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Introduction: Serum heat shock protein (HSP) concentrations have been reported as potential biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigate the role of serum HSP70, HSP90, and DNAJC7 as biomarkers for ALS. Methods: Serum samples were collected from ALS patients and volunteer controls from three different clinical cohorts (in Germany, Ireland, and Italy). Serum HSP concentrations were determined using enzyme-linked immunosorbent assay. Descriptive statistics, generalized logistic regression, and Cox proportional hazards models were used to model associations between log serum HSP concentrations and ALS risk. Results: In total, 251 ALS patients and 184 healthy volunteers were included. Logistic regression models failed to find associations between ALS risk and log serum concentration of HSP70 (OR 0.43, 95% CI: 0.10-1.78, p = 0.242), HSP90 (OR 0.95, 95% CI: 0.39-2.37, p = 0.904), or DNAJC7 (OR 1.55, 95% CI: 0.90-2.68, p = 0.118). Survival of ALS patients was not associated with log serum concentration of HSP HSP70 (HR1.06, 95% CI: 0.36-3.14, p = 0.916), HSP90 (HR 1.17, 95% CI: 0.67-2.02, p = 0.584), or DNAJC7 (HR 0.83, 95% CI: 0.57-1.21, p = 0.337). Discussion: We did not replicate previous findings that serum HSP70 and HSP90 concentrations were associated with risk of ALS. DNAJC7 was not associated with ALS risk, and there were no obvious longitudinal patterns in log serum concentrations of HSP70, HSP90, or DNAJC7. In addition, serum HSP concentrations were not associated with ALS survival.
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BACKGROUND: Due to climate change, the increasing frequency of hot summer days and heat waves can result in occupational heat strain, especially in non-air-conditioned workplaces. Healthcare workers (HCW) engaged in patient care are particularly affected, as they are additionally exposed to physical stress. The use of personal protective equipment (PPE) can aggravate heat strain in HCW. This study aimed to examine the subjective well-being of HCW when exposed to heat and PPE under controlled conditions. METHODS: This study was designed as a randomized crossover trial. Participants performed standardized healthcare tasks in a climatic chamber for approximately 3.5 h at different indoor temperatures (22 °C and 27 °C) and varied working conditions (with or without PPE). The effects on participants' subjective well-being, encompassing thermal, physiological and psychological stress were assessed using a customized questionnaire. RESULTS: Heat had a greater effect than PPE on thermal, physical and psychological stress. Conversely, PPE had a greater effect on physical demand and effort. For the majority of outcomes, combined exposure to heat and PPE resulted in the highest perceived discomfort. Furthermore, the participants reported increased sweating and other discomforts when working at elevated temperatures or with PPE. CONCLUSIONS: In this study, heat and PPE, but particularly the combination of both factors, were identified as unfavorable working environments. Although the trials were conducted in a controlled environment, the outcomes provide valuable information about the effect of heat and PPE on HCW in a real-life setting. Furthermore, the design used in this study can be beneficial in evaluating the effect of mitigation strategies.
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Environmental exposure to lead substantially decreased over the past decades. However, soil of former mining areas still contains high lead levels. We therefore performed a biomonitoring study among children living in two former mining communities in Lower Saxony, Germany. In these communities, soil contains lead levels of 1000 to 30,000 mg/kg. Overall, 75 children (6-10 years of age) attending the two primary schools of the study area took part in the study. Parents completed a short questionnaire on sociodemographics, and children provided capillary whole blood samples. We analysed lead using inductively coupled plasma tandem mass spectrometer. We compared the results to current German (20 µg/l for boys, 15 µg/l for girls) and US (35 µg/l) reference values. Potential associations between questionnaire information and lead results were tested using lead as continuous outcome and using lead dichotomized at the reference values. Finally, we analysed spatial patterns of elevated biomonitoring results. Of all children, 48% exceeded the German reference values for lead (5% expected) and 8% the US reference value (2.5% expected). Children 6-8 years of age were more likely to exceed German reference values (63%) than 9-10 year old children were (32%; pFisher = 0.01). No other questionnaire information was statistically significantly associated with biomonitoring results. Additionally, we did not find any indication of spatial clustering. In conclusion, we observed elevated blood lead levels in primary school children living in a former mining area. In the next step, exposure pathways need to be identified to implement effective public health measures.
