Risk Factors for Mortality in Denim Sandblasters Silicosis: Selecting Candidate for Lung Transplantation.

OBJECTIVE: This study aimed to review the risk factors for silicosis together with survival analysis and a perspective for lung transplantation with data from a single center. MATERIAL AND METHODS: We reviewed the medical records of denim sandblasters who were referred to our center between January 2006 and December 2011 and evaluated 219 patients with a history of denim sandblasting with a minimum follow-up period of 5 years until 2016. We analyzed several personal and occupational features, together with functional and radiologic data. RESULTS: Of the 219 denim sandblasters, 107 (49%) had been diagnosed with silicosis. In the logistic regression analysis, the duration of exposure was the only independent risk factor for the development of silicosis, indicating a 9% increased risk of silicosis for every month of exposure (p<0.001; odds ratio 1.09; 95% confidence interval 1.050-1.132). Of the patients, 7 (3%) died. A forced expiratory volume in the first second of <44% and a forced vital capacity of <47% were associated with an increased risk of mortality. Mortality was significantly higher in the international labor office category 3 patients, and 5-year survival rates of patients with A, B, and C lung opacities were 88%, 67%, and 25%, respectively. CONCLUSION: Silicosis still kills young workers. Severe radiologic involvement and decreased lung volumes are related to mortality, and lung transplantation is the only therapeutic option.

Assessment of Diastolic Function and Thiol-Disulphide Homeostasis in Arsenic-Exposed Workers.

OBJECTIVES: Exposure to arsenic is associated with various cardiovascular diseases. The imbalance between antioxidant and oxidant homeostasis plays a crucial role in the cardiovascular effects of arsenic. The aim of this study was to investigate the effect of arsenic exposure on diastolic function by measuring thiol and disulphide in arsenic-exposed workers. METHODS AND RESULTS: A total of 107 male arsenic-exposed workers and 36 healthy subjects were enrolled. Mitral inflow velocity and parameters of diastolic function were measured. As oxidative stress indicators, total thiol, native thiol, disulphide, and their percent ratios were determined. The mean age was 39.1 ± 9.5 years in the arsenic-exposed group and 37.4 ± 9.6 years in the controls. The median blood arsenic level was 42 µg/dL in the arsenic-exposed group and 3.75 µg/dL in the controls. E-wave, E/A ratio, and e' wave were lower and left atrial diameter, A-wave, average E/e' ratio, and tricuspid regurgitation velocity were higher in the arsenic-exposed group. Native and total thiol concentrations were lower, and disulphide/native and disulphide/total thiol ratios were higher in the arsenic-exposed group. Fourteen (13.1%) workers had diastolic dysfunction, 26 (24.3%) had indeterminate, and 67 (62.6%) had normal diastolic function, compared to 1 (2.8%), 2 (5.6%), and 33 (97.7%) in the control group, respectively. In regression analysis, disulphide/native thiol ratio (p < 0.001) and blood arsenic level (p < 0.001) predicted increased average E/e' ratio in the arsenic-exposed group. CONCLUSIONS: This study showed strong associations among arsenic exposure, oxidative stress, and diastolic function, and revealed the influence of arsenic exposure on diastolic dysfunction through oxidative stress.

