Publications by authors named "Daniela Pelclova"

99 Publications

Response to the questions related to the article: "Osmium absorption after osmium tetroxide skin and eye exposure".

Basic Clin Pharmacol Toxicol 2021 Apr 9;128(4):555-556. Epub 2021 Feb 9.

Internal Department, Third Faculty of Medicine, Charles University, Faculty Thomayer Hospital, Prague, Czech Republic.

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http://dx.doi.org/10.1111/bcpt.13562DOI Listing
April 2021

Three-Year Study of Markers of Oxidative Stress in Exhaled Breath Condensate in Workers Producing Nanocomposites, Extended by Plasma and Urine Analysis in Last Two Years.

Nanomaterials (Basel) 2020 Dec 6;10(12). Epub 2020 Dec 6.

J. Heyrovský Institute of Physical Chemistry CAS, Dolejškova 3, 182 23 Prague 8, Czech Republic.

Human data concerning exposure to nanoparticles are very limited, and biomarkers for monitoring exposure are urgently needed. In a follow-up of a 2016 study in a nanocomposites plant, in which only exhaled breath condensate (EBC) was examined, eight markers of oxidative stress were analyzed in three bodily fluids, i.e., EBC, plasma and urine, in both pre-shift and post-shift samples in 2017 and 2018. Aerosol exposures were monitored. Mass concentration in 2017 was 0.351 mg/m during machining, and 0.179 and 0.217 mg/m during machining and welding, respectively, in 2018. In number concentrations, nanoparticles formed 96%, 90% and 59%, respectively. In both years, pre-shift elevations of 50.0% in EBC, 37.5% in plasma and 6.25% in urine biomarkers were observed. Post-shift elevation reached 62.5% in EBC, 68.8% in plasma and 18.8% in urine samples. The same trend was observed in all biological fluids. Individual factors were responsible for the elevation of control subjects' afternoon vs. morning markers in 2018; all were significantly lower compared to those of workers. Malondialdehyde levels were always acutely shifted, and 8-hydroxy-2-deoxyguanosine levels best showed chronic exposure effect. EBC and plasma analysis appear to be the ideal fluids for bio-monitoring of oxidative stress arising from engineered nanomaterials. Potential late effects need to be targeted and prevented, as there is a similarity of EBC findings in patients with silicosis and asbestosis.
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http://dx.doi.org/10.3390/nano10122440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762143PMC
December 2020

Markers of oxidative stress after three days of nanoTiO sunscreen use in humans: a pilot study.

Cent Eur J Public Health 2020 10;28 Suppl:S17-S21

Department of Occupational Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

Objective: Recent experimental studies point to a high reactivity of nanoparticles and the potential of sunscreens to penetrate the skin. We measured 20 markers of oxidative stress and inflammation to find out whether skin exposure to nanoTiO sunscreen may elevate the level of the markers in exhaled breath condensate (EBC) and urine of exposed subjects, as was suggested by our earlier study.

Methods: Six volunteers (3 males and 3 females), with a mean age of 48.0 ± 6.7 years, used commercial sunscreen for three days continuously. The first samples were collected before the test. The second samples were collected on day 4, before the sunscreen was washed off, and the third samples on day 11. The following biomarkers were measured: malondialdehyde, 4-hydroxy-trans-hexenal, 4-hydroxy-trans-nonenal, aldehydes C6-C12, 8-isoProstaglandin F2α, o-tyrosine, 3-chlorotyrosine, 3-nitrotyrosine, 8-hydroxy-2-deoxyguanosine, 8-hydroxyguanosine, 5-hydroxymethyl uracil, and leukotrienes B4, C4, D4, and E4, using liquid chromatography-electrospray ionisation-tandem mass spectrometry.

Results: In the urine, 4-hydroxy-trans-hexenal was significantly higher in post-exposure sample 2, and the same trend was seen in all urinary markers. In EBC, no difference was seen between the mean values of 20 post-test markers as compared with pre-test samples.

Conclusion: This study suggests potential side effects of the sunscreen - borderline elevation of markers of oxidative stress/inflammation - which may relate to the absorption of the nanoTiO, and the non-significant difference may be explained by the small number of subjects. The effect was not seen in EBC, where nanoTiO was not found. A larger study is needed, as according to our previous study, the beneficial effect of the sunscreen to suppress oxidative stress caused by UV radiation may be questioned.
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http://dx.doi.org/10.21101/cejph.a6158DOI Listing
October 2020

The genotoxic effects in the leukocytes of workers handling nanocomposite materials.

Mutagenesis 2020 09;35(4):331-340

Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska, Prague, Czech Republic.

The extensive development of nanotechnologies and nanomaterials poses a number of questions to toxicologists about the potential health risks of exposure to nanoparticles (NP). In this study, we analysed DNA damage in the leukocytes of 20 workers who were long-term exposed (18 ± 10 years) to NP in their working environment. Blood samples were collected in September 2016, before and after a shift, to assess (i) the chronic effects of NP on DNA (pre-shift samples) and (ii) the acute effects of exposure during the shift (the difference between pre- and post-shift samples). The samples from matched controls were taken in parallel with workers before the shift. Leukocytes were isolated from heparinised blood on a Ficoll gradient. The enzyme-modified comet assay (DNA formamido-pyrimidine-glycosylase and endonuclease III) demonstrated a considerable increase of both single- and double-strand breaks in DNA (DNA-SB) and oxidised bases when compared with the controls (2.4× and 2×, respectively). Acute exposure induced a further increase of DNA-SB. The welding and smelting of nanocomposites represented a higher genotoxic risk than milling and grinding of nanocomposite surfaces. Obesity appeared to be a factor contributing to an increased risk of oxidative damage to DNA. The data also indicated a higher susceptibility of males vs. females to NP exposure. The study was repeated in September 2017. The results exhibited similar trend, but the levels of DNA damage in the exposed subjects were lower compared to previous year. This was probably associated with lower exposure to NP in consequence of changes in nanomaterial composition and working operations. The further study involving also monitoring of personal exposures to NP is necessary to identify (i) the main aerosol components responsible for genotoxic effects in workers handling nanocomposites and (ii) the primary cause of gender differences in response to NP action.
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http://dx.doi.org/10.1093/mutage/geaa016DOI Listing
September 2020

Osmium absorption after osmium tetroxide skin and eye exposure.

Basic Clin Pharmacol Toxicol 2020 Nov 27;127(5):429-433. Epub 2020 Jun 27.

Internal Department, Third Faculty of Medicine Charles University, Thomayer Hospital, Prague, Czech Republic.

