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1.
Occupational exposure to hexavalent chromium. Part I. Hazard assessment of non-cancer health effects.
Hessel, EVS, Staal, YCM, Piersma, AH, den Braver-Sewradj, SP, Ezendam, J
Regulatory toxicology and pharmacology : RTP. 2021;:105048
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Abstract
Hexavalent chromium (Cr(VI)) compounds have been studied extensively and several agencies have described their toxicological profile. In the past, personnel of the Dutch Ministry of Defence may have been exposed to Cr(VI) during maintenance activities. To investigate if this exposure may have caused irreversible adverse health effects, the Dutch National Institute for Public Health and the Environment (RIVM) summarized all available knowledge from previous evaluations. This information was complemented with a scoping review to retrieve new scientific literature. All scientific evidence was evaluated in workshops with external experts to come to an overview of irreversible adverse health effects that could be caused by occupational exposure to Cr(VI) compounds. This review focuses on non-cancer health effects. It was concluded that occupational exposure to Cr(VI) can cause perforation of the nasal septum by chromium ulcers, chronic lung diseases, including asthma, rhinitis, pulmonary fibrosis and COPD, skin ulcers and allergic contact dermatitis in humans. It is currently insufficiently clear if Cr(VI) can cause irreversible diseases due to disturbances of the immune system (other than allergic contact eczema, allergic asthma and rhinitis and chronic lung diseases) or adverse effects on fertility or prenatal development in humans.
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Potential ocular and systemic COVID-19 prophylaxis approaches for healthcare professionals.
Shetty, R, Lalgudi, VG, Khamar, P, Gupta, K, Sethu, S, Nair, A, Honavar, SG, Ghosh, A, D'Souza, S
Indian journal of ophthalmology. 2020;(7):1349-1356
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Abstract
The COVID-19 pandemic has brought with it, innumerable challenges in healthcare, both through the direct burden of morbidity and mortality of the disease, and also by the curtailing of other essential albeit less emergency medical services to reduce the risk of community spread. Reports from around the world are showing mounting number of cases even in healthcare professionals spite of usage of adequate personal protective equipment. There are a number of factors which could account for this, be it the affinity of the virus to the respiratory and other mucosa or to patient risk factors for developing severe forms of the disease. In view of the growing need for resuming other medical services, it is essential to find newer ways to protect ourselves better, whether by systemic or topical mucosal prophylaxis with various medications or lifestyle changes promoting wellbeing and immunity. This article discusses additional prophylactic measures including drug repurposing or new indication paradigms to render protection. Certain medications such as chloroquine, trehalose, antihistaminics, and interferons used topically for various ocular conditions with reasonably good safety records are known to have anti-viral properties. Hence, can be harnessed in preventing SARS-CoV-2 attachment, entry, and/or replication in host cells. Similarly, use of hypertonic saline for nasal and oral mucosa and dietary changes are possible methods of improving our resistance. These additional prophylactic measures can be cautiously explored by healthcare professionals to protect themselves and their patients.
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Omega 3 Supplementation Can Regulate Inflammatory States in Gas Station Workers: A Double-Blind Placebo-Controlled Clinical Trial.
Barkhordari, S, Mirmosayyeb, O, Mansourian, M, Hosseininasab, F, Ramezani, S, Barzegar, M, Amin, MM, Poursafa, P, Esmaeil, N, Kelishadi, R
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. 2020;(5):262-267
Abstract
Environmental exposure to diesel particulate matter and commercial gasoline in gas station workers might induce oxidative stress and changes in the balance of the immune system. In this study, the immunomodulatory impacts of omega 3 fatty acid (ω3FA) supplement were assessed on inflammatory and anti-inflammatory markers in gas station workers in a double-blind placebo-controlled clinical trial. Fifty-three men working in gas stations were treated with ω3FA (n = 29) or placebo (n = 24) for 60 days. C-reactive protein, interleukin-12 (IL-12), transforming growth factor β (TGF-β), interferon γ (IFN-γ), tumor necrosis factor α, IL-10, and IL-17 levels were measured by enzyme-linked immunosorbent assay method before and after the completion of the trial. The concentrations of IFN-γ and IL-17 were significantly decreased in ω3FA group compared with the placebo group (P < 0.001). Moreover, the levels of inhibitory cytokines including TGF-β and IL-10 significantly were increased in ω3FA group (P < 0.001). Overall, ω3FA nutritional supplementation can be useful in reducing inflammatory immune responses and maintaining immune tolerance in people with high exposure to inflammation-inducing factors. [Figure: see text].