Subject(s)
Biological Monitoring , Environmental Exposure , Lead , Mining , Humans , Germany , Child , Lead/blood , Male , Female , Environmental Monitoring/methods , Surveys and QuestionnairesABSTRACT
PURPOSE: As climate change accelerates, healthcare workers (HCW) are expected to be more frequently exposed to heat at work. Heat stress can be exacerbated by physical activity and unfavorable working requirements, such as wearing personal protective equipment (PPE). Thus, understanding its potential negative effects on HCW´s health and working performance is becoming crucial. Using wearable sensors, this study investigated the physiological effects of heat stress due to HCW-related activities. METHODS: Eighteen participants performed four experimental sessions in a controlled climatic environment following a standardized protocol. The conditions were (a) 22 °C, (b) 22 °C and PPE, (c) 27 °C and (d) 27 °C and PPE. An ear sensor (body temperature, heart rate) and a skin sensor (skin temperature) were used to record the participants´ physiological parameters. RESULTS: Heat and PPE had a significant effect on the measured physiological parameters. When wearing PPE, the median participants' body temperature was 0.1 °C higher compared to not wearing PPE. At 27 °C, the median body temperature was 0.5 °C higher than at 22 °C. For median skin temperature, wearing PPE resulted in a 0.4 °C increase and higher temperatures in a 1.0 °C increase. An increase in median heart rate was also observed for PPE (+ 2/min) and heat (+ 3/min). CONCLUSION: Long-term health and productivity risks can be further aggravated by the predicted temperature rise due to climate change. Further physiological studies with a well-designed intervention are needed to strengthen the evidence for developing comprehensive policies to protect workers in the healthcare sector.
Subject(s)
Heat Stress Disorders , Wearable Electronic Devices , Humans , Personal Protective Equipment , Skin Temperature , Temperature , Health Personnel , Heat Stress Disorders/prevention & controlABSTRACT
Hyperthermic intrathoracic chemotherapy (HITOC) is an additional intraoperative treatment option within the multimodality therapy of pleural malignancies. A chemotherapy perfusion with high-dose cisplatin is performed over a period of 60 min after surgical cytoreduction to improve local tumour control through the eradication of residual tumour cells. Although HITOC is increasingly used, there is only little scientific evidence about the necessary safety measures after HITOC. Therefore, the objective of this study was an analysis of cisplatin excretion via various body fluids after HITOC, with the aim of providing recommendations on occupational health and safety. Five patients undergoing HITOC were included. Before and after the HITOC, as well as during the following days, serum, urine, and bronchial secretion, as well as pleural effusion, were sampled. The platinum levels in the samples were measured using ICP-MS (inductively coupled plasma-mass spectrometry). Immediately after the HITOC, the mean levels of cisplatin increased dramatically in the serum (from 0.79 to 1349 µg/L), urine (from 3.48 to 10,528 µg/g creatinine), and bronchial secretion (from 0.11 to 156 µg/L). Thereafter, the cisplatin levels dropped to 133 µg/L in the serum and 994 µg/g creatinine in the urine within nine days after the HITOC. The AUC ratio shows 59% of the cisplatin being excreted via the urine after 48 h. The sampling of pleural effusion started 24 h after the HITOC, and the cisplatin levels decreased from 618 to 93 µg/L within nine days. Although the cisplatin levels in the body fluids of HITOC patients are much lower compared to patients receiving intravenous chemotherapy, a significant amount of cisplatin is excreted via these body fluids. Consequently, safety precautions must be implemented in the post-HITOC care of patients to avoid occupational exposure to cisplatin.
