Pathogenic Mechanisms and Therapeutic Implication in Nickel-Induced Cell Damage.

BACKGROUND: Nickel (Ni) is mostly applied in a number of industrial areas such as printing inks, welding, alloys, electronics and electrical professions. Occupational or environmental exposure to nickel may lead to cancer, allergy reaction, nephrotoxicity, hepatotoxicity, neurotoxicity, as well as cell damage, apoptosis and oxidative stress. METHODS: In here, we focused on published studies about cell death, carcinogenicity, allergy reactions and neurotoxicity, and promising agents for the prevention and treatment of the toxicity by Ni. RESULTS: Our review showed that in the last few years, more researches have focused on reactive oxygen species formation, oxidative stress, DNA damages, apoptosis, interaction with involving receptors in allergy and mitochondrial damages in neuron induced by Ni. CONCLUSION: The collected data in this paper provide useful information about the main toxicities induced by Ni, also, their fundamental mechanisms, and how to discover new ameliorative agents for prevention and treatment by reviewing agents with protective and therapeutic consequences on Ni induced toxicity.

Functional symptoms in dermatology: Part 2.

Functional disorders within dermatology present as various constellations of skin symptoms, but without evidence of organic pathology. Examples can include mucocutaneous pain syndromes, functional pruritus, somatoform pain disorder and rarer entities, such as undifferentiated somatoform idiopathic anaphylaxis and multiple chemical sensitivity syndrome. These conditions can have a significant impact on a patient's quality of life, and can present challenges in communication, investigation and management. The aetiology of functional disorders is not fully understood, but with an effective collaborative approach, a psychological explanation for these symptoms is often found. A structured approach to assessment can lead to a confident diagnosis, and understanding a patient's belief system and the impact of symptoms on their functioning can give better grounding for successful management. Treatment is dependent on the level of the patient's engagement with healthcare professionals, and often takes a measured and rehabilitative approach. Psychological therapies have been shown to be effective, often alongside both psychopharmacological and topical medications.

Impact of Heavy Metals on Host Cells: Special Focus on Nickel-Mediated Pathologies and Novel Interventional Approaches.

BACKGROUND: Heavy metals [arsenic, aluminium, cadmium, chromium, cobalt, lead, nickel (Ni), palladium and titanium] are environmental contaminants able to impact with host human cells, thus, leading to severe damage. OBJECTIVE: In this review, the detrimental effects of several heavy metals on human organs will be discussed and special emphasis will be placed on Ni. In particular, Ni is able to interact with Toll-like receptor-4 on immune and non-immune cells, thus, triggering the cascade of pro-inflammatory cytokines. Then, inflammatory and allergic reactions mediated by Ni will be illustrated within different organs, even including the central nervous system, airways and the gastrointestinal system. DISCUSSION: Different therapeutic strategies have been adopted to mitigate Ni-induced inflammatoryallergic reactions. In this context, the ability of polyphenols to counteract the inflammatory pathway induced by Ni on peripheral blood leukocytes from Ni-sensitized patients will be outlined. In particular, polyphenols are able to decrease serum levels of interleukin (IL)-17, while increasing levels of IL- 10. These data suggest that the equilibrium between T regulatory cells and T helper 17 cells is recovered with IL-10 acting as an anti-inflammatory cytokine. In the same context, polyphenols reduced elevated serum levels of nitric oxide, thus, expressing their anti-oxidant potential. Finally, the carcinogenic potential of heavy metals, even including Ni, will be highlighted. CONCLUSION: Heavy metals, particularly Ni, are spread in the environment. Nutritional approaches seem to represent a novel option in the treatment of Ni-induced damage and, among them, polyphenols should be taken into consideration for their anti-oxidant and anti-inflammatory activities.

Medical management, prevention and mitigation of environmental risks factors in Neurology.

The human environment and exposures arising therefrom are major contributors to neurological disorders ranging from stroke to neurodegenerative diseases. Reduction of exposure to environmental risk factors, with the goal of disease prevention or control, is addressed at the individual as well as the societal level and in recognition of differential subject vulnerability. We examine some practical solutions in high-income countries that may allow a better adaptation to environmental risks and reduce their adverse impact on the nervous system. We consider the citizen's role in reducing unhealthy exposures and explore new approaches to treatment.

The World Federation of Neurology and the challenges in Environment Neurology.