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A randomized multicenter clinical trial to evaluate the efficacy of melatonin in the prophylaxis of SARS-CoV-2 infection in high-risk contacts (MeCOVID Trial): A structured summary of a study protocol for a randomised controlled trial.
García, IG, Rodriguez-Rubio, M, Mariblanca, AR, de Soto, LM, García, LD, Villatoro, JM, Parada, JQ, Meseguer, ES, Rosales, MJ, González, J, et al
Trials. 2020;(1):466
Abstract
OBJECTIVES Primary objective: to evaluate the efficacy of melatonin as a prophylactic treatment on prevention of symptomatic SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Secondary objectives: To evaluate the efficacy of melatonin as a prophylactic treatment on prevention of asymptomatic SARS-CoV-2 infection.To evaluate the efficacy of melatonin to prevent the development of severe COVID-19 in the participants enrolled in this study who develop SARS-CoV-2 infection along the trial.To evaluate the duration of COVID-19 symptoms in participants receiving melatonin before the infection.To evaluate seroconversion timing post-symptom onset. Exploratory objectives:To compare severity of COVID-19 between men and women.To evaluate the influence of sleep and diet on prevention from SARS-CoV-2 infection.To evaluate the effect of melatonin on the incidence and characteristics of lymphopenia and increase of inflammatory cytokines related to COVID-19. TRIAL DESIGN This is a two-arm parallel randomised double-blind controlled trial to evaluate the efficacy of melatonin versus placebo in the prophylaxis of coronavirus disease 2019 among healthcare workers. PARTICIPANTS Inclusion Criteria: Male or female participants ≥ 18 and ≤ 80 years of age.Healthcare workers from the public and private Spanish hospital network at risk of SARS-CoV 2 infection.Not having a previous COVID19 diagnosis.Understanding the purpose of the trial and not having taken any pre-exposure prophylaxis (PrEP) including HIV PrEP from March 1st 2020 until study enrolment.Having a negative SARS-CoV 2 reverse-transcription PCR (RT-PCR) result or a negative serologic rapid test (IgM/IgG) result before randomization.Premenopausal women must have a negative urinary pregnancy test in the 7 days before starting the trial treatment.Premenopausal women and males with premenopausal couples must commit to using a high efficiency anticonceptive method. EXCLUSION CRITERIA HIV infection.Active hepatitis B infection.Renal failure (CrCl < 60 mL/min/1.73 m2) or need for hemodialysis.Osteoporosis.Myasthenia gravis.Pre-existent maculopathy.Retinitis pigmentosa.Bradycardia (less than 50 bpm).Weight less than 40 Kg.Participant with any immunosuppressive condition or hematological disease.Treatment with drugs that may prolong QT in the last month before randomization for more than 7 days including: azithromycin, chlorpromazine, cisapride, clarithromycin, domperidone, droperidol, erythromycin, halofantrine, haloperidol, lumefantrine, mefloquine, methadone, pentamidine, procainamide, quinidine, quinine, sotalol, sparfloxacin, thioridazine, amiodarone.Hereditary intolerance to galactose, Lapp lactase deficiency or glucose or galactose malabsorption.Treatment with fluvoxamine.Treatment with benzodiazepines or benzodiazepine analogues such as zolpidem, zopiclone or zaleplon.Pregnancy.Breastfeeding.History of potentially immune derived diseases such as: lupus, Crohn's disease, ulcerative colitis, vasculitis or rheumatoid arthritis.Insulin-dependent diabetes mellitus.Known history of hypersensitivity to the study drug or any of its components.Patients that should not be included in the study at the judgment of the research team. Participants will be recruited from the following eight hospitals in Madrid, Spain: Hospital Universitario La Paz, Hospital Ramón y Cajal, Hospital Infanta Sofía, Hospital 12 de Octubre, Hospital Clínico San Carlos, Hospital Central de la defensa Gómez Ulla,Hospital de La Princesa and Hospital Infanta Leonor. INTERVENTION AND COMPARATOR Experimental: Melatonin (Circadin®, Exeltis Healthcare, Spain): 2 mg of melatonin orally before bedtime for 12 weeks. Comparator: Identical looking placebo (Laboratorios Liconsa, Spain) orally before bedtime for 12 weeks. MAIN OUTCOMES Number of SARS-CoV-2 (COVID-19) symptomatic infections confirmed by polymerase chain reaction (PCR) test or serologic test or according to each centre diagnosis protocol. Primary outcome will be measured until the end of treatment