Resolution Computed Tomography (HRCT) chest scans carried out between June 2009 and June 2015 in Biancavilla municipality hospital site (exposed subjects) were reviewed. The exposed groups were 1:1 subjects, matched according to age and sex distributions, with unexposed subjects (n.1.240) randomly selected among HRCT chest scans carried out in a Hospital 30km away from Biancavilla. Subjects from Biancavilla with PPs were significantly more numerous than the control group ones (218 vs 38). Average age of either group was >60 years; the age of exposed subjects was significantly (p=0.0312) lesser than the unexposed group. In exposed subjects, in most PPs thickness ranged between 2 and 4.9cm(38%, n=83); while in unexposed ones PPs thickness was less than 2cm (55%, n=21). As to the size of PPs in exposed subjects, in most cases it ranged between 1cm and 24% of chest wall (53%, n=116); while in unexposed ones the size of PPs was lesser than 1cm (23%, n=58). Among exposed subjects, 36 cases (17%) PPs were detected with calcification, whereas in unexposed ones only three (8%) presented calcification. 137 lung parenchymal abnormalities were observed in exposed group; whereas, 12 lung parenchymal involvement were registered in unexposed subjects. The RR for PPs is 6,74 CI 95% (4,47-9,58) p<0,0001 in the exposed population. These findings, suggested the urge to extend the screening on the possible involvement of the respiratory tract to all Biancavilla's population, particularly in those aged more than 30. Besides, it seems essential to start indoor monitoring Biancavilla's municipality.
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http://dx.doi.org/10.1016/j.envres.2016.05.024DOI Listing
October 2016

Occupational exposure and risk of breast cancer.

Authors:
Concettina Fenga

Biomed Rep 2016 Mar 21;4(3):282-292. Epub 2016 Jan 21.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Occupational Medicine Section, 'Policlinico G. Martino' Hospital, University of Messina, Messina I-98125, Italy.

Breast cancer is a multifactorial disease and the most commonly diagnosed cancer in women. Traditional risk factors for breast cancer include reproductive status, genetic mutations, family history and lifestyle. However, increasing evidence has identified an association between breast cancer and occupational factors, including environmental stimuli. Epidemiological and experimental studies demonstrated that ionizing and non-ionizing radiation exposure, night-shift work, pesticides, polycyclic aromatic hydrocarbons and metals are defined environmental factors for breast cancer, particularly at young ages. However, the mechanisms by which occupational factors can promote breast cancer initiation and progression remains to be elucidated. Furthermore, the evaluation of occupational factors for breast cancer, particularly in the workplace, also remains to be explained. The present review summarizes the occupational risk factors and the associated mechanisms involved in breast cancer development, in order to highlight new environmental exposures that could be correlated to breast cancer and to provide new insights for breast cancer prevention in the occupational settings. Furthermore, this review suggests that there is a requirement to include, through multidisciplinary approaches, different occupational exposure risks among those associated with breast cancer development. Finally, the design of new epigenetic biomarkers may be useful to identify the workers that are more susceptible to develop breast cancer.
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http://dx.doi.org/10.3892/br.2016.575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774377PMC
March 2016

Critical Roles of EGFR Family Members in Breast Cancer and Breast Cancer Stem Cells: Targets for Therapy.

Curr Pharm Des 2016 ;22(16):2358-88

Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Brody Building 5N98C, Greenville, NC 27858 USA.

The roles of the epidermal growth factor receptor (EGFR) signaling pathway in various cancers including breast, bladder, brain, colorectal, esophageal, gastric, head and neck, hepatocellular, lung, neuroblastoma, ovarian, pancreatic, prostate, renal and other cancers have been keenly investigated since the 1980's. While the receptors and many downstream signaling molecules have been identified and characterized, there is still much to learn about this pathway and how its deregulation can lead to cancer and how it may be differentially regulated in various cell types. Multiple inhibitors to EGFR family members have been developed and many are in clinical use. Current research often focuses on their roles and other associated pathways in cancer stem cells (CSCs), identifying sites where therapeutic resistance may develop and the mechanisms by which microRNAs (miRs) and other RNAs regulate this pathway. This review will focus on recent advances in these fields with a specific focus on breast cancer and breast CSCs. Relatively novel areas of investigation, such as treatments for other diseases (e.g., diabetes, metabolism, and intestinal parasites), have provided new information about therapeutic resistance and CSCs.
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http://dx.doi.org/10.2174/1381612822666160304151011DOI Listing
November 2017