Oxidative stress, glutathione status, sirtuin and cellular stress response in type 2 diabetes.

Oxidative stress has been suggested to play a main role in the pathogenesis of type 2 diabetes mellitus and its complications. As a consequence of this increased oxidative status a cellular adaptive response occurs requiring functional chaperones, antioxidant production and protein degradation. This study was designed to evaluate systemic oxidative stress and cellular stress response in patients suffering from type 2 diabetes and in age-matched healthy subjects. Systemic oxidative stress has been evaluated by measuring plasma reduced and oxidized glutathione, as well as pentosidine, protein carbonyls lipid oxidation products 4-hydroxy-2-nonenal and F2-isoprostanes in plasma, and lymphocytes, whereas the lymphocyte levels of the heat shock proteins (HSP) HO-1, Hsp72, Sirtuin-1, Sirtuin-2 and thioredoxin reductase-1 (TrxR-1) have been measured to evaluate the systemic cellular stress response. Plasma GSH/GSSG showed a significant decrease in type 2 diabetes as compared to control group, associated with increased pentosidine, F2-isoprostanes, carbonyls and HNE levels. In addition, lymphocyte levels of HO-1, Hsp70, Trx and TrxR-1 (P<0.05 and P<0.01) in diabetic patients were higher than in normal subjects, while sirtuin-1 and sirtuin-2 protein was significantly decreased (p<0.05). In conclusion, patients affected by type 2 diabetes are under condition of systemic oxidative stress and, although the relevance of downregulation in sirtuin signal has to be fully understood, however induction of HSPs and thioredoxin protein system represent a maintained response in counteracting systemic pro-oxidant status. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

Toxicological effects of titanium dioxide nanoparticles: a review of in vitro mammalian studies.

BACKGROUND AND OBJECTIVE: Recent rapid advances in nanotechnology raise concerns about development, production route, and diffusion in industrial and consumer products of titanium dioxide nanoparticles (TiO2-NPs). In fact, compared to recent increase in applications of this nanomaterial, the health effects of human exposure have not been systematically investigated. The aim of this review was to provide a comprehensive overview on the current knowledge regarding the effects of TiO2-NPs on mammalian cells. EVIDENCE AND INFORMATION SOURCES: This review is based on an analysis of the current literature on this topic. STATE OF THE ART: Fine TiO2 particles have been considered as safe and to pose little risk to humans, suggesting that exposure to this material is relatively harmless. However, available data in the literature showed that TiO2-NPs can cause several adverse effects on mammalian cells such as increase of reactive oxygen species (ROS) production and cytokines levels, reduction of cell viability and proliferation, induction of apoptosis and genotoxicity. PERSPECTIVES AND CONCLUSIONS: Additional research is needed to obtain up-to-date knowledge on health effects of TiO2-NPs and to avoid any potential risk correlated to their exposure. Consequently, future studies need to: (1) use an homogeneous and rigorous exposure classification to clarify how the physicochemical properties of TiO2-NPs correlate with their toxicological effects; (2) assess the potential adverse effects of low level exposures to TiO2-NPs, as most of the information currently available originates from studies in which exposure levels were excessively and unrealistically high; (3) identify the possible roles of TiO2-NPs in genotoxicity and carcinogenicity (4) carry out epidemiologic studies of exposed workers to provide an assessment of possible risks correlated to the occupational exposure to TiO2-NPs.

Shift or night shift work and dementia risk: a systematic review.