Since its establishment the World Federation of Neurology (WFN) has manifested a keen interest in the environment and its relation to neurological diseases. Thus, in 2007 the WFN renamed the "Neurotoxicological Research Group" to "Environmental Neurology Research Group". In this short article, we review some recent events which illustrate the WFN involvement in Environmental Neurology as well its concerns about global health matters involving environmental issues.

[One or more functional somatic syndromes? Comparison of the health status of fibromyalgia and electro-hypersensitive people]. / Un ou plusieurs syndromes somatiques fonctionnels ? Comparaison de l'état de santé de personnes fibromyalgiques et électro-hypersensibles.

INTRODUCTION: Functional somatic syndromes, grouping somatic symptoms without an organic explanation, are defined either by their predominant symptoms or by an attribution to an, often hypothetical, cause. Due to many similarities, some authors consider that there is only one FSS due to a general phenomenon of "somatization". The objective of this work was to compare two functional somatic syndromes, one defined by its symptoms, fibromyalgia, and the other by a specific contested attribution, electro-hypersensitivity. METHOD: Fibromyalgia or electro-hypersensitive participants (EHS) were recruited from September 2016 to April 2017 through associations of patients in Auvergne-Rhône-Alpes. Home interviews included the collection of medical, psychopathological, and symptom histories. The assessment of psychological distress, quality of life and the search for other functional somatic syndromes was performed through structured questionnaires, self-administrated scales, and clinical examination. RESULTS: Sixteen fibromyalgia subjects and sixteen EHS subjects were included. There are differences in symptomatology, although many symptoms are common to both conditions. Lifetime history of psychiatric disorders and current psychological distress and psychopathology are frequent in both groups but more prevalent in fibromyalgia subjects. The experience of the symptoms, their interpretation, the diagnostic itineraries and the therapeutic behaviours differ radically according to the group, even if for all socio-professional impact is high and quality of life are altered. CONCLUSION: The health status of fibromyalgia persons is overall worse than the health status of electro-hypersensitive individuals in this small sample. Despite the overlap in symptoms and a similar impact on daily functioning, this exploratory study suggests that heterogeneous mechanisms of "somatization" may be at stake in functional somatic syndromes.

¿Es negligente el tratamiento actual de la intolerancia ambiental idiopática? / Is the current treatment of idiopathic environmental intolerance negligent?

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Desensitization to chemical and food sensitivities by low-dose immunotherapy ascertained by provocation neutralization is associated with reduced influx of calcium ions into lymphocytes.

Background Food and chemical sensitivities have detrimental effects on health and the quality of life. The natural course of such sensitivities can potentially be altered through various types of allergen-specific immunotherapy, including low-dose immunotherapy. The molecular mechanism by which low-dose immunotherapy causes desensitization has not thus far been elucidated. While resting lymphocytes maintain a low cytosolic calcium ion concentration, antigen receptor signaling results in calcium ion influx, predominantly via store-operated calcium channels. We therefore hypothesized that desensitization by low-dose immunotherapy is associated with reduced influx of calcium ions into lymphocytes. The aim of this study was to test this hypothesis. Methods Intracellular lymphocytic calcium ion concentrations were assayed in a total of 47 patients, following incubation with picogram amounts of the test allergens, using a cell-permeable calcium-sensing ratiometric fluorescent dye and fluorescence spectroscopy, both at baseline and following successful provocation neutralization treatment with low-dose immunotherapy. Results Low-dose immunotherapy was associated with a reduction in lymphocytic intracellular calcium ion concentration following treatment of: 23 % for metabisulfite sensitivity (p<0.0004); 12 % for salicylate sensitivity (p<0.01); 23 % for benzoate sensitivity (p<0.01); 30 % for formaldehyde sensitivity (p<0.0001); 16 % for sensitivity to petrol exhaust (p<0.003); 16 % for natural gas sensitivity (p<0.001); 13 % for nickel sensitivity (p<0.05); 30 % for sensitivity to organophosphates (p<0.01); and 24 % for sensitivity to nitrosamines (p<0.05). Conclusions Low-dose immunotherapy may affect baseline levels of intracellular calcium in lymphocytes, supporting the premise that allergens affect cell signaling in immune cells and provocation neutralization immunotherapy helps to promote more normal immune cell signaling.

EUROPAEM EMF Guideline 2016 for the prevention, diagnosis and treatment of EMF-related health problems and illnesses.