Serum endocan level and diastolic functions in the case of lead exposure

Background/aim: Lead can cause morphological and functional changes in heart, and inflammation and endothelial dysfunction in vasculature. Endocan, as a novel indicator of endothelial dysfunction, has been used for cardiovascular diseases. This study investigated the relationship between lead exposure, endocan levels, and diastolic functions. Materials and methods: A total of 51 lead-exposed workers without a known cardiovascular disease or risk factors and 54 healthy controls were enrolled. All participants underwent transthoracic echocardiography. Blood lead and serum endocan levels were analyzed. Results: Baseline demographic and clinical characteristics were found to be similar between groups. Median blood lead (32 vs 1.5 µg/dL, P < 0.001) and serum endocan levels (67 vs 57.1 pg/mL, P = 0.02) were significantly higher in the lead-exposed group. Serum endocan level showed a positive correlation with blood lead levels (r = 0.404, P = 0.003) in lead-exposed workers. Serum endocan level was an independent risk factor for increased E/E' ratio (ß = 0.704, P = 0.002) and left atrial volume index (ß = 1.158, P = 0.011) and higher level of lead in blood was an independent risk factor for increased E wave (ß = 8.004, P = 0.022) in lead-exposed workers. Conclusion: Worsened diastolic functions may be seen in the course of lead exposure. Due to sharing a similar mechanism, a higher serum level of endocan may be a valuable laboratory clue for impaired diastolic function in this population.

Maternal second trimester blood levels of selected heavy metals in pregnancies complicated with neural tube defects.

PURPOSE: Neural tube defects (NTDs) are the most common malformations of the central nervous system (CNS). There is continuing research for the identification of risk factors and interventions for prevention of NTDs. The aim of this study was to investigate the maternal second trimester blood levels of selected heavy metals namely, arsenic (As), cadmium (Cd), mercury (Hg), manganese (Mn), nickel (Ni), and lead (Pb) and their possible relation with the occurrence of NTDs. METHODS: Twenty-one healthy second trimester pregnant women with fetuses affected with NTD (cases) were matched with 21 healthy pregnant women with unaffected fetuses (controls) with respect to age, body mass index (BMI), and gestational age. Maternal blood levels of heavy metals were measured after an overnight fasting period. RESULTS: No significant differences were observed in terms of maternal blood levels of As, Cd, Hg, and Ni between NTD-affected and unaffected pregnancies. The blood Pb and Mn levels were found to be higher in pregnant women with a fetus affected with NTD when compared with pregnant women with unaffected fetuses (for Pb, in cases 12.3 ± 5.5 µg/L, in controls 7.8 ± 2.4 µg/L; for Mn in cases 3.6 ± 1.4 µg/L, in controls 2.4 ± 1.0 µg/L, p < .05). CONCLUSIONS: High maternal second trimester blood levels of Pb and Mn during pregnancy are associated with NTDs in the newborn.

Fixed drug eruption due To 2,3-dimercapto-1-propanesulfonic acid (DMPS) treatment for mercury poisoning: a rare adverse effect.

BACKGROUND: Fixed drug eruptions (FDE) are characterized by recurrent, usually solitary erythematous or dark red macular, plaque or bullous lesions, all at the same site. Among the first choices for antidotal treatment in mercury exposure, 2,3-dimercapto-1-propanesulfonic acid (DMPS) is generally a drug with a low incidence of side effects. FDE due to DMPS was not detected in our literature research and so we aimed to present this rare case. CASE REPORT: Forty-eight-year-old male patient, gunpowder and explosives factory worker, was admitted to our hospital because of mercury exposure and we started DMPS treatment. On the second day of chelation treatment, swelling and felting on lips and complaints of wound formation in genital areas started. Annular, purple color plaque on penis with no angioedema was observed. Case was regarded as FDE. Systemic and topical steroid therapy was started after termination of chelation therapy and lesions regressed with steroids. DISCUSSION: Drug eruptions are substantially common dermatological problems and can be seen in about 2.2% of inpatients. The most common unexpected effects of DMPS are allergic skin reactions. The clinical state regress rapidly after the cessation of chelation therapy.