OBJECTIVE: Dementia is a neurodegenerative disorder characterized by a progressive decline in multiple cognitive domains. Individual and/or environmental risk factors, i.e., aging, are involved in its pathogenesis. It is possible that shift and night works, affecting circadian rhythms, may contribute to the occurrence/progression of the disease. Therefore, aim of this review was to provide an overview on the possible association between shift or night work and cognitive decline. MATERIALS AND METHODS: A systematic review of literature studies available in PubMed, Scopus, and ISI Web of Science databases, addressing the possible relationship between shift or night work and dementia was performed. RESULTS: Not-homogeneous findings emerged from the revised studies. Some results supported a positive association between shift work and increased risk of dementia, although with a not unique evidence concerning the role of night work schedules and the consequent circadian misalignment in disease pathogenesis. Cardiometabolic disorders, underlying lifestyles, and additional occupational risk factors, including, psychosocial stress, may act as mediators in the shift work-dementia relationship, that may be overall affected by the individual genetic susceptibility too. Length of employment in shift works was also suggested to be responsible for cognitive damaging effects. CONCLUSIONS: The limited number of available studies, the several and different work schedules analyzed, together with the possible co-exposure to other occupational risk factors prevent to draw conclusions on shift work-dementia relationship. Further research should confirm such association and the causal relation with early cognitive alterations in order to guide suitable occupational risk assessment, as well as to promote healthy lifestyle and occupational management strategies, with the ultimate goal of preventing cognitive decline of shift workers. This may overall support the active aging of the workforce while providing benefits for the public health system.

Inflammatory bowel diseases and work disability: a systematic review of predictive factors.

OBJECTIVE: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and Ulcerative Colitis (UC), are chronic, relapsing intestinal disorders that may severely compromise patients' labour force participation. In this context, the present review aims to provide an overview on possible IBD pathological, socio-demographic, and treatment-related factors predictive for work disability with the purpose to provide guidance for a successful clinical and occupational management. MATERIALS AND METHODS: A systematic review of PubMed, Scopus, and ISI Web of Science databases was performed to retrieve all the studies addressing IBD-related predictors for work disability. RESULTS: Several factors have been suggested to predict work disability in the 15 revised investigations, although with not homogeneous results. Having CD was reported as a significantly better predictor for permanent work disability compared to UC, maybe in relation to the generally more serious disease course. Activity and severity of IBD, also indicated by the need for surgical treatment and comorbidities, was related to a significantly greater risk for work disability, although the exact role of other variables, i.e., specific symptoms, disease pattern and inflammatory parameters are still unclear. Among demographic factors, a significant predictive role has been suggested for female gender. CONCLUSIONS: Further research seems necessary to confirm the role of IBD related factors on work disability, and on other parameters of work impairment, i.e., absenteeism, presenteeism, activity and productivity loss. Additionally, work disability should be evaluated in relation to specific occupational risk factors. Overall, this may require a multidisciplinary approach aimed to achieve an adequate IBD clinical evaluation and management, an improvement of patients' psychosocial and professional well-being, while appropriately assessing and managing risks in the workplace.

Chemical hazard for dental hygienists: a systematic review.

OBJECTIVE: Dental hygienists (DHs) are professionals responsible for oral health. They deal with professional oral hygiene, counselling, and screening patients for oral health, as well as preventing and treating oral diseases. However, DH responsibilities and duties may vary worldwide, characterising changeable occupational exposure scenarios and making it difficult to achieve a suitable evaluation of workplace risks, particularly regarding chemical exposure. Therefore, the aim of the present work was to provide a comprehensive overview on the current knowledge on DH chemical risks. MATERIALS AND METHODS: According to the PRISMA guidelines, a systematic review of PubMed, Scopus, and Isi Web of Knowledge databases was performed to retrieve all articles assessing DH occupational chemical exposures. RESULTS: Fragmented data are currently available on DH chemical risk, due to the limited number of studies on the topic and few DHs enrolled, as well as their frequent assimilation to other oral healthcare professionals. The majority of the retrieved investigations focused on possible hypersensitivity reactions caused by natural rubber latex exposure, but not on potential risks derived from other currently employed substances or innovative wide-spreading compounds. CONCLUSIONS: Future research should be focused on assessing DH chemical risks according to a more comprehensive and toxicologically standardised approach to achieve an appropriate awareness among the DH workforce concerning the possibility for hazardous exposure and adverse health effects. Overall, this may lead to the adoption/implementation of adequate preventive measures to protect the health and safety of these oral healthcare professionals.