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PURPOSE: The handling of antineoplastic drugs represents an occupational health risk for employees in pharmacies. To minimize exposure and to evaluate cleaning efficacy, wipe sampling was used to analyze antineoplastic drugs on surfaces. In 2009, guidance values were suggested to facilitate the interpretation of results, leading to a decrease in surface contamination. The goal of this follow-up was to evaluate the time trend of surface contamination, to identify critical antineoplastic drugs and sampling locations and to reassess guidance values. METHODS: Platinum, 5-fluorouracil, cyclophosphamide, ifosfamide, gemcitabine, methotrexate, docetaxel and paclitaxel were analyzed in more than 17,000 wipe samples from 2000 to 2021. Statistical analysis was performed to describe and interpret the data. RESULTS: Surface contaminations were generally relatively low. The median concentration for most antineoplastic drugs was below the limit of detection except for platinum (0.3 pg/cm2). Only platinum and 5-fluorouracil showed decreasing levels over time. Most exceedances of guidance values were observed for platinum (26.9%), cyclophosphamide (18.5%) and gemcitabine (16.6%). The most affected wipe sampling locations were isolators (24.4%), storage areas (17.6%) and laminar flow hoods (16.6%). However, areas with no direct contact to antineoplastic drugs were also frequently contaminated (8.9%). CONCLUSION: Overall, the surface contaminations with antineoplastic drugs continue to decrease or were generally at a low level. Therefore, we adjusted guidance values according to the available data. The identification of critical sampling locations may help pharmacies to further improve cleaning procedure and reduce the risk of occupational exposure to antineoplastic drugs.
Subject(s)
Antineoplastic Agents , Occupational Exposure , Pharmacies , Humans , Platinum/analysis , Environmental Monitoring/methods , Equipment Contamination , Antineoplastic Agents/analysis , Fluorouracil/analysis , Cyclophosphamide/analysis , Gemcitabine , Occupational Exposure/analysisABSTRACT
3-D printers are widely used. Based on previous findings, we hypothesized that their emissions could enhance allergen responsiveness and reduce lung diffusing capacity. Using a cross-over design, 28 young subjects with seasonal allergic rhinitis were exposed to 3-D printer emissions, either from polylactic acid (PLA) or from acrylonitrile butadiene styrene copolymer (ABS), for 2 h each. Ninety minutes later, nasal allergen challenges were performed, with secretions sampled after 1.5 h. Besides nasal functional and inflammatory responses, assessments included diffusing capacity. There was also an inclusion day without exposure. The exposures elicited slight reductions in lung diffusing capacity for inhaled nitric oxide (DLNO ) that were similar for PLA and ABS. Rhinomanometry showed the same allergen responses after both exposures. In nasal secretions, concentrations of interleukin 6 and tumor necrosis factor were slightly reduced after ABS exposure versus inclusion day, while that of interleukin 5 was slightly increased after PLA exposure versus inclusion.
Subject(s)
Acrylonitrile , Air Pollution, Indoor , Rhinitis, Allergic, Seasonal , Humans , Air Pollution, Indoor/analysis , Allergens , Carbon Monoxide , Lung , Nitric Oxide , Polyesters , Printing, Three-Dimensional , Cross-Over StudiesABSTRACT
INTRODUCTION: Lead exposure remains of continuing concern due to its known and suspected impacts on human health and has been designated as a priority substance for investigation in human biomonitoring studies by the EU. The aims of this study were to measure blood lead levels (BLL) in a population based cohort of middle-aged individuals without major current exposures to lead, and to compare these to historical blood lead levels obtained thirty years earlier. METHODS: The population-based KORA study from 1984 to 2001 included inhabitants of the Augsburg Region, Germany. During 2018 to 2019, a subsample of these participants (KORA-Fit) was invited for interview regarding demographic and lifestyle factors, physical examination and blood withdrawal. Blood samples were stored at -80C prior to measurement of BLL via graphite furnace atomic absorption spectroscopy (GF-AAS). Descriptive and multivariable analyses were performed. RESULTS: BLLs were measured in 3033 eligible persons aged 54 to 73, establishing a geometric mean (GM) BLL of 24.8 µg/l in 2018/19. Of these, 555 (18%) had BLL above proposed 95th percentile reference values of the German Environment Agency. Only small differences were found in BLL stratified by sociodemographic categories, however regular smokers had higher GM BLL (26.1 µg/l) compared to never smokers (23.7 µg/l), and an increasing BLL with increased wine consumption was noted. For 556 individuals, BLLs (GM: 54.0 µg/l) reduced by 35% in men and 50% in women compared to levels in 1987/88 with only 1.4% of individuals having an unchanged or increased BLL. DISCUSSION: KORA-Fit provided contemporary normative data for BLL in a Western European population without major current sources of lead exposure. Mean BLLs have fallen since the 1980s using historical BLL data which is likely linked to the ban of leaded gasoline. Nevertheless, BLLs in this population remain elevated at levels associated with morbidity and mortality.