Serum S100B, NSE, and GRIA1 levels as neurological biomarkers in lead exposure

Background/aim: The central nervous system is one of the major targets in lead exposure. Biomarkers for the diagnosis and follow-up of lead exposure have not been identified. In this study, serum S100B, neuron-specific enolase (NSE), and glutamate receptor 1 (GRIA1) levels were determined as possible biomarkers for lead neurotoxicity. Material and methods: Twenty-five subjects with chronic lead exposure and 25 controls were included in the study. NSE and S100B were measured by electrochemiluminescence immunoassay with a Cobas E601 analyzer. GRIA1 levels were measured with an ELISA kit using a quantitative sandwich enzyme immunoassay technique. Results: GRIA1 levels were significantly higher in the lead exposure group than in the control group. No significant differences for NSE, S100B, ALT, AST, or creatinine in sera were found between lead exposure and control groups. Conclusion: Subjects with chronic lead exposure are found to have increased glutamate receptor levels and do not seem to have glial or neuronal damage, which can be demonstrated with the elevation of NSE and S100B levels. GRIA1 levels might be used as a biomarker for the neurotoxicity of lead.

Assessment of DNA damage in ceramic workers.

It is known that ceramic workers are potentially exposed to complex mixture of chemicals such as silica, inorganic lead, lime, beryllium and aluminum that can be associated with an increased risk of several diseases. All operations in the ceramic industries such as mixing, moulding, casting, shaking out and finishing jobs, have been associated with the higher exposure levels and in most of the silica-related industries, average overall exposure exceeded permissible exposure levels for respirable crystalline silica. The aim of this study was to evaluate the possible genotoxic damage in ceramic workers exposed to complex mixture of chemicals mainly crystalline silica. For this purpose, the blood and buccal epithelial cell samples were taken from the ceramic workers (n = 99) and their controls (n = 81). The genotoxicity was assessed by the alkaline comet assay in isolated lymphocytes and whole blood. Micronucleus (MN), binucleated (BN), pyknotic (PYC), condensed chromatin (CC), karyolytic (KYL), karyorrhectic (KHC) and nuclear bud (NBUD) frequencies in buccal epithelial cells and plasma 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) levels were also evaluated. In the study, 38 workers were diagnosed with silicosis, 9 workers were suspected to have silicosis, whereas 52 workers were found to be healthy. DNA damage in blood and lymphocytes; MN, CC + KHC, PYC frequencies in buccal epithelial cells and 8-oxodG levels in plasma were increased in workers compared to their controls. These results showed that occupational chemical mixture exposure in ceramic industry may cause genotoxic damage that can lead to important health problems in the workers.

Alteration of thiol-disulfide homeostasis in workers occupationally exposed to arsenic.

This study evaluates the redox state in occupationally arsenic-exposed workers (n = 71) by assessing the dynamic serum thiol-disulfide homeostasis. We determined the serum thiol-disulfide homeostasis parameters of exposed workers and controls (n = 43) using a novel automated colorimetric assay. Median urinary As and 8-isoprostane levels of exposed group were significantly higher than control group (16.40 µg/L vs 2µg/L, p < .001 and 2.28 ng/ml vs 0.54 ng/ml, p < .001, respectively). Disulfide level, disulfide/native thiol ratio, and disulfide/total thiol ratio were significantly higher in exposed group. The mean ceruloplasmine and myeloperoxidase activities of As-exposed group were significantly higher than control group (117.15 U/L vs 87.02 U/L, p = .035 and 148.53 U/L vs 97.75 U/L, p = .000, respectively). The median catalase activity did not differ in the two groups. Our findings revealed that As disrupts the thiol-disulfide homeostasis in favor of disulfide.

Possible changes of New-Generation inflammation markers with occupational lead exposure.