Chronic diseases and illnesses associated with non-specific symptoms are on the rise. In addition to chronic stress in social and work environments, physical and chemical exposures at home, at work, and during leisure activities are causal or contributing environmental stressors that deserve attention by the general practitioner as well as by all other members of the health care community. It seems necessary now to take "new exposures" like electromagnetic fields (EMF) into account. Physicians are increasingly confronted with health problems from unidentified causes. Studies, empirical observations, and patient reports clearly indicate interactions between EMF exposure and health problems. Individual susceptibility and environmental factors are frequently neglected. New wireless technologies and applications have been introduced without any certainty about their health effects, raising new challenges for medicine and society. For instance, the issue of so-called non-thermal effects and potential long-term effects of low-dose exposure were scarcely investigated prior to the introduction of these technologies. Common electromagnetic field or EMF sources: Radio-frequency radiation (RF) (3 MHz to 300 GHz) is emitted from radio and TV broadcast antennas, Wi-Fi access points, routers, and clients (e.g. smartphones, tablets), cordless and mobile phones including their base stations, and Bluetooth devices. Extremely low frequency electric (ELF EF) and magnetic fields (ELF MF) (3 Hz to 3 kHz) are emitted from electrical wiring, lamps, and appliances. Very low frequency electric (VLF EF) and magnetic fields (VLF MF) (3 kHz to 3 MHz) are emitted, due to harmonic voltage and current distortions, from electrical wiring, lamps (e.g. compact fluorescent lamps), and electronic devices. On the one hand, there is strong evidence that long-term exposure to certain EMFs is a risk factor for diseases such as certain cancers, Alzheimer's disease, and male infertility. On the other hand, the emerging electromagnetic hypersensitivity (EHS) is more and more recognized by health authorities, disability administrators and case workers, politicians, as well as courts of law. We recommend treating EHS clinically as part of the group of chronic multisystem illnesses (CMI), but still recognizing that the underlying cause remains the environment. In the beginning, EHS symptoms occur only occasionally, but over time they may increase in frequency and severity. Common EHS symptoms include headaches, concentration difficulties, sleep problems, depression, a lack of energy, fatigue, and flu-like symptoms. A comprehensive medical history, which should include all symptoms and their occurrences in spatial and temporal terms and in the context of EMF exposures, is the key to making the diagnosis. The EMF exposure is usually assessed by EMF measurements at home and at work. Certain types of EMF exposure can be assessed by asking about common EMF sources. It is very important to take the individual susceptibility into account. The primary method of treatment should mainly focus on the prevention or reduction of EMF exposure, that is, reducing or eliminating all sources of high EMF exposure at home and at the workplace. The reduction of EMF exposure should also be extended to public spaces such as schools, hospitals, public transport, and libraries to enable persons with EHS an unhindered use (accessibility measure). If a detrimental EMF exposure is reduced sufficiently, the body has a chance to recover and EHS symptoms will be reduced or even disappear. Many examples have shown that such measures can prove effective. To increase the effectiveness of the treatment, the broad range of other environmental factors that contribute to the total body burden should also be addressed. Anything that supports homeostasis will increase a person's resilience against disease and thus against the adverse effects of EMF exposure. There is increasing evidence that EMF exposure has a major impact on the oxidative and nitrosative regulation capacity in affected individuals. This concept also may explain why the level of susceptibility to EMF can change and why the range of symptoms reported in the context of EMF exposures is so large. Based on our current understanding, a treatment approach that minimizes the adverse effects of peroxynitrite - as has been increasingly used in the treatment of multisystem illnesses - works best. This EMF Guideline gives an overview of the current knowledge regarding EMF-related health risks and provides recommendations for the diagnosis, treatment and accessibility measures of EHS to improve and restore individual health outcomes as well as for the development of strategies for prevention.

Comparing cognitive-behavioural psychotherapy and psychoeducation for non-specific symptoms associated with indoor air: a randomised control trial protocol.