Osmium tetroxide is a strong oxidizing agent used in electron microscopy. Eye exposure may cause severe burns, and after inhalation or ingestion damage to the respiratory or gastrointestinal tract occurs. Exposure to osmium and its compounds is extremely rare. We present a case of a 32-year-old female stained by 9 mL of 2% osmium tetroxide in acetone during an accident in the laboratory, with rare dermal and ocular findings. Due to lack of data in toxicological databases and the absence of antidote, the therapy was symptomatic. Osmium was detected in serum 19 hours later (0.22 μg/L) and in urine during the 15-hour collection (three samples-7.05, 1.65 and 8.45 μg/L). In blood serum on admission, after 1 and 2 days after exposure, the levels of iron (28.2, 39.8 and 50.5 μmol/L; reference range 5.8-34.5 μmol/L) and transferrin receptor/ferritine were elevated. To our knowledge, this is the first paper documenting a significant absorption from the skin and potentially from the eye conjunctiva, based on serum and urine analysis. The relationship between increased iron in blood and exposure has not been described yet, and the mechanism remains unknown. The patient is being followed up for the unknown long-term effects.
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http://dx.doi.org/10.1111/bcpt.13450DOI Listing
November 2020

DNA Methylation Profiles in a Group of Workers Occupationally Exposed to Nanoparticles.

Int J Mol Sci 2020 Mar 31;21(7). Epub 2020 Mar 31.

Department of Machining and Assembly, Department of Engineering Technology, Department of Material Science, Faculty of Mechanical Engineering, Technical University in Liberec, Studentska 1402/2 Liberec, Czech Republic.

The risk of exposure to nanoparticles (NPs) has rapidly increased during the last decade due to the vast use of nanomaterials (NMs) in many areas of human life. Despite this fact, human biomonitoring studies focused on the effect of NP exposure on DNA alterations are still rare. Furthermore, there are virtually no epigenetic data available. In this study, we investigated global and gene-specific DNA methylation profiles in a group of 20 long-term (mean 14.5 years) exposed, nanocomposite, research workers and in 20 controls. Both groups were sampled twice/day (pre-shift and post-shift) in September 2018. We applied Infinium Methylation Assay, using the Infinium MethylationEPIC BeadChips with more than 850,000 CpG loci, for identification of the DNA methylation pattern in the studied groups. Aerosol exposure monitoring, including two nanosized fractions, was also performed as proof of acute NP exposure. The obtained array data showed significant differences in methylation between the exposed and control groups related to long-term exposure, specifically 341 CpG loci were hypomethylated and 364 hypermethylated. The most significant CpG differences were mainly detected in genes involved in lipid metabolism, the immune system, lung functions, signaling pathways, cancer development and xenobiotic detoxification. In contrast, short-term acute NP exposure was not accompanied by DNA methylation changes. In summary, long-term (years) exposure to NP is associated with DNA epigenetic alterations.
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http://dx.doi.org/10.3390/ijms21072420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177382PMC
March 2020

Fractional Exhaled Nitric Oxide and Nanomaterial Exposure in Workplaces.

Curr Med Chem 2020 ;27(42):7200-7212

Department of Occupational Medicine, First Faculty of Medicine, Charles University and General University Hospital, Na Bojisti 1, 120,00 Prague, Czech Republic.

Background: The widespread application of engineered nanomaterials (ENMs) and the increasing likelihood of general and occupational exposure raised concerns on their possible human health impact. ENMs, in fact, may induce alterations in different organ systems, and particularly in the respiratory tract. This makes it important to identify possible biomarkers of early lung effect in exposed workers. In this regard, the possibility to use the fractional exhaled levels of nitric oxide (FENO) in biological monitoring has attracted considerable interest.

Objective: To comprehensively assess the role of FENO as a possible biomarker of lung effect in ENM exposed workers.

Methods: A systematic search was performed on Pubmed, Scopus, and ISI Web of Knowledge databases according to the PRISMA guidelines.

Results: Seven studies investigated FENO in workers exposed to different kinds of metal- (i.e. silver and gold), metal oxide- (titanium and silica dioxide), and carbon-based ENMs (carbon nanotubes). In general, no significant alterations were detected between exposed workers and controls.

Conclusion: Definite conclusion on the function of FENO in occupational biological monitoring cannot be extrapolated due to the limited number of available studies and the small size of investigated populations. Additionally, the lack of environmental monitoring data and the fragmented knowledge on ENM modes of action prevent to establish dose-response relationships. Future research appears necessary to deeply define the possibility to employ FENO as an early biomarker of lung effects taking in consideration possible occupational exposure issues, i.e. differently characterized ENMs and work tasks, as well as individual influencing factors, i.e. smoking and atopy.
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http://dx.doi.org/10.2174/0929867327666200320154545DOI Listing
February 2021

Health-related quality of life determinants in survivors of a mass methanol poisoning outbreak: six-year prospective cohort study.

Clin Toxicol (Phila) 2020 09 8;58(9):870-880. Epub 2020 Jan 8.

Department of Occupational Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic.

The effect of acute methanol poisoning on the follow-up quality of life of survivors in mass poisoning outbreaks is not known. The objective of this is to study the impact of visual and central nervous system (CNS) sequelae of methanol poisoning on long-term health-related quality of life (QoL) of survivors, its clinical determinants, and dynamics. A total of 54 patients with confirmed methanol poisoning (mean age 46.7 ± 13.4 years, 9 females) were examined consequently three times within six-year prospective cohort study and compared to 23 controls with the history of chronic alcohol abuse. The following tests were performed: SF-36 QoL questionnaire, visual evoked potentials (VEP) of optic nerve, ocular examination with retinal nerve fiber layer (RNFL) thickness measurement, brain magnetic resonance imaging (MRI), and biochemical and toxicological tests. Acute methanol poisoning led to significant decrease in physical component summary (PCS) compared to PCS of age-adjusted controls (mean score with SD 46.8 ± 11.0 versus 52.3 ± 9.4 points;  = .003). In 17/40 (42.5%) patients with three rounds of examination, signs of severe disability (≤30 points in at least one score) were present six years after discharge, with negative dynamics of PCS score during the observation period. The patients with abnormal RNFL thickness had lower PCS (mean difference 10.5 points; 95%CI 3.5-17.5,  = .004) and mental component summary score (9.5 points; 95%CI 1.9-17.1,  = .015) compared to the patients with normal RNFL. Signs of physical and mental adaptation to long-term visual sequelae were registered with gradual reduction of difference in most of physical and mental components scores compared to the patients with normal RNFL during six years of observation. Signs of hemorrhagic brain lesions were associated with permanent decrease of PCS score (mean difference 7.4 points; 95%CI 0.6-14.0;  = .033), bodily pain (8.7 points; 95%CI 1.6-17.6;  = .018), and social functioning (8.2 points; 95%CI 3.0-17.4;  = .005) six years after discharge. No effect of type of antidote (fomepizole versus ethanol) and extracorporeal enhanced elimination modality (intermittent hemodialysis versus continuous renal replacement therapy) applied in hospital on long-term QoL was found (all  > .05). Acute methanol poisoning was associated with a significant decrease of health-related quality of life of survivors persisting for at least six years after discharge. The more pronounced decrease in QoL scores was observed in the patients with hemorrhagic brain lesions and visual sequelae of poisoning with abnormal RNFL thickness.
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http://dx.doi.org/10.1080/15563650.2019.1702994DOI Listing
September 2020

The impact of co-morbidities on a 6-year survival after methanol mass poisoning outbreak: possible role of metabolic formaldehyde.