OBJECTIVES: Occupational lead (Pb) exposure is still an important health problem in the world. Long-term Pb exposure causes several adverse effects. The aim of this study was to investigate the changes of inflammation markers with chronic Pb exposure by analyzing neopterin levels and kynurenine (Kyn) to tryptophan (Trp) ratio that reflects indolamine 2,3-dioxygenase activity and to compare with healthy volunteers' parameters. METHODS: Blood lead levels (BLLs) were analyzed by atomic absorption spectrometry. Urinary neopterin and serum Kyn and Trp levels were analyzed by high-performance liquid chromatography. RESULTS: According to our results, mean BLL of the 29 workers was 20.4±9.6 µg/dl. Urinary neopterin levels, serum Kyn levels, and Kyn/Trp of Pb workers (188±52 µmol/mol creatinine, 2.70±0.66 µM, and 43.19±10.38 µmol/mmol, respectively) were significantly higher than controls (144±35 µmol/mol creatinine, 2.08±0.34 µM, and 32.24±7.69 µmol/mmol, respectively). Pb-exposed workers were divided into further three groups according to their BLLs: as 10-19 µg/dl (n=18), 20-29 µg/dl (n=8), and 30-49 µg/dl (n=3). Neopterin levels of the workers with BLL of 30-49 µg/dl were significantly higher than those of BLL with 10-29 µg/dl, while Trp levels decreased. Kyn/Trp of workers with BLL of 30-49 µg/dl were elevated significantly compared with the workers with BLL<30 µg/dl. In addition to neopterin, Kyn and Kyn/Trp levels were positively influenced by Pb exposure. CONCLUSIONS: Increased level of inflammation markers confirms the adverse effects of Pb even low BLLs, and we suggest that monitoring BLLs with inflammation markers could help to prevent serious occupational health problems.

Evaluation of the ambulatory arterial stiffness index in lead-exposed workers.

OBJECTIVE: Lead exposure has been associated with various cardiovascular disorders. It may also cause increased inflammation and fibrosis in the arterial system resulting in an increase in arterial stiffness. In this study, the ambulatory arterial stiffness index (AASI), which is a technique that measures arterial stiffness, was evaluated in occupationally lead-exposed workers. METHODS: In this cross-sectional study, 68 lead-exposed workers without known cardiovascular risk factors and 68 healthy subjects were evaluated according to the 24-hour ambulatory blood pressure monitorization (ABPM) profiles and blood and 24-hour urine lead levels. A regression slope of diastolic over systolic blood pressure (BP) was computed in each participant. AASI was defined as 1 minus the regression slope. RESULTS: There were no significant differences in terms of baseline demographic, clinical, echocardiographic characteristics, and ABPM profiles between the groups. In lead-exposed workers, the mean age was 34.7±8.1 years, and the median blood and urine lead levels were 40.5 µg/dL and 34.9 µg/L, respectively. AASI was 0.42±0.10 in lead-exposed workers and 0.37±0.10 in control subjects (p=0.007). In correlation analysis, AASI was correlated with both blood (r=0.417, p<0.001) and urine lead (r=0.242, p=0.047) levels. In regression analysis, blood lead level was found to be associated with AASI (ß=0.086, p<0.001). CONCLUSION: AASI, which is an indicator of arterial stiffness, was found to be higher in lead-exposed workers than in healthy individuals. Increased AASI may be considered an early sign of arterial involvement in case of lead exposure.

Assessment of heart rate response to exercise and recovery during treadmill testing in arsenic-exposed workers.

BACKGROUND: Arsenic exposure is associated with various cardiovascular diseases. The aim of the present study was to assess cardiac autonomic function via heart rate response to exercise and recovery period of treadmill testing in arsenic-exposed workers. METHODS: Sixty-five (65) occupationally arsenic-exposed workers and 35 healthy controls were enrolled. Blood and urinary arsenic levels were analyzed and symptom limited maximal treadmill exercise test were performed. Chronotropic response to exercise including age-predicted maximal heart rate (APMHR), heart rate reserve (HRreserve ), age-predicted HRreserve (APHRreserve ) and adjusted HRreserve and 1st-, 2nd-and 3rd-min heart rate recovery (HRR) indices were calculated. RESULTS: Baseline clinical and echocardiographic parameters, exercise test duration, resting and maximal heart rate, peak exercise capacity, HRreserve , APMHR, APHRreserve , and adjusted HRreserve were found to be similar between groups. HRR1 (22.0 ± 4.3 vs. 24.3 ± 3.1 bpm, p = .003) and HRR2 (43.2 ± 6.2 vs. 46.7 ± 6.4 bpm, p = .012) were significantly lower in arsenic-exposed workers compared to controls. Blood and urinary arsenic levels negatively correlated with HRR1 (r = -.477, p < .001 and r = -.438, p < .001, respectively) and HRR2 (r = -.507, p < .001 and r = -.412, p < .001 respectively). CONCLUSIONS: Arsenic-exposed workers had lower HRR indices than normal subjects but chronotropic response were similar. Cardiac autonomic dysregulation may be one of the cardiovascular consequences of arsenic exposure.