State and trait anxiety and depression in patients affected by gastrointestinal diseases: psychometric evaluation of 1641 patients referred to an internal medicine outpatient setting.

OBJECTIVES: To evaluate state and trait form of anxiety and current depression in patients affected by gastrointestinal diseases. METHODS: We studied 1641 outpatients with gastrointestinal disorders, consecutively referred to our Internal Medicine outpatients from 1997 to 2005. State and trait anxiety were assessed by the State and Trait Anxiety Inventory. Current depression was assessed by the Zung self-rating depression scale. RESULTS: Among patients, 1379 (84.1%) showed state anxiety, 1098 (67%) showed trait anxiety and 442 (27%) showed current depression. The number of gastrointestinal diseases was directly correlated to state anxiety (p < 0.001) and trait anxiety (p = 0.04). Females showed higher levels of anxiety and depression than males (p < 0.001). State anxiety was related to food allergies (p < 0.001), small intestinal bacterial overgrowth (SIBO) (p = 0.001), Hp infection (p = 0.01) and ulcerative colitis in active phase (p = 0.03). Trait anxiety was related to irritable bowel syndrome (IBS) (p < 0.001), Helicobacter pylori (Hp) infection (p = 0.001), food allergies (p = 0.001) and SIBO (p = 0.001). Current depression was related to IBS (p < 0.001) and coeliac disease (p = 0.01), SIBO (p = 0.02). A predicted probability of 0.77 +/- 0.16 to have state anxiety, of 0.66 +/- 0.12 to have trait anxiety and of 0.39 +/- 0.14 to have depression was found in these patients. CONCLUSIONS: Most of the patients who seek medical consultation for gastrointestinal problems show an associated affective disorder. These patients should be managed by a team including gastroenterologists, psychologists and/or psychiatrists, or by a gastroenterologist having expertise in the treatment of psychological disorders.

Biological monitoring of workers exposed to engineered nanomaterials.

As the number of nanomaterial workers increase there is need to consider whether biomonitoring of exposure should be used as a routine risk management tool. Currently, no biomonitoring of nanomaterials is mandated by authoritative or regulatory agencies. However, there is a growing knowledge base to support such biomonitoring, but further research is needed as are investigations of priorities for biomonitoring. That research should be focused on validation of biomarkers of exposure and effect. Some biomarkers of effect are generally nonspecific. These biomarkers need further interpretation before they should be used. Overall biomonitoring of nanomaterial workers may be important to supplement risk assessment and risk management efforts.

Palladium nanoparticle effects on endocrine reproductive system of female rats.

The widespread industrial application of nanomaterials (NMs) has dramatically increased the likelihood of environmental and occupational exposure of humans to such xenobiotics. This issue, together with the increasing public health interest in understanding the effects of chemicals on endocrine system, encouraged to investigate the disruptive potential of NMs on the endocrine function. Therefore, the aim of this study was to evaluate the effects of palladium nanoparticles (Pd-NPs) on the female reproductive system of Wistar rats, intravenously exposed to different doses (0.12, 1.2, and 12 µg/kg), through the assessment of possible quantitative changes in the serum concentrations of several sex hormones. Our results demonstrated that the highest exposure doses significantly reduced the estradiol and testosterone concentrations, while increased the luteinizing hormone levels in treated animals compared to controls. Such alterations are indicative for an abnormal reproductive axis function. However, further investigations are needed to clarify the role of the different NP physicochemical properties in determining such effects, and possible underlining molecular mechanisms, as well as their relevance for the development of diseases in the female reproductive system. Overall, this may be helpful to define accurate risk assessment and management strategies to protect the health of the general and occupational populations exposed to Pd-NPs.

Subchronic exposure to palladium nanoparticles affects serum levels of cytokines in female Wistar rats.