Clin Toxicol (Phila) 2020 04 12;58(4):241-253. Epub 2019 Jul 12.

Department of Occupational Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic.

The influence of co-morbid conditions on the outcome of acute methanol poisoning in mass poisoning outbreaks is not known. The objective of this is to study the impact of burden of co-morbidities, complications, and methanol-induced brain lesions on hospital, follow-up, and total mortality. All patients hospitalized with methanol poisoning during a mass poisoning outbreak were followed in a prospective cohort study until death or final follow-up after 6 years. The age-adjusted Charlson co-morbidity index (ACCI) score was calculated for each patient. A multivariate Cox regression model was used to calculate the adjusted hazards ratio (HR) for death. The survival was modeled using the Kaplan-Meier method. Of 108 patients (mean age with SD 50.9 ± 2.6 years), 24 (54.4 ± 5.9 years) died during hospitalization (mean survival with SD 8 ± 4 days) and 84 (49.9 ± 3.0 years;  = .159) were discharged, including 27 with methanol-induced brain lesions. Of the discharged patients, 15 (56.3 ± 6.8 years) died during the follow-up (mean survival 37 ± 11 months) and 69 (48.5 ± 3.3 years;  = .044) survived. The hospital mortality was 22%, the follow-up mortality was 18%; the total mortality was 36%. Cardiac/respiratory arrest, acute respiratory failure, multiorgan failure syndrome, and arterial hypotension increased the HR for hospital and total (but not follow-up) mortality after adjustment for age, sex, and arterial pH (all  < .05). All patients who died in the hospital had at least one complication. A higher ACCI score was associated with greater total mortality (HR 1.22; 1.00-1.48 95% CI;  = .046). Of those who died, 35 (90%) had a moderate-to-high ACCI. The Kaplan-Meier curve demonstrated that patients with a high ACCI had greater follow-up mortality compared to ones with low ( = .027) or moderate ( = .020) scores. For the patients who died during follow-up, cancers of different localizations were responsible for 7/15 (47%) of the deaths. The character and number of complications affected hospital but not follow-up mortality, while the burden of co-morbidities affected follow-up mortality. Methanol-induced brain lesions did not affect follow-up mortality. Relatively high cancer mortality rate may be associated with acute exposure to metabolic formaldehyde produced by methanol oxidation.
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http://dx.doi.org/10.1080/15563650.2019.1637525DOI Listing
April 2020

The repeated cytogenetic analysis of subjects occupationally exposed to nanoparticles: a pilot study.

Mutagenesis 2019 09;34(3):253-263

Department of Machining and Assembly, Technical University in Liberec, Liberec, Czech Republic.

The application of nanomaterials has been rapidly increasing during recent years. Inhalation exposure to nanoparticles (NP) may result in negative toxic effects but there is a critical lack of human studies, especially those related to possible DNA alterations. We analyzed pre-shift and post-shift a group of nanocomposite researchers with a long-term working background (17.8 ± 10.0 years) and matched controls. The study group consisted of 73.2% males and 26.8% females. Aerosol exposure monitoring during a working shift (involving welding, smelting, machining) to assess the differences in exposure to particulate matter (PM) including nanosized fractions <25-100 nm, and their chemical analysis, was carried out. A micronucleus assay using Human Pan Centromeric probes, was applied to distinguish between the frequency of centromere positive (CEN+) and centromere negative (CEN-) micronuclei (MN) in the binucleated cells. This approach allowed recognition of the types of chromosomal damage: losses and breaks. The monitoring data revealed differences in the exposure to NP related to individual working processes, and in the chemical composition of nanofraction. The cytogenetic results of this pilot study demonstrated a lack of effect of long-term (years) exposure to NP (total frequency of MN, P = 0.743), although this exposure may be responsible for DNA damage pattern changes (12% increase of chromosomal breaks-clastogenic effect). Moreover, short-term (daily shift) exposure could be a reason for the increase of chromosomal breaks in a subgroup of researchers involved in welding and smelting processes (clastogenic effect, P = 0.037). The gender and/or gender ratio of the study participants was also an important factor for the interpretation of the results. As this type of human study is unique, further research is needed to understand the effects of long-term and short-term exposure to NP.
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http://dx.doi.org/10.1093/mutage/gez016DOI Listing
September 2019

NanoTiO Sunscreen Does Not Prevent Systemic Oxidative Stress Caused by UV Radiation and a Minor Amount of NanoTiO is Absorbed in Humans.

Nanomaterials (Basel) 2019 Jun 17;9(6). Epub 2019 Jun 17.

Czech University of Life Sciences, Kamycka 129, 165 00 Prague 6, Czech Republic.

The present pilot study tested the efficiency of nanoTiO sunscreen to prevent the oxidative stress/inflammation caused by ultraviolet (UV) radiation using biomarkers in subjects' blood, urine, and exhaled breath condensate (EBC). In addition, the skin absorption of nanoTiO was studied. Six identical subjects participated in three tests: (A) nanoTiO sunscreen, (B) UV radiation, and (C) sunscreen + UV. The first samples were collected before the test and the second after sunscreen application and/or UV exposure. On day 4, the third samples were collected, and the sunscreen was washed off, and the fourth samples were collected on day 11. The following biomarkers were measured: malondialdehyde, 4-hydroxy--hexenal, 4-hydroxy--nonenal, aldehydes C6-C12, 8--Prostaglandin F2α, o-tyrosine, 3-chlorotyrosine, 3-nitrotyrosine, 8-hydroxy-2-deoxyguanosine, 8-hydroxyguanosine, 5-hydroxymethyl uracil, and leukotrienes, using liquid chromatography-electrospray ionisation-tandem mass spectrometry. Titania was measured using inductively coupled plasma mass spectrometry and TiO nanoparticles by transmission and scanning electron microscopy. Sunscreen alone did not elevate the markers, but UV increased the biomarkers in the plasma, urine, and EBC. The sunscreen prevented skin redness, however it did not inhibit the elevation of oxidative stress/inflammatory markers. Titania and nanoTiO particles were found in the plasma and urine (but not in the EBC) in all sunscreen users, suggesting their skin absorption.
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http://dx.doi.org/10.3390/nano9060888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631994PMC
June 2019

Methanol Poisoning as an Acute Toxicological Basal Ganglia Lesion Model: Evidence from Brain Volumetry and Cognition.