Dynamic disulfide/thiol homeostasis in lead exposure denoted by a novel method.

Lead is a toxic heavy metal, and prevention of human exposure to lead has not been accomplished yet. The toxicity of lead is continually being investigated, and the molecular mechanisms of its toxicity are still being revealed. In this study, we used a novel method to examine thiol (SH)/disulfide homeostasis in workers who were occupationally exposed to lead. A total of 80 such workers and 70 control subjects were evaluated, and their native and total SH values were measured in serum using a novel method; their blood lead levels were also assessed. The novel method used for SH measurements was based on the principle of measuring native SH, after which disulfide bonds were reduced and total SHs were measured. These measurements allowed us to calculate disulfide amounts, disulfide/total SH percent ratios, disulfide/native SH percent ratios, and native SH /total SH percent ratios. We found that disulfide levels were significantly higher in workers who were exposed to lead (21.08(11.1-53.6) vs. 17.9(1.7-25), p < 0.001). Additionally, the disulfide/native SH and disulfide/total SH percent ratios were higher in exposed workers, while the native SH/total SH percent ratios were higher in the control subjects. Furthermore, the lead and disulfide levels showed a positive correlation, with p < 0.001 and a correlation coefficient of 0.378. Finally, the novel method used in this study successfully showed a switch from SH to disulfide after lead exposure, and the method is fully automated, easy, cheap, reliable, and reproducible. Use of this method in future cases may provide valuable insights into the management of lead exposure.

Exercise heart rate recovery assessment of the cardiac autonomic nervous system in workers occupationally exposed to lead.

OBJECTIVE: The aim of the present study was to assess cardiac autonomic function via indices of exercise heart rate recovery (HRR) in workers occupationally exposed to lead. METHODS: A total of 98 lead-exposed workers and 98 healthy controls were enrolled. All underwent exercise testing and transthoracic echocardiography. HRR indices were calculated by subtracting 1st- (HRR1), 2nd- (HRR2), and 3rd-minute (HRR3) heart rates from maximal heart rate (HR). Exercise test parameters- HRR in particular- were compared between groups, and correlation analysis of blood, 24-hour urine lead levels, and test parameters was performed. RESULTS: Baseline demographic and clinical characteristics were found to be similar between groups. Mean HRR1 (26.2±3.6 vs 29.0±4.1 bpm, p<0.001), HRR2 (42.6±3.9 vs 46.9±3.7 bpm, p<0.001), and HRR3 (56.6±4.5 vs 61.8±4.3 bpm, p<0.001) values were significantly lower in the lead-exposed group than in the healthy controls. HRR1 was found to be significantly correlated with blood (r:-0.415; p<0.001) and 24-hour urine lead levels (r:-0.446; p<0.001). HRR2 and HRR3 were significantly correlated with 24-hour urine lead level (r:-0.396; p<0.001 and r:-0.233; p=0.021, respectively). CONCLUSION: Lead-exposed workers had lower HRR indices than normal subjects. Blood and 24-hour urine lead levels were significantly associated with HRR indices. Cardiac autonomic functions may be affected by exposure to lead, and those occupationally exposed should be closely followed for adverse cardiovascular outcome.

Assessment of the Cardiac Autonomic Nervous System in Mercury-Exposed Individuals via Post-Exercise Heart Rate Recovery.