Recently, palladium nanoparticles (PdNPs) have been increasingly used in many industrial sectors, and this has led to a significant release of nano-sized palladium particles into the environment. However, despite the increase in occupational and general population exposure, information on the potential adverse effects of these PdNPs is still limited and their impact on the immune system constitutes a major health concern. Therefore, the aim of this study was to investigate the potential adverse effects induced by subchronic intravenous administration of PdNPs on the immune system of female Wistar rats by evaluating alterations in Interleukin (IL)-1α, IL-2, IL-4, IL-6, IL-10, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), Interferon (INF)-γ, and Tumor Necrosis Factor (TNF)-α serum levels. Exposed and control animals were randomly divided into five groups (0, 0.012, 0.12, 1.2, and 12 µg PdNPs per kg body weight) which were treated with repeated intravenous injections of vehicle or PdNPs (on day 1, 30, and 60). Subchronic exposure to PdNPs induced a decreasing trend in serum levels in most of the cytokines investigated, with the highest concentration (12 µg/kg) determining significant inhibitory effects. Overall, these results showed that PdNPs are able to alter cytokine serum levels in subchronically treated Wistar rats, suggesting a possible impact of these xenobiotics on the immune system after long-term exposures.

In vitro evaluation of the potential toxic effects of palladium nanoparticles on fibroblasts and lung epithelial cells.

Palladium nanoparticles have been increasingly used in catalytic processes, wastewater treatment, electronics, and biomedicine. However, recent evidence proved that these nanoparticles are able to induce adverse effects both in in vitro and in vivo models. Nevertheless, molecular mechanisms underlying the toxic effects are still poorly understood. Therefore, this study aimed to investigate the potential toxicological mechanisms of palladium nanoparticles assessing their effects on normal diploid rat fibroblast and lung carcinoma human epithelial cell lines. Several endpoints such as cell growth, cell cycle progression, DNA damage, induction of apoptosis, reactive oxygen species production and expression of cell cycle regulatory proteins were evaluated. Results showed that palladium nanoparticles inhibited cell growth in a dose- and time-dependent manner in both cell lines, although with a more evident action on fibroblasts. Interestingly, inhibition of cell growth was not associated with the induction of apoptosis. Cell cycle progression was arrested in the G0/G1 phase and DNA damage was evident in both cell lines even if only a slight increase in the intracellular reactive oxygen species levels was detected. These findings provide valuable insight into understanding the molecular mechanisms responsible of palladium nanoparticles toxicity whose identification is essential to define an adequate risk assessment process.

Occupational risk factors in inflammatory bowel disease.

OBJECTIVE: Crohn's disease and ulcerative colitis are the two main forms of inflammatory bowel disease (IBD). Although the aetiology of IBD is not completely understood, an interaction between genetic and environmental factors has been proposed. In this context, however, environmental epidemiology lacks a comprehensive evaluation of the possible role of occupational exposures in IBD development and progression. Therefore, aim of our review was to evaluate how certain occupational risk factors may affect IBD pathogenesis, clinical history and severity of disease manifestations. MATERIALS AND METHODS: A critical revision of available literature concerning exposure to groups of potential workplace hazardous agents and IBD, as it appears in Medline and Web of knowledge, was performed. RESULTS: The role of workplace exposures to chemical and biological agents, ionizing or non-ionizing radiations, shift-works, indoor, and sedentary works as well as job strain on IBD has been critically revised. However, the limited number of studies addressing these issues prevented us from extrapolating definite conclusions. CONCLUSIONS: Our review pointed out some critical aspects concerning the relationship between occupational factors and IBD, in terms of causative pathways, hazardous exposure, susceptibility and consequences of IBD functional limitations on career choice and fitness for work that need future investigations. Overall, this seems a challenging public health issue, considering the strong IBD impact on patients' quality of life, work productivity and costs to society. Moreover, this review may encourage concerted actions of health care specialists, occupational physicians, employers and IBD workers to plan preventive and protective measures for "healthier patterns of work" for IBD and to develop innovative perspectives for an integrated management of "IBD at work".