Alcohol Clin Exp Res 2019 07 28;43(7):1486-1497. Epub 2019 May 28.

Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.

Background: Acute methanol poisoning leads to optic neuropathy and necrotic lesions of basal ganglia (BG) and subcortical white matter. Survivors of methanol poisoning exhibit long-term executive and memory deficits. Associations between brain volumetry parameters and cognitive sequelae of methanol poisoning are not known. The aim of our study was to identify long-term associations between the cognitive performance of survivors of methanol poisoning and the volume of the brain structures that are selectively vulnerable to methanol.

Methods: We conducted a cross-sectional follow-up study on a sample of patients (n = 33, age 50 ± 14 years, 82% males) who survived acute methanol poisoning during methanol mass poisoning outbreak from September 2012 till January 2013 in the Czech Republic. A battery of neuropsychological tests and brain magnetic resonance imaging were included in the clinical examination protocol. Specific brain structures (putamen, globus pallidus, nucleus caudatus, and frontal white matter) were selected as regions of interest, and their volumes were estimated using the MorphoBox prototype software.

Results: In robust multiple regression models, sustained visual attention performance (as assessed by Trail Making Test and Prague Stroop Test) was positively associated with BG structures and frontal white matter volumes (Wald = 9.03 to 85.50, p < 0.01), sensitivity to interference (as assessed by Frontal Battery Assessment) was negatively associated with frontal white matter volume (Wald = 35.44 to 42.25, p < 0.001), and motor performance (as assessed by Finger Tapping Test) was positively associated with globus pallidus and frontal white matter volumes (Wald = 9.66 to 13.29, p < 0.01).

Conclusions: Our results demonstrate that smaller volumes of elements of BG-thalamocortical circuitry, namely the BG and frontal white matter, relate to attention and motor performance in methanol poisoning from a long-term perspective. Disruption of those functional circuits may underlie specific cognitive deficits observed in methanol poisoning.
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http://dx.doi.org/10.1111/acer.14077DOI Listing
July 2019

Leukocyte telomere length is not affected by long-term occupational exposure to nano metal oxides.

Ind Health 2019 Nov 28;57(6):741-744. Epub 2019 Mar 28.

Institute of Chemical Process Fundamentals CAS, Czech Republic.

The aim of this study was to ascertain whether long-term occupational exposure to nanoparticles would affect relative leukocyte telomere length (LrTL). We analysed occupational exposure to size-resolved aerosol particles, with special emphasis on nanoparticles at two workshops: i/ the production of nanocomposites containing metal oxides; ii/ laboratory to test experimental exposure of nano-CuO to rodents. Thirty five exposed researchers (age 39.5 ± 12.6 yr; exposure duration 6.0 ± 3.7 yr) and 43 controls (40.4 ± 10.5 yr) were examined. LrTL did not significantly (p=0.14) differ between the exposed researchers (0.92 ± 0.13) and controls (0.86 ± 0.15). In addition, no significant correlation (r=-0.22, p=0.22) was detected between the duration of occupational exposure and LrTL. The results remained non-significant after multiple adjustments for age, sex and smoking status. Our pilot results suggest that relative leukocyte telomere length is not affected by occupational exposure to nanoparticles.
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http://dx.doi.org/10.2486/indhealth.2018-0146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885603PMC
November 2019

Diagnostics and acknowledgement of occupational diseases - topics and challenges in the Czech Republic.

Cas Lek Cesk 2018 Dec;157(8):396-399

The causes of occupational diseases are changing, thats why a regular update of Czech List of Occupational Diseases is needed. New compensable occupational diseases, such as cancer of the larynx and ovarian cancer due to asbestos, and chronic obstructive pulmonary diseases due to black coal dust were included in the last two updates of the Czech List. The need of an early examination at the Centers of Occupational Diseases is stressed in this article, especially before a surgery or other treatment of epicondylitis and carpal tunnel syndrome. These treatments may suppress the diagnostic hallmarks requested for acknowledgements of these disorders. Extrinsic allergic alveolitis, allergic rhinitis and bronchial asthma are underdiagnosed, and isocyanates belong among the key factors. Only about 10 % patients with mesotheliomas due to asbestos are compensated. The latency in cancers due to asbestos may reach more than 50 years.
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December 2018

Deep Airway Inflammation and Respiratory Disorders in Nanocomposite Workers.

Nanomaterials (Basel) 2018 Sep 16;8(9). Epub 2018 Sep 16.

UMass, Lowell, Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, Lowell, MA 01854, USA.

Thousands of researchers and workers worldwide are employed in nanocomposites manufacturing, yet little is known about their respiratory health. Aerosol exposures were characterized using real time and integrated instruments. Aerosol mass concentration ranged from 0.120 mg/m³ to 1.840 mg/m³ during nanocomposite machining processes; median particle number concentration ranged from 4.8 × 10⁴ to 5.4 × 10⁵ particles/cm³. The proportion of nanoparticles varied by process from 40 to 95%. Twenty employees, working in nanocomposite materials research were examined pre-shift and post-shift using spirometry and fractional exhaled nitric oxide (FeNO) in parallel with 21 controls. Pro-inflammatory leukotrienes (LT) type B4, C4, D4, and E4; tumor necrosis factor (TNF); interleukins; and anti-inflammatory lipoxins (LXA4 and LXB4) were analyzed in their exhaled breath condensate (EBC). Chronic bronchitis was present in 20% of researchers, but not in controls. A significant decrease in forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) was found in researchers post-shift ( ˂ 0.05). Post-shift EBC samples were higher for TNF ( ˂ 0.001), LTB4 ( ˂ 0.001), and LTE4 ( ˂ 0.01) compared with controls. Nanocomposites production was associated with LTB4 ( ˂ 0.001), LTE4 ( ˂ 0.05), and TNF ( ˂ 0.001), in addition to pre-shift LTD4 and LXB4 (both ˂ 0.05). Spirometry documented minor, but significant, post-shift lung impairment. TNF and LTB4 were the most robust markers of biological effects. Proper ventilation and respiratory protection are required during nanocomposites processing.
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http://dx.doi.org/10.3390/nano8090731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164906PMC
September 2018

Markers of Oxidative Stress in the Exhaled Breath Condensate of Workers Handling Nanocomposites.