Subject(s)
Graphite , Lead Poisoning , Environmental Exposure , Female , Gasoline , Humans , Lead , Lead Poisoning/epidemiology , Male , Middle AgedABSTRACT
Human biomonitoring studies are of increasing importance in regulatory toxicology; however, there is a paucity of human biomonitoring data for the Irish population. In this study, we provide new data for urinary biomarker concentrations of aluminium, arsenic, cadmium, chromium, copper, mercury, manganese, lead and selenium. One hundred urine samples, collected between 2011 and 2014 from healthy participants of the EuroMOTOR project, were randomly selected. Metal concentrations were measured via ICPMS. Descriptive statistics for each of the metals stratified by gender were performed. There were 58 male and 42 female participants and metals were detectable for all samples. Geometric mean urinary concentrations for each metal in males were as follows: aluminium 8.5 µg/L, arsenic 8.1 µg/L, cadmium 0.3 µg/L, chromium 0.5 µg/L, copper 5.1 µg/L, mercury 0.4 µg/L, manganese 0.3 µg/L, lead 1.3 µg/L and selenium 10.8 µg/L; and in females: aluminium 8.5 µg/L, arsenic 10.2 µg/L, cadmium 0.4 µg/L, chromium 0.6 µg/L, copper 5.6 µg/L, mercury 0.3 µg/L, manganese 0.2 µg/L, lead 1.6 µg/L and selenium 13.7 µg/L. We observed higher geometric mean concentrations in women for arsenic, cadmium, chromium, copper, lead and selenium, with equal geometric mean concentrations for aluminium and manganese, leaving only mercury with lower geometric mean concentrations in women. Aluminium, cadmium, chromium, lead and urinary concentrations of metals were slightly elevated compared to European data, while for arsenic, copper, manganese and selenium, Irish levels were lower. Our findings highlight that there are differences in urinary metal concentrations between European populations.
Subject(s)
Arsenic , Mercury , Selenium , Trace Elements , Adult , Aluminum , Arsenic/urine , Cadmium , Chromium , Copper , Female , Humans , Male , Manganese/urine , Metals/urineABSTRACT
Mercury (Hg) is a global pollutant and a danger to human health. Human biomonitoring of Hg using a dried blood matrix instead of venous blood sampling for exposure assessment is of growing interest. This study aims to develop, validate, and evaluate the application of volumetric absorptive microsampling (VAMS) for Hg biomonitoring in humans. Sampling, drying, and storage conditions were evaluated during method development. Storage in pre-cleaned glass vials after drying for 2 h in a desiccator ensured analyte stability for at least 4 weeks. Sixty-eight paired capillary VAMS and venous blood samples from volunteers in Munich, Germany, were used for method validation. Hg levels in VAMS and venous blood samples were determined by direct mercury analysis. The limits of detection and quantitation for VAMS were 0.18 and 0.61 µg/l, respectively. However, sensitivity could be improved by using two microsamples for analysis instead of one. Hg levels in VAMS samples correlated very well with Hg levels in venous blood samples (R2 = 0.958). Furthermore, VAMS showed a high accuracy (median recovery: 117%) and precision (median relative standard deviation: 8.7%), especially for Hg concentrations above 1.0 µg/l. In fact, accuracy and precision of VAMS improved with increasing Hg concentrations. In conclusion, VAMS in combination with direct mercury analysis is an accurate and viable alternative for human biomonitoring of Hg.