for each participant (until the date of the last dose taken by each patient). RANDOMISATION Patients who meet all inclusion and no exclusion criteria will be randomised, stratified by centres, sex and age (<50 and ≥ 50 years old). The randomisation sequence was created using SAS version 9.4 statistical software (procedure 'PROC PLAN') with a 1:1 allocation. No randomisation seed was specified. The randomisation seed was generated taking the hour of the computer where the program was executed. Randomization will be done centrally through the electronic system RedCAP® in order to conceal the sequence until interventions are assigned BLINDING (MASKING): Participants, caregivers, and those assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 450 participants are planned to be enrolled in this clinical trial, 225 in the experimental arm and 225 in the placebo arm. TRIAL STATUS Protocol version 3.0, 17th of April 2020. Recruitment ongoing. First participant was recruited on the 21st of April 2020. The final participant is anticipated to be recruited on the 31st of May 2020. As of May 18th, 2020, a total of 312 participants have been enrolled (154 at Hospital La Paz, 85 at Hospital Infanta Sofía and 73 at Hospital 12 de Octubre). TRIAL REGISTRATION EU Clinical Trials Register: 2020-001530-35; Date of trial registration: 13th of April 2020; https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001530-35/ES FULL PROTOCOL The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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Serum content of total adipionectin in the ChNPP accident clean up workers of the «iodine period» suffering from type 2 diabetes mellitus (literature review and research data).
Dombrovska, NS, Pleskach, OY
Problemy radiatsiinoi medytsyny ta radiobiolohii. 2017;:353-371
Abstract
OBJECTIVE assay of the total adiponectin level in the ChNPP accident clean up workers (ACUW) of the «iodine peri od» exposed to ionizing radiation in a young age and suffering now from type 2 diabetes mellitusMaterials and methods. The Chernobyl Nuclear Power Plant accident clean up workers (ACUW) of the iodine period (n=111) exposed to ionizing radiation at a young age (18-35 years) were examined in two groups: Group I (main study group, n=66) of persons with type 2 diabetes mellitus (DM) and Group II (comparison group, n=45) of persons with normal glucose challenge test results. Total radiation doses varied in the range of 10.0-860.0 mSv. Group III (nosological control group, n=20) included persons suffering type 2 DM but not exposed to ionizing radiation (IR) and Group IV were apparently healthy. All study groups were representative by the age. Anthropometric data and parameters of glycemic control were assayed. Index of the homeostatic model for assessing insulin resistance (HOMA IR) was calculated. Level of total adiponectin was assayed by the immune enzyme method. Statistical pro cessing of the data was carried out using Missrosoft® Exxel 2002 software. RESULTS AND CONCLUSIONS Serum concentration of total adiponectin in the Chornobyl NPP ACUW of the iodine peri od and suffering type 2 DM despite having normal body weight or overweight or any degree of obesity was signifi cantly lower compared to apparently healthy persons ACUW with and normal glycemic control. Moderate negative correlation was found between the level of total adiponectin and degree of obesity in the ACUW suffering type 2 DM (t = 0.367, p <0.05). With an increase in the duration of the disease there was a decrease in serum concentration of total adiponectin in the Chornobyl NPP ACUW of iodine period suffering type 2 DM and in the group of nosologi cal control. The most favorable type of glycemic profile was peculiar for patients in the main group with higher lev els of total serum adiponectin and the lowest body mass index (up to 25 kg/m2). An increase in the body mass index was accompanied by an adverse combination of abnormalities in glycemic metabolism (increased glucose concen tration, IRI, and HbA1c), insulin resistance (a significant increase in HOMA) against the background of a decrease in concentration of total adiponectin. No significant differences were found in adiponectin levels in dose subgroups. At the same time, the reliable differences between the main group and comparison group were found in the 2-5th dose subgroups, which are due to differences in numbers of people with metabolic syndrome (obesity) in the groups.