Nanomaterials (Basel) 2018 Aug 10;8(8). Epub 2018 Aug 10.

Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, Lowell, MA 01854, USA.

Researchers in nanocomposite processing may inhale a variety of chemical agents, including nanoparticles. This study investigated airway oxidative stress status in the exhaled breath condensate (EBC). Nineteen employees (42.4 ± 11.4 y/o), working in nanocomposites research for 18.0 ± 10.3 years were examined pre-shift and post-shift on a random workday, together with nineteen controls (45.5 ± 11.7 y/o). Panels of oxidative stress biomarkers derived from lipids, nucleic acids, and proteins were analyzed in the EBC. Aerosol exposures were monitored during three major nanoparticle generation operations: smelting and welding (workshop 1) and nanocomposite machining (workshop 2) using a suite of real-time and integrated instruments. Mass concentrations during these operations were 0.120, 1.840, and 0.804 mg/m³, respectively. Median particle number concentrations were 4.8 × 10⁴, 1.3 × 10⁵, and 5.4 × 10⁵ particles/cm³, respectively. Nanoparticles accounted for 95, 40, and 61%, respectively, with prevailing Fe and Mn. All markers of nucleic acid and protein oxidation, malondialdehyde, and aldehydes C₆⁻C were elevated, already in the pre-shift samples relative to controls in both workshops. Significant post-shift elevations were documented in lipid oxidation markers. Significant associations were found between working in nanocomposite synthesis and EBC biomarkers. More research is needed to understand the contribution of nanoparticles from nanocomposite processing in inducing oxidative stress, relative to other co-exposures generated during welding, smelting, and secondary oxidation processes, in these workshops.
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http://dx.doi.org/10.3390/nano8080611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116291PMC
August 2018

Exposure criteria for evaluating lumbar spine load.

Cent Eur J Public Health 2018 Jun;26(2):98-103

Department of Occupational Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

Objective: As a part of regular revision of the List of Occupational Diseases in the Czech Republic, efforts have been made to add a new item so that lumbar spine disease caused by overload may be recognized as occupational one, with adherence to the valid national rules, that is, clinical criteria are met and objective assessment confirms working conditions under which, according to recent scientific knowledge, such an occupational disease develops. The aim is to provide information on the use of a proposed method for working condition assessment in a real setting, based on the initial experiences gained from a pilot study carried out to validate the method.

Methods: Working conditions were assessed in 55 individuals with chronic low back pain (25 males, 30 females; mean age 45.6 years; mean length of employment 15.6 years). The assessment was based on estimating compressive force on the L4/L5 intervertebral disc when performing potentially high-risk work tasks which were entered into four types of checklists throughout their work shifts. The compression values were calculated using a special module that was developed.

Results: In 24 cases comprehensive assessment of all tasks performed showed fulfillment of the proposed criteria of working conditions needed for recognition of occupational disease. Those included healthcare, foundry and forest workers, production operators, cabinetmakers, locksmiths, bricklayers, etc. In all the cases, lumbar spine overload was associated with work tasks requiring combinations of manual handling of objects and trunk rotation or bending. The criteria were not met in 31 subjects. The mean length of employment was 15.4 and 15.8 years in patients who met and did not meet the proposed criteria, respectively.

Conclusion: The proposed method proved to be applicable in occupational hygiene evaluation in a real setting.
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http://dx.doi.org/10.21101/cejph.a4941DOI Listing
June 2018

Progressive Chronic Retinal Axonal Loss Following Acute Methanol-induced Optic Neuropathy: Four-Year Prospective Cohort Study.

Am J Ophthalmol 2018 07 28;191:100-115. Epub 2018 Apr 28.

Toxicological Information Centre, Department of Occupational Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. Electronic address:

Purpose: To study the dynamics and clinical determinants of chronic retinal nerve fiber layer thickness (RNFL) loss after methanol-induced optic neuropathy.

Design: Prospective cohort study.

Methods: All patients underwent complete ophthalmic evaluation including spectral-domain optical coherence tomography 3 times during 4 years of observation: 4.9 (±0.6), 25.0 (±0.6), and 49.9 (±0.5) months after discharge.

Participants: Eighty-four eyes of 42 survivors of methanol poisoning, mean age (standard deviation) of 45.7 (±4.4) years; and 82 eyes of 41 controls, mean age 44.0 (±4.2) years.

Main Outcome Measures: Global and temporal RNFL loss.

Results: Abnormal RNFL thickness was registered in 13 of 42 (31%) survivors of methanol poisoning and chronic axonal loss in 10 of 42 (24%) patients. Significant decrease of global/temporal RNFL thickness during the observation period was found in the study population compared to the controls (P < .001). The risk estimate of chronic global RNFL loss for arterial blood pH < 7.3 at admission was 11.65 (95% confidence interval 1.91-71.12) after adjusting for age and sex. The patients with chronic axonal degeneration demonstrated progressive visual loss in 7 of 10 cases. The patients with abnormal RNFL thickness had magnetic resonance signs of brain damage in 10 of 13 vs 8 of 29 cases with normal RNFL thickness (P = .003). Signs of brain hemorrhages were present in 7 of 13 patients with abnormal RNFL thickness vs 5 of 29 cases with normal RNFL thickness (P = .015).

Conclusions: Methanol-induced optic neuropathy may lead to chronic retinal axonal loss during the following years. Arterial blood pH on admission is the strongest predictor of chronic RNFL thickness decrease. Chronic retinal neurodegeneration is associated with the progressive loss of visual functions and necrotic brain lesions.
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http://dx.doi.org/10.1016/j.ajo.2018.04.015DOI Listing
July 2018

Diabetes, Cardiovascular Disorders and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Body Burden in Czech Patients 50 Years After the Intoxication.

Basic Clin Pharmacol Toxicol 2018 Sep 7;123(3):356-359. Epub 2018 May 7.

Department of Occupational Medicine, 1st Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.