INTRODUCTION: Indoor air-related conditions share similarities with other conditions that are characterised by medically unexplained symptoms (MUS)-a combination of non-specific symptoms that cannot be fully explained by structural bodily pathology. In cases of indoor air-related conditions, these symptoms are not fully explained by either medical conditions or the immunological-toxicological effects of environmental factors. The condition may be disabling, including a non-adaptive health behaviour. In this multifaceted phenomenon, psychosocial factors influence the experienced symptoms. Currently, there is no evidence of clinical management of symptoms, which are associated with the indoor environment and cannot be resolved by removing the triggering environmental factors. The aim of this study is to compare the effect of treatment-as-usual (TAU) and two psychosocial interventions on the quality of life, and the work ability of employees with non-specific indoor air-related symptomatology. METHODS AND ANALYSES: The aim of this ongoing randomised controlled trial is to recruit 60 participants, in collaboration with 5 occupational health service units. The main inclusion criterion is the presence of indoor air-related recurrent symptoms in ≥2 organ systems, which have no pathophysiological explanation. After baseline clinical investigations, participants are randomised into interventions, which all include TAU: cognitive-behavioural psychotherapy, psychoeducation and TAU (control condition). Health-related quality of life, measured using the 15D-scale, is the primary outcome. Secondary outcomes include somatic and psychiatric symptoms, occupational factors, and related underlying mechanisms (ie, cognitive functioning). Questionnaires are completed at baseline, at 3, 6 and 12-month follow-ups. Data collection will continue until 2017. The study will provide new information on the individual factors related to indoor air-associated symptoms, and on ways in which to support work ability. ETHICS AND DISSEMINATION: The Coordinating Ethics Committee of the Hospital District of Helsinki and Uusimaa, Finland, has granted approval for the study. The results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02069002; Pre-results.

Fine particulate air pollution and outpatient department visits for headache in Taipei, Taiwan.

This study was undertaken to determine whether there was an association between fine particle matter (PM(2.5)) levels and daily outpatient department visits (OPD) for headaches in Taipei, Taiwan. Daily OPD visits for headaches and ambient air pollution data for Taipei were obtained for the period 2006-2011. The relative risk of visits for OPD headaches was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased OPD visits for headaches were significantly associated with levels of PM(2.5) both on warm days (>23°C) and cool days (<23°C), with an interquartile range rise associated with a 12% (95% CI = 10-14%) and 3% (95% CI = 1-5%) elevation in OPD visits for headaches, respectively. In the two-pollutant models, PM(2.5) remained significant after inclusion of sulfur dioxide (SO2) or ozone (O3) on both warm and cool days. This study provides evidence that higher levels of PM(2.5) increase the risk of OPD visits for headaches in Taipei, Taiwan.

The air quality health index and emergency department visits for urticaria in Windsor, Canada.

Ambient air pollution exposure has been associated with several health conditions, limited not only to respiratory and cardiovascular systems but also to cutaneous tissues. However, few epidemiological studies examined pollution exposure on skin problems. Basically, the common mechanism by which pollution may affect skin physiology is by induction of oxidative stress and inflammation. Urticaria is among the skin pathologies that have been associated with pollution. Based on the combined effects of three ambient air pollutants, ozone (O3), nitrogen dioxide (NO2), and fine particulate matter (PM) with a median aerodynamic diameter of less than 2.5 µm (PM(2.5)), on mortality, the Air Quality Health Index (AQHI) in Canada was developed. The aim of this study was to examine the associations of short-term changes in AQHI with emergency department (ED) visits for urticaria in Windsor-area hospitals in Canada. Diagnosed ED visits were retrieved from the National Ambulatory Care Reporting System (NACRS). A time-stratified case-crossover design was applied to 2905 ED visits (males = 1215; females = 1690) for urticaria from April 2004 through December 2010. Odds ratios (OR) and their corresponding 95% confidence intervals (95%CI) for ED visits associated with increase by one unit of risk index were calculated employing conditional logistic regression. Positive and significant results were observed between AQHI levels and OR for ED visits for urticaria in Windsor for lags 2 and 3 days. A distributed lag nonlinear model technique was applied to daily counts of ED visits for lags 0 to 10 and significant results were obtained from lag 2 to lag 5 and for lag 9. These findings demonstrated associations between ambient air pollution and urticarial confirming that air pollution affects skin conditions.

Sublingual Immunotherapy for Allergic Fungal Sinusitis.

Allergic fungal sinusitis (AFS) is a condition that has an allergic basis caused by exposure to fungi in the sinonasal tract leading to chronic inflammation. Despite standard treatment modalities, which typically include surgery and medical management of allergies, patients still have a high rate of recurrence. Subcutaneous immunotherapy (SCIT) has been used as adjuvant treatment for AFS. Evidence exists to support the use of sublingual immunotherapy (SLIT) as a safe and efficacious method of treating allergies, but no studies have assessed the utility of SLIT in the management of allergic fungal sinusitis. A record review of cases of AFS that are currently or previously treated with sublingual immunotherapy from 2007 to 2011 was performed. Parameters of interest included serum IgE levels, changes in symptoms, Lund-McKay scores, decreased sensitization to fungal allergens associated with AFS, and serum IgE levels. Ten patients with diagnosed AFS were treated with SLIT. No adverse effects related to the use of SLIT therapy were identified. Decreases in subjective complaints, exam findings, Lund-McKay scores, and serum IgE levels were observed. Thus, sublingual immunotherapy appears to be a safe adjunct to the management of AFS that may improve patient outcomes.