Subject(s)
Biological Monitoring , Mercury , Adult , Blood Specimen Collection/methods , Dried Blood Spot Testing/methods , Environmental Monitoring , Humans , Tandem Mass Spectrometry/methodsABSTRACT
PURPOSE: Hyperthermic intrathoracic chemotherapy (HITOC) is an additive, intraoperative treatment for selected malignant pleural tumors. To improve local tumor control, the thoracic cavity is perfused with a cisplatin-containing solution after surgical cytoreduction. Since cisplatin is probably carcinogenic to humans, potential contamination of surfaces and pathways of exposure should be systematically investigated to enable risk assessments for medical staff and thus derive specific recommendations for occupational safety. METHODS: Wipe sampling was performed at pre-selected locations during and after ten HITOC procedures, including on the surgeon's gloves, for the quantitation of surface contaminations with cisplatin. After extraction of the samples with hydrochloric acid, platinum was determined as a marker for cisplatin by voltammetry. RESULTS: High median concentrations of cytostatic drugs were detected on the surgeons' (1.73 pg Cis-Pt/cm2, IQR: 9.36 pg Cis-Pt/cm2) and perfusionists' (0.69 pg Cis-Pt/cm2, IQR: 1.73 pg Cis-Pt/cm2) gloves. The display of the perfusion device showed partially elevated levels of cisplatin up to 4.92 pg Cis-Pt/cm2 and thus could represent an origin of cross-contamination. In contrast, cisplatin levels on the floor surfaces in the area of the surgeon and the perfusion device or in the endobronchial tube were relatively low. CONCLUSION: With a correct use of personal protective equipment and careful handling, intraoperative HITOC appears to be safe to perform with a low risk of occupational exposure to cisplatin.
Subject(s)
Antineoplastic Agents , Hyperthermia, Induced , Occupational Exposure , Pleural Neoplasms , Cisplatin , Humans , Occupational Exposure/prevention & control , Operating RoomsABSTRACT
People living and working in artisanal and small-scale gold mining (ASGM) areas are frequently exposed to elemental mercury (Hg), which is used for gold extraction. However, additional exposure to other toxic metals such as arsenic (As), cadmium (Cd) and lead (Pb) may result from mining-related activities and could be ingested via dust, water or food. In these areas, only limited biomonitoring data is available for toxic metals other than Hg. In particular, data about the exposure to As, Cd and Pb is unavailable for the Zimbabwean population. Therefore, we conducted a cross-sectional study in two ASGM areas in Zimbabwe to evaluate the internal exposure to these metals. In total, urine and blood samples from 207 people that identified themselves as miners were collected and analysed for As and Cd in urine as well as Pb in blood by GF-AAS. Median levels (interquartile ranges in µg/l) of As and Pb were 9.7 µg/l (4.0, 18.5) and 19.7 µg/l (12.5, 34.5), respectively. The 25th percentile and the median for Cd were below the limit of detection (0.5 µg/l); the 75th percentile was at 0.9 µg/l. The results were compared to reference values found for the general population in the USA and Germany, and a significant number of participants exceeded these values (As, 33 %; Cd, 27 %; Pb, 32 %), indicating a relevant exposure to toxic metals. Although not representative for the Zimbabwean population, our results demonstrate that the exposure to toxic metals is relevant for the public health in Zimbabwe and requires further investigation.
Subject(s)
Arsenic , Mercury , Arsenic/analysis , Biological Monitoring , Cadmium , Cross-Sectional Studies , Environmental Monitoring , Gold , Humans , Lead , Mercury/analysis , Mining , ZimbabweABSTRACT
People in artisanal and small-scale gold mining (ASGM) areas are frequently exposed to high levels of mercury (Hg). Hg analyses in urine and whole blood are the gold standard of biomonitoring, although this may not provide sufficient information about the source of exposure, e.g., due to the use of Hg for gold extraction or due to nutrition. To evaluate, whether the pharmacokinetic properties of individual Hg species may be useful for exposure assessment, we determined the Hg levels in different blood components from 199 participants. Therefore, whole blood was centrifuged on-site to yield erythrocytes and plasma. Globin was isolated from the erythrocytes by precipitation with ethyl acetate. Albumin was isolated from plasma by gradual precipitation with saturated ammonium sulfate solution. Hg levels in all samples were determined by using a direct Hg analyzer. Median Hg levels for whole blood, erythrocytes, and plasma were 2.7, 3.7, and 1.3 µg/l, respectively. In globin and albumin, median Hg levels were 10.3 and 7.9 µg/kg, respectively. The distribution of Hg was strongly correlated with whole blood Hg levels (p < 0.01) and the time between the last use of Hg and the date of the participation (p < 0.01). The results suggest that the distribution of Hg in blood is substantially affected by the extent and the frequency of the exposure to elemental Hg. Therefore, the analysis of Hg in erythrocytes and plasma may be a valuable tool for Hg exposure assessment in ASGM areas.