The correlation between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication and the parameters of metabolic impairment was examined in the last eight male survivors of 80 workers exposed to TCDD during the production of herbicides in a chemical factory in 1965-1967. Their median TCDD blood level was 112 (46-390) pg/g lipids, and the median TCDD body deposit was 3.9 (0.8-11.7) μg. This puts these patients into the most severely intoxicated group of subjects, according to back-calculated levels of TCDD. The median TCDD blood level in eight controls was 12 pg/g (<0.10 to 22.2 pg/g). Markers of metabolic impairment - diabetes, dyslipidaemia, arterial hypertension, carotid artery plaque, skin microvascular reactivity, eye fundus hypertensive angiopathy and history of coronary heart disease - were assessed and compared to a general male population of comparable age. Measured parameters compared with a population of comparable age were as follows: prevalence of diabetes (62.5% versus 17.6%), arterial hypertension (87.5% versus 71.8%), dyslipidaemia (87.5% versus 88.8%), history of coronary heart disease (62.5% versus 26.0%) and eye fundus hypertension angiopathy (50% versus 14%). All eight patients (100% versus 43%) developed plaques in carotid arteries, six had stenosis >50% and two had a carotid intervention (stenting or endarterectomy). Total cholesterol levels decreased compared to the earlier study this patient group in 2008, most likely due to a more intensive use of lipid-lowering drugs. Several metabolic parameters were higher (diabetes as much as 3.5-fold) in the group of severely TCDD-intoxicated subjects than in a general population of comparable age. This suggests that TCDD plays a role in the development of metabolic impairment and vascular changes.
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http://dx.doi.org/10.1111/bcpt.13013DOI Listing
September 2018

A response to the Comment on Tomaskova et al. Mortality in Miners with Coal-Workers' Pneumoconiosis in the Czech Republic in the Period 1992-2013. Int. J. Environ. Res. Public Health, 2017, 14, 269 by the Author Mei Yong.

Int J Environ Res Public Health 2018 02 13;15(2). Epub 2018 Feb 13.

Institute of Public Health, 70200 Ostrava, Czech Republic.

At first, we would like to thank Mei Yong for the comments on our article Mortality in Miners with Coal-Workers' Pneumoconiosis in the Czech Republic in the Period 1992-2013 [...].
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http://dx.doi.org/10.3390/ijerph15020322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858391PMC
February 2018

Burnout syndrome as an occupational disease in the European Union: an exploratory study.

Ind Health 2018 Apr 3;56(2):160-165. Epub 2017 Nov 3.

Department of Occupational Medicine, First Medical Faculty, Charles University in Prague and General University Hospital in Prague, Czech Republic.

The risk of psychological disorders influencing the health of workers increases in accordance with growing requirements on employees across various professions. This study aimed to compare approaches to the burnout syndrome in European countries. A questionnaire focusing on stress-related occupational diseases was distributed to national experts of 28 European Union countries. A total of 23 countries responded. In 9 countries (Denmark, Estonia, France, Hungary, Latvia, Netherlands, Portugal, Slovakia and Sweden) burnout syndrome may be acknowledged as an occupational disease. Latvia has burnout syndrome explicitly included on the List of ODs. Compensation for burnout syndrome has been awarded in Denmark, France, Latvia, Portugal and Sweden. Only in 39% of the countries a possibility to acknowledge burnout syndrome as an occupational disease exists, with most of compensated cases only occurring in recent years. New systems to collect data on suspected cases have been developed reflecting the growing recognition of the impact of the psychosocial work environment. In agreement with the EU legislation, all EU countries in the study have an action plan to prevent stress at the workplace.
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http://dx.doi.org/10.2486/indhealth.2017-0132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889935PMC
April 2018

Neurological and Neurophysiological Findings in Workers with Chronic 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Intoxication 50 Years After Exposure.

Basic Clin Pharmacol Toxicol 2018 Feb 27;122(2):271-277. Epub 2017 Sep 27.

Department of Occupational Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

The last eight survivors of 80 workers accidentally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during production of herbicides based on trichlorophenoxyacetic acid in 1965-1967 in a chemical factory were followed. All were men, mean age 72.4 ± 1.3 years. Their current median TCDD blood level was 112 (46-390) pg/g lipids. Neurological examination revealed central nervous system impairment in all individuals and signs of polyneuropathy in 87.5%, which was confirmed by a nerve conduction study (NCS) in 75%. A Lanthony test demonstrated acquired dyschromatopsia in 87.5% of the patients, with deterioration of mean colour confusion index (CCI) from 1.52 ± 0.39 in 2010 to 1.73 ± 0.41 in 2016. Single-photon emission computer tomography (SPECT) of the brain showed focal reduction of perfusion in various brain locations in all patients and worsening in six patients. Visual-evoked potentials (VEP) was abnormal in 62.6% of individuals. Most patients complained of psychological problems. The neuropsychological test battery showed most positive impairments in the Trail Making Test evaluating processing speed (average level in the range of mild neurocognitive impairment), which correlated with mean CCI (p < 0.05).

Conclusion: Fifty years after exposure, blood levels of TCDD are still 10 times higher than the general population. NCS, VEP, Lanthony test and SPECT findings deteriorated from examination of these patients in 2004 and in 2010. The total of abnormal tests per patient in 2016 is very high. Minor differences among patients and their reduced count may explain why the number of impairments in 2016 does not correlate with TCDD blood level.
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http://dx.doi.org/10.1111/bcpt.12899DOI Listing
February 2018

Intermittent versus continuous renal replacement therapy in acute methanol poisoning: comparison of clinical effectiveness in mass poisoning outbreaks.

Ann Intensive Care 2017 Dec 20;7(1):77. Epub 2017 Jul 20.

The Norwegian CBRNE Centre of Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Background: Intermittent hemodialysis (IHD) is the modality of choice in the extracorporeal treatment (ECTR) of acute methanol poisoning. However, the comparative clinical effectiveness of intermittent versus continuous modalities (CRRT) is unknown. During an outbreak of mass methanol poisoning, we therefore studied the effect of IHD versus CRRT on mortality and the prevalence of visual/central nervous system (CNS) sequelae in survivors.

Methods: The study was designed as prospective observational cohort study. Patients hospitalized with a diagnosis of acute methanol poisoning were identified for the study. Exploratory factor analysis and multivariate logistic regression were applied to determine the effect of ECTR modality on the outcome.

Results: Data were obtained from 41 patients treated with IHD and 40 patients with CRRT. The follow-up time in survivors was two years. Both groups of patients were comparable by age, time to presentation, laboratory data, clinical features, and other treatment applied. The CRRT group was more acidemic (arterial blood pH 6.96 ± 0.08 vs. 7.17 ± 0.07; p < 0.001) and more severely poisoned (25/40 vs. 9/41 patients with Glasgow Coma Scale (GCS) ≤ 8; p < 0.001). The median intensive care unit length of stay (4 (range 1-16) days vs. 4 (1-22) days; p = 0.703) and the number of patients with complications during the treatment (11/41 vs. 13/40 patients; p = 0.576) did not differ between the groups. The mortality was higher in the CRRT group (15/40 vs. 5/41; p = 0.008). The number of survivors without sequelae of poisoning was higher in the IHD group (23/41 vs. 10/40; p = 0.004). There was a significant association of ECTR modality with both mortality and the number of survivors with visual and CNS sequelae of poisoning, but this association was not present after adjustment for arterial blood pH and GCS on admission (all p > 0.05).