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Biomonitoring of a population of Portuguese workers exposed to lead.
García-Lestón, J, Roma-Torres, J, Vilares, M, Pinto, R, Cunha, LM, Prista, J, Teixeira, JP, Mayan, O, Pásaro, E, Méndez, J, et al
Mutation research. 2011;(1):81-8
Abstract
Lead is a heavy metal that has been used for many centuries and it is still used for various industrial purposes thanks to its physical and chemical characteristics. Human exposure to lead can result in a wide range of biological effects depending upon the level and duration of exposure. Despite the fact that lead has been found capable of eliciting genotoxic responses in a wide range of tests, not all studies have been conclusive. Although several experimental studies have shown that lead may modulate immune responses, data in exposed humans are still preliminary. The purpose of our study was to evaluate the genotoxic and immunotoxic effects of lead exposure in a group of 70 male workers from two Portuguese factories. The control group comprised 38 healthy males. The exposed individuals showed significantly higher levels of lead in blood and zinc protoporphyrin, and significantly lower δ-aminolevulinic acid dehydratase activity than the controls, suggesting a relatively high lead exposure. Nevertheless, the limit of 70 μg/dl for lead in blood established by the Portuguese regulation was never reached. Results of the comet assay were not modified by the exposure, but a significant increase in the mutation frequency in the exposed workers was obtained in the T-cell receptor mutation assay. Furthermore, data obtained in the analysis of the different lymphocyte subsets showed a significant decrease in %CD8+ cells and a significant increase in the %CD4+/%CD8+ ratio in exposed individuals with regard to the controls. No clear effect was observed for vitamin D receptor genetic polymorphism on the parameters evaluated. In view of our results showing mutagenic and immunotoxic effects related to lead exposure in occupational settings, it seems that the Portuguese biological exposure limit for lead needs to be revised in order to increase the safety of exposed workers.
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Selenium and immunocompetence in patients with head and neck cancer.
Kiremidjian-Schumacher, L, Roy, M, Glickman, R, Schneider, K, Rothstein, S, Cooper, J, Hochster, H, Kim, M, Newman, R
Biological trace element research. 2000;(2):97-111
Abstract
This randomized double-blind placebo-controlled study aimed to determine whether oral intake of 200 microg/d of sodium selenite, a dose within the safe and adequate daily intake (50-200 microg/d) recommended by the U.S. Food and Nutrition Board, will abrogate depressed or enhance normal-level immune functions of patients receiving therapy for squamous cell carcinoma of the head and neck. Subjects were given one selenium/placebo tablet/d for 8 wk, beginning on the day of their first treatment for the disease (e.g., surgery, radiation, or surgery and radiation) and their immune functions were monitored. Supplementation with selenium (Se) during therapy resulted in a significantly enhanced cell-mediated immunue responsiveness, as reflected in the ability of the patient's lymphocytes to respond to stimulation with mitogen, to generate cytotoxic lymphocytes, and to destroy tumor cells. The enhanced responsiveness was evident during therapy and following conclusion of therapy. In contrast, patients in the placebo arm of the study showed a decline in immune responsiveness during therapy, which was followed, in some patients, by an enhancement, but the responses of the group remained significantly lower than baseline values. The data also show that at baseline, patients entered in the study had significantly lower plasma Se levels than healthy individuals, and patients in stage I or II of disease had significantly higher plasma selenium levels than patients in stage III or IV of disease.