Subject(s)
Mercury , Biological Monitoring , Environmental Monitoring , Humans , Mercury/analysis , Mining , ZimbabweABSTRACT
We report the severe mercury poisoning of a 4-year-old child by a so far unknown route of exposure, namely, by skin-to-skin contact. The child was admitted to the hospital with episodic pain in his extremities, tachycardia, hypertension, increased sweating, behavioral changes and weight loss. Extensive examinations eventually revealed an acute mercury poisoning. The initial mercury levels were 19 µg/L in urine (reference level 0.4 µg/L) and 37 µg/L in blood (reference level 0.8 µg/L). A facial cream bought online, containing approximately 18% mercury, was identified as the primary source of intoxication. The symptoms improved after disposal of the cream and chelation therapy. Further analyses, home visits and interviews suggested that the child was accidently intoxicated by skin-to-skin contact with the mother, although other routes of exposure such as dust ingestion and surface-to-skin contact cannot be excluded. The mercury levels in urine and blood samples of the child and other family members as well as in domestic dust samples decreased considerably over time.
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Advanced glycation end products (AGEs) accumulate with age in human lens capsules. AGEs in lens capsules potentiate the transforming growth factor beta-2-mediated mesenchymal transition of lens epithelial cells, which suggests that they play a role in posterior capsule opacification after cataract surgery. We measured AGEs by liquid chromatography-mass spectrometry in capsulorhexis specimens obtained during cataract surgery from nondiabetic and diabetic patients with and without established retinopathy. Our data showed that the levels of most AGEs (12 out of 13 measured) were unaltered in diabetic patients and diabetic patients with retinopathy compared to nondiabetic patients. There was one exception: glucosepane, which was significantly higher in diabetic patients, both with (6.85 pmol/µmol OH-proline) and without retinopathy (8.32 pmol/µmol OH-proline), than in nondiabetic patients (4.01 pmol/µmol OH-proline). Our study provides an explanation for the similar incidence of posterior capsule opacification between nondiabetic and diabetic cataract patients observed in several studies.
Subject(s)
Cataract/metabolism , Diabetic Retinopathy/metabolism , Glycation End Products, Advanced/metabolism , Lens Capsule, Crystalline/metabolism , Aged , Blood Glucose/metabolism , Capsulorhexis , Cataract/pathology , Chromatography, Liquid , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Diabetic Retinopathy/pathology , Female , Glycated Hemoglobin/metabolism , Humans , Lens Capsule, Crystalline/pathology , Male , Middle Aged , Tandem Mass SpectrometryABSTRACT
Venous blood is a preferred matrix for the determination of total mercury (Hg) in human biomonitoring but has some drawbacks such as the requirement for an uninterrupted cold chain for transport and storage and the need of medical personnel for sample collection. Therefore, we tested and implemented a simpler and less expensive method for measuring Hg in human blood using dried blood spots (DBS). For method development, we investigated the influence of different storage conditions (temperature, storage vessel, time) on DBS samples. For method validation, we compared DBS and venous blood and investigated whether DBS sampling is suitable for measuring Hg in the general population in countries with low Hg exposure such as Germany. Based on our results, we found that pre-cleaned glass tubes were most suitable for storage of DBS samples, as this allowed the samples to remain stable for at least 4 weeks even at high temperatures (40 °C). When comparing venous blood and DBS, a very good correlation (r = 0.95, p < 0.01, Spearman-Rho) and high precision of DBS (mean relative standard deviation 8.2% vs. 7.2% in venous blood samples) were observed. Comparing the recoveries of both matrices in different concentration ranges, the variation of the recoveries decreases with increasing Hg concentration. The mean recoveries also decreased with increasing Hg concentration. Overall, we found comparable results for DBS and venous blood using direct Hg analysis. Furthermore, we demonstrated that DBS are suitable for Hg biomonitoring in the general population in Germany and improved the storage conditions for the DBS.
Subject(s)
Mercury , Adult , Biological Monitoring , Dried Blood Spot Testing , Environmental Monitoring , Germany , HumansABSTRACT
BACKGROUND: Chronic beryllium disease (CBD), a granulomatous disease with similarities to sarcoidosis, arises only in individuals exposed to beryllium. Inhaled beryllium can elicit a T-cell-dominated alveolitis leading nonnecrotizing granulomata. CBD can be distinguished from sarcoidosis by demonstrating beryllium sensitization in a lymphocyte proliferation test. RESEARCH QUESTION: Beryllium exposure usually occurs in an occupational setting. Because of the diagnosis of CBD in a patient without evident beryllium exposure, we performed a beryllium-lymphocyte proliferation test (BeLPT) among his work colleagues. STUDY DESIGN AND METHODS: This field study investigated a cohort of work colleagues without obvious beryllium exposure. Twenty-one of 30 individuals were assessed in our outpatient clinic for beryllium sensitization. Therefore, BeLPT was performed with freshly collected peripheral blood mononuclear cells. Data were extracted from clinical charts, including geographical data. Beryllium content in dust samples collected at the workplace was measured by graphite-furnace atomic absorption spectroscopy and was compared with samples from different areas of Germany. RESULTS: For the initial patient, the diagnosis of sarcoidosis was reclassified as CBD based on two positive BeLPT results. Assessment of his workplace did not identify a source of beryllium. However, BeLPTs performed on his workmates demonstrated beryllium sensitization in 5 of 21 individuals, suggesting a local beryllium source. Concrete dust obtained from the building yard, the workplace of the index patient, contained high amounts of beryllium (1138 ± 162 µg/kg), whereas dust from other localities (control samples) showed much lower beryllium content (range, 147 ± 18-452 ± 206 µg/kg). Notably, the control dust collected from different places all over Germany exhibit different beryllium concentrations. INTERPRETATION: We describe a cluster of beryllium-sensitized workers from an industry not related to beryllium caused by environmental exposure to beryllium-containing concrete dust, which exhibited markedly elevated beryllium content. Importantly, analyses of dust samples collected from different localities showed that they contain markedly different amounts of beryllium. Thus, besides workplace-related exposure, environmental factors also are capable of eliciting a beryllium sensitization.
Subject(s)
Berylliosis , Beryllium , Dust/analysis , Environmental Exposure , Granuloma, Respiratory Tract , Lymphocyte Activation/immunology , Sarcoidosis, Pulmonary/diagnosis , Adult , Berylliosis/diagnosis , Berylliosis/etiology , Berylliosis/immunology , Berylliosis/prevention & control , Beryllium/analysis , Beryllium/toxicity , Construction Industry , Diagnosis, Differential , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Female , Germany/epidemiology , Granuloma, Respiratory Tract/chemically induced , Granuloma, Respiratory Tract/diagnosis , Humans , Immunologic Tests/methods , Leukocytes, Mononuclear , Male , Space-Time Clustering , Workplace/standardsABSTRACT
Proteins in the eye lens have negligible turnover and therefore progressively accumulate chemical modifications during aging. Carbonyls and oxidative stresses, which are intricately linked to one another, predominantly drive such modifications. Oxidative stress leads to the loss of glutathione (GSH) and ascorbate degradation; this in turn leads to the formation of highly reactive dicarbonyl compounds that react with proteins to form advanced glycation end products (AGEs). The formation of AGEs leads to the crosslinking and aggregation of proteins contributing to lens aging and cataract formation. To inhibit AGE formation, we developed a disulfide compound linking GSH diester and mercaptoethylguanidine, and we named it carboxitin. Bovine lens organ cultured with carboxitin showed higher levels of GSH and mercaptoethylguanidine in the lens nucleus. Carboxitin inhibited erythrulose-mediated mouse lens protein crosslinking, AGE formation and the formation of 3-deoxythreosone, a major ascorbate-derived AGE precursor in the human lens. Carboxitin inhibited the glycation-mediated increase in stiffness in organ-cultured mouse lenses measured using compressive mechanical strain. Delivery of carboxitin into the lens increases GSH levels, traps dicarbonyl compounds and inhibits AGE formation. These properties of carboxitin could be exploited to develop a therapy against the formation of AGEs and the increase in stiffness that causes presbyopia in aging lenses.