Approach to patients with unexplained multimorbidity with sensitivities.

OBJECTIVE: To explore the underlying causation of unexplained multimorbidity with sensitivities and to discuss the management of patients who present with this perplexing condition. SOURCES OF INFORMATION: Medical and scientific literature was used from MEDLINE (PubMed), several books, toxicology and allergy journals, conference proceedings, government publications, and environmental health periodicals. MAIN MESSAGE: Multimorbidity with sensitivities has become an increasingly common and confusing primary care dilemma. Escalating numbers of debilitated individuals are now presenting to family physicians and specialists with multisystem health complaints, including sensitivities and fatigue, with no obvious causation, a paucity of laboratory findings, and a lack of straightforward solutions. In the recent scientific literature, there is discussion of sensitivity-related illness, an immune-mediated disorder that frequently manifests with multisystem symptoms, commonly including sensitivities and fatigue. This condition appears to be originally caused by adverse environmental exposures and toxicant bioaccumulation-an increasingly prevalent and well-documented problem in contemporary culture. CONCLUSION: Various toxic exposures and their bioaccumulation within the body frequently manifest as sensitivity-related illness. In clinical settings, patients with this disorder often present with otherwise unexplained multimorbidity and sensitivities. The health status of patients with this condition can be ameliorated by removing triggers (eg, scented products), optimizing biochemistry, removing further sources of toxicant exposures, and eliminating the internal dose of persistent toxicants.

[Analysis of the quality of data issued from Beirut's hospitals in order to measure short-term health effects of air pollution]. / Analyse de la qualité des données issues des hôpitaux de Beyrouth Municipe pour mesurer les effets à court terme de la pollution atmosphérique.

BACKGROUND: The effects of air pollution on human health have been the subject of much public health research. Several techniques and methods of analysis have been developed. Thus, Beirut Air Pollution and Health Effects (BAPHE) was designed to develop a methodology adapted to the context of the city of Beirut in order to quantify the short-term health effects of air pollution. METHODS: The quality of data collected from emergency units was analyzed in order to properly estimate hospitalizations via these units. This study examined the process of selecting and validating health and pollution indicators. RESULTS: The different sources of data from emergency units were not correlated. BAPHE was therefore reoriented towards collecting health data from the emergency registry of each hospital. A pilot study determined the appropriate health indicators for BAPHE and created a classification methodology for data collection. CONCLUSION: In Lebanon, several studies have attempted to indirectly assess the impact of air pollution on health. They had limitations and weaknesses and offered no recommendations regarding the sources and quality of data. The present analysis will be useful for BAPHE and for planning further studies.

The search for reliable biomarkers of disease in multiple chemical sensitivity and other environmental intolerances.

Whilst facing a worldwide fast increase of food and environmental allergies, the medical community is also confronted with another inhomogeneous group of environment-associated disabling conditions, including multiple chemical sensitivity (MCS), fibromyalgia, chronic fatigue syndrome, electric hypersensitivity, amalgam disease and others. These share the features of poly-symptomatic multi-organ cutaneous and systemic manifestations, with postulated inherited/acquired impaired metabolism of chemical/physical/nutritional xenobiotics, triggering adverse reactions at exposure levels far below toxicologically-relevant values, often in the absence of clear-cut allergologic and/or immunologic involvement. Due to the lack of proven pathogenic mechanisms generating measurable disease biomarkers, these environmental hypersensitivities are generally ignored by sanitary and social systems, as psychogenic or "medically unexplained symptoms". The uncontrolled application of diagnostic and treatment protocols not corresponding to acceptable levels of validation, safety, and clinical efficacy, to a steadily increasing number of patients demanding assistance, occurs in many countries in the absence of evidence-based guidelines. Here we revise available information supporting the organic nature of these clinical conditions. Following intense research on gene polymorphisms of phase I/II detoxification enzyme genes, so far statistically inconclusive, epigenetic and metabolic factors are under investigation, in particular free radical/antioxidant homeostasis disturbances. The finding of relevant alterations of catalase, glutathione-transferase and peroxidase detoxifying activities significantly correlating with clinical manifestations of MCS, has recently registered some progress towards the identification of reliable biomarkers of disease onset, progression, and treatment outcomes.