Conclusions: In spite of the faster correction of the acidosis and the quicker removal of the toxic metabolite in intermittent dialysis, we did not find significant differences in the treatment outcomes between the two groups after adjusting for the degree of acidemia and the severity of poisoning on admission. These findings support the strategy of "use what you have" in situations with large outbreaks and limited dialysis capacity.
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http://dx.doi.org/10.1186/s13613-017-0300-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519513PMC
December 2017

Gait and Balance Impairment after Acute Methanol Poisoning.

Basic Clin Pharmacol Toxicol 2018 Jan 6;122(1):176-182. Epub 2017 Sep 6.

Department of Neurology, Charles University, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.

Neurological sequelae including gait impairment were reported in survivors after methanol intoxication; however, no systematic study has been published so far. We aimed to analyse gait and balance impairment in a group of Czech methanol poisoning survivors. We examined 43 patients (age 46 ± 13 years) 2-8 months after methanol poisoning and 43 healthy controls. Investigations contained a shortened version of Falls Efficacy Scale (FES), clinical tests of gait and balance including Timed Up and Go test (TUG) and gait analysis using GaitRite system, neurological and neuropsychological examination, brain imaging, EMG and tests of alcohol consumption. Nineteen patients admitted balance and gait impairment according to FES. Mild to moderate parkinsonian signs showed seven patients. Patients were slower (8.8 versus 5.7 s, p < 0.001) and performed more steps (11.1 versus 7.9, p < 0.001) in TUG compared with the controls. Gait analysis revealed shorter step length (76.5 versus 88.7 cm, p < 0.001), increased double support phase (18.8 versus 15.5%, p < 0.001) and wider base of support (11.3 versus 9.6 cm, p = 0.006) in patients. Eleven patients had deficit of executive function and performed higher cadence compared to the patients with normal execution (122.7 versus 115.0 step/min., p = 0.025). Lower limb polyneuropathy was verified in nine patients, without relation with gait or balance parameters. Neuroimaging revealed lesions mainly in the basal ganglia. Methanol poisoning survivors presented slower wide-based gait with shortened steps corresponding with frontal gait disorder. Higher stepping cadence associated with executive deficit supported the evidence of frontal lobe dysfunction related to impairment of basal ganglia and connections in frontal cortico-basal ganglia loops.
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http://dx.doi.org/10.1111/bcpt.12853DOI Listing
January 2018

Positive serum ethanol concentration on admission to hospital as the factor predictive of treatment outcome in acute methanol poisoning.

Monatsh Chem 2017 25;148(3):409-419. Epub 2016 Oct 25.

Toxicological Information Centre, General University Hospital in Prague, Na Bojisti 1, 120 00 Prague 2, Czech Republic.

Abstract: Mass methanol poisonings present a serious problem for health systems worldwide, with poor outcome associated with delayed treatment. Positive pre-hospital serum ethanol concentration may have predictive value as the prognostic factor of the treatment outcome. We studied the effect of positive serum ethanol level on admission to hospital on survival in patients treated during the Czech methanol outbreak during 2012-2014. Cross-sectional cohort study was performed in 100 hospitalized patients with confirmed methanol poisoning. Pre-hospital ethanol was administered in 42 patients (by paramedic/medical staff to 30 patients and self-administered by 12 patients before admission); 58 patients did not receive pre-hospital ethanol. Forty-two patients had detectable serum ethanol concentration on admission to hospital [median 18.3 (IQR 6.6-32.2) mmol dm]. Pre-hospital ethanol administration by paramedic/medical staff had a significant effect on survival without visual and CNS sequelae when adjusted for arterial blood pH on admission (OR 8.73; 95 % CI 3.57-21.34;  < 0.001). No patients receiving pre-hospital ethanol died compared with 21 not receiving ( < 0.001). Positive serum ethanol concentration on admission to hospital was a predictor for survival without health sequelae when adjusted for arterial blood pH (OR 8.10; 95 % CI 2.85-23.02;  < 0.001). The probability of visual and CNS sequelae in survivors reduced with increasing serum ethanol concentration on admission.

Graphical Abstract:
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http://dx.doi.org/10.1007/s00706-016-1846-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346122PMC
October 2016

Cost-effectiveness of hospital treatment and outcomes of acute methanol poisoning during the Czech Republic mass poisoning outbreak.

J Crit Care 2017 06 6;39:190-198. Epub 2017 Mar 6.

Department of Occupational Medicine, 1st Faculty of Medicine, Charles University and General University Hospital, Toxicological Information Centre, Na Bojisti 1, 120 00 Prague 2, Czech Republic. Electronic address:

Purpose: During an outbreak of mass methanol poisoning in the Czech Republic in 2012-2014, we compared the total hospital costs and one-year medical costs in the patients treated with different antidotes (fomepizole versus ethanol) and modalities of hemodialysis (intermittent hemodialysis, IHD, versus continuous renal replacement therapy, CRRT).

Methods: Cross-sectional study in 106 patients with confirmed diagnosis treated in 30 ICU settings. For each patient, the following data were analyzed: admission laboratory data, GCS, PSS, ICU length of stay, organ failures, treatment, outcome, and total hospital costs. Of 83 survivors, in 54 (65%) patients the follow-up examination, quality of life measurement with SF36 questionnaire two years after discharge, and one-year medical costs analysis were performed.

Results: The median total hospital costs were 7200 (IQR 1500-10,900) euros and the median one-year medical costs were 1447 (IQR 133-1163) euros in the study population. The total hospital costs were higher in the patients treated with fomepizole comparing to ethanol: 12,890 (IQR 6910-16,210) versus 5590 (IQR 1430-6940) euros (p<0.001). The hospital costs in the patients treated with IHD were 5400 (IQR 1520-6910) versus 12,410 (IQR 5380-16,960) euros in the patients with CRRT (p=0.317). The geometric mean ratio for increased hospital costs in the patients treated with fomepizole versus ethanol adjusted for the severity of poisoning was 3.30 (1.70-3.80 CI 95%), p<0.001, and in the patients treated with IHD versus CRRT - 0.70 (0.60-0.99 CI 95%), p=0.047. The patients with visual sequelae had higher total hospital costs than those without sequelae: 10,419 (IQR 2984-14,355) versus 4605 (IQR 1303-4505) euros (p=0.009). The patients with GCS≤13 on admission had higher one-year medical costs as well (p<0.001). No difference was found in physical and mental condition scores in the patients treated with different antidotes and modalities of hemodialysis two years after discharge (both p>0.05).

Conclusion: The total hospital costs in the patients with acute methanol poisoning were more than three times higher in the patients treated with fomepizole than in the patients treated with ethanol after adjustment for the severity of poisoning. The dialysis modality did not affect the total hospital costs, but the trend to lower costs was present in IHD-group.
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http://dx.doi.org/10.1016/j.jcrc.2017.03.001DOI Listing
June 2017

Mortality in Miners with Coal-Workers' Pneumoconiosis in the Czech Republic in the Period 1992-2013.

Int J Environ Res Public Health 2017 03 7;14(3). Epub 2017 Mar 7.

Institute of Public Health, Ostrava 70200, Czech Republic.

While working underground, miners are exposed to a number of risk factors that have a negative impact on their health and may be a cause of an increased mortality in miners. The aim of the study was to compare total and specific mortality in black coal miners with acknowledged coal-workers' pneumoconiosis (CWP) and without CWP, and the mortality of the general male population in the Czech Republic in the period 1992-2013. The sample consisted of 3476 coal miners with CWP and 6687 ex-coal miners without CWP, who were removed after achieving the maximum permissible exposure (MPE). The mortality risk differences were analyzed with the use of the standardized mortality ratio (SMR) and 95% confidence interval. Significantly higher total mortality (SMR = 1.10; 95% CI: 1.02-1.17), and mortality from malignant neoplasm (SMR = 1.16; 95% CI: 1.03-1.30), lung cancers (SMR = 1.70; 95% CI: 1.41-2.04), and non-malignant respiratory diseases (SMR = 2.78; 95% CI: 2.32-3.31) were found in the sample of coal miners with CWP. In this sample, the severity of CWP was assessed, and the SMR increased with the severity of CWP. The total (SMR = 0.86; 95% CI: 0.82-0.91) and specific mortality of miners without CWP were not higher compared with the general population. In the case where the miners were removed from underground work after achieving the MPE (without CWP), their mortality was not higher than that of the general population, but the mortality of miners with CWP was higher compared to the general population. This mortality was affected by malignant and non-malignant respiratory diseases.
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http://dx.doi.org/10.3390/ijerph14030269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369105PMC
March 2017

Markers of nucleic acids and proteins oxidation among office workers exposed to air pollutants including (nano)TiO2 particles.

Neuro Endocrinol Lett 2016 Dec;37(Suppl1):13-16

Charles University and General University Hospital in Prague, 1st Faculty of Medicine, Department of Occupational Medicine, Prague, Czech Republic.

Objectives: Experimental studies using nanoscale TiO2 have documented lung injury, inflammation, oxidative stress, and genotoxicity. Human health data are extremely scarce.

Methods: In exhaled breath condensate (EBC) and urine of 22 office employees occupationally exposed to TiO2 during their visit in the production workshops for average 14±9 min/day a panel of biomarkers of nucleic acids and proteins oxidation was studied, specifically 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), 5-hydroxymethyl uracil (5-OHMeU), o-tyrosine (o-Tyr), 3-chlorotyrosine (3-ClTyr), and 3-nitrotyrosine (3-NOTyr). Examination was performed also in 14 comparable controls.

Results: The median respirable TiO2 mass concentration in the workshops was 0.40 mg/m3, median number concentration was 2.32×104 particles/cm3 with 80% of the particles being <100 nm in diameter. All 6 markers of oxidation were elevated in EBC in factory office employees relative to controls (p<0.01). Significant association was found between their job in TiO2 production plant and 5 markers of oxidation (except 3-NOTyr) in the EBC in multivariate analysis. No elevation of markers was detected in the urine.

Conclusion: This pilot study suggests that even short nanoTiO2 exposure may lead to pulmonary oxidative stress; however this effect may be short-term and reversible. The clinical significance of these findings is unclear and more studies are needed.
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December 2016

Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning.

Clin Toxicol (Phila) 2017 Apr 6;55(4):249-259. Epub 2017 Feb 6.

a Department of Occupational Medicine, First Faculty of Medicine , Charles University , Prague , Czech Republic.

Context: The role of neuroinflammation in methanol-induced toxic brain damage has not been studied.

Objective: We studied acute concentrations and the dynamics of leukotrienes (LT) in serum in hospitalized patients with acute methanol poisoning and in survivors.

Methods: Series of acute cysteinyl-LT and LTB4 concentration measurements were performed in 28/101 hospitalized patients (mean observation time: 88 ± 20 h). In 36 survivors, control LT measurements were performed 2 years after discharge.

Results: The acute maximum (C) LT concentrations were higher than concentrations in survivors: C for LTC4 was 80.7 ± 5.6 versus 47.9 ± 4.5 pg/mL; for LTD4, 51.0 ± 6.6 versus 23.1 ± 2.1 pg/mL; for LTE4, 64.2 ± 6.0 versus 26.2 ± 3.9 pg/mL; for LTB4, 59.8 ± 6.2 versus 27.2 ± 1.4 pg/mL (all p < 0.001). The patients who survived had higher LT concentrations than those who died (all p < 0.01). Among survivors, patients with CNS sequelae had lower LTE4 and LTB4 than did those without sequelae (both p < 0.05). The LT concentrations increased at a rate of 0.4-0.5 pg/mL/h and peaked 4-5 days after admission. The patients with better outcomes had higher cys-LTs (all p < 0.01) and LTB4 (p < 0.05). More severely poisoned patients had lower acute LT concentrations than those with minor acidemia. The follow-up LT concentrations in survivors with and without CNS sequelae did not differ (all p > 0.05). The mean decrease in LT concentration was 30.9 ± 9.0 pg/mL for LTC4, 26.3 ± 8.6 pg/mL for LTD4, 37.3 ± 6.4 pg/mL for LTE4, and 32.0 ± 8.8 pg/mL for LTB4.

Conclusions: Our findings suggest that leukotriene-mediated neuroinflammation may play an important role in the mechanisms of toxic brain damage in acute methanol poisoning in humans. Acute elevation of LT concentrations was moderate, transitory, and was not followed by chronic neuroinflammation in survivors.
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http://dx.doi.org/10.1080/15563650.2017.1284332DOI Listing
April 2017