OBJECTIVE: The aim of this study was to assess exercise heart rate recovery (HRR) indices in mercury-exposed individuals when evaluating their cardiac autonomic function. SUBJECTS AND METHODS: Twenty-eight mercury-exposed individuals and 28 healthy controls were enrolled. All the subjects underwent exercise testing and transthoracic echocardiography. The HRR indices were calculated by subtracting the first- (HRR1), second- (HRR2) and third-minute (HRR3) heart rates from the maximal heart rate. The two groups were evaluated in terms of exercise test parameters, especially HRR, and a correlation analysis was performed between blood, 24-hour urine and hair mercury levels and the test parameters. RESULTS: The mercury-exposed and control groups were similar in age (37.2 ± 6.6 vs. 36.9 ± 9.0 years), had an identical gender distribution (16 females and 12 males) and similar left ventricular ejection fractions (65.5 ± 3.1 vs. 65.4 ± 3.1%). The mean HRR1 [25.6 ± 6.5 vs. 30.3 ± 8.2 beats per min (bpm); p = 0.009], HRR2 (43.5 ± 5.3 vs. 47.8 ± 5.5 bpm; p = 0.010) and HRR3 (56.8 ± 5.1 vs. 59.4 ± 6.3 bpm; p = 0.016) values were significantly lower in the mercury-exposed group than in the healthy controls. However, there were no significant correlations between blood, urine and hair mercury levels and exercise test parameters. CONCLUSIONS: Mercury-exposed individuals had lower HRR indices than normal subjects. In these individuals, mercury exposure measurements did not show correlations with the exercise test parameters, but age did show a negative correlation with these parameters. Therefore, cardiac autonomic functions might be involved in cases of mercury exposure.

Thiol/disulfide homeostasis in asphalt workers.

The aim of this study was to investigate thiol/disulfide homeostasis in asphalt workers who are exposed to polycyclic aromatic hydrocarbons occupationally. The study was carried out in 34 nonsmoker asphalt workers. Additionally, 35 healthy nonsmoker volunteers were recruited as control group. Thiol and disulfide concentrations were determined using the novel automated measurement method. Levels of urinary 1-OH-pyrene were analyzed by liquid chromatography. Disulfide/thiol ratio was significantly higher in exposed group (p = .034). Also, a positive correlation was detected between disulfide/thiol ratio and 1-OH-pyrene values (r = .249, p = .036). Thiol/disulfide homeostasis was found to be disturbed in asphalt workers. The novel test used in this study may be useful for evaluating the oxidative status in polycyclic aromatic hydrocarbon (PAH) exposure.

Arsenic related hearing loss in miners.

PURPOSE: Arsenic is a toxic metalloid that carries number of potential risks to human health, although there is little evidence of the ototoxic effect of arsenic. The aim of this study was to identify the relationship between arsenic exposure and hearing loss by measuring blood arsenic concentrations and hearing among miners. MATERIALS AND METHODS: This research is a retrospective case control study. Included in the study were miners employed in a single silver mine whose blood arsenic concentrations were high. A comparison was made on the pure tone audiometry measurements taken from miners exposed only to arsenic (Group 1), those exposed to both arsenic and noise (Group 2) and a control group exposed to neither arsenic nor noise (Group 3). RESULTS: It was found that for both ears at all frequencies, the hearing level of Group 3 was better than the hearing levels of both Group 1 and Group 2. There was no correlation between the blood arsenic levels and hearing levels in both ears. CONCLUSION: This study has revealed the ototoxic effects of arsenic. As blood arsenic concentrations do not reflect long-term exposure, no correlation was identified between blood arsenic concentrations and hearing levels. Further studies will be needed to clarify the mechanisms involved in the effect of arsenic on hearing. This paper represents the largest study to date focusing on the isolated effects of arsenic on hearing through the use of a clinical